Respiratory gases, acid-base balance, and lactate and hemoglobin concentrations were measured in 14 fetal blood samples between 17 and 21 weeks of gestation. The samples were obtained at the time of ...fetoscopy performed for prenatal diagnosis. Results have been compared with two reference groups: (a) 4 patients in whom fetal cord blood sampling was performed at 32-36 weeks of gestation, and (b) 10 patients at the time of elective cesarean section, 35-39 weeks. PO2 and oxygen saturations were significantly higher and hemoglobin concentration lower in the mid-gestation fetus. Acid-base balance was not significantly different. There was a significant correlation between maternal and fetal hemoglobin concentrations. The oxygen affinity of fetal blood was not significantly different from that described for term fetuses with a oxygen saturation of less than 90%.
Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The ...objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis.
Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start).
Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis.
This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.
The switch from cartilage template to bone during endochondral ossification of the growth plate requires a dynamic and close interaction between cartilage and the developing vasculature. Vascular ...invasion of the primarily avascular hypertrophic chondrocyte zone brings chondroclasts, osteoblast- and endothelial precursor cells into future centres of ossification.Vascularization of human growth plates of polydactylic digits was studied by immunohistochemistry, confocal-laser-scanning-microscopy and RT-qPCR using markers specific for endothelial cells CD34 and CD31, smooth muscle cells α-SMA, endothelial progenitor cells CD133, CXCR4, VEGFR-2 and mesenchymal progenitor cells CD90 and CD105. In addition, morphometric analysis was performed to quantify RUNX2+ and DLX5+ hypertrophic chondrocytes, RANK+ chondro- and osteoclasts, and CD133+ progenitors in different zones of the growth plate.
New vessels in ossification centres were formed by sprouting of CD34+ endothelial cells that did not co-express the mature endothelial cell marker CD31. These immature vessels in the growth plate showed no abluminal coverage with α-SMA+ smooth muscle cells, but in their close proximity single CD133+ precursor cells were found that did not express VEGFR-2, a marker for endothelial lineage commitment. In periosteum and in the perichondrial groove of Ranvier that harboured CD90+/CD105+ chondro-progenitors, in contrast, mature vessels were found stabilized by α-SMA+ smooth muscle cells.
Vascularization of ossification centres of the growth plate was mediated by sprouting of capillaries coming from the bone collar or by intussusception rather than by de-novo vessel formation involving endothelial progenitor cells. Vascular invasion of the joint anlage was temporally delayed compared to the surrounding joint tissue.
Diseases of intestinal inflammation like necrotizing enterocolitis (NEC) are associated with impaired epithelial barrier integrity and the sustained release of intestinal nitric oxide (NO). NO ...modifies the cytoskeletal regulator RhoA-GTPase, suggesting that NO could affect barrier healing by inhibiting intestinal restitution. We now hypothesize that NO inhibits enterocyte migration through RhoA-GTPase and sought to determine the pathways involved. The induction of NEC was associated with increased enterocyte NO release and impaired migration of bromodeoxyuridine-labeled enterocytes from terminal ileal crypts to villus tips. In IEC-6 enterocytes, NO significantly inhibited enterocyte migration and activated RhoA-GTPase while increasing the formation of stress fibers. In parallel, exposure of IEC-6 cells to NO increased the phosphorylation of focal adhesion kinase (pFAK) and caused a striking increase in cell-matrix adhesiveness, suggesting a mechanism by which NO could impair enterocyte migration. NEC was associated with increased expression of pFAK in the terminal ileal mucosa of wild-type mice and a corresponding increase in disease severity compared with inducible NO synthase knockout mice, confirming the dependence of NO for FAK phosphorylation in vivo and its role in the pathogenesis of NEC. Strikingly, inhibition of the protein tyrosine phosphatase SHP-2 in IEC-6 cells prevented the activation of RhoA by NO, restored focal adhesions, and reversed the inhibitory effects of NO on enterocyte migration. These data indicate that NO impairs mucosal healing by inhibiting enterocyte migration through activation of RhoA in a SHP-2-dependent manner and support a possible role for SHP-2 as a therapeutic target in diseases of intestinal inflammation like NEC.
Provider: - Institution: - Data provided by Europeana Collections- Der vorliegende Bericht enthält eine Einführung in das laufende Forschungsprojekt "Identität und Akkulturation von Migranten", in ...welchem vor allem der Stellenwert der Einbürgerung als Integrationsmaßnahme untersucht wird. Der Bericht stellt die Ergebnisse der Hauptanalysegruppe dar, die sich aus im ersten Halbjahr des Jahres 2007 eingebürgerten Migranten und Migrantinnen zusammensetzt. Es wurden hierzu ca. 300 Neu-Deutsche regional breit gestreut zu ihrer individuellen Disposition und Identität, zu spezifischen Akkulturationsorientierungen, ihrem Einbürgerungsprozess, ihren Einwanderungsmotiven und ihren soziokulturellen Differenzen befragt. Es waren Personen zwischen 16 und 70 Jahren vertreten, die aus verschiedenen Herkunftskulturen stammen und sich unterschiedlich lang in Deutschland aufhalten. Die Untersuchung widmet sich insbesondere der Rolle der Staatsbürgerschaft: Werden zum Beispiel Zugehörigkeitsgefühl zur und Integrationsbereitschaft in die deutsche Gesellschaft durch den Prozess der Einbürgerung gefördert oder ist der deutsche Pass nur ein "Stück Papier" und der/die "Neue Deutsche" bleibt weiterhin ein Türke/eine Türkin mit deutschem Pass? (ICI2)- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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