Croup: diagnosis and treatment

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Epidermal growth factor signalling pathway in endochondral ossification. an evidence-based narrative review

During endochondral bone development, a complex process that leads to the formation of the majority of skeletal elements, mesenchymal cells condense, differentiating into chondrocytes and producing the foetal growth plate. Chondrocytes progressively hypertrophy, induce angiogenesis and are then gradually replaced by bone. Epidermal Growth Factor (EGF), one of many growth factors, is the prototype of the EGF-ligand family, which comprises several proteins involved in cell proliferation, migration and survival. In bone, EGF pathway signalling finely tunes the first steps of chondrogenesis by maintaining mesenchymal cells in an undifferentiated stage, and by promoting hypertrophic cartilage replacement. Moreover, EGF signalling modulates bone homeostasis by stimulating osteoblast and osteoclast proliferation, and by regulating osteoblast differentiation under specific spatial and temporal conditions. This evidence-based narrative review describes the EGF pathway in bone metabolism and endochondral bone development. This comprehensive description may be useful in light of possible clinical applications in orthopaedic practice. A deeper knowledge of the role of EGF in bone may be useful in musculoskeletal conditions which may benefit from the modulation of this signalling pathway. Key messages The EGF pathway is involved in bone metabolism. EGF signalling is essential in the very early stages of limb development by maintaining cells in an undifferentiated stage. EGF pathway positively regulates chondrocyte proliferation, negatively modulates hypertrophy, and favours cartilage replacement by bone. EGF and EGF-like proteins finely tune the proliferation and differentiation of bone tissue cells, and they also regulate the initial phases of endochondral ossification

Effect of Chemically Induced Hypoxia on Osteogenic and Angiogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in Direct Coculture

Bone is an active tissue where bone mineralization and resorption occur simultaneously. In the case of fracture, there are numerous factors required to facilitate bone healing including precursor cells and blood vessels. To evaluate the interaction between bone marrow-derived mesenchymal stem cells (BMSC)-the precursor cells able to differentiate into bone-forming cells and human umbilical vein endothelial cells (HUVEC)-a cell source widely used for the study of blood vessels. We performed direct coculture of BMSC and HUVEC in normoxia and chemically induced hypoxia using Cobalt(II) chloride and Dimethyloxaloylglycine and in the condition where oxygen level was maintained at 1% as well. Cell proliferation was analyzed by crystal violet staining. Osteogenesis was examined by Alizarin Red and Collagen type I staining. Expression of angiogenic factor-vascular endothelial growth factor (VEGF) and endothelial marker-von Willebrand factor (VWF) were demonstrated by immunohistochemistry and enzyme-linked immunosorbent assay. The quantitative polymerase chain reaction was also used to evaluate gene expression. The results showed that coculture in normoxia could retain both osteogenic differentiation and endothelial markers while hypoxic condition limits cell proliferation and osteogenesis but favors the angiogenic function even after 1 of day treatment

Hypertrophic cardiomyopathy: two-dimensional echocardiographic score versus clinical and electrocardiographic findings.

The severity and site of hypertrophy is important in determining the clinical picture and the natural history of hypertrophic cardiomyopathy (HCM). We evaluated left ventricular hypertrophy by means of two-dimensional echocardiographic score and score index, and correlated these findings with symptoms, electrovector-cardiographic data, and ventricular arrhythmias. A total of 42 patients with HCM were studied by clinical examination, ECG, VCG, M-mode and 2D echocardiography, and 24-h Holter monitoring. The extent and severity of the hypertrophic process were calculated by a score system. The left ventricle was divided into 11 segments and a hypertrophic score (HS) was given to each segment. A hypertrophy score index (HSI) was also calculated by dividing the number of hypertrophied segments by 13. No correlation was found between symptoms and HS and HSI, nor ECG-VCG abnormalities and HS and HSI. A statistically significant relationship between the severity of ventricular arrhythmias and HS and HSI was found (p less than 0.01). The mechanism responsible for ventricular tachyarrhythmias in severe and diffuse hypertrophy might reside in the high intraventricular pressures which produce or worsen areas of myocardial ischemia

Beta-tricalcium phosphate ceramic triggers fast and robust bone formation by human mesenchymal stem cells

Due to their osteoconductive and inductive properties, a variety of calcium phosphate (CaP) scaffolds are commonly used in orthopaedics as graft material to heal bone defects. In this study, we have used two CaP scaffolds with different hydroxyapatite (HA) and \u3b2-tricalcium phosphate (\u3b2-TCP) ratios (MBCP\uae; 60/40 and MBCP+\uae; 20/80) to investigate their intrinsic capacity to favour human bone marrow stem cells (hBMSCs) osteogenic differentiation capacity. We report that MBCP+\uae showed in in vitro culture model a higher rate of calcium ion release in comparison with MBCP\uae. In two defined coculture systems, the hBMSC seeded onto MBCP+\uae presented an increased amount of VEGF secretion, resulting in an enhanced endothelial cell proliferation and capillary formation compared with hBMSC seeded onto MBCP\uae. When both ceramics combined with hBMSC were implanted in a nude mouse model, we observed a faster osteogenic differentiation and enhancement mature bone deposition sustained by the presence of a vast host vasculature within the MBCP+\uae ceramics. Bone formation was observed in samples highly positive to the activation of calcium sensing receptor protein (CaSr) on the surface of seeded hBMSC that also shown higher BMP-2 protein expression. With these data we provide valuable insights in the possible mechanisms of ossification and angiogenesis by hBMSC that we believe to be primed by calcium ions released from CaP scaffolds. Evidences could lead to an optimization of ceramic scaffolds to prime bone repair

Evaluation of a new turbidimetric assay for von Willebrand factor activity useful in the general screening of von Willebrand disease

We evaluated a new assay (HemosIL™VWF Activity on ACL-Futura) in the screening of VWD. Samples from healthy donors and previously diagnosed VWD patients were blindly analyzed by this new activity assay and standard VWF:RCo. Results agreed and both assays showed a similar sensitivity for the screening of VWD

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012

Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

PLCγ03B3 binds Spry1 and Spry2. Overexpression of Spry decreased PLCγ03B3 activity and IP3 and DAG production, whereas Spry-deficient cells yielded more IP3. Spry overexpression inhibited T-cell receptor signaling and Spry1 null T-cells hyperproliferated with TCR ligation. Through action of PLCγ03B3, Spry may influence signaling through multiple receptors