-
Armstrong Deleon heeft een update geplaatst 3 maanden, 4 weken geleden
Advances in systems biology and whole-cell modelling demand increasingly comprehensive mathematical models of cellular biochemistry. Such models require the development of simplified representations of specific processes which capture essential biophysical features but without unnecessarily complexity. Recently there has been renewed interest in thermodynamically-based modelling of cellular processes. Here we present an approach to developing of simplified yet thermodynamically consistent (hence physically plausible) models which can readily be incorporated into large scale biochemical descriptions but which do not require full mechanistic detail of the underlying processes. We illustrate the approach through development of a simplified, physically plausible model of the mitochondrial electron transport chain and show that the simplified model behaves like the full system. We present a physiologically-based pharmacokinetic modeling platform capable of simulating the biodistribution of different therapeutic agents, including cells, their interactions within the immune system, redistribution across lymphoid compartments, and infiltration into tumor tissues. This transport-based platform comprises a distinctive implementation of a tumor compartment with spatial heterogeneity which enables the modeling of tumors of different size, necrotic state, and agent infiltration capacity. We provide three validating and three exploratory examples that illustrate the capabilities of the proposed approach. The results show that the model can recapitulate immune cell balance across different compartments, respond to antigen stimulation, simulate immune vaccine effects, and immune cell infiltration to tumors. Based on the results, the model can be used to study problems pertinent to current immunotherapies and has the potential to assist medical techniques that rely on the transport of biological species. OBJECTIVES This study investigated the effect of Liraglutide (LIRA) on osteogenic differentiation of human periodontal ligament cells (hPDLCs) stimulated by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) and its mechanismin in vitro. Further, investigated the osteoprotective and anti-inflammatory effects of LIRA in periodontitis in vivo. MATERIALS AND METHODS ALP staining, Alizarin red staining(AR-S), qRT-PCR, Western Blot, and immunofluorescence staining were used to elucidate the effect of LIRA on osteogenesis of hPDLCs. Western Blot was performed to evaluate the Wnt/β-catenin signaling-related protein. Moreover, male Wistar rats model of periodontitis were established to assess the anti-inflammatory and osteoprotective effect of LIRA in vivo. RESULTS After LIRA treatment, the formation of mineralized nodules was increased, the expression of ALP and Runx2 were upregulated. https://www.selleckchem.com/products/LBH-589.html Moreover, Pg-LPS strongly activated the Wnt/β-catenin signaling pathway and reduced the osteogenesis of hPDLCs. But these effects were reversed by LIRA. The in vivo results showed that treatment with LIRA resulted in reduced inflammatory cell infiltration in periodontal tissues and decreased concentrations of TNF-α, IL-1β, and IL-6, and it reduced alveolar bone resorption. CONCLUSIONS Systemic administration of LIRA solution is a potential treatment for reducing inflammation and bone loss in periodontal disease. This suggests that LIRA can be used as a potential drug for the treatment of periodontitis. CLINICAL SIGNIFICANCE We showed that systemic administration of LIRA can have a beneficial effect in periodontitis. It can be used as a potential drug for the treatment of periodontitis. OBJECTIVES To examine the current arrangements and trends in the teaching of removable partial dentures (RPDs) in dental schools in Oceania. METHODS A validated and trialled 30-item electronic survey was sent via e-mail to 12 dental schools in Oceania that offered undergraduate dentistry. The survey explored various aspects of the teaching of RPDs in preclinical and clinical courses including educational content and process, staff members involved, facilities and techniques utilized, clinical requirements, coursework evaluation and perceived challenges to RPD teaching. RESULTS The response rate of the survey was 75 % (n = 9). All respondent schools taught a preclinical course in RPD design and production, with the majority (67 %) starting the clinical provision of RPD patients in Year 3. The mean duration of the course was 63 h for hands-on activities and 23 h for didactic teaching. The courses were mainly taught by senior lecturers. On average, students made four units of acrylic RPD and two cobalt-chromium RPDs during the course. All respondent schools taught prescription writing for RPD. The majority of schools (n = 8) stated that they had an adequate patient pool for students to treat. Lack of adequately trained staff for teaching and pressure on teaching time from other sources were the most commonly reported challenges. CONCLUSION The structure and content of RPD courses in dental schools of Oceania provide an adequate level of competence on the subject, and is broadly similar to other parts of the world. Plans should be in place to maintain and improve the quality of educational programmes to keep pace with growing student numbers and the rapidly evolving profession. CLINICAL SIGNIFICANCE With increasing numbers of patients presenting to general dental practitioners requiring complex RPDs, it is paramount that undergraduate training programs produce graduates with the competencies necessary to care for such patients to a high standard. INTRODUCTION Non-linguistic properties of speech are widely heterogeneous and require complex neurological integration. The association between white matter integrity and the severity of dysarthria was investigated in a group of patients diagnosed with amyotrophic lateral sclerosis (ALS). METHODS Thirty-six patients diagnosed with amyotrophic lateral sclerosis completed a magnetic resonance imaging protocol inclusive of diffusion-weighted images. A clinical assessment of pneumo-phono-articulatory abilities was conducted for each patient, and a composite score of residual speech capacity was calculated. Tract-Based Spatial Statistics was carried out to model the potential association between residual speech capacity and microstructural properties of white matter (fractional anisotropy, mean and radial diffusivity). RESULTS A significant negative association was found between residual speech capacity and mean diffusivity in a large white matter cluster located in frontal, parietal and right temporal regions. These subcortical areas were characterised by pathological microstructural disruption, as revealed by post hoc analyses.