Influence of the biomechanical variables of the gait cycle in running economy. [Influencia de variables biomecánicas del ciclo de paso en la economía de carrera].

<p algn="justify">The aim of this study was to investigate the relationships between biomechanical variables and running economy (RE). Eleven recreational (RR) and 14 well-trained runners (WT) completed 4 min stages on a treadmill at different speeds. During the test, biomechanical variables such as ground contact time (tc), swing time (tsw), stride length, frequency and angle and the length of the different subphases of ground contact were calculated using an optical measurement system. VO2 was measured in order to calculate RE. The WT runners were more economical than the RR at all speeds and presented lower tc, higher tsw, longer strides, lower stride frequencies and higher stride angles (P<0.05). Similarly, the WT runners experienced a later propulsion subphase than the RR runners (P<0.05). RE was positively related to tc, stride frequency and 10-km race pace, whereas it was negatively related to tsw, stride length, stride angle and the propulsive subphase. Our results suggest that running patterns characterized by longer stride lengths and higher stride angles, lower stride frequencies and tc, higher tsw and later propulsion suphases may enable an efficient energy use per stride. </p> Resumen <p align="justify">El objetivo de este estudio fue el investigar las relaciones entre diferentes variables biomecánicas y la economía de carrera (RE). Once atletas populares (RR) y 14 atletas altamente entrenados (WT) completaron estadios de 4 min en tapiz rodante a diferentes velocidades. Durante el test, el tiempo de contacto (tc) y de vuelo (tsw), la longitud, frecuencia y ángulo de zancada y la duración de las diferentes sub-fases del tiempo de contacto se calcularon usando un sistema óptico. Se midió el VO2 para calcular la RE. Los atletas WT fueron más económicos que los RR y presentaron menores tc, mayores tsw, zancadas más largas, frecuencias más bajas y ángulos mayores (P<0.05). Además, los atletas WT experimentaron la sub-fase propulsiva más tarde que los RR (P<0.05). La RE estuvo positivamente relacionada con el tc, la frecuencia de zancada y el ritmo de 10 km, mientras que estuvo negativamente relacionada con el tsw, longitud y ángulo de zancada y la sub-fase propulsiva. Estos resultados sugieren que una biomecánica caracterizada por zancadas más largas, ángulos de zancada y tsw mayores, menores frecuencias y tc, y sub-fases propulsivas más tardías pueden favorecer un uso energético más eficiente.</p

The relative age effect in young athletes: a countywide analysis of 9–14-year-old participants in all competitive sports

[EN] The relative age effect (RAE) has primarily been investigated in male athletes involved in popular sports and high-level competitions. However, occurrence of RAE in other types of sports at the grassroots level, particularly in female athletes, is less well-studied. Thus, we examined the RAE in a large cohort of young athletes who participated in all competitive sports in Bizkaia, Spain, according to gender and specificity of the sport. The birth dates of 38,381 participants (65.1% males and 34.9% females) aged 9–14 years old in 37 competitive sports were analyzed. Birth dates were divided into four birth-quarters and compared to those of all children born in the same period using a χ2 goodness-of-fit test and standardized residuals. The effect size Cramer’s V was measured, and odds ratio and 95% confidence intervals were calculated to determine the odds of athletes born in January playing in the highest leagues. In the total sample, in boys RAE was evident in football, but only in highercompetition leagues (p<0.001, large effect size). In girls, RAE was evident in the most popular team sports: basketball (p<0.001, large effect size in basketball 1st league), handball and football (p<0.05, both small effect sizes). Players born in January were 3.23- and 2.89-times more likely to play in the 1st leagues than those born in December, for boys (football) and girls (basketball) respectively. In the overall analysis and in the remaining sports, presence of RAE was negligible. Therefore, the date of birth does not seem to be a constraint to participating in most sports in Bizkaia. The potential mechanisms for RAE are multifactorial and complex, yet a combination of factors, such as the popularity of a sport and the depth of competition, physicality and social influences may be involved. We discuss these mechanisms and potential measures to mitigate RAE.This work was partially supported by the University of the Basque Country (UPV/EHU) (https://www.ehu.eus/es/) under grant PPGA19/53 and the Basque government (https://www.euskadi. eus/gobierno-vasco/inicio/) under grant IT922-16. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Características físicas y antropométricas, y análisis de juego en jugadores de pádel de elite

The goals of the present study were, on the one hand, to determine the anthropometric,strength (measured by jump and hand-grip tests) compared to other racquet sports,and on the other hand, to analyze the time-motion characteristics during the under-23Spanish Paddle championships. Thus, 14 men (20,38 ± 1,92 yr) and 12 women(19.73 ± 2,37 yr) participated in this study. Firstly, participants were assessed foranthropometric measurements; secondly, strength was measured by jump andhand-grip tests before and immediately after the match; finally, the time-motion ofmatches were quantified during the under-23 Spanish Championship in 2012. Theanthropometric characteristics of paddle players were slightly different in comparisonto players of other racket sports. In respect of strength parameters, there were notsignificant differences between pre-match and post-match measurements, indicatingno fatigue component after competition. In respect to time motion analyses, restingperiods were significantly longer compared to the effective playing time. Paddle seemsto have less time active than table-tennis and badminton, but more time active thantennis.&nbsp; &nbsp; &nbsp; Los objetivos de este estudio son, por un lado, determinar las características antropométricas y de fuerza (medida mediante test de hand-grip y salto vertical con brazos libres) comprándolo con otros deportes de raqueta, y por otro, analizar las características propias del juego durante el Campeonato de España de Pádel sub-23. Para ello 14 hombres (20,38 ± 1,92 años) y 12 mujeres (19,73 ± 2,37 años) participaron en este estudio. A todos ellos se les realizó unas mediciones antropométricas, y unos tests de fuerza de miembro superior (hand-grip) y de miembro inferior (salto vertical con brazos libres) antes y después de los partidos. Por último, se registraron los datos de analisis de juego durante dicho evento. Los resultados muestran que las características antropométricas de los jugadores de pádel difieren ligeramente de las de los jugadores de otros deportes de raqueta. Los valores de fuerza, no disminuyeron después del partido, no observándose ningún indicio de fatiga. Respecto al análisis de las características del juego, el pádel se caracteriza por tener menos tiempo activo que el tenis de mesa y el badminton, pero más tiempo activo que el tenis

Hazkundea, heltzea eta lesioak gizonezkoen goi-mailako futbolari gazteetan

Injuries are very frequent in elite male football academies and have a negative impact on players’ development and health. Thus, identifying injury risk factors is vital. According to recent research, growth and maturity are related with injury occurrence. Nonetheless, the effects are not clear and results are controversial. In this article, we explain the main concepts of growth and maturity and their possible relationship with injury epidemiology.; Lesioak oso ohikoak dira gizonezkoen goi-mailako futbol taldeetan, eta jokalarien garapenean eta osasunean ondorio negatiboak dituzte. Hori dela eta, futbolarien lesioetan eragina izan dezaketen arrisku-faktoreak identifikatzea ezinbestekoa da. Azken urteotan egindako ikerketen arabera, hazkundeak eta heltzeak lesioen agerpenarekin erlazioa dutela aztertu arren, eragina ez dago guztiz argi eta kontraesanak daude. Lan honetan, hazkundearen eta heltzearen kontzeptu nagusiak laburbildu eta horien eta lesioen arteko harreman posibleak azaltzen dira

Identification of Androgen Receptor Metabolic Correlome Reveals the Repression of Ceramide Kinase by Androgens

Prostate cancer (PCa) is one of the most prevalent cancers in men. Androgen receptor signaling plays a major role in this disease, and androgen deprivation therapy is a common therapeutic strategy in recurrent disease. Sphingolipid metabolism plays a central role in cell death, survival, and therapy resistance in cancer. Ceramide kinase (CERK) catalyzes the phosphorylation of ceramide to ceramide 1-phosphate, which regulates various cellular functions including cell growth and migration. Here we show that activated androgen receptor (AR) is a repressor of CERK expression. We undertook a bioinformatics strategy using PCa transcriptomics datasets to ascertain the metabolic alterations associated with AR activity. CERK was among the most prominent negatively correlated genes in our analysis. Interestingly, we demonstrated through various experimental approaches that activated AR reduces the mRNA expression of CERK: (i) expression of CERK is predominant in cell lines with low or negative AR activity; (ii) AR agonist and antagonist repress and induce CERK mRNA expression, respectively; (iii) orchiectomy in wildtype mice or mice with PCa (harboring prostate-specific Pten deletion) results in elevated Cerk mRNA levels in prostate tissue. Mechanistically, we found that AR represses CERK through interaction with its regulatory elements and that the transcriptional repressor EZH2 contributes to this process. In summary, we identify a repressive mode of AR that influences the expression of CERK in PCa.A.G.-M. is funded by the MINECO (SAF2016-79695-R) and the department of education (IKERTALDE IT1106-16). V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia and the Basque Department of Health (2016111109) and the MINECO RTI2018-097267-B-I00. The work of A. Carracedo is supported by the Basque Department of Industry, Tourism and Trade (Elkartek), the department of education (IKERTALDE IT1106-16) and health (RIS3), the MICINN (PID2019-108787RB-I00 (FEDER/EU); Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks RED2018-102769-T), the AECC (GCTRA18006CARR), La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/ and the European Research Council (Consolidator Grant 819242). CIBERONC was co-funded with FEDER funds and funded by ISCIII

Low-dose statin treatment increases prostate cancer aggressiveness

Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer

Low-dose statin treatment increases prostate cancer aggressiveness

Altres ajuts: NM-M was supported by the Spanish Association Against Cancer (AECC), AECC JP Vizcaya. VT is supported by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the department of health of the Basque Government (2016111109) and the 2016 grant of the AECC (Junta provincial de Bizkaia). LA, AA-A and LV-J were supported by the Basque Government of education. The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek) and the department of education (IKERTALDE IT1106-16), FERO VIII Fellowship, the BBVA foundation, Severo Ochoa. Excellence Accreditation SEV-2016-0644) and the European Research Council (Starting Grant 336343; Proof of Concept 754627). The participation of AC, VT, NM-M, SF and AZ as part of CIBERONC was co-funded with FEDER funds.Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer

Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa

PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

[EN] Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.We are grateful to the Carracedo lab for valuable input, to Drs. Ana M. Aransay, James D. Sutherland and F. Elortza for technical advice, and Drs. Michelle Clasquin, Katie Sellers and Katya Marjon at Agios Pharmaceuticals for performing, processing and analyzing the metabolomics experiments. We thank the Basque Biobank for Research (BIOEF) for the support with prostate specimen acquisition and management. A.A-A. was funded by the Basque Government (predoctoral fellowship). V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia, the Basque Department of Health (2016111109) and the MICINN RTI2018-097267-B-I00. I.M. is supported by Fundación Cris Contra el Cáncer (PR_TPD_2020-19). The work of A. Carracedo is supported by the Basque Department of Industry, Tourism and Trade (Elkartek), the department of education (IKERTALDE IT1106-16) and health (RIS3), the BBVA foundation, the MICINN (SAF2016-79381-R; PID2019-108787RB-I00 (FEDER/EU); Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks RED2018-102769-T), the AECC (GCTRA18006CARR), Vencer el Cáncer Foundation, La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/ and the European Research Council (Starting Grant 336343, PoC 754627, Consolidator Grant 819242). CIBERONC was co-funded with FEDER funds and funded by ISCIII. We are grateful for the support of Mondravember and Movembergara. A.E. was supported by MCIN/AEI/10.13039/501100011033 and the EU programme NextGenerationEU/PRTR (IJC2020-043583-I). The work of JM Mato was supported by NIH grant R01CA172086 and SAF2017-88041-R. EB is funded by the MICINN (BFU2016-76872-R (FEDER/EU), PID2019-108112RB-I00, and Excellence Networks SAF2017-90794-REDT)

Genomic and functional regulation of TRIB1 contributes to prostate cancer pathogenesis

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer