ResearchPad - Physiology (medical) https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The Association between Physical Activity and Eating Self-Regulation in Overweight and Obese Women]]> https://www.researchpad.co/product?articleinfo=5b460f42463d7e5878be0009

Objective

Successful weight management relies heavily on eating and exercise behaviors. However, little is known about the association between both on a psychosocial level. This study examined the relationship between exercise and eating regulation by exploring the mediating effects of negative body image investment and depressive mood, and their stability through time.

Methods

Analyses were conducted at two different moments (12 and 36 months), involving a sample of 221 overweight/obese women (age: 37.6 ± 7 years; BMI: 31.6 ± 4.1 kg/m2) that participated in a behavioral weight control intervention. Bivariate correlations and mediation analyses using Preacher & Hayes resampling procedures were conducted.

Results

At 12 months, negative body image investment was the only significant mediator of the exercise-eating relationship. This variable explained larger portions of the indirect effects of structured rather than lifestyle exercise on eating. At 36 months, negative investment and to a lesser extent depressive mood partially explained the exercise-eating association.

Conclusions

Our findings suggest that, besides physiological effects of exercise, psychological mechanisms related to body image and mood also explain the role of physical activity as a ‘gateway behavior’ for improved eating regulation in overweight women. These effects appear to be stable and may help understand the key role of exercise in long-term weight management.

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<![CDATA[Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin]]> https://www.researchpad.co/product?articleinfo=5b460f88463d7e5878be000a

Objective

The food contaminants bisphenol A (BPA), diethylhexylphthalate (DEHP), and tributyltin (TBT) are potent endocrine-disrupting compounds (EDC) known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes.

Methods

Multipotent murine mesenchymal stem cells (C3H10T1/2) were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT), and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT). The exposure was performed either for the entire culture time (0-12 days) or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG), and adipogenic marker gene expression were analyzed.

Results

MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis.

Conclusion

In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments.

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<![CDATA[A Scenario-Based Evaluation of the Middle East Respiratory Syndrome Coronavirus and the Hajj]]> https://www.researchpad.co/product?articleinfo=5ba8a31d40307c0931592a91

Between April 2012 and June 2014, 820 laboratory‐confirmed cases of the Middle East respiratory syndrome coronavirus (MERS‐CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS‐CoV in the population, with a lower reproductive number, some evidence of human‐to‐human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS‐CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human‐to‐human cases, or a combination of the two. Furthermore, MERS‐CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.

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<![CDATA[Mitochondrial Ca2+ uniporter (MCU)-dependent and MCU-independent Ca2+ channels coexist in the inner mitochondrial membrane]]> https://www.researchpad.co/product?articleinfo=5ba4d73740307c5e4d8e76c8

A protein referred to as CCDC109A and then renamed to mitochondrial calcium uniporter (MCU) has recently been shown to accomplish mitochondrial Ca2+ uptake in different cell types. In this study, we investigated whole-mitoplast inward cation currents and single Ca2+ channel activities in mitoplasts prepared from stable MCU knockdown HeLa cells using the patch-clamp technique. In whole-mitoplast configuration, diminution of MCU considerably reduced inward Ca2+ and Na+ currents. This was accompanied by a decrease in occurrence of single channel activity of the intermediate conductance mitochondrial Ca2+ current (i-MCC). However, ablation of MCU yielded a compensatory 2.3-fold elevation in the occurrence of the extra large conductance mitochondrial Ca2+ current (xl-MCC), while the occurrence of bursting currents (b-MCC) remained unaltered. These data reveal i-MCC as MCU-dependent current while xl-MCC and b-MCC seem to be rather MCU-independent, thus, pointing to the engagement of at least two molecularly distinct mitochondrial Ca2+ channels.

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<![CDATA[Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome]]> https://www.researchpad.co/product?articleinfo=5b7d2531463d7e4bac518883

The experiments investigated the applicability of two established criteria for arrhythmogenicity in Scn5a+/Δ and Scn5a+/− murine hearts modelling the congenital long QT syndrome type 3 (LQT3) and the Brugada syndrome (BrS). Monophasic action potentials (APs) recorded during extrasystolic stimulation procedures from Langendorff-perfused control hearts and hearts treated with flecainide (1 μM) or quinidine (1 or 10 μM) demonstrated that both agents were pro-arrhythmic in wild-type (WT) hearts, quinidine was pro-arrhythmic in Scn5a+/Δ hearts, and that flecainide was pro-arrhythmic whereas quinidine was anti-arrhythmic in Scn5a+/− hearts, confirming clinical findings. Statistical analysis confirmed a quadratic relationship between epicardial and endocardial AP durations (APDs) in WT control hearts. However, comparisons between plots of epicardial against endocardial APDs and this reference curve failed to correlate with arrhythmogenicity. Restitution curves, relating APD to diastolic interval (DI), were then constructed for the first time in a murine system and mono-exponential growth functions fitted to these curves. Significant (P < 0.05) alterations in the DI at which slopes equalled unity, an established indicator of arrhythmogenicity, now successfully predicted the presence or absence of arrhythmogenicity in all cases. We thus associate changes in the slopes of restitution curves with arrhythmogenicity in models of LQT3 and BrS.

