Journal of Geophysical Research最新文献

Introduction: A 21 tobacco age of sale has been proposed for European nations.

Methods: We briefly review past studies of underage purchase policies and their enforcement.

Results: Past evaluations and modeling studies indicate important public health gains from 21 tobacco age of sale laws. However, further attention should be given to issues of compliance, the availability of social sources, and the breadth of coverage. In particular, the application of the law to e-cigarettes merits further attention.

Conclusions: Past literature indicates potential benefits of a 21 tobacco age of sale in terms of reducing tobacco use in European nations.

Implications: We review past studies of underage purchase laws, and the potential implications of applying that law to e-cigarettes. Past studies indicate the effectiveness of raising tobacco age of sale laws to 21. This law should be implemented and enforced in Europe.

Background: Adverse drug reactions and medication nonadherence are well-known causes of sub-optimal disease control and worsened disease outcomes in patients who are treated for type 2 diabetes. Metformin sustained release (SR) might reduce these adverse events and improve medication adherence via a simplified treatment regimen for metformin immediate release (IR)-intolerant patients.

Objectives: The aim of this study is to estimate the budget impact of metformin SR for the treatment of type 2 diabetes in the Netherlands, compared to the current standard of care (SoC) with metformin IR.

Methods: A budget impact model was built to represent the course of the disease and treatment pathway of type 2 diabetes patients eligible for metformin SR from a healthcare payer's perspective. Patients were considered eligible if they used less than 2000 mg metformin IR per day, but suffered from adverse events that might lead to therapy discontinuation, and if they were newly diagnosed with type 2 diabetes. The costs of type 2 diabetes treatment and related complications over a time horizon of 3 years were calculated. Univariate sensitivity analyses were conducted to show which parameters have the biggest influence on the budget impact.

Results: The budget impact analysis showed cost-savings of - €1,962,335 over a period of 3 years through implementation of metformin SR as an alternative to SoC with metformin IR. Savings were mostly driven by the delay of other, more expensive type 2 diabetes treatments, such as insulin. In sensitivity analyses, medication adherence and persistence appeared to have the biggest influence on the budget impact.

Conclusion: Metformin SR could potentially be a cost-saving alternative to metformin IR for the treatment of type 2 diabetes in the Netherlands, especially in patients experiencing adverse events with metformin IR. However, more research is needed to better predict the effect of using once-daily metformin, compared to multiple dosages, on medication adherence and persistence and to evaluate whether metformin SR really decreases the amount of adverse events.

Genome-scale metabolic models have been successfully applied to study the metabolism of multiple plant species in the past decade. While most existing genome-scale modelling studies have focussed on studying the metabolic behaviour of individual plant metabolic systems, there is an increasing focus on combining models of multiple tissues or organs to produce multi-tissue models that allow the investigation of metabolic interactions between tissues and organs. Multi-tissue metabolic models were constructed for multiple plants including Arabidopsis, barley, soybean and Setaria. These models were applied to study various aspects of plant physiology including the division of labour between organs, source and sink tissue relationship, growth of different tissues and organs and charge and proton balancing. In this review, we outline the process of constructing multi-tissue genome-scale metabolic models, discuss the strengths and challenges in using multi-tissue models, review the current status of plant multi-tissue and whole plant metabolic models and explore the approaches for integrating genome-scale metabolic models into multi-scale plant models.

Bone marrow (BM) Ang II (angiotensin II) is a major participant in the regulation of hematopoiesis and immunity. The novel tissue substrate Ang-(1-12) [angiotensin-(1-12)] and its cleaving enzyme chymase are an essential source of Ang II production in cardiac tissue. We hypothesized this noncanonical chymase-mediated Ang II-producing mechanism exists in the BM tissue. Immunohistostaining and flow cytometry confirmed the presence of Ang-(1-12) immunoreaction in the BM of SD (Sprague Dawley) rats. Chymase-mediated Ang II-producing activity in BM was ≈1000-fold higher than ACE (angiotensin-converting enzyme)-mediated Ang II-producing activity (4531±137 and 4.2±0.3 fmol/min per mg, respectively; n=6; P<0.001) and 280-fold higher than chymase activity in the left ventricle of 16.3±1.7 fmol/min per mg (P<0.001). Adding a selective chymase inhibitor, TEI-F00806, eliminated almost all ¹²⁵I-Ang II production. Flow cytometry demonstrated that delta median fluorescence intensity of chymase in cluster of differentiation 68 positive cells was significantly higher than that in cluster of differentiation 68 negative cells (1546±157 and 222±48 arbitrary units, respectively; P=0.0021). Cluster of differentiation 68 positive and side scatter low subsets, considered to be myeloid progenitors, express the highest chymase fluorescence intensity in rat BM. Chymase activity and cellular expression was similar in both male and female rats. In conclusion, myeloid lineage cells, especially myeloid progenitors, have an extraordinary Ang II-producing activity by chymase in the BM.