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Purpose: To quantify and compare loads encountered in individual training sessions and games during noncongested and congested weeks in semiprofessional women basketball players. Methods: Using an observational, longitudinal design, 12 players from the same team had their external (PlayerLoad, relative PlayerLoad, and total and high-intensity inertial movement analysis variables) and internal load (session rating of perceived exertion [sRPE], sRPE-load, percentage of heart rate peak, and modified summated-heart-rate-zones load) monitored across a regular season. Training and game data were categorized into noncongested (0–1 game) and congested weeks (2–3 games). Linear mixed models and Cohen d effect sizes were used for analyses. Results: Comparisons between training sessions revealed higher (P <.05, d = 1.35–5.33) PlayerLoad, total inertial movement analysis, sRPE, and sRPE-load during training session 1 than training session 2 in congested weeks. Comparisons between training sessions and games revealed higher (P ≤.001, d = 1.10–1.66) sRPE and sRPE-load during games than training sessions 1 and 2 in noncongested weeks, alongside higher (P ≤.001, d = 1.87–3.55) sRPE during game 1 than training sessions 1 and 2 in congested weeks. Comparisons between games revealed higher (P <.05, d = 0.57–2.82) loads in game 3 during congested weeks compared with all other games. Conclusions: Training appeared to be tapered in congested weeks, likely to account for upcoming increases in game loading, but remained relatively consistent across sessions during noncongested weeks. Individual game loads remained relatively consistent but were noticeably increased when a third game was played in the week. [ABSTRACT FROM AUTHOR]

Purpose: This preliminary study examined the influence of estimated menstrual-cycle (MC) phase on responses to soccer matches and training sessions in preparation for and during the FIFA (Fédération internationale de football association) Women's World Cup 2019. Methods: Twenty outfield players representing a national team were tracked over a 45-day period. External (10-Hz global positioning system; total and distance covered at high-metabolic power [≥20 W·kg−1]) and internal load measures (minutes ≥80% heart-rate maximum, sessional ratings of perceived exertion) were collected during all training and matches, with single-item wellness measures (fatigue, soreness, sleep quality, and sleep duration) collected each morning prior to activity. MC phase was estimated individually via an algorithm, informed from pretournament survey responses and ongoing symptom reporting (FitrWoman). Model comparison statistics were used to determine the impact of estimated MC phase in nonhormonal contraceptive users (n = 16). Results: Sessional rating of perceived exertion responses to total distances ≥5 km were higher during the luteal phase (+0.6–1.0 au; P ≤.0178) versus menstruation (phase 1), but no other observable dose–response trends were observed. Sleep, fatigue, and soreness ratings were not typically associated with MC phase, with the exception of exacerbated fatigue ratings in luteal versus follicular phase 48 hours postmatch (−0.73 au, P =.0275). Conclusions: Preliminary findings suggest that estimated MC phase may contribute to the understanding of the dose–response to soccer training and matches. [ABSTRACT FROM AUTHOR]

The chromatin-associated protein WDR5 has been widely studied due to its role in histone modification and its potential as a pharmacological target for the treatment of cancer. In humans, the protein with highest sequence homology to WDR5 is encoded by the retrogene WDR5B, which remains unexplored. Here, we used CRISPR-Cas9 genome editing to generate WDR5B knockout and WDR5B-FLAG knock-in cell lines for further characterization. In contrast to WDR5, WDR5B exhibits low expression in pluripotent cells and is upregulated upon neural differentiation. Loss or shRNA depletion of WDR5B impairs cell growth and increases the fraction of non-viable cells in proliferating retinal pigment epithelial (RPE) cultures. CUT&RUN chromatin profiling in RPE and neural progenitors indicates minimal WDR5B enrichment at established WDR5 binding sites. These results suggest that WDR5 and WDR5B exhibit several divergent biological properties despite sharing a high degree of sequence homology.

MicroRNAs (miRs) are short, evolutionarily conserved noncoding RNAs that canonically downregulate expression of target genes. The miR family composed of miR-204 and miR-211 is among the most highly expressed miRs in the retinal pigment epithelium (RPE) in both mouse and human and also retains high sequence identity. To assess the role of this miR family in the developed mouse eye, we generated two floxed conditional KO mouse lines crossed to the RPE65-ERT2-Cre driver mouse line to perform an RPE-specific conditional KO of this miR family in adult mice. After Cre-mediated deletion, we observed retinal structural changes by optical coherence tomography; dysfunction and loss of photoreceptors by retinal imaging; and retinal inflammation marked by subretinal infiltration of immune cells by imaging and immunostaining. Single-cell RNA sequencing of diseased RPE and retinas showed potential miR-regulated target genes, as well as changes in noncoding RNAs in the RPE, rod photoreceptors, and Müller glia. This work thus highlights the role of miR-204 and miR-211 in maintaining RPE function and how the loss of miRs in the RPE exerts effects on the neural retina, leading to inflammation and retinal degeneration.

Congenital ocular malformations originate from defective morphogenesis during early eye development and cause 25% of childhood blindness. Formation of the eye is a multi-step, dynamic process; it involves evagination of the optic vesicle, followed by distal and ventral invagination, leading to the formation of a two-layered optic cup with a transient optic fissure. These tissue folding events require extensive changes in cell shape and tissue growth mediated by cytoskeleton mechanics and intercellular adhesion. We hypothesized that the Rho GTPase Cdc42 may be an essential, convergent effector downstream of key regulatory factors required for ocular morphogenesis. CDC42 controls actin remodeling, apicobasal polarity, and junction assembly. Here we identify a novel essential function for Cdc42 during eye morphogenesis in mouse; in Cdc42 mutant eyes expansion of the ventral optic cup is arrested, resulting in microphthalmia and a wide coloboma. Our analyses show that Cdc42 is required for expression of the polarity effector proteins PRKCZ and PARD6, intercellular junction protein tight junction protein 1, β -catenin, actin cytoskeleton F-actin, and contractile protein phospho myosin light chain 2. Expression of RPE fate determinants OTX2 and MITF, and formation of the RPE layer are severely affected in the temporal domain of the proximal optic cup. EdU incorporation is significantly downregulated. In addition, mitotic retinal progenitor cells mislocalize deeper, basal regions, likely contributing to decreased proliferation. We propose that morphogenesis of the ventral optic cup requires Cdc42 function for coordinated optic cup expansion and establishment of subretinal space, tissue tension, and differentiation of the ventral RPE layer. [ABSTRACT FROM AUTHOR]

Extensive research has supported the positive effects of music on exercise performance and enjoyment. However, the extent literature does not fully examine the effect of music presentation timing on exercise experience. Therefore, this experimental study tests the effects of music presentation timing on perceived exertion, attention, and emotional state during aerobic exercise. Researchers randomly assigned 43 participants to either a control or one of two experimental groups. In the first experimental group, participants listened to music throughout the entire exercise while participants in the second experimental group began listening to music when they reached or exceed RPE 11. Participants completed a modified Balke and Ware exercise test while reporting their HR, RPE, and attention every minute. Results indicated a significant time point by music group interaction on RPE, with no-music resulting in significantly higher RPEs than music-throughout or delayed-music at exercise completion, but not before. Similarly, a time point by music group interaction indicated that participants' attention in the no-music group was more associative than participants in the music-throughout or delayed-music groups at exercise completion. These changes did not have a significant effect on affective response. These results replicated previous research on music during exercise but did not find evidence for further dissociation and reduction of RPE with delayed-music stimuli. [ABSTRACT FROM AUTHOR]

Purpose: To simplify the electro-oculography (EOG) method and integrate it into the full-field electroretinogram (ffERG) protocol for screening purposes. Methods: 20 control subjects and 5 patients with Best vitelliform macular dystrophy (BVMD) underwent EOG recording according to both the standard protocol and screening EOG protocol that was integrated as part of ffERG testing. Mean values of light peak-to-dark trough ratio (LP:DT ratio) were compared between both protocols using the Student's t-test, sensitivity and specificity for the detection of RPE dysfunction were evaluated with ROC analysis and a survey on the difficulty of each protocol was completed by each subject. Results: With the standard EOG mean LP:DT ratio was 2.67 ± 0.61 in controls and 1.12 ± 0.16 in BVMD patients (p < 0.001). With the screening protocol mean LP:DT ratio was 1.98 ± 0.33 in controls and 1.02 ± 0.14 in BVMD (p < 0.001). A comparison of LP:DT ratios showed significant difference between the standard and the screening protocol (p < 0.01 in controls; p = 0.02 in BVMD), however both protocols showed 100% sensitivity and 100% specificity for detection of BVMD. Patients stated that participation in the screening protocol was easier and less uncomfortable. Conclusions: Screening EOG performed as part of ffERG gives comparable results to standard EOG, examination is patient-friendly, time saving and can be used as a preliminary test for the assessment of RPE function. [ABSTRACT FROM AUTHOR]

This study examined the effects of distractions on ratings of perceived exertion (RPE) and affective responses during acute high intensity cycling exercises. Eighteen young males (age: 22.2 ± 1.7 years) visited the laboratory on four sessions. Participants performed three experimental trials following an incremental maximal test. During the three trials, participants performed cycling exercises at 70% VO2max for 20 min under three conditions: control, active distraction, and involuntary distraction. The participants rated their overall and peripheral RPE at 5-min intervals during the 20-min cycling period. Participants’ affective responses were assessed before and after cycling including positive engagement (PE), negative affect (N-affect), and tranquility. There were no significant differences in RPEs among the three conditions. For affective responses, a significant main effect of condition was seen only for N-affect. This study suggested that active and involuntary distractions do not influence perceived exertion when participants perform 20-min vigorous-intensity exercises. One possible reason for the result is that an inadequate method was used as the active distraction. Further research is required to examine the appropriate methods that promote distraction from bodily sensations during high-intensity exercise.

The purpose of this study was to compare average rate of oxygen consumption (VO2), slow component of oxygen consumption (VO2 drift), heart rate (HR) and rating of perceived exertion (RPE) while wearing compression pants vs. a control garment during long-distance running. Methods: Nine injury-free and recreationally active participants (32 ± 11 years) were recruited for this study. Participants ran in full-leg compression pants (COMP) and a loose-fitting control garment (CON). Participants ran in each condition for 40 min at a preferred submaximal speed. The rate of oxygen consumption (VO2) was measured continuously via a metabolic cart throughout each condition. Both HR and RPE were recorded every 5 min during each condition. Oxygen consumption was averaged across the entirety of the steady state during the 40 min conditions for analysis. Additionally, the average from the first five minutes of the steady state was subtracted from the average of the last five minutes to assess VO2. A paired t-test was used to assess for differences for both variables. Both HR and RPE were each compared between conditions using 2 (garment) × 8 (time) repeated measure ANOVAs (α = 0.05). Results: There were no differences between VO2 or VO2 drift while running with full-leg compression pants vs. the control garment (p > 0.05). Neither RPE nor HR were influenced by the garments (p > 0.05) or time (p > 0.05) during each condition. Conclusion: Wearing compression pants did not result in reduced VO2, VO2 drift, HR or RPE during a long-distance run. Although measured performance variables were not aided using compression pants, there were no negative effects to the use of compression pants.

Age-related macular degeneration (AMD) is a major cause of blindness that affects people over 60. While aging is the prominent factor in AMD, studies have reported a higher prevalence of AMD in women compared to age-matched men. Higher levels of the innate immune response's effector proteins complement factor B and factor I were also found in females compared to males in intermediate AMD. However, the mechanisms underlying these differences remain elusive. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and metabolic pathways. Previously, we showed that Pgc-1α repression and high-fat diet induce drastic AMD-like phenotypes in mice. Our recent data revealed that Pgc-1α repression alone can also induce retinal pigment epithelium (RPE) and retinal dysfunction in mice, and its inhibition in vitro results in lipid droplet accumulation in human RPE. Whether sex is a contributing factor in these phenotypes remains to be elucidated. Using electroretinography, we demonstrate that sex could influence RPE function during aging independent of Pgc-1α in wild-type (WT) mice. We further show that Pgc-1α repression exacerbates RPE and retinal dysfunction in females compared to aged-match male mice. Gene expression analyses revealed that Pgc-1α differentially regulates genes related to antioxidant enzymes and mitochondrial dynamics in males and females. RPE flat mounts immunolabeled with TOMM20 and DRP1 indicated a sex-dependent role for Pgc-1α in regulating mitochondrial fission. Analyses of mitochondrial network morphology suggested sex-dependent effects of Pgc-1α repression on mitochondrial dynamics. Together, our study demonstrates that inhibition of Pgc-1α induces a sex-dependent decline in RPE and retinal function in mice. These observations on the sex-dependent regulation of RPE and retinal function could offer novel insights into targeted therapeutic approaches for age-related RPE and retinal degeneration. [ABSTRACT FROM AUTHOR]

The retina is composed of neuronal layers that include several types of interneurons and photoreceptor cells, and separate underlying retinal pigment epithelium (RPE), Bruch's membrane, and choroid. Different regions of the human retina include the fovea, macula, and periphery, which have unique physiological functions and anatomical features. These regions are also unique in their protein expression, and corresponding cellular and molecular responses to physiological and pathophysiological stimuli. Skeie and Mahajan analyzed regional protein expression in the human choroid–RPE complex. Mitogen-Activated Protein Kinase (MAPK) signaling pathways have been implicated in responses to stimuli such as oxidative stress and inflammation, which are critical factors in retina diseases including age-related macular degeneration. We, therefore, analyzed the Skeie and Mahajan, 2014, dataset for regional differences in the expression of MAPK-related proteins and discussed the potential implications in retinal diseases presenting with regional signs and symptoms. Regional protein expression data from the Skeie and Mahajan, 2014, study were analyzed for members of signaling networks involving MAPK and MAPK-related proteins, categorized by specific MAPK cascades, such as p38, ERK1/2, and JNK1/2, both upstream or downstream of the respective MAPK and MAPK-related proteins. We were able to identify 207 MAPK and MAPK-related proteins, 187 of which belonging to specific MAPK cascades. A total of 31 of these had been identified in the retina with two proteins, DLG2 and FLG downstream, and the other 29 upstream, of MAPK proteins. Our findings provide evidence for potential molecular substrates of retina region-specific disease manifestation and potential new targets for therapeutics development. [ABSTRACT FROM AUTHOR]

