The prevalence of abnormal ECG in trained sportsmen

Background

Competitive sports training causes structural and conductive system changes manifesting by various electrocardiographic alterations. We undertook this study to assess the prevalence of abnormal ECG in trained Indian athletes and correlate it with the nature of sports training, that is endurance or strength training.

Methods

We evaluated a standard resting, lying 12 lead Electrocardiogram (ECG) in 66 actively training Indian athletes. Standard diagnostic criteria were used to define various morphological ECG abnormalities.

Results

33/66 (50%) of the athletes were undertaking endurance training while the other 33 (50%) were involved in a strength-training regimen. Overall 54/66 (81%) sportsmen had significant ECG changes. 68% of these changes were considered as normal training related features, while the remaining 32% were considered abnormal. There were seven common training related ECG changes–Sinus Bradycardia (21%), Sinus Arrhythmia (16%), 1st degree Atrioventricular Heart Block (6%), Type 1 2nd-degree Atrioventicular Heart Block (3%), Incomplete Right bundle branch block (RBBB) (24%), Early Repolarization (42%), Left Ventricular Hypertrophy (LVH) (14%); while three abnormal ECG changes--T-wave inversion (13%), RBBB(4%), Right ventricular hypertrophy (RVH) with strain (29%) were noted. Early repolarization (commonest change), sinus bradycardia, and incomplete RBBB were the commoner features noticed, with a significantly higher presence in the endurance trained athletes.

Conclusion

A high proportion of athletes undergoing competitive level sports training are likely to have abnormal ECG recordings. Majority of these are benign, and related to the physiological adaptation to the extreme levels of exertion. These changes are commoner during endurance training (running) than strength training (weightlifting).     

Identification of the Human P-450 Enzymes Responsible for the Sulfoxidation and Thiono-Oxidation of Diethyldithiocarbamate Methyl Ester: Role of P-450 Enzymes in Disulfiram Bioactivation

Diethyldithiocarbamate methyl ester (DDTC-Me) is a precursor to the formation of S-methyl-N,N-diethyliolcarbamate sulfoxide, the active metabolite proposed to be responsible for the alcohol deterrent effects of disulfiram. The present study investigated the role of human cytochrome P-450 (CYP) enzymes in sulfoxidation and thiono-oxidation of DDTC-Me, intermediary steps in the activation of disulfiram. Several approaches were used in an attempt to delineate the particular P-450 enzyme(s) involved in the sulfoxidation and thiono-oxidation of DDTC-Me. These approaches included the use of cDNA-expressed human P-450 enzymes, correlation analysis with sample-to-sample variation in human P-450 enzymes in a bank of human liver microsomes, and chemical and antibody inhibition studies. Multiple human P-450 enzymes (CYP3A4, CYPlA2, CYP2A6, and CYP2D6) catalyzed the sulfoxidation of DDTC-Me, as determined with cDNA-expressed enzymes. Several lines of evidence suggest that the sulfoxidation of DDTC-Me by human liver microsomes is primarily catalyzed by CYP3A4/5, including (1) a high correlation between DDTC-Me sulfoxidation and testosterone 6β-hydroxylation; (2) increased DDTC-Me sulfoxidation in the presence of α-naphthoflavone, an activator of CYP3A enzymes; (3) inhibition of this reaction by inhibitors of CYP3A4/5 enzymes, such as troleandomycin and ketoconazole; and (4) inhibition of DDTC-Mesulfoxidation by antibodies against CYP3A enzymes. On the other hand, several lines of evidence suggested that the thiono-oxidation of DDTC-Me by human liver microsomes is catalyzed in part by CYPlA2, CYP266, CYPPEl, and CYP3A4/5, including (1) these human P450 enzymes among others have the capacity to catalyze this reaction, as determined with cDNA-expressed enzymes; (2) a high correlation between DDTC-Me thiono-oxidation and testosterone 6β-hydroxylation, weak inhibition by ketoconazole, troleandomycin, and anti-CYP3A antibodies suggested a minor role for CYP3A4; (3) a high correlation with immunoreactive CYP2B6 suggested involvement of this enzyme; (4) weak inhibition of DDTC-Me thiono-oxidation by furafylline and anti-CYPlA antibody suggested involvement of CYPlA2, and (5) inhibition of DDTC-Me thiono-oxidation by DDTC and anti-CYP2E antibodies suggested a role for CYP2E1. Collectively, these data suggested CYP3A4/5 enzymes are the major contributors to the sulfoxidation of DDTC-Me by human liver microsomes, and CYPlA2, CYP2B6, CYP2E1, and CYP3A4/5 contribute toward DDTC-Me thiono-oxidation by human liver microsomes. This study, in conjunction with others (Madan et al., Drug Metab. Dispos. 23:1153–1162, 1995), may help explain the variability in disulfiram's effectiveness as an alcohol deterrent.     

