tbuckley/cabot-search huggingface dataset:
EFFECTIVELY TRAINING PHYSICAL EDUCATION TEACHERS TO IMPLEMENT INJURY PREVENTIVE STRATEGIES INTO THEIR PE LESSONS
Authors: Sien Vercruysse
Journal: British Journal of Sports Medicine (2017)

Background Physical education teachers (PETs) can be effectively trained to implement injury preventive strategies into their own lives.1 However, to decrease negative effects of sports injuries in adolescents, injury prevention within this population is needed as well. Therefore, the current study trains PETs to implement injury preventive strategies both in their own lives and in their PE lessons. Objective Aim 1 was investigating whether an intervention can effectively improve PETs' injury preventive knowledge. Aim 2 was investigating whether the intervention led to more injury preventive implementation in PETs own extracurricular sporting activities. Aim 3 was investigating whether the intervention enhanced PET injury preventive implementation in their PE lessons. Design An RCT was conducted. Setting Secondary school PETs, active in second grade (14–16 years), were recruited. Participants Fourteen PETs were randomly assigned to either intervention (Mage 41.43±10.21) or control group (Mage 38.86±8.32). Per PET one of their classes of pupils from second grade was questioned (n=271). Interventions An effective injury prevention intervention1 was provided with adaptations for a more easily implementation in PE lessons. Main Outcome Measurements PET injury preventive knowledge, preventive behaviour in extracurricular sporting activities and during PE lessons were assessed at three different time points; before the intervention (pre), 4 (post) and 7 weeks (follow-up) after receiving the intervention. Pupils filled out a questionnaire on their PET injury preventive teaching behaviour (pre-post-follow-up). Results The injury prevention intervention resulted in an improvement of PET injury preventive knowledge (F(10,2)=7.718, p=0.005), PET preventive behaviour in own extracurricular sporting activities (F(14,2)=4.105; p=0.047) and in their teaching behaviour towards the pupils in PE lessons (F(14,2)=3.147; p=0.061). Reports of pupils pointed in the same direction as the reports of PETs. Conclusions The intervention improved PET injury preventive knowledge and behaviour, both in their own lives as in their PE lessons.
イソプロテレノールはSTAT3/MicroRNA373カスケードを介して胃癌細胞におけるCD44発現を調節する【Powered by NICT】
Authors: Wei Bo, Sun Xiaoyan, Geng Zhijun, Shi Ming, Chen Zhida, Chen Lin, Wang Yongan, Fu Xiaobing
Journal: Biomaterials (2016)
Plasmid-borne colistin resistance gene mcr-3 in Salmonella isolates from human infections, Denmark, 2009–17
Authors: Eva Litrup, Kristoffer Kiil, Anette M Hammerum, Louise Roer, Eva M Nielsen, Mia Torpdahl
Journal: Eurosurveillance (2017)

This report describes one Salmonella isolate harbouring both mcr-1 and mcr-3. We also found nine other Salmonella isolates positive for the plasmid-borne colistin resistance gene, mcr-3. The strains were isolated from patients in Denmark between 2009 and 2017 and five of the patients had travelled to Asia. In addition to mcr-3, all strains were found positive for blaTEM-1, strA, strB, sul2 and tet(A) or tet(B), and most strains were positive for blaCTX-M-55 and qnrS.
The Tragic Case of Charlie Gard
Authors: John D. Lantos
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
04.03 Tgfβ-induced protein (tgfβi) is dysregulated in osteoarthritis
Authors: Maxime Ruiz, Marie Maumus, Karine Toupet, Guillaume Fonteneau, Yves-Marie Pers, Xavier Houard, Francis Berenbaum, Christian Jorgensen, Danièle Noël
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Backgrounds and objectives</h3> Osteoarthritis (OA) is the most common rheumatic disease affecting all joint tissues and Transforming Growth Factor β (TGFβ) pathway dysregulation in bone marrow mesenchymal stem cells (MSCs) has been proposed to be involved in OA physiopathology. Based on secretome analysis of MSCs, we identified several TGFβ family members and focused our attention on Transforming Growth Factor β-Induced (TGFβI), a poorly studied extracellular matrix (ECM) component. <h3>Materials and methods</h3> Human bone marrow MSCs were isolated from OA patients (OA-MSCs) and healthy donors (H-MSCs) while chondrocytes were isolated from OA patients (OA-CH). Chondrogenic differentiation of MSCs was induced in micropellet for 21 days. TGFβI expression was analysed by RT-qPCR and ELISA. Murine articular chondrocytes were isolated from 3 days old C57/BL6 mice and OA-like murine chondrocytes were obtained by addition of 1 ng/mL IL1β for 24 hour. Transfection of siRNA directed against TGFβI (siTGFβI) was performed using oligofectamine. The collagenase-induced murine model of OA was used for immunohistochemical analysis of cartilage and RNA extraction with TRIzol and acid phenol. <h3>Results</h3> In humans, TGFβI mRNA expression was 2.5 fold lower in OA-MSCs than in H-MSCs and 10 fold lower in OA-MSCs than in OA-CH. We also found out that TGFβI was highly induced (by a 10 fold factor) during the first three days of chondrogenic differentiation but decreased to reach levels similar to those found in MSCs. In the mouse, immunohistochemical analysis revealed high expression of TGFβI in healthy cartilage as compared to OA cartilage. In murine MSCs, expression of TGFβI is 3.8 fold lower than in chondrocytes. In OA-like chondrocytes, characterised by reduced expression of anabolic markers and increased levels of catabolic markers, TGFβI mRNA levels were significantly lower than in healthy chondrocytes. Rapid decline of TGFβI expression was also observed in OA-like dedifferentiated chondrocytes. Finally, transfection of siTGFβI in murine chondrocytes resulted in alteration of their metabolic activity. <h3>Conclusion</h3> Altogether, our results indicate that expression of TGFβI is higher in articular cartilage than in MSCs, and loss of TGFβI is associated with OA phenotype. TGFβI might be a key regulator of joint homeostasis involved in chondrogenesis and ECM integrity.
02.46 Microrna-146a and disease activity in sle patients
Authors: Russka Shumnalieva, Darina Kachakova, Simeon Monov, Radka Kaneva, Viara Choumnalieva–Ivanova, Zlatimir Kolarov, Rasho Rashkov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Altered expression of microRNAs have been implicated in the pathogenesis of SLE due to their role in both the adaptive and innate immunity. Recent studies are trying to identify aberrant microRNA level as a diagnostic signature of SLE as well as to understand a role of specific microRNAs as biomarkers for disease activity (DA) and progression. The aim of our study was to evaluate the peripheral blood (PB) expression of microRNA-146a (miR-146a) in SLE patients and to determine its correlation with the DA in the clinical practice. <h3>Materials and methods</h3> 40 SLE patients were included in the study. miR-146a expression levels in whole PB samples were determined by PCR (SYBR Green technology). 2<sup>-ΔΔCt</sup> method was used for analysis. 32 healthy donors were used as controls. The DA was determined by DA index (SLEDAI) with 24 descriptors. SPSS v20 was used for ROC curve and Spearman correlation analysis. <h3>Results</h3> miR-146a was overexpressed in 62.5% of the patients and none of the patients showed underexpression of miR-146a. ROC curve analysis showed that the expression levels of miR-146a (AUC-0.711, p=0.002) in PB could discriminate SLE patients from HCs with 82.5% sensitivity and 56.2% specificity. miR-146a showed statistically significant correlation with the diagnosis (r<sub>s</sub> 0.363) and age (r<sub>s</sub> 0.239) but there was no correlations with SLEDAI nor with the immunological activity according to ANA titer, a-dsDNA, a-Sm, a-b2GPI, a-CL antibodies, C3 and C4 complement levels. <h3>Conclusions</h3> miR-146a is a known negative regulator of the type I interferon pathway by targeting the key signalling proteins and its underexpression may contribute to the disease activity of SLE as well as to the disease development. We didn't find a correlation between the levels of miR-146a and DA as a whole as well as with the immunological activity which might reflect the variants of SLE DA in the patients who participated in the study, the difference in their genetic background or in the used medications but larger study is needed to confirm these results in the clinical practice. <h3>Acknowledgement</h3> The study was supported by Grant 53/2014 funded by Medical University – Sofia, Bulgaria.
