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Jimmy D Bartlett,1 Michael S Keith,2 Lavanya Sudharshan,3 Sonya J Snedecor3 1Department of Optometry, School of Optometry, The University of Alabama at Birmingham, Birmingham, AL, 2Global Health Economics, Outcomes Research, and Epidemiology Department, Research and Development Division, Shire, Wayne, PA, 3Pharmerit International, Bethesda, MD, USA Purpose: The accurate diagnosis and classification of dry eye disease (DED) is challenging owing to wide variations in symptoms and lack of a single reliable clinical assessment. In addition, changes and severity of clinical signs often do not correspond to patient-reported symptoms. To better understand the inconsistencies observed between signs and symptoms, we conducted a systematic literature review to evaluate published studies reporting associations between patient-reported symptoms and clinical signs of DED.Methods: PubMed and Embase were searched for English-language articles on the association between clinical signs and symptoms of DED up to February 2014 (no lower limit was set).Results: Thirty-four articles were identified that assessed associations between signs and symptoms, among which 33 unique studies were reported. These included 175 individual sign–symptom association analyses. Statistical significance was reported for associations between sign and symptom measures in 21 of 33 (64%) studies, but for only 42 of 175 (24%) individual analyses. Of 175 individual analyses, 148 reported correlation coefficients, of which the majority (129/148; 87%) were between –0.4 and 0.4, indicating low-to-moderate correlation. Of all individual analyses that demonstrated a statistically significant association, one-half (56%) of reported correlation coefficients were in this range. No clear trends were observed in relation to the strength of associations relative to study size, statistical methods, or study region, although results from three studies did suggest that disease severity may be a factor.Conclusion: Associations between DED signs and symptoms are low and inconsistent, which may have implications for monitoring the response to treatment, both in the clinic and in clinical trials. Further studies to increase understanding of the etiopathogenesis of DED and to identify the most reliable and relevant measures of disease are needed to enhance clinical assessment of DED and the measurement of response to therapeutic interventions. Keywords: associations, correlations, dry eye disease, signs, symptoms, systematic literature review

The molecular mechanisms that underlie dental fluorosis are poorly understood. The retention of enamel proteins hallmarking fluorotic enamel may result from impaired hydrolysis and/or removal of enamel proteins. Previous studies have suggested that partial inhibition of Mmp20 expression is involved in the etiology of dental fluorosis. Here we ask if mice expressing only one functional Mmp20 allele are more susceptible to fluorosis. We demonstrate that Mmp20 (+/-) mice express approximately half the amount of MMP20 as do wild-type mice. The Mmp20 heterozygous mice have normal-appearing enamel, with Vickers microhardness values similar to those of wild-type control enamel. Therefore, reduced MMP20 expression is not solely responsible for dental fluorosis. With 50-ppm-fluoride (F(-)) treatment ad libitum, the Mmp20 (+/-) mice had F(-) tissue levels similar to those of Mmp20 (+/+) mice. No significant difference in enamel hardness was observed between the F(-)-treated heterozygous and wild-type mice. Interestingly, we did find a small but significant difference in quantitative fluorescence between these two groups, which may be attributable to slightly higher protein content in the Mmp20 (+/-) mouse enamel. We conclude that MMP20 plays a nominal role in dental enamel fluorosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex) in healthy volunteers. RESEARCH DESIGN AND METHODS: In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n = 306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm. CLINICAL TRIALS REGISTRATION: ClinicalTrials. gov, NCT 00532961. RESULTS: The 97.5% confidence intervals for the lower bound were within -10 for all of the seven comfort/ tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p < 0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p < or = 0.04); for pain, stinging/burning, and foreignbody sensation at visit 5 (p < or = 0.03), and for dryness and light sensitivity at visit 6 (p < or = 0.05). CONCLUSIONS: LE/T satisfied all conditions of noninferiority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T. LIMITATIONS: The study population consisted of healthy volunteers. [ABSTRACT FROM AUTHOR]

ADAM10 is a multi-functional proteinase that can cleave approximately 100 different substrates. Previously, it was demonstrated that ADAM10 is expressed by ameloblasts, which are required for enamel formation. The goal of this study was to determine if ADAM10 is necessary for enamel development. Deletion of Adam10 in mice is embryonically lethal and deletion of Adam10 from epithelia is perinatally lethal. We therefore deleted Adam10 from ameloblasts. Ameloblast-specific expression of the Tg( Amelx -i Cre )872pap construct was confirmed. These mice were crossed with Adam10 floxed mice to generate Amelx- i Cre ; Adam10 fl/fl mice ( Adam10 cKO). The Adam10 cKO mice had discolored teeth with softer than normal enamel. Notably, the Adam10 cKO enamel density and volume were significantly reduced in both incisors and molars. Moreover, the incisor enamel rod pattern became progressively more disorganized, moving from the DEJ to the outer enamel surface, and this disorganized rod structure created gaps and S-shaped rods. ADAM10 cleaves proteins essential for cell signaling and for enamel formation such as RELT and COL17A1. ADAM10 also cleaves cell-cell contacts such as E- and N-cadherins that may support ameloblast movement necessary for normal rod patterns. This study shows, for the first time, that ADAM10 expressed by ameloblasts is essential for proper enamel formation.

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax , p21 , and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53 , Bad , and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2 , while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development.