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<![CDATA[Restitution analysis of alternans and its relationship to arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts]]> https://www.researchpad.co/product?articleinfo=5b7d2533463d7e4bac518885

Alternans and arrhythmogenicity were studied in hypokalaemic (3.0 mM K+) Langendorff-perfused murine hearts paced at high rates. Epicardial and endocardial monophasic action potentials were recorded and durations quantified at 90% repolarization. Alternans and arrhythmia occurred in hypokalaemic, but not normokalaemic (5.2 mM K+) hearts (P < 0.01): this was prevented by treatment with lidocaine (10 μM, P < 0.01). Fourier analysis then confirmed transition from monomorphic to polymorphic waveforms for the first time in the murine heart. Alternans and arrhythmia were associated with increases in the slopes of restitution curves, obtained for the first time in the murine heart, while the anti-arrhythmic effect of lidocaine was associated with decreased slopes. Thus, hypokalaemia significantly increased (P < 0.05) maximal gradients (from 0.55 ± 0.14 to 2.35 ± 0.67 in the epicardium and from 0.67 ± 0.13 to 1.87 ± 0.28 in the endocardium) and critical diastolic intervals (DIs) at which gradients equalled unity (from −2.14 ± 0.52 ms to 50.93 ± 14.45 ms in the epicardium and from 8.14 ± 1.49 ms to 44.64 ± 5 ms in the endocardium). While treatment of normokalaemic hearts with lidocaine had no significant effect (P > 0.05) on either maximal gradients (0.78 ± 0.27 in the epicardium and 0.83 ± 0.45 in the endocardium) or critical DIs (6.06 ± 2.10 ms and 7.04 ± 3.82 ms in the endocardium), treatment of hypokalaemic hearts with lidocaine reduced (P < 0.05) both these parameters (1.05 ± 0.30 in the epicardium and 0.89 ± 0.36 in the endocardium and 30.38 ± 8.88 ms in the epicardium and 31.65 ± 4.78 ms in the endocardium, respectively). We thus demonstrate that alternans contributes a dynamic component to arrhythmic substrate during hypokalaemia, that restitution may furnish an underlying mechanism and that these phenomena are abolished by lidocaine, both recapitulating and clarifying clinical findings.

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<![CDATA[Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes]]> https://www.researchpad.co/product?articleinfo=5b7d0c7b463d7e3157f9a0c7

The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl2, on the expression and secretion of inflammation-related adipokines was examined in human adipocytes. Hypoxia led to a rapid and substantial increase (greater than sevenfold by 4 h of exposure to 1% O2) in the hypoxia-sensitive transcription factor, HIF-1α, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O2 or CoCl2) led to a reduction (up to threefold over 24 h) in adiponectin and haptoglobin mRNA levels; adiponectin secretion also decreased. No changes were observed in TNFα expression. In contrast, hypoxia resulted in substantial increases in FIAF/angiopoietin-like protein 4, IL-6, leptin, MIF, PAI-1 and vascular endothelial growth factor (VEGF) mRNA levels. The largest increases were with FIAF (maximum 210-fold), leptin (maximum 29-fold) and VEGF (maximum 23-fold); these were reversed on return to normoxia. The secretion of IL-6, leptin, MIF and VEGF from the adipocytes was also stimulated by exposure to 1% O2. These results demonstrate that hypoxia induces extensive changes in human adipocytes in the expression and release of inflammation-related adipokines. Hypoxia may underlie the development of the inflammatory response in adipocytes, leading to obesity-associated diseases.

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<![CDATA[Transmural variations in gene expression of stretch-modulated proteins in the rat left ventricle]]> https://www.researchpad.co/product?articleinfo=5b7cd662463d7e25009cf699

The properties of left ventricular cardiac myocytes vary transmurally. This may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. We tested the hypothesis that within the rat left ventricle there are transmural differences in the expression of genes for proteins that are involved in mechanosensitive pathways and in associated physiological responses. Real time reverse transcription polymerase chain reaction was used to measure messenger RNA (mRNA) levels of selected targets in sub-epicardial (EPI) and sub-endocardial (ENDO) myocardium. Carbon fibres were attached to single myocytes to stretch them and to record contractility. We observed that the slow positive inotropic response to stretch was not different between EPI and ENDO myocytes and consistent with this, that the mRNA expression of two proteins implicated in the slow response, non-specific cationic mechanosensitive channels (TRPC-1) and Na/H exchanger, were not different. However, mRNA levels of other targets, e.g. the mechanosensitive K+ channel TREK-1, Brain Natriuretic Peptide and Endothelin-1 receptor B, were significantly greater in ENDO than EPI. No targets had significantly greater mRNA levels in EPI than ENDO. On the basis of these findings, we suggest that the response of the ventricle to stretch will depend upon both the regional differences in stimuli and the relative expression of the mechanosensitive targets and that generally, stretch sensitivity is predicted to be greater in ENDO.

