Extended bidomain modeling of defibrillation: quantifying virtual electrode strengths in fibrotic myocardium

Defibrillation is a well-established therapy for atrial and ventricular arrhythmia. Here, we shed light on defibrillation in the fibrotic heart. Using the extended bidomain model of electrical conduction in cardiac tissue, we assessed the influence of fibrosis on the strength of virtual electrodes caused by extracellular electrical current. We created one-dimensional models of rabbit ventricular tissue with a central patch of fibrosis. The fibrosis was incorporated by altering volume fractions for extracellular, myocyte and fibroblast domains. In our prior work, we calculated these volume fractions from microscopic images at the infarct border zone of rabbit hearts. An average and a large degree of fibrosis were modeled. We simulated defibrillation by application of an extracellular current for a short duration (5 ms). We explored the effects of myocyte-fibroblast coupling, intra-fibroblast conductivity and patch length on the strength of the virtual electrodes present at the borders of the normal and fibrotic tissue. We discriminated between effects on myocyte and fibroblast membranes at both borders of the patch. Similarly, we studied defibrillation in two-dimensional models of fibrotic tissue. Square and disk-like patches of fibrotic tissue were embedded in control tissue. We quantified the influence of the geometry and fibrosis composition on virtual electrode strength. We compared the results obtained with a square and disk shape of the fibrotic patch with results from the one-dimensional simulations. Both, one- and two-dimensional simulations indicate that extracellular current application causes virtual electrodes at boundaries of fibrotic patches. A higher degree of fibrosis and larger patch size were associated with an increased strength of the virtual electrodes. Also, patch geometry affected the strength of the virtual electrodes. Our simulations suggest that increased fibroblast-myocyte coupling and intra-fibroblast conductivity reduce virtual electrode strength. However, experimental data to constrain these modeling parameters are limited and thus pinpointing the magnitude of the reduction will require further understanding of electrical coupling of fibroblasts in native cardiac tissues. We propose that the findings from our computational studies are important for development of patient-specific protocols for internal defibrillators

Data Combinations Accounting for LISA Spacecraft Motion

LISA is an array of three spacecraft in an approximately equilateral triangle configuration which will be used as a low-frequency gravitational wave detector. We present here new generalizations of the Michelson- and Sagnac-type time-delay interferometry data combinations. These combinations cancel laser phase noise in the presence of different up and down propagation delays in each arm of the array, and slowly varying systematic motion of the spacecraft. The gravitational wave sensitivities of these generalized combinations are the same as previously computed for the stationary cases, although the combinations are now more complicated. We introduce a diagrammatic representation to illustrate that these combinations are actually synthesized equal-arm interferometers.Comment: 10 pages, 3 figure

Role of K(ATP)(+) channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

The role of ATP-sensitive K(+) (K(ATP)(+)) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of K(ATP)(+) channels to vasomotor tone regulation in the systemic, pulmonary, and coronary vascular bed in nine treadmill-exercising swine. Exercise up to 85% of maximum heart rat

Olive oil and prevention of chronic diseases: summary of an International conference

Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans

Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: Systematic review and meta-analysis

Objective: To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. Design: Systematic review and meta-analysis. Data sources: Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. Eligibility criteria: Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. Results: 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish

An adverbial approach for the formal specification of topological constraints involving regions with broad boundaries

Topological integrity constraints control the topological properties of spatial objects and the validity of their topological relationships in spatial databases. These constraints can be specified by using formal languages such as the spatial extension of the Object Constraint Language (OCL). Spatial OCL allows the expression of topological constraints involving crisp spatial objects. However, topological constraints involving spatial objects with vague shapes (e.g., regions with broad boundaries) are not supported by this language. Shape vagueness requires using appropriate topological operators (e.g., strongly Disjoint, fairly Meet) to specify valid relations between these objects; otherwise, the constraints cannot be respected. This paper addresses the problem of the lack of terminology to express topological constraints involving regions with broad boundaries. We propose an extension of Spatial OCL based on a geometric model for objects with vague shapes and an adverbial approach for topological relations between regions with broad boundaries. This extension of Spatial OCL is then tested on an agricultural database

Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: prospective cohort study

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases

Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studie

Aims/hypothesis: Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes. Methods: We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses’ Health Study, 84,310 women from the Nurses’ Health Study II and 35,743 men from the Health Professionals’ Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis. Results: We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], ptrend <0.0001; 1.29 [1.22, 1.36], ptrend <0.0001 and 1.32 [1.24, 1.40], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], ptrend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). Conclusions/interpretation: This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality

Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying efects of the TCF7L2-rs7903146 polymorphism

Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated