Activity of alkoxyamide-based histone deacetylase inhibitors against Plasmodium falciparum malaria parasites.

There are more than 240 million cases of malaria and 600,000 associated deaths each year, most due to infection with Plasmodium falciparum parasites. While malaria treatment options exist, new drugs with novel modes of action are needed to address malaria parasite drug resistance. Protein lysine deacetylases (termed HDACs) are important epigenetic regulatory enzymes and prospective therapeutic targets for malaria. Here we report the antiplasmodial activity of a panel of 17 hydroxamate zinc binding group HDAC inhibitors with alkoxyamide linkers and different cap groups. The two most potent compounds (4a and 4b) were found to inhibit asexual P. falciparum growth with 50% inhibition concentrations (IC50's) of 0.07 µM and 0.09 µM, respectively, and demonstrated >200-fold more selectivity for P. falciparum parasites versus human neonatal foreskin fibroblasts (NFF). In situ hyperacetylation studies demonstrated that 4a, 4b and analogs caused P. falciparum histone H4 hyperacetylation, suggesting HDAC inhibition, with structure activity relationships providing information relevant to the design of new Plasmodium-specific aliphatic chain hydroxamate HDAC inhibitors.

Thymidine Kinase-Independent Click Chemistry DNADetect Probes for DNA Proliferation Assessment in Malaria Parasites.

Metabolic chemical probes are small-molecule reagents that utilize naturally occurring biosynthetic enzymes for in situ incorporation into biomolecules of interest. These reagents can be used to label, detect, and track important biological processes within living cells including protein synthesis, protein glycosylation, and nucleic acid proliferation. A limitation of current chemical probes, which have largely focused on mammalian cells, is that they often cannot be applied to other organisms due to metabolic differences. For example, the thymidine derivative 5-ethynyl-2'-deoxyuridine (EdU) is a gold standard metabolic chemical probe for assessing DNA proliferation in mammalian cells; however, it is unsuitable for the study of malaria parasites due to Plasmodium species lacking the thymidine kinase enzyme that is essential for metabolism of EdU. Herein, we report the design and synthesis of new thymidine-based probes that sidestep the requirement for a thymidine kinase enzyme in Plasmodium. Two of these DNADetect probes exhibit robust labeling of replicating asexual intraerythrocytic Plasmodium falciparum parasites, as determined by flow cytometry and fluorescence microscopy using copper-catalyzed azide-alkyne cycloaddition to a fluorescent azide. The DNADetect chemical probes are synthetically accessible and thus can be made widely available to researchers as tools to further understand the biology of different Plasmodium species, including laboratory lines and clinical isolates.

Isolation and In Vitro and In Vivo Activity of Secondary Metabolites from Clerodendrum polycephalum Baker against Plasmodium Malaria Parasites.

Chemical investigation of the antimalarial medicinal plant Clerodendrum polycephalum led to the isolation of five new diterpenoids, including ajugarins VII-X (1-4) and teuvincenone K (5), along with four known compounds, namely, 12,16-epoxy-6,11,14,17-tetrahydroxy-17(15 → 16)-abeo-5,8,11,13,15-abietapentaen-7-one (6), methyl pheophorbide A (7), loliolide (8), and acacetin (9). The chemical structures of the new compounds were elucidated using NMR spectroscopy, mass spectrometry, circular dichroism, as well as density functional theory calculations. All compounds were evaluated for in vitro activity against Plasmodium falciparum 3D7 malaria parasites with methyl pheophorbide A (7) showing the strongest activity (IC50 4.49 µM). Subsequent in vivo testing in a Plasmodium berghei chemosuppression model showed that compound 7 significantly attenuated peripheral blood parasitemia, leading to 79% and 87% chemosuppression following oral doses at 10 and 20 mg/kg, respectively.

An exploratory analysis examining differences in physical activity and motor competence in children with and without asthma: brief report.

OBJECTIVE: The purpose of this pilot study was to examine potential differences in motor competence (MC) and physical activity (PA) between children with and without asthma. METHODS: Thirty-seven children and adolescents completed the Exercises for a Healthy Asthma Lifestyle and Enjoyment study (46% with asthma, 51% female, 11.1 ± 0.4 years, and 46% White). Motor competence was assessed using the Movement Assessment Battery for Children 2nd edition (MABC-2). PA was assessed using accelerometry. RESULTS: Children with asthma had significantly lower MC in the domain of aiming and catching (with asthma: 8.2 ± 0.4 vs. without asthma: 9.9 ± 0.5; p = 0.03) and fewer daily minutes spent in moderate-to-vigorous PA (MVPA) (with asthma: 18.0 ± 2.3 min vs. without asthma: 27.2 ± 3.6 min; p = 0.047). There were no significant group differences in manual dexterity, balance, total MABC-2 score, or total daily PA (all ps > 0.05). CONCLUSIONS: This study provides confirmatory evidence that children with asthma display lower MC and spend less time in MVPA compared to children without asthma. Because MC is a prerequisite for engaging in PA, future research should seek to determine if the differences observed in MC contribute to disparities in MVPA observed in this clinical population.

Protocol for a cluster randomized clinical trial of a mastery-climate motor skills intervention, Children's Health Activity and Motor Program (CHAMP), on self-regulation in preschoolers.

INTRODUCTION: Self-regulation (SR) is critical to healthy development in children, and intervention approaches (i.e., professional training, classroom-based curricula, parent-focused intervention) have shown to support or enhance SR. However, to our knowledge, none have tested whether changes in children's SR across an intervention relate to changes in children's health behavior and outcomes. This study, the Promoting Activity and Trajectories of Health (PATH) for Children-SR Study uses a cluster-randomized control trial to examine the immediate effects of a mastery-climate motor skills intervention on SR. Secondly, this study examines the associations between changes in SR and changes in children's health behaviors (i.e., motor competence, physical activity, and perceived competence) and outcomes (i.e., body mass index and waist circumference) (ClinicalTrials.gov Identifier, NCT03189862). METHODS AND ANALYSIS: The PATH-SR study will be a cluster-randomized clinical trial. A total of 120 children between the ages of 3.5 to 5 years of age will be randomized to a mastery-climate motor skills intervention (n = 70) or control (n = 50) condition. SR will be assessed using measures that evaluate cognitive SR (cognitive flexibility and working memory), behavioral SR (behavioral inhibition), and emotional SR (emotional regulation). Health behaviors will be assessed with motor skills, physical activity, and perceived competence (motor and physical) and health outcomes will be waist circumference and body mass index. SR, health behaviors, and health outcomes will be assessed before and after the intervention (pre-test and post-test). Given the randomization design, 70 children in the intervention group and 50 in the control group, we have 80% power to detect an effect size of 0.52, at a Type I error level of 0.05. With the data collected, we will test the intervention effect on SR with a two-sample t-test comparing the intervention group and the control group. We will further evaluate the associations between changes in SR and changes in children's health behaviors and health outcomes, using mixed effect regression models, with a random effect to account for within-subject correlations. The PATH-SR study addresses gaps in pediatric exercise science and child development research. Findings hold the potential to help shape public health and educational policies and interventions that support healthy development during the early years. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained through the Health Sciences and Behavioral Sciences Institutional Review Board, University of Michigan (HUM00133319). The PATH-SR study is funded by the National Institutes of Health Common Fund. Findings will be disseminated via print, online media, dissemination events and practitioner and/or research journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier, NCT03189862.

Structured Observations of Child Behaviors during a Mastery-Motivational Climate Motor Skill Intervention: An Exploratory Study.

This exploratory study aimed to quantify children's engagement behaviors during a mastery-motivational climate intervention. We also completed an exploratory factor analysis to elucidate if child engagement changed across intervention sessions. METHOD: 35 children (17 boys; 18 girls) completed a 10-week mastery-motivational climate motor skill intervention. Engagement was operationalized as the time children were appropriately involved in the intervention and was assessed using momentary time sampling during the motor skill practice portion of the intervention. RESULTS: Overall, children were engaged 36% of the motor skills practice time (37% for boys; 36% for girls). Children who initially had below-average skills engaged for 36% (36% for boys; 35% for girls) of the motor skills practice time, and children who were average or above-average at the start of the intervention engaged in skill practice for 39% (39% for boys; 36% for girls). Differences in engagement in skill type (e.g., locomotor vs. ball skills) and trends over time were observed. CONCLUSION: These findings support that children engage in mastery-motivation climates, but the amount of participation may be influenced by individual factors of sex and initial skill level.

Two birds in the hand: Concurrent and switching cognitive flexibility in preschoolers.

Cognitive flexibility, the ability to think of something in more than one way, has been studied in preschoolers from two different approaches. Within executive function research, most studies operationalize cognitive flexibility using sequential tasks in which children must think of a specific stimulus first in one way and then in another way (switching cognitive flexibility). In contrast, Piagetian multiplicative classification tasks also require cognitive flexibility by asking children to consider multiple dimensions of a single stimulus at the same time. Piagetian tasks are typically inductive and require abstraction skills. Although research with Piagetian tasks suggests that children are unable to consider multiple dimensions simultaneously until they reach the concrete operational stage, there is some evidence that preschoolers can coordinate two dimensions simultaneously in deductive tasks. In this study, we examined a deductive version of a matrix completion task in which preschoolers (N = 102) were asked to consider two dimensions of a given stimulus simultaneously. We show that 4- and 5-year-olds can succeed on this task and compare children's performance on the matrix completion task with their performance on a widely used switching cognitive flexibility task, the Dimensional Change Card Sort. We discuss the implications of relating the two aspects of cognitive flexibility development.

Considerations for a Social Media Physical Activity Program: Exploratory Study.

BACKGROUND: Social media may be a powerful platform to combat parents' and children's low physical activity levels. OBJECTIVE: This study surveyed parents' beliefs about physical activity in order to expand the extant literature concerning the interest in and the design of an effective and feasible social media physical activity (SMPA) program. METHODS: Primary caregivers (n=250; 215 [86%] mothers, 164 [65.6%] White) of children aged 6-12 years completed an online questionnaire. Interest was examined through responses on the questionnaire; beliefs (ie, perceptions, knowledge, and support) about physical activity were examined using Spearman correlations; and to support the SMPA program design, researchers examined a combination of multiple-choice and free-response questions. For the free-response questions, the researchers performed open coding related to perceived benefits, barriers, and motivators. RESULTS: Parent respondents (n=215, 86%) were interested in a SMPA program tailored for families. Regarding beliefs, parents exhibited a monotonic relationship between 2 questions related to perceptions of physical activity levels in their children (rs(250)=.310, P<.001), knowledge about physical activity and motor skills (rs(250)=.328, P<.001), and support of physical activity and motor skills (rs(250)=.385, P<.001). Parents perceived benefits of a SMPA program, highlighting family time and health. Barriers included time constraints, a lack of motivation, and environmental factors. CONCLUSIONS: Parents are interested in supporting healthy family behaviors using a SMPA program. An effective program should emphasize motor skill activities, be fun and family oriented, and incorporate incentives, goal setting, and advice and tips. SMPA also needs to address identified barriers, such as those regarding time and environment.

Psychological Responses to Intermittent Activities in Children With and Without Asthma.

PURPOSE: The purpose of this study was to examine the psychological responses to intermittent activities of varying intensities and types among children with and without asthma. METHODS: A total of 37 children and adolescents (51% male, aged 8-16 y, 54% nonwhite, and 54% without asthma) participated in this study. Participants completed 5 exercises in the same order: self-paced walking, resistance activities, dance video, gamified obstacle course, and step test. In-task mood was assessed using the Feeling Scale, in-task perceived exertion was assessed via the ratings of perceived exertion scale, and postactivity enjoyment was assessed using the Physical Activity Enjoyment Scale. RESULTS: There was a significant main effect of exercise type on mood (P < .001), ratings of perceived exertion (P < .001), and enjoyment (P < .002). There was not a significant main effect of asthma status on mood, ratings of perceived exertion, or enjoyment (Ps > .05). Children with asthma reported significantly lower in-task mood during the step exercise (P < .037) and reported significantly lower postactivity enjoyment after the walk and obstacle course exercises (Ps < .03). CONCLUSIONS: Regardless of differences by asthma status for in-task mood during the obstacle course and for postactivity enjoyment during the walk and step exercises, both children with and without asthma reported high in-task mood and postactivity enjoyment during all 5 exercises.

QSAR Classification Models for Prediction of Hydroxamate Histone Deacetylase Inhibitor Activity against Malaria Parasites.