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<![CDATA[Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use]]> https://www.researchpad.co/product?articleinfo=5b7cba91463d7e2027cafbb6

Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 ± 4% of maximal O2 uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg−1 h−1) or without (CON placebo trial; water only). Continuous infusions with [U-13C] palmitate and [6,6-2H2] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (Ra) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 ± 19 and 57 ± 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA Ra and subsequent plasma FFA concentrations were lower, resulting in a 34 ± 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 ± 21 and 78 ± 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men.

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<![CDATA[Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia]]> https://www.researchpad.co/product?articleinfo=5b7cba9d463d7e2027cafbc0

Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS). After LPS+, proximal tubular damage and a reduction in renal function were observed. Furthermore, iNOS mRNA and protein, and the amount of NO metabolites in plasma and urine, increased compared to the LPS group. Coadministration with aminoguanidine resulted in an attenuation of iNOS induction and reduction of renal damage. Gene expression of 20 ABC transporters was determined. After LPS+, a clear up-regulation in Abca1, Abcb1/P-glycoprotein (P-gp), Abcb11/bile salt export pump (Bsep), and Abcc2/multidrug resistance protein (Mrp2) was found, whereas Abcc8 was down-regulated. Up-regulation of Abcc2/Mrp2 was accompanied by enhanced calcein excretion. Aminoguanidine attenuated the effects on transporter expression. Our data indicate that NO, produced locally by renal iNOS, regulates the expression of ABC transporters in vivo. Furthermore, we showed, for the first time, expression and subcellular localization of Abcb11/Bsep in rat kidney.

Electronic supplementary material

The online version of this article (doi: 10.1007/s00424-007-0210-x) contains supplementary material, which is available to authorized users.

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<![CDATA[The endothelial glycocalyx: composition, functions, and visualization]]> https://www.researchpad.co/product?articleinfo=5b7cba4e463d7e2027cafb7e

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging.

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<![CDATA[ISCEV standard for clinical pattern electroretinography—2007 update]]> https://www.researchpad.co/product?articleinfo=5b7c8caa463d7e1d320a021c

The pattern electroretinogram (PERG) is a retinal response evoked by viewing a temporally alternating pattern, usually a black and white checkerboard or grating. The PERG is important in clinical and research applications because it provides information both about retinal ganglion cell function and, because the stimulus is customarily viewed with central fixation, the function of the macula. The PERG can therefore facilitate interpretation of an abnormal pattern VEP by revealing the retinal responses to a similar stimulus to that used for the VEP. However, practitioners may have difficulty choosing between the different techniques for recording the PERG that have been described in the literature. The International Society for Clinical Electrophysiology of Vision published a standard for clinical PERG recording in 2000 to assist practitioners in obtaining good quality reliable responses and to facilitate inter-laboratory communication and comparison. This document is the scheduled revision of that standard.

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<![CDATA[The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts]]> https://www.researchpad.co/product?articleinfo=5b7c4db0463d7e12395af840

The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K+) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 μM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD90), ventricular effective refractory period (VERP), and transmural conduction time (Δlatency), where appropriate, were applied to normokalemic (5.2 mM K+) and hypokalemic hearts. Hypokalemia increased epicardial APD90 from 46.6 ± 1.2 to 53.1 ± 0.7 ms yet decreased epicardial VERP from 41 ± 4 to 29 ± 1 ms, left endocardial APD90 unchanged (58.2 ± 3.7 to 56.9 ± 4.0 ms) yet decreased endocardial VERP from 48 ± 4 to 29 ± 2 ms, and left Δlatency unchanged (1.6 ± 1.4 to 1.1 ± 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD90 (54.8 ± 2.7 to 60.6 ± 2.7 ms), epicardial VERP (84 ± 5 to 81 ± 7 ms), endocardial APD90 (56.6 ± 4.2 to 63.7 ± 6.4 ms), endocardial VERP (80 ± 2 to 84 ± 4 ms), and Δlatency (12.5 ± 6.2 to 7.6 ± 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD90 might diverge sharply from VERP.

