Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded) allograft

Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP) and tricalcium phosphate (TCP), respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT) analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated

Evaluation of the Diurnal Cycle in the Atmospheric Boundary Layer Over Land as Represented by a Variety of Single-Column Models: The Second GABLS Experiment

We present the main results from the second model intercomparison within the GEWEX (Global Energy andWater cycle EXperiment) Atmospheric Boundary Layer Study (GABLS). The target is to examine the diurnal cycle over land in today’s numerical weather prediction and climate models for operational and research purposes. The set-up of the case is based on observations taken during the Cooperative Atmosphere-Surface Exchange Study-1999 (CASES-99), which was held in Kansas, USA in the early autumn with a strong diurnal cycle with no clouds present. The models are forced with a constant geostrophic wind, prescribed surface temperature and large-scale divergence. Results from 30 different model simulations and one large-eddy simulation (LES) are analyzed and compared with observations. Even though the surface temperature is prescribed, the models give variable near-surface air temperatures. This, in turn, gives rise to differences in low-level stability affecting the turbulence and the turbulent heat fluxes. The increase in modelled upward sensible heat flux during the morning transition is typically too weak and the growth of the convective boundary layer before noon is too slow. This is related to weak modelled nearsurface winds during the morning hours. The agreement between the models, the LES and observations is the best during the late afternoon. From this intercomparison study, we find that modelling the diurnal cycle is still a big challenge. For the convective part of the diurnal cycle, some of the first-order schemes perform somewhat better while the turbulent kinetic energy (TKE) schemes tend to be slightly better during nighttime conditions. Finer vertical resolution tends to improve results to some extent, but is certainly not the solution to all the deficiencies identifie

Quantification and clinical validation of the selective MET kinase inhibitor DO-2 and its metabolites DO-5 and M3 in human plasma

DO-2 is a highly selective MNNG HOS transforming (MET) inhibitor. This deuterated drug is thought to diminish the formation of the Aldehyde Oxidase 1 inactive metabolite M3. For various reasons, quantification of DO-2 and its metabolites M3 and DO-5 is highly relevant. In this study, we present an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to quantify DO-2, M3 and DO-5. Rolipram served as the internal standard. Aliquots of 25 µL were mixed with 100 µL internal standard consisting of 10 ng/mL rolipram in acetonitrile. Separation of the analytes was achieved on an Acquity UPLC ® HSS T3 column, utilizing gradient elution with water/formic acid and acetonitrile/formic acid at a flow-rate of 0.400 mL/min. Calibration curves were linear in the range of 1.00 – 1000 ng/mL for DO-2 and DO-5, and 2.00 – 2000 ng/mL for M3 in human plasma. The within-run and between-run precisions of DO-2, DO-5 and M3, also at the level of the LLQ, were within 12.1%, while the accuracy ranged from 89.5 to 108.7%. All values for accuracy, within-run and between-run precisions met the criteria set by the Food and Drug Administration. The method was effectively employed in the analysis of samples obtained from a clinical trial.</p

Quantification and clinical validation of the selective MET kinase inhibitor DO-2 and its metabolites DO-5 and M3 in human plasma

DO-2 is a highly selective MNNG HOS transforming (MET) inhibitor. This deuterated drug is thought to diminish the formation of the Aldehyde Oxidase 1 inactive metabolite M3. For various reasons, quantification of DO-2 and its metabolites M3 and DO-5 is highly relevant. In this study, we present an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to quantify DO-2, M3 and DO-5. Rolipram served as the internal standard. Aliquots of 25 µL were mixed with 100 µL internal standard consisting of 10 ng/mL rolipram in acetonitrile. Separation of the analytes was achieved on an Acquity UPLC ® HSS T3 column, utilizing gradient elution with water/formic acid and acetonitrile/formic acid at a flow-rate of 0.400 mL/min. Calibration curves were linear in the range of 1.00 – 1000 ng/mL for DO-2 and DO-5, and 2.00 – 2000 ng/mL for M3 in human plasma. The within-run and between-run precisions of DO-2, DO-5 and M3, also at the level of the LLQ, were within 12.1%, while the accuracy ranged from 89.5 to 108.7%. All values for accuracy, within-run and between-run precisions met the criteria set by the Food and Drug Administration. The method was effectively employed in the analysis of samples obtained from a clinical trial.</p

Environmental determinants of fruit and vegetable consumption among adults: a systematic review

The current ecological approach in health behaviour research recognises that health behaviour needs to be understood in a broad environmental context. This has led to an exponential increase in the number of studies on this topic. It is the aim of this systematic review to summarise the existing empirical evidence pertaining to environmental influences on fruit and vegetable (FV) consumption. The environment was defined as ‘all factors external to the individual’. Scientific databases and reference lists of selected papers were systematically searched for observational studies among adults (18–60 years old), published in English between 1 January 1980 and 31 December 2004, with environmental factor(s) as independent factor(s), and fruit intake, vegetable intake or FV intake combined as one outcome measure as dependent factor(s). Findings showed there was a great diversity in the environmental factors studied, but that the number of replicated studies for each determinant was limited. Most evidence was found for household income, as people with lower household incomes consistently had a lower FV consumption. Married people had higher intakes than those who were single, whereas having children showed mixed results. Good local availability (e.g. access to one’s own vegetable garden, having low food insecurity) seemed to exert a positive influence on intake. Regarding the development of interventions, improved opportunities for sufficient FV consumption among low-income households are likely to lead to improved intakes. For all other environmental factors, more replicated studies are required to examine their influence on FV intake