Malaria, caused by Plasmodium parasites, results in >400,000 deaths annually. There is no effective vaccine, and new drugs with novel modes of action are needed because of increasing parasite resistance to current antimalarials. Histone deacetylases (HDACs) are epigenetic regulatory enzymes that catalyze post-translational protein deacetylation and are promising malaria drug targets. Here, we describe quantitative structure-activity relationship models to predict the antiplasmodial activity of hydroxamate-based HDAC inhibitors. The models incorporate P. falciparum in vitro activity data for 385 compounds containing a hydroxamic acid and were subject to internal and external validation. When used to screen 22 new hydroxamate-based HDAC inhibitors for antiplasmodial activity, model A7 (external accuracy 91%) identified three hits that were subsequently verified as having potent in vitro activity against P. falciparum parasites (IC50 = 6, 71, and 84 nM), with 8 to 51-fold selectivity for P. falciparum versus human cells.

Empathetic Concern in Emerging Adolescents: The Role of Theory of Mind and Gender Roles.

The current study examined the roles of gender, and gender-role orientation in young adolescents' empathetic concern. In addition, this study aimed to explore the contribution of Theory of Mind in participants' empathetic concern. Finally, this study examined whether gender and gender-role orientation were implicated in emerging adolescents' Theory of Mind understanding. One-hundred-fifty 11- to 12-year-olds (79 self-identified females) completed questionnaires measuring their empathetic concern, Theory of Mind, and their perceived gender-role orientation. Results showed that gender-role orientation, specifically, femininity and masculinity predicted empathetic concern above and beyond gender. In addition, the effects of cognitive and affective Theory of Mind are explored and discussed in relation to empathetic concern. Finally, neither gender nor gender-role orientation was found to contribute to participants' Theory of Mind understanding. These findings suggest that emerging adolescents' perceived gender roles, as well as their ability to consider another's beliefs, play a role in their expression of empathetic concern.

Histone deacetylase inhibitor AR-42 and achiral analogues kill malaria parasites in vitro and in mice.

Malaria is caused by infection with Plasmodium parasites and results in significant health and economic impacts. Malaria eradication is hampered by parasite resistance to current drugs and the lack of a widely effective vaccine. Compounds that target epigenetic regulatory proteins, such as histone deacetylases (HDACs), may lead to new therapeutic agents with a different mechanism of action, thereby avoiding resistance mechanisms to current antimalarial drugs. The anticancer HDAC inhibitor AR-42, as its racemate (rac-AR-42), and 36 analogues were investigated for in vitro activity against P. falciparum. Rac-AR-42 and selected compounds were assessed for cytotoxicity against human cells, histone hyperacetylation, human HDAC1 inhibition and oral activity in a murine malaria model. Rac-AR-42 was tested for ex vivo asexual and in vitro exoerythrocytic stage activity against P. berghei murine malaria parasites. Rac-AR-42 and 13 achiral analogues were potent inhibitors of asexual intraerythrocytic stage P. falciparum 3D7 growth in vitro (IC50 5-50 nM), with four of these compounds having >50-fold selectivity for P. falciparum versus human cells (selectivity index 56-118). Rac-AR-42 induced in situ hyperacetylation of P. falciparum histone H4, consistent with PfHDAC(s) inhibition. Furthermore, rac-AR-42 potently inhibited P. berghei infected erythrocyte growth ex vivo (IC50 40 nM) and P. berghei exoerythrocytic forms in hepatocytes (IC50 1 nM). Oral administration of rac-AR-42 and two achiral analogues inhibited P. berghei growth in mice, with rac-AR-42 (50 mg/kg/day single dose for four days) curing all infections. These findings demonstrate curative properties for HDAC inhibitors in the oral treatment of experimental mouse malaria.

Perceived Physical Competence Predicts Gains in Children's Locomotor but Not Ball Skills across an Intervention.

The purpose of this pre/post experimental study was to examine if children's perceived physical competence predicted changes in motor skills across an intervention. Sixty-seven children (Mage = 53.2 ± 3.7 months) participated in a 16-week, mastery-climate motor skill intervention. Perceived physical competence was assessed before the intervention using the physical competence subscale of the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children. Motor skills were assessed using the Test of Gross Motor Development-3rd Edition before and after the intervention. Results revealed that controlling for pretest skills, perceived physical competence significantly predicted posttest locomotor (p < 0.05) and total skills (p < 0.05) but did not predict posttest ball skills (p > 0.05). These results indicate that perceived physical competence may be a significant factor that predicts children's gains in locomotor or total skills, but not ball skills, across an intervention.

