The Influence of Cholesterol-Related Membrane Fluidity on the Shear Stress Control of Neutrophil Adhesion and Its Implications in Hypercholesterolemia

Hypercholesterolemia is a significant risk factor in the development of cardiovascular disease and is associated with chronic leukocyte adhesion in the microvasculature. While the underlying mechanisms behind this have yet to be determined, it may be possible that hypercholesterolemia impairs the fluid shear stress (FSS) inactivation of neutrophils through the rigidifying effect of cholesterol on membrane fluidity. FSS restricts surface expression of CD18 integrins through cathepsin B (ctsB) proteolysis, which minimizes neutrophil adhesivity. If hypercholesterolemia blocks FSS mechanotransduction, then the inhibition of CD18 cleavage may link pathologic blood cholesterol elevations with dysregulated neutrophil adhesion. We hypothesized that elevated cholesterol contributes to dysregulated neutrophil adhesion by impairing ctsB FSS-induced CD18 cleavage through membrane fluidity changes. In the first part of this study, we demonstrated that FSS-induced CD18 cleavage is a robust response of neutrophils and involves selective cleavage of macrophage 1-antigen (Mac1) through ctsB proteolysis. The second part of this study confirmed that ctsB regulates neutrophil adhesion through its proteolytic actions on Mac1, an important integrin involved in adhesion and chemotaxis. Specifically, ctsB accelerated neutrophil motility through an effect on Mac1 integrins during pseudopod retraction. Furthermore, by using a flow-based assay to quantify the mechanoregulation of neutrophil adhesivity, we demonstrated that FSS-induced ctsB release promoted neutrophil detachment from platelet-coated substrates and unstimulated endothelium. For the third part of this study, we linked cholesterol-related membrane fluidity changes with the ability of FSS to restrict neutrophil adhesion through Mac1. We also determined that pathologic cholesterol elevations associated with hypercholesterolemia could block FSS-induced Mac1 cleavage and were linked to disrupted tissue blood flow. This was accomplished using low-density lipoprotein receptor deficient (LDLR-/-) mice fed a high-fat diet. Ultimately, the results provided in the present study confirmed that cholesterol-related changes in membrane fluidity blocked the ability of ctsB to regulate neutrophil adhesion through FSS-induced Mac1 cleavage. This implicates an impaired neutrophil FSS mechanotransduction response in the dysregulation of neutrophil adhesion associated with hypercholesterolemia. Since dysregulated adhesion may be one of the earliest upstream features of cardiovascular disease associated with hypercholesterolemia, the present study provides a foundation for identifying a new mechanobiological factor in the pathobiology of microcirculatory dysfunction

Fifth metatarsal stress fracture in elite male football players:An on-field analysis of plantar loading

ObjectiveEvaluate plantar loading during ‘on-field’ common football movements in players after fifth metatarsal (MT-5) stress fracture and compare with matched healthy players.MethodsFourteen elite male soccer players participated in the study conducted on a natural grass playing surface using firm ground football boots. Seven players who had suffered a primary stress fracture (MT-5 group) and seven matched healthy players (controls, CON) performed three common football movements while in-shoe plantar loading data were collected.ResultsLarge between-group differences exist for maximal vertical force normalised to bodyweight (Fmax) at the lateral toes (2-5) of the stance leg during a set-piece kick (MT-5: 0.2±0.06 bodyweight (BW), CON: 0.1±0.05 BW, effect size (ES) 1.4) and the curved run where the MT-5 group showed higher Fmaxwith very large effect size at the lateral forefoot of the injured (closest to curve) limb when running a curve to receive a pass (MT-5 injured−CON=0.01 BW, ES 1.5). Small between-group differences were evident during straight-line running. However, between-limb analysis of MT-5 group showed significant unloading of the lateral forefoot region of the involved foot.ConclusionsElite male football players who have returned to play after MT-5 stress fracture display significantly higher maximum plantar force at the lateral forefoot and lateral toes (2-5) compared with healthy matched control players during two football movements (kick and curved run) with the magnitude of these differences being very large. These findings may have important implications for manipulating regional load during rehabilitation or should a player report lateral forefoot prodromal symptoms.</jats:sec

