Limits of ventricular function: from athlete's heart to a failing heart

The interest in the study of ventricular function has grown considerably in the last decades. In this review, we analyse the extreme values of ventricular function as obtained with Doppler echocardiography. We mainly focus on the parameters that have been used throughout the history of Doppler echocardiography to assess left ventricular (LV) systolic and diastolic function. The ‘athlete's heart’ would be the highest expression of ventricular function whereas its lowest expression is represented by the failing heart, independently from the original aetiology leading to this condition. There are, however, morphological similarities (dilation and hypertrophy) between the athlete's and the failing heart, which emerge as physiological and pathophysiological adaptations, respectively. The introduction of new assessment techniques, specifically speckle tracking, may provide new insight into the properties that determine ventricular filling, specifically left ventricular twisting. The concept of ventricular function must be always considered, although it may not be always possible to distinguish the normal heart of sedentary individuals from that of highly trained hearts based solely on echocardiographic or basic studies.

The impact of short duration, high intensity exercise on cardiac troponin release

The aim of this study was to assess the appearance of cardiac troponins (cTnI and/or cTnT) after a short bout (30 s) of ‘all-out’ intense exercise and to determine the stability of any exercise-related cTnI release in response to repeated bouts of high intensity exercise separated by 7 days recovery. Eighteen apparently healthy, physically active, male university students completed two all-out 30 s cycle sprint, separated by 7 days. cTnI, blood lactate and catecholamine concentrations were measured before, immediately after and 24 h after each bout. Cycle performance, heart rate and blood pressure responses to exercise were also recorded. Cycle performance was modestly elevated in the second trial [6·5% increase in peak power output (PPO)]; there was no difference in the cardiovascular, lactate or catecholamine response to the two cycle trials. cTnI was not significantly elevated from baseline through recovery (Trial 1: 0·06 ± 0·04 ng ml−1, 0·05 ± 0·04 ng ml−1, 0·03 ± 0·02 ng ml−1; Trial 2: 0·02 ± 0·04 ng ml−1, 0·04 ± 0·03 ng ml−1, 0·05 ± 0·06 ng ml−1) in either trial. Very small within subject changes were not significantly correlated between the two trials (r = 0·06; P>0·05). Subsequently, short duration, high intensity exercise does not elicit a clinically relevant response in cTnI and any small alterations likely reflect the underlying biological variability of cTnI measurement within the participants.

Control circuits for avalanche photodiodes

Avalanche Photodiodes (APDs) have been used in a wide range of low light sensing applications such as DNA sequencing, quantum key distribution, LIDAR and medical imaging. To operate the APDs, control circuits are required to achieve the desired performance characteristics. This thesis presents the work on development of three control circuits including a bias circuit, an active quench and reset circuit and a gain control circuit all of which are used for control and performance enhancement of the APDs. The bias circuit designed is used to bias planar APDs for operation in both linear and Geiger modes. The circuit is based on a dual charge pumps configuration and operates from a 5 V supply. It is capable of providing milliamp load currents for shallow-junction planar APDs that operate up to 40 V. With novel voltage regulators, the bias voltage provided by the circuit can be accurately controlled and easily adjusted by the end user. The circuit is highly integrable and provides an attractive solution for applications requiring a compact integrated APD device. The active quench and reset circuit is designed for APDs that operate in Geiger-mode and are required for photon counting. The circuit enables linear changes in the hold-off time of the Geiger-mode APD (GM-APD) from several nanoseconds to microseconds with a stable setting step of 6.5 ns. This facilitates setting the optimal `afterpulse-free' hold-off time for any GM-APD via user-controlled digital inputs. In addition this circuit doesn’t require an additional monostable or pulse generator to reset the detector, thus simplifying the circuit. Compared to existing solutions, this circuit provides more accurate and simpler control of the hold-off time while maintaining a comparable maximum count-rate of 35.2 Mcounts/s. The third circuit designed is a gain control circuit. This circuit is based on the idea of using two matched APDs to set and stabilize the gain. The circuit can provide high bias voltage for operating the planar APD, precisely set the APD’s gain (with the errors of less than 3%) and compensate for the changes in the temperature to maintain a more stable gain. The circuit operates without the need for external temperature sensing and control electronics thus lowering the system cost and complexity. It also provides a simpler and more compact solution compared to previous designs. The three circuits designed in this project were developed independently of each other and are used for improving different performance characteristics of the APD. Further research on the combination of the three circuits will produce a more compact APD-based solution for a wide range of applications.

Electrochemical biosensor based on microfabricated electrode arrays for life sciences applications

In developing a biosensor, the utmost important aspects that need to be emphasized are the specificity and selectivity of the transducer. These two vital prerequisites are of paramount in ensuring a robust and reliable biosensor. Improvements in electrochemical sensors can be achieved by using microelectrodes and to modify the electrode surface (using chemical or biological recognition layers to improve the sensitivity and selectivity). The fabrication and characterisations of silicon-based and glass-based gold microelectrode arrays with various geometries (band and disc) and dimension (ranging from 10 μm-100 nm) were reported. It was found that silicon-based transducers of 10 μm gold microelectrode array exhibited the most stable and reproducible electrochemical measurements hence this dimension was selected for further study. Chemical electrodeposition on both 10 μm microband and microdisc were found viable by electro-assisted self-assembled sol-gel silica film and nanoporous-gold electrodeposition respectively. The fabrication and characterisations of on-chip electrochemical cell was also reported with a fixed diameter/width dimension and interspacing variation. With this regard, the 10 μm microelectrode array with interspacing distance of 100 μm exhibited the best electrochemical response. Surface functionalisations on single chip of planar gold macroelectrodes were also studied for the immobilisation of histidine-tagged protein and antibody. Imaging techniques such as atomic force microscopy, fluorescent microscopy or scanning electron microscope were employed to complement the electrochemical characterisations. The long-chain thiol of self-assembled monolayer with NTA-metal ligand coordination was selected for the histidine-tagged protein while silanisation technique was selected for the antibody immobilisation. The final part of the thesis described the development of a T-2 labelless immunosensor using impedimetric approach. Good antibody calibration curve was obtained for both 10 μm microband and 10 μm microdisc array. For the establishment of the T-2/HT-2 toxin calibration curve, it was found that larger microdisc array dimension was required to produce better calibration curve. The calibration curves established in buffer solution show that the microelectrode arrays were sensitive and able to detect levels of T-2/HT-2 toxin as low as 25 ppb (25 μg kg-1) with a limit of quantitation of 4.89 ppb for a 10 μm microband array and 1.53 ppb for the 40 μm microdisc array.

Anatomical identification of extracellularly recorded cells in large-scale multielectrode recordings.

This study combines for the first time two major approaches to understanding the function and structure of neural circuits: large-scale multielectrode recordings, and confocal imaging of labeled neurons. To achieve this end, we develop a novel approach to the central problem of anatomically identifying recorded cells, based on the electrical image: the spatiotemporal pattern of voltage deflections induced by spikes on a large-scale, high-density multielectrode array. Recordings were performed from identified ganglion cell types in the macaque retina. Anatomical images of cells in the same preparation were obtained using virally transfected fluorescent labeling or by immunolabeling after fixation. The electrical image was then used to locate recorded cell somas, axon initial segments, and axon trajectories, and these signatures were used to identify recorded cells. Comparison of anatomical and physiological measurements permitted visualization and physiological characterization of numerically dominant ganglion cell types with high efficiency in a single preparation.

In vivo small animal micro-CT using nanoparticle contrast agents.

Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

Variaciones termométricas en la planta del pie y piernas valorada en corredores antes y después de correr 30 km

La termometría es una técnica no invasiva que permite cuantificar los cambios en la temperatura cutánea y evaluarla de forma cuantitativa. El aumento significativo de la temperatura puede indicar la existencia de patología. Se ha demostrado que la actividad muscular induce procesos de transferencia de calor entre los músculos y las capas superficiales de tejido. En este estudio queremos cuantificar los cambios de temperatura que se producen en los músculos del pie y miembro inferior tras una carrera de 30 km, para ello hemos utilizado una cámara termográfica de alta resolución. Contamos con la colaboración voluntaria de 32 sujetos sanos a los que procedimos a tomar fotografías de la planta del pie, parte anterior de la pierna, parte posterior de la pierna, parte anterior del muslo y parte posterior del muslo en dos etapas, primero antes de la carrera y segunda toma después de la carrera de 30 km, de esta manera pudimos valorar si había o no variación de temperatura en las zonas seleccionadas. Tras el análisis de los datos obtenidos encontramos significativas variaciones térmicas en Talón, cabeza primer metatarsiano, cabeza segundo metatarsiano, cabeza tercer metatarsiano, cabeza cuarto metatarsiano, cabeza quinto metatarsiano, apófisis estiloides quinto metatarsiano, arco longitudinal interno, maléolo interno, maléolo externo, peroneo lateral largo, vasto interno, vasto externo, recto femoral, tensor de la fascia lata, inserción cuádriceps, gemelo interno, tendón de Aquiles y Biceps femoral.

Second Metatarsophalangeal joint Synovitis: Update

In podiatric clinics is very common to find inflamatory process in metatarsophalangeal joint capsule , plantar plate and collateral ligaments damage, but it is not clearly recognized. Many authors hipotetized with joint instability of multiple aetiology and his concomitant evolution in different stages with own joint disease. This pathology has more incidence in second metatarsophalangeal joint than third and others and it is a common etiology of metatarsal pain. Bad biomechanics alters forefoot function and can produce overload in capsular joint, decreasing mobility and getting worse the pathology.

ROLE OF CAVEOLIN-3 IN THE MODULATION OF HERG POTASSIUM CHANNEL

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr) that is important for cardiac repolarization. Previously, we have discovered that hERG channels rapidly internalize in low extracellular K+ ([K+]o). In cell culture, this process is driven by the endocytic protein, caveolin-1 (Cav1), which is an integral player in the caveolae-dependant endocytosis pathway. However, in the heart, Caveolin-3 (Cav3) is, in fact, the predominant form in the myocyte, and thus may play a direct role in regulating hERG expression in the heart. Thus, I hypothesize that this reduction of hERG conductance in cardiac myocytes derives from the presence of Cav3, which is integral regulator of hERG homeostasis innately in the heart. To investigate the effect of Cav3 on hERG, I overexpressed Cav3 in human embryonic kidney 293 (HEK-293) cells stably expressing hERG channels. Cav3 overexpression significantly and specifically decreased both the hERG current amplitude and the mature channel expression in normal culture conditions. Co-immunoprecipitation analysis and confocal imaging demonstrated an association between hERG and Cav3 in HEK cells as well as rat and rabbit cardiomyocytes. Mechanistically, I discovered that Cav3 possesses a faster turnover rate compared to Cav1, and can enhance hERG degradation through up-regulating mature channel ubiquitination via the ubiquitin ligase, NEDD4-2. Knockdown of Cav3 in neonatal cardiac myocytes also enhanced hERG expression. My data indicate that Cav3 participates in hERG trafficking, and is an important regulator of hERG channel homeostasis in cardiac myocytes. This information provides a platform for future intervention of the hERG-induced type-2 long QT syndrome (LQTS).

Microtubules as antiparasitic drug targets

Background: Parasitic diseases including malaria, leishmaniasis and schistosomiasis take a terrible toll of human life, health and productivity, especially in tropical and subtropical regions, and are also highly significant in animal health worldwide. Antiparasitic drugs are the mainstays of control of most of these diseases, but in many cases current therapies are inadequate and in some the situation is deteriorating because of drug resistance. Microtubules, as essential components of almost all eukaryotic cells, are proven drug targets in many helminth diseases and show promise as targets for the development of new antiprotozoal drugs. Objective: This article reviews the chemistry of the microtubule inhibitors in current use and under investigation as antiparasitic agents, their activities against the major parasites and their mechanisms of action. New directions in both inhibitor chemistry and biological evaluation are discussed. Conclusions: The most promising immediate avenues for discovery and design appear to lie in development of novel benzimidazoles for helminth parasites and compounds based on antimitotic herbicides for protozoal parasites. New understanding from functional genomics, structural biology and microtubular imaging will help accelerate the development of completely novel antiparasitic drugs targeting microtubules.

A study of magnetic bright points in the Na I D1 line.

High-cadence, multiwavelength, optical observations of solar magnetic bright points (MBPs), captured at the disk center using the ROSA and IBIS imaging systems on the Dunn Solar Telescope, are presented. MBPs manifesting in the Na I D-1 core are found to preferentially exist in regions containing strong downflows, in addition to cospatial underlying photospheric magnetic field concentrations. Downdrafts within Na I D-1 bright points exhibit speeds of up to 7 km s(-1), with preferred structural symmetry in intensity, magnetic field, and velocity profiles about the bright point center. Excess intensities associated with G-band and Ca II K observations of MBPs reveal a power-law trend when plotted as a function of the magnetic flux density. However, Na I D-1 observations of the same magnetic features indicate an intensity plateau at weak magnetic field strengths below approximate to 150 G, suggesting the presence of a two-component heating process: one which is primarily acoustic and the other predominantly magnetic. We suggest that this finding is related to the physical expansion of magnetic flux tubes, with weak field strengths (approximate to 50 G) expanding by similar to 76%, compared to a similar to 44% expansion when higher field strengths (approximate to 150 G) are present. These observations provide the first experimental evidence of rapid downdrafts in Na I D-1 MBPs and reveal the nature of a previously unresolved intensity plateau associated with these structures.