An Intervention-Related Comparison of Preschoolers' Scores on the TGMD-2 and TGMD-3.

This study compared preschoolers' fundamental motor skills (FMS) on the Test of Gross Motor Development 2nd and 3rd editions (TGMD-2 and TGMD-3) before (pretest) and after (posttest) a motor skill intervention. This study also compared FMS changes (TGMD raw and percentile scores for total score, and locomotor and object control/ball subscales) across the intervention when FMS were measured using the two editions. Sixty-four preschoolers (Mage = 4.4, SD = 0.44 years) completed the TGMD-2 and TGMD-3 before and after a motor skill intervention. We determined the level of agreement between assessments using intra-class correlations (ICC), Lin's Concordance Correlation Coefficient, and Bland-Altman plots. Overall, our results support an acceptable relative agreement between the TGMD-2 and TGMD-3 for raw scores, but there were variable strengths of agreement (by subscales) for percentile scores. Both assessments supported the efficacy of the intervention. This consistent demonstration of efficacy but varied strength of agreement suggests that the TGMD-2 and TGMD-3 are similar but not interchangeable.

Impact of the Epithelial Lining Fluid Milieu on Amikacin Pharmacodynamics Against Pseudomonas aeruginosa.

BACKGROUND: Even though nebulised administration of amikacin can achieve high epithelial lining fluid concentrations, this has not translated into improved patient outcomes in clinical trials. One possible reason is that the cellular and chemical composition of the epithelial lining fluid may inhibit amikacin-mediated bacterial killing. OBJECTIVE: The objective of this study was to identify whether the epithelial lining fluid components inhibit amikacin-mediated bacterial killing. METHODS: Two amikacin-susceptible (minimum inhibitory concentrations of 2 and 8 mg/L) Pseudomonas aeruginosa isolates were exposed in vitro to amikacin concentrations up to 976 mg/L in the presence of an acidic pH, mucin and/or surfactant as a means of simulating the epithelial lining fluid, the site of bacterial infection in pneumonia. Pharmacodynamic modelling was used to describe associations between amikacin concentrations, bacterial killing and emergence of resistance. RESULTS: In the presence of broth alone, there was rapid and extensive (> 6 - log10) bacterial killing, with emergence of resistance identified in amikacin concentrations < 976 mg/L. In contrast, the rate and extent of bacterial killing was reduced (≤ 5 - log10) when exposed to an acidic pH and mucin. Surfactant did not appreciably impact the bacterial killing or resistance emergence when compared with broth alone for either isolate. The combination of mucin and an acidic pH further reduced the rate of bacterial killing, with the maximal bacterial killing occurring 24 h following initial exposure compared with approximately 4-8 h for either mucin or an acidic pH alone. CONCLUSIONS: Our findings indicate that simulating the epithelial lining fluid antagonises amikacin-mediated killing of P. aeruginosa, even at the high concentrations achieved following nebulised administration.

Pharmacodynamics of once- versus twice-daily dosing of nebulized amikacin in an in vitro Hollow-Fiber Infection Model against 3 clinical isolates of Pseudomonas aeruginosa.

This study aims to compare the bacterial killing of once- versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and to determine the optimal duration of therapy. Three clinical P. aeruginosa isolates (amikacin MICs 2, 8, and 64 mg/L) were exposed to simulated epithelial lining fluid exposures of nebulized amikacin with dosing regimens of 400 mg and 800 mg once- or twice-daily up to 7-days using the in vitro hollow-fiber infection model. Quantitative cultures were performed. Simulated amikacin dosing regimens of 400 mg twice-daily and 800 mg once-daily achieved ≥2-log reduction in the bacterial burden within the first 24-hours of therapy for all isolates tested. No dosing regimen suppressed the emergence of amikacin resistance. No difference in bacterial killing or regrowth was observed between 3- and 7-days of amikacin. Amikacin doses of 800 mg once-daily for up to 3-days may be considered for future clinical trials.

Investigation of the in vitro and in vivo efficacy of peptoid-based HDAC inhibitors with dual-stage antiplasmodial activity.

Histone deacetylases (HDACs) have been identified as emerging antiplasmodial drug targets. In this work, we report on the synthesis, structure-activity relationships, metabolic stability and in vivo efficacy of new peptoid-based HDAC inhibitors with dual-stage antiplasmodial activity. A mini library of HDAC inhibitors was synthesized using a one-pot, multi-component protocol or submonomer pathways. The screening of the target compounds for their activity against asexual blood stage parasites, human cell cytotoxicity, liver stage parasites, and selected human HDAC isoforms provided important structure-activity relationship data. The most promising HDAC inhibitor from this series, compound 3n, demonstrated potent activity against drug-sensitive and drug-resistant asexual stage P. falciparum parasites and was selective for the parasite versus human cells (Pf3D7 IC50 0.016 µM; SIHepG2/Pf3D7 573; PfDd2 IC50 0.002 µM; SIHepG2/PfDd2 4580) combined with activity against P. berghei exoerythrocytic liver stages (PbEEF IC50 0.48 µM). While compound 3n displayed high stability in human (Clint 5 µL/min/mg) and mouse (Clint 6 µL/min/mg) liver microsomes, only modest oral in vivo efficacy was observed in P. berghei infected mice. Together these data provide a foundation for future work to improve the properties of these dual-stage inhibitors as drug leads for malaria.

Parents accurately perceive problematic eating behaviors but overestimate physical activity levels in preschool children.

PURPOSE: The aim of this study is to examine the associations between parents' perceptions of their child's physical activity and eating behaviors to actual physical activity, body mass index percentage (BMI%), and body fat percentage (BF%). A secondary aim is to examine additional parental determinants to child's physical activity. METHODS: Participants were preschool children (N = 114, 59 females, Mage= 4.06) from three University-sponsored centers and parents (N = 114, 107 mothers). Parents self-reported physical activity, perceptions of child's physical activity, and completed "The Child Eating Behavior Questionnaire". Children physical activity was collected with accelerometers. RESULTS: Whereas 97% of the 68 parents with children meeting physical activity guidelines accurately identified their child as active, 93% of the 14 parents with children not meeting physical activity guidelines inaccurately identified their child as active (X2(1, N = 82) = 0.58, p = 0.446)). Regarding eating behaviors, child BMI% was moderately correlated with parent's perceptions of their child's Emotional Overeating (r(74) = 0.416, p < 0.001) and Food Responsiveness (r(74) = 0.543, p < 0.001). Parent's engagement in vigorous physical activity demonstrated a positive relationship to child's physical activity (r(78) = 0.297, p = 0.008). CONCLUSION: Parents of inactive children have inaccurate perceptions of their child's physical activity. The association between children's BMI% and eating behaviors indicates parents can accurately perceive problematic eating behaviors. Parents, who accurately perceive their child's behaviors, may be in a better position to identify deficiency and seek early intervention. Additionally, parent's physical activity may have implications to children's physical activity. LEVEL OF EVIDENCE: Level V: Descriptive cross-sectional study.

The Feasibility and Challenges of Conducting Online Research to Examine Movement Behavior in Parents and Children During the COVID-19 Pandemic.

The global pandemic of COVID-19 shifted the methodology of this research project. The purpose of this perspective article is to discuss the feasibility and challenges of converting an in-person mixed methods study that examined associations among and beliefs about physical activity, motor competence, and perceived competence to an online format with parents and children during the COVID-19 pandemic. Recruitment was conducted through a University research registry, social media, and public listservs. All correspondence with participants was through email and secure platforms. Physical activity was assessed with accelerometers mailed to participants. Motor competence was assessed through participant-filmed trials of motor skills. Perceived competence was assessed with the Self-Perception Profile for Adults and Children delivered on Qualtrics. Semi- structured interviews to examine beliefs were conducted over Zoom. Approximately 200 families expressed interest in the study, 76 parent-child dyads consented and assented, and 61 parent-child dyads completed at least one component of the study. It is feasible to conduct online research that contributes to scientific knowledge and has potential advantages. However, various challenges need to be considered regarding the application of online research. These challenges included recruitment, the data collection process, and data quality. Future research needs to address these challenges by utilizing wide-reaching and diverse recruitment methods, easing participants' burden with technology, and developing motor competence and perceived competence assessments that can be administered online. The way research was conducted changed due to COVID-19 and adapting to and/or integrating online methods is both necessary and feasible, but modifications must be taken into consideration.