Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

PERK is a critical metabolic hub for immunosuppressive function in macrophages.

Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages

The biology of platelet-rich plasma and its application in oral surgery: literature review.

Item does not contain fulltextPlatelet-rich plasma (PRP) is a new approach in tissue regeneration and a developing area for clinicians and researchers. It is used in various surgical fields, including oral and maxillofacial surgery. PRP is prepared from the patient's own blood and contains growth factors that influence wound healing. Of these growth factors, platelet-derived growth factor, transforming growth factor, insulin-like growth factor, and epidermal growth factor play a pivotal role in tissue repair mechanisms. Although the growth factors and mechanisms involved are still poorly understood, the easy application of PRP in the clinic and its possible beneficial outcome, including reduction of bleeding, rapid soft tissue healing, and bone regeneration, hold promise for new treatment approaches. However, animal studies and human trials demonstrate conflicting results regarding the application of PRP. Therefore the aim of this literature review is to evaluate the scientific evidence regarding the use of PRP in dentistry, to describe the different bioactive substances included in PRP and their participation in the healing process, to elucidate the different techniques and available technology for PRP preparation, to review animal and human studies, to clarify risks, and to provide guidance for future research

Where is the value-added in the cluster approach? Hermeneutic theorizing, economic geography and clusters as a multi-perspectival approach

Summary. Barnes has argued that (new) economic geography has moved in to a phase of theory development that he describes as ‘hermeneutic ’ theorising. This epistemological position is characterised by an interpretive, reflexive and open-ended mode of inquiry that recognises the diversity of sources available for theorising and the subsequent conversations that will ensue from such diversity. In a recent deconstruction of the clusters concept in economic geography, and especially that version (or brand) expounded by Michael Porter, Martin and Sunley ask the question as to what added value is delivered by the concept’s gatecrashing of academic and policy debates. This paper argues that clusters should not be overendowed as a singular ‘brand’, but recognised as an emergent set of multiple perspectives in dialogue. From a position of hermeneu-tic theorising, ‘clusters ’ have the potential to add value by allowing theoretical debate across a wide range of (overlapping and competing) perspectives whose partiality and situatedness are made explicit. The possibilities for theoretical, empirical and policy cross-fertilisation from the difficult act of holding together these threads is one potential drawn from the conversations engendered through hermeneutic theorising in economic geography. Nevertheless, this ‘work in progress ’ must be deepened and extended if the potential of clusters is to be realised. There is no doubt that what it means ‘to do ’ theory is quite different between the old and the new economic geographies, and in the process redefining the very discipline itself (Barnes, 2000, p. 19). Hermeneutic theorising … is a much bet-ter description of the kind of theorising found in the new economic geography, and marked by an interpretive mode of inquiry that is reflexive, open-ended and catholic in its theoretical sources (Barnes, 2000, p. 546)