The increasing use of contact lenses, artificial tears, and anti-vascular endothelial growth factor (anti-VEGF) drug injections for age-related macular degeneration has heightened the likelihood of eye exposure to microplastic particles. Extensive research has established that microplastic particles can induce oxidative stress on the ocular surface, resulting in damage. However, the impact of these particles on the retina remains unclear. Therefore, this study investigated whether microplastics/nanoplastics (MPs/NPs) cause retinal damage. In vitro human retinal pigment epithelial (RPE) cells were exposed to polystyrene MPs and NPs for 48 h. Assessment of cell viability using WST-8; evaluation of TNF-α and IL-1β expression; observation of cell morphology and particle invasion via TEM; measurement of ROS levels using the DCFDA reagent; and western blot analysis of SOD2, FIS1, Drp1, and LC3B expression were conducted. In vivo experiments involved intravitreal injection of MPs/NPs in rats, followed by retinal H&E staining 24 h later and evaluation of TNF-α and IL-1β expression. Results indicated that exposure to MPs did not significantly alter RPE cell viability, whereas exposure to NPs led to a noticeable decrease. TEM images revealed NPs' penetration into cells, causing increased oxidative stress (SOD2), mitochondrial fission (FIS1, Drp1), and mitochondrial autophagy (LC3B). In vivo experiments demonstrated an increase in inflammatory cells in retinal tissues exposed to NPs, along with elevated levels of TNF-α and IL-1β. Conclusively, both MPs and NPs impact the retina, with NPs displaying greater toxicity. NPs significantly elevate ROS levels in the retina and induce mitochondrial fission and mitophagy in RPE cells compared to MPs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare average rate of oxygen consumption (VO2), slow component of oxygen consumption (VO2 drift), heart rate (HR) and rating of perceived exertion (RPE) while wearing compression pants vs. a control garment during long-distance running. Methods: Nine injury-free and recreationally active participants (32 ± 11 years) were recruited for this study. Participants ran in full-leg compression pants (COMP) and a loose-fitting control garment (CON). Participants ran in each condition for 40 min at a preferred submaximal speed. The rate of oxygen consumption (VO2) was measured continuously via a metabolic cart throughout each condition. Both HR and RPE were recorded every 5 min during each condition. Oxygen consumption was averaged across the entirety of the steady state during the 40 min conditions for analysis. Additionally, the average from the first five minutes of the steady state was subtracted from the average of the last five minutes to assess VO2. A paired t-test was used to assess for differences for both variables. Both HR and RPE were each compared between conditions using 2 (garment) × 8 (time) repeated measure ANOVAs (α = 0.05). Results: There were no differences between VO2 or VO2 drift while running with full-leg compression pants vs. the control garment (p > 0.05). Neither RPE nor HR were influenced by the garments (p > 0.05) or time (p > 0.05) during each condition. Conclusion: Wearing compression pants did not result in reduced VO2, VO2 drift, HR or RPE during a long-distance run. Although measured performance variables were not aided using compression pants, there were no negative effects to the use of compression pants. [ABSTRACT FROM AUTHOR]

Inherited retinal degenerations (IRDs) are a group of genetic disorders characterized by the progressive degeneration of retinal cells, leading to irreversible vision loss. SLC4A7 has emerged as a candidate gene associated with IRDs, yet its mechanisms remain largely unknown. This study aims to investigate the role of slc4a7 in retinal development and its associated molecular pathogenesis in zebrafish. Morpholino oligonucleotide knockdown, CRISPR/Cas9 genome editing, quantitative RT-PCR, eye morphometric measurements, immunofluorescent staining, TUNEL assays, visual motor responses, optokinetic responses, rescue experiments, and bulk RNA sequencing were used to assess the impact of slc4a7 deficiency on retinal development. Our results demonstrated that the knockdown of slc4a7 resulted in a dose-dependent reduction in eye axial length, ocular area, and eye-to-body-length ratio. The fluorescence observations showed a significant decrease in immunofluorescence signals from photoreceptors and in mCherry fluorescence from RPE in slc4a7-silenced morphants. TUNEL staining uncovered the extensive apoptosis of retinal cells induced by slc4a7 knockdown. Visual behaviors were significantly impaired in the slc4a7-deficient larvae. GO and KEGG pathway analyses reveal that differentially expressed genes are predominantly linked to aspects of vision, ion channels, and phototransduction. This study demonstrates that the loss of slc4a7 in larvae led to profound visual impairments, providing additional insights into the genetic mechanisms predisposing individuals to IRDs caused by SLC4A7 deficiency. [ABSTRACT FROM AUTHOR]

Mitochondrial malfunction, excessive production of reactive oxygen species (ROS), deficient autophagy/mitophagy, and chronic inflammation are hallmarks of age-related macular degeneration (AMD). Metformin has been shown to activate mitophagy, alleviate inflammation, and lower the odds of developing AMD. Here, we explored the ability of metformin to activate mitophagy and alleviate inflammation in retinal pigment epithelium (RPE) cells. Human ARPE-19 cells were pre-treated with metformin for 1 h prior to exposure to antimycin A (10 µM), which induced mitochondrial damage. Cell viability, ROS production, and inflammatory cytokine production were measured, while autophagy/mitophagy proteins were studied using Western blotting and immunocytochemistry. Metformin pre-treatment reduced the levels of proinflammatory cytokines IL-6 and IL-8 to 42% and 65% compared to ARPE-19 cells exposed to antimycin A alone. Metformin reduced the accumulation of the autophagy substrate SQSTM1/p62 (43.9%) and the levels of LC3 I and II (51.6% and 48.6%, respectively) after antimycin A exposure. Metformin also increased the colocalization of LC3 with TOM20 1.5-fold, suggesting active mitophagy. Antimycin A exposure increased the production of mitochondrial ROS (226%), which was reduced by the metformin pre-treatment (84.5%). Collectively, metformin showed anti-inflammatory and antioxidative potential with mitophagy induction in human RPE cells suffering from mitochondrial damage. [ABSTRACT FROM AUTHOR]

The human retinal pigment epithelium (RPE) cell line ARPE‐19 is widely used as an alternative to primary RPE despite losing many features of primary RPE. We aimed to determine whether a combination of RPE‐specific laminin (LN) and nicotinamide (NAM) could improve ARPE‐19 redifferentiation to resemble mature RPE and improve the assessment of RPE‐specific gene therapy strategies. ARPE‐19 cells were propagated on tissue culture plastic supplemented with NAM and human recombinant LN521‐coating. RPE maturation was performed by immunocytochemistry and gene expression by qPCR. Viral transduction experiments with adeno‐associated virus (AAV)1 or AAV2, carrying a VMD2‐driven GFP, were assessed at 2‐ and 4‐weeks post‐plating in the different culturing conditions with a low multiplicity of infection. The combination of LN521 coating with NAM supplementation promoted cytoskeletal and tight junction protein reorganization. The expression of maturation markers bestrophin‐1 and RPE 65 was promoted concomitantly with a reduction of several epithelial‐mesenchymal transition markers, such as TNF‐α, TGF‐β, CDH2, and vimentin. Redifferentiated ARPE‐19 transduced at low multiplicity of infection of both AAV1‐ and AAV2‐VMD2‐GFP. Expression of GFP was detected at 2 weeks and increased at 4 weeks post‐plating. AAV1 exhibited a greater expression efficacy compared to AAV2 in maturated ARPE‐19 cells already after 2 weeks with increased efficiency after 4 weeks. Our study demonstrates an improved maturation protocol for ARPE‐19 cells in vitro, mimicking an in vivo phenotype with the expression of signature genes and improved morphology. Viral‐mediated RPE‐specific gene expression demonstrates that the combination cultures mimic in vivo AAV tropism essential to test new gene therapies for RPE‐centered diseases. [ABSTRACT FROM AUTHOR]

