Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease.
Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature.
Introduction: There have been recent mounting concerns regarding multiple reports stating a significantly elevated relative-risk of COVID-19 mortality amongst the Black and Minority Ethnic (BAME) population. An urgent national enquiry investigating the possible reasons for this phenomenon has been issued in the UK. Inflammation is at the forefront of COVID-19 research as disease severity appears to correlate with pro-inflammatory cytokine dysregulation. This narrative review aims to shed light on the novel, pathophysiological role of inflammation in contributing towards the increased COVID-19 mortality risk amongst the BAME population. Methods: Searches in PubMed, Medline, Scopus, medRxiv and Google Scholar were performed to identify articles published in English from inception to 18 th June 2020. These databases were searched using keywords including: 'COVID-19' or 'Black and Minority Ethnic' or 'Inflammation'. A narrative review was synthesized using these included articles. Results: We suggest a novel pathophysiological mechanism by which acute inflammation from COVID-19 may augment existing chronic inflammation, in order to potentiate a 'cytokine storm' and thus the more severe disease phenotype observed in the BAME population. Obesity, insulin resistance, cardiovascular disease, psychological stress, chronic infections and genetic predispositions are all relevant factors which may be contributing to elevated chronic systemic inflammation amongst the BAME population. Conclusion: Overall, this review provides early insights and directions for ongoing research regarding the pathophysiological mechanisms that may explain the severe COVID-19 disease phenotype observed amongst the BAME population. We suggest 'personalization' of chronic disease management, which can be used with other interventions, in order to tackle this.
Background: Within the UK, COVID-19 has contributed towards over 103,000 deaths. Although multiple risk factors for COVID-19 have been identified, using this data to improve clinical care has proven challenging. The main aim of this study is to develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, thus enabling risk-stratification and earlier clinical decision-making. Methods: Anonymised data consisting of 44 independent predictor variables from 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case–control analysis. Primary outcomes included inpatient mortality, required ventilatory support, and duration of inpatient treatment. Pulmonary embolism sequala was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were then learned and constructed using Bayesian networks. Results: The proposed probabilistic models were able to predict, using feature selected risk factors, the probability of the mentioned outcomes. Overall, our findings demonstrate reliable, multivariable, quantitative predictive models for four outcomes, which utilise readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as risk stratification and clinical decision-making tools.
Background: Diet plays a major role in cardiovascular disease (CVD) risk. Objectives: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD. Methods: We searched for randomised controlled trials (RCTs) of Mediterranean-style diets in healthy adults and those at increased risk of CVD (primary prevention) and with established CVD (secondary prevention). Results: Thirty RCTs were included, 22 in primary prevention and eight in secondary prevention. Clinical endpoints were reported in two trials where there was moderate quality evidence for a reduction in strokes for primary prevention, and low quality evidence for a reduction in total and CVD mortality in secondary prevention. We found moderate quality evidence of improvement in CVD risk factors for primary prevention and low quality evidence of little or no effect in secondary prevention. Conclusions: There is still some uncertainty regarding the effects of a Mediterranean-style diet in CVD prevention.
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