Ottesenmarks0340

These results may provide a broader understanding of the potential mechanism of biomineralization and be critical in the design of biomimetic scaffolds for bone tissue engineering. Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma. BACKGROUND Immunoglobulins are widely used across multiple therapeutic areas such as immunodeficiency syndromes, infection and autoimmune diseases. The pharmacokinetics (PK) of immunoglobulins are well characterized in adults, but very little is known about the PK of immunoglobulins in neonates and infants. OBJECTIVE The objective of the present study was to characterize the PK of Gammagard, an immunoglobulin, in very low birth weight preterm neonates. METHOD Gammagard concentration-time data from very low birth weight neonates (bodyweight range 0.78-1.38 kg, n = 20) following intravenous administration of 500 mg/kg and 750 mg/kg were obtained from the literature. The data were analyzed with and without baseline correction using extensive blood samples (8 blood samples). Model-independent (non-compartmental) analysis was used to characterize the PK of Gammagard. RESULTS Based on uncorrected baseline concentration-time data, the clearance and half-life of Gammagard were 3.1 ± 0.7 mL/day and 22 ± 6 days, respectively. Based on corrected baseline concentration-time data, the clearance and half-life of Gammagard were 20.2 ± 7.4 mL/day and 5.3 ± 2.2 days, respectively. CONCLUSION The dose of immunoglobulins should be adjusted based on the PK of baseline corrected rather than baseline uncorrected profiles because baseline corrected PK parameters especially half-life reconciles with PK principles. OBJECTIVE Pristimerin is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been described. In this study, to investigate the therapeutic mechanism of pristimerin, we examined the effect of pristimerin on TNF-α-induced endothelial inflammatory response both in vitro and in vivo. METHODS Leukocyte-endothelium Adhesion Assay was use to evaluate the endothelial cell-monocyte interaction. Western blotting was used to confirm protein expression. NF-κB p65 nuclear translocation in endothelial cells was detected using immunofluorescent microscopy. In vivo leukocyte infiltration was evaluated using acute lung inflammation model. RESULTS Pristimerin profoundly inhibited TNF-α-induced adhesion of monocytes to human endothelial cells and the leukocyte transmigration. Pristimerin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)). Pristimerin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, pristimerin also suppressed the TNF-α-activated Nuclear factor kappa B (NF-κB) activation. CONCLUSIONS Pristimerin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of NF-κB activation, which may have a potential therapeutic effects for inflammatory vascular diseases. V.The study aimed to develop a novel and reliable age estimation method using three-dimensional surface area analyses of maxillary canine apices among Malaysian children using CBCT data. A validated regression equation for age estimation was derived and correlation between chronological age and the surface areas of the developing maxillary canine's apices were investigated. Variations based on ethnicities, gender and status of root development were also investigated in terms of fit to the age estimation model. CBCT images of the patients ranging in age from 7 to 14 years were included in the study. Training sample of 191 intact permanent maxillary canines was selected from 191 CBCT images belonging to 100 Malays and 91 Chinese. Moreover, an independent validation sample of 96 permanent maxillary canines was selected from 96 CBCT images belonging to 48 Malays and 48 Chinese. Three-dimensional image modeling and surface area analyses of the developing canine's apices were performed using Mimics and 3-Matics software. A strong correlation (r = 0.978) was observed between chronological age and surface area of the developing maxillary canine's apices. 95.6% of the variation in age can be explained by surface area of canine's apices, gender and status of the root development (open/closed apices). However, ethnicity did not contributed to the fit of age estimation model. Female showed advanced development as compared to male. Mean absolute error values indicated that this newly developed 3D surface area analyses of canine apex can be used as a reliable method for age estimation among Malaysian children. Exposure therapy is a well-studied and highly efficacious treatment for phobic disorders. Although the neurobiological model of fear is well underpinned by various studies, the mechanisms of exposure therapy are still under discussion. Partly, this is due to the fact that most neurophysiological methods like fMRI are not able to be used in the natural therapeutic settings. The current study used in situ measurements of cortical blood oxygenation (O2Hb) during exposure therapy by means of functional near-infrared spectroscopy. 