Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

Electrocoagulation treatment of furniture industry wastewater.

Electrocoagulation was investigated as a method for treating wastewater containing polyvinyl acetate (PVAc) from the furniture industry. The study evaluated the evolution of iron concentration and passivation during the treatment process. Laboratory-scale experiments were conducted to evaluate the effects of inter-electrode distance (d), current density, and mode on treatment performance. Three values of d (0.3, 0.6, and 0.9 cm) were studied and found to have no significant effect on performance. However, lower d values resulted in reduced energy consumption due to a decrease in applied voltage. Three values of current density (132, 158, and 197 A m-2) were studied under two current modes, Direct Current (DC) and Alternating Pulsed Current (APC). The best treatment performance for DC occurred under 158 A m-2 (the treated wastewater was characterized by pH = 4.59 ± 0.02, conductivity = 996 ± 21 µS cm-1, COD = 1940 ± 55 mgO2 L-1, TSS = 105 ± 14 mg L-1, and Fe = 50.39 ± 1.87 mgFe L-1). For APC, the best performance was achieved under 197 A m-2 (the treated wastewater was characterized by pH = 6.33 ± 0.06, conductivity = 988 ± 17 µS cm-1, COD = 1942 ± 312 mgO2 L-1, TSS = 199 ± 55 mg L-1, and Fe = 44.68 ± 4.60 mgFe L-1). Despite the promising results, treatment performance was insufficient to meet the legal requirements for water discharge. APC was found to be a more economically viable approach, as it reduced anode wear, electrode passivation, and energy consumption. The quantity of iron released increased with d, and the effect of current density on iron concentration was found to be non-linear. However, applying APC reduced the iron content for all tested current densities. The tests showed that EC was effective in removing chemical oxygen demand (COD) and total suspended solids (TSS), achieving removal efficiencies above 92% and 99%, respectively. However, the studied treatment procedures were insufficient to meet the EU legal requirements for water discharge. Therefore, the obtained wastewater should undergo a post-treatment process.

Antileishmanial activity, cytotoxicity and cellular response of amphotericin B in combination with crotamine derived from Crotalus durissus terrificus venom using in vitro and in silico approaches.

OBJECTIVE: To investigate the in vitro activity, synergism, cytotoxicity and cellular immunological response, as well as the molecular affinity between amphotericin B (AmB) and crotamine (CTA), derived from Crotalus durissus terrificus venom against Leishmania amazonensis. METHODS: This study performed the inhibition of promastigotes and amastigotes' growth under different concentrations of the drug and pharmacological combinations (AmB + CTA) based on the Berimbaum method (synergism study). The lactate dehydrogenase (LDH) quantification method was used to determine the cytotoxicity of the drug and combinations employing four cell lines (J774, HepG2, VERO, and C2C12). Following, the levels of Tumour Necrose Factor-alpha (TNF-α) and Interleukin-12 (IL-12) cytokines, using enzyme-linked immunosorbent assay (ELISA) and nitrites, as an indirect measure of Nitric Oxide (NO), using the Griess reaction were assessed in the supernatants of infected macrophages. In silico approach (molecular docking and dynamics) and binding affinity (surface plasmon resonance) between the drug and toxin were also investigated. RESULTS: CTA enhanced AmB effect against promastigote and amastigote forms of L. amazonensis, decreased the drug toxicity in different cell lines and induced the production of important Th1-like cytokines and NO by infected macrophages. The pharmacological combination also displayed consistent molecular interactions with low energy of coupling and a concentration-dependent profile. CONCLUSION: Our data suggest that this pharmacological approach is a promising alternative treatment against L. amazonensis infection due to the improved activity (synergistic effect) achieved against the parasites' forms and to the decreased cytotoxic effect.

Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.

Poly(A) Binding Proteins (PABPs) are major eukaryotic RNA-binding proteins (RBPs) with multiple roles associated with mRNA stability and translation and characterized mainly from multicellular organisms and yeasts. A variable number of PABP homologues are seen in different organisms however the biological reasons for multiple PABPs are generally not well understood. In the unicellular Leishmania, dependent on post-transcriptional mechanisms for the control of its gene expression, three distinct PABPs are found, with yet undefined functional distinctions. Here, using RNA-immunoprecipitation sequencing analysis we show that the Leishmania PABP1 preferentially associates with mRNAs encoding ribosomal proteins, while PABP2 and PABP3 bind to an overlapping set of mRNAs distinct to those enriched in PABP1. Immunoprecipitation studies combined to mass-spectrometry analysis identified RBPs differentially associated with PABP1 or PABP2, including RBP23 and DRBD2, respectively, that were investigated further. Both RBP23 and DRBD2 bind directly to the three PABPs in vitro, but reciprocal experiments confirmed preferential co-immunoprecipitation of PABP1, as well as the EIF4E4/EIF4G3 based translation initiation complex, with RBP23. Other RBP23 binding partners also imply a direct role in translation. DRBD2, in contrast, co-immunoprecipitated with PABP2, PABP3 and with RBPs unrelated to translation. Over 90% of the RBP23-bound mRNAs code for ribosomal proteins, mainly absent from the transcripts co-precipitated with DRBD2. These experiments suggest a novel and specific route for translation of the ribosomal protein mRNAs, mediated by RBP23, PABP1 and the associated EIF4E4/EIF4G3 complex. They also highlight the unique roles that different PABP homologues may have in eukaryotic cells associated with mRNA translation.

