Post-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology

We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling. Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca2+ current, transient outward and inward rectifier K+ currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (∼20%) in those with and without post-CS AF. Conclusion: Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment

Association of Video Game Use With Body Mass Index and Other Energy-Balance Behaviors in Children

Importance Childhood obesity is one of the biggest public health threats facing the UK, and video game use is considered a risk behavior for obesity among children. However, few studies have explored the prospective association between video game use and body mass index (BMI) or the potential mediators of this association. Objectives To investigate whether a longer-term association exists between video game use at a young age and BMI SD score in later years, independent of television use, and to ascertain whether this association is mediated by other energy-balance behaviors. Design, Setting, and Participants This cohort study is a secondary analysis of data from the Millennium Cohort Study, a nationally representative sample of children who were born in the UK between September 1, 2000, and January 31, 2002, that focused on data collected when the children were aged 5, 7, 11, and 14 years. Data for all variables, except BMI, were provided by parental or caregiver reporting if the children were younger than 14 years of age. At age 14 years, the children self-reported their own behavior. Initial data analysis was conducted between September 18, 2018, and September 28, 2018, with supplementary analyses conducted from October 7, 2019, to November 22, 2019. Main Outcomes and Measures The main outcome variable was BMI SD scores, with video game use as the exposure variable of interest. Physical activity, bedtime regularity, sugar-sweetened beverage consumption, and high-calorie food consumption were included as potential mediating behaviors. Results The full sample comprised 16 376 children and had a nearly equal number of boys (8393 [51.3%]) and girls (7983 [48.7%]). Every 1 SD increase in the number of hours of video game use at age 5 years was associated with a β = 0.018 higher BMI SD score at age 14 years (95% CI, 0.004-0.032). A small partial mediation of this association was found (direct association: β = 0.017 [95% CI, 0.003-0.031]; indirect association: β = 0.0011 [95% CI, 0.0003-0.0019]), suggesting that irregular bedtimes and higher consumption of sugar-sweetened beverages were mediators. The mediation model accounted for 36.7% (95% CI, 35.5-37.8) of the variance of the BMI SD score at age 14 years. Conclusions and Relevance Results of this study suggest a small (and not clinically meaningful) association between video game use in early childhood and higher BMI in later years, which may be mediated by irregular bedtimes and higher consumption of sugar-sweetened beverages. Future interventions to prevent childhood obesity should incorporate health promotion in mainstream video games to target children most at risk because of their high level of video game use

Circulating Extracellular Vesicles Are Strongly Associated With Cardiovascular Risk Markers

Data Availability Statement: The datasets presented in this study can be found in an online repository, which is the University of Reading Research Data Archive at https://doi.org/10.17864/1947.000366.Copyright © 2022 Zhou, Bozbas, Allen-Redpath and Yaqoob. Background: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs. Objective: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs. Design: Subjects (n = 40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs. Results: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk. Conclusion: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs.Biotechnology and Biological Sciences Research Council (BBSRC) and the Diet and Health Research Industry Club (DRINC) (Research Grant BB/N021185/1)

Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome

Intestinal helminth infections occur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection

Associations between abundances of free-roaming gamebirds and common buzzards Buteo buteo are not driven by consumption of gamebirds in the buzzard breeding season

Releasing gamebirds in large numbers for sport shooting may directly or indirectly influence the abundance, distribution and population dynamics of native wildlife. The abundances of generalist predators have been positively associated with the abundance of gamebirds. These relationships have implications for prey populations, with the potential for indirect impacts of gamebird releases on wider biodiversity. To understand the basis of these associations, we investigated variation in territory size, prey provisioning to chicks, and breeding success of common buzzards Buteo buteo, and associations with variation in the abundances of free- roaming gamebirds, primarily pheasants Phasianus colchicus, and of rabbits Oryctolagus cuniculus and field voles Microtus agrestis, as important prey for buzzards. The relative abundance of game-birds, but not those of rabbits or voles, was weakly but positively correlated with our index of buzzard territory size. Gamebirds were rarely brought to the nest. Rabbits and voles, and not gamebirds, were provisioned to chicks in proportion to their relative abundance. The number of buzzard chicks increased with provisioning rates of rabbits, in terms of both provisioning frequency and biomass, but not with provisioning rates for gamebirds or voles. Associations between the abundances of buzzards and gamebirds may not be a consequence of the greater availability of gamebirds as prey during the buzzard breeding season. Instead, the association may arise either from habitat or predator management leading to higher densities of alternative prey (in this instance, rabbits), or from greater availability of gamebirds as prey or carrion during the autumn and winter shooting season. The interactions between gamebird releases and associated practices of predator control and shooting itself require better understanding to more effectively intervene in any one aspect of this complex social-ecological system

Evaluating Bayesian stable isotope mixing models of wild animal diet and the effects of trophic discrimination factors and informative priors

1. Ecologists quantify animal diets using direct and indirect methods, including analysis of faeces, pellets, prey items and gut contents. For stable isotope analyses of diet, Bayesian stable isotope mixing models (BSIMMs) are increasingly used to infer the relative importance of food sources to consumers. Although a powerful approach, it has been hard to test BSIMM performance for wild animals because precise, direct dietary data are difficult to collect.2. We evaluated the performance of BSIMMs in quantifying animal diets when using δ13C and δ15N stable isotope ratios from the feathers and red blood cells of common buzzard Buteo buteo chicks. We analysed mixing model outcomes with various trophic discrimination factors (TDFs), with and without informative priors, and compared these to direct observations of prey provisioned to chicks by adults at nests, using remote cameras.3. Although BSIMMs with different TDFs varied markedly in their performance, the statistical package SIDER generated TDFs for both feathers and blood that resulted in model outputs that accorded well with direct observations of prey provisioning. Using feather TDFs derived from captive peregrines Falco peregrinus resulted in estimates of diet composition that were also similar to provisioned prey, although blood TDFs from the same study performed poorly. The inclusion of informative priors, based on conventional analysis of pellet and prey remains, markedly reduced model performance.4. BSIMMs can provide accurate assessments of diet in wild animals. TDF estimates from the SIDER package performed well. The inclusion of informative priors from conventional methods in Bayesian mixing models can transfer biases into model outcomes, leading to erroneous results. <br/

Experimental evidence that livestock grazing intensity affects cyclic vole population regulation processes

Peer reviewedPublisher PD