The quantification of within week session intensity, duration and intensity distribution across a season in Australian Football using the session RPE method

Purpose: Training in team sports requires the daily manipulation of intensity, duration andfrequency with pre-season focusing on meeting the demands of in-season competition and inseason on recovery from competition. In order to provide information about daily training inAustralian Football (AF), this study aimed to quantify session duration, intensity anddistribution across a full season.Methods: Intensity (Ratings of Perceived Exertion, RPE) and duration were collected fromforty-five professional male AF for every training session and game. Each RPE wascategorized into the corresponding intensity zone; Low (Results: The distribution of the mean session intensity across the season was 29% low-, 57%moderate- and 14% high-intensity. While 96% of games were high-intensity, 44% and 49%of skills training sessions were low- and moderate-intensity, respectively. Running had thehighest proportion of high-intensity training sessions (27%). Pre-season displayed highertraining session intensity and duration, while in-season game intensity and duration werehigher.Conclusion: By using a cost-effective monitoring tool, this study provides information aboutthe intensity and duration of all training types across different phases of the season, thusallowing a greater understanding of the training and competition demands of AustralianFootballers

Systematic Reductions in Differential Ratings of Perceived Exertion Across a 2-Week Repeated-Sprint-Training Intervention That Improved Soccer Players’ High-Speed-Running Abilities

To quantify changes in differential ratings of perceived exertion (dRPE) across a 2-wk repeated-sprint-training intervention that improved high-intensity intermittent-running ability and linear speed of semiprofessional soccer players. Thirteen players completed 3 (sessions 1–3) or 4 (sessions 4–6) sets of 7 sprints (group 1 [n = 7]: 30-m straight; group 2 [n = 6]: 2 × 10-m shuttle), with 20 s and 4 min of recovery between sprints and sets, respectively. Postset perceptions of breathlessness (RPE-B) and leg-muscle exertion (RPE-L) were rated using the CR100 scale. Overall, RPE-B (mean [SD]: 46 [13] arbitrary units [AU], “hard”) was most likely higher than RPE-L (39 [13] AU, “somewhat hard,” mean difference: 8 AU; 90% confidence limits [CLs]: ±2). Set-to-set increases in dRPE (in AU; 90% CL: approximately ±2) were large in session 1 (RPE-B: 15; RPE-L: 14), moderate in sessions 2–5 (RPE-B: 7–10; RPE-L: 7–8), and small (RPE-B: 6) to moderate (RPE-L: 7) in session 6. Across the intervention, RPE-B reduced moderately in sets 3 (−13; 90% CL: ±4) and 4 (−12; 90% CL: ±12) and RPE-L reduced by a small magnitude in set 3 (−5; 90% CL: ±6). The set 4 change in RPE-L was unclear (−11; 90% CL: ±13). Conclusions The authors observed systematic intrasession and intersession changes in dRPE across a 2-wk repeated-sprint-training intervention, with a fixed prescription of external load that improved semiprofessional soccer players’ high-speed-running abilities. These findings could support dRPE as a measure of internal load and highlight its usefulness in evaluating repeated-sprint-training dose–response

The Same Story or a Unique Novel? Within-Participant Principle Component Analysis of Training Load Measures in Professional Rugby Union Skills Training.

PURPOSE: The study aimed to identify which combination of external and internal training load (TL) metrics capture similar or unique information for individual professional players during skills training in rugby union using principal component analysis (PCA). METHOD: TL data were collected from twenty-one male professional rugby union players across a competitive season. This included PlayerLoad™, total distance (TD), and individualised high-speed distance (HSD; >61% maximal velocity; all external TL) obtained from a micro-technology device worn by each player (Optimeye X4, Catapult Innovations, Melbourne, Australia) and the session-rating of perceived exertion (sRPE; internal TL). PCA was conducted on each individual to extract the underlying combinations of the four TL measures that best describe the total information (variance) provided by the measures. TL measures with PC "loadings" (PCL) above 0.7 were deemed to possess well-defined relationships with the extracted PC. RESULTS: The findings show that from the four TL measures, the majority of an individual's TL information (1st PC: 55 to 70%) during skills training can be explained by either sRPE (PCL: 0.72 to 0.95), TD (PCL: 0.86 to 0.98) or PlayerLoad™ (PCL: 0.71 to 0.98). HSD was the only variable to relate to the 2nd PC (PCL: 0.72 to 1.00), which captured additional TL information (+19 to 28%). CONCLUSIONS: Findings suggest practitioners could quantify the TL of rugby union skills training with one of PlayerLoad™, TD, or sRPE plus HSD whilst limiting omitted information of the TL imposed during professional rugby union skills training

Are Current Physical Match Performance Metrics in Elite Soccer Fit for Purpose or is the Adoption of an Integrated Approach Needed?

Time-motion analysis is a valuable data-collection technique used to quantify the physical match performance of elite soccer players. For over 40 years researchers have adopted a 'traditional' approach when evaluating match demands by simply reporting the distance covered or time spent along a motion continuum of walking through to sprinting. This methodology quantifies physical metrics in isolation without integrating other factors and this ultimately leads to a one-dimensional insight into match performance. Thus, this commentary proposes a novel 'integrated' approach that focuses on a sensitive physical metric such as high-intensity running but contextualizes this in relation to key tactical activities for each position and collectively for the team. In the example presented, the 'integrated' model clearly unveils the unique high-intensity profile that exists due to distinct tactical roles, rather than one-dimensional 'blind' distances produced by 'traditional' models. Intuitively this innovative concept may aid the coaches understanding of the physical performance in relation to the tactical roles and instructions given to the players. Additionally, it will enable practitioners to more effectively translate match metrics into training and testing protocols. This innovative model may well aid advances in other team sports that incorporate similar intermittent movements with tactical purpose. Evidence of the merits and application of this new concept are needed before the scientific community accepts this model as it may well add complexity to an area that conceivably needs simplicity

Are there differences in elite youth soccer player work rate profiles in congested versus regular match schedules?

Official international tournaments in which youth soccer players participate can involve very congested schedules. Yet no information regarding physical and technical match performance during congested versus regular (non-congested) cycles is available. In this study, accelerations, decelerations, mean metabolic power, and technical performance (offensive and defensive variables) were compared across very congested (VCM; 10 international matches played over 3 successive days, including 2 days with 2 consecutive matches separated by a 4-5 hr interval) and 10 regular (non-congested) match periods (NCM) in elite male Under 15 (U15, n=11) and Under 17 (U17, n=13) soccer players. Players wore a 15-Hz GPS unit with a 100-Hz tri-axial accelerometer. The session-RPE was assessed 30 min post-match. Results showed a higher number of accelerations/min observed in VCM vs NCM (U15; 2.27±0.35 vs 2.12±0.23; effect size [ES]=0.49; U17; 2.27±0.41 vs 2.01±0.31; ES=0.69). Decelerations/min were higher during VCM (U15; 1.99±0.27 vs 1.84±0.25; ES=0.55; and U17; 1.98±0.35 vs 1.80±0.27; ES=0.56). Mean metabolic power was higher in the VCM (U15; 0.42±0.06 vs 0.37±0.02; ES=1.08; U17; 0.46±0.03 vs 0.30±0.03; ES=1.94). Technical actions/min were higher in the VCM for U17 (ES=1.60 and 1.37, for offensive and defensive performance, respectively); but lower (during VCM) for U15 (ES=3.59 and 0.28, for offensive and defensive performance). U15 reported a higher session-RPE in the VCM (7.9±0.5 AU vs 6.9±0.5 AU). The findings suggest that running activity in these youth players was unaffected overall in tournaments with congested schedules and that the intensity of match-play was actually greater than in regular match schedules