Cyclosporine A Delays the Terminal Disease Stage in the Tfam KO Mitochondrial Myopathy Mouse Model Without Improving Mitochondrial Energy Production.

Introduction And Aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.

Social Gaming to Decrease Loneliness in Older Adults: Recruitment Challenges and Attrition Analysis in a Digital Mixed Methods Feasibility Study.

Background: Digital mental health interventions could sustainably and scalably prevent and reduce loneliness in older adults. We designed an app containing 29 text-based games and a questionnaire-administering chatbot to stimulate intergenerational contact.

Objective: This study aims to evaluate the feasibility of a social gaming app in reducing loneliness among older adults by evaluating recruitment strategies, data collection procedures, and gameplay activity.

A Digital Gaming Intervention to Strengthen the Social Networks of Older Dutch Adults: Mixed Methods Process Evaluation of a Digitally Conducted Randomized Controlled Trial.

Background: Digital loneliness interventions for older adults are promising, yet conclusive evidence is lacking due to a lack of randomized controlled trials (RCTs) and difficulties with recruitment. Process evaluation of performed RCTs is essential to inform future interventions. Still, it is rarely carried out, resulting in an overly optimistic view of the impact of eHealth interventions on loneliness in older adults and options to conduct such research entirely remotely.

Older Adults' Views on Social Interactions and Online Socializing Games - A Qualitative Study.

Age-related difficulties and quarantine restrictions impede the possibilities to maintain contact with one's social network. Maintaining these contacts may be supported by digital games. To develop effective and feasible digital tools to foster social interaction, we aimed to explore what older adults find important in social contact and what barriers and enablers they foresee in digital gaming interventions as network support aids.

Effects of Hydroxyurea on Skeletal Muscle Energetics and Function in a Mildly Anemic Mouse Model.

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor most commonly used as a therapeutic agent in sickle cell disease (SCD) with the aim of reducing the risk of vaso-occlusion and improving oxygen transport to tissues. Previous studies suggest that HU may be even beneficial in mild anemia. However, the corresponding effects on skeletal muscle energetics and function have never been reported in such a mild anemia model.

A Global Sharing Mechanism of Resources: Modeling a Crucial Step in the Fight against Pandemics.

To face crises like the COVID-19 pandemic, resources such as personal protection equipment (PPE) are needed to reduce the infection rate and protect those in close contact with patients. The increasing demand for those products can, together with pandemic-related disruptions in the global supply chain, induce major local resource scarcities. During the first phase of the COVID-19 pandemic, we witnessed a reflex of 'our people first' in many regions.

Refining the causal loop diagram: A tutorial for maximizing the contribution of domain expertise in computational system dynamics modeling.

Complexity science and systems thinking are increasingly recognized as relevant paradigms for studying systems where biology, psychology, and socioenvironmental factors interact. The application of systems thinking, however, often stops at developing a conceptual model that visualizes the mapping of causal links within a system, e.g.

Is the Energy Cost of Rowing a Determinant Factor of Performance in Elite Oarsmen?

In elite oarsmen, the rowing ergometer is a valuable tool for both training and studying rowing performance determinants. However, the energy cost of rowing, often reported as a determinant of performance, has never been described for ergometer rowing. Therefore, this study aimed to characterize the energy cost of ergometer rowing (ECR) in elite oarsmen, its contribution to 2,000 m performance, and its determinants.

Lower Muscle and Blood Lactate Accumulation in Sickle Cell Trait Carriers in Response to Short High-Intensity Exercise.

It remains unclear whether sickle cell trait (SCT) should be considered a risk factor during intense physical activity. By triggering the polymerization-sickling-vaso-occlusion cascade, lactate accumulation-associated acidosis in response to high-intensity exercise is believed to be one of the causes of complications. However, our understanding of lactate metabolism in response to high-intensity exercise in SCT carriers is incomplete.

Delayed Rebound of Glycemia During Recovery Following Short-Duration High-Intensity Exercise: Are There Lactate and Glucose Metabolism Interactions?

Lactate constitutes the primary gluconeogenic precursor in healthy humans at rest and during low-intensity exercise. Data on the interactions between lactate and glucose metabolisms during recovery after short-duration high-intensity exercise are sparse. The aim of the present study was to describe blood glucose ([glucose]) and lactate ([lactate]) concentration curves during recovery following short-duration high-intensity exercise.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model.

Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death.

In vivo muscle function and energetics in women with sickle cell anemia or trait: a P-magnetic resonance spectroscopy study.

Sickle cell anemia (SCA) is a genetic hemoglobinopathy associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes and increase intramuscular acidosis. These alterations have been already reported in the Townes mouse model of SCA but the corresponding changes in humans have not been documented. In the present study, we used 31-phosphorus magnetic resonance spectroscopy to investigate in vivo the metabolic changes induced by a moderate-intensity exercise in twelve SCA patients, eight sickle cell trait (SCT) carriers, and twelve controls women.

Effects of Individualized Treadmill Endurance Training on Oxidative Stress in Skeletal Muscles of Transgenic Sickle Mice.

Oxidative stress is a key feature in the pathophysiology of sickle cell disease. Endurance training has been shown to reduce oxidative stress in the heart and the liver of sickle mice. However, the effects of endurance training on skeletal muscles, which are major producers of reactive oxygen species during exercise, are currently unknown.

Ischaemia-induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease.

New Findings: What is the central question of this study? The aim of this study was to evaluate the potential beneficial effects of endurance training during an ischaemia-reperfusion protocol in a mouse model of sickle cell disease (SCD). What is the main finding and its importance? Endurance training did not reverse the metabolic defects induced by a simulated vaso-occlusive crisis in SCD mice, with regard to intramuscular acidosis, mitochondrial dysfunction or anatomical properties. Our results suggest that endurance training would reduce the number of vaso-occlusive crises rather than the complications related to vaso-occlusive crises.

Exacerbated metabolic changes in skeletal muscle of sickle cell mice submitted to an acute ischemia-reperfusion paradigm.

Sickle cell disease (SCD) is characterized by painful vaso-occlusive crisis. While there are several metabolic abnormalities potentially associated with muscular ischemia-reperfusion cycles that could be harmful in the context of SCD, the metabolic consequences of such events are still unknown. Ten controls (HbAA), thirteen heterozygous (HbAS), and ten homozygous (HbSS) SCD mice were submitted to a standardized protocol of rest-ischemia-reperfusion of the left leg during which adenosine triphosphate, phosphocreatine, and inorganic phosphate concentrations as well as intramuscular pH were measured using phosphorous magnetic resonance spectroscopy (MRS).

Comparison of Prolonged Rowing on Fixed and Free-floating Ergometers in Competitive Rowers.

This study aimed to compare the effect of a 40-min submaximal rowing exercise performed on ergometers with fixed and free-floating designs. Heart rate, blood lactate concentration, force and rate of force development (RFD) at the handle, stroke rate, duty factor, movement kinematics of upper and lower limbs, and muscle activity of lumbar spine muscles and (IC and ESL) were measured at the beginning and at the end of a 40-min rowing exercise at ~60% of peak power output, in eleven competitive rowers. Force of lumbar extension decreased, and blood lactate increased following submaximal exercise on both ergometers.

How Sickle Cell Disease Impairs Skeletal Muscle Function: Implications in Daily Life.

Sickle cell disease (SCD) is the most frequent life-threatening genetic hemoglobinopathy in the world and occurs due to the synthesis of abnormal hemoglobin S (HbS). hemoglobin S-containing red blood cells (RBC) are fragile, leading to hemolysis and anemia, and adhere to the endothelium, leading to hemorheological and hemodynamical disturbances. In its deoxygenated form, HbS may polymerize, leading to sickling of red blood cells and potentially to vasoocclusive crises.

Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?

New Findings: What is the topic of this review? The aim of this review is to discuss the potential involvement of exercise-induced acidosis in the commonly reported complications in sickle cell disease. What advances does it highlight? Blood acidosis appears clearly to be a risk factor for HbS polymerization, red blood cell sickling and the occurrence of vaso-occlusive crisis and could induce hyperkalaemia-related complications. It could be of great interest to try to avoid blood acidosis during exercise, which could be done using some alkalinizing solutions or adapted endurance training interventions.

Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease.

Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n=10), HbAS (HbAS-END, n=11) and HbSS (HbSS-END, n=8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest - exercise - recovery protocols during which muscle energetics and function were measured.

Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles.

Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb.

Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse.

While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest - exercise - recovery at two different intensities in ten SCD mice.

Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice.

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, = 9) and heterozygous (HbAS, = 10) SCD (Townes) mice in comparison to control (HbAA, = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities.

Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: insights from MCT1 haploinsufficient mice.

The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1 mice). Twenty-four MCT1 and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation.

Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease.

Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability.