Are ethnic disparities in HbA1c levels explained by mental wellbeing? Analysis of population-based data from the Health Survey for England

Aims: It is unclear how ethnic differences in HbA1c levels are affected by individual variations in mental wellbeing. Thus, the aim of this study was to assess the extent to which HbA1c disparities between Caucasian and South Asian adults are mediated by various aspects of positive psychological functioning. Methods: Data from the 2014 Health Survey for England was analysed using bootstrapping methods. A total of 3894 UK residents with HbA1c data were eligible to participate. Mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-Being Scale. To reduce bias BMI, blood pressure, diabetes status, and other factors were treated as covariates. Results: Ethnicity directly predicted blood sugar control (unadjusted coefficient -2.15; 95% CI -3.64, -0.67), with Caucasians generating lower average HbA1c levels (37.68 mmol/mol (5.6%)) compared to South Asians (39.87 mmol/mol (5.8%)). This association was mediated by positive mental wellbeing, specifically concerning perceived vigour (unadjusted effect 0.30; 95% CI 0.13, 0.58): South Asians felt more energetic than Caucasians (unadjusted coefficient -0.32; 95% CI -0.49, -0.16), and greater perceived energy predicted lower HbA1c levels (unadjusted coefficient -0.92; 95% CI -1.29, -0.55). This mediator effect accounted for just over 14% of the HbA1c variance, and was negated after adjusting for BMI. Conclusions: Caucasian experience better HbA1c levels compared with their South Asian counterparts. However, this association is partly confounded by individual differences in perceived energy levels, which is implicated in better glycaemic control, and appears to serve a protective function in South Asians

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

Serum from Calorie-Restricted Rats Activates Vascular Cell eNOS through Enhanced Insulin Signaling Mediated by Adiponectin

eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO• signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR

Minimizing discordances in automated classification of fractionated electrograms in human persistent atrial fibrillation

Ablation of persistent atrial fibrillation (persAF) targeting complex fractionated atrial electrograms (CFAEs) detected by automated algorithms has produced conflicting outcomes in previous electrophysiological studies. We hypothesize that the differences in these algorithms could lead to discordant CFAE classifications by the available mapping systems, giving rise to potential disparities in CFAE-guided ablation. This study reports the results of a head-to-head comparison of CFAE detection performed by NavX (St. Jude Medical) versus CARTO (Biosense Webster) on the same bipolar electrogram data (797 electrograms) from 18 persAF patients. We propose revised thresholds for both primary and complementary indices to minimize the differences in CFAE classification performed by either system. Using the default thresholds [NavX: CFEMean ≤ 120 ms; CARTO: ICL ≥ 7], NavX classified 70 % of the electrograms as CFAEs, while CARTO detected 36 % (Cohen’s kappa κ ≈ 0.3, P < 0.0001). Using revised thresholds found using receiver operating characteristic curves [NavX: CFE-Mean ≤ 84 ms, CFE-SD ≤ 47 ms; CARTO: ICL ≥ 4, ACI ≤ 82 ms, SCI ≤ 58 ms], NavX classified 45 %, while CARTO detected 42 % (κ ≈ 0.5, P < 0.0001). Our results show that CFAE target identification is dependent on the system and thresholds used by the electrophysiological study. The thresholds found in this work counterbalance the differences in automated CFAE classification performed by each system. This could facilitate comparisons of CFAE ablation outcomes guided by either NavX or CARTO in future works

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Reactive oxygen species scavenging by catalase is important for female lutzomyia longipalpis fecundity and mortality

The phlebotomine sand fly Lutzomyia longipalpis is the most important vector of American visceral leishmaniasis (AVL), the disseminated and most serious form of the disease in Central and South America. In the natural environment, most female L. longipalpis are thought to survive for less than 10 days and will feed on blood only once or twice during their lifetime. Successful transmission of parasites occurs when a Leishmania-infected female sand fly feeds on a new host. Knowledge of factors affecting sand fly longevity that lead to a reduction in lifespan could result in a decrease in parasite transmission. Catalase has been found to play a major role in survival and fecundity in many insect species. It is a strong antioxidant enzyme that breaks down toxic reactive oxygen species (ROS). Ovarian catalase was found to accumulate in the developing sand fly oocyte from 12 to 48 hours after blood feeding. Catalase expression in ovaries as well as oocyte numbers was found to decrease with age. This reduction was not found in flies when fed on the antioxidant ascorbic acid in the sugar meal, a condition that increased mortality and activation of the prophenoloxidase cascade. RNA interference was used to silence catalase gene expression in female Lu. longipalpis. Depletion of catalase led to a significant increase of mortality and a reduction in the number of developing oocytes produced after blood feeding. These results demonstrate the central role that catalase and ROS play in the longevity and fecundity of phlebotomine sand flies