Effect of 3 Weeks Use of Compression Garments on Stride and Impact Shock during a Fatiguing Run.

Excessive and prolonged exposure to impact acceleration during running is associated with increased injury rate. Acute use of compressive garments has been speculated to improve attenuation. However, it is unknown how longer interventions of compressive garments influence attenuation in running. 40 runners trained with compressive and placebo stockings for 3 weeks. Perception of comfort, stride parameters (rate, length) and impact acceleration (head and tibial peak acceleration, magnitude, acceleration rate and attenuation) were measured every 5 min during a fatigue run (30 min at 80% of the individual's maximal aerobic speed). Compressive stockings reduced tibial peak acceleration and magnitude compared to placebo stockings at every minute (p<0.05) except for the initial measurement (p>0.05). Moreover, compressive stockings led to a lower rate of increase in tibial peak acceleration (14%, p<0.005) and magnitude (16%, p<0.001) as a result of the development of fatigue compared to placebo stockings (24% and 26% increase, p=0.014 and p=0.003, respectively). Similar perception of comfort was reported for both garments. Training with compressive stockings for 3 weeks reduced impact acceleration and the rate of increase in acceleration compared to placebo stockings. These findings suggest that compressive stockings may play a protective role by reducing impact accelerations during running.

Effects of graduated compression stockings on skin temperature after running.

High skin temperatures reduce the thermal gradient between the core and the skin and they can lead to a reduction in performance and increased risk of injury. Graduated compression stockings have become popular among runners in the last years and their use may influence the athlete's thermoregulation. The aim of this study was to investigate the effects of graduated compression stockings on skin temperature during running in a moderate indoor environment. Forty-four runners performed two running tests lasting 30min (10min of warm-up and 20min at 75% of their maximal aerobic speed) with and without graduated compressive stockings. Skin temperature was measured in 12 regions of interest on the lower limb by infrared thermography before and after running. Heart rate and perception of fatigue were assessed during the last minute of the running test. Compression stockings resulted in greater increase of temperature (p=0.002 and ES=2.2, 95% CI [0.11-0.45°C]) not only in the body regions in contact (tibialis anterior, ankle anterior and gastrocnemius) but also in the body regions that were not in contact with the garment (vastus lateralis, abductor and semitendinosus). No differences were observed between conditions in heart rate and perception of fatigue (p>0.05 and ES<0.8). In conclusion, running with graduated compression stockings produces a greater increase of skin temperature without modifying the athlete's heart rate and perception of fatigue.

Long-term effects of graduated compression stockings on cardiorespiratory performance.

The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) - a 5-min maximal effort run in order to determine the participants' maximal aerobic speed; and tests 2) and 3) - a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners.

Influence of foot orthosis customisation on perceived comfort during running.

Although running is associated with many health benefits, it also exposes the body to greater risk of injury. Foot orthoses are an effective strategy to prevent such injuries. Comfort is an essential element in orthosis design since any discomfort alters the runner's biomechanics, compromising performance and increasing the risk of injury. The present study analyses the perceived comfort of three types of orthoses: custom-made, prefabricated and original running shoe insoles. Nine comfort variables for each insole were assessed in a sample of 40 runners. Custom-made and prefabricated insoles were both perceived as significantly more comfortable than the original insoles. The differences were clinically relevant and were potentially causes of modifications in running gait. Although the prefabricated insoles were rated slightly higher than the custom-made insoles, the differences were not statistically significant. This study shows that prefabricated insoles constitute a reasonable alternative to custom-made insoles in terms of comfort. PRACTITIONER SUMMARY: The perceived level of comfort of footwear is considered to be a protective measure of the potential risk of running injuries. We here compared runners' perception of comfort of custom-made and prefabricated orthoses while running. We found that even though custom-made orthoses are closely matched to each individual's foot, such customisation does not necessarily imply greater comfort.

Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages.

Blood vessels originate as simple endothelial cell tubes. It has been proposed that platelet-derived growth factor B polypeptide (Pdgfb) secreted by these endothelial cells drives the formation of the surrounding muscular wall by recruiting nearby mesenchymal cells. However, targetted inactivation of the Pdgfb gene or the Pdgf receptor beta (Pdgfrb) gene, by homologous recombination, does not prevent the development of apparently normal large arteries and connective tissue. We have used an in vivo competition assay in which we prepared chimaeric blastocysts, composed of a mixture of wild-type (Pdgfrb[+/+]) and Pdgfrb(+/-) or wild-type and Pdgfrb(-/-) cells, and quantified the relative success of cells of the two component genotypes in competing for representation in different cell lineages as the chimaeric embryos developed. This study revealed that the participation of Pdgfrb(-/-) cells in all muscle lineages (smooth, cardiac, skeletal and pericyte) was reduced by eightfold compared with Pdgfrb(+/+) cells, and that participation of Pdgfrb(+/-) cells was reduced by twofold (eightfold for pericytes). Pdgfrb inactivation did not affect cell contribution to non-muscle mesodermal lineages, including fibroblasts and endothelial cells. Chimaera competition is therefore a sensitive, quantitative method for determining developmental roles of specific genes, even when those roles are not apparent from analysis of purebred mutants; most likely because they are masked by homeostatic mechanisms.

Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy.

Expansion of a CTG trinucleotide repeat in the 3' UTR of the gene DMPK at the DM1 locus on chromosome 19 causes myotonic dystrophy, a dominantly inherited disease characterized by skeletal muscle dystrophy and myotonia, cataracts and cardiac conduction defects. Targeted deletion of Dm15, the mouse orthologue of human DMPK, produced mice with a mild myopathy and cardiac conduction abnormalities, but without other features of myotonic dystrophy, such as myotonia and cataracts. We, and others, have demonstrated that repeat expansion decreases expression of the adjacent gene SIX5 (refs 7,8), which encodes a homeodomain transcription factor. To determine whether SIX5 deficiency contributes to the myotonic dystrophy phenotype, we disrupted mouse Six5 by replacing the first exon with a beta-galactosidase reporter. Six5-mutant mice showed reporter expression in multiple tissues, including the developing lens. Homozygous mutant mice had no apparent abnormalities of skeletal muscle function, but developed lenticular opacities at a higher rate than controls. Our results suggest that SIX5 deficiency contributes to the cataract phenotype in myotonic dystrophy, and that myotonic dystrophy represents a multigenic disorder.

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

Successful allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia in a patient with hepatic echinococcal cyst managed by delayed hepatectomy.

We report the case of a patient who underwent cytotoxic chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia in the presence of hepatic cystic echinococcal infection. The presence of Echinococcus granulosus infection in an immunocompromised host is extremely rare, with lack of established data regarding optimal management. Successful management of the patient's disease processes required a multidisciplinary approach, which included systemic chemotherapy, HSCT, treatment of chronic graft-versus-host-disease, and elective en bloc resection of the hepatic cyst.

Zoo animals as sentinels for Schmallenberg virus monitoring in Spain.

Schmallenberg virus (SBV) is a newly emerged vector-borne pathogen that affects many domestic and wild animal species. A serosurvey was carried out to assess SBV exposure in zoo animals in Spain and to determine the dynamics of seropositivity in longitudinally sampled individuals. Between 2002 and 2019, sera from 278 animals belonging to 73 different species were collected from five zoos (A-E). Thirty-one of these animals were longitudinally sampled at three of these zoo parks during the study period. Seropositivity was detected in 28 (10.1 %) of 278 animals analyzed by blocking ELISA. Specific anti-SBV antibodies were confirmed in 20 (7.2 %; 95 %CI: 4.2-10.3) animals of six different species using virus neutralization test (VNT). The multiple logistic regression model showed that "order" (Artiodactyla) and "zoo provenance" (zoo B; southern Spain) were risk factors potentially associated with SBV exposure. Two (8.7 %) of the 31 longitudinally-sampled individuals showed specific antibodies against SBV at all samplings whereas seroconversion was detected in one mouflon (Ovis aries musimon) and one Asian elephant (Elephas maximus) in 2016 and 2019, respectively. To the best of the author's knowledge, this is the first surveillance conducted on SBV in zoos in Spain. The results confirm SBV exposure in zoo animals in this country and indicate circulation of the virus before the first Schmallenberg disease outbreak was reported in Spain. Surveillance in zoological parks could be a complementary approach to monitoring SBV activity. Further studies are warranted to assess the impact of this virus on the health status of susceptible zoo animals.

A variable presentation of Joubert syndrome: Case report and a brief review.

Joubert syndrome is a rare neurological manifestation usually present in late infancy or early childhood with characteristic episodes of abnormal breathing pattern along with the neurological and other systemic involvement.We report a case of confirmed Joubert syndrome present in the immediate neonatal period with isolated spells of oxygen desaturations not accompanied by the classically described breathing pattern and absent neurological symptoms causing delay in the diagnosis. Isolated oxygen desaturation episodes could be a presenting manifestation of Joubert syndrome in a neonatal period.

NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice.

Src-related nonreceptor protein tyrosine kinases in nerve growth cones (p59fyn, pp60c-src, and pp62c-yes) are potential intracellular signaling molecules for cell adhesion molecule-directed axonal growth. To determine whether src-related tyrosine kinases mediate NCAM-dependent neurite outgrowth, cultures of cerebellar and sensory neurons from fyn-, src-, and yes- minus mice were analyzed for neurite outgrowth on monolayers of NCAM140-transfected L fibroblasts. NCAM-dependent neurite outgrowth was selectively inhibited in cultures of cerebellar and dorsal root ganglion neurons from fyn-, but not src- or yes- mice. Neurite outgrowth by fyn-, src-, or yes- neurons on untransfected fibroblast monolayers was unaffected, indicating that these kinases do not contribute significantly to axon growth on at least some integrins or other adhesive substrates present on fibroblasts. This study demonstrates that p59fyn is an essential component of the NCAM signaling pathway leading to axonal growth.