This study describes the training demands of highly trained male youth basketball players, based on training year, term and playing position. Data was collected from 41 male youth basketballers over two seasons from all on-court coach-led training sessions utilising an LPS. Linear mixed-models and pairwise comparisons were used to analyse by training year (Y1, Y2 and Y3), term (T1, T2, T3 and T4) and playing position (Backcourt, Frontcourt). Results showed no differences in external load metrics between training years. Significant differences existed between training terms, with total distance greater in both T3 and T4 than T1 and 2 ( p  < 0.03). Total PlayerLoad was significantly greater in T4 than T1 ( p  < 0.001) and T3 ( p  = 0.004). Distance/min was greater in T2, T3 and T4 than T1 ( p  < 0.01). PlayerLoad/min was higher in T4 than T1 and T2 ( p  < 0.01). Backcourt players showed significantly greater distance/min ( p  = 0.011), PlayerLoad/min ( p  = 0.011) and deceleration counts ( p  < 0.001). Overall, limited year-on-year change existed in external training load metrics ( p  > 0.05), though volume ( p  < 0.001) and intensity ( p  < 0.001) differed between terms. Backcourt players completed higher intensities ( p  = 0.011) than Frontcourt players. This study provides a description of external loads of training in highly trained youth basketball players assisting coaches and performance practitioners to better understand physical demands within youth basketball development pathways.

The relationship between heart rate variability (HRV) and training load in team-sport is unknown. We therefore assessed relations between completed training-load in the previous 1-, 3- and 7-days and waking HRV in professional Australian Rules Football. Linear-mixed models analysed changes in HRV, considering training load from the previous 1-, 3- and 7-days. Total Distance (TD), distance >14.4 km ‧ h-1 (HSR) and >24.9 km ‧ h-1 (Sprint-Distance), duration >85% max heart rate and Rating of Perceived Exertion were included as independent variables. Sub-group analysis of season-phase and years of professional experience was also conducted. Increased three-day Sprint-Distance reduced HRV in the first 8-weeks of pre-season (-13.1 ms, p = 0.03) and across the data collection period (-3.75 ms, p = 0.01). In first-year players, higher previous-day (-63.3 ms, p=0.04) and seven-day TD (-38.2 ms, p = 0.02) reduced HRV, whilst higher seven-day HSR increased HRV (34.5 ms, p = 0.01). In players with five-to-seven years of professional experience, higher three-day (-14.4 ms, p = 0.02) and seven-day TD (-15.7 ms, p = 0.01) reduced HRV, while higher three-day HSR increased HRV (12.5 ms, p = 0.04). In players with greater than eight years of professional experience, higher previous-day Sprint-Distance reduced HRV (-13.1 ms, p < 0.008). Completed training load across the previous 7-days influences HRV, but the relation between variables is complex and influenced by professional experience and season-phase.

Abstract: Lever, JR, Duffield, R, Murray, A, Bartlett, JD, and Fullagar, HHK. Longitudinal internal training load and exposure in a high-performance basketball academy. J Strength Cond Res 38(8): 1464-1471, 2024-This study describes the longitudinal training exposure (session counts) and internal training load (Rating of Perceived Exertion [RPE] and Session Rating of Perceived Exertion [sRPE]) of youth basketball players at a high-performance academy, based on the training year, training term, and playing position. Historical internal training load and training exposure data were collated from 45 male high-performance youth basketball athletes between 2015 and 2019. Data included session duration, RPE, sRPE, training type, and date. Linear mixed models and pairwise comparisons were performed on the weekly means and categorized by training year (year 1, year 2, year 3), term (term 1, term 2, term 3, term 4), and playing position (Backcourt, Frontcourt). Linear mixed models indicate that the individual athlete had the greatest influence on variance in training load and exposure. Significant differences were observed for increased session count, duration, and sRPE ( p < 0.001) in year 2 compared with year 1. These measures also increased within each year whereby term 3 and term 4 ( p < 0.001) were significantly greater than term 1 and term 2. No significant differences were observed between playing position ( p > 0.05). Training exposure and internal training load increase in year 2 from year 1 for high-performance youth basketball academy athletes. Differences between training load and exposure for terms (i.e., training blocks) suggest the phase of season influences training prescription, while playing position has limited effect., (Copyright © 2024 National Strength and Conditioning Association.)

Mood state and alertness are negatively affected by sleep loss, and can be positively influenced by exercise. However, the potential mitigating effects of exercise on sleep-loss-induced changes in mood state and alertness have not been studied comprehensively. Twenty-four healthy young males were matched into one of three, 5-night sleep interventions: normal sleep (NS; total sleep time (TST) per night = 449 ± 22 min), sleep restriction (SR; TST = 230 ± 5 min), or sleep restriction and exercise (SR + EX; TST = 235 ± 5 min, plus three sessions of high-intensity interval exercise (HIIE)). Mood state was assessed using the profile of mood states (POMS) and a daily well-being questionnaire. Alertness was assessed using psychomotor vigilance testing (PVT). Following the intervention, POMS total mood disturbance scores significantly increased for both the SR and SR + EX groups, and were greater than the NS group (SR vs NS; 31.0 ± 10.7 A.U., [4.4-57.7 A.U.], p = 0.020; SR + EX vs NS; 38.6 ± 14.9 A.U., [11.1-66.1 A.U.], p = 0.004). The PVT reaction times increased in the SR (p = 0.049) and SR + EX groups (p = 0.033) and the daily well-being questionnaire revealed increased levels of fatigue in both groups (SR; p = 0.041, SR + EX; p = 0.026) during the intervention. Despite previously demonstrated physiological benefits of performing three sessions of HIIE during five nights of sleep restriction, the detriments to mood, wellness, and alertness were not mitigated by exercise in this study. Whether alternatively timed exercise sessions or other exercise protocols could promote more positive outcomes on these factors during sleep restriction requires further research., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free-living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance-only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance-only exercise (RE, n = 8), RE plus high-intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre- and post-training, was used to determine MyoPS using orally administered deuterium oxide (D 2 O). In both weeks, MyoPS rates were comparable between groups. Post-exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order-dependent responses. In Week 10, exercise-induced changes in MyoPS and some genes (PGC-1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance-only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training., (© 2023 Federation of American Societies for Experimental Biology.)

