Prophages carrying Zot toxins on different Vibrio genomes: A comprehensive assessment using multilayer networks.

Vibrios, a group of bacteria that are among the most abundant in marine environments, include several species such as Vibrio cholerae and Vibrio parahaemolyticus, which can be pathogenic to humans. Some species of Vibrio contain prophages within their genomes. These prophages can carry genes that code for toxins, such as the zonula occludens toxin (Zot), which contribute to bacterial virulence. Understanding the association between different Vibrio species, prophages and Zot genes can provide insights into their ecological interactions. In this study, we evaluated 4619 Vibrio genomes from 127 species to detect the presence of prophages carrying the Zot toxin. We found 2030 potential prophages with zot-like genes in 43 Vibrio species, showing a non-random association within a primarily modular interaction network. Some prophages, such as CTX or Vf33, were associated with specific species. In contrast, prophages phiVCY and VfO3K6 were found in 28 and 20 Vibrio species, respectively. We also identified six clusters of Zot-like sequences in prophages, with the ZOT2 cluster being the most frequent, present in 34 Vibrio species. This analysis helps to understand the distribution patterns of zot-containing prophages across Vibrio genomes and the potential routes of Zot-like toxin dissemination.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

Assessing the Match Physical Responses of International Referees for Footballers with Cerebral Palsy: A Tournaments and Halves Comparative Analysis.

Similar to conventional football, the modality dedicated to footballers with cerebral palsy (CP) requires referees who cope with the physical demands imposed during competitive matches to apply the rules of the game. While a significant body of research has explored the physical demands on referees in mainstream football, there is a noticeable lack of data regarding CP football. This study aimed to examine the physical response of international referees participating in different levels of world competitions for footballers with CP. Thirteen international referees, who officiated 49 matches in the men's 2022 World Cup (1st to 15th ranked teams) and 2022 World Championships (16th to 30th ranked teams), participated in this study. A cross-sectional design was used to determine the physical responses and compare the 1st and 2nd halves and the performance in the different tournaments, recording physical variables throughout the matches. Significant higher physical responses were observed in the World Cup in comparison to the World Championship. Overall, high-level tournaments have been shown to elicit more intense physical responses from referees officiating CP football matches compared to lower-level tournaments. For the World Cup, a significantly higher number of accelerations and decelerations were registered in the 1st half compared to the 2nd half. This information may be useful for the strength and conditioning coaches of referees to plan weekly training sessions more specifically and adjust the periodical training load and post-match recovery protocols.

A Systematic Review of Decision Aids in Hematologic Malignancies: What Are Currently Available and What Are We Missing?

BACKGROUND: Patient decision aids (PDAs) are tools designed to facilitate decision-making. In this systematic review, we summarized existing studies on the development and evaluation of PDAs for patients with hematologic malignancies. PATIENTS AND METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for articles in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. We included studies, abstracts, and clinical trial protocols available in English involving PDAs for patients age ≥18 diagnosed with a hematologic malignancy and/or their caregivers. Data were summarized using descriptive statistics. RESULTS: Of the 5281 titles/abstracts screened, 15 were included: 1 protocol, 7 abstracts, and 7 full-texts. Six were PDA developmental studies, 6 were pilot studies, and 3 were randomized trials. PDA formats included electronic with web content, videos, and/or audio, questionnaires, bedside instruments, and a combination of various formats. Average participant age ranged from 36.0 to 62.4 years. Patients and caregivers identified efficacy, adverse effects, cost, and quality of life as important decision-making factors. PDAs were associated with increased knowledge and patient satisfaction as well as decreased decisional conflict and attitudinal barriers. Research on PDAs for adult patients with hematologic malignancies and their caregivers is limited. Among the studies, PDAs appear to support patients in shared decision-making. CONCLUSION: While current literature examining the use of PDAs for adults with hematologic malignancies is limited, the positive impact of PDAs on shared decision-making and patient outcomes warrants additional research in this field.

Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

LC/MS-Based Untargeted Metabolomics Analysis in Women with Morbid Obesity and Associated Type 2 Diabetes Mellitus.

Obesity is a chronic and complex disease, with an increasing incidence worldwide that is associated with metabolic disorders such as type 2 diabetes mellitus (T2DM). Thus, it is important to determine the differences between metabolically healthy obese individuals and those with metabolic disorders. The aim of this study was to perform an untargeted metabolomics assay in women with morbid obesity (MO) compared to a normal weight group, and to differentiate the metabolome of these women with MO who present with T2DM. We carried out a liquid chromatography-mass spectrometry-based untargeted metabolomics assay using serum samples of 209 Caucasian women: 73 with normal weight and 136 with MO, of which 71 had T2DM. First, we found increased levels of choline and acylglycerols and lower levels of bile acids, steroids, ceramides, glycosphingolipids, lysophosphatidylcholines, and lysophosphatidylethanolamines in MO women than in the control group. Then, in MO women with T2DM, we found increased levels of glutamate, propionyl-carnitine, bile acids, ceramides, lysophosphatidylcholine 14:0, phosphatidylinositols and phosphoethanolamines, and lower levels of Phe-Ile/Leu. Thus, we found metabolites with opposite trends of concentration in the two metabolomic analyses. These metabolites could be considered possible new factors of study in the pathogenesis of MO and associated T2DM in women.

Increased Hepatic ATG7 mRNA and ATG7 Protein Expression in Nonalcoholic Steatohepatitis Associated with Obesity.

The autophagy gene ATG7 has been shown to be essential for the induction of autophagy, a process that used to be suppressed in nonalcoholic fatty liver disease (NAFLD). However, the specific role of ATG7 in NAFLD remains unclear. The aim of this study was to analyze hepatic ATG7 mRNA and ATG7 protein expression regarding obesity-associated NAFLD. Patients included women classified into normal weight (NW, n = 6) and morbid obesity (MO, n = 72). The second group was subclassified into normal liver (NL, n = 11), simple steatosis (SS, n= 29), and nonalcoholic steatohepatitis (NASH, n = 32). mRNA expression was analyzed by RT-qPCR and protein expression was evaluated by Western blotting. Our results showed that NASH patients presented higher ATG7 mRNA and ATG7 protein levels. ATG7 mRNA expression was increased in NASH compared with SS, while ATG7 protein abundance was enhanced in NASH compared with NL. ATG7 mRNA correlated negatively with the expression of some hepatic lipid metabolism-related genes and positively with endocannabinoid receptors, adiponectin hepatic expression, and omentin levels. These results suggest that ATG7-mediated autophagy may play an important role in the pathogenesis of NAFLD, especially in NASH, perhaps playing a possible protective role. However, this is a preliminary study that needs to be further studied.

The Role of Olfactomedin 2 in the Adipose Tissue-Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease.

This study's objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue-liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT-qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.

Comparison of the Physical Response During Official Matches and Small-Sided Games in International Cerebral Palsy Footballers: Implications for Evidence-Based Classification.

This study aimed to analyze whether there are differences and associations in the physical responses in international-level cerebral palsy footballers between official matches and 2v2 small-sided games (2v2-SSG). One hundred seventy international cerebral palsy footballers participated in this study during three international championships. The physical responses of mean and maximum velocities, total distance, distance covered at different intensities, short-term actions, and player load were collected during 2v2-SSG and the real competition. The mean velocity, total distance, jogging, medium- and high-intensity distances, the number of moderate/high accelerations, decelerations, and player load were relatively higher in the 2v2-SSG than in the official matches. Even though the 2v2-SSG could become an appropriate drill to include during the classification process, due to the differences between a 2v2-SSG and the official competition, it is necessary to deepen the scientific knowledge for developing observation methods during real competition to strengthen the relationships between eligible impairments and activity limitation.

Effects of pitch size on soccer players' physiological, physical, technical, and tactical responses during small-sided games: a meta-analytical comparison.

