Global signal peptide profiling reveals principles of selective Sec61 inhibition.

Cotransins target the Sec61 translocon and inhibit the biogenesis of an undefined subset of secretory and membrane proteins. Remarkably, cotransin inhibition depends on the unique signal peptide (SP) of each Sec61 client, which is required for cotranslational translocation into the endoplasmic reticulum. It remains unknown how an SP's amino acid sequence and biophysical properties confer sensitivity to structurally distinct cotransins. Here we describe a fluorescence-based, pooled-cell screening platform to interrogate nearly all human SPs in parallel. We profiled two cotransins with distinct effects on cancer cells and discovered a small subset of SPs, including the oncoprotein human epidermal growth factor receptor 3 (HER3), with increased sensitivity to the more selective cotransin, KZR-9873. By comparing divergent mouse and human orthologs, we unveiled a position-dependent effect of arginine on SP sensitivity. Our multiplexed profiling platform reveals how cotransins can exploit subtle sequence differences to achieve SP discrimination.

The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes.

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.

Proteasome composition in immune cells implies special immune­cell­specific immunoproteasome function.

Immunoproteasomes are a special class of proteasomes, which can be induced with IFN-γ in an inflammatory environment. In recent years, it became evident that certain immune cell types constitutively express high levels of immunoproteasomes. However, information regarding the basal expression of proteolytically active immunoproteasome subunits in different types of immune cells is still rare. Hence, we quantified standard proteasome subunits (ß1c, ß2c, ß5c) and immunoproteasome subunits (LMP2, MECL-1, LMP7) in the major murine (CD4+ T cells, CD8+ T cells, CD19+ B cells, CD11c+ dendritic cells, CD49d+ natural killer cells, Ly-6G+ neutrophils) and human immune cell (CD4+ T cells, CD8+ T cells, CD19+ B cells, CD1c+CD141+ myeloid dendritic cells, CD56+ natural killer cells, granulocytes) subsets. The different human immune cell types were isolated from peripheral blood and the murine immune cell subsets from spleen. We found that proteasomes of most immune cell subsets mainly consist of immunoproteasome subunits. Our data will serve as a reference and guideline for immunoproteasome expression and imply a special role of immunoproteasomes in immune cells.

Strength and Conditioning (S&C) Practices of Judo Athletes and S&C Coaches: A Survey-Based Investigation.

ABSTRACT: Weldon, A, Cloak, R, Kirk, C, Ruddock, A, Langan-Evans, C, Detanico, D, Loturco, I, and Kons, R. Strength and conditioning (S&C) practices of judo athletes and S&C coaches: A survey-based investigation. J Strength Cond Res 38(4): e160-e173, 2024-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.

The Relationships Between External and Internal Training Loads in Mixed Martial Arts.

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.

A 5-Year Analysis of Age, Stature and Armspan in Mixed Martial Arts.

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. Methods and Results: 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.

Signal peptide mimicry primes Sec61 for client-selective inhibition.

Preventing the biogenesis of disease-relevant proteins is an attractive therapeutic strategy, but attempts to target essential protein biogenesis factors have been hampered by excessive toxicity. Here we describe KZR-8445, a cyclic depsipeptide that targets the Sec61 translocon and selectively disrupts secretory and membrane protein biogenesis in a signal peptide-dependent manner. KZR-8445 potently inhibits the secretion of pro-inflammatory cytokines in primary immune cells and is highly efficacious in a mouse model of rheumatoid arthritis. A cryogenic electron microscopy structure reveals that KZR-8445 occupies the fully opened Se61 lateral gate and blocks access to the lumenal plug domain. KZR-8445 binding stabilizes the lateral gate helices in a manner that traps select signal peptides in the Sec61 channel and prevents their movement into the lipid bilayer. Our results establish a framework for the structure-guided discovery of novel therapeutics that selectively modulate Sec61-mediated protein biogenesis.

Combat Sports as a Model for Measuring the Effects of Repeated Head Impacts on Autonomic Brain Function: A Brief Report of Pilot Data.

Automated pupil light reflex (PLR) is a valid indicator of dysfunctional autonomic brain function following traumatic brain injury. PLR's use in identifying disturbed autonomic brain function following repeated head impacts without outwardly visible symptoms has not yet been examined. As a combat sport featuring repeated 'sub-concussive' head impacts, mixed martial arts (MMA) sparring may provide a model to understand such changes. The aim of this pilot study was to explore which, if any, PLR variables are affected by MMA sparring. A cohort of n = 7 MMA athletes (age = 24 ± 3 years; mass = 76.5 ± 9 kg; stature = 176.4 ± 8.5 cm) took part in their regular sparring sessions (eight rounds × 3 min: 1 min recovery). PLR of both eyes was measured immediately pre- and post-sparring using a Neuroptic NPi-200. Bayesian paired samples t-tests (BF10 ≥ 3) revealed decreased maximum pupil size (BF10 = 3), decreased minimum pupil size (BF10 = 4) and reduced PLR latency (BF10 = 3) post-sparring. Anisocoria was present prior to sparring and increased post-sparring, with both eyes having different minimum and maximum pupil sizes (BF10 = 3-4) and constriction velocities post-sparring (BF10 = 3). These pilot data suggest repeated head impacts may cause disturbances to autonomic brain function in the absence of outwardly visible symptoms. These results provide direction for cohort-controlled studies to formally investigate the potential changes observed.

Intra-unit reliability and movement variability of submission grappling external load as measured by torso mounted accelerometery.

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.

Development of subunit selective substrates for Trichomonas vaginalis proteasome.

The protozoan parasite, Trichomonas vaginalis (Tv) causes trichomoniasis, the most common, non-viral, sexually transmitted infection in the world. Only two closely related drugs are approved for its treatment. The accelerating emergence of resistance to these drugs and lack of alternative treatment options poses an increasing threat to public health. There is an urgent need for novel effective anti-parasitic compounds. The proteasome is a critical enzyme for T. vaginalis survival and was validated as a drug target to treat trichomoniasis. However, to develop potent inhibitors of the T. vaginalis proteasome, it is essential that we understand which subunits should be targeted. Previously, we identified two fluorogenic substrates that were cleaved by T. vaginalis proteasome, however after isolating the enzyme complex and performing an in-depth substrate specificity study, we have now designed three fluorogenic reporter substrates that are each specific for one catalytic subunit. We screened a library of peptide epoxyketone inhibitors against the live parasite and evaluated which subunits are targeted by the top hits. Together we show that targeting of the ß5 subunit of T. vaginalis is sufficient to kill the parasite, however, targeting of ß5 plus either ß1 or ß2 results in improved potency.

Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses.

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.

Co-inhibition of immunoproteasome subunits LMP2 and LMP7 enables prevention of transplant arteriosclerosis.

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 (ß5i) and LMP2 (ß1i) 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.

Rapid Weight Gain and Weight Differential Predict Competitive Success in 2100 Professional Combat-Sport Athletes.

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.

Effective therapy of polymyositis in mice via selective inhibition of the immunoproteasome.

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.

Inhibition of the Sec61 translocon overcomes cytokine-induced glucocorticoid resistance in T-cell acute lymphoblastic leukaemia.

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.

Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism.

The proteasome is responsible for mediating intracellular protein degradation and regulating cellular function with impact on tumor and immune effector cell biology. The proteasome is found predominantly in two forms, the constitutive proteasome and the immunoproteasome. It has been validated as a therapeutic drug target through regulatory approval with 2 distinct chemical classes of small molecular inhibitors (boronic acid derivatives and peptide epoxyketones), including 3 compounds, bortezomib (VELCADE), carfilzomib (KYPROLIS), and ixazomib (NINLARO), for use in the treatment of the plasma cell neoplasm, multiple myeloma. Additionally, a selective inhibitor of immunoproteasome (KZR-616) is being developed for the treatment of autoimmune diseases. Here, we compare and contrast the pharmacokinetics (PK), pharmacodynamics (PD), and metabolism of these 2 classes of compounds in preclinical models and clinical studies. The distinct metabolism of peptide epoxyketones, which is primarily mediated by microsomal epoxide hydrolase, is highlighted and postulated as a favorable property for the development of this class of compound in chronic conditions.

Role of Epoxide Hydrolases and Cytochrome P450s on Metabolism of KZR-616, a First-in-Class Selective Inhibitor of the Immunoproteasome.

KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and based on promising therapeutic activity in animal models of rheumatoid arthritis and systemic lupus erythematosus KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (P450) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro. These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by coadministration of inhibitors or inducers of P450 and sEH. SIGNIFICANCE STATEMENT: This work presents a thorough and systematic investigation of metabolism and kinetics of KZR-616 and related analogs in in vitro and cell-based enzymatic systems. Information gained could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. These studies also demonstrate a robust source in vitro test system that correlated with in vivo pharmacokinetics for KZR-616 and two additional tripeptide epoxyketones.

Quantification of training load distribution in mixed martial arts athletes: A lack of periodisation and load management.

The aim of this study was to quantify typical training load and periodisation practices of MMA athletes. MMA competitors (n = 14; age = 22.4 ± 4.4 years; body mass = 71.3 ± 7.7 kg; stature = 171 ±9.9 cm) were observed during training for 8 consecutive weeks without intervention. Seven athletes were training for competitive bouts whilst the remaining 7 were not. Daily training duration, intensity (RPE), load (sRPE and segRPE), fatigue (short questionnaire of fatigue) and body region soreness (CR10 scale) were recorded. Using Bayesian analyses (BF10≥3), data demonstrate that training duration (weekly mean range = 3.9-5.3 hours), sRPE (weekly mean range = 1,287-1,791 AU), strain (weekly mean range = 1,143-1,819 AU), monotony (weekly mean range = 0.63-0.83 AU), fatigue (weekly mean range = 16-20 AU) and soreness did not change within or between weeks. Between weeks monotony (2.3 ± 0.7 AU) supported little variance in weekly training load. There were no differences in any variable between participants who competed and those who did not with the except of the final week before the bout, where an abrupt step taper occurred leading to no between group differences in fatigue. Training intensity distribution corresponding to high, moderate and low was 20, 33 and 47%, respectively. Striking drills accounted for the largest portion of weekly training time (20-32%), with MMA sparring the least (2-7%). Only striking sparring and wrestling sparring displayed statistical weekly differences in duration or load. Athletes reported MMA sparring and wrestling sparring as high intensity (RPE≥7), BJJ sparring, striking sparring and wrestling drills as moderate intensity (RPE 5-6), and striking drills and BJJ drills as low intensity (RPE≤4). We conclude that periodisation of training load was largely absent in this cohort of MMA athletes, as is the case within and between weekly microcycles.

Pre-competition body mass loss characteristics of Brazilian jiu-jitsu competitors in the United Kingdom.

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.