Cause, consequence or coincidence: the relationship between psychiatric disease and metabolic syndrome

It is now well established that severe mental illness (SMI) is associated with a reduced lifespan and increased risk of cardiovascular disease (CVD). Individuals with SMI often have abnormalities of lipid metabolism, glucose homeostasis, an increased prevalence of obesity and hypertension. They also have an increased prevalence of Metabolic Syndrome (MetS). The reasons for this are not entirely clear, but are likely to be multifactorial. Whilst there have been numerous studies investigating the prevalence of MetS in patients with SMI, many have been in small, mixed population samples, that have not been adequately controlled for the background population from which they have been drawn. This is important because of the wide range of prevalence estimates that have been reported, and variations of MetS prevalence with ethnicity. The negative impact of treatment with second-generation antipsychotic (SGA) drugs on the risk of MetS also appears clear in most populations, although the mechanisms accounting for this increased risk are yet to be clarified. Despite this high prevalence of CVD risk factors in patients with SMI, most studies report a poor implementation of screening for CVD risk factors at baseline, and following initiation of treatment with SGAs. Not all patients with SMI are susceptible to the adverse effects of SGAs, but in those that are, switching to an anti-psychotic that is less likely to cause metabolic disturbance, starting statin therapy and a reduction in CVD risk factors through changes in lifestyle may all be important strategies

Hypoxia enhances the tissue protective effect of erythropoietin and its analogues in an endothelial cell injury model

PO has tissue protective activities in ischemic disease but also has prothrombotic, erythropoietic effects. Carbamylated EPO (CEPO) retains the protective actions without the erythropoietic effects. To assess the potential of these molecules in atherosclerosis (an ischemic heart disease), we investigated EPO and CEPO in an in vitro model of injury using bovine aortic endothelial cells (BAEC) in hypoxia and normoxia.. BAECs were grown to confluence in 10% FBS in 12 well culture plates. They were then cultured under normoxia (21% oxygen) or hypoxia (5% oxygen) 24 h prior to their use in an injury model using the ‘scratch assay.’ The effects of EPO and CEPO on endothelial closure were assessed using a range of concentrations (0-10 ng/mL). In separate experiments, the effects of EPO and CEPO on BAEC proliferation and chemotaxis were also assessed under similar hypoxic conditions. Gene expression of the receptors that may be involved in their protective pathway [EPOR and the β common chain receptor (βCR)] were assessed using quantitative PCR. The effects of both EPO and CEPO were enhanced under hypoxic conditions (13 ± 2.6 %, and 10 ± 1.69 %, p0.05). Whilst, the expression of EPOR gene increased by 2.1 ± 0.8 folds (p<0.05) In hypoxia, βCR expression was not affected by the change in oxygen tension. The effects of EPO and CEPO in the scratch assay appeared to be mediated by enhancing cell proliferation and migration of BAECs (p<0.05). In conclusion, the enhanced effects of EPO and CEPO on endothelial cells under hypoxia requires further investigation in processes in which hypoxia may play a role, e.gfor example. in atherogenesis and re-stensosis following angioplasty

Hypoxia, angiogenesis and atherogenesis

The balance between vascular oxygen supply and metabolic demand for oxygen within the vasculature is normally tightly regulated. An imbalance leads to hypoxia and a consequential cascade of cellular signals that attempt to offset the effects of hypoxia. Hypoxia is invariably associated with atherosclerosis, wound repair, inflammation and vascular disease. The anoxaemia hypothesis proposes that an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerosis and plaque angiogenesis. There is now substantial evidence that hypoxia plays an essential role in angiogenesis as well as plaque angiogenesis. It controls the metabolism, and responses of many of the cell types found within the developing plaque and whether the plaque will evolve into a stable or unstable phenotype. Hypoxia is characterized in molecular terms by the stabilization of hypoxia-inducible factor (HIF) 1a, a subunit of the heterodimeric nuclear transcriptional factor HIF-1 and a master regulator of oxygen homeostasis. The expression of HIF-1 is localized to perivascular tissues, inflammatory macrophages and smooth muscle cells where it regulates several genes that are important to vascular function including vascular endothelial growth factor, nitric oxide synthase, endothelin-1 and erythropoietin. This chapter summarizes the effects of hypoxia on the functions of cells involved in angiogenesis as well as atherogenesis (plaque angiogenesis) and the evidence for its potential importance from experimental models and clinical studies

Functional Foods and Nutraceuticals in the Primary Prevention of Cardiovascular Diseases

Cardiovascular disease (CVD) is now the leading cause of death globally and is a growing health concern. Dietary factors are important in the pathogenesis of CVD and may to a large degree determine CVD risk, but have been less extensively investigated. Functional foods are those that are thought to have physiological benefits and/or reduce the risk of chronic disease beyond their basic nutritional functions. The food industry has started to market products labelled as “functional foods.” Although many review articles have focused on individual dietary variables as determinants of CVD that can be modified to reduce the risk of CVD, the aim of this current paper was to examine the impact of functional foods in relation to the development and progression of CVD. Epidemiologic studies have demonstrated the association between certain dietary patterns and cardiovascular health. Research into the cardio-protective potential of their dietary components might support the development of functional foods and nutraceuticals. This paper will also compare the effect of individual bioactive dietary compounds with the effect of some dietary patterns in terms of their cardiovascular protection

Heavy Metal Poisoning and Cardiovascular Disease

Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed

Fourth-year medical students’ experiences of diagnostic consultations in a simulated primary care setting

Objectives: The aim was to explore the experiences of fourth-year medical students of diagnostic consultations in a simulated primary care setting, in order to gain an insight into the suitability of such simulated consultations for assessing the diagnostic reasoning skills of medical students. Methods: This single-centre study employed a qualitative, cross-sectional design. Twelve fourth-year medical students volunteered to be filmed across 21 simulated, primary care consultations. The setting closely resembled OSCE stations, with a clinician present at each station monitoring the students’ performance using a station-checklist. Upon completion of each station, participants reflected on their experiences using video-stimulated recall. Interviews were transcribed and analysed using Interpretative Phenomenological Analysis. Results: The simulated scenarios were often perceived to have limited fidelity with predictable outcomes. At times, preoccupation with the assessment checklist meant that students were more likely to focus on asking questions than interpreting the information they were gaining. Some students felt scrutinized during the consultations, while others struggled to adapt to the time pressure. Overall, the artificial setting seemed to promote a reductionist diagnostic approach and an attitude of ‘ticking boxes’ rather than engaging in active diagnostic reasoning. Conclusions: The present findings call into question the assumption that observation-based assessment of the performance of medical students during simulated consultations can be reliably used to assess their diagnostic skills. Future studies need to explore how current assessment modalities could be better adapted to facilitate active engagement in diagnostic reasoning

Altered antioxidant and trace-element status in adolescent female gymnasts

Physical activity is associated with the generation of reactive oxygen species and may lead to decreased levels of plasma antioxidants and increased oxidant stress. Some studies have reported that antioxidant supplements can reduce the consequences of oxidative stress during exercise. In this study the authors aimed to assess the chronic effects of exercise on endogenous serum antioxidant enzyme concentrations. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were measured in adolescent girls who were either competitive gymnasts or sedentary controls. The relationship between age, body-mass index, dietary intake, trace-element status, and serum GPx and SOD was determined. The participants in the study were part of a 3-yr longitudinal investigation of exercise and peak bone-mass development in 38 competitive gymnasts and 40 healthy sedentary adolescent females 8-17 yr of age. Serum GPx and SOD were measured using colorimetric assays, and trace elements were measured using inductively coupled plasma mass spectrometry. The mean serum GPx concentrations were significantly higher in the gymnasts than in the sedentary females (157 ± 11.1 vs. 126 ± 8.8 U/ml, p < .05). In contrast, serum SOD concentrations were significantly lower in the gymnasts than in the sedentary group (7.24 ± 2.6 vs. 8.57 ± 2.3 U/ml, p < .05). Serum selenium, zinc, and copper were higher in the physically active group than in the inactive group (0.89 ± 0.03, 10.86 ± 0.39, 14.50 ± 0.50 vs. 0.81 ± 0.03, 10.32 ± 0.28, and 14.38 ± 0.42 µmol/L, respectively), although only serum selenium reached statistical significance (p < .05). The findings show that young female gymnasts have an altered antioxidant enzyme profile compared with their less physically active peer

Hypoxia enhances the regenerative effects of erythropoietin and its non-erythropoietic peptide analogue in models of endothelial cell injury

Background: Hypoxia is invariably associated with wound repair, inflammation, and vascular disease. The induction of Hypoxia Inducible Factor-1 (HIF-1) is a characteristic feature of hypoxia, and orchestrates the profound changes in transcription that accompany hypoxia. HIF-1 expression is localized to several cell types, and regulates several genes that are important to vascular function including vascular endothelial growth factor (VEGF), nitric oxide synthase (NOS), endothelin-1 and erythropoietin (EPO). In fact, EPO derived from vascular endothelial cells appears to be important in protecting the endothelium against ischemic injury. The non-erythropietic analogue of EPO; pyroglutamate helix B surface peptide (pHBSP) retains the protective actions of EPO without its erythropoietic effects. The aim of our study was to assess the reparative effects of these molecules when used in combination with HIF inducers. Method: The reparative effects of EPO and pHBSP were assessed under hypoxia (1% O2) and normoxia (21% O2) as well as in the presence or absence of DMOG; a HIF-1 inducer. An in vitro model of wound healing (the scratch assay) was used: a monolayer of rat aortic endothelial cells (RAECs) was scraped to produce a reproducible injury, and the scratch closure was assessed over 24 h. An in vivo model of vascular injury using a 2F fogarty balloon catheter was introduced into the common carotid artery causing complete removal of the vascular endothelium. Drugs were applied locally onto the injured arteries using a hydrogel (30% w/v) and re-endothelialisation assessed using Evans blue staining injected 30 min intravenously before culling the rat. The effects of EPO and pHBSP on cell proliferation, chemotaxis and apoptosis were assessed in both the in vitro and in vivo models. The potential molecular mechanisms of these effects were also explored. Results: In vitro, EPO and its analogues only exhibited a reparative effect under hypoxic conditions (13 ± 2.6 %, and 10 ± 1.69 %, p0.05). These effects appeared to be mediated by promoting RAEC proliferation and migration of (p<0.05). The priming effect of hypoxia was associated with stabilization of HIF-1α. Hypoxia was associated with a reduction in nitric oxide (NO) production as assessed by its oxidation products nitrite and nitrate, and this was consistent with the oxygen requirement for the endogenous production of NO by NO synthase (NOS).The HIF-1 inducer; DMOG also exhibited reparative effects in a concentration dependent manner. Similar results were observed in vivo where DMOG and EPO accelerated the repair of injured arteries (35 ± 9.8 % recovery compared to untreated injured arteries respectively). This mode of application also caused site-specific increase in VEGF expression on treated arteries compared to untreated ones within the same animal. Conclusion and implication: The tissue-protective effects of EPO-related cytokines in pathophysiological settings are enhanced by hypoxia. These findings may be particularly relevant to atherogenesis and post-angioplasty restenosi

Twitter: an effective learning tool within medical education

Educational social media platforms such as dedicated Facebook pages and Twitter hashtags are increasingly being used by anatomy educators as learning support tools with positive outcomes such as: increasing student engagement with the subject of anatomy, facilitating communication with educators and reducing student anxiety levels in the lead up to assessments by offering learning support information. There have been less reports on whether these platforms impact on student’s anatomy knowledge. One previous investigation demonstrated that the frequency of student engagement with a dedicated Twitter hashtag did not increase their exam scores, however the methodology did not provide specific learning feedback opportunities to students. Since then, Twitter introduced a polling tool. This project investigated whether the polling tool could effectively be used to deliver regular MCQ style questions (followed by feedback) to students and whether student’s use of this tool had an effect on exam scores. Second year medical students enrolled on the Musculoskeletal and Immunity Module 2015 (n=140) at Brighton Sussex Medical School were offered the #m204anatomy Twitter hashtag as a learning support tool which included weekly Twitter polls questioning student’s anatomy knowledge. Students were invited to complete a questionnaire asking whether they had answered Twitter polls and for consent to use their exam scores to compare against their use of the polls. Student opinions on the hashtag were also obtained during a focus group with five students. Ninety-three students successfully completed the questionnaire and gave consent. 62% of students didn’t used the Twitter polls and their mean anatomy exam score was 59.7%. 38% of students did answer the Twitter polls and their mean exam score was 67.2%, which showed to be significantly higher (p = 0.012) than those who did not use the Twitter polling tool. This indicates that the Twitter polling tool can be used as a formative assessment tool to enhance student anatomy knowledge. However, the majority of students are reluctant to engage with educational social media platforms and findings from this study indicate this is due to a fear that students will be identified as lacking knowledge and breaching professionalism guidelines. Keywords: Social media, Twitter, Medical education, Professionalism, Learning experienc