Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

AbstractObjective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery

Feeding efficiency gains can increase the greenhouse gas mitigation potential of the Tanzanian dairy sector.

We use an attributional life cycle assessment (LCA) and simulation modelling to assess the effect of improved feeding practices and increased yields of feed crops on milk productivity and GHG emissions from the dairy sector of Tanzania’s southern highlands region. We calculated direct non-CO2 emissions from dairy production and the CO2 emissions resulting from the demand for croplands and grasslands using a land footprint indicator. Baseline GHG emissions intensities ranged between 19.8 and 27.8 and 5.8–5.9 kg CO2eq kg−1 fat and protein corrected milk for the Traditional (local cattle) and Modern (improved cattle) sectors. Land use change contributed 45.8–65.8% of the total carbon footprint of dairy. Better feeding increased milk yields by up to 60.1% and reduced emissions intensities by up to 52.4 and 38.0% for the Traditional and Modern sectors, respectively. Avoided land use change was the predominant cause of reductions in GHG emissions under all the scenarios. Reducing yield gaps of concentrate feed crops lowered emissions further by 11.4–34.9% despite increasing N2O and CO2 emissions from soils management and input use. This study demonstrates that feed intensification has potential to increase LUC emissions from dairy production, but that fertilizer-dependent yield gains can offset this increase in emissions through avoided emissions from land use change

Embedding stakeholders’ priorities into the low-emission development of the East African dairy sector

A growing body of evidence shows that more intensive dairy systems can be good for both nature and people. Little research considers whether such systems correspond with local priorities and preferences. Using a mixed methods approach, this study examined the effects of three intensification scenarios on milk yield and emission intensities in Kenya and Tanzania. Scenarios included (a) an incremental change to feed management; (b) adaptive change by replacing poor quality grass with nutrient-rich fodder crops; and (c) multiple change involving concurrent improvements to breeds, feeds and concentrate supplementation. These scenarios were co-constructed with diverse stakeholder groups to ensure these resonate with local preferences and priorities. Modelling these scenarios showed that milk yield could increase by 2%–15% with incremental changes to over 200% with multiple changes. Greenhouse gas emission intensities are lowest under the multiple change scenario, reducing by an estimated 44%. While raising yields, incremental change conversely raises emission intensities by 9%. Our results suggest that while future interventions that account for local priorities and preferences can enhance productivity and increase the uptake of practices, far-reaching shifts in practices are needed to reduce the climatic footprint of the dairy sector. Since top-down interventions does not align with local priorities and preferences in many situations, future low-emission development initiatives should place more emphasis on geographic and stakeholder heterogeneity when designing targeting and implementation strategies. This suggests that in low-income countries, bottom-up approaches may be more likely to improve dairy productivity and align with mitigation targets than one-size-fits-all approaches

Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure

Upon myocardial damage, the release of cardiac proteins induces a strong antibody-mediated immune response, which can lead to adverse cardiac remodeling and eventually heart failure (HF). Stem cell therapy using mesenchymal stromal cells (MSCs) or cardiomyocyte progenitor cells (CPCs) previously showed beneficial effects on cardiac function despite low engraftment in the heart. Paracrine mediators are likely of great importance, where, for example, MSC-derived extracellular vesicles (EVs) also show immunosuppressive properties in vitro. However, the limited capacity of MSCs to differentiate into cardiac cells and the sufficient scaling of MSC-derived EVs remain a challenge to clinical translation. Therefore, we investigated the immunosuppressive actions of endogenous CPCs and CPC-derived EVs on antibody production in vitro, using both healthy controls and end-stage HF patients. Both MSCs and CPCs strongly inhibit lymphocyte proliferation and antibody production in vitro. Furthermore, CPC-derived EVs significantly lowered the levels of IgG1, IgG4, and IgM, especially when administered for longer duration. In line with previous findings, plasma cells of end-stage HF patients showed high production of IgG3, which can be inhibited by MSCs in vitro. MSCs and CPCs inhibit in vitro antibody production of both healthy and end stage HF-derived immune cells. CPC-derived paracrine factors, such as EVs, show similar effects, but do not provide the complete immunosuppressive capacity of CPCs. The strongest immunosuppressive effects were observed using MSCs, suggesting that MSCs might be the best candidates for therapeutic targeting of B-cell responses in HF

Integrating place-specific livelihood and equity outcomes into global assessments of bioenergy deployment

__Abstract__ Integrated assessment models suggest that the large-scale deployment of bioenergy could contribute to ambitious climate change mitigation efforts. However, such a shift would intensify the global competition for land, with possible consequences for 1.5 billion smallholder livelihoods that these models do not consider. Maintaining and enhancing robust livelihoods upon bioenergy deployment is an equally important sustainability goal that warrants greater attention. The social implications of biofuel production are complex, varied and place-specific, difficult to model, operationalize and quantify. However, a rapidly developing body of social science literature is advancing the understanding of these interactions. In this letter we link human geography research on the interaction between biofuel crops and livelihoods in developing countries to integrated assessments on biofuels. We review case-study research focused on first-generation biofuel crops to demonstrate that food, income, land and other assets such as health are key livelihood dimensions that can be impacted by such crops and we highlight how place-specific and global dynamics influence both aggregate and distributional outcomes across these livelihood dimensions. We argue that place-specific production models and land tenure regimes mediate livelihood outcomes, which are also in turn affected by global and regional markets and their resulting equilibrium dynamics. The place-specific perspective suggests that distributional consequences are a crucial complement to aggregate outcomes; this has not been given enough weight in comprehensive assessments to date. By narrowing the gap between place-specific case studies and global models, our discussion offers a route towards integrating livelihood and equity considerations into scenarios of future bioenergy deployment, thus contributing to a key challenge in sustainability sciences

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Increased circulating IgG levels, myocardial immune cells and IgG deposits support a role for an immune response in pre- and end-stage heart failure

The chronic inflammatory response plays an important role in adverse cardiac remodelling and the development of heart failure (HF). There is also evidence that in the pathogenesis of several cardiovascular diseases, chronic inflammation is accompanied by antibody and complement deposits in the heart, suggestive of a true autoimmune response. However, the role of antibody-mediated immune responses in HF progression is less clear. We assessed whether immune cell infiltration and immunoglobulin levels are associated with HF type and disease stage, taking sex differences into account. We found IgG deposits and increased infiltration of immune cells in the affected myocardium of patients with end-stage HF with reduced ejection fraction (HFrEF, n = 20). Circulating levels of IgG1 and IgG3 were elevated in these patients. Furthermore, the percentage of transitional/regulatory B cells was decreased (from 6.9% to 2.4%) compared with healthy controls (n = 5). Similarly, increased levels of circulating IgG1 and IgG3 were observed in men with left ventricular diastolic dysfunction (LVDD, n = 5), possibly an early stage of HF with preserved EF (HFpEF). In conclusion, IgG deposits and infiltrates of immune cells are present in end-stage HFrEF. In addition, both LVDD patients and end-stage HFrEF patients show elevated levels of circulating IgG1 and IgG3, suggesting an antibody-mediated immune response upon cardiac remodelling, which in the early phase of remodelling appear to differ between men and women. These immunoglobulin subclasses might be used as marker for pre-stage HF and its progression. Future identification of auto-antigens might open possibilities for new therapeutic interventions