Correlates of Toddlers' Physical Activity Levels and Sedentary Behavior During Unstructured Outdoor Play in Early Childhood Education and Daycare Settings.

Despite recent research showing that early childhood education and daycare settings (ECEC) have an important role in promoting toddlers' physical activity (PA), crucial information gaps remain regarding toddlers' PA and sedentary behavior (SB) in these outdoor settings. We aimed in this study to: (a) analyze PA patterns and SB during unstructured outdoor play time in preschool and daycare environments using accelerometry and systematic observation; (b) provide concurrent accelerometry and observational data to help validate the Observational System for Recording Physical Activity in Children-Preschool Version (OSRAC-P); and (c) examine individual, social and environmental correlates of PA and SB during toddlers' unstructured outdoor play time. We found that: (a) toddlers displayed high amounts of PA with no sex, BMI, and/or age differences in PA and SB levels,; (b) environmental variables (e.g., fixed equipment and playground density) were not associated with PA levels or SB intensity; (c) the OSRAC-P was a reliable and valid means of observing and analyzing toddlers' PA patterns during unstructured outdoor play time; and (e) different social patterns between boys and girls did not impact PA levels or patterns. Combining different measurement methods permitted an improved understanding of unstructured outdoor play in preschool and daycare settings.

Role of Spanish Toddlers' Education and Care Institutions in Achieving Physical Activity Recommendations in the COVID-19 Era: A Cross-Sectional Study.

To our knowledge, there are no published studies that describe the physical activity (PA) levels and objectively measure them through accelerometry in toddlers (2-3 years old) attending early childhood education and care (ECEC) institutions during the COVID-19 pandemic. The aims of this study were two-fold: (a) to analyse toddlers' PA levels and sedentary behaviour (SB) during school hours in ECEC institutions, as well as the rate of adherence to specific recommendations on total PA (TPA) and moderate-vigorous PA (MVPA); and (b) to evaluate the characteristics correlates (age, gender, and body mass index -BMI) of young children and the school environment on toddlers' TPA, light PA (LPA), MVPA, and SB during school hours in ECEC institutions. PA was evaluated with ActiGraph accelerometers. The main findings were that: (a) toddlers engaged in very high amounts of TPA and MVPA during ECEC hours; (b) girls and boys displayed similar levels of LPA, TPA, and SB, while girls had lower levels of MVPA, compared to boys, and younger toddlers were less active than older ones; (c) BMI was not associated with PA of any intensity or SB; (d) playground and classroom density were not associated with higher levels of PA of any intensity, though classroom density was associated with SB. These ECEC institutions provide and challenge the new COVID-19 scenario, as well as supportive environments for toddlers' PA.

Relationship Between the Physical Environment and Physical Activity Levels in Preschool Children: A Systematic Review.

PURPOSE OF REVIEW: The aim of this study was to understand the influence of the physical environment on the physical activity (PA) behavior of preschool children (aged 2 to 6 years), in order to provide an overview of these influences from the perspective of the ecological model. RECENT FINDINGS: PA is of great importance for the prevention of obesity and cardiovascular diseases since childhood. The physical environment has a direct relationship with the different domains, where people can spend their time being physically active. Nonetheless, despite the importance of the physical environment to engagement in PA, very few reviews have focused on this relationship in the context of the growing problem of physical inactivity among preschool children. Studies that had analyzed the school domain had found that greater availability of a wider variety of portable play equipment, presence of certain fixed playground equipment, and presence of open spaces had favored PA levels. Furthermore, different studies had shown that the natural environment and the presence of hills were important for children's PA. Thus, despite the associations with PA we were able to identify in this review, new studies will still be needed to link the physical environment with PA levels, especially regarding transportation and leisure time. In conclusion, promoting studies on this subject from an early age will allow us to obtain information that could allow the adaptation, design, and construction of healthier homes, neighborhoods, and schools that promote children's health.

Physical Activity and Motor Competence in Preschool Children.

Longitudinal evidence has demonstrated that engagement in physical activity (PA) and the development of motor competence (MC) have numerous tangible health and developmental benefits [...].

The Role of Preschool Hours in Achieving Physical Activity Recommendations for Preschoolers.

Research on physical activity (PA) in different educational settings could elucidate which interventions promote a healthy school lifestyle in early childhood education (ECE). The aims of this study were: (a) to analyse the PA levels of preschoolers during school hours, as well as the rate of compliance with specific recommendations on total PA (TPA) and moderate-vigorous PA (MVPA); (b) to examine the role of structured movement sessions and recess time in the MVPA levels during school hours; (c) to evaluate the sociodemographic correlates of preschoolers and the school environment on MVPA behaviour during school hours. PA was evaluated with Actigraph accelerometers. Our main findings were that: (a) preschoolers engaged in very little TPA and MVPA during school hours; (b) children showed significantly higher MVPA levels on days with versus without structured movement sessions, and the contribution of the structured sessions to MVPA was significantly higher than that of recess time; (c) gender and age were associated with PA, and a high density of young children on the playground was associated with high levels of vigorous PA, whereas in the classroom, high density was associated with more sedentary behaviour. Structured PA could reduce the gap in achieving international recommendations.

Pharmacological properties of physical exercise in the elderly.

Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise and aging are associated with oxidative stress so the paradox arises, and is discussed, as to whether exercise would be advisable for the aged population from an oxidative stress point of view. Two of the main redox-sensitive signaling pathways altered in old skeletal muscle during exercise, NF-κB and PGC-1α, are also reviewed. The last section of the manuscript is devoted to the age-associated diseases in which exercise is contraindicated. Finally, we address the option of applying exercise mimetics as an alternative for disabled old people. The overall denouement is that exercise is so beneficial that it should be deemed a drug both for young and old populations. If old adults adopted a more active lifestyle, there would be a significant delay in frailty and dependency with clear benefits to individual well-being and to the public's health.

PPARgamma agonist pioglitazone does not enhance performance in mice.

Peroxisome-proliferator-activated receptor (PPAR) delta and adenosine monophosphate (AMP)-activated protein kinases (AMPKs) regulate the metabolic and contractile characteristics of myofibres. PPAR proteins are nuclear receptors that function as transcription factors and regulate the expression of multiple genes. AMPK has been described as a master metabolic regulator which also controls gene expression through the direct phosphorylation of some nuclear proteins. Since it was discovered that both PPARdelta agonists (GW1516) and AMPK activators (5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside, known as AICAR) are very effective performance-enhancing substances in sedentary mice, the World Anti-doping Agency (WADA) included AICAR and GW1516 in the prohibited list of substances as metabolic modulators in the class 'Hormone and metabolic modulators'. Thiazolidinediones are PPARgamma agonists that can induce similar biological effects to those of PPARdelta and PPARdelta-AMPK agonists. Thus in this study, the effects of pioglitazone on mitochondrial biogenesis and performance were evaluated. Blood glucose levels and the protein expression of the intermediates involved in the mitochondrial biogenesis pathway and the citrate synthase activity were determined in both gastrocnemius and soleus muscles. Maximal aerobic velocity (MAV), endurance capacity, and grip strength before and after the training period were also determined. The MAV endurance capacity and grip strength of trained animals significantly increased. We found that the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and the nuclear respiratory factor-1 (NRF-1) protein content and citrate synthase activity significantly increased in the soleus muscle of trained animals. No effect of treatment was found. Therefore in our study, pioglitazone administration did not affect mitochondrial biogenesis signaling pathway.

Vitamin C supplementation does not improve hypoxia-induced erythropoiesis.

Hypoxia induces reactive oxygen species production. Supplements with antioxidant mixtures can compensate for the decline in red cell membrane stability following intermittent hypobaric hypoxia by decreasing protein and lipid oxidation. We aimed to determine whether supplementation with vitamin C is implicated in the regulation of erythropoiesis and in the oxygen-carrying capacity of the blood, and also whether antioxidant supplementation prevents the oxidative stress associated to intermittent hypoxia. Twenty-four male Wistar rats were randomly divided into four experimental groups: normoxia control (n=6), normoxia + vitamin C (n=6), hypoxia control (12 h pO(2) 12%/12 h pO(2) 21%) (n=6), and hypoxia + vitamin C (n=6). Animals were supplemented with vitamin C at a dose of 250 mg·kg(-1)·day(-1) for 21 days. Red blood cell count, hemoglobin, hematocrit, reticulocytes, erythropoietin, and oxidative stress parameters such as malondialdehyde and protein oxidation in plasma were analyzed at two different time points: basal sample (day zero) and final sample (day 21). Similar RBC, Hb, Hct, and Epo increments were observed in both hypoxic groups regardless of the vitamin C supplementation. There was no change on MDA levels after intermittent hypoxic exposure in any experimental group. However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure.

Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats

The blood O(2)-carrying capacity is maintained by the O(2)-regulated production of erythropoietin (Epo), which stimulates the proliferation and survival of red blood cell progenitors. Epo has been thought to act exclusively on erythroid progenitor cells. However, recent studies have identified the erythropoietin receptor (EpoR) in other cells, such as neurons, astrocytes, microglia, heart, cancer cell lines, and skeletal muscle provides evidence for a potential role of Epo in other tissues. In this study we aimed to determine the effect of recombinant human erythropoietin (rHuEpo) on skeletal muscle adaptations such as mitochondrial biogenesis, myogenesis, and angiogenesis in different muscle fibre types. Fourteen male Wistar rats were randomly divided into two experimental groups, and saline or rHuEpo (300 IU) was administered subcutaneously three times a week for 3 weeks. We evaluated the protein expression of intermediates involved in the mitochondrial biogenesis cascade, the myogenic cascade, and in angiogenesis in the oxidative soleus muscle and in the glycolytic gastrocnemius muscle. Contrary to our expectations, rHuEpo significantly hampered the mitochondrial biogenesis pathway in gastrocnemius muscle (PGC-1Alpha, mTFA and cytochrome c). We did not find any effect of the treatment on cellular signals of myogenesis (MyoD and Myf5) or angiogenesis (VEGF) in either soleus or gastrocnemius muscles. Finally, we found no significant effect on the maximal aerobic velocity at the end of the experiment in the rHuEpo-treated animals. Our findings suggest that 3 weeks of rHuEpo treatment, which generates an increase of oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre-specific dependent manner

Inhibition of xanthine oxidase by allopurinol prevents skeletal muscle atrophy: role of p38 MAPKinase and E3 ubiquitin ligases.

Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinase, and the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFbx; also known as atrogin-1) and Muscle RING (Really Interesting New Gene) Finger-1 (MuRF-1). We found that hindlimb unloading induced a significant increase in XO activity and in the protein expression of the antioxidant enzymes CuZnSOD and Catalase in skeletal muscle. The most relevant new fact reported in this paper is that inhibition of XO with allopurinol, a drug widely used in clinical practice, prevents soleus muscle atrophy by ~20% after hindlimb unloading. This was associated with the inhibition of the p38 MAPK-MAFbx pathway. Our data suggest that XO was involved in the loss of muscle mass via the activation of the p38MAPK-MAFbx pathway in unloaded muscle atrophy. Thus, allopurinol may have clinical benefits to combat skeletal muscle atrophy in bedridden, astronauts, sarcopenic, and cachexic patients.

Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats.

The blood O(2)-carrying capacity is maintained by the O(2)-regulated production of erythropoietin (Epo), which stimulates the proliferation and survival of red blood cell progenitors. Epo has been thought to act exclusively on erythroid progenitor cells. However, recent studies have identified the erythropoietin receptor (EpoR) in other cells, such as neurons, astrocytes, microglia, heart, cancer cell lines, and skeletal muscle provides evidence for a potential role of Epo in other tissues. In this study we aimed to determine the effect of recombinant human erythropoietin (rHuEpo) on skeletal muscle adaptations such as mitochondrial biogenesis, myogenesis, and angiogenesis in different muscle fibre types. Fourteen male Wistar rats were randomly divided into two experimental groups, and saline or rHuEpo (300 IU) was administered subcutaneously three times a week for 3 weeks. We evaluated the protein expression of intermediates involved in the mitochondrial biogenesis cascade, the myogenic cascade, and in angiogenesis in the oxidative soleus muscle and in the glycolytic gastrocnemius muscle. Contrary to our expectations, rHuEpo significantly hampered the mitochondrial biogenesis pathway in gastrocnemius muscle (PGC-1α, mTFA and cytochrome c). We did not find any effect of the treatment on cellular signals of myogenesis (MyoD and Myf5) or angiogenesis (VEGF) in either soleus or gastrocnemius muscles. Finally, we found no significant effect on the maximal aerobic velocity at the end of the experiment in the rHuEpo-treated animals. Our findings suggest that 3 weeks of rHuEpo treatment, which generates an increase of oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre-specific dependent manner.

Current limitations of the Athlete's Biological Passport use in sports.