Aims: The objective of the study was to evaluate the relationship between perceived effort and external load markers in the opening match evaluated in sequential matches within a youth soccer international tournament. Methods: Data were obtained from a total of 6 games of the FIFA® under-17 World Cup 2019 and were analyzed in each period and the full match time (entire match). Physical activity profiles were obtained using GPS units. The match activities were divided into the following categories: total load (TL), total distance covered (TDC), number of accelerations (Acc) and decelerations (Dec), distance covered at high-speed (HSR), and distance covered sprinting (Sprint). The rating of perceived exertion (RPE) was obtained after every match. Results: The TL observed in the first period and the entire match was higher compared to the average of the other matches. However, the RPE in the first match was lower when compared to the average of the other matches. Consequently, TL/RPE ratio was higher in the first match compared to the average for the other matches. The TDC, the HSR and the Sprint were higher in the first half and the entire match in the first match compared to the average of the following matches. Conclusions: The data found in the present study indicate that the first match may present higher mental and psychological stress relative to the physical strain compared to the ongoing matches during the tournament and may be an important information for coaches during short-term international tournaments. [ABSTRACT FROM AUTHOR]

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This study aims to determine the effect of using massage gun media on RPE (Rated Perceived Exertion) in soccer players. The method used is an experimental approach with a one-group pretest-posttest model design. The research instrument used is RPE. The population of this study consisted of 30 athletes from Persib Bandung Academy who were around sixteen years old and attended intensive training four times a week. Using a purposive sampling approach, 18 athletes were selected as research subjects. To determine the RPE scale, subjects underwent high-intensity training using the Yo-Yo Intermittent Recovery Test. After the exercise, a 15-minute massage was performed using a massage gun, and then RPE was measured again. The results of data analysis showed that the massage method using a massage gun had a significant impact on reducing RPE, with a value of p=0.000. This indicates that the use of massage guns can significantly reduce the fatigue level of athletes after intensive training. In conclusion, a massage gun effectively reduces fatigue as measured by RPE. Nevertheless, improving the quality of research is still needed by increasing the number of participants and developing a more structured training program both in time and day. [ABSTRACT FROM AUTHOR]

Monitoring training load, recovery, and wellness in maturation ages is even more relevant than in adulthood, especially during congested schedules. The objective of this study was to quantify and describe the differences in external and internal load, recovery, and perceived wellness in elite under-16 female players during a period of three competitions in seven days based on their participation during matches. An observational design was used to quantify the external load (total distance, high-speed distance, and PlayerLoad) and internal load (differential sRPE), as well as the recovery and wellness of 18 international under-16 players during a development tournament. The external load pattern of the starting players was undulating, with matches showing the highest internal load values compared to training sessions and non-starters. Non-starter players (whether training or matches) showed similar external load and differential sRPE values throughout the tournament (p > 0.05). Starting players experienced higher internal load than non-starters during matches (p < 0.037), without differences between training sessions (p > 0.05). No changes were seen in wellness or recovery (all p-values > 0.05), except for non-starters in Session 3 compared to Session 7 (p = 0.024). Starting players had more weekly total minutes (p = 0.018), differential sRPE (breath: p = 0.002; leg: p = 0.002; cognitive: p = 0.003), total distance (p = 0.003), and PlayerLoad (p = 0.008) than non-starters. Our results indicate differing load patterns between starters and non-starters, which do not affect wellness and recovery differently. Starters accumulate more weekly total load. Coaches can use these findings to guide decisions and load compensations in high competition contexts for young female soccer players. [ABSTRACT FROM AUTHOR]

Endurance athletes often aim to improve their aerobic metabolism. The aim of this pilot study was to examine if malic acid and L-citrulline supplementation can improve aerobic metabolism and lactate elimination. Nine young (23.9 ± 1.9 years) recreational male athletes participated in this study. Following a standardised breakfast and a body composition analysis (InBody720), 6000 mg of citrulline and 3000 mg of malic acid or a placebo of 300 mL of water were consumed on three separate days in a cross-over design using a double-blind method. Sixty minutes after the supplementation, participants completed a ramp bicycle spiroergometer protocol (35 W/3 min) until reaching a respiratory exchange ratio (RER) of 1.1, followed by a 9 min active recovery. Cadence, heart rate (HR), rate of perceived exertion (RPE), respiratory parameters and lactate levels were registered. The RPExHR value was calculated to accurately characterise exhaustion. During the exercise protocol, citrulline supplementation induced significantly lower RER values at 70-105-140 W compared to malic acid and the placebo, respectively. There was no difference in lactate levels neither during rest nor at RER 1.1. RPExHR rate values were significantly lower after malic acid supplementation compared to placebo at 175 and 210 W. Power at RER 1.1 was higher after malic acid (+4 W) and citrulline (+5 W) supplementation. Although the supplementation failed to decrease lactate levels, lower RER and RPE values may indicate a performance-enhancing benefit. [ABSTRACT FROM AUTHOR]

During tissue regeneration, proliferation, dedifferentiation and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina through retinal pigment epithelium (RPE) reprogramming when treated with fibroblast factor 2 (FGF2). Using transcriptome profiling, we uncovered extensive regulation of gene sets pertaining to proliferation, neurogenesis and glycolysis throughout RPE-to-neural retina reprogramming. By manipulating cell media composition, we determined that glucose, glutamine or pyruvate are individually sufficient to support RPE reprogramming, identifying glycolysis as a requisite. Conversely, the activation of pyruvate dehydrogenase by inhibition of pyruvate dehydrogenase kinases, induces epithelial-to-mesenchymal transition, while simultaneously blocking the activation of neural retina fate. We also identified that epithelial-to-mesenchymal transition fate is partially driven by an oxidative environment. Our findings provide evidence that metabolism controls RPE cell fate decisions and provide insights into the metabolic state of RPE cells, which are prone to fate changes in regeneration and pathologies, such as proliferative vitreoretinopathy. [ABSTRACT FROM AUTHOR]

Perceived exertion (RPE, RPEdur) and wellness scores (Hooper) are common methods to assess the training load and readiness in football. However, in professional football, there is a lack of data concerning the application of these tools in microcycles of different durations. Therefore, the purpose of this study was to explore the correlations between (a) RPE, RPEdur, and weekly external load (EXLD) and (b) Hooper and EXLD within microcycles of different durations. Independent of the microcycle's length, RPE and RPEdur correlated with the EXLD. In MIC5, RPE and RPEdur correlated with the EXLD, except for accelerations > 3 m/s2 (ACh) and distance > 25.5 km/h (SPvh). In MIC6, RPE and RPEdur correlated with the EXLD, except Ach (with RPE). In MIC7 and MIC9, RPE and RPEdur correlated with the EXLD, except RPE with ACh. For Hooper variables, independent of the microcycle duration, SRN and FTG had more correlations in comparison to SLP; the same finding was observed in MIC7 and MIC9, but SRN and SLP in MIC5 and MIC6, respectively, had no correlations. Multiple regression analysis showed that for RPE, the main predictors are total distance (TD), metabolic power distance > 50 w/kg (PWvh), and ACh, which can explain 31% of the variance, but for RPEdur, 58% can be explained by DUR, TD, and PWvh. For SLP, the predictors FTG and SRN can explain a very small percentile of the variance (1%, 4%, and 6%, respectively). The main findings were the multiple correlations between RPE, RPEdur, Hooper, and microcycles of different durations; most of them were found for long durations. This tendency is similar to that described in the literature for microcycles of the same duration. (a) EXLD has a stronger correlation with RPEdur than with RPE, and (b) FTG and SRN are the best predictors of the EXLD during the upcoming training session. It is recommended that fitness coaches use these tools to assess and forecast the training load; thus, they will be able to prepare more effective sessions during microcycles of different durations. [ABSTRACT FROM AUTHOR]