Estimating Postmatch Fatigue in Soccer: The Effect of Individualization of Speed Thresholds on Perceived Recovery.

PURPOSE: To investigate the effectiveness of different individualization methods of speed zones during match play to estimate postmatch perceptual recovery in soccer. METHODS: Twelve players under the age of 19 y undertook field-based assessments to determine their maximal aerobic speed (MAS) and maximal sprint speed (MSS). External load (extracted from 10-Hz GPS over 10 official matches) was measured and classified into 4 categories as follows: low-speed running, moderate-speed running, high-speed running, and sprinting. Match running distribution into different speed zones was categorized using either MAS, MSS, MAS and MSS as measures of locomotor capacities, and absolute values. Players perceived recovery status was recorded immediately postmatch (Post) and 24 (G+24H) and 48 hours (G+48H) after each game. RESULTS: Different individualization methods resulted in distinct match outputs in each locomotor category. Perceived recovery status was lower (P < .001) at Post (3.8 [1.32], 95% confidence interval [CI], 3.6 to 4.2), G+24H (5.2 [1.48], 95% CI, 4.9 to 5.6), and G+48H (6.0 [1.22], 95% CI, 5.7 to 6.3) compared with prematch values (7.1 [1.05], 95% CI, 6.8 to 7.3). The absolute perceived recovery-status score was better associated with high-speed running using the locomotor-capacities method at Post (ß = -1.7, 95% CI, -3.2 to -0.22, P = .027), G+24H (ß = -2.08, 95% CI, -3.22 to -0.95, P = .001), and G+48H (ß = -1.32, 95% CI, -2.2 to -0.4, P = .004) compared with other individualization methods. CONCLUSION: The authors' results suggest that locomotor capacities may better characterize the match intensity distribution (particularly for the high-speed running and sprinting categories) and should be preferred over MAS and MSS to estimate perceived recovery.

Monitoring the Athlete Match Response: Can External Load Variables Predict Post-match Acute and Residual Fatigue in Soccer? A Systematic Review with Meta-analysis.

BACKGROUND: Monitoring athletes' external load during a soccer match may be useful to predict post-match acute and residual fatigue. This estimation would allow individual adjustments to training programs to minimize injury risk, improve well-being, and restore players' physical performance and inform the recovery process. METHODS: Using a systematic review and meta-analysis of the literature, the aim is to determine which monitoring variables would be the strongest predictors of acute (immediately) and residual (up to 72 h) fatigue states in soccer. PubMed, SPORTDiscus, and Web of Science databases were searched (until September 2018). Studies concurrently examining soccer match-related external load metrics and subjective and/or objective measures were selected to determine pooled correlations ([Formula: see text]) with confidence intervals (CI). The quality and strength of the findings of each study were evaluated to identify overall levels of evidence. RESULTS: Eleven studies were included (n = 165 athletes). Acute ([Formula: see text] = 0.67; 95% CI = [0.40, 0.94]) and residual (24 h post-match, [Formula: see text] = 0.54; 95% CI = [0.35, 0.65]) changes in muscle damage markers and countermovement jump peak power output (CMJPPO) were, with moderate to strong evidence, largely correlated with running distance above 5.5 m s-1. No other external load metric was largely correlated with both biochemical and neuromuscular markers. For every 100-m run above 5.5 m·s-1, CK activity measured 24 h post-match increased by 30% and CMJPPO decreased by 0.5%. Conversely, the total distance covered did not present any evidence of a clear relationship with any fatigue-related marker at any time-point. CONCLUSIONS: Running distance above 5.5 m·s-1 represents the most sensitive monitoring variable characterizing biochemical and neuromuscular responses, at least when assessed during the initial 24 h (not at 48 h/72 h) post-match recovery period. In addition, total distance covered is not sensitive enough to inform decision-making during the fatigue monitoring process.