Enamel forming ameloblasts move away from the dentino-enamel junction and also move relative to each other to establish enamel shape during the secretory stage of enamel development. Matrix metalloproteinase-20 (MMP20) is a tooth specific proteinase essential for proper enamel formation. We previously reported that MMP20 cleaves cadherins and may regulate ameloblast movement. Here, we used an Amelx promoter driven tdTomato reporter to label mouse ameloblasts. With these transgenic mice, we assessed ameloblast mobility group dynamics and gene expression. Three-dimensional imaging of mouse ameloblasts were observed in hemi-mandibles by using a tissue clearing technique. The three-dimensional ameloblast layer in Tg(Amelx-Mmp20) mice that overexpress MMP20 was uneven and the ameloblasts migrated away from this layer. Mouse ameloblast movement toward incisal tips was monitored by ex vivo time-lapse imaging. Gene expression related to cell migration and adhesion was analyzed in ameloblasts from wild-type mice, Mmp20 -/- mice with no functional MMP20 and from Tg(Amelx-Mmp20) overexpressing mice. Gene expression was altered in Mmp20 -/- and Tg(Amelx-Mmp20) mice compared to wild type. Among the genes assessed, those encoding laminins and a gap junction protein were upregulated in Mmp20 -/- mice. New techniques and findings described in this study may lead to an improved understanding of ameloblast movement during enamel formation., (© 2023. The Author(s).)

Transient receptor potential melastatin 7 (TRPM7) is a unique ion channel connected to a kinase domain. We previously demonstrated that Trpm7 expression is high in mouse ameloblasts and odontoblasts, and that amelogenesis is impaired in TRPM7 kinase-dead mice. Here, we analyzed TRPM7 function during amelogenesis in Keratin 14-Cre;Trpm7 fl/fl conditional knockout (cKO) mice and Trpm7 knockdown cell lines. cKO mice showed lesser tooth pigmentation than control mice and broken incisor tips. Enamel calcification and microhardness were lower in cKO mice. Electron probe microanalysis (EPMA) showed that the calcium and phosphorus contents in the enamel were lower in cKO mouse than in control mice. The ameloblast layer in cKO mice showed ameloblast dysplasia at the maturation stage. The morphological defects were observed in rat SF2 cells with Trpm7 knockdown. Compared with mock transfectants, the Trpm7 knockdown cell lines showed lower levels of calcification with Alizarin Red-positive staining and an impaired intercellular adhesion structures. These findings suggest that TRPM7 is a critical ion channel in enamel calcification for the effective morphogenesis of ameloblasts during amelogenesis., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca 2+ and Mg 2+ . Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation. Prx1-Cre-dependent Trpm7 mesenchymal-deleted mice were generated to examine the role of TRPM7 in bone development. We found that Prx1-Cre;Trpm7 fl/fl mice had shortened bones and impaired trabecular bone formation. Trabecular bone parameters, such as the bone volume (BV/TV), and trabecular number (Tb.N), were decreased in Prx1-Cre;Trpm7 fl/fl mice. The cortical bone parameters of cortical bone area (Ct.Ar) and cortical bone thickness (Ct.Th) were also down-regulated in these mice. The bone formation rate in Prx1-Cre;Trpm7 fl/fl mice was unchanged, but the hypertrophic area and cell size of the zone were smaller, and the expression of Col2a1, Col10a1 and Mmp13 was downregulated compared with control mice. These findings suggest impaired chondrogenesis in Prx1-Cre;Trpm7 fl/fl mice compared to control mice. The receptor activator of nuclear factor-kappa B ligand (RANKL) expression was increased, and RANKL-positive cells and osteoclasts were markedly accumulated in the boundary region between the growth plate and trabecular bone. In contrast, TRPM7 KR mice, which are kinase-dead mutants in which the TRPM7 ion channel function has not been altered, showed no marked differences in trabecular or cortical bone parameters compared to wild-type mice. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone development via the regulation of chondrogenesis., Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

ADAM10 is A Disintegrin And Metalloproteinase (ADAM) family member that is membrane bound with its catalytic domain present on the cell surface. It is a sheddase that cleaves anchored cell surface proteins to shed them from the cell surface. ADAM10 can cleave at least a hundred different proteins and is expressed in most tissues of the body. ADAM10 is best characterized for its role in Notch signaling. Interestingly, ADAM10 is transported to specific sites on the cell surface by six different tetraspanins. Although the mechanism is not clear, tetraspanins can regulate ADAM10 substrate specificity, which likely contributes to the diversity of ADAM10 substrates. In developing mouse teeth, ADAM10 is expressed in the stem cell niche and subsequently in pre-ameloblasts and then secretory stage ameloblasts. However, once ameloblasts begin transitioning into the maturation stage, ADAM10 expression abruptly ceases. This is exactly when ameloblasts stop their movement that extends enamel crystallites and when the enamel layer reaches its full thickness. ADAM10 may play an important role in enamel development. ADAM10 can cleave cadherins and other cell-cell junctions at specific sites where the tetraspanins have transported it and this may promote cell movement. ADAM10 can also cleave the transmembrane proteins COL17A1 and RELT. When either COL17A1 or RELT are mutated, malformed enamel may occur in humans and mice. So, ADAM10 may also regulate these proteins that are necessary for proper enamel development. This mini review will highlight ADAM10 function, how that function is regulated by tetraspanins, and how ADAM10 may promote enamel formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shahid, Ikeda, Layana and Bartlett.)

Background: Inadequate sleep is associated with many detrimental health effects, including increased risk of developing insulin resistance and type 2 diabetes. These effects have been associated with changes to the skeletal muscle transcriptome, although this has not been characterised in response to a period of sleep restriction. Exercise induces a beneficial transcriptional response within skeletal muscle that may counteract some of the negative effects associated with sleep restriction. We hypothesised that sleep restriction would down-regulate transcriptional pathways associated with glucose metabolism, but that performing exercise would mitigate these effects., Methods: 20 healthy young males were allocated to one of three experimental groups: a Normal Sleep (NS) group (8 h time in bed per night (TIB), for five nights (11 pm - 7 am)), a Sleep Restriction (SR) group (4 h TIB, for five nights (3 am - 7 am)), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB, for five nights (3 am - 7 am) and three high-intensity interval exercise (HIIE) sessions (performed at 10 am)). RNA sequencing was performed on muscle samples collected pre- and post-intervention. Our data was then compared to skeletal muscle transcriptomic data previously reported following sleep deprivation (24 h without sleep)., Results: Gene set enrichment analysis (GSEA) indicated there was an increased enrichment of inflammatory and immune response related pathways in the SR group post-intervention. However, in the SR+EX group the direction of enrichment in these same pathways occurred in the opposite directions. Despite this, there were no significant changes at the individual gene level from pre- to post-intervention. A set of genes previously shown to be decreased with sleep deprivation was also decreased in the SR group, but increased in the SR+EX group., Conclusion: The alterations to inflammatory and immune related pathways in skeletal muscle, following five nights of sleep restriction, provide insight regarding the transcriptional changes that underpin the detrimental effects associated with sleep loss. Performing three sessions of HIIE during sleep restriction attenuated some of these transcriptional changes. Overall, the transcriptional alterations observed with a moderate period of sleep restriction were less evident than previously reported changes following a period of sleep deprivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Saner, Weng, Caruana, Botella, Kuang, Lee, Jamnick, Pitchford, Garnham, Bartlett, Chen and Bishop.)

Abstract: O'Connor, FK, Doering, TM, Minett, GM, Reaburn, PR, Bartlett, JD and Coffey, VG. Effect of divergent solar radiation exposure with outdoor versus indoor training in the heat: implications for performance. J Strength Cond Res 36(6): 1622-1628, 2022-The aim of this study was to determine physiological and perceptual responses and performance outcomes when completing high-intensity exercise in outdoor and indoor hot environments with contrasting solar radiation exposure. Seven cyclists and 9 Australian Football League (AFL) players undertook cycling trials in hot conditions (≥30 °C) outdoors and indoors. Cyclists completed 5 × 4 minutes intervals (∼80% peak power output [PPO]) with 2 minutes recovery (∼40% PPO) before a 20-km self-paced ride. Australian Football League players completed a standardized 20 minutes warm-up (∼65% mean 4-minute power output) then 5 × 2 minutes maximal effort intervals. Heart rate (HR), PO, ratings of perceived exertion (RPE), thermal comfort (TC), and thermal sensation (TS) were recorded. Core (Tc) and skin temperature (Tsk) were monitored in cyclists alone. In both studies, ambient temperature, relative humidity, and solar radiation were monitored outdoors and matched for ambient temperature and relative humidity indoors, generating different wet bulb globe temperature (WBGT) for cyclists, but the similar WBGT for AFL players through higher relative humidity indoors. The statistical significance was set at p ≤ 0.05. Cyclists' HR (p = 0.05), Tc (p = 0.03), and Tsk (p = 0.03) were higher outdoors with variable effects for increased RPE, TS, and TC (d = 0.2-1.3). Power output during intervals was not different between trials, but there were small-moderate improvements in cyclists' PO and 20-km time indoors (d = 0.3-0.6). There was a small effect (d = 0.2) for AFL players' mean PO to increase outdoors for interval 4 alone (p = 0.04); however, overall there were small-moderate effects for lower RPE and TS indoors (d = 0.2-0.5). Indoor training in hot conditions without solar radiation may promote modest reductions in physiological strain and improve performance capacity in well-trained athletes., (Copyright © 2020 National Strength and Conditioning Association.)

Following dislocation of the glenohumeral joint with an isolated greater tuberosity fracture, closed reduction in the emergency department can lead to fracture propagation or iatrogenic fractures. This article assesses the evidence regarding when anterior dislocations of the shoulder with an isolated fracture of the greater tuberosity can be safely reduced in the emergency department, as there is currently no clear guidance on this. A total of eight articles described 172 cases which underwent closed reduction, which resulted in 22 cases of iatrogenic fractures. Female sex, increased patient age and fragments of the greater tuberosity were associated with an increased risk of iatrogenic fractures. Closed reduction in the emergency department appears to be a safe option in younger patients and those with greater tuberosity fractures less than 40% of the width of the humeral head.

The revolution in genetics has rapidly increased our knowledge of human and mouse genes that are critical for the formation of dental enamel and helps us understand how enamel evolved. In this graphical review we focus on the roles of 41 genes that are essential for the secretory stage of amelogenesis when characteristic enamel mineral ribbons initiate on dentin and elongate to expand the enamel layer to the future surface of the tooth. Based upon ultrastructural analyses of genetically modified mice, we propose a molecular model explaining how a cell attachment apparatus including collagen 17, α6ß4 and αvß6 integrins, laminin 332, and secreted enamel proteins could attach to individual enamel mineral ribbons and mold their cross-sectional dimensions as they simultaneously elongate and orient them in the direction of the retrograde movement of the ameloblast membrane., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Robust randomised trial data have shown that routine preoperative (pre-op) testing for cataract surgery patients is inappropriate. While guidelines have discouraged testing since 2002, cataract pre-op testing rates have remained unchanged since the 1990s. Given the challenges of reducing low-value care despite strong consensus around the evidence, innovative approaches are needed to promote high-value care. This trial evaluates the impact of an interdisciplinary electronic health record (EHR) intervention that is informed by behavioural economic theory., Methods and Analysis: This pragmatic randomised trial is being conducted at UCLA Health between June 2021 and June 2022 with a 12-month follow-up period. We are randomising all UCLA Health physicians who perform pre-op visits during the study period to one of the three nudge arms or usual care. These three nudge alerts address (1) patient harm, (2) increased out-of-pocket costs for patients and (3) psychological harm to the patients related to pre-op testing. The nudges are triggered when a physician starts to order a pre-op test. We hypothesise that receipt of a nudge will be associated with reduced pre-op testing. The primary outcome will be the change in the percentage of patients undergoing pre-op testing at 12 months. Secondary outcomes will include the percentage of patients undergoing specific categories of pre-op tests (labs, EKGs, chest X-rays (CXRs)), the efficacy of each nudge, same-day surgery cancellations and cost savings., Ethics and Dissemination: The study protocol was approved by the institutional review board of the University of California, Los Angeles as well as a nominated Data Safety Monitoring Board. If successful, we will have created a tool that can be disseminated rapidly to EHR vendors across the nation to reduce inappropriate testing for the most common low-risk surgical procedures in the country., Trial Registration Number: ClinicalTrials.gov identifier: NCT04104256., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults METHODS: Pupil size was measured in 56 eyes of 28 volunteer participants using a pupillometer under scotopic conditions. Age, gender, and iris color were recorded. Subjects using any ophthalmic medications other than artificial tears were excluded. The pupil size was subsequently measured again under scotopic conditions 60 min after instillation of brimonidine tartrate 0.025% ophthalmic solution., Results: Statistically significant miosis was seen after instillation of brimonidine tartrate 0.025% (p = 0.04). Average pupil size prior to brimonidine 0.025% instillation was 7.28 ± 1.05 mm, and average pupil size after instillation of brimonidine 0.025% was 6.36 ± 1.68 mm, a reduction of - 23.7% in pupil area. Subjects with light irides demonstrated a greater miotic effect than subjects with dark irides (1.55 mm vs. 0.67 mm, p < 0.0001), with a pupil area reduction of - 37.6% and - 17.4%, respectively. The amount of miosis was independent of initial pupil size., Conclusions: Brimonidine tartrate 0.025% causes significant miosis in scotopic settings, although the effect is not as great in darker colored eyes. Further studies are needed to determine the latency and duration of the effect and whether the amount of miosis is clinically significant., (© 2021. The Author(s).)

Sport Science is considered the study and application of scientific principles and techniques to improve sporting performance. Thus, a key role of the Sport Scientist is to translate complex information into usable and contextual performance solutions for a range of different stakeholders. These stakeholders consist of athletes, coaches, recruiting, performance support, medical, administration and operations staff and have varying interests and priorities meaning the information required can be vastly different. In addition to these different needs, sport is fast-moving, diverse and complex meaning there are a number of potential translational barriers. Sport Science training programmes entail the development of technical knowledge and practical skills; however, little is considered in view of interpersonal craft skill development and knowledge translation (KT). Given the reported barriers and challenges to effective KT in sport, this lack of specific training may render KT as ineffective and suboptimal. Accordingly, in this article, we propose a framework and work-based training model with the aim of developing the KT process and performance delivery of Sport Scientists operating in professional sport. Firstly, we define the current perspectives and challenges for Sport Scientists in the context of KT, before proposing a framework that focusses on Evidence-Based-Practice, Philosophy, Recipients and Facilitation, in which Sport Scientists can use to develop their interpersonal craft and subsequent KT approach. We finish by presenting a model of sport science practitioner training; the professional sport-doctoral training programme, that combined with the framework, can be effective in developing Sport Scientists.

Dental enamel forms extracellularly as thin ribbons of amorphous calcium phosphate (ACP) that initiate on dentin mineral in close proximity to the ameloblast distal membrane. Secreted proteins are critical for this process. Enam -/- and Ambn -/- mice fail to form enamel. We characterize enamel ribbon formation in wild-type (WT), Amelx -/- and Mmp20 -/- mouse mandibular incisors using focused ion beam scanning electron microscopy (FIB-SEM) in inverted backscatter mode. In Amelx -/- mice, initial enamel mineral ribbons extending from dentin are similar in form to those of WT mice. As early enamel development progresses, the Amelx -/- mineral ribbons develop multiple branches, resembling the staves of a Japanese fan. These striking fan-shaped structures cease growing after attaining ~ 20 µm of enamel thickness (WT is ~ 120 µm). The initial enamel mineral ribbons in Mmp20 -/- mice, like those of the Amelx -/- and WT, extend from the dentin surface to the ameloblast membrane, but appear to be fewer in number and coated on their sides with organic material. Remarkably, Mmp20 -/- mineral ribbons also form fan-like structures that extend to ~ 20 µm from the dentin surface. However, these fans are subsequently capped with a hard, disorganized outer mineral layer. Amelogenin cleavage products are the only matrix components absent in both Amelx -/- and Mmp20 -/- mice. We conclude that MMP20 and amelogenin are not critical for enamel mineral ribbon initiation, orientation, or initial shape. The pathological fan-like plates in these mice may form from the lack of amelogenin cleavage products, which appear necessary to form ordered hydroxyapatite.

The trace element fluoride can be beneficial for oral health by preventing dental caries. However, fluoride is also known as an environmental pollutant. Fluoride pollution can lead to fluoride over-ingestion and can cause health issues, including dental fluorosis. Curcumin attenuated fluoride-induced toxicity in animal models, however the molecular mechanisms of how curcumin affects fluoride toxicity remain to be elucidated. We hypothesized that curcumin attenuates fluoride toxicity through modulation of Ac-p53. Here we investigated how curcumin affects the p53-p21 pathway in fluoride toxicity. LS8 cells were treated with NaF with/without curcumin. Curcumin significantly increased phosphorylation of Akt [Thr308] and attenuated fluoride-mediated caspase-3 cleavage and DNA damage marker γH2AX expression. Curcumin-mediated attenuation of caspase-3 activation was reversed by Akt inhibitor LY294002 (LY). However, LY did not alter curcumin-mediated γH2AX suppression. These results suggest that curcumin inhibited fluoride-mediated apoptosis via Akt activation, but DNA damage was suppressed by other pathways. Curcumin did not suppress/alter fluoride-mediated Ac-p53. However, curcumin itself significantly increased Ac-p53 and upregulated p21 protein levels to suppress cell proliferation in a dose-dependent manner. Curcumin suppressed fluoride-induced phosphorylation of p21 and increased p21 levels within the nuclear fraction. However, curcumin did not reverse fluoride-mediated cell growth inhibition. These results suggest that curcumin-induced Ac-p53 and p21 led to cell cycle arrest, while curcumin attenuated fluoride-mediated apoptosis via activation of Akt and suppressed fluoride-mediated DNA damage. By inhibiting DNA damage and apoptosis, curcumin may potentially alleviate health issues caused by fluoride pollution. Further studies are required to better understand the mechanism of curcumin-induced biological effects on fluoride toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Serious thromboembolic events with concurrent thrombocytopenia, sometimes accompanied by bleeding, have occurred very rarely following administration of the ChAdOx1 nCoV-19 vaccine. We report the case of a 59-year-old male with an unremarkable medical history who presented to the emergency department with increasing breathlessness five days after receiving the first dose of ChAdOx1 nCov-19. The patient's blood results showed mild thrombocytopenia and a very high D-dimer, and a pulmonary embolism was confirmed through a CT pulmonary angiogram, which led to a provisional diagnosis of vaccine-induced immune thrombotic thrombocytopenia. The condition was then treated with immunoglobulin and intravenous argatroban in line with the guidance from the Expert Haematology Panel focussed on Vaccine-induced Thrombosis and Thrombocytopenia before conversion to apixaban.

Objective: Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Because exercise improves glucose tolerance and mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep., Methods: To minimize between-group differences of baseline characteristics, 24 healthy young males were allocated into one of the three experimental groups: a Normal Sleep (NS) group (8 h time in bed (TIB) per night, for five nights), a Sleep Restriction (SR) group (4 h TIB per night, for five nights), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB per night, for five nights and three high-intensity interval exercise (HIIE) sessions). Glucose tolerance, mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS), and diurnal measures of peripheral skin temperature were assessed pre- and post-intervention., Results: We report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002), which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O 2 .s -1 .mg -1 , P = 0.001), a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001), and reduced amplitude of diurnal rhythms. These effects were not observed when incorporating three sessions of HIIE during this period (SR+EX: glucose AUC 67 ± 57, P = 0.239, mitochondrial respiratory function: 0.6 ± 11.8 pmol O 2 .s -1 .mg -1 , P = 0.997, and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971)., Conclusions: A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance. We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction. These data therefore provide evidence in support of the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: As attention to the potential negative outcomes of childhood trauma has grown, so have calls for schools to take an active role in supporting students experiencing trauma. These calls extend beyond efforts initiated by individual schools to include those mandated by state law, which largely focus on teacher training and on screening for adversity., Methods: This article explores the evidence base and limitations for current approaches in state law and explores how policies to address other student health, safety, and wellness issues can help either ameliorate or exacerbate students' experiences with trauma., Results: Few trainings for nonclinical staff have rigorous evidence of effectiveness, and based on evidence of teacher trainings on other topics, cannot work in environments that do not actively reinforce and encourage the application of that knowledge. Trainings also largely do not acknowledge the structures and systems, including systemic racism within schools, that may contribute to disparate rates of adversity for black and American Indian and Alaskan Native children. Screening carries several risks, including confounding adversity with experiencing trauma, missing broader contextual adversity, and potentially retraumatizing children., Conclusions: State policymakers need to take a more holistic approach in creating policies to support students experiencing trauma., (© 2020 The Authors. Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

Background: Little is known about contrast training and post-activation performance enhancement (PAPE) in a same day concurrent training model. The aim of the current study was to examine the use of two short duration (1-min and 4-min) recovery periods on drop jump performance in same day concurrently trained athletes., Methods: Ten professional Australian Rules footballers (age, 20.6 ± 1.9 yr; height, 184.8 ± 6.9 cm; body mass, 85.8 ± 8.4 kg) completed two resistance training sessions with different PAPE recovery durations; 1-min and 4-min, 1 h following a field-based endurance session. Baseline (pre) drop jumps were compared to post-test maximal drop jumps, performed after each set of three squats (where each participant was encouraged to lift as heavy as they could), to determine changes between 1-min and 4-min recovery periods. Data were analysed by fitting a mixed model (significance was set at P ≤ 0.05). Corrected Hedges' g standardised effect sizes ±95% confidence limits were calculated using group means ± SDs., Results: There were no significant differences between baseline and experimental sets 1, 2 and 3 for reactive strength index (RSI), flight time, and total and relative impulse for either recovery duration. However, for contact time, 1-min baseline was significantly different from set 2 (mean difference; 95% CI [0.029; 0.000-0.057 s], P = 0.047, ES; 95% CI [-0.27; -1.20 to 0.66]). For RSI and flight time, 1-min was significantly higher than 4-min (RSI: 0.367; 0.091 to 0.642, P = 0.010, ES; 95% CI [0.52; -0.37 to 1.42]; flight time: 0.033; 0.003 to 0.063 s, P = 0.027, ES; 95% CI [0.86; -0.06 to 1.78])., Discussion: Short recovery periods of 1-min may be a time-efficient form of prescribing strength-power exercise in contrast loading schemes. Longer recovery periods do not appear to benefit immediate, subsequent performance., Competing Interests: Justin Keogh is an Academic Editor for PeerJ. Dean Ritchie is employed by the Gold Coast Suns FC., (© 2020 Ritchie et al.)

The incisors of rodents comprise an iron-rich enamel and grow throughout adult life, making them unique models of iron metabolism and tissue homeostasis during aging. Here, we deleted Atg7 (autophagy related 7) in murine ameloblasts, i.e. the epithelial cells that produce enamel. The absence of ATG7 blocked the transport of iron from ameloblasts into the maturing enamel, leading to a white instead of yellow surface of maxillary incisors. In aging mice, lack of ATG7 was associated with the growth of ectopic incisors inside severely deformed primordial incisors. These results suggest that 2 characteristic features of rodent incisors, i.e. deposition of iron on the enamel surface and stable growth during aging, depend on autophagic activity in ameloblasts. Abbreviations : ATG5: autophagy related 5; ATG7: autophagy related 7; CMV: cytomegalovirus; Cre: Cre recombinase; CT: computed tomography; FTH1: ferritin heavy polypeptide 1; GFP: green fluorescent protein; KRT5: keratin 5; KRT14: keratin 14; LGALS3: lectin, galactose binding, soluble 3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NCOA4: nuclear receptor coactivator 4; NRF2: nuclear factor, erythroid 2 like 2; SQSTM1: sequestosome 1.

This study examined the relationship between dual-energy x-ray absorptiometry (DXA)-derived estimates of energy balance (EB) and changes in body composition across various seasonal phases in team sport athletes. Forty-five Australian rules footballers underwent six DXA scans across a 12-month period (off-season [OS, Week 0-13], early [PS1, Week 13-22] and late pre-season [PS2, Week 22-31] and early [IS1, Week 3-42] and late in-season [IS2, Week 42-51]). EB (kcal·day -1 ) was estimated from changes in fat free soft tissue mass (FFSTM) and fat mass (FM) between scans according to a validated formula. An EB threshold of ± 123 kcal·day -1 for >60 days demonstrated a very likely (>95% probability) change in FFSTM (>1.0 kg) and FM (>0.7 kg). There were small to almost perfect relationships between EB and changes in FM ( r =  0.97, 95% CI, 0.96-0.98), FFSTM ( r = - 0.41, -0.92 to -0.52) and body mass ( r =  0.27, 0.14-0.40). EB was lowest during PS1 compared to all other phases (range, -265 to -142 kcal·day -1 ), with no other changes at any time. Increases in FFSTM were higher during OS compared to PS2 (1.6 ± 0.4 kg), and higher during PS1 compared to PS2, IS1, and IS2 (range, 1.6-2.1 kg). There were no changes during in-season (-0.1-0.05 kg). FM decreased only in PS1 compared to all other seasonal phases (-1.8 to -1.0 kg). Assessments of body composition can be used as a tool to estimate EB, which practically can be used to indicate athlete's training and nutrition behaviours/practices.

