Acute and Delayed Effects of Time-Matched Very Short “All Out” Efforts in Concentric vs. Eccentric Cycling

[EN] Abstract: Background: To the authors’ knowledge, there have been no studies comparing the acute responses to “all out” efforts in concentric (isoinertial) vs. eccentric (isovelocity) cycling. Methods: After two familiarization sessions, 12 physically active men underwent the experimental protocols consisting of a 2-min warm-up and 8 maximal efforts of 5 s, separated by 55 s of active recovery at 80 rpm , in concentric vs. eccentric cycling. Comparisons between protocols were conducted during, immediately after, and 24-h post-sessions. Results: Mechanical (Work: 82,824 ± 6350 vs. 60,602 ± 8904 J) and cardiometabolic responses (mean HR: 68.8 ± 6.6 vs. 51.3 ± 5.7% HRmax, lac- tate: 4.9 ± 2.1 vs. 1.8 ± 0.6 mmol/L) were larger in concentric cycling (p < 0.001). The perceptual responses to both protocols were similarly low. Immediately after concentric cycling, vertical jump was potentiated (p = 0.028). Muscle soreness (VAS; p = 0.016) and thigh circumference (p = 0.045) were slightly increased only 24-h after eccentric cycling. Serum concentrations of CK, BAG3, and MMP-13 did not change significantly post-exercise. Conclusions: These results suggest the appro- priateness of the eccentric cycling protocol used as a time-efficient (i.e., ~60 kJ in 10 min) and safe (i.e., without exercise-induced muscle damage) alternative to be used with different populations in future longitudinal interventions

Effects of a Dynamic Chair on Chair Seat Motion and Trunk Muscle Activity during Office Tasks and Task Transitions

Employing dynamic office chairs might increase the physical (micro-) activity during prolonged office sitting. We investigated whether a dynamic BioSwing; ®; chair increases chair sway and alters trunk muscle activation. Twenty-six healthy young adults performed four office tasks (reading, calling, typing, hand writing) and transitions between these tasks while sitting on a dynamic and on a static office chair. For all task-transitions, chair sway was higher in the dynamic condition (; p; &lt; 0.05). Muscle activation changes were small with lower mean activity of the left obliquus internus during hand writing (; p; = 0.07), lower mean activity of the right erector spinae during the task-transition calling to hand writing (; p; = 0.036), and higher mean activity of the left erector spinae during the task-transition reading to calling (; p; = 0.07) on the dynamic chair. These results indicate that an increased BioSwing; ®; chair sway only selectively alters trunk muscle activation. Adjustments of chair properties (i.e., swinging elements, foot positioning) are recommended

Epithelial restitution in 3D - Revealing biomechanical and physiochemical dynamics in intestinal organoids via fs laser nanosurgery

Intestinal organoids represent a three-dimensional cell culture system mimicking the mammalian intestine. The application of single-cell ablation for defined wounding via a femtosecond laser system within the crypt base allowed us to study cell dynamics during epithelial restitution. Neighboring cells formed a contractile actin ring encircling the damaged cell, changed the cellular aspect ratio, and immediately closed the barrier. Using traction force microscopy, we observed major forces at the ablation site and additional forces on the crypt sides. Inhibitors of the actomyosin-based mobility of the cells led to the failure of restoring the barrier. Close to the ablation site, high-frequency calcium flickering and propagation of calcium waves occured that synchronized with the contraction of the epithelial layer. We observed an increased signal and nuclear translocation of YAP-1. In conclusion, our approach enabled, for the first time, to unveil the intricacies of epithelial restitution beyond in vivo models by employing precise laser-induced damage in colonoids

Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: A potential link between β-cell lipotoxicity and islet inflammation

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ∼2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation. Copyright © 2013 by The Endocrine Society

Restricted nasal-only breathing during self-selected low intensity training does not affect training intensity distribution

Introduction: Low-intensity endurance training is frequently performed at gradually higher training intensities than intended, resulting in a shift towards threshold training. By restricting oral breathing and only allowing for nasal breathing this shift might be reduced.Methods: Nineteen physically healthy adults (3 females, age: 26.5 ± 5.1 years; height: 1.77 ± 0.08 m; body mass: 77.3 ± 11.4 kg; VO2peak: 53.4 ± 6.6 mL·kg−1 min−1) performed 60 min of self-selected, similar (144.7 ± 56.3 vs. 147.0 ± 54.2 W, p = 0.60) low-intensity cycling with breathing restriction (nasal-only breathing) and without restrictions (oro-nasal breathing). During these sessions heart rate, respiratory gas exchange data and power output data were recorded continuously.Results: Total ventilation (p &lt; 0.001, ηp2 = 0.45), carbon dioxide release (p = 0.02, ηp2 = 0.28), oxygen uptake (p = 0.03, ηp2 = 0.23), and breathing frequency (p = 0.01, ηp2 = 0.35) were lower during nasal-only breathing. Furthermore, lower capillary blood lactate concentrations were found towards the end of the training session during nasal-only breathing (time x condition-interaction effect: p = 0.02, ηp2 = 0.17). Even though discomfort was rated marginally higher during nasal-only breathing (p = 0.03, ηp2 = 0.24), ratings of perceived effort did not differ between the two conditions (p ≥ 0.06, ηp2 = 0.01). No significant “condition” differences were found for intensity distribution (time spent in training zone quantified by power output and heart rate) (p ≥ 0.24, ηp2 ≤ 0.07).Conclusion: Nasal-only breathing seems to be associated with possible physiological changes that may help to maintain physical health in endurance athletes during low intensity endurance training. However, it did not prevent participants from performing low-intensity training at higher intensities than intended. Longitudinal studies are warranted to evaluate longitudinal responses of changes in breathing patterns

A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models

In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial.

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (β = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580

Designing electronic collaborative learning environments

Electronic collaborative learning environments for learning and working are in vogue. Designers design them according to their own constructivist interpretations of what collaborative learning is and what it should achieve. Educators employ them with different educational approaches and in diverse situations to achieve different ends. Students use them, sometimes very enthusiastically, but often in a perfunctory way. Finally, researchers study them and—as is usually the case when apples and oranges are compared—find no conclusive evidence as to whether or not they work, where they do or do not work, when they do or do not work and, most importantly, why, they do or do not work. This contribution presents an affordance framework for such collaborative learning environments; an interaction design procedure for designing, developing, and implementing them; and an educational affordance approach to the use of tasks in those environments. It also presents the results of three projects dealing with these three issues

An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method. One implant type was made of PL-DL-lactide (PLA), the second one was a titanium core partially covered with PLA. Healing period was 2 and 6 months, with 3 sheep per group. Bone samples were evaluated radiologically, histologically and histomorphometrically for bone remodeling and inflammatory reactions. Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone

Storage of Factor VIII Variants with Impaired von Willebrand Factor Binding in Weibel-Palade Bodies in Endothelial Cells

BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser) to severe (Tyr1680Phe, Ser2119Tyr) VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo