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Purpose: As a multidisciplined combat sport, relationships between external and internal training loads and intensities of mixed martial arts (MMA) have not been described. The aim of this study was to determine the external loads and intensities of MMA training categories and their relationship to internal loads and intensities. Methods: Twenty MMA athletes (age = 23.3 [5.3] y, mass = 72.1 [7.2] kg, stature = 171.5 [8.4] cm) were observed for 2 consecutive weeks. Internal load and intensity (session rating of perceived exertion [sRPE]) were calculated using the Foster RPE for the session overall (sRPE-training load [TL]) and segmented RPE (segRPE-TL) for each training category: warm-up, striking drills, wrestling drills, Brazilian jiujitsu (BJJ) drills, striking sparring, wrestling sparring, BJJ sparring, and MMA sparring. External load and intensity were measured via Catapult OptimEye S5 for the full duration of each session using accumulated Playerload (PLdACC) and PLdACC per minute (PLdACC·min−1). Differences in loads between categories and days were assessed via Bayesian analysis of variance (BF10 ≥ 3). Predictive relationships between internal and external variables were calculated using Bayesian regression. Results: Session overall sRPE-TL = 448.6 (191.1) arbitrary units (AU); PLdACC = 310.6 (112) AU. Category segRPE-TL range = 33.8 (22.6) AU (warm-up) to 122.8 (54.6) AU (BJJ drills). Category PLdACC range = 44 (36.3) AU (warm-up) to 125 (58.8) AU (MMA sparring). Neither sRPE-TL nor PLdACC changed between days. PLdACC was different between categories. Evidence for regressions was strong-decisive except for BJJ drills (BF10 = 7, moderate). R2 range =.50 to.77, except for warm-up (R2 =.17), BJJ drills (R2 =.27), BJJ sparring (R2 =.49), and session overall (R2 =.13). Conclusions: While MMA training categories may be differentiated in terms of external load, overall session external load does not change within or between weeks. Resultant regression equations may be used to appropriately plan MMA technical/tactical training loads. [ABSTRACT FROM AUTHOR]

Purpose: Combat-sport athletes commonly undergo rapid weight loss prior to prebout weigh-in and subsequently rapid weight gain (RWG) prior to competition. This investigation aimed to evaluate the effect of RWG and weight differential (WD) between opponents on competitive success. Methods: A retrospective cohort study was performed using data from professional mixed martial arts (MMA) and boxing events held between 2015 and 2019. The primary outcome was RWG (relative and absolute) between weigh-in and competition stratified by bout winners and losers. Binary logistic regression was used to explore the relationships among bout outcome, RWG, and WD between competitors on the day of their bout. Results: Among 708 MMA athletes included, winners regained more relative body mass (8.7% [3.7%] vs 7.9% [3.8%], P <.01) than losers. In 1392 included male boxers, winners regained significantly more relative body mass (8.0% [3.0%] vs 6.9% [3.2%], P <.01) than losers. Each percentage body mass increase resulted in a 7% increased likelihood of victory in MMA and a 13% increase in boxing. The relationship between RWG and competitive success remained significant in regional and male international MMA athletes, as well as boxers. WD predicted victory in international mixed martial artists and boxers. WD predicted victory by knockout or technical knockout in international MMA athletes and regional boxers. Conclusion: This analysis of combat-sport athletes indicates that RWG and WD influence competitive success. These findings raise fair-play and safety concerns in these popular sports and may help guide risk-mitigating regulation strategies. [ABSTRACT FROM AUTHOR]

