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• Manoomin (wild rice) is a sacred food and relative for Great Lakes American Indians. • University-tribal partnership transforms interdisciplinary research on manoomin. • Ten tenets for responsible university research with Indigenous peoples. • Collaborative research to support tribal sovereignty and environmental justice. Manoomin, the Ojibwe word for wild rice, grows in shallow lakes and streams and provides physical, spiritual, and cultural sustenance as a sacred food and relative for Indigenous peoples across the Great Lakes region of North America. Unfortunately, Manoomin has been declining due to multiple environmental stressors. In 2018, an interdisciplinary group from the University of Minnesota came together with natural resource managers from tribes and inter-tribal organizations to understand Manoomin within its socio-environmental context. This partnership grew despite a history fraught with settler colonial structures of knowledge production and commodification. Based on lessons learned from building this transformational partnership, this paper describes ten tenets for responsible research: 1) Honor Indigenous sovereignty and rights; 2) Address past and present harms; 3) Be on the path together with researchers and Indigenous partners; 4) Recognize, respect, and value Indigenous participation and intellectual labor; 5) Encourage the robust exchange of ideas; 6) Recognize that documents formalizing a relationship are not the whole relationship; 7) Make a plan for identifying and protecting sensitive Indigenous data; 8) Be prepared to navigate institutional obstacles; 9) Seek, support, and collaborate with diverse students; and 10) Actively listen and be open to different ways of engaging with the world. These lessons can serve as tools to form accountable partnerships that enable robust, nuanced, and effective environmental science, policy, and stewardship. [ABSTRACT FROM AUTHOR]

Background: Regional Restitution Instability Index (R2I2) and Peak ECG Restitution Slope (PERS) are promising sudden cardiac death (SCD) risk markers. R2I2 and PERS use the standard 12‑lead ECG to measure properties of electrical restitution implicated in ventricular arrhythmogenesis. We investigated the relationship between R2I2, PERS and autonomic function to inform future application of these risk markers.Methods: Blinded, prospective, observational study of 44 patients with ischaemic cardiomyopathy undergoing risk stratification for an ICD. Patients underwent an electrophysiological study for determination of R2I2 and PERS. 24-hour ambulatory ECG monitoring was carried out for determination of time-domain heart rate variability (HRV).Results: During median follow up of 22 months, 11 patients experienced ventricular arrhythmia (VA)/SCD. Weak inverse correlation was seen between R2I2 and HRV-i (rho: -0.36, p = 0.02). R2I2 and PERS were significantly higher in patients experiencing VA/SCD than those not (mean ± SEM:1.14 ± 0.11 vs 0.84 ± 0.05, p = 0.01) and (1.73 ± 0.27 vs 1.07 ± 0.08, p = 0.002) respectively. Patients with low HRV-i and high PERS had an incidence rate ratio for VA/SCD 14.5 times that of patients with high HRV-i and low PERS (p = 0.02).Conclusion: This small study suggests that there is minimal correlation between R2I2, PERS and autonomic function as measured by HRV. Combining PERS with HRV identified patients at particularly high risk of ventricular arrhythmia/SCD. A combined PERS+HRV risk marker may improve SCD risk stratification in patients with ischaemic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: The intrinsic cardiac nervous system is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function.Objective: The goals of this study were to provide a complete picture of the neurotransmitter/neuromodulator profile of the rabbit intrinsic cardiac nervous system and to determine the influence of spatially divergent ganglia on cardiac electrophysiology.Methods: Nicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff-perfused rabbit heart. Functional effects on sinus rate and atrioventricular conduction were measured. Immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase, and/or neuronal nitric oxide synthase (nNOS) was performed using whole mount preparations.Results: Stimulation within all ganglia produced either bradycardia, tachycardia, or a biphasic brady-tachycardia. Electrical stimulation of the right atrial and right neuronal cluster regions produced the largest chronotropic responses. Significant prolongation of atrioventricular conduction was predominant at the pulmonary vein-caudal vein region. Neurons immunoreactive (IR) only for ChAT, tyrosine hydroxylase, or nNOS were consistently located within the limits of the hilum and at the roots of the right cranial and right pulmonary veins. ChAT-IR neurons were most abundant (1946 ± 668 neurons). Neurons IR only for nNOS were distributed within ganglia.Conclusion: Stimulation of intrinsic ganglia, shown to be of phenotypic complexity but predominantly of cholinergic nature, indicates that clusters of neurons are capable of independent selective effects on cardiac electrophysiology, therefore providing a potential therapeutic target for the prevention and treatment of cardiac disease. [ABSTRACT FROM AUTHOR]

