Faculty Bibliography

Twelve healthy participants performed two identical high-intensity 40 km cycling trials (morning and evening) under controlled laboratory conditions. Echocardiograms and venous blood samples were collected before and after each exercise bout. Cardiac electro-mechanical-delay (cEMD) was measured as QRS-complex onset to peak systolic (S') and early diastolic (E') tissue velocities. Myocardial strain and strain rates were assessed in longitudinal, circumferential and radial planes at the left ventricular apex and base. Cardiac troponin I (cTnI) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) were assessed as biomarkers of cardiomyocyte damage and wall stress. cEMD was lengthened after both morning (S': 160 ± 30 vs. 193 ± 27; E': 478 ± 60 vs. 620 ± 87, P < 0.05) and evening (S': 155 ± 29 vs. 195 ± 31; E': 488 ± 42 vs. 614 ± 61, P < 0.05) trials. A reduction in peak S' (morning: 6.96 ± 1.12 vs. 6.66 ± 0.89; evening: 7.09 ± 0.94 vs. 7.02 ± 0.76) was correlated with cEMD (r = -0.335, P < 0.05). Peak longitudinal strain was reduced, atrial strain rates were sporadically increased in both trials post-cycling. cTnI was elevated in only two participants (0.04 µg · L(-1), 0.03 µg · L(-1)), whilst NT-proBNP was below the clinical cut-off point in all participants. Prolonged-cycling resulted in a lengthening of cEMD, small changes in aspects of left ventricular deformation and sporadic increases in cardiac biomarkers. None of these effects were moderated by time-of-day.

We present two electromagnetic frameworks to compare the surface stresses on spheroidal particles in the optical stretcher (a dual-beam laser trap that can be used to capture and deform biological cells). The first model is based on geometrical optics (GO) and limited in its applicability to particles that are much greater than the incident wavelength. The second framework is more sophisticated and hinges on the generalized Lorenz-Mie theory (GLMT). Despite the difference in complexity between both theories, the stress profiles computed with GO and GLMT are in good agreement with each other (relative errors are on the order of 1-10%). Both models predict a diminishing of the stresses for larger wavelengths and a strong increase of the stresses for shorter laser-cell distances. Results indicate that surface stresses on a spheroid with an aspect ratio of 1.2 hardly differ from the stresses on a sphere of similar size. Knowledge of the surface stresses and whether or not they redistribute during the stretching process is of crucial importance in real-time applications of the stretcher that aim to discern the viscoelastic properties of cells for purposes of cell characterization, sorting, and medical diagnostics.

Myelination and its regenerative counterpart remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo CNS environment. Little is known of how variation in mechanical properties over the physiological range affects OPC biology. Here, we show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and differentiation capacity in vitro depend on the mechanical stiffness of polymer hydrogel substrata. Most of these properties are optimal at the intermediate values of CNS tissue stiffness. Moreover, many of these properties measured for cells on gels of optimal stiffness differed significantly from those measured on glass or polystyrene. The dependence of OPC differentiation on the mechanical properties of the extracellular environment provides motivation to revisit results obtained on nonphysiological, rigid surfaces. We also find that OPCs stiffen upon differentiation, but that they do not change their compliance in response to substratum stiffness, which is similar to embryonic stem cells, but different from adult stem cells. These results form the basis for further investigations into the mechanobiology of cell function in the CNS and may specifically shed new light on the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis.

Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥ 2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts.

The combination of high power laser beams with microfluidic delivery of cells is at the heart of high-throughput, single-cell analysis and disease diagnosis with an optical stretcher. So far, the challenges arising from this combination have been addressed by externally aligning optical fibres with microfluidic glass capillaries, which has a limited potential for integration into lab-on-a-chip environments. Here we demonstrate the successful production and use of a monolithic glass chip for optical stretching of white blood cells, featuring microfluidic channels and optical waveguides directly written into bulk glass by femtosecond laser pulses. The performance of this novel chip is compared to the standard capillary configuration. The robustness, durability and potential for intricate flow patterns provided by this monolithic optical stretcher chip suggest its use for future diagnostic and biotechnological applications.

OBJECTIVES/OBJECTIVE:To evaluate the electrocardiographic (ECG) characteristics of West-Asian, black and Caucasian male athletes competing in Qatar using the 2010 recommendations for 12-lead ECG interpretation by the European Society of Cardiology (ESC). DESIGN/METHODS:Cardiovascular screening with resting 12-lead ECG analysis of 1220 national level athletes (800 West-Asian, 300 black and 120 Caucasian) and 135 West-Asian controls was performed. RESULTS:Ten per cent of athletes presented with 'uncommon' ECG findings. Black African descent was an independent predictor of 'uncommon' ECG changes when compared with West-Asian and Caucasian athletes (p<0.001). Black athletes also demonstrated a significantly greater prevalence of lateral T-wave inversions than both West-Asian and Caucasian athletes (6.1% vs 1.6% and 0%, p<0.05). The rate of 'uncommon' ECG changes between West-Asian and Caucasian athletes was comparable (7.9% vs 5.8%, p>0.05). Seven athletes (0.6%) were identified with a disease associated with sudden death; this prevalence was two times higher in black athletes than in West-Asian athletes (1% vs 0.5%), and no cases were reported in Caucasian athletes and West-Asian controls. Eighteen West-Asian and black athletes were identified with repolarisation abnormalities suggestive of a cardiomyopathy, but ultimately, none were diagnosed with a cardiac disease. CONCLUSION/CONCLUSIONS:West-Asian and Caucasian athletes demonstrate comparable rates of ECG findings. Black African ethnicity is positively associated with increased frequencies of 'uncommon' ECG traits. Future work should examine the genetic mechanisms behind ECG and myocardial adaptations in athletes of diverse ethnicity, aiding in the clinical differentiation between physiological remodelling and potential cardiomyopathy or ion channel disorders.

Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (<seconds). Intriguingly, only the two circulating myeloid cell types have increased short time scale compliance and flow better through microfluidic constrictions. Moreover, all three differentiated cell types reduce their steady-state viscosity by more than 50% and show over 140% relative increase in their ability to migrate through tissue-like pores at long time-scales (>minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies.

OBJECTIVES/OBJECTIVE:Seventeen male participants (mean (SD) (range): age 33.5 (6.5) years (46-26 years), body mass 80 (9.2) kg (100-63 kg), height 1.81 (0.06) m (1.93- 1.70 m)) ran a marathon to investigate the relationship between systolic function (using cardiac magnetic resonance (CMR)) and diastolic function (using echocardiography) against biomarkers of cardiac damage. METHODS:Echocardiographic and cardiac troponin I (cTnI)/N-terminal pro-B-type natriuretic peptide (NTproBNP) data were collected 24 h premarathon, immediately postmarathon and 6 h postmarathon. CMR data were collected 24 h premarathon and at 6 h postmarathon. RESULTS:Body mass was significantly reduced postmarathon (80 (9.2) vs 78.8 (8.6) kg; p<0.001). There was a significant E/A reduction postmarathon (1.11 (0.34) vs 1.72 (0.44); p<0.05) that remained depressed 6 h postmarathon (1.49 (0.43); p<0.05). CMR demonstrated left ventricular end-diastolic and end-systolic volumes were reduced postmarathon, with a preserved stroke volume. Left ventricular ejection fraction 6 h postmarathon significantly increased (64.4% (4.2%) vs 67.4% (5%); p<0.05). There were significant elevations in cTnI (0.00 vs 0.04 (0.03) μg/l; p<0.05) and NTproBNP (37.4 (24.15) ng/l vs 59.34 (43.3) ng/l; p<0.05) immediately postmarathon. Eight runners had cTnI elevations immediately postmarathon above acute myocardial infarction cutoff levels (≥0.03 μg/l). No correlations between cTnI/NTproBNP and measures of diastolic function (E, A, E/A, isovolumic relaxation time, E deceleration time and E/E') or measures of systolic function (stroke volume or ejection fraction) were observed immediately postmarathon or 6 h postmarathon. CONCLUSIONS:Biomarkers of cardiac damage after prolonged exercise are not associated with either systolic or diastolic functional measures.