Background: Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear., Methods: We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20 -/- mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing., Results: We identified six novel MMP20 disease-causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin-like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%-69% of control. Characterization of Mmp20 -/- mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization., Conclusion: These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Context: Exercise in hot environments increases body temperature and thermoregulatory strain. However, little is known regarding the magnitude of effect that ambient temperature (Ta), relative humidity (RH), and solar radiation individually have on team-sport athletes., Purpose: To determine the effect of these individual heat-stress variables on team-sport training performance and recovery., Methods: Professional Australian Rules Football players (N = 45) undertook 8-wk preseason training producing a total of 579 outdoor field-based observations with Ta, RH, and solar radiation recorded at every training session. External load (distance covered, in m/min; percentage high-speed running [%HSR] >14.4 km/h) was collected via a global positioning system. Internal load (ratings of perceived exertion and heart rate) and recovery (subjective ratings of well-being and heart-rate variability [root mean square of the successive differences]) were monitored throughout the training period. Mixed-effects linear models analyzed relationships between variables using standardized regression coefficients., Results: Increased solar-radiation exposure was associated with reduced distance covered (-19.7 m/min, P < .001), %HSR (-10%, P < .001) during training and rMSSD 48 h posttraining (-16.9 ms, P = .019). Greater RH was associated with decreased %HSR (-3.4%, P = .010) but increased percentage duration >85% HRmax (3.9%, P < .001), ratings of perceived exertion (1.8 AU, P < .001), and self-reported stress 24 h posttraining (-0.11 AU, P = .002). In contrast, higher Ta was associated with increased distance covered (19.7 m/min, P < .001) and %HSR (3.5%, P = .005)., Conclusions: The authors show the importance of considering the individual factors contributing to thermal load in isolation for team-sport athletes and that solar radiation and RH reduce work capacity during team-sport training and have the potential to slow recovery between sessions.

Introduction: Decreases in trainees' working hours, coupled with evidence of worse outcomes when hip arthroscopies are performed by inexperienced surgeons, mandate an additional means of training. Though virtual reality simulation has been adopted by other surgical specialities, its slow uptake in arthroscopic training is due to a lack of evidence as to its benefits. These benefits can be demonstrated through learning curves associated with simulator training-with practice reflecting increases in validated performance metrics., Methods: Twenty-five medical students with no previous experience of hip arthroscopy completed seven weekly simulated arthroscopies of a healthy virtual hip joint using a 70° arthroscope in the supine position. Twelve targets were visualised within the central compartment, six via the anterior portal, three via the anterolateral portal and three via the posterolateral portal. Task duration, number of collisions (bone and soft-tissue), and distance travelled by arthroscope were measured by the simulator for every session of each student., Results: Learning curves were demonstrated by the students, with improvements in time taken, number of collisions (bone and soft-tissue), collision length and efficiency of movement (all p < 0.01). Improvements in time taken, efficiency of movement and number of collisions with soft-tissue were first seen in session 3 and improvements in all other parameters were seen in session 4. No differences were found after session 5 for time taken and length of soft-tissue collision. No differences in number of collisions (bone and soft-tissue), length of collisions with bone, and efficiency of movement were found after session 6., Conclusions: The results of this study demonstrate learning curves for a hip arthroscopy simulator, with significant improvements seen after three sessions. All performance metrics were found to improved, demonstrating sufficient visuo-haptic consistency within the virtual environment, enabling individuals to develop basic arthroscopic skills.

Background: The importance of concurrent exercise order for improving endurance and resistance adaptations remains unclear, particularly when sessions are performed a few hours apart. We investigated the effects of concurrent training (in alternate orders, separated by ~3 hours) on endurance and resistance training adaptations, compared to resistance-only training., Materials and Methods: Twenty-nine healthy, moderately-active men (mean ± SD; age 24.5 ± 4.7 y; body mass 74.9 ± 10.8 kg; height 179.7 ± 6.5 cm) performed either resistance-only training (RT, n = 9), or same-day concurrent training whereby high-intensity interval training was performed either 3 hours before (HIIT+RT, n = 10) or after resistance training (RT+HIIT, n = 10), for 3 d.wk-1 over 9 weeks. Training-induced changes in leg press 1-repetition maximal (1-RM) strength, countermovement jump (CMJ) performance, body composition, peak oxygen uptake ([Formula: see text]), aerobic power ([Formula: see text]), and lactate threshold ([Formula: see text]) were assessed before, and after both 5 and 9 weeks of training., Results: After 9 weeks, all training groups increased leg press 1-RM (~24-28%) and total lean mass (~3-4%), with no clear differences between groups. Both concurrent groups elicited similar small-to-moderate improvements in all markers of aerobic fitness ([Formula: see text] ~8-9%; [Formula: see text] ~16-20%; [Formula: see text] ~14-15%). RT improved CMJ displacement (mean ± SD, 5.3 ± 6.3%), velocity (2.2 ± 2.7%), force (absolute: 10.1 ± 10.1%), and power (absolute: 9.8 ± 7.6%; relative: 6.0 ± 6.6%). HIIT+RT elicited comparable improvements in CMJ velocity only (2.2 ± 2.7%). Compared to RT, RT+HIIT attenuated CMJ displacement (mean difference ± 90%CI, -5.1 ± 4.3%), force (absolute: -8.2 ± 7.1%) and power (absolute: -6.0 ± 4.7%). Only RT+HIIT reduced absolute fat mass (mean ± SD, -11.0 ± 11.7%)., Conclusions: In moderately-active males, concurrent training, regardless of the exercise order, presents a viable strategy to improve lower-body maximal strength and total lean mass comparably to resistance-only training, whilst also improving indices of aerobic fitness. However, improvements in CMJ displacement, force, and power were attenuated when RT was performed before HIIT, and as such, exercise order may be an important consideration when designing training programs in which the goal is to improve lower-body power., Competing Interests: The authors have declared that no competing interests exist.