Introduction: Esports or competitive video gaming is a rapidly growing sector and an integral part of today's (youth) culture. Esports athletes are exposed to a variety of burdens, that can potentially impact an athlete's health and performance. Therefore, it is important that esports athletes are aware of (physical) burden and exertion associated with esports. For this purpose, a study was conducted to evaluate the influence of competitive video gaming on the perceived physical exertion and the perceived physical state (PEPS). Methods: Thirty-two healthy male esports athletes participated in two competitive video gaming sessions lasting 90-120 min, interrupted by a 10-minute passive sitting break. Repeated measures of perceived physical exertion (Borg Categorial Ratio-10 scale) and perceived physical state were recorded before, during, and after each video game session. Repeated measures ANOVA and Friedman's test were used for statistical analysis. Results: The results showed a significant difference in all dimensions of the PEPS (p < 0.05) as well as in Borg scale (p< 0.001). Post-hoc tests revealed significant increases in Borg scale between baseline measurements (T0: 1.0 ± 1.0) and after the first competitive video gaming session (T1: 2.4 ± 1.3, p < 0.001), as well as after the second competitive video gaming session (T3: 3.0 ± 1.7, p < 0.001). Furthermore, there was a significant reduction in perceived exertion between the measurement time after the first competitive video gaming session (T1) and the break (T2: 1.3 ± 1.2, p < 0.001). The PEPS dimensions activation, trained, and mobility showed similar significant changes in post-hoc analysis. Discussion: The results indicate that the perceived physical burden significantly increases during esports participation. As the duration of competitive video gaming extends, the perceived physical state decreases and perceived physical exertion increases. A passive break between two video game sessions can at least partially restore physical exertion and physical state. However, this break neither returns the scores to their baseline levels nor prevents a further decline in scores during the second video game session. Over time and with a lack of observation, this could result in health and performance limitations. [ABSTRACT FROM AUTHOR]

Virtual reality and technology-driven 'exergaming' have grown in tandem to expand the possibilities of exercise. However, few studies have investigated these aspects together in the context of treadmill walking. This study examined the effects of immersive virtual reality (IVR) on heart rate (HR) and ratings of perceived exertion (RPE) while walking on a treadmill at three different speeds, only one of which was disclosed to participants. Using a single-blinded, randomized control trial with a crossover research design, sixteen college-aged adults (eight females, mean age of 20.5 ± 1.2 years) were randomly assigned a testing order for six trials of treadmill walking. Three 10 min trials were conducted with IVR and three were conducted without on two separate days; a 3 min break was given in between trials. Borg RPE scores were assessed after each trial, while HR was monitored throughout. The IVR trials produced lower mean RPE scores in comparison to the non-IVR group at 3.5 and 3.7 mph. The IVR trials also yielded a lower mean HR compared to the non-IVR trials at the highest speed of 3.7 mph. These findings suggest that IVR may be able to attenuate RPE scores and HR while walking on a treadmill. [ABSTRACT FROM AUTHOR]

Activity simulation protocols offer useful applications in research and practice; however, the specificity of such protocols to basketball game-play is currently lacking. Consequently, this study aimed to develop a game-specific basketball activity simulation protocol representative of typical playing durations and assess its reliability and discriminant validity. The simulation protocol was modified from an original version (i.e., Basketball Exercise Simulation Test) to incorporate regular breaks indicative of time-outs, free-throws, and substitutions. Twelve competitive male and female adult basketball players competing in the fourth or fifth Spanish basketball division underwent repeated trials of the simulation protocol (min. 4 to max. 14 days apart) for reliability analyses. In turn, 13 competitive male (fifth division), 9 competitive female (fourth division), and 13 recreational male adult basketball players completed the simulation protocol to assess discriminant validity via comparisons between sexes (competitive players) and playing levels (males). A range of physical, technical, and perceptual-physiological variables were collected during and following the simulation protocol. Several physical and heart rate variables displayed the strongest reliability (intraclass correlation coefficient [ICC] = 0.72-0.96; coefficient of variation [CV] = 1.78-6.75%), with physical decrement, technical, blood lactate concentration, and rating of perceived exertion (RPE) variables having the weakest (ICC = 0.52-0.75; CV = 10.34-30.85%). Regarding discriminant analyses between sexes, males demonstrated significantly greater physical outputs in several variables and lower RPE compared to females (p < 0.05, moderate-to-large effects). Comparisons between playing levels revealed competitive males had significantly greater physical outputs across many variables, alongside higher mean heart rate and lower RPE than recreational males (p < 0.05, moderate-to-large effects). This study presents a novel game-specific basketball activity simulation protocol replicating actual playing durations and game configurations that might be successfully applied for both training and research purposes. Reliability statistics are provided for several variables to inform end-users on potential measurement error when implementing the simulation protocol. Discriminant validity of the simulation protocol was supported for several variables, suggesting it may hold practical utility in benchmarking or selecting players. Future research on this topic is encouraged examining wider samples of male and female basketball players at different levels as well as additional forms of validity for the protocol. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) is a non‐intoxicating phytocannabinoid which has been proposed to possess anti‐inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day−1) improved performance in a 10‐min performance‐trial on a cycle ergometer. In a randomized, double‐blind and placebo‐controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10‐min performance trials on a WattBike cycle ergometer interspersed with a 3‐week supplementation period. Supplementation involved either 150 mg day−1 oral CBD or 150 mg day−1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6–20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two‐way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10‐min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad‐spectrum CBD supplement did not improve performance via any change in RPE during a 10‐min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad‐spectrum CBD supplements could be performance‐enhancing in this exercise modality. Highlights: 3 weeks supplementation of 150 mg/day broad‐spectrum cannabidiol (CBD) does not influence perceived exertion during a 10‐min aerobic performance trial.3 weeks supplementation of 150 mg/day broad CBD does not improve physical performance in a 10‐min aerobic performance trialAthletes should continue abstinence of "Off‐the‐shelf" CBD supplements to avoid anti‐doping rule violations from The World Anti‐Doping Agency. [ABSTRACT FROM AUTHOR]

The implications of aerobic exercise on functional work capacity of Human Immunodeficiency Virus (HIV) positive clients on antiretroviral therapy (ART) in Uganda have been established. ART and the efforts to scale it up have significantly improved the value of life and life's hope of among PLHIV. Despite the presence of ART HIV disease is still seen in wards and a significant loss of life due to AIDS. This study provides useful information to the Ministry of Health of Uganda on the implications of aerobic exercises on functional work capacity as a clinical outcome to HIV positive clients in Uganda. This helps in refining the existing information on aerobic exercises and their relevancy in management of HIV positive clients. An experimental study was conducted among HIV positive clients who had been on treatment for at least 12 months prior to the study. Volunteers were randomly assigned to a control group (Group 1), where no treatment was administered, and an experimental group (Group 2), where a twelve-week moderate intensity aerobic exercise was administered. Assessment of functional work capacity was done as a pre-test and post-test for both groups. The results showed that aerobic exercises significantly improved both heart rate and VO2max with p-values of <0.001 indicating a significant improvement of VO2max from 25.13 to 34.19ml/kg/min while the control group improved by 3.73ml/kg/min. Aerobic exercise can, therefore, improve the quality of life; reduce the cost of management, mobility and mortality rates in HIV positive clients on ART in Uganda. [ABSTRACT FROM AUTHOR]