Abstract 393: MCL-1 Promotes Survival and Influences Mitochondrial Dynamics in Cardiac Myocytes
Authors: Alexandra G Moyzis, Robert L Thomas, Jennifer Kuo, Åsa B Gustafsson
Journal: Circulation Research (2015)

The BCL-2 family proteins are important regulators of mitochondrial structure and integrity. MCL-1 is an anti-apoptotic BCL-2 protein that is highly expressed in the myocardium compared to the other anti-apoptotic proteins BCL-2 and BCL-X L. Recently, we reported that MCL-1 is essential for myocardial homeostasis. Cardiac-specific deletion of MCL-1 in mice led to rapid mitochondrial dysfunction, hypertrophy, and lethal cardiomyopathy. Surprisingly, MCL-1 deficient myocytes did not undergo apoptotic cell death. Instead, the cells displayed signs of mitochondrial deterioration and necrotic cell death, suggesting that MCL-1 has an additional role in maintaining mitochondrial function in cardiac myocytes. Similarly, deletion of MCL-1 in fibroblasts caused rapid mitochondrial fragmentation followed by cell death at 72 hours. Interestingly, the MCL-1 deficient fibroblasts retained cytochrome c in the mitochondria , confirming that the cells were not undergoing apoptotic cell death. We have also identified that MCL-1 localizes to the mitochondrial outer membrane (OM) and the matrix in the myocardium and that the two forms respond differently to stress. MCL-1 OM was rapidly degraded after myocardial infarction or fasting, whereas MCL-1 Matrix levels were maintained. Similarly, starvation of MEFs resulted in rapid degradation of MCL-1 OM , whereas MCL-1 Matrix showed delayed degradation. Treatment with the mitochondrial uncoupler FCCP led to rapid degradation of both forms. This suggests that the susceptibility to degradation is dependent on its localization and the nature of the stress. Our data also suggests that these two forms perform distinct functions in regulating mitochondrial morphology and survival. Overexpression of MCL-1 Matrix promoted mitochondrial fusion in fibroblasts under baseline conditions and protected cells against FCCP-mediated mitochondrial fission and clearance by autophagosomes. Thus, our data suggest that MCL-1 exists in two separate locations where it performs different functions. MCL-1 Matrix promotes mitochondrial fusion, which protects cells against excessive mitochondrial clearance during unfavorable conditions.
02.05 Integrin α11β1 mediates adhesion and migration in synovial fibroblasts during RA
Authors: Kerstin Katharina Rauwolf, Denise Beckmann, Uwe Hansen, Daniel Kronenberg, Donald Gullberg, Thomas Pap, Adelheid Korb-Pap
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Integrins are involved in regulating and controlling cellular proliferation, migration, tissue invasion, cytokine and MMP production – key mechanisms leading to joint destruction during rheumatoid arthritis (RA). In this context, integrin α11β1 (ITGA11) is of special interest, because it is mainly expressed in cellular adhesive structures of mesenchymal cells and its role in regulating cartilage degradation due to altered interactions of synovial fibroblasts with ECM components in inflammatory arthritis is still unknown. <h3>Materials and methods</h3> ITGA11 expression levels in SF of wild type and arthritic hTNFtg mice were analysed by Western Blot (WB) and immunofluorescence as well as immunohistochemistry using paraffin-embedded hind paws. Furthermore, different extracellular matrix substrates and their influence on ITGA11 expression and its subcellular location as well as integrin down-stream signalling pathways such as FAK and src and interaction partners (eg, vinculin) were investigated using WB and immunofluorescence. Next, we analysed isolated SF of ITGA11<sup>-/-</sup> mice in functional studies (proliferation assay, modified scratch assay and electric cell-substrate impedance sensing) to identify differences in migration and adhesion. To identify an effect of integrin α11β1 loss on expression levels of other β1 integrins e.g integrin α2β1, we performed WB and immunofluorescence analyses. <h3>Results</h3> hTNFtg SF showed an enrichment of focal adhesions with increased and most prominent expression of ITGA11. Furthermore, ITGA11<sup>-/-</sup> SF showed a modified cytoskeleton arrangement compared to wt SF. Analyses of the functional assays showed a reduced proliferation rate of ITGA11<sup>-/-</sup> SF (−41,2% vs wt SF), an altered coating-dependent migration rate (−29,7% vs wt SF at 48 hours with fibronectin coating, −66% vs wt SF at 48 hours with collagen I coating) and adhesion capacity of ITGA11<sup>-/-</sup> SF in comparison to wt SF and an altered cell-cell and cell-matrix interaction. WB analyses showed only a slight increase of ITGA2 expression in ITGA11<sup>-/-</sup> SF compared to wt SF. <h3>Conclusion</h3> Integrin α11β1 is induced under inflammatory conditions and contributes to the migratory and adhesive capacity of SF.
Phase 1 study of investigational oral mTORC1/2 inhibitor TAK-228 (MLN0128): Tolerability and food effects of a milled formulation in patients (pts) with advanced solid tumors
Authors: K.N. Moore, T.M. Bauer, G. Falchook, C. Patel, R. Neuwirth, A. Enke, F. Zohren, M.R. Patel
Journal: Annals of Oncology (2016)
SP0135 Myostatin, sclerostin, syndecan and more
Authors: T Pap
Journal: Annals of the Rheumatic Diseases (2017)

Rheumatoid arthritis (RA) is the prototype of an inflammatory arthritis that is characterized by chronic inflammation, progressive cartilage destruction and bone erosion. Development of RA is marked by the hyperplasia of the synovial membrane as caused by an infiltration and accumulation of inflammatory cells such as macrophages and lymphocytes as well as an increase in the number of resident mesenchymal cells. These fibroblast-like synoviocytes (FLS) are a key part of the local immune system in the joints and integrate signals form different sources into a pathological tissue response. Resorption of the juxtaarticular bone is part of this pathological tissue response and is denoted as focal bone erosion which occurs early in this disease and over time is associated with significant morbidity. Focal bone erosions are observed at the interface of pannus and bone tissue both marginally, where pannus invades cortical bone, and in the immediate subchondral bone, where the pannus invades the marrow space. Many of the cytokines and growth factors implicated in the inflammatory processes are secreted by FLS and have also been demonstrated to impact directly or indirectly on osteoblast and/or osteoclast differentiation and function. However, research of the last years has also identified some novel pathways by which i) osteoclast- mediated bone resorption is regulated and fine-tuned under inflammatory conditions such as in RA and that ii) link inflammatory bone resorption to other features of systemic autoimmunity such as the activation of developmental pathways or muscle weakness. This lecture will review some of these novel mediators and pathways, including members of the Wnt- signalling pathway (e.g. sclerostin), members of the GDF- family of growth differentiation factors (e.g. myostatin) and cells surface anchored proteoglycans (e.g., syndecans). Focusing on the role of these molecules in the FLS-mediated regulation of osteoclastic bone resorption, the lecture will point to general principles of inflammatory bone remodelling and discuss potential therapeutic implications for RA. <h3>Disclosure of Interest</h3> None declared
A phase I study with an expansion cohort of the combination of ipilimumab and brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma: A trial of the ECOG-ACRIN Cancer Research Group (E4412).
Authors: Catherine S. Magid Diefenbach, Hailun Li, Brad S. Kahl, Michael J. Robertson, Jonathan Cohen, Ranjana H. Advani, Richard Ambinder, Timothy S. Fenske, Stephen Maxted Ansell
Journal: Journal of Clinical Oncology (2015)

TPS8602 Background: E4412 is a phase 1 study with an expansion cohort of the combination of brentuximab vedotin (BV) and ipilumumab in patients with relapsed and refractory Hodgkin lymphoma (HL). Despite advances in chemotherapy, relapsed HL remains a significant problem, with over 1,000 lives lost annually. HL has a unique biology in which a small number of malignant Hodgkin Reed-Sternberg (HRS) cells propagate an immunosuppressive microenvironment. In E4412 the peri-tumoral T cells are primed with ipilimumab and the HRS cells targeted with the CD30 specific antibody-drug conjugate BV. We hypothesize that this immuno-chemotherapy approach may overcome tumor cell resistance and deepen clinical response. E4412 is the first clinical trial targeting the HL tumor microenvironment in conjunction with HRS tumor cell targeting. Methods: E4412 is currently open at 7 sites within ECOG. A modified 3+3 dose escalation design is used; 6 patients are tested at each dose level if no more than one DLT is observed in the first 3 patients. All DLT are evaluated within the first cycle (1 cycle = 21 days). The primary endpoint is the maximum tolerated dose (MTD) of the combination. Secondary endpoints include complete response (CR) rate, partial response (PR) rate, overall response (ORR) rate, duration of response (DOR), overall survival (OS) and progression-free survival (PFS). Response rates are reported along 95% confidence intervals. DOR, PFS and OS are estimated using Kaplan-Meier methodology. BV is given at 1.8mg/kg and ipilimumab at 1mg/kg (cohort 1) and 3mg/kg (cohort 2) every 21 days for 4 cycles. From cycle 5 BV is given q 21 days, and ipilimumab on cycles 8, 12, and 16. Once the MTD is established, 9 patients are treated in an expansion cohort with BV at 1.8mg/kg and ipilumumab at MTD. Eligibility Criteria include: age > 18, relapsed HL, measurable disease, no prior relapse on BV, no active GVHD or immunosuppressive therapy, ECOG 0-2, FEV1/FVC > 60%, hematology and chemistry labs within standard parameters, no uncontrolled systemic illness. Cohorts I and II have been completed. Expansion cohort enrollment opened on February 3rd, 2015. Clinical trial information: NCT01896999.
Abstract P074: Loss of Function of TRPC4 Protects Against Cardiac Dysfunction Progression After Myocardial Infarction
Authors: Hongyu Zhang, Catherine Makarewich, Erhe Gao, Hajime Kubo, Hui Gao, Fang Wang, Remus Berretta, Walter Koch, Jeffery Molkentin, Steven Houser
Journal: Circulation Research (2011)

The source of Ca 2+ to hypertrophic signaling after myocardial infarction (MI) is not clearly defined. Transient Receptor Potential Canonical (TRPC) channels could be an important source of hypertrophic Ca 2+ after MI. The objective of this study was to determine if TRPC 4 is a major source of Ca 2+ influx mediating cardiac dysfunction after MI. Methods: Cardiac-specific transgenic mice that express a dominant-negative (dn) TRPC4 that reduces the activity of the TRPC1/4/5 subfamily of channels in the heart were used. MI was produced and in-vivo cardiac function was measured with ECHO. Myocytes were isolated and isoproterenol (ISO) effects on LTCC Current ( I Ca-L ), fractional shortening (FS) and Ca 2+ transients were measured 6 weeks after MI. Results: Baseline ejection fraction (EF) and fractional shortening (FS) were greater in (dn) TRPC4 vs. WT mice. Two weeks after MI, EF and FS were significantly decreased in all animals (WT: 37.1% and 18.2%; (dn) TRPC4: 41.7% and 20.5%), but there was no significant difference between WT and (dn) TRPC4 mice. Six weeks after MI, EF and FS were significant greater in (dn) TRPC4 compared with WT mice (WT: 37.4% and 18.2%; (dn) TRPC4: 52.2% and 27.4%). Heart weight and lung weight were significantly increased after 2 weeks MI, but there were significant lower heart and lung weight in (dn) TRPC4 vs. WT mice after 6 weeks MI. I Ca-L [[Unsupported Character - Codename &amp;shy;]] after 6 weeks MI was smaller than that in sham myocytes, and there was no significant difference between (dn) TRPC4 and WT myocytes. Contractions and Ca 2+ transients were significantly greater in sham and post-MI (dn) TRPC4 vs. WT myocytes. ISO increased contractions and Ca 2+ transients to a similar extent in all myocytes. Conclusions: (dn) TRPC4 mice have greater baseline cardiac and myocyte function. While initial effects of MI were similar to control, there was improved function in these mice by 6 weeks. These results suggest that blocking TRPC4 after MI may reduce pathological cardiac remodeling.