Progress towards Mechanism-Based Treatment for Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplastic anemia, characterized by macrocytic anemia, reticulocytopenia, and severely reduced numbers of erythroid precursors in the bone marrow. For more than fifty years, glucocorticoids have remained the main option for pharmacological treatment of DBA. While continuous glucocorticoid administration increases hemoglobin levels in a majority of DBA patients, it also causes severe side effects. There is therefore a great need for more specific and effective treatments to boost or replace the use of glucocorticoids. Over the years, many alternative therapies have been tried out, but most of them have shown to be ineffective. Here we review previous and current attempts to develop such alternative therapies for DBA. We further discuss how emerging knowledge regarding the pathological mechanism in DBA and the therapeutic mechanism of glucocorticoids treatment may reveal novel drug targets for DBA treatment

Pion photoproduction cross section at large momentum transfer

The Real Compton Scattering experiment was performed in all A at the Thomas Jefferson National Accelerator Facility. It was designed to measure, for Compton scattering and π 0 -photoproduction, the differential cross section over a range of kinematic points and the polarisation transfer to the proton at a single kinematic point. The full range of the experiment in Mandelstam variables t and s was 1.64−6.46 GeV 2 and 4.82−10.92 GeV 2 respectively with beam energies of 2−6 GeV. The motivation for the experiment is to test the cross section and polarisation trans- fer predictions of perturbative QCD versus that of predictions from Generalised Parton Distribution models. This thesis will give an overview of the pertinent theory, experimental setup in Hall A and the extracting of the π 0 -photoproduction cross section

The Role of IGF-1 for Fracture Risk in Men

Growth hormone and insulin-like growth factor-1 (IGF-1) are essential for the achievement of normal longitudinal bone growth and bone mass. Preclinical studies using various knockout models have shown that both endocrine (mostly liver-derived) IGF-1 and bone-derived IGF-1 contribute to normal longitudinal skeletal growth and cortical bone size. Since bone size is an important determinant of bone strength, and hence fracture risk, we evaluated the predictive role of serum IGF-1 for fracture risk. The population-based Osteoporotic Fractures in Men Sweden cohort recently showed for the first time that older men with low serum IGF-1 levels have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. This association between serum IGF-1 and incident fracture risk is partly mediated via bone mineral density. Future studies are required to identify the mechanisms by which endocrine and local IGF-1 regulate skeletal growth and bone size. In addition, possible mediators affecting the impact of IGF-1 on fractures in men remain to be elucidated

Ekonomisk värdering av återanskaffningskostnaden för träd - Alnarpsmodellen 2.0

Betydelsen av att kunna ekonomiskt värdera träd har alltid varit ett viktigt redskap för att dels kunna försvara trädens betydelse, men även för att hindra skadegörelse eller sätta viten vid byggnation. Denna rapport redogör för arbetet med en ny värderingsmodell, Alnarpsmodellen, som är tänkt att användas som en nationell värderingsmodell för träd som inte är planterade i produktionssyfte. Modellen bygger på den prisutveckling som finns för olika trädstorlekar i plantskolorna och värdet justeras sedan endast på grund av eventuella skador eller minskad vitalitet, tills sist adderas ett schablonvärde för planterings- och etableringskostnaden. Modellen bygger alltså på mycket få parametrar som samtliga är väl förankrade i verkliga prissättningar av träd. Modellen fungerar för samtliga trädslag som finns att tillgå i plantskolor och den bygger endast på objektiva värden. Förhoppningen är att Alnarpsmodellen ska fungera väl i rättsliga sammanhang där subjektiva värden ofta ifrågasätts

Trädvärdering i stadsmiljö

Att kunna värdera urbana träd ekonomiskt är viktigt för att försvara trädens betydelse i stadsmiljön samt för att förhindra skadegörelse och kunna sätta viten för trädskador vid byggnation. Detta Movium Fakta redogör för arbetet med en ny värderingsmodell framtagen vid SLU i Alnarp – Alnarpsmodellen – som är tänkt att användas på nationell nivå för ekonomisk värdering av park- och gatuträd

Right ventricular performance after valve repair for chronic degenerative mitral regurgitation.

Our aim was to assess right ventricular (RV) performance after mitral valve repair by use of RV focused echocardiography and to evaluate the influence of elevated pulmonary artery systolic pressure (PASP) on RV recovery

Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury

Producción CientíficaObjective: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype. Approach and Results: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function. Conclusions: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells.Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional (grant RD12/0042/0006)Ministerio de Economía, Industria y Competitividad (grants BFU2010-15898 and BFU2013-45867-R

Thrombus aspiration during ST-segment elevation myocardial infarction.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality.We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days.No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI.Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.).Swedish Research Council, Swedish Association of Local Authorities and Regions, Terumo Medical Corporation, Medtronic, Vascular Solutions, Swedish Heart-Lung Foundation/20100178/ B0010401 Biotronik, Stentys, Abbott Vascular, St. Jude Medical, Boston Scientific, EPS Vascular, Cardiac Dimensions, AstraZeneca, Edwards Lifesciences