This scoping review aimed to systematically explore the breadth and extent of the literature regarding the relationship between contextual factors (CFs) and training load (TL) in adolescent soccer players. Further aims included comprehending potential underlying mechanisms and identifying knowledge gaps. CFs were defined as factors not part of the main training process, such as the coach–athlete relationship and educational responsibilities. PubMed, EBSCO APA PsycINFO, Web of Science, ProQuest Dissertations & Theses A&I, and SportRxiv were searched. Studies involving adolescent soccer players that investigated the CF–TL relationship and measured TL indicators were deemed eligible. Seventeen studies were included, reflecting the limited number of articles published regarding the CF–TL relationship. CFs were mostly related to match-play (N = 13) and phase of the season (N = 7). Moreover, these factors appeared to affect TL. CF related to players' personal environment (N = 3) were underrepresented in the reviewed studies. Overall, the CF–TL relationship appears to be rarely scrutinized. A likely cause for this lack of research is the segregation of the physiological and psychological research domains, where the CF–TL relationship is often speculated upon but not measured. Therefore, a holistic approach is warranted which also investigates the effect of personal environment, such as stressful life stress events, on TL. [ABSTRACT FROM AUTHOR]

Congenital ocular malformations originate from defective morphogenesis during early eye development and cause 25% of childhood blindness. Formation of the eye is a multi-step, dynamic process; it involves evagination of the optic vesicle, followed by distal and ventral invagination, leading to the formation of a two-layered optic cup with a transient optic fissure. These tissue folding events require extensive changes in cell shape and tissue growth mediated by cytoskeleton mechanics and intercellular adhesion. We hypothesized that the Rho GTPase Cdc42 may be an essential, convergent effector downstream of key regulatory factors required for ocular morphogenesis. CDC42 controls actin remodeling, apicobasal polarity, and junction assembly. Here we identify a novel essential function for Cdc42 during eye morphogenesis in mouse; in Cdc42 mutant eyes expansion of the ventral optic cup is arrested, resulting in microphthalmia and a wide coloboma. Our analyses show that Cdc42 is required for expression of the polarity effector proteins PRKCZ and PARD6, intercellular junction protein tight junction protein 1, β-catenin, actin cytoskeleton F-actin, and contractile protein phospho myosin light chain 2. Expression of RPE fate determinants OTX2 and MITF, and formation of the RPE layer are severely affected in the temporal domain of the proximal optic cup. EdU incorporation is significantly downregulated. In addition, mitotic retinal progenitor cells mislocalize deeper, basal regions, likely contributing to decreased proliferation. We propose that morphogenesis of the ventral optic cup requires Cdc42 function for coordinated optic cup expansion and establishment of subretinal space, tissue tension, and differentiation of the ventral RPE layer.

Microglia exhibit both maladaptive and adaptive roles in the pathogenesis of neurodegenerative diseases and have emerged as a cellular target for central nervous system (CNS) disorders, including those affecting the retina. Replacing maladaptive microglia, such as those impacted by aging or over-activation, with exogenous microglia that can enable adaptive functions has been proposed as a potential therapeutic strategy for neurodegenerative diseases. To investigate microglia replacement as an approach for retinal diseases, we first employed a protocol to efficiently generate human-induced pluripotent stem cell (hiPSC)-derived microglia in quantities sufficient for in vivo transplantation. These cells demonstrated expression of microglia-enriched genes and showed typical microglial functions such as LPS-induced responses and phagocytosis. We then performed xenotransplantation of these hiPSC-derived microglia into the subretinal space of adult mice whose endogenous retinal microglia have been pharmacologically depleted. Long-term analysis post-transplantation demonstrated that transplanted hiPSC-derived microglia successfully integrated into the neuroretina as ramified cells, occupying positions previously filled by the endogenous microglia and expressed microglia homeostatic markers such as P2ry12 and Tmem119. Furthermore, these cells were found juxtaposed alongside residual endogenous murine microglia for up to 8 months in the retina, indicating their ability to establish a stable homeostatic state in vivo. Following retinal pigment epithelial cell injury, transplanted microglia demonstrated responses typical of endogenous microglia, including migration, proliferation, and phagocytosis. Our findings indicate the feasibility of microglial transplantation and integration in the retina and suggest that modulating microglia through replacement may be a therapeutic strategy for treating neurodegenerative retinal diseases.

Transplanting microglia derived from human stem cells into mice reveals new possibilities for treating neurodegenerative eye diseases.

Age-related macular degeneration (AMD) is a common retinal pathology characterized by degeneration of macula’s retinal pigment epithelium (RPE) and photoreceptors, visual impairment, or loss. Compared to wet AMD, dry AMD is more common, but lacks cures; therefore, identification of new potential therapeutic targets and treatments is urgent. Increased oxidative stress and declining antioxidant, detoxifying systems contribute to the pathophysiologic mechanisms underlying AMD. The present work shows that the Embryonic Lethal Abnormal Vision-Like 1/Human antigen R (ELAVL1/HuR) and the Vascular Endothelial Growth Factor (VEGF) protein levels are higher in the RPE of both dry and wet AMD patients compared to healthy subjects. Moreover, increased HuR protein levels are detected in the retina, and especially in the RPE layer, of a dry AMD model, the nuclear factor erythroid 2-related factor 2 (Nrf2) / peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) double knock-out mouse. The crosstalk among Nrf2, HuR and VEGF has been also studied in ARPE-19 cells in basal and stressful conditions related to the AMD context (i.e., oxidative stress, autophagy impairment, Nrf2 deficit), offering new evidence of the mutual influence between Nrf2 and HuR, of the dependence of VEGF expression and secretion by these two factors, and of the increased susceptibility of cells to stressful conditions in Nrf2- or HuR-impaired contexts. Overall, this study shows evidence of the interplay among Nrf2, HuR and VEGF, essential factors for RPE homeostasis, and represents an additional piece in the understanding of the complex pathophysiologic mechanisms underlying AMD.

Objectives: Mutations in Tissue Inhibitor of Metalloproteinases 3 (TIMP3) cause Sorsby's Fundus Dystrophy (SFD), a dominantly inherited, rare form of macular degeneration that results in vision loss. TIMP3 is synthesized primarily by retinal pigment epithelial (RPE) cells, which constitute the outer blood-retinal barrier. One major function of RPE is the synthesis and transport of vital nutrients, such as glucose, to the retina. Recently, metabolic dysfunction in RPE cells has emerged as an important contributing factor in retinal degenerations. We set out to determine if RPE metabolic dysfunction was contributing to SFD pathogenesis. Methods: Quantitative proteomics was conducted on RPE of mice expressing the S179C variant of TIMP3, known to be causative of SFD in humans. Proteins found to be differentially expressed (P

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment.STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.

The photoreceptor outer segment (OS) is the phototransductive organelle in the vertebrate retina. OS tips are regularly ingested and degraded by the adjacent retinal pigment epithelium (RPE), offsetting the addition of new disk membrane at the base of the OS. This catabolic role of the RPE is essential for photoreceptor health, with defects in ingestion or degradation underlying different forms of retinal degeneration and blindness. Although proteins required for OS tip ingestion have been identified, spatiotemporal analysis of the ingestion process in live RPE cells is lacking; hence, the literature reflects no common understanding of the cellular mechanisms that affect ingestion. We imaged live RPE cells from mice (both sexes) to elucidate the ingestion events in real time. Our imaging revealed roles for f-actin dynamics and specific dynamic localizations of two BAR (Bin-Amphiphysin-Rvs) proteins, FBP17 and AMPH1-BAR, in shaping the RPE apical membrane as it surrounds the OS tip. Completion of ingestion was observed to occur by scission of the OS tip from the remainder of the OS, with a transient concentration of f-actin forming around the site of imminent scission. Actin dynamics were also required for regulating the size of the ingested OS tip, and the time course of the overall ingestion process. The size of the ingested tip is consistent with the term phagocytosis. However, phagocytosis usually refers to engulfment of an entire particle or cell, whereas our observations of OS tip scission indicate a process that is more specifically described as trogocytosis, in which one cell nibbles another cell.SIGNIFICANCE STATEMENT The ingestion of the photoreceptor outer segment (OS) tips by the retinal pigment epithelium (RPE) is a dynamic cellular process that has fascinated scientists for 60 years. Yet its molecular mechanisms had not been addressed in living cells. We developed a live-cell imaging approach to investigate OS tip ingestion, and focused on the dynamic participation of actin filaments and membrane-shaping BAR proteins. We observed scission of OS tips for the first time, and were able to monitor local changes in protein concentration preceding, during, and following scission. Our approach revealed that actin filaments were concentrated at the site of OS scission and were required for regulating the size of the ingested OS tip and the time course of the ingestion process.

Abstract Background Physical inactivity is a growing risk factor worldwide, therefore getting people into sports is necessary. When prescribing physical activity, it is essential to recommend the correct training intensities. Cardiopulmonary exercise testing (CPX) enables precise determination of individuals’ training intensities but is unavailable for a broad population. Therefore, the Borg scale allows individuals to assess perceived exertion and set their intensity easily and cost-efficiently. In order to transfer CPX to rating of perceived exertion (RPE), previous studies investigated RPE on specific physiological anchors, e.g. blood lactate (bLa) concentrations, but representativeness for a broad population is questionable. Some contradictory findings regarding individual factors influencing RPE occur, whereas univariable analysis has been performed so far. Moreover, a multivariable understanding of individual factors influencing RPE is missing. This study aims to determine RPE values at the individual anaerobic threshold (LT2) and defined bLa concentrations in a large cohort and to evaluate individual factors influencing RPE with multivariable analysis. Methods CPX with bicycle or treadmill ergometer of 6311 participants were analyzed in this cross-sectional study. RPE values at bLa concentrations 2 mmol/l, 3 mmol/l, 4 mmol/l, and LT2 (first rise in bLa over baseline + 1.5 mmol/l) were estimated by spline interpolation. Multivariable cumulative ordinal regression models were performed to assess the influence of sex, age, type of ergometry, VO2max, and duration of exercise testing on RPE. Results Median values [interquartile range (IQR)] of the total population were RPE 13 [11; 14] at 2 mmol/l, RPE 15 [13; 16] at 3 mmol/l, RPE 16 [15; 17] at 4 mmol/l, and RPE 15 [14; 16] at LT2. Main influence of individual factors on RPE were seen especially at 2 mmol/l: male sex (odds ratio (OR) [95%-CI]: 0.65 [0.587; 0.719]), treadmill ergometry (OR 0.754 [0.641; 0.886]), number of stages (OR 1.345 [1.300; 1.394]), age (OR 1.015 [1.012; 1.018]), and VO2max (OR 1.023 [1.015; 1.030]). Number of stages was the only identified influencing factor on RPE at all lactate concentrations/LT2 (3 mmol/l: OR 1.290 [1.244; 1.336]; 4 mmol/l: OR 1.229 [1.187; 1.274]; LT2: OR 1.155 [1.115; 1.197]). Conclusion Our results suggest RPE ≤ 11 for light intensity, RPE 12–14 for moderate intensity, and RPE 15–17 for vigorous intensity, which slightly differs from the current American College of Sports Medicine (ACSM) recommendations. Additionally, we propose an RPE of 15 delineating heavy and severe intensity domain. Age, sex, type of ergometry, duration of exercise, and cardiopulmonary fitness should be considered when recommending individualized intensities with RPE, primarily at lower intensities. Therefore, this study can be used as a new guideline for prescribing individual RPE values in the clinical practice, predominantly for endurance type exercise.

Abstract Background Monitoring of training load is done to improve physical performance and minimize the incidence of injuries. The study examined the correlation between accumulated training load parameters based on periods with maturity (i.e., maturity offset and peak height velocity -PHV- and wellness variables -e.g., stress and sleep quality-). The second aim was to analyze the multi-linear regression between the above indicators. Methods Twenty elite young U14 soccer players (M = 13.26 ± 0.52 years, 95% CI [13.02, 13.51]) were evaluated over 26 weeks (early, mid, and end-season) to obtain stress, sleep quality, and measures of workload in the season (accumulated acute workload [AW], accumulated chronic workload [CW], accumulated acute: chronic workload ratio [ACWLR], accumulated training monotony [TM], accumulated training strain [TS]). Results The analysis revealed a moderate, statistically significant negative correlation between sleep quality and training monotony (r = -0.461, p 0.05). In the multi-linear regression analysis, maturity, PHV, sleep, and stress collectively accounted for variances of 17% in AW, 17.1% in CW, 11% in ACWLR, 21.3% in TM, and 22.6% in TS. However, individual regression coefficients for these predictors were not statistically significant (p > 0.05), indicating limited predictive power. Conclusion The study highlights the impact of sleep quality on training monotony, underscoring the importance of managing training load to mitigate the risks of overtraining. The non-significant regression coefficients suggest the complexity of predicting training outcomes based on the assessed variables. These insights emphasize the need for a holistic approach in training load management and athlete wellness monitoring.

BACKGROUND: Exon-skipping is a powerful genetic tool, especially when delivering genes using an AAV-mediated full-length gene supplementation strategy is difficult owing to large length of genes. Here, we used engineered human induced pluripotent stem cells and artificial intelligence to evaluate clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9-based exon-skipping vectors targeting genes of the retinal pigment epithelium (RPE). The model system was choroideremia; this is an X-linked inherited retinal disease caused by mutation of the CHM gene. METHODS: We explored whether artificial intelligence detected differentiation of human OTX2, PAX6 and MITF (hOPM) cells, in which OTX2, PAX6 and MITF expression was induced by doxycycline treatment, into RPE. Plasmid encoding CHM exon-skipping modules targeting the splice donor sites of exons 6 were constructed. A clonal hOPM cell line with a frameshift mutation in exon 6 was generated and differentiated into RPE. CHM exon 6-skipping was induced, and the effects of skipping on phagocytic activity, cell death and prenylation of Rab small GTPase (RAB) were evaluated using flow cytometry, an in vitro prenylation assay and western blotting. RESULTS: Artificial intelligence-based evaluation of RPE differentiation was successful. Retinal pigment epithelium cells with a frameshift mutation in exon 6 showed increased cell death, reduced phagocytic activity and increased cytosolic unprenylated RABs only when oxidative stress was in play. The latter two phenotypes were partially rescued by exon 6-skipping of CHM. CONCLUSIONS: CHM exon 6-skipping contributed to RPE phagocytosis probably by increasing RAB38 prenylation under oxidative stress.

Although AMD is a complex disease, oxidative stress is a crucial contributor to its development, especially in view of the higher oxygen demand of the retina. Paraoxonase 2 (PON2) is a ubiquitously and constitutively expressed antioxidant protein that is found intracellularly associated with mitochondrial membranes and modulates mitochondrial ROS production and function. The contribution of PON2 to AMD has not been studied to date. In this study, we examined the role of PON2 in AMD utilizing both in vitro and in vivo models of AMD with emphasis on mitochondrial function. Mitochondrial localization and regulation of PON2 following oxidative stress were determined in human primary cultured retinal pigment epithelium (hRPE) cells. PON2 was knocked down in RPE cells using siRNA and mitochondrial bioenergetics were measured. To investigate the function of PON2 in the retina, WT and PON2-deficient mice were administered NaIO3 (20 mg/kg) intravenously; fundus imaging, optical coherence tomography (OCT), electroretinography (ERG) were conducted; and retinal thickness and cell death were measured and quantified. In hRPE, mitochondrial localization of PON2 increased markedly with stress. Moreover, a time-dependent regulation of PON2 was observed following oxidative stress, with an initial significant increase in expression followed by a significant decrease. Mitochondrial bioenergetic parameters (basal respiration, ATP production, spare respiratory capacity, and maximal respiration) showed a significant decrease with oxidative stress, which was further exacerbated in the absence of PON2. NaIO3 treatment caused significant retinal degeneration, retinal thinning, and reduced rod and cone function in PON2-deficient mice when compared to WT mice. The apoptotic cells and active caspase 3 significantly increased in PON2-deficient mice treated with NaIO3, when compared to WT mice. Our investigation demonstrates that deficiency of PON2 results in RPE mitochondrial dysfunction and a decline in retinal function. These findings imply that PON2 may have a beneficial role in retinal pathophysiology and is worthy of further investigation.

Background: Physical inactivity is a growing risk factor worldwide, therefore getting people into sports is necessary. When prescribing physical activity, it is essential to recommend the correct training intensities. Cardiopulmonary exercise testing (CPX) enables precise determination of individuals' training intensities but is unavailable for a broad population. Therefore, the Borg scale allows individuals to assess perceived exertion and set their intensity easily and cost-efficiently. In order to transfer CPX to rating of perceived exertion (RPE), previous studies investigated RPE on specific physiological anchors, e.g. blood lactate (bLa) concentrations, but representativeness for a broad population is questionable. Some contradictory findings regarding individual factors influencing RPE occur, whereas univariable analysis has been performed so far. Moreover, a multivariable understanding of individual factors influencing RPE is missing. This study aims to determine RPE values at the individual anaerobic threshold (LT2) and defined bLa concentrations in a large cohort and to evaluate individual factors influencing RPE with multivariable analysis. Methods: CPX with bicycle or treadmill ergometer of 6311 participants were analyzed in this cross-sectional study. RPE values at bLa concentrations 2 mmol/l, 3 mmol/l, 4 mmol/l, and LT2 (first rise in bLa over baseline + 1.5 mmol/l) were estimated by spline interpolation. Multivariable cumulative ordinal regression models were performed to assess the influence of sex, age, type of ergometry, VO2max, and duration of exercise testing on RPE. Results: Median values [interquartile range (IQR)] of the total population were RPE 13 [11; 14] at 2 mmol/l, RPE 15 [13; 16] at 3 mmol/l, RPE 16 [15; 17] at 4 mmol/l, and RPE 15 [14; 16] at LT2. Main influence of individual factors on RPE were seen especially at 2 mmol/l: male sex (odds ratio (OR) [95%-CI]: 0.65 [0.587; 0.719]), treadmill ergometry (OR 0.754 [0.641; 0.886]), number of stages (OR 1.345 [1.300; 1.394]), age (OR 1.015 [1.012; 1.018]), and VO2max (OR 1.023 [1.015; 1.030]). Number of stages was the only identified influencing factor on RPE at all lactate concentrations/LT2 (3 mmol/l: OR 1.290 [1.244; 1.336]; 4 mmol/l: OR 1.229 [1.187; 1.274]; LT2: OR 1.155 [1.115; 1.197]). Conclusion: Our results suggest RPE ≤ 11 for light intensity, RPE 12–14 for moderate intensity, and RPE 15–17 for vigorous intensity, which slightly differs from the current American College of Sports Medicine (ACSM) recommendations. Additionally, we propose an RPE of 15 delineating heavy and severe intensity domain. Age, sex, type of ergometry, duration of exercise, and cardiopulmonary fitness should be considered when recommending individualized intensities with RPE, primarily at lower intensities. Therefore, this study can be used as a new guideline for prescribing individual RPE values in the clinical practice, predominantly for endurance type exercise. Key Points: To promote physical activity, the Borg Scale (6–20) is an easy and accessible tool for the recommendation of training intensities. Our results suggest RPE ≤ 11 for light intensity, RPE 12–14 for moderate intensity, and RPE 15–17 for vigorous intensity, and RPE 15 delineating heavy and severe intensity domain. In clinical routine, physicians and therapists should consider age, sex, type of ergometry, duration of exercise, and cardiopulmonary fitness as factors influencing RPE, especially with lower intensities. [ABSTRACT FROM AUTHOR]

Purpose: TRIMP and sRPE are both representative indicators of training load(TL), and the correlation between two has been widely demonstrated across various sports. The aim of this study was to investigate the reliability of sRPE-TRIMP correlation across different intensities/duration of training in cross-country skiing, and whether sRPE can serve as an validity supplement to TRIMP data in cases of lost heart rate data. Method: 10 athletes were used as the experimental objects. The intensity, duration and RPE of 273 different types of training sessions were collected, and statistical methods were used for data analysis. Results: 1. There was a significant correlation between sRPE and TRIMP (r = 0.68, p < 0.05), but the correlation differs among the LIT, MIT and HIT groups (r = 0.70, 0.46, r = 0.31, p < 0.05) 2. sRPE-TRIMP correlation among three different time duration in the LIT group (0-60 min, 60-120 min and 120-180 min), are all highly significant (r = 0.70, 0.67, 0.69, p < 0.05) and the LRsRPE-TRIMP of 3 duration have no significant differences (chow test, p > 0.05). 3. The difference in actual training duration between samples was the main reason for the difference in the application effect of sRPE, because the actual training duration ratio of LIT was 89.7 ± 16.4%; MIT, 98.5 ± 6.2%; and HIT, 94.4 ± 13.5%. Conclusion: 1. The linear relationship between sRPE and TRIMP (LRsRPETRIMP) is more significant in LIT compared to that in MIT and HIT. 2. Variations in the duration of LIT sessions do not affect the consistency of the relationship between sRPE and TRIMP. 3. Discrepancies between actual and planned training durations directly impact the significance of the LRsRPE-TRIMP. [ABSTRACT FROM AUTHOR]