Natural attenuation of organic contaminants in groundwater can give rise to a series of complex biogeochemical reactions that release secondary contaminants to groundwater. In a crude oil contaminated aquifer, biodegradation of petroleum hydrocarbons is coupled with the reduction of ferric iron (Fe(III)) hydroxides in aquifer sediments. As a result, naturally occurring arsenic (As) adsorbed to Fe(III) hydroxides in the aquifer sediment is mobilized from sediment into groundwater. However, Fe(III) in sediment of other zones of the aquifer has the capacity to attenuate dissolved As via resorption. In order to better evaluate how long-term biodegradation coupled with Fe-reduction and As mobilization can redistribute As mass in contaminated aquifer, we quantified mass partitioning of Fe and As in the aquifer based on field observation data. Results show that Fe and As are spatially correlated in both groundwater and aquifer sediments. Mass partitioning calculations demonstrate that 99.9% of Fe and 99.5% of As are associated with aquifer sediment. The sediments act as both sources and sinks for As, depending on the redox conditions in the aquifer. Calculations reveal that at least 78% of the original As in sediment near the oil has been mobilized into groundwater over the 35-year lifespan of the plume. However, the calculations also show that only a small percentage of As (∼0.5%) remains in groundwater, due to resorption onto sediment. At the leading edge of the plume, where groundwater is suboxic, sediments sequester Fe and As, causing As to accumulate to concentrations 5.6 times greater than background concentrations. Current As sinks can serve as future sources of As as the plume evolves over time. The mass balance approach used in this study can be applied to As cycling in other aquifers where groundwater As results from biodegradation of an organic carbon point source coupled with Fe reduction. [ABSTRACT FROM AUTHOR]

Background: Identification of arrhythmogenic regions remains a challenge in persistent atrial fibrillation (persAF). Frequency and phase analysis allows identification of potential ablation targets.Objective: This study aimed to investigate the spatiotemporal association between dominant frequency (DF) and reentrant phase activation areas.Methods: A total of 8 persAF patients undergoing first-time catheter ablation procedure were enrolled. A noncontact array catheter was deployed into the left atrium (LA) and 2048 atrial fibrillation electrograms (AEGs) were acquired for 15 seconds following ventricular far-field cancellation. DF and phase singularity (PS) points were identified from the AEGs and tracked over consecutive frames. The spatiotemporal correlation of high DF areas and PS points was investigated, and the organization index at the core of high-DF areas was compared with that of their periphery.Results: The phase maps presented multiple simultaneous PS points that drift over the LA, with preferential locations. Regions displaying higher PS concentration showed a degree of colocalization with DF sites, with PS and DF regions being neighbors in 61.8% and with PS and DF regions overlapping in 36.8% of the time windows. Sites with highest DF showed a greater degree of organization at their core compared with their periphery. After ablation, the PS incidence reduced over the entire LA (36.2% ± 23.2%, P < .05), but especially at the pulmonary veins (78.6% ± 22.2%, P < .05).Conclusion: Multiple PS points drifting over the LA were identified with their clusters correlating spatially with the DF regions. After pulmonary vein isolation, the PS's complexity was reduced, which supports the notion that PS sites represent areas of relevance to the atrial substrate. [ABSTRACT FROM AUTHOR]

