AMPK activation during ischemia helps the myocardium to cope with the deficit of energy production. As AMPK activity is considered to be impaired in diabetes, we hypothesized that enhancing AMPK activation during ischemia above physiological levels would protect the ischemic diabetic heart through AMPK activation and subsequent inhibition of mitochondrial permeability transition pore (mPTP) opening. Isolated perfused hearts from normoglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (n ≥ 6/group) were subjected to 35 min of ischemia in the presence of 10, 20, and 40 μM of A-769662, a known activator of AMPK, followed by 120 min of reperfusion with normal buffer. Myocardial infarction and AMPK phosphorylation were assessed. The effect of A-769662 on mPTP opening in adult cardiomyocytes isolated from both strains was also determined. A-769662 at 20 μM reduced infarct size in both Wistar (30.5 ± 2.7 vs. 51.8 ± 3.9% vehicle; P < 0.001) and GK hearts (22.7 ± 3.0 vs. 48.5 ± 4.7% vehicle; P < 0.001). This protection was accompanied by a significant increase in AMPK and GSK-3β phosphorylation. In addition, A-769662 significantly inhibited mPTP opening in both Wistar and GK cardiomyocytes subjected to oxidative stress. We demonstrate that AMPK activation during ischemia via A-769662 reduces myocardial infarct size in both the nondiabetic and diabetic rat heart. Furthermore, this cardioprotective effect appears to be mediated through inhibition of mPTP opening. Our findings suggest that improving AMPK activation during ischemia can be another mechanism for protecting the ischemic heart.

BackgroundSystemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease, the etiology of which remains only partially characterized. Strong evidence implicates chronic infections in the development and chronicity of autoimmune conditions. Recently, an association has been demonstrated between periodontitis and rheumatoid arthritis. Such observations have led to the investigation of the possible role of periodontitis and oral dysbiosis in other systemic inflammatory conditions, including SLE. The aim of this study was to examine whether there is an association between SLE and periodontitis.MethodsMEDLINE via OVID, EMBASE via OVID, and PsycINFO via OVID databases were searched to identify eligible studies, screened by two independent authors and verified by a third. Studies comparing presence of periodontitis in SLE cases to controls without SLE were included. Data were extracted using a predefined table and papers were appraised using Down’s and Black tool. Mantel–Haenszel meta-analysis was performed using RevMan.ResultsEight case–control studies were included, with 487 SLE cases and a total of 1,383 participants. On meta-analysis of four studies, risk of periodontitis in SLE cases compared to controls was significantly greater with a risk ratio of 1.76 (95% CI 1.29–2.41, p = 0.0004). No statistical difference was found in individual measures of periodontitis, such as probing depth or clinical attachment loss, between SLE cases and controls.ConclusionOur study found a statistically significant increased risk of periodontitis in patients with SLE compared to controls. This finding suggests a possible association between these two conditions. Larger longitudinal studies are needed to confirm this possible association.

The oral cavity is home to vast populations of commensal microbial organisms which constitute the 'healthy oral microbiome.' Periodontitis is a destructive, infectious, inflammatory condition affecting the gums. Initially, a biofilm structure develops, causing localized inflammation. This biofilm is then colonized by certain anaerobic bacteria, including the 'red complex' organisms. There is an increasing interest in the communication between these organisms and host immune surveillance, a dialog which may plays an important role in the development of autoimmune diseases. Studies have shown an association between periodontitis and other inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and systemic lupus. The advent of accessible 16S ribosomal sequencing has led to exciting developments in the characterization of the human microbiome and the ability to study this interaction in more detail. The transmucosal communication between periodontitis and host immunity may provide avenues of discovery regarding the etiology and progression of rheumatic diseases.

A 51-year-old man gave a 2-year history of worsening mobility, cognitive decline and headaches. He had a history of thromboembolic stroke, recurrent transient ischaemic attacks and a spontaneous intraventricular haemorrhage. On examination, he had livedo reticularis and perniosis and a systolic murmur. Catheter cerebral angiography showed peripheral small-vessel and medium-vessel vasculopathy resulting in pruning of the distal cortical vessels and tortuous irregular distal collaterals. Skin biopsy showed subtle vasculopathy with ectasia of capillaries and postcapillary venules but no frank vasculitis or arterial thrombosis. Repeated serum antiphospholipid antibody titres were negative. The clinical features, skin biopsy and angiogram findings strongly supported a diagnosis of Sneddon's syndrome. Clinicians should consider Sneddon's syndrome in patients with livedo reticularis and stroke. There are treatment dilemmas in this situation when ischaemic and haemorrhagic cerebral events coexist.

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Background:Rheumatological diseases are common in Sub-Saharan Africa [1] but specialist healthcare is limited and there are less than 150 rheumatologists currently serving 1 billion people in Sub-Saharan Africa [2]. Rheumatologists practising in the UK NHS are likely to be exposed to migrant patients. There is therefore, an unmet need for health care providers to understand the differences in rheumatology healthcare provision between Sub-Saharan Africa and the UK and the barriers which migrants face in their transition of rheumatology care.Objectives:To gain an understanding of the experiences of patients with rheumatological conditions, about their past healthcare in Sub-Saharan Africa and their transition of care to the UK.Methods:A qualitative study using semi-structured interviews was conducted. Participants were recruited from two rheumatology outpatient clinics in London. Thematic analysis was applied to identify key themes.Results:Seven participants were recruited. Five had rheumatoid arthritis, one had ankylosing spondylitis and one had undifferentiated inflammatory arthritis. Participants described the significant impact their rheumatological conditions had on their physical and emotional wellbeing, including their social and financial implications. Compared to the UK, rheumatology healthcare in Sub-Saharan Africa was characterised by higher costs, limited access to specialists, lack of investigations and treatments, the use of traditional medicines and poor communication by clinicians. Barriers to transition of rheumatology care to the UK were: poor understanding of rheumatological conditions by the public and primary care providers, lack of understanding of NHS entitlements by migrants, fear of data sharing with immigration services and delayed referral to specialist care. Patient, doctor and public education were identified by participants as important ways to improve access to healthcare.Conclusion:This study has described, for the first time, patients’ perspectives of rheumatology health care in Sub-Saharan Africa and the transition of their care to the UK. These initial findings allow healthcare providers in the UK to tailor management for this migrant population and suggests that migrants need more information about their NHS entitlements and specific explanations on what non-clinical data will be shared with immigration services. To increase access to appropriate care, a concerted effort by clinicians and public health authorities is necessary to raise awareness and provide better education to patients and migrant populations about rheumatological conditions.References:[1]G. Mody, “Rheumatology in Africa-challenges and opportunities,” Arthritis Res. Ther., vol. 19, no. 1, p. 49, 2017.[2]M. A. M. Elagib et al., “Sudan and Sweden Active Rheumatoid Arthritis in Central Africa: A Comparative Study Between,” J. Rheumatol. J. Rheumatol. January, vol. 43, no. 10, pp. 1777–1786, 2016.Acknowledgments:We are grateful to the patients involved in this study for their time and involvement.Disclosure of Interests:None declared