Purpose: Athlete stature and armspan is anecdotally assumed to provide an advantage in mixed martial arts (MMA), despite an absence of supporting data. In contrast, winners of MMA bouts have been shown to be younger than bouts losers. Whilst absolute measurements of stature, armspan and armspan:stature scale (A:S) have been shown to not distinguish between winners and losers of MMA bouts, relative differences between competitors have not been analysed. This study aimed to analyse 5 years of athlete age and morphological data to replicate and expand previous studies to determine whether absolute and/or relative age and morphological variables effect winning and losing in MMA. MethodsandResults: Bayes factor (BF>3) inferential analyses conducted on the cohort overall (n = 2,229 professional bouts), each year sampled and each individual body mass division found that only absolute (winners = 29.8 ± 4 years; losers = 30.7 ± 4.2 years) and relative age (winners = 0.82 ± 5.3 years younger than losers) differentiates between winners and losers across the whole cohort, in 4 of the 5 years, and in 4 of the 13 divisions sampled. Armspan appears to provide an advantage in heavyweight only (winners = 198.4 ± 6.6cm; losers = 196.1 ± 7.7cm), with greater A:S being a disadvantage (winners = 1.003 ± 0.022cm∙cm−1; losers = 1.010 ± 0.023 cm∙cm−1) in women's strawweight only. No variables had any effect on how bouts were won. Conclusions: These results confirm previous reports that the effect of athlete morphology is greatly overstated in MMA, appearing to be irrelevant in most divisions. Bout winners tend to be younger than losers, particularly in divisions displaying more diverse skill requirements. [ABSTRACT FROM AUTHOR]

The benefits of strength and conditioning (S&C) for improving judo performance and reducing injuries have been widely studied. However, the S&C practices used and perspectives held by those delivering S&C have yet to be elucidated. Therefore, this study investigated the S&C practices and perspectives of judokas and S&C coaches working within judo. Forty-two judokas and 9 S&C coaches completed an online survey comprising 6 sections: (a) written informed consent; (b) background information; (c) education, qualifications, and prescription; (d) views on S&C (e) exercise selection; and (f) issues and improvements. Frequency analysis was used to report responses to fixed-response questions and thematic analysis for open-ended questions. Results indicated that S&C coaches were primarily responsible for delivering S&C programs (60%), and S&C information was predominantly sourced from S&C coaches (43%). Strength and conditioning was deemed very important for randori (78-88%), overall judo performance (67-79%), and judo fitness (62-78%). Similarly, S&C was considered very important for the development of speed and power (76-89%), strength (71-89%), and injury reduction (69-78%). Novel findings were also observed, such as integrating judo-specific training within S&C practice, which may be partly explained by more S&C coaches holding judo belts (67%) than S&C qualifications (11%). This study supports practitioners delivering S&C in judo by offering a base of information to critique or align with their existing S&C practices and perspectives. Furthermore, our results may help identify potential gaps between methods used, proposed guidelines, and actual practice, facilitating the development of research and education resources tailored to the current climate. [ABSTRACT FROM AUTHOR]

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male‐born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case‐by‐case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision‐making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports. [ABSTRACT FROM AUTHOR]

The article addresses the renewed debate over eligibility criteria for women's sports following controversies at the Paris 2024 Olympics, where athletes with alleged male advantages competed in the female category. Topics discussed include the necessity of excluding male advantages for fair competition, the limitations and ethical concerns of past sex verification methods, and the proposal for modern genetic screening as a solution to ensure fair and safe participation in female sports.

This letter to the editor responds to a recent article that reviewed the effects of gender-affirming hormone therapy on physical performance, particularly in relation to transgender individuals in competitive sports. The authors of the letter raise concerns about the terminology used in the original article and argue that the adjustment of absolute measures by stature, rather than mass, is not justified. They also highlight the importance of considering absolute measures alongside relative measures, as transgender women retain significant advantages over cisgender females in terms of absolute strength and other variables. The authors criticize the conclusions of the original article for not reflecting the contents of the paper and for lacking supporting evidence. The letter is written by Christopher Kirk and Georgina K Stebbings and is funded by the IOC Medical and Scientific Research Fund. [Extracted from the article]

Body mass (BM) manipulation via rapid weight loss (RWL) and rapid weight gain (RWG) is a common practice among mixed martial art (MMA) athletes to ensure qualification for the division in which the athlete wishes to compete. Professional MMA competitors in California are required to weigh in twice: 24 hr prior to competition and immediately prior to the bout after they have typically engaged in RWG. In analyzing data from five MMA events sanctioned by the Californian State Athletic Commission, the authors used Bayesian analyses to compare bout winners (n = 31) and losers (n = 31) in terms of in-competition BM (in kilograms) and the amount of BM regained between the two weigh-ins (in kilograms). These data do not support the hypothesis that differences in in-competition BM (Bayes factor [BF10] = 0.667, d = 0.23) or the amount of BM regained between the two weigh-ins (BF10 = 0.821, d = 0.23) determine winning or losing. In addition, there was no statistical difference between bouts ending via strikes, submission, or decision for either in-competition BM (BF10 = 0.686, ω2 < 0.01) or the amount of BM regained between the two weigh-ins (BF10 = 0.732, ω2 = 0.054). In conclusion, the authors report for the first time that the magnitude of RWG does not predict winning or losing in a professional cohort of MMA athletes. In addition, they also report that MMA athletes typically compete at a BM that is at least 1–2 divisions higher than the division in which they officially weighed-in. These analyses may provide impetus for governing bodies and coaches to enact changes at both professional and amateur levels to reduce negative health consequences associated with extreme RWL and RWG. [ABSTRACT FROM AUTHOR]

Submission grappling consists of skills and movements used in combat sports to physically control opponents whilst trying to apply choke holds and joint locks. There is currently no accepted method of monitoring external load in grappling-based sports due to the absence of key variables such as distance, velocity or time. The primary aim of this study was to determine whether PlayerLoad is a reliable variable for measuring external load of submission grappling movements, with a secondary aim of determining the between repetition variance of submission grappling movements. 7 experienced submission grapplers were recruited. Each wore a torso mounted Catapult® Optimeye S5 microelectromechanical systems (MEMS) device and completed 5 repetitions of each of the following: 4 submission techniques; 5 transition techniques; 2 guard pass techniques; 2 takedown techniques. Accumulated PlayerLoad (PLdACC) was recorded as a marker of absolute load, with accumulated PlayerLoad per minute (PLdACC⋅min-1) representing relative load. Reliability of each was assessed using intraclass correlation coefficient (ICC(3,1)) (≥ 0.70). Between repetition movement variation was assessed via coefficient of variation with 95% confidence intervals (CV, 95%CI) (acceptable ≤ 15%, good ≤ 10%). PLdACC ICC(3,1) range = 0.78--0.98, with CV range = 9--22%. PLdACC⋅min-1 ICC(3,1) range = 0.83--0.98, with CV range = 11--19%. Though several variables displayed CV > 15%, all had 95%CI lower boundaries ≤ 15%. Whilst PlayerLoad was found to be a reliable measure for submission grappling, relatively high CVs across most techniques examined suggest PlayerLoad may not be appropriate for measuring changes in external load for individual movements in submission grappling. However, it may prove a useful tool for monitoring the external load of full, grappling-based, training sessions within an individual. [ABSTRACT FROM AUTHOR]

Aims The loss of vascular wall cells in allotransplanted arteries is the initial event leading to transplant arteriosclerosis (TA) and ensuing loss of allograft function. Pharmacological agents able to prevent TA are currently lacking. We previously showed that selective inhibition of the immunoproteasome prevented the chronic rejection of renal allografts. However, the role and mechanisms of selective inhibition of a single immunoproteasome subunit to prevent immune-mediated vascular allograft rejection and TA is not clear. Methods and results The effect and potential mechanism of combined or individual inhibition of peptidolytically active immunoproteasome LMP7 (β5i) and LMP2 (β1i) subunits on immune rejection-mediated TA was investigated using the epoxyketone inhibitor ONX 0914, and the recently developed LMP7-selective inhibitor KZR-329 and LMP2-selective inhibitor KZR-504 in a rat aorta transplantation model. We find that co-inhibition of LMP7 and LMP2 in allogeneic recipients significantly suppressed T-cell activation and function by expressing inhibitory surface markers and then activating inhibitory signals. Moreover, co-inhibition of LMP7 and LMP2 substantially reduced the number of immunoglobulin G-secreting cells and plasma cells and production of alloantibodies through activating the unfolded protein response and incapacitating the survival niche of plasma cells in the bone marrow. Consequentially, the accumulation of inflammatory cytokines, complement, and antibodies is reduced and the apoptosis of vascular wall cells decreased in aortic allografts via LMP7 and LMP2 co-inhibition with ONX 0914 treatment or combined KZR-329 and KZR-504 treatment. However, neither individual inhibition of LMP7 by KZR-329 nor individual inhibition of LMP2 by KZR-504 showed suppression of immune rejection and TA. Conclusions We define a critical role of LMP7 and LMP2 in TA and strongly propose co-inhibition of both immunoproteasome subunits as promising therapeutic approach to suppress TA and allograft rejection. [ABSTRACT FROM AUTHOR]

Zetomipzomib (KZR-616) is a selective inhibitor of the immunoproteasome currently undergoing clinical investigation in autoimmune disorders. Here, we characterized KZR-616 in vitro and in vivo using multiplexed cytokine analysis, lymphocyte activation and differentiation, and differential gene expression analysis. KZR-616 blocked production of >30 pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs), polarization of T helper (Th) cells, and formation of plasmablasts. In the NZB/W F1 mouse model of lupus nephritis (LN), KZR-616 treatment resulted in complete resolution of proteinuria that was maintained at least 8 weeks after the cessation of dosing and was mediated in part by alterations in T and B cell activation, including reduced numbers of short and long-lived plasma cells. Gene expression analysis of human PBMCs and tissues from diseased mice revealed a consistent and broad response focused on inhibition of T, B, and plasma cell function and the Type I interferon pathway and promotion of hematopoietic cell lineages and tissue remodeling. In healthy volunteers, KZR-616 administration resulted in selective inhibition of the immunoproteasome and blockade of cytokine production following ex vivo stimulation. These data support the ongoing development of KZR-616 in autoimmune disorders such as systemic lupus erythematosus (SLE)/LN. [ABSTRACT FROM AUTHOR]

Polymyositis (PM) is a chronic autoimmune inflammatory myopathy resulting in muscle weakness. The limited approved therapies and their poor efficacy contribute to its comorbidity. We investigated the therapeutic use of ONX 0914 and KZR‐616, selective inhibitors of the immunoproteasome, in C protein‐induced myositis (CIM), a mouse model of PM that closely resembles the human disease. Diseased mice (day 13 postimmunization) were treated with 10 mg/kg ONX 0914, KZR‐616, or vehicle on alternate days until day 28. Endpoints included muscle strength assessed by a grip strength meter, serum creatine kinase activity, histology, and immunohistochemistry analysis. Treatment with ONX 0914 or KZR‐616 prevented the loss of grip strength in mice after CIM induction, while vehicle‐treated animals displayed progressive muscle weakness. Immunoproteasome inhibition lowered PM‐associated leukocyte infiltration of the muscle and prevented increased serum creatine kinase levels. LMP7‐deficient mice were resistant to CIM induction, as they showed no alterations in grip strength or creatine kinase (CK) levels or muscular alterations. In conclusion, selective inhibition of the immunoproteasome displays therapeutic efficacy in a preclinical mouse model of PM with suppression of muscle inflammation and preservation of muscle strength. Positive results from this study support the rationale for using KZR‐616 in clinical studies. [ABSTRACT FROM AUTHOR]

Brazilian jiu-jitsu (BJJ) is a grappling-based combat sport performed either with a traditional uniform, the gi, or without, known as no-gi. Differences between the two when it comes to gripping, pace, and ruleset can affect match characteristics, which has implications for how athletes approach competition. The present study investigated timemotion and technical-tactical characteristics in matches from official no-gi submission-only BJJ tournaments. The analysis included 26 regional and 26 international athletes from the light-feather to super-heavy weight class. Match characteristics did not differ between competition levels, style (guard or pass player), or weight (p > 0.05). The duration of positional dominance was similar between competition levels and styles (p > 0.05), but significantly different between winners and losers (p < 0.05; effect size (ES) = 0.39). Positional dominance also correlated with upper-body submissions (r = 0.50; p < 0.05). Interestingly, positional dominance appeared inconsequential in matches determined by lower-body submissions. In fact, athletes winning by lower-body submissions, in most cases a heel hook, exerted no positional control prior to their victory. The high- to low-intensity ratio was 1:2 and 1:1, for regional and international athletes, respectively. The standing to ground time ratio was 1:2 for both groups. In addition to the novel competition characteristics of competitive no-gi BJJ, these findings indicate that there are strategical discrepancies that precede distinctly different submission holds. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC) resistance is a poor prognostic factor in T‐cell acute lymphoblastic leukaemia (T‐ALL). Interleukin‐7 (IL‐7) mediates GC resistance via GC‐induced upregulation of IL‐7 receptor (IL‐7R) expression, leading to increased pro‐survival signalling. IL‐7R reaches the cell surface via the secretory pathway, so we hypothesized that inhibiting the translocation of IL‐7R into the secretory pathway would overcome GC resistance. Sec61 is an endoplasmic reticulum (ER) channel that is required for insertion of polypeptides into the ER. Here, we demonstrate that KZR‐445, a novel inhibitor of Sec61, potently attenuates the dexamethasone (DEX)‐induced increase in cell surface IL‐7R and overcomes IL‐7‐induced DEX resistance. [ABSTRACT FROM AUTHOR]

A trans-acting protein interacting with a specific sequence motif proximal to the transcriptional start site of the L-asparaginase promoter has been observed previously (E. Vincze, J. M. Reeves, E. Lamping, K. J. F. Farnden, and P. H. S. Reynolds, Plant Mol. Biol. 26:303-311, 1994). Gel retardation experiments in which protein extracts of Mesorhizobium loti and developing nodules were used suggested a bacterial origin for the repressor binding protein (rep2037). Nodulation tests were performed by using different [Fix.sup.-] Tn5 mutants of M. loti. Analyses of these mutants revealed a correlation between the presence of Mesorhizobium in the nodule-like structures and the ability of nodule protein extracts to bind the repressor binding domain (RBD). Through the use of mutated RBD sequences, the RBD sequence was identified as CTAAAAT. The repressor protein was isolated from M. loti NZP2037 by multiple chromatographic procedures and affinity separation by using concatemers of RBD attached to magnetic beads. Sequencing of the recovered protein resulted in identification of the repressor protein as the sarcosine oxidase [alpha] subunit. This was confirmed by expression of the gene encoding the M. loti [alpha] subunit of sarcosine oxidase in Escherichia coli. When the expressed peptide was bound to RBD, the gel retardation result was identical to the result obtained with rep2037 from M. loti strain NZP2037.

Background: Brazilian jiu-jitsu (BJJ) is a grappling-based combat sport in which competitors engage in pre-competition acute 'weight' loss (AWL) and rapid 'weight' loss (RWL) to achieve the body mass (BM) required for their desired division. AWL/RWL practices of UK BJJ competitors have not previously been reported. Aim: Our aim in this study was to determine the prevalence, magnitude and stakeholder influences of AWL and RWL amongst BJJ participants in the United Kingdom (UK). A secondary aim was to explore whether there is any influence of time spent in the sport or competition frequency on AWL/RWL practices. Methods: In this study we used the rapid weight loss questionnaire (RWLQ) adapted for BJJ to determine the prevalence and magnitude of AWL/RWL in UK BJJ, the prevalence of methods used and the key stakeholder influences on these practices. As a secondary investigation we aimed to determine whether there was any effect of age starting BJJ on AWL/RWL. Results: Of 115 completed responses, 59% stated they performed AWL/RWL before competition. Mean BM loss for this competition was 1.9 ± 3.8 kg (2.3 ± 4.6%), with 34% of participants starting BM loss 3–7 days prior and 16% starting 0–2 days prior. Methods used tend to be achieving calorie deficit via exercise and diet rather than hypohydration, with little advice from formally qualified personnel. Participants who perform AWL/RWL started training (BF10 = 199, d =.72) and competing (BF10 = 107, d =.68) in BJJ younger than those who do not perform AWL/RWL. Conclusions: AWL/RWL is prevalent in UK BJJ, but not at the magnitude of other combat sports or countries. Though negative effects of extreme hypohydration are unlikely, there may be a higher chance of eating disorders in BJJ, particularly due to the young age of AWL/RWL commencement. [ABSTRACT FROM AUTHOR]

Abstract Background In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. Methods Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). Results Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10–12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive β5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2–4 fold increase in the mRNA and protein levels of the constitutive β5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. Conclusions These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease.