The feasibility of implementing high-intensity interval training in cardiac rehabilitation settings: A retrospective analysis

Background: Cardiovascular disease is the leading cause of death worldwide. Notwithstanding the well-known benefits of cardiac rehabilitation (CR), adherence to CR remains low, particularly in women. High-intensity interval training (HIIT) has received specific attention as an emerging exercise-training paradigm that addresses frequently cited barriers to CR (i.e. lack of motivation/enjoyment and time, perceiving exercise regime as tiring/boring) and improves cardiovascular risk factors. Previous studies have examined the safety of HIIT in CR; there is little evidence on the feasibility of HIIT in CR. The aims of this study were to evaluate the feasibility of HIIT within a CR setting and examine the sex differences regarding the feasibility of such programming. Methods: Patients attended an on-site HIIT CR program (10-min warm-up, 25 min of interspersed high-intensity [HI - 4 min at 85–95% HRpeak] and lower intensity [LO - 3 min at 60–70% HRpeak] intervals, 10-min cool-down) twice weekly for 10 weeks. Heart rate (HR) and the Borg rating of perceived exertion (RPE) scale (6–20 points) were recorded at each session. Feasibility was assessed by: [1] attendance and compliance: the number of sessions attended and the compliance to the prescribed HI and LO HR ranges; [2] the patient experience: patients’ perceived effort, program difficulty, if the program was challenging and satisfying; and, [3] safety. Descriptive statistics were used to report the means and their variations. Mann-Whitney U tests and Chi-square analyses were performed to examine sex-differences. Results: A total of 151 patients (33% women, 57.5 ± 9.1 years) attended the HIIT program and completed 16 ± 5 classes with a low attrition rate (11.3%). Most patients met or exceeded the prescribed target HR for the HI (80%) and LO (84%) intervals, respectively. Patients reported a “somewhat hard” RPE for HI (14 ± 2 points) and “very light” for LO (10 ± 2 points) intervals. All patients were satisfied with the program and found it challenging. Most patients found HIIT to be difficult (7 ± 2 points, scale range 0–10 points), yet safe (97%). Three vasovagal episodes occurred and more women dropped-out of the program than men (p < 0.01). Conclusions: HIIT is a feasible, safe and well-received exercise paradigm in a CR setting

Lagrange Multipliers in Infinite-Dimensional Systems, Methods of

International audienceThis entry will describe Lagrange multipliers method using a formulation which is valid for infinite-dimensional dynamical systems. The method of Lagrange multipliers is employed to deal with systems subject to constraints. The theoretical foundations of this method are presented, and a proof of the main theorem is illustrated for the relevant case of constraints defined on a Banach vector space

Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells

Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells. Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in MCF-7 (drug-sensitive) and MDA-MB-231 (drug-insensitive) cells. Furthermore, when we transiently silenced Bcl-2, both cisplatin and paclitaxel induced apoptosis more than parental cells. Dose dependent induction of apoptosis by drugs was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin was significant on both cell lines, the effect of paclitaxel was much less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in MDA-MB-231 cells pretreated with HA14-1, caspases and Bcl-2 family proteins were studied. The apoptotic effect of cisplatin with or without HA14-1 pre-treatment is shown to be caspase-dependent. Among pro-apoptotic Bcl-2 proteins, Bax and Puma were found to be up-regulated whereas Bcl-2 and Bcl-x(L) were down-regulated when cells were pretreated with HA14-1 followed by paclitaxel or cisplatin. Enforced Bcl-2 expression in MDA-MB-231 cells abrogated the sensitizing effect of HA14-1 in cisplatin induced apoptosis. These results suggest that the potentiating effect of HA14-1 is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs

A methodology for obtaining plasticity characteristics of metallic coatings via instrumented indentation

A methodology is presented for inferring the yield stress and work-hardening characteristics of metallic coatings from indentation data. It involves iterative use of FEM modelling, with predicted outcomes (load-displacement relationships and residual indent shapes) being systematically compared with experimental data. The cases being considered are ones in which the indenter penetration depth is a significant fraction of the coating thickness, so that the properties of the substrate, and possibly of the interface, are of significance. The methodology is thus suitable for the testing of thin coatings. In the present work, the coatings were in fact relatively thick (hundreds of microns) and the (spherical) indenter penetration was a substantial fraction of this. In this way, the basic validity of the methodology could be investigated with minimal complications from effects related to microstructure, oxide films, surface roughness etc. Furthermore, the properties of both coating and substrate (in the through-thickness direction) were established separately via conventional compression testing. The systems studied were copper (yield stress ~15 MPa) on stainless steel (yield stress ~350 MPa) and vice versa. Both exhibited significant work hardening. It is concluded that the methodology is basically reliable, with relatively good sensitivity and resolution, although this does depend on several factors, which are highlighted in the paper. It is unlikely to be suitable for very thin (sub-micron) films, but should be reasonably accurate for coatings of thickness down to a few microns.This work has been supported by EPSRC (grant RG62695) and also by AWE, as part of an ongoing collaboration aimed at the development of robust and user-friendly tools for the extraction of mechanical property characteristics from instrumented indentation data.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ijsolstr.2015.10.029 In compliance with current EPSRC requirements, the input data for the indentation modeling described in this paper, including meshing and boundary condition specifications, are available at the following URL: www.ccg.msm.cam.ac.uk/publications/resources. These files can be downloaded and used in ABAQUS FEM models. Data supplied are for a representative case (with a spherical indenter and radial symmetry)

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

Carbon-fiber tips for scanning probe microscopes and molecular electronics experiments

We fabricate and characterize carbon-fiber tips for their use in combined scanning tunneling and force microscopy based on piezoelectric quartz tuning fork force sensors. An electrochemical fabrication procedure to etch the tips is used to yield reproducible sub-100-nm apex. We also study electron transport through single-molecule junctions formed by a single octanethiol molecule bonded by the thiol anchoring group to a gold electrode and linked to a carbon tip by the methyl group. We observe the presence of conductance plateaus during the stretching of the molecular bridge, which is the signature of the formation of a molecular junction.Comment: Conference Proceeding (Trends in NanoTechnology 2011, Tenerife SPAIN); Nanoscale Research Letters, (2012) 7:25

A model for selection of eyespots on butterfly wings

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell

Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets

<p>Abstract</p> <p>Background:</p> <p><it>Mycobacterium tuberculosis </it>continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuberculosis target metabolic enzymes. Genome-scale models can be used for analysis, discovery, and as hypothesis generating tools, which will hopefully assist the rational drug development process. These models need to be able to assimilate data from large datasets and analyze them.</p> <p>Results:</p> <p>We completed a bottom up reconstruction of the metabolic network of <it>Mycobacterium tuberculosis </it>H37Rv. This functional <it>in silico </it>bacterium, <it>iNJ</it>661, contains 661 genes and 939 reactions and can produce many of the complex compounds characteristic to tuberculosis, such as mycolic acids and mycocerosates. We grew this bacterium <it>in silico </it>on various media, analyzed the model in the context of multiple high-throughput data sets, and finally we analyzed the network in an 'unbiased' manner by calculating the Hard Coupled Reaction (HCR) sets, groups of reactions that are forced to operate in unison due to mass conservation and connectivity constraints.</p> <p>Conclusion:</p> <p>Although we observed growth rates comparable to experimental observations (doubling times ranging from about 12 to 24 hours) in different media, comparisons of gene essentiality with experimental data were less encouraging (generally about 55%). The reasons for the often conflicting results were multi-fold, including gene expression variability under different conditions and lack of complete biological knowledge. Some of the inconsistencies between <it>in vitro </it>and <it>in silico </it>or <it>in vivo </it>and <it>in silico </it>results highlight specific loci that are worth further experimental investigations. Finally, by considering the HCR sets in the context of known drug targets for tuberculosis treatment we proposed new alternative, but equivalent drug targets.</p