A cellular solution to an information-processing problem

Signaling receptors on the cell surface are mobile and have evolved to efficiently sense and process mechanical or chemical information. We pose the problem of identifying the optimal strategy for placing a collection of distributed and mobile sensors to faithfully estimate a signal that varies in space and time. The optimal strategy has to balance two opposing objectives: the need to locally assemble sensors to reduce estimation noise and the need to spread them to reduce spatial error. This results in a phase transition in the space of strategies as a function of sensor density and efficiency. We show that these optimal strategies have been arrived at multiple times in diverse cell biology contexts, including the stationary lattice architecture of receptors on the bacterial cell surface and the active clustering of cell-surface signaling receptors in metazoan cells.The molecular characteristics of signaling receptors and their spatiotemporal organization have evolved to optimize different facets of information processing at the cell surface. A canonical information-processing problem involves designing strategies for a collection of distributed, noisy, mobile sensors to faithfully estimate a signal or function that varies in space and time (1). This problem appears naturally in many contexts, biological and nonbiological: (i) chemoattractant protein sensors on the bacteria cell surface (2, 3); (ii) galectin-glycoprotein assemblies designed for effective immune response on the surface of metazoan cells (4, 5); (iii) ligand-activated signaling protein receptors on the surface of eukaryotic cells (6–10); (iv) coclustering of integrin receptors to faithfully read and discriminate the rigidity and chemistry of a substrate (11); (v) clustering of e-cadherin receptors for effective adherence at cell–cell junctions (12); and even (vi) radio frequency (RF) sensor networks monitoring the environment or mobile targets (13). In the signal-processing community, this problem is known as data fusion or more generally information fusion (14, 15); however typical applications do not consider mobile sensors.In this paper we show how biology has, on multiple occasions, arrived at a solution to this optimization problem. The optimal solution needs to balance two opposing objectives, the need to locally assemble sensors to reduce estimation noise and the need to spread them out for broader spatial coverage. We show that in the space of strategies, this leads to a phase transition as a function of sensor density, sensor characteristics, and function properties. At very low sensor density, the optimal design corresponds to freely diffusing sensors. For sensor density above a threshold, there are two different optimal solutions as a function of a dimensionless parameter constructed from the sensor advection velocity and the correlation length and time of the incident signal. One optimal solution is that the sensors are static and located on a regular lattice grid. This is the strategy used in bacteria, such as Escherichia coli, to organize their chemoattractant receptors in a regular lattice array (3, 16), and in metazoan cells, where galectin-glycoproteins are organized in a lattice on the cell surface to effect an optimal immune response (4, 5). To realize this strategy, the cell needs to provide a rigid cortical scaffold that holds the receptors in place. Another optimal solution is to make the receptors mobile in such a way that a fraction of them form multiparticle nanoclusters, which then break up and reform randomly, the rest being uniformly distributed. Recent studies on the steady-state distribution of several cell-surface proteins reveal a stereotypical distribution of a fixed fraction of monomers and dynamic nanoclusters (6–9), and our information theoretic perspective could provide a general explanation for this. To realize this dynamic strategy, the cell surface needed to be relieved of the constraints imposed by the rigid scaffold and to be more regulatable. This strategy change needed the innovation of motor proteins and dynamic actin filaments, a regulated actomyosin machinery fueled by ATP, and a coupling of components of the cell surface to this cortical dynamic actin (17).     

Worksite Health and Wellness Programs in India

Worksite health and wellness (WH&W) are gaining popularity in targeting cardiovascular (CV) risk factors among various industries. India is a large country with a larger workforce in the unorganized sector than the organized sector. This imbalance creates numerous challenges and barriers to implementation of WH&W programs in India. Large scale surveys have identified various CV risk factors across various industries. However, there is scarcity of published studies focusing on the effects of WH&W programs in India. This paper will highlight: 1) the current trend of CV risk factors across the industrial community, 2) the existing models of delivery for WH&W in India and their barriers, and 3) a concise evidence based review of various WH&W interventions in India.