Antiarrhythmic drug therapy has seen significant challenges over the past 3 decades with unexpected results from clinical trials such as CAST, SWORD and more recently PALLAS showing harm in patients whom antiarrhythmic drugs were given based on their intended antiarrhythmic actions and previously demonstrated efficacy. These results question whether the precise mechanism of action of the drugs was understood and highlight the complexity of the situation where there is the combination of multiple actions of the antiarrhythmic drugs on various molecular systems, some of which may be unknown with associated adverse outcome, and their interaction with pre-existing abnormality in disease states in patients treated. In addition, there is no effective drug strategy for complex arrhythmias such as atrial and ventricular fibrillation. Their complex dynamics are not adequately described by the classical mechanisms of automaticity, triggered activity and re-entry. Experimental data showing that flattening of the electrical restitution curve can convert ventricular fibrillation into stable tachycardia and prevent its initiation via wavebreak, and the advancement of computation biology in the describing the behaviour of wavetip and rotors in driving fibrillation have ignited the quest for more detailed understanding of the mechanisms underlying these complex arrhythmias. Their precise ionic basis which could be targeted for drug therapy remains to be fully characterised and tested in appropriate disease models and preparations. This review summarises some of these developments in the context of antiarrhythmic drug therapy consideration. [ABSTRACT FROM AUTHOR]

Chronic gastritis from Helicobacter pylori infection is a major factor in the development of gastric adenocarcinoma. Factors that regulate gastritis severity are important in determining which individuals are susceptible to H. pylori-associated disease. Although protease-activated receptor 1 (PAR1) has been identified as one such host factor, its mechanism of action is unknown. Using chimeric mice, we demonstrated that PAR1-mediated protection against H. pylori gastritis requires bone marrow-derived cells. Analyses of the gastric mucosa revealed that PAR1 suppresses cellular infiltration and both T helper type 1 (Th1) and T helper type 17 (Th17) responses to infection. Moreover, PAR1 expression was associated with reduced vaccine-mediated protection against H. pylori. Analyses of H. pylori-stimulated macrophages revealed that PAR1 activation suppressed secretion of interleukin (IL)-12 and IL-23, key drivers of Th1 and Th17 immunity, respectively. Furthermore, PAR1 suppressed interferon regulatory factor 5 (IRF5), an important transcription factor for IL-12 and IL-23, both in the infected mucosa and following bacterial stimulation. PAR1 suppression of IRF5 and IL-12/23 secretion by macrophages provides a novel mechanism by which the host suppresses the mucosal Th1 and Th17 response to H. pylori infection. Dysregulation of this process is likely an important factor in the susceptibility of some individuals to H. pylori-associated disease. [ABSTRACT FROM AUTHOR]

Introduction: Changes in atrioventricular (AV) conduction and need for permanent pacemaker (PPM) are a recognized complication after open aortic valve replacement. We hypothesized that the need for PPM after CoreValve (Corevalve Inc, Irvine, CA) can be predicted with a combination of baseline variables. Methods: In patients undergoing transcatheter aortic valve implantation, potential clinical, electrocardiographic and echocardiographic predictors of permanent pacing requirement were studied. Results: Between January 2007 and March 2008, 34 patients with severe symptomatic aortic stenosis were recruited in a single center. Mean age was 84.4 years (SD 5.4, range 71-93). Of 34 cases paced at baseline, 3 (8.8%) were excluded from this analysis, as was the single periprocedural mortality. Of the remaining 30, 10 underwent permanent pacemaker implantation during the same admission (33.3%). PPM was for prolonged high-grade AV block in 4 cases, episodic high-grade AV block in 5, and sinus node disease in 1. Need for pacemaker was correlated to left axis deviation at baseline (P = .004, r = 0.508) and left bundle-branch block with left axis deviation (P = .002, r = 0.548). It was related to diastolic interventricular septal dimension on transthoracic echocardiography >17 mm (P = .045, r = 0.39) and the baseline thickness of the native noncoronary cusp (P = .002, r = 0.655). A susceptibility model was generated, and if at least one of (1) left bundle-branch block with left axis deviation, (2) interventricular septal dimension >17 mm, or (3) noncoronary cusp thickness >8 mm was present, the likelihood of PPM could be predicted with 75% sensitivity and 100% specificity and a receiver operating characteristic curve area of 0.93 ± 0.055 (P < .001). Conclusions: After transcatheter aortic valve implantation with CoreValve, permanent pacing was performed in around a third of patients and we present preliminary concepts towards a predictive model for this phenomenon. [Copyright &y& Elsevier]