Switching between pitch surfaces: practical applications and future perspectives for soccer training.

INTRODUCTION: Soccer training and completion is conventionally practiced on natural grass (NG) or artificial turf (AT). Recently, AT pitches for training/competition, and of unstable surfaces for injury prevention training has increased. Therefore, soccer players are frequently exposed to variations in pitch surface during either training or competition. These ground changes may impact physical and physiological responses, adaptations as well as the injury. The aim of this review was to summarize the acute physical and physiological responses, chronic adaptations, and injury risk associated with exercising on different pitch surfaces in soccer. EVIDENCE ACQUISITION: Eligible studies were published in English, had pitch surface as an independent variable, and had physical, physiological or epidemiological information as outcome variables. Specific data extracted from the articles included the training response, training adaptations or injury outcomes according to different pitch surfaces. A total of 224 studies were retrieved from a literature search. EVIDENCE SYNTHESIS: Twenty articles met the inclusion criteria: 9 for acute physical and physiological responses, 2 for training adaptations and 9 for injury assessment. The literature lacks consistent evidence regarding the effects of pitch surface on performance and health outcomes in soccer players. However, it seems that occasionally switching training surfaces seems a valuable strategy for focusing on specific musculoskeletal queries and enhancing players' fitness. For instance, sand training may be occasionally proposed as complementary training strategy, given the recruitment of additional musculature probably not involved on firmer surfaces, but the possible training-induced adaptations of non-conventional soccer surfaces (e.g., sand) might potentially result into a negative transfer on AT or NG. CONCLUSIONS: Since the specific physical demands of soccer can differ between surfaces, coaches should resort to the use of non-traditional surfaces with parsimony, emphasizing the specific surface-related motor tasks, normally observed on natural grass or artificial turf. Further studies are required to better understand the physiological effects induced by systematic surface-specific training, or switching between pitch surfaces.

Variability of activity profile during medium-sided games in professional soccer.

BACKGROUND: In Southern European countries it is very frequent to perform medium-sized games (MSG) as last training drill. We analyzed the individual variability and changes in activity patterns during MSG throughout the preseason. METHODS: Activity profile during MSGs (10v10+goalkeepers, duration: 10-min, field length: 50 m, width: 90 m, area per player: 204.5 m2) was quantified using a GPS in 14 professional male players (6 defenders, 5 midfielders 5 and attackers). RESULTS: Inter-individual variability was higher for high-intensity (HIR), very-high speed (VHS), maximum acceleration (Accmax) and maximum deceleration (Decmax) distance (CV=25.2 to 43.3%), compared to total distance (TD), total acceleration (Acctot) and total deceleration (Dectot) distance (CV= 8.3 to 18.3%). Defenders showed higher variability in TD, HIR, VHS, Acctot and Dectot (ES= 1.30 to 11.28) compared to the other field positions, whereas attackers showed higher variability in HIR, VHS Accmax and Decmax (ES=-4.92 to 2.07) than other the field positions. Variability in TD regularly increased (ES= -2.13 to -0.91) towards the end of the preseason, while HIR and VHS variability tended to increase over the 3rd and the 4th preseason week (ES=-0.94 to -3.05). However, the behavior of variability across the preseason period was more unpredictable for Acctot and Dectot, both decreasing in the 3rd week (ES= 0.70 to 1.20), while Decmax increased in the 4th week (ES=-0.91±0.59). CONCLUSIONS: During MSGs, individual variability of activity differs among field positions, and tends to increase with either speed or acceleration intensity, underlining the need of an individualized approach for training load monitoring.

Does Early Recruitment Predict Greater Physical Performance in Academy Soccer Players?

The purpose of this longitudinal study was to investigate whether recruitment status influences neuromuscular and endurance performances in academy soccer players over a 2-year training period (from Under-16 to Under-18). Thirty-seven male soccer players from an elite academy were selected and divided in two cohorts according to their recruitment status: Early Recruitment group (ER; n = 16), training and competing for the academy since Under-14 and Under-15 age groups, and; Late Recruitment group (LR; n = 21) included in the academy training process at Under-16. Squat (SJ) and countermovement jump with (CMJwA) and without arms swing (CMJ), 10-m sprint time, and Vam-Eval test (MAV) were performed in three successive occasions always pre-season (Under-16, Under-17 and Under-18 age groups, T1, T2, and T3 respectively). A two-way (recruitment status × time) analysis of variance with repeated measurements was performed as well as the magnitude of difference using both effect size and magnitude-based inferences. There was no difference between ER and LR for MAV, 10 m-sprint, and SJ from T1 to T3. However, LR players presented non-significant small and possibly greater improvement in CMJ (ES = 0.4) and CMJwA (ES = 0.4) than ER players at T2. These data indicate that early recruitment is not likely to result in greater physical performance improvement at the age of 18.