37 subjects (N = 30 completers) underwent exposure therapy during 5 adapted sessions in which subjects were exposed to Tegenaria Domestica (domestic house spider - experimental condition) and Dendrobaena Veneta/ Eisenaia hortensis (red earthworm - control condition). Compared to the control condition, patients showed higher O2Hb levels in the anticipation and exposure phase of spider exposure in areas of the cognitive control network (CCN). Further, significant decreases in O2Hb were observed during the session accompanied by reductions in fear related symptoms. However, while symptoms decreased in a linear quadratic manner, with higher reductions in the beginning of the session, CCN activity decreased linearly. Further, higher anxiety at the beginning of session one was associated with increased O2Hb in the CCN. This association decreased within the following sessions. The current study sheds light on the neuronal mechanisms of exposure therapy. The results are discussed in light of a phase model of exposure therapy that posits a role of cognitive control in the beginning and routine learning at the end of the therapy session. Human rhinovirus (hRV) is a predominant respiratory viral pathogen. The determinants that lead to adverse clinical outcomes in hospitalized patients are unclear. Our objective was to analyze the epidemiological and clinical characteristics of hRV infections in a hospitalized population and to compare non-severe and severe infections. The study was based on data from all patients with a respiratory episode admitted to Hospital from October 2015 to September 2016. Epalrestat order During the study period, out of 2465 respiratory episodes, 434 were detected positive for hRV. Most of the coinfections involved the respiratory syncytial virus (RSV) and very few influenza viruses. A possible interference between rhinovirus and influenza virus is suggested. Airway involvement was present in a large part of hRV infections with 28.4 % (n = 48/169) of bronchiolitis and 3.6 % (n = 6/169) of bronchitis. One third of patients had at least one of the following severity criteria need for oxygen therapy, hospitalization ≥ 5 days, and admission to the ICU. On multivariate analysis, a respiratory co-infection with RSV and the presence of a chronic respiratory disease (including a history of asthma) were shown to be independent risk factors for the onset of a severe infection in patients ≤ 2 years old. In a case control study based on 70 patients, hRV-A was the predominant lineage, followed closely by hRV-C. High viral load or viral genotypes were not associated with severe infection. PURPOSE EPID dosimetry in the Unity MR-Linac system allows for reconstruction of absolute dose distributions within the patient geometry. Dose reconstruction is accurate for the parts of the beam arriving at the EPID through the MRI central unattenuated region, free of gradient coils, resulting in a maximum field size of ~10 × 22 cm2 at isocentre. The purpose of this study is to develop a Deep Learning-based method to improve the accuracy of 2D EPID reconstructed dose distributions outside this central region, accounting for the effects of the extra attenuation and scatter. METHODS A U-Net was trained to correct EPID dose images calculated at the isocenter inside a cylindrical phantom using the corresponding TPS dose images as ground truth for training. The model was evaluated using a 5-fold cross validation procedure. The clinical validity of the U-Net corrected dose images (the so-called DEEPID dose images) was assessed with in vivo verification data of 45 large rectum IMRT fields. The sensitivity of DEEPID to leaf bank position errors (±1.5 mm) and ±5% MU delivery errors was also tested. RESULTS Compared to the TPS, in vivo 2D DEEPID dose images showed an average γ-pass rate of 90.2% (72.6%-99.4%) outside the central unattenuated region. Without DEEPID correction, this number was 44.5% (4.0%-78.4%). DEEPID correctly detected the introduced delivery errors. CONCLUSIONS DEEPID allows for accurate dose reconstruction using the entire EPID image, thus enabling dosimetric verification for field sizes up to ~19 × 22 cm2 at isocentre. The method can be used to detect clinically relevant errors.