Ligament Injuries in Professional Male Handball Players: A 6-Year Longitudinal Study.

Handball is a sport that involves high-intensity actions throughout the game, such as sprints, jumps, landings, and high-speed, repeated throws. This, along with competitive and tactical factors, congested schedules, and the need to maintain a high level of performance throughout the season, contributes to a high injury rate. This study aimed to analyse ligament injuries in a professional handball team over six consecutive seasons. A total of 68 elite male Spanish handball players participated, with 54 time-loss injuries (i.e., injuries involving at least one day of absence) observed during this study period. Ligament injury information was recorded following the International Olympic Committee consensus statement. The overall incidence was 0.89 ligament injuries per 1000 h of exposure. Additionally, a higher incidence and burden of ligament injuries was observed during match-play compared to training. Most ligament injuries were classified as minor or moderate (i.e., 79.63% of the total), and 46.29% were reinjuries. A significantly higher incidence of ligament injuries was suffered in the lower limbs compared to the upper limbs (0.81 vs. 0.08 ligament injuries per 1000 h; p < 0.001). Specifically, the highest incidence was observed in the anterior talofibular ligament of the ankle (0.57 injuries per 1000 h of exposure), while the greatest burden was related to the anterior cruciate ligament (24.08 absence days per 1000 h of exposure). This study provides an overview of ligament injuries among professional handball players, highlighting the need to implement strategies with positive effects during competition (e.g., specific activation strategies or training programmes based on strength and balance) and to reduce injury recurrences.

Ligilactobacillus salivarius PS11610 exerts an effect on the microbial and immunological profile of couples suffering unknown infertility.

PROBLEM: Unknown or idiopathic infertility has been associated with urogenital tract dysbiosis, reducing pregnancy and delivery ratios during assisted reproductive treatments (ART). The Ligilactobacillus salivarius PS11610 strain has shown extraordinary antimicrobial activity in vitro against urogenital pathogens as well as other probiotic characteristics. Therefore, an intervention study was performed to evaluate the effect of L. salivarius PS11610 on the microbial composition of urogenital tract in infertile couples with bacterial dysbiosis. METHOD OF STUDY: Seventeen couples undergoing ART diagnosed with unknown infertility were selected. After confirming urogenital dysbiosis, they started a 6-month treatment with L. salivarius PS11610 (1 dose/12 h for female and 1 dose/24 h for male). Vaginal, seminal, glans, uterine and plasma samples were collected for determination of the microbiome and immune profile at the beginning and the end of the treatment. RESULTS: Supplementation with L. salivarius PS11610 significantly modified the urogenital microbiome composition in male and female samples, solving dysbiosis of 67% of the couples. Pathogens disappeared from the vaginal samples whereas Lactobacilli percentage increased after 3 and 6 months of treatment. Moreover, L. salivarius PS11610 changed the uterine microbiome that could be associated with a change of the uterine immune profile. Additionally, the probiotic intake could be associated with the observed change in the systemic immunological profile of couples. Finally, the pregnant and delivery ratio were improved. CONCLUSIONS: Probiotic supplementation with L. salivarius PS11610 improved the male and female urogenital tract microbiome, modulating the immune system and increasing pregnancy success in couples undergoing ART.

Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effect of Two Probiotics on the Preterms' Gut Microbiota.

OBJECTIVE: To evaluate the effect of a new probiotic strain combination, Ligilactobacillus salivarius subsp infantis PS11603 and Bifidobacterium longum PS10402, on gut bacterial colonization of preterm infants. METHODS: A randomized, double-blind, placebo-controlled study was conducted in preterm infants from 28 weeks + 0days to 30 weeks + 6days of gestation. Thirty preterm infants were randomly selected after birth to receive either probiotics or placebo. Stool samples were collected before product intake and then sequentially during the first weeks of their admission. Classical microbiological, metagenomics and multiplex immunological analyses were performed to assess the bacterial and immune profile of the samples. RESULTS: Twenty-seven infants completed the study (14 vs 13, probiotic and placebo groups). A higher number of participants were colonized by Lactobacilli in the probiotic group than in the placebo group (93% vs 46%; P  = 0.013). Similar results were obtained when analysing bifidobacterial colonization (100% vs 69%; P  = 0.041). Earlier colonization was observed in the probiotics group versus the placebo group, specifically 5 weeks for Lactobacillus and 1 week for Bifidobacterium. Although no effect was observed in the faecal immunological profile, a decreasing trend could be observed in Th17 response during the first week of probiotic treatment. None of the adverse events (AEs) registered were related to product intake. CONCLUSION: Probiotic supplementation with L salivarius PS11603 and B longum subsp. infantis PS10402 enhanced an earlier colonization of Lactobacillus and Bifidobacterium in preterm infants' guts in 5 and 1 week, respectively. A higher number of infants were colonized by Lactobacilli with the probiotics' intake at the end of the study.