Technical and physical analysis of the 2014 FIFA World Cup Brazil: winners vs. losers.

BACKGROUND: The purpose of the present study was to investigate the technical and physical performance parameters that distinguish between teams winning and losing matches in the 2014 FIFA World Cup Brazil. METHODS: Data were derived from the FIFA website and from live-statistics provided during each game of the world cup. Twelve physical (such as total distance covered in meters (TD), TD in distinct locomotor categories: low-intensity running (LIR; <11 km/h), moderate-intensity running (MIR; 11 to 14 km/h) and high-intensity-running (HIR; >14 km/h)) and 21 technical parameters (total passes, short-, medium- and long-distance passes, total pass completion rate, dangerous attacks, attacking attempts, delivery in penalty area, ball possession, goals, goals from set-pieces, goals per shot on goal, defending saves, shots, shots on goal, shot accuracy, set-pieces, crosses, corners, clearances, yellow cards) were analyzed. Forty-two games in which a winner and consequently a loser were presented after 90 minutes of game time were investigated with independent t-tests. A binary-logistic regression was utilized to investigate whether the significant variables predicted success of the winning teams. RESULTS: The winning teams scored significantly (P<0.05) greater amount of goals, goals per set-pieces, goals per shots on goals, shots on goal and shot accuracy and received significantly lower yellow cards. The binary-logistic regression utilized showed that shot accuracy was the best predictor for success. The physical parameters did not differ between teams winning and losing a match. CONCLUSIONS: Technical performance related to goal scoring parameters play a decisive role in World Cup games. Furthermore, scoring efficacy from open-play as well as from set-pieces are crucial to win matches in a World Cup tournament. At this level, physical performance was not the factor to discriminate between winners and losers.

Strength training in soccer with a specific focus on highly trained players.

BACKGROUND: Data concerning the physical demands of soccer (e.g., activity pattern) suggest that a high level of performance requires well-developed neuromuscular function (NF). Proficient NF may be relevant to maintain and/or increase players' short- (intense periods of soccer-specific activity; accelerations, decelerations, and sprinting) and long-term performance during a match and throughout the season. OBJECTIVE: This review examines the extent to which distinct modes of strength training improve soccer players' performance, as well as the effects of concurrent strength and endurance training on the physical capacity of players. DATA SOURCES: A selection of studies was performed in two screening phases. The first phase consisted of identifying articles through a systematic search using relevant databases, including the US National Library of Medicine (PubMed), MEDLINE, and SportDiscus. Several permutations of keywords were utilized (e.g., soccer; strength; power; muscle function), along with the additional scanning of the reference lists of relevant manuscripts. Given the wide range of this review, additional researchers were included. The second phase involved applying six selection criteria to the articles. RESULTS AND CONCLUSIONS: After the two selection phases, 24 manuscripts involving a total sample of 523 soccer players were considered. Our analysis suggests that professional players need to significantly increase their strength to obtain slight improvements in certain running-based actions (sprint and change of direction speed). Strength training induces greater performance improvements in jump actions than in running-based activities, and these achievements varied according to the motor task [e.g., greater improvements in acceleration (10 m) than in maximal speed (40 m) running movements and in non-squat jump (SJ) than in SSC-based actions (countermovement jump)]. With regard to the strength/power training methods used by soccer players, high-intensity resistance training seems to be more efficient than moderate-intensity resistance training (hypertrophic). From a training frequency perspective, two weekly sessions of strength training are sufficient to increase a player's force production and muscle power-based actions during pre-season, with one weekly session being adequate to avoid in-season detraining. Nevertheless, to further improve performance during the competitive period, training should incorporate a higher volume of soccer-specific power-based actions that target the neuromuscular system. Combined strength/power training programs involving different movement patterns and an increased focus on soccer-specific power-based actions are preferred over traditional resistance exercises, not only due to their superior efficiency but also due to their ecological value. Strength/power training programs should incorporate a significant number of exercises targeting the efficiency of stretch-shortening-cycle activities and soccer-specific strength-based actions. Manipulation of training surfaces could constitute an important training strategy (e.g., when players are returning from an injury). In addition, given the conditional concurrent nature of the sport, concurrent high-intensity strength and high-intensity endurance training modes (HIT) may enhance a player's overall performance capacity. Our analysis suggests that neuromuscular training improves both physiological and physical measures associated with the high-level performance of soccer players.

Neuromuscular function, hormonal and redox status and muscle damage of professional soccer players after a high-level competitive match.

The main aim was to analyse the impact of an official match on hormonal and redox status, muscle damage and inflammation and neuromuscular function. Seven high-level male soccer players from the same team performed an official match and data were collected 72 h before, 24, 48 and 72 h post-match. Plasma testosterone/cortisol ratio (T/C), creatine kinase (CK), superoxide dismutase (SOD), glutathione peroxidase (GPX) and reductase (GR) activities, myoglobin (Mb), C-reactive protein (CRP), uric acid (UA), protein sulfhydryls (-SH), malondialdehyde (MDA) concentrations and total antioxidant status (TAS) were measured. Sprint, jump and change of direction performance, and maximal isokinetic knee extension and flexion were obtained as neuromuscular functional parameters. Cortisol increased and T/C decreased until 48 h recovery (P < 0.05). Mb, CRP and -SH (P < 0.05) increased at 24 h and CK, TAS, SOD and MDA (P < 0.05) increased up to 48 h recovery. GR increased and GPX decreased at 24 h recovery (P < 0.05). Jump performance decreased 24 h post-match (P < 0.05), but no significant alterations in sprint, change of direction and muscle strength were observed. In conclusion, an official match resulted in changes in plasma biomarkers until 48 h of recovery period, without major impact on performance.

Training status and match activity of professional soccer players throughout a season.

The purpose of this study was to examine match activity (MA) and fatigue development (FD) during official soccer games in different moments of a season and the influence of training status (TS) on MA and FD. Match activity of 13 professional players was examined by time-motion analysis at 4 time points of a competitive season. In addition, per time point within the 2-week period between the 2 games video-filmed, players performed the following physical tests: countermovement jump, 5- and 30-m sprints, change of direction, knee extensor and flexor isokinetic strength, and Yo-Yo intermittent endurance test-level 2. The players covered a greater high-intensity distance running (HI; p < 0.05) in the last quarter of the season (E4) than in the second (E2) and the third (E3) quarters. Within each assessment period, a greater distance was covered in HI during the peak 5-minute period of the match (P5-min) than in the 5-minute period after P5-min (Next5-min) and the remaining 5-minute periods (Av5-min; p < 0.05) of the match. Also, P5-min was higher in E4 than in the beginning of the season (E1, E2, and E3; p < 0.05). The physical fitness variables, composites scores of power-related and isokinetic strength tests were correlated (r ranging between 0.59 and 0.73, p < 0.05) with game physical parameters (GPPs) analyzed by time motion. Soccer players were found to cover more HI during the game and in the P5-min toward end of season. The players with greater muscle strength and power expressed lower performance decrements in the GPPs. In conclusion, the results highlight the relevance of players' neuromuscular function on game physical performance.

Individual match playing time during the season affects fitness-related parameters of male professional soccer players.

The purpose of this study was to analyze the effects of an entire season on physical fitness parameters (PFPs) in male professional soccer players (N = 18). Performance in 5- and 30-m sprint (T5 and T30), countermovement jump (CMJ), agility (T-test), knee extensor (KE) and knee flexor (KF) isokinetic strength, hamstrings/quadriceps strength ratio (H/Q) and bilateral differences (BDs), and Yo-Yo intermittent endurance test 2 (YYIE2) was evaluated in 4 moments (E1-E4) throughout the season. Individual match playing time was quantified. Significant improvements in CMJ and YYIE2 from E1 to E2 were observed (p < 0.05-0.01). The T30 improved from E2 to E3 (p < 0.01). The CMJ decreased from E2 to E3 and E4, and YYIE2 from E2 to E4 (p < 0.05). There were increments in the H/Q ratio and Agility from E1 and E2 to E3 and E4 (p < 0.05-0.01). Significant correlations were found in all evaluation points between different PFPs and between changes in strength parameters and agility, T5 and T30, CMJ, and YYIE2 (p < 0.05-0.001). Influence of individual match playing time was correlated to changes in T5 (E1 to E3; r = -0.705), KE nondominant leg (KEND; E2 to E3; r = 0.786), and KF (E3 to E4; r = 0.575-0.590). The interrelationship between muscle strength (e.g., KE), sprint (e.g., T5), and jump abilities (CMJ) suggests the importance of muscle strength and power training for soccer. This study suggests that the systematic participation of the players in soccer matches favors the increase and maintenance of soccer players KE and KF muscle strength and sprint ability (T5). Thus, given the unique demands of actual match play, coaches should try to incorporate a competitive friendly match in the weekly training cycle of nonstarter players.