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Despite the focus placed on cardiovascular research, the prevalence of vascular and valvular calcification is increasing and remains a leading contributor of cardiovascular morbidity and mortality. Accumulating studies provide evidence that cardiovascular calcification is an inflammatory disease in which innate immune signaling becomes sustained and/or excessive, shaping a deleterious adaptive response. The triggering immune factors and subsequent inflammatory events surrounding cardiovascular calcification remain poorly understood, despite sustained significant research interest and support in the field. Most studies on cardiovascular calcification focus on innate cells, particularly macrophages' ability to release pro-osteogenic cytokines and calcification-prone extracellular vesicles and apoptotic bodies. Even though substantial evidence demonstrates that macrophages are key components in triggering cardiovascular calcification, the crosstalk between innate and adaptive immune cell components has not been adequately addressed. The only therapeutic options currently used are invasive procedures by surgery or transcatheter intervention. However, no approved drug has shown prophylactic or therapeutic effectiveness. Conventional diagnostic imaging is currently the best method for detecting, measuring, and assisting in the treatment of calcification. However, these common imaging modalities are unable to detect early subclinical stages of disease at the level of microcalcifications; therefore, the vast majority of patients are diagnosed when macrocalcifications are already established. In this review, we unravel the current knowledge of how innate and adaptive immunity regulate cardiovascular calcification; and put forward differences and similarities between vascular and valvular disease. Additionally, we highlight potential immunomodulatory drugs with the potential to target calcification and propose avenues in need of further translational inquiry.

In a crisis, there is widespread recognition and acceptance that not all lives can be saved. But whose lives can legitimately be saved and who decides? Recent scholarship has begun to examine how refugees perceived as 'vulnerable', such as women and children, are frequently prioritized over other groups in humanitarian responses. Such analyses, however, fail to adequately explain why some groups - such as older persons - are considered vulnerable and yet are largely neglected. Based on the case of older Syrian refugees in Jordan, this article critically examines the ways in which humanitarian health actors make sense of the humanitarian principle of 'impartiality' in the face of limited resources. Based on 61 interviews and observational data collected in Jordan between 2017 and 2019, my results show that humanitarians routinely classify older refugees as 'vulnerable' and in need of medical assistance. Yet I find that three neoliberal considerations - including perceptions of the reduced lifespan, disproportionate disease burden, and limited contributions to the economy of older refugees - make this demographic low 'value for money'. This article expands our understanding of how medical humanitarian understandings of 'deservingness' are increasingly shaped by market-driven logics, and how these (re)create ageist, gendered and racialized hierarchies within refugee health.

Cardiovascular diseases are the most common cause of death around the world. This includes atherosclerosis and the adverse effects of its treatment, such as restenosis and thrombotic complications. The development of these arterial pathologies requires a series of highly-intertwined interactions between immune and arterial cells, leading to specific inflammatory and fibroproliferative cellular responses. In the last few years, the study of phosphoinositide 3-kinase (PI3K) functions has become an attractive area of investigation in the field of arterial diseases, especially since inhibitors of specific PI3K isoforms have been developed. The PI3K family includes 8 members divided into classes I, II or III depending on their substrate specificity. Although some of the different isoforms are responsible for the production of the same 3-phosphoinositides, they each have specific, non-redundant functions as a result of differences in expression levels in different cell types, activation mechanisms and specific subcellular locations. This review will focus on the functions of the different PI3K isoforms that are suspected as having protective or deleterious effects in both the various immune cells and types of cell found in the arterial wall. It will also discuss our current understanding in the context of which PI3K isoform(s) should be targeted for future therapeutic interventions to prevent or treat arterial diseases.

The development of processes to dehydrogenate C3–C4 paraffins to the corresponding mono-olefins has been pushed by the market demand. A technology based on a bubbling fluidized bed reactor-regenerator system is proposed to solve the problems involved in the industrial application of such processes.

Estradiol (E2) regulates gene transcription through nuclear Estrogen Receptor alpha (ERα) thanks to two Activation Functions, AF-1 and AF- 2, but can activate membrane ERαand thereby rapid « non genomic » signals. Some tissue-specific stimulatory roles of these ERα functions have already been described: for instance ERα AF1 and membrane ERα activation are each necessary and sufficient to induce endometrial epithelial proliferation and to accelerate endothelial healing respectively in response to E2. E2 can also inhibit vascular smooth muscle cell proliferation, but the mechanisms of this action are poorly recognized. Using a mouse model of femoral artery injury, we found that 1) E2 prevents intimal smooth muscle hyperplasia. 2) Selective inactivation of ERαin smooth muscle cells abrogates this protective action, whereas its endothelial and hematopoietic inactivation did not alter this effect. 3) Estrogen dendrimer conjugate, a selective activator of membrane ERa, fail to prevent intimal hyperplasia. 4) E2 does not inhibit post-injury arterial smooth muscle cell proliferation in mice selectively deficient in ERαAF1 (through deletion of the N-terminal A/B domain which harbors this function), demonstrating that ERαAF1 is necessary to mediate this effect, 5) Finally, tamoxifen, a selective partial AF-1 activator of ERα, is sufficient to prevent the hyperplasia. Altogether, we demonstrate here, for the first time, that ERαAF1 activation is both necessary and sufficient to prevent post-injury arterial smooth muscle cell proliferation, in striking contrast to its stimulatory action on the endometrial epithelium. This underlines the exquisite tissue-specific actions of ERαsubfunctions as well as of selective ER modulators, and shed some light on one of the most intriguing mysteries of biology of estrogens.