Background: Restitution kinetics (RK) of action potential duration (APD) are classically studied by applying an extra impulse at varying diastolic intervals (DI) and might differ from RK elicited by sympathetic nerve stimulation (SNRK). Objective: To measure ''Physiological'' RK during gradual increases in heart rate caused by sympathetic nerve stimulation (SNS) and its possible spatial heterogeneities caused by non-uniform innervation of the myocardium. Methods: The SNRK was measured from rabbit hearts with intact sympathetic innervation using optical mapping. APD versus DI were plotted from left ventricles during SNS, then with pacing using identical activation interval (AI) sequences. Results: AI decreased (444 ± 18 ms to 284 ± 9 ms) in 25 s and recovered to baseline on SNS suspension (n = 10). APD versus DI plots were identical for SNS and pacing except that when maximum heart rate was reached, SNS elicited a further APD shortening compared with pacing. During SNS, APDs decreased from 216 ± 9 ms to 154 ± 7 ms (29% ± 2%) at the base and from 206 ± 12 ms to 158 ± 7 ms (20% ± 2%) at the apex. During pacing, APDs at the base decreased from 216 ± 9 ms to 170 ± 7 ms (21% ± 1%, SNS versus pacing: P < .05). In contrast, RK were similar at the apex for SNS and pacing. During SNS, the extra APD shortening at the base was associated with longer segments of RK curves with negative slopes and extra DI prolongation. Perfusion with the IKs inhibitor HMR 1556 (0.5 μM; n = 5) abolished differences in RK between SNS and pacing. Levels of KCNQ1 and tyrosine hydroxylase proteins were greater at the base than apex (n = 4), implying that apex–base distributions for IKs and sympathetic innervation are congruent with SNRK heterogeneities. Conclusion: The findings shed further insights on heterogeneities of sympathetic nerves, RK, and the role of IKs in cardiac repolarization. [Copyright &y& Elsevier]

This study evaluated the physiological demands and low back neuromuscular fatigue patterns following a daytime work shift of 21 female nurses working in geriatric wards. Subjects' heart rate (HR) at work was monitored for 8 h and surface electromyogram (EMG) of their back muscle was recorded during a 1-minute horizontal trunk holding test before and after work. Results showed that the nurses had heart rates exceeding 90 beats/min in 57% and 110 beats/min in 19% of their working hours. The EMG revealed a significant drop in initial median frequency (MF) (p = 0.04) and increase in negative slope of the MF/time plot (p<0.001) of the back muscle after work. These suggest that the muscles were fatigued after work. The nurses rated patient lifting, transfer and turning as most physically demanding, and these corresponded to the highest heart rates recorded. The physiological and neuromuscular strain on the nurses indicated that extreme care should be exercised at work, particularly towards the end of a work shift when the muscles have become fatigued. [ABSTRACT FROM AUTHOR]

Background/objectives: Cardiac contractility modulation (CCM) is a new treatment being developed for heart failure (HF) involving application of electrical current during the absolute refractory period. We have previously shown that CCM increases ventricular force through β1-adrenoceptor activation in the whole heart, a potential pro-arrhythmic mechanism. This study aimed to investigate the effect of CCM on ventricular fibrillation susceptibility. Methods: Experiments were conducted in isolated New Zealand white rabbit hearts (2.0–2.5kg, n =25). The effects of CCM (±20mA, 10ms phase duration) on the left ventricular basal and apical monophasic action potential duration (MAPD) were assessed during constant pacing (200bpm). Ventricular fibrillation threshold (VFT) was defined as the minimum current required to induce sustained VF with rapid pacing (30×30ms). Protocols were repeated during perfusion of the β1-adrenoceptor antagonist metoprolol (1.8μM). In separate hearts, the dynamic and spatial electrophysiological effects of CCM were assessed using optical mapping with di-4-ANEPPS. Results: CCM significantly shortened MAPD close to the stimulation site (Basal: 102±5 [CCM] vs. 131±6 [Control] ms, P<0.001). VFT was reduced during CCM (2.6±0.6 [CCM] vs. 6.1±0.8 [Control] mA, P<0.01) and was correlated (r2 =0.40, P<0.01) with increased MAPD dispersion (26±4 [CCM] vs. 5±1 [Control] ms, P<0.01) (n=8). Optical mapping revealed greater spread of CCM induced MAPD shortening during basal vs. apical stimulation. CCM effects were abolished by metoprolol and exogenous acetylcholine. No evidence for direct electrotonic modulation of APD was found, with APD adaptation occurring secondary to adrenergic stimulation. Conclusions: CCM decreases VFT in a manner associated with increased MAPD dispersion in the crystalloid perfused normal rabbit heart. [ABSTRACT FROM AUTHOR]

Abstract: The ‘Lambeth Conventions’ is a guidance document, written in 1987 (Walker et al., 1988), intended to be of practical value in the investigation of experimental arrhythmias induced by ischaemia, infarction, and reperfusion. This is an update, expanded to include guidance on the study of supraventricular arrhythmias, drug-induced arrhythmias, heritable arrhythmias, and advances in our knowledge in core areas since 1987. We have updated the guidance on the design and execution of experiments and the definition, classification, quantification, and analysis of all types of arrhythmias. Investigators are encouraged to adopt the conventions and test their validity in the hope that this will improve uniformity and interlaboratory comparisons, aid clinical research, facilitate antiarrhythmic drug discovery and safety assessment, and improve antiarrhythmic drug deployment for different cardiac conditions. We note that there is a gap between some definitions proposed here and their conventional clinical counterparts, and encourage the research necessary to bridge that translational gap. A web link offers the chance to vote and comment on the new conventions (https://bscr.wufoo.com/forms/z7x0x5/). [Copyright &y& Elsevier]

This paper presents an innovative approach for T-wave peak detection and subsequent T-wave end location in 12-lead paced ECG signals based on a mathematical model of a skewed Gaussian function. Following the stage of QRS segmentation, we establish search windows using a number of the earliest intervals between each QRS offset and subsequent QRS onset. Then, we compute a template based on a Gaussian-function, modified by a mathematical procedure to insert asymmetry, which models the T-wave. Cross-correlation and an approach based on the computation of Trapezium's area are used to locate, respectively, the peak and end point of each T-wave throughout the whole raw ECG signal. For evaluating purposes, we used a database of high resolution 12-lead paced ECG signals, recorded from patients with ischaemic cardiomyopathy (ICM) in the University Hospitals of Leicester NHS Trust, UK, and the well-known QT database. The average T-wave detection rates, sensitivity and positive predictivity, were both equal to 99.12%, for the first database, and, respectively, equal to 99.32% and 99.47%, for QT database. The average time errors computed for T-wave peak and T-wave end locations were, respectively, −0.38±7.12ms and −3.70±15.46ms, for the first database, and 1.40±8.99ms and 2.83±15.27ms, for QT database. The results demonstrate the accuracy, consistency and robustness of the proposed method for a wide variety of T-wave morphologies studied. [ABSTRACT FROM AUTHOR]