Injury Profile in Professional Handball Players During 4 Consecutive Seasons According to Playing Positions: A Longitudinal Study.

BACKGROUND: The injury profile of each playing position in handball is a key factor in being able to improve the injury risk management process. Therefore, the aim of this study was to longitudinally analyze the differences in professional handball players' injury profile according to their playing position (ie, goalkeeper, back, wing, and line). HYPOTHESIS: Injury incidence and burden would be higher in back players compared with the other playing positions, while ligament and knee would be the most common injury type and location. STUDY DESIGN: Prospective cohort design. LEVEL OF EVIDENCE: Level 4. METHODS: Sixty-eight male handball players belonging to the same professional team participated in this study over 4 consecutive seasons. Injury incidence and injury burden were recorded as well as the severity, type, and location following the International Olympic Committee consensus statement. RESULTS: Although nonsignificant differences in injury incidence were found according to playing position (rate ratios [RRs] from 0.43 to 2.47; P > 0.05), back players reported the highest burden (60.65 absence days/1000 h; RR from 0.12 to 7.75;P < 0.05), with wing players showing a greater burden (54.29 absence days/1000 h; RR from 0.09 to 4.91; P < 0.05) in comparison with goalkeepers (12.19 absence days/1000 h) and line players (13.10 absence days/1000 h). Muscle/tendon injuries and sprains presented higher incidence and burden than other type of injuries, and a greater incidence and burden was reported for knee injuries in all playing positions. CONCLUSION: The highest injury incidence and injury burden is in back players in professional handball. CLINICAL RELEVANCE: This study provides comprehensive information on the injury profile of professional handball players, which can be useful for strength and conditioning coaches when developing specific injury risk management programs.

Longitudinal differences in the injury profile of professional male handball players according to competitive-level.

The aim was to analyse the differences in professional handball players` injury profile according to the team`s competitive-level (i.e., First division vs. Second division). Fifty-three professional male handball players participated in this study during four consecutive seasons in the same team (2015-16 and 2016-17 for the First division league and 2017-18 and 2018-19 for the Second division league). No significant differences in overall incidence were observed between groups (3.69 vs 4.19 injuries/1000 h, RR = 0.88, 95% CI 0.64-1.22, P = 0.44), although significantly greater injury incidence during training sessions was observed in the Second division group (3.06 vs 1.61 injuries/1000 h, RR = 0.52, 95% CI 0.34-0.81, P = 0.01), while greater injury incidence during matches was reported in the First division group (84.03 vs 49.88 injuries/1000 h, RR = 1.68, 95% CI 1.00-2.83, P = 0.05). The second division group presented the greatest injury burden attending to overall, training and match exposure, as well as in most locations and injury types. Given the between groups differences found in the injury profile of handball player, it is suggested to implement specific preventive strategies attending to the characteristics of each level-group.

Effects of Gluteal Muscles Strengthening on Lower-Limb Injuries in Male Professional Handball Players: A Preliminary Study.

ABSTRACT: Raya-González, J, García-Esteban, S, Hume, P, and Castillo, D. Effects of gluteal muscles strengthening on lower-limb injuries in male professional handball players: a preliminary study. J Strength Cond Res 35(6): 1593-1598, 2021-This study aimed to analyze the effects of a strength training injury-prevention program (STIPP) on injuries associated with weakness of the gluteal muscles in professional handball players. Twenty-seven professional Spanish male handball players from the same club, who competed at the Spanish Second National League level, participated in this study. The investigation was conducted over 2 consecutive seasons (2017-2018 and 2018-2019). The first season served as the control season (n = 21), and the second season served as the experimental season (n = 20). The STIPP was conducted 2 times per week, for 32 weeks, during the in-season period. There were no significant improvements in the injury incidence, pattern, or type for the experimental season group compared with the control season group (injury rate ratio [IRR] = 1.47; 95% confidence interval [CI]: 0.84-2.58; p = 0.17). However, there was a meaningful reduction in the number and burden of lumbar injuries after the STIPP (IRR = 55.83; 95% CI: 0.11-89.01; p = 0.001). In addition, burden values (number of absence days/1000 hours exposure) in all injury pathologies were lower during the experimental season compared with the control season. The STIPP focused on the gluteal muscles could be effective in reducing the number and burden of lumbar injuries in professional handball players.

A new robust adaptive mixing control for trajectory tracking with improved forward flight of a tilt-rotor UAV.

A new robust adaptive mixing control (RAMC) is proposed in order to accomplish trajectory tracking of a tilt-rotor unmanned aerial vehicle (UAV) configuration. This kind of system is a hybrid aerial vehicle that combines advantages of rotary-wing aircraft, like hovering flight and vertical take-off and landing (VTOL), and those of fixed-wing aircraft, as improved forward flight. Although the VTOL and cruise flight regimes present different dynamic behaviors, in this work a unified, highly coupled, nonlinear model is developed to cope with the considered tilt-rotor UAV full flight envelope, that is, the axial flight, hovering, transition/cruise and turning flight. The modeling is performed via Euler-Lagrange formulation considering the tilt-rotor UAV as a multi-body system and taking into account aerodynamic effects and the dynamics of the tilting servomotors. Accordingly, in order to comply with the trajectory tracking requirements and improve the tilt-rotor UAV forward flight, this paper presents a novel robust adaptive mixing controller which is formulated to deal with linear parameter-varying (LPV) systems dependent on not known a priori large parameters but measured or estimated online, and also to provide robustness against unknown disturbances. Additionally, a rigorous closed-loop stability analysis is performed. The controller performance is validated with numerical experiments conducted using a high fidelity simulator developed on Gazebo and Robot Operating System (ROS) platforms.

Remodeling of the Microvasculature: May the Blood Flow Be With You.

The vasculature ensures optimal delivery of nutrients and oxygen throughout the body, and to achieve this function it must continually adapt to varying tissue demands. Newly formed vascular plexuses during development are immature and require dynamic remodeling to generate well-patterned functional networks. This is achieved by remodeling of the capillaries preserving those which are functional and eliminating other ones. A balanced and dynamically regulated capillary remodeling will therefore ensure optimal distribution of blood and nutrients to the tissues. This is particularly important in pathological contexts in which deficient or excessive vascular remodeling may worsen tissue perfusion and hamper tissue repair. Blood flow is a major determinant of microvascular reshaping since capillaries are pruned when relatively less perfused and they split when exposed to high flow in order to shape the microvascular network for optimal tissue perfusion and oxygenation. The molecular machinery underlying blood flow sensing by endothelial cells is being deciphered, but much less is known about how this translates into endothelial cell responses as alignment, polarization and directed migration to drive capillary remodeling, particularly in vivo. Part of this knowledge is theoretical from computational models since blood flow hemodynamics are not easily recapitulated by in vitro or ex vivo approaches. Moreover, these events are difficult to visualize in vivo due to their infrequency and briefness. Studies had been limited to postnatal mouse retina and vascular beds in zebrafish but new tools as advanced microscopy and image analysis are strengthening our understanding of capillary remodeling. In this review we introduce the concept of remodeling of the microvasculature and its relevance in physiology and pathology. We summarize the current knowledge on the mechanisms contributing to capillary regression and to capillary splitting highlighting the key role of blood flow to orchestrate these processes. Finally, we comment the potential and possibilities that microfluidics offers to this field. Since capillary remodeling mechanisms are often reactivated in prevalent pathologies as cancer and cardiovascular disease, all this knowledge could be eventually used to improve the functionality of capillary networks in diseased tissues and promote their repair.

Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis.

Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP in endothelial cells (MT1iΔEC ) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS-induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1-MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C-terminal fragment of MT1-MMP substrate thrombospondin-1 (TSP1) to CD47/αvß3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti-MT1-MMP inhibitory antibody or a nonamer peptide spanning the αvß3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1-MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.

KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer.

KISS1 is a metastasis suppressor lost in several solid malignancies. We evaluated the clinical relevance of KiSS-1 methylation and its protein expression in colorectal cancer. The epigenetic silencing of KiSS-1 by hypermethylation was tested in colon cancer cells (n = 5) before and after azacytidine treatment. KiSS-1 methylation was evaluated by methylation-specific PCR in colorectal cancer cells, and normal, benign, and tumor tissues (n = 352) were grouped in a training set (n = 62) and two independent validation cohorts (n = 100 and n = 190). KiSS-1 protein expression was analyzed by immunohistochemistry on tissue arrays. KiSS-1 hypermethylation correlated with transcript and protein expression loss, being increased in vitro by azacytidine. Methylation rates were 53.1, 70.0, and 80.0 % in the training and validation sets, respectively. In the training set, KiSS-1 methylation rendered a diagnostic accuracy of 72.7 % (p = 0.002). Combination of KiSS-1 methylation and serum CEA (p = 0.001) increased the prognostic utility of CEA alone (p = 0.022). In the first validation set, KiSS-1 methylation correlated with tumor grade (p = 0.011), predicted recurrence (p = 0.009), metastasis (p = 0.004), disease-free (p = 0.034), and overall survival (p = 0.015). In the second validation cohort, KiSS-1 methylation predicted disease-specific survival (p = 0.030). In the training set, cytoplasmic KiSS-1 expression was significantly higher in nonneoplastic biopsies as compared to colorectal tumors (p < 0.0005). In the validation set, loss of cytoplasmic expression correlated with tumor stage (p = 0.007), grade (p = 0.035), recurrence (p = 0.017), and disease-specific survival (p = 0.022). KiSS-1 was revealed epigenetically modified in colorectal cancer. The diagnostic and prognostic utility of KiSS-1 methylation and expression patterns suggests their assessment for the clinical management of colorectal cancer patients.

Diagnostic and prognostic utility of methylation and protein expression patterns of myopodin in colon cancer.

Myopodin is an actin-binding protein believed to play a tumor suppressor role in several solid neoplasias. We evaluated the potential differential myopodin methylation and expression and their clinical relevance in colon cancer. The epigenetic silencing of myopodin by hypermethylation was tested in colon cancer cells (n = 5) before and after azacitidine treatment. Myopodin methylation status was evaluated by methylation-specific PCR in colon cancer cells and colorectal tissues (n = 210) grouped in a training set (n = 62) and two independent validation series (n = 100 and n = 48) collected at independent clinical settings. Myopodin expression patterns were analyzed by immunohistochemistry on tissue arrays. Myopodin hypermethylation correlated with gene and protein expression loss, being increased in vitro by azacitidine. Myopodin was frequently methylated in colon cancer cells (four out of five). Methylation rates were 90.3%, 70.0%, and 47.8% in the training and validation sets, respectively. Myopodin methylation rendered a diagnostic accuracy of 83.9% (p < 0.0005). Cytoplasmic myopodin expression was significantly higher in non-neoplastic biopsies compared to colon tumors (p < 0.0005). Loss of myopodin expression correlated with increasing tumor stage (p = 0.011), methylation (p = 0.005), and poor overall survival (p = 0.003). In the first validation set (n = 100), myopodin methylation predicted disease-free (p = 0.046) and overall survival (p = 0.031). In the second validation cohort, myopodin methylation and protein expression patterns predicted disease-specific (p = 0.012 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.043, respectively). Thus, myopodin was revealed to be epigenetically modified in colon cancer. The diagnostic and prognostic clinical utility of myopodin methylation and expression patterns suggest considering their assessment for the clinical management of colon cancer patients.

Profilin 1 is a potential biomarker for bladder cancer aggressiveness.

Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a "gold mine" for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography tandem MS. Among the identified proteins, multiple corresponded to proteins with affinity for metals and/or reported to be phosphorylated and included proteins with demonstrated association with BC such as MMP9, fibrinogen forms, and clusterin. In agreement to the immobilized metal affinity chromatography results, aminopeptidase N, profilin 1, and myeloblastin were further found to be differentially expressed in urine from patients with invasive compared with non invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless exhibiting high interindividual variability. By tissue microarray analysis, profilin 1 was found to have a marked decrease of expression in the epithelial cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with occasional expression in stroma; importantly, this pattern strongly correlated with poor prognosis and increased mortality. The functional relevance of profilin 1 was investigated in the T24 BC cells where blockage of the protein by the use of antibodies resulted in decreased cell motility with concomitant decrease in actin polymerization. Collectively, our study involves the application of a fractionation method of urinary proteins and as one main result of this analysis reveals the association of profilin 1 with BC paving the way for its further investigation in BC stratification.

Eficacia de los procedimientos diagnósticos en la patología médico-quirúrgica de las glándulas salivales / The efficacy of diagnostic procedures in medical-surgical pathology of the salivary glands

Objetivos. Establecer la eficacia diagnóstica de los procedimientos clínicos y complementarios para diagnosticar la patología médico-quirúrgica de las glándulas salivales. Diseño. Estudio retrospectivo de 436 casos de patologías médico-quirúrgicas (1985-97) en glándulas salivales, comparando los informes de anatomía patológica y microbiología frente a los informes diagnósticos de las pruebas complementarias más habituales: radiografía simple, sialografía, ecografía, tomografía axial computarizada (TAC), resonancia magnética (RM) y punción aspiración con aguja fina (PAAF). Resultados y conclusiones. El diagnóstico clínico de presunción tiene una sensibilidad y especificidad superior a 0,80 para determinar si el proceso es o no benigno/maligno. Sin embargo, tiene una baja exactitud para tipificarlo. La PAAF tiene una alta sensibilidad, excepto para el carcinoma adenoide quístico, pero desciende su eficacia en la tipificación. La especificidad es más elevada y ofrece una mayor exactitud para tipificar el proceso. La ecografía debe sustituir a la sialografía en los procesos inflamatorios y obstructivos de las glándulas salivales. La TAC y la RM no aportan beneficios superiores a otras exploraciones; deben reservarse para establecer el estadiaje, comprobar la afectación o no del lóbulo profundo de la parótida, y determinar la relación de los tumores con las estructuras adyacentes (AU)