The Athletes Biological Passport (ABP) has received both criticisms and support during this year. In a recent issue of The Lancet, Michael Wozny considered that the use of the ABP makes it more difficult to take banned substances and that it was successfully used against the Italian elite cyclist Franco Pellizotti. After that, Italy's anti-doping tribunal considered that there was not enough evidence to prove manipulation of his own blood profile in Pellizotti's case. However, the UCI appealed to the Court of Arbitration for Sport (CAS) that sanctioned Pellizotti with a suspension of 2 years. Since its implementation, some problems have emerged. From 2010 to date, a large number of reports regarding the stability of the blood variables used to determine the ABP have been published, showing mixed results. This study considers that there is a risk of misinterpreting the physiological variations of the hematological parameters determined by the anti-doping authorities in the ABP. The analytical variability due to exercise training and competitions and/or to different metabolic energy demands, hypoxia treatments, etc. could lead to an increase in false-positives when using the ABP with the dramatic consequences that they might cause in major sports events like the forthcoming London Olympic Games. Moreover, the ABP characteristics, procedures, thresholds, or individual determination of reference ranges, abnormal out-comes, strikes, "how the profile differs from what is expected in clean athletes" should be clearly stated and explained in a new public technical document to avoid misunderstandings and to promote transparency.

Free [NADH]/[NAD(+)] regulates sirtuin expression.

Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.

Repeated muscle biopsies through a single skin incision do not elicit muscle signaling, but IL-6 mRNA and STAT3 phosphorylation increase in injured muscle.

To determine if muscle biopsies can be repeated using a single small (5-6 mm) skin incision without inducing immediate MAPK activation or inflammation in the noninjured areas, the phosphorylation of ERK1/2, p38-MAPK, c-Jun NH(2)-terminal kinases (JNKs), IκBα, IKKα, and signal transducer and activator of transcription 3 (STAT3) was examined concurrent with IL-6 mRNA in six muscle biopsies obtained from the vastus lateralis of five men. Four biopsies were obtained through the same incision (5-6 mm) from the right leg (taken at 0, 30, 123, and 126 min) and another two each from new incisions performed in the left leg (at 31 and 120 min), while the subjects rested supine. The first three biopsies from the right leg were taken ∼3 cm apart from prebiopsied areas. The last biopsy was obtained from the same point from which the second biopsy was sampled. The three biopsies performed through the same skin incision from noninjured muscle areas showed similar levels of ERK1/2, p38-MAPK, JNK, IKKα, IκBα, and STAT3 phosphorylation and similar IL-6 mRNA content. There were no significant differences in the levels of ERK1/2, p38-MAPK, JNK, IKKα, and IκBα phosphorylation between the mean of the three biopsies obtained from the same incision and the sixth biopsy obtained from an injured area. STAT3 phosphorylation was increased by ∼3.5-fold in the sixth biopsy compared with the mean the three biopsies obtained from the same incision (P < 0.05), and IL-6 mRNA content was increased by 1.8-fold (P < 0.05). In summary, repeated muscle biopsies can be performed through a single 5- to 6-mm skin incision without eliciting muscle signaling through cascades responding to cellular stress, inflammation, or muscle damage. STAT3 phosphorylation is an early event in the healing response to muscle injury, probably mediated by the autocrine production of IL-6.

Mitochondrial biogenesis in exercise and in ageing.

Mitochondrial biogenesis is critical for the normal function of cells. It is well known that mitochondria are produced and eventually after normal functioning they are degraded. Thus, the actual level of mitochondria in cells is dependent both on the synthesis and the degradation. Ever since the proposal of the mitochondrial theory of ageing by Jaime Miquel in the 70's, it was appreciated that mitochondria, which are both a target and a source of radicals in cells, are most important organelles to understand ageing. Thus, a common feature between cell physiology of ageing and exercise is that in both situations mitochondria are critical for normal cell functioning. Mitochondrial synthesis is stimulated by the PGC-1alpha-NRF1-TFAM pathway. PGC-1alpha is the first stimulator of mitochondrial biogenesis. NRF1 is an intermediate transcription factor which stimulates the synthesis of TFAM which is a final effector activating the duplication of mitochondrial DNA molecules. This pathway is impaired in ageing. On the contrary, exercise, particularly aerobic exercise, activates mitochondriogenesis in the young animal but its effects on mitochondrial biogenesis in the old animal are doubtful. In this chapter we consider the interrelationship between mitochondrial biogenesis stimulated by exercise and the possible impairment of this pathway in ageing leading to mitochondrial deficiency and eventually muscle sarcopenia.