A Central Role for Monocyte-Platelet Interactions in Heart Failure

Heart failure (HF) is an increasingly prevalent and costly multifactorial syndrome with high morbidity and mortality rates. The exact pathophysiological mechanisms leading to the development of HF are not completely understood. Several emerging paradigms implicate cardiometabolic risk factors, inflammation, endothelial dysfunction, myocardial fibrosis, and myocyte dysfunction as key factors in the gradual progression from a healthy state to HF. Inflammation is now a recognized factor in disease progression in HF and a therapeutic target. Furthermore, the monocyte-platelet interaction has been highlighted as an important pathophysiological link between inflammation, thrombosis, endothelial activation, and myocardial malfunction. The contribution of monocytes and platelets to acute cardiovascular injury and acute HF is well established. However, their role and interaction in the pathogenesis of chronic HF are not well understood. In particular, the cross talk between monocytes and platelets in the peripheral circulation and in the vicinity of the vascular wall in the form of monocyte-platelet complexes (MPCs) may be a crucial element, which influences the pathophysiology and progression of chronic heart disease and HF. In this review, we discuss the role of monocytes and platelets as key mediators of cardiovascular inflammation in HF, the mechanisms of cell activation, and the importance of monocyte-platelet interaction and complexes in HF pathogenesis. Finally, we summarize recent information on pharmacological inhibition of inflammation and studies of antithrombotic strategies in the setting of HF that can inform opportunities for future work. We discuss recent data on monocyte-platelet interactions and the potential benefits of therapy directed at MPCs, particularly in the setting of HF with preserved ejection fraction.

Appropriate Polypharmacy and Medicine Safety: When Many is not Too Many

The use of multiple medicines (polypharmacy) is increasingly common in middle-aged and older populations. Ensuring the correct balance between the prescribing of ‘many’ drugs and ‘too many’ drugs is a significant challenge. Clinicians are tasked with ensuring that patients receive the most appropriate combinations of medications based on the best available evidence, and that medication use is optimised according to patients’ clinical needs (appropriate polypharmacy). Historically, polypharmacy has been viewed negatively because of the associated medication safety risks, such as drug interactions and adverse drug events. More recently, polypharmacy has been identified as a risk factor for under-prescribing, such that patients do not receive necessary medications and this can also pose risks to patients’ safety and well-being. The negative connotations that have long been associated with the term polypharmacy could potentially be acting as a driving factor for under-prescribing, whereby clinicians are reluctant to prescribe necessary medicines for patients who are already receiving ‘many’ medicines. It is now recognised that the prescribing of ‘many’ medicines can be entirely appropriate in patients with several chronic conditions and that the risks of adverse drug events that have been associated with polypharmacy may be greatly reduced when patients’ clinical context is taken into consideration. In this article, we outline the current perspectives on polypharmacy and make the case for adopting the term ‘appropriate polypharmacy’ in differentiating between the prescribing of ‘many’ drugs and ‘too many’ drugs. We also outline the inherent challenges in doing so and provide recommendations for future clinical practice and research.

‘New’ migrant identities: unravelling opportunities and restrictions

Labour and capital mobility from globalisation has given rise to significant increases in the reliance of migrant labour in established gateways, but also in new migration destinations. Many aspects of migrant incorporation in new migration destinations have received some attention, not least regarding employer and employee relations. Less attention has been focused on the construction of migrant as a marker of identification, although identities, particularly regarding gender and ethnicity, in the workplace have received considerable attention. This article aims to illuminate knowledge on how migration produces social change thereby responding to a call from Batnitzky et al. (2009, p. 1290) for additional attention on what ‘the practical and symbolic effects of migration are as people move across different structures and institutions of social control….’ Mindful of Goffman’s (1969, 1983) emphasis on individual interactions and experiences, it examines what it means to be a migrant in terms of everyday encounters and experiences. It investigates the array and interplay of internal and external processes that create migrant identities and the implications of this for social integration.

The paper argues that one of the paradoxes of globalisation, and of the associated increased levels of migrant labour, is the construction of the migrant identity that ultimately impedes social integration. It shows how the application of migrant identity (internally and externally) bestows a particular status that affects (options for) individual behaviour and subsequent actions and outcomes. The paper argues that while migrants value the migrant identity status because of the benefits that it brings, this status can also cause high levels of dissatisfaction among migrants and it can exclude migrants from wider benefits of full citizenship. Migrants have individual identification processes, but external forces, including social structures and institutions, also affect migrant identity. These forces help to shape individual expectations and standards, contributing to identity interruption and dissonance.

The paper is structured as follows: it uses social identity theory as a means of understanding what it is to be a ‘migrant’ in a new destination, while simultaneously recognising the inevitability of this generic label - migrants are an extremely heterogeneous group, made up of individuals with different experiences, values and so forth. The analysis considers the significance of context and of social interactions, thus paying attention to how identity is constructed and performed by the individual and also assigned by others. Empirical evidence is used to examine how having a migrant status affects individual prospects. The paper evaluates the extent to which patterns and processes of migration present an opportunity for social change, positive or negative.

LES of flame acceleration and DDT in hydrogen-air mixture using artificially thickened flame approach and detailed chemical kinetics

A large eddy simulation is performed to study the deflagration to detonation transition phenomenon in an obstructed channel containing premixed stoichiometric hydrogen–air mixture. Two-dimensional filtered reactive Navier–Stokes equations are solved utilizing the artificially thickened flame approach (ATF) for modeling sub-grid scale combustion. To include the effect of induction time, a 27-step detailed mechanism is utilized along with an in situ adaptive tabulation (ISAT) method to reduce the computational cost due to the detailed chemistry. The results show that in the slow flame propagation regime, the flame–vortex interaction and the resulting flame folding and wrinkling are the main mechanisms for the increase of the flame surface and consequently acceleration of the flame. Furthermore, at high speed, the major mechanisms responsible for flame propagation are repeated reflected shock–flame interactions and the resulting baroclinic vorticity. These interactions intensify the rate of heat release and maintain the turbulence and flame speed at high level. During the flame acceleration, it is seen that the turbulent flame enters the ‘thickened reaction zones’ regime. Therefore, it is necessary to utilize the chemistry based combustion model with detailed chemical kinetics to properly capture the salient features of the fast deflagration propagation.