Phosphorylation of c-Src on tyrosine 527 by another protein tyrosine kinase.

The protein tyrosine kinase activity of the cellular Src protein is negatively regulated by phosphorylation at tyrosine residue 527 (Tyr527). It has not been established whether this regulatory modification of Src is mediated by autophosphorylation or by another cellular protein kinase. The phosphorylation of a modified form of c-Src that lacks kinase activity was examined in mouse cells that do not express endogenous Src (because of the targeted disruption of both src alleles). Phosphorylation of the inactive form of Src on Tyr527 occurred to a similar extent in cells lacking endogenous Src as it did in cells expressing Src. Therefore, Tyr527 phosphorylation, and thus negative control of Src kinase activity, is mediated by another cellular protein tyrosine kinase.

Tissue-specific and ectopic expression of genes introduced into transgenic mice by retroviruses.

Recombinant retroviruses containing the complete genomic human beta globin gene (under the control of its own promoter) and the bacterial neomycin phosphotransferase gene (under the control of the normal or enhancerless viral promoter) were used to derive transgenic mouse strains by infection of preimplantation embryos. Expression of the beta globin gene in hematopoietic tissues was observed in all transgenic strains. In addition, one strain showed ectopic expression of beta globin in the same tissues that also expressed high levels of RNA from the viral promoter. It is likely that expression from the long terminal repeat (LTR), in contrast to expression from the internal promoter, is dependent on the site of integration. Thus, retroviral vectors can be used for tissue-specific expression of foreign genes in transgenic mice, as well as for the identification of loci that allow developmental activation of a provirus.

Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.

Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and abl, were used to study the role of these kinases in long-term potentiation (LTP) and in the relation of LTP to spatial learning and memory. All four kinases were expressed in the hippocampus. Mutations in src, yes, and abl did not interfere with either the induction or the maintenance of LTP. However, in fyn mutants, LTP was blunted even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation, were normal. In parallel with the blunting of LTP, fyn mutants showed impaired spatial learning, consistent with a functional link between LTP and learning. Although fyn is expressed at mature synapses, its lack of expression during development resulted in an increased number of granule cells in the dentate gyrus and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.

Effects of prefabricated and custom-made foot orthoses on skin temperature of the foot soles after running.

OBJECTIVE: Foot orthoses are increasingly used by runners despite the controversy about whether their use can reduce the risk of overuse injuries. Some authors have found modifications in plantar pressures with the use of foot orthoses, which could produce changes in the surface skin temperature of the foot soles. The aim of this study was to analyse the effects of custom-made and prefabricated foot orthoses on the skin temperature of different regions of both foot soles after running. APPROACH: Twenty-four participants carried out a maximal aerobic speed test as a pre-test, and three running tests at the laboratory wearing different foot orthoses conditions (control, prefabricated and custom-made) previously randomized. Skin temperature of four regions of interest of the foot soles was assessed before, immediately after and ten minutes after running. MAIN RESULTS: The use of prefabricated and custom-made foot orthoses did not produce changes on skin temperature of the foot soles neither in absolute temperatures (p > 0.05), nor in temperature variations: between immediately after and before running (p > 0.05), and between ten minutes after and immediately after running (p > 0.05). Otherwise, higher values were found with no insoles than with prefabricated foot orthoses, 10 min after running in relation to before running, in forefoot [mean (standard deviation): 5.6 (2.4) versus 3.7 (2.7) °C; p = 0.02; effect size (ESd) = 0.72], midfoot [3.7 (1.5) versus 2.7 (1.5) °C; p = 0.03; ESd = 0.65] and rearfoot [4.18 (2.05) versus 2.9 (1.82) °C; p = 0.02; ESd = 0.64)]. SIGNIFICANCE: In conclusion, the use of foot orthoses, in general, does not affect the surface skin temperature of the foot soles after an intense run.

Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.

The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-, and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.

Mena is required for neurulation and commissure formation.

Mammalian enabled (Mena) is a member of a protein family thought to link signal transduction pathways to localized remodeling of the actin cytoskeleton. Mena binds directly to Profilin, an actin-binding protein that modulates actin polymerization. In primary neurons, Mena is concentrated at the tips of growth cone filopodia. Mena-deficient mice are viable; however, axons projecting from interhemispheric cortico-cortical neurons are misrouted in early neonates, and failed decussation of the corpus callosum as well as defects in the hippocampal commissure and the pontocerebellar pathway are evident in the adult. Mena-deficient mice that are heterozygous for a Profilin I deletion die in utero and display defects in neurulation, demonstrating an important functional role for Mena in regulation of the actin cytoskeleton.

Genetics of signal transduction: tales from the mouse.

Recent progress in understanding signal transduction owes much to new genetic approaches, first by unraveling the molecular basis of classic mutations, and then by the use of gene targeting. Recent studies have examined mammalian signal transduction from cell surface to nucleus, especially ligand-receptor systems and cytosolic signal transducers.