One of the most often-used task constraints in designing small-sided games (SSGs) is the manipulation of pitch size to promote increases or decreases in the relative area per player. Such adjustments cause changes in the acute responses during SSGs. This systematic review with meta-analysis aimed to compare the effects of smaller vs. larger pitch sizes on soccer players' physiological, physical, technical, and tactical responses during SSGs. Comparisons between smaller and larger pitches were not considered based on a specific size, but also between using at least two dimensions in the same comparative study, aiming to understand differences between using smaller and larger (independently of the specific dimensions). The data sources utilized were PubMed, PsycINFO, Scielo, Scopus, SPORTDiscus, and Web of Science. The database search initially yielded 249 titles. From those, 41 articles were eligible for the systematic review and meta-analysis. Results revealed that, compared to smaller pitches, SSGs played on larger pitches induced greater values for heart rate (p < 0.001; ES = 0.50), rate of perceived exertion (p < 0.001; ES = 0.70), total distance (p < 0.001; ES = 1.95), high-speed running (p < 0.001; ES = 1.20), stretch index (p < 0.001; ES = 1.02) and surface area (p < 0.001; ES = 1.54). No significant differences were found between pitch size regarding the numbers of accelerations (p = 0.232; ES = 0.45), decelerations (p = 0.111; ES = 0.85), passes (p = 0.897; ES = 0.02), dribbles (p = 0.823; ES = -0.05), or positional centroid (p = 0.053; ES = 0.56). Larger pitch sizes can be implemented as a meaningful task constraint to increase the internal and external load experienced by soccer players during SSGs, as well as to increase the dispersion of players while acting together. These results were found independent of format and age group.

Physical responses by cerebral palsy footballers in matches played at sea level and moderate altitude.

The main objective of this study was to compare the physical response of para-footballers with cerebral palsy (CP) in official international football matches played at moderate altitude and sea level locations. Eighty-seven international CP footballers participated in this study. We divided participants according to the place of the international competition [sea level group (SLG) and moderate altitude group (MAG)], sport classes (i.e., FT1, FT2, and FT3), and match playing time (i.e., <20 min, 20‒40 min, and >40 min). We recorded the physical response using global position system devices during matches. This study showed that MAG described a lower physical response than SLG on total distance, distance covered at different intensities, and the number of accelerations and decelerations. FT2 and FT3 presented a similar pattern, where we found significant differences for total distance, distance covered at lower and high intensities and moderate accelerations, and decelerations. Considering the playing time during altitude matches, the 20‒40 min and >40 min groups obtained more marked differences in the physical response variables. Para-footballers with CP who competed under altitude conditions showed a lower physical response during football matches, suggesting the implementation of specific preparation and training strategies to face the demanding environmental conditions.

Chronic effects of flywheel training on physical capacities in soccer players: a systematic review.

The aims of the current systematic review were to evaluate the current literature surrounding the chronic effect of flywheel training on the physical capacities of soccer players, and to identify areas for future research to establish guidelines for its use.Studies were identified following a search of electronic databases (PubMed and SPORTDiscus) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA).Eleven studies met the inclusion criteria and were included. The methodological quality of the included studies ranged between 10 and 18 with an average score of 15 points using the PEDro scale. The training duration ranged from 6 weeks to 27 weeks, with volume ranging from 1 to 6 sets and 6 to 10 repetitions, and frequency from 1 to 2 times a week. This systematic review reported that a diverse range of flywheel training interventions can effectively improve strength, power, jump, and changes of direction in male soccer players of varying levels.Flywheel training interventions improve the physical capacities of soccer players of varying levels. Nonetheless, the current literature suggests contrasting evidence regarding flywheel training induced changes in sprint speed and acceleration capacity of soccer players.

Reversible mutations in gliding motility and virulence genes: A flexible and efficient phage defence mechanism in Flavobacterium psychrophilum.

Flavobacteria are among the most important pathogens in freshwater salmonid aquaculture worldwide. Due to concerns regarding development of antibiotic resistance, phage therapy has been proposed as a solution to decrease pathogen load. However, application of phages is challenged by the development of phage resistance, and knowledge of the mechanisms and implications of phage resistance is therefore required. To study this, 27 phage-resistant isolates of F. psychrophilum were genome sequenced and characterized to identify genetic modifications and evaluate changes in phenotypic traits, including virulence against rainbow trout. Phage-resistant isolates showed reduction or loss of gliding motility, proteolytic activity, and adhesion to surfaces, and most isolates were completely non-virulent against rainbow trout fry. Genomic analysis revealed that most phage-resistant isolates had mutations in genes associated with gliding motility and virulence. Reversal of these mutations in a sub-set of isolates led to regained motility, proteolytic activity, virulence and phage susceptibility. Although costly, the fast generation of phage resistance driven by single, reversible mutations likely represents a flexible and efficient phage defence mechanism in F. psychrophilum. The results further suggest that phage administration in aquaculture systems to prevent F. psychrophilum outbreaks selects for non-virulent phage-resistant phenotypes.

New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease.

Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.

Increased Secreted Frizzled-Related Protein 5 mRNA Expression in the Adipose Tissue of Women with Nonalcoholic Fatty Liver Disease Associated with Obesity.

Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed.

Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.

The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.

Effects of plyometric jump training on soccer player's balance: a systematic review and meta-analysis of randomized-controlled trials.

Plyometric jump training (PJT) can be used for improving balance through bilateral and unilateral jump-landing drills. Since the increased number of articles testing the effects of PJT on dynamic and static balance, it is relevant to summarize the evidence and determine the effects across different original articles. This systematic review with meta-analysis was conducted to assess the effects of PJT programs on dynamic and static balance in soccer players. The data sources utilized were Cochrane, Medline (PubMed), SPORTDiscus, and Web of Science. (i) Soccer players of any age or sex without injury, illness, or other clinical conditions; (ii) PJT-based programs restricted to a minimum of three weeks (duration); (iii) passive or active control groups; (iv) pre-post interventions values of dynamic and/or static balance; (v) randomized-controlled trials; and (vi) peerreviewed original full-text studies written in English, Portuguese, and/or Spanish. The database search initially identified 803 titles. From those, eight articles were eligible for the systematic review and meta-analysis. The results showed no significant differences between PJT and active controls in dynamic anterior, postero-medial, or postero-lateral balance for both left and right legs (p > 0.05). Additionally, no significant differences were found between PJT and active controls in terms of static balance (p = 0.495). The current evidence suggests that PJT has no significant advantage over active control groups in terms of dynamic or static balance.

The effects of jump training on measures of physical performance, lower extremities injury incidence and burden in highly trained male soccer players.

This study aimed to analyse the effects of a 16-week jump training program on the physical performance and lower extremities injury profile in semi-professional male soccer players. Participants were randomly assigned to the control group (CG; n = 13; age = 21.7 ± 3.6 years) or the experimental group (EG; n = 10; age = 22.3 ± 3.5 years). Countermovement jump (CMJ) height (cm), 30 m linear sprint time (s) with split times at 10 m and 20 m distances, and change of direction speed (CODS; 10 + 10 m with 90° turn) time (s) with turns using the dominant or non-dominant leg, were assessed before and after the intervention. Lower extremity injuries sustained throughout the intervention period were collected. Significant within-group improvements were found in EG in CMJ (p = 0.01; effect size [ES] = 1.03; large). Additionally, between-group difference after intervention was found in CMJ (F = 4.42; p = 0.013) in favour of EG. Injury burden was 194.86 (CG) vs 71.37 (EG) days of absence/1,000 h (RR = 2.73; 95% CI 2.10-3.54; p < 0.001). No other significant within-group or between-group differences were found. In conclusion, compared to regular soccer training, jump training was effective to improve jumping ability and burden in soccer players.

Glutaminolysis-induced mTORC1 activation drives non-alcoholic steatohepatitis progression.

BACKGROUND & AIMS: A holistic insight on the relationship between obesity and metabolic dysfunction-associated fatty liver disease is an unmet clinical need. Omics investigations can be used to investigate the multifaceted role of altered mitochondrial pathways to promote nonalcoholic steatohepatitis, a major risk factor for liver disease-associated death. There are no specific treatments but remission via surgery might offer an opportunity to examine the signaling processes that govern the complex spectrum of chronic liver diseases observed in extreme obesity. We aim to assess the emerging relationship between metabolism, methylation and liver disease. METHODS: We tailed the flow of information, before and after steatohepatitis remission, from biochemical, histological, and multi-omics analyses in liver biopsies from patients with extreme obesity and successful bariatric surgery. Functional studies were performed in HepG2 cells and primary hepatocytes. RESULTS: The reversal of hepatic mitochondrial dysfunction and the control of oxidative stress and inflammatory responses revealed the regulatory role of mitogen-activated protein kinases. The reversible metabolic rearrangements leading to steatohepatitis increased the glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy. The signaling activity of α-ketoglutarate and the associated metabolites also affected methylation-related epigenomic remodeling enzymes. Integrative analysis of hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. CONCLUSION: We provide evidence supporting the multifaceted potential of the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation as a conceivable source of the inefficient adaptive responses leading to steatohepatitis. LAY SUMMARY: Steatohepatitis is a frequent and threatening complication of extreme obesity without specific treatment. Omics technologies can be used to identify therapeutic targets. We highlight increased glutaminolysis-induced α-ketoglutarate production as a potential source of signals promoting and exacerbating steatohepatitis.