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<![CDATA[Compromised redox homeostasis, altered nitroso–redox balance, and therapeutic possibilities in atrial fibrillation]]> https://www.researchpad.co/product?articleinfo=5af9adc1463d7e1b78533ad7

Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso–redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF.

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<![CDATA[Changes in Respiratory Parameters and Fin-Swimming Performance Following a 16-Week Training Period with Intermittent Breath Holding]]> https://www.researchpad.co/product?articleinfo=5af820e7463d7e01c311d660

The purpose of this study was to examine the effects of training with intermittent breath holding (IBH) on respiratory parameters, arterial oxygen saturation (SpO2) and performance. Twenty-eight fin-swimming athletes were randomly divided into two groups and followed the same training for 16 weeks. About 40% of the distance of each session was performed with self-selected breathing frequency (SBF group) or IBH (IBH group). Performance time of 50 and 400 m at maximum intensity was recorded and forced expired volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and SpO2 were measured before and after the 50 m test at baseline and post-training. Post-training, the respiratory parameters were increased in the IBH but remained unchanged in the SBF group (FEV1: 17 ±15% vs. −1 ±11%; FVC: 22 ±13% vs. 1 ±10%; PEF: 9 ±14% vs. −4 ±15%; p<0.05). Pre compared to post-training SpO2 was unchanged at baseline and decreased post-training following the 50 m test in both groups (p<0.05). The reduction was higher in the IBH compared to the SBF group (p<0.05). Performance in the 50 and 400 m tests improved in both groups, however, the improvement was greater in the IBH compared to the SBF group in both 50 and 400 m tests (p<0.05). The use of IBH is likely to enhance the load on the respiratory muscles, thus, contributing to improvement of the respiratory parameters. Decreased SpO2 after IBH is likely due to adaptation to hypoventilation. IBH favours performance improvement at 50 and 400 m fin-swimming.

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<![CDATA[Molecular profiling of childhood cancer: Biomarkers and novel therapies]]> https://www.researchpad.co/product?articleinfo=5af5f64f463d7e3573d5edf8

Background

Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies.

Scope of review

This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type.

Major conclusions

There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies.

General significance

The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

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<![CDATA[The Effect of the Number of Sets on Power Output for Different Loads]]> https://www.researchpad.co/product?articleinfo=5aec3117463d7e37c22c695a

There is much debate concerning the optimal load (OL) for power training. The purpose of this study was to investigate the effect of the number of sets performed for a given load on mean power output (Pmean). Fourteen physically active men performed 3 sets of 3 bench-press repetitions with 30, 40 and 50 kg. The highest mean power value (Pmax) across all loads and Pmean were compared when data were taken from the first set at each absolute load vs. from the best of three sets performed. Pmean increased from the first to the third set (from 5.99 ± 0.81 to 6.16 ± 0.96 W·kg−1, p = 0.017), resulting in a main effect of the set number (p < 0.05). At the 30 kg load Pmean increased from the first to the third set (from 6.01 ± 0.75 to 6.35 ± 0.85 W·kg−1; p < 0.01). No significant effect was observed at 40 and 50 kg loads (p > 0.05). Pmax and velocity were significantly affected by the method employed to determine Pmean at each load (p < 0.05). These results show a positive effect of the number of sets per load on Pmean, affecting Pmax, OL and potentially power training prescription.

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<![CDATA[Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation]]> https://www.researchpad.co/product?articleinfo=5adda0a5463d7e39b2e95868

Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H2O2 depending on the vascular bed and experimental conditions, this study was performed to assess whether H2O2 acts as a vasodilator in the rat mesenteric artery and, if so, to determine the underlying mechanisms. H2O2 elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of H2O2 was reversed by treatment with dithiothreitol. H2O2-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca2+-activated K+ channels and inward rectifier K+ channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that H2O2 increased Kv currents in a concentration-dependent manner. H2O2 speeded up Kv channel activation and shifted steady state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The H2O2-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of H2O2. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of H2O2 to stimulate Kv channels. Not only was the H2O2 stimulatory effect much weaker, but the inhibitory effect of H2O2 was unmasked. These data suggest that H2O2 activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to H2O2.

Electronic supplementary material

The online version of this article (doi:10.1007/s00424-014-1513-3) contains supplementary material, which is available to authorized users.

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<![CDATA[Posture, Flexibility and Grip Strength in Horse Riders]]> https://www.researchpad.co/product?articleinfo=5ada7333463d7e1c57de6b47 <![CDATA[Monoamine oxidase inhibition prevents mitochondrial dysfunction and apoptosis in myoblasts from patients with collagen VI myopathies]]> https://www.researchpad.co/product?articleinfo=5ad911dc463d7e02ae93b0dc

Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases.

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