Physical inactivity links depressive symptoms and cognitive functioning among individuals with Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder caused by disruption of dopamine-producing cells. PD is associated with motor symptoms and nonmotor symptoms including depression and cognitive impairment. Past research suggests an association between depression and cognitive impairment in PD. Physical activity may have a therapeutic effect on both depression and cognitive impairment. The present study investigates if physical activity mediates the association between depressive symptoms and cognition in a longitudinal sample of individuals with PD. METHOD: Participants include individuals newly diagnosed with PD (N = 487) enrolled in the Parkinson's Progression Marker Initiative (PPMI). Participants completed an array of neuropsychological tests over the course of 5 years, as well as questionnaires of depression and physical activity. Between-person and within-person effects of depression and cognition mediated through physical activity were analyzed using structural equation modeling. RESULTS: A significant direct effect demonstrated depression was associated with worse global cognitive functioning. Furthermore, there was a significant indirect within-person effect, indicating that physical activity fully mediated the association between depression and cognition. Individuals who became more depressed over time became less physically active and subsequently experienced cognitive decline over the 5-year period. CONCLUSIONS: Findings have implications for prognostic detection and/or the role of physical activity interventions to buffer effects of depression on cognitive impairment among individuals diagnosed with PD. Physical interventions may potentially be implemented among depressed persons to preserve cognitive functioning. Worsened depression early during PD may be a risk factor for inactivity and cognitive diminishment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

History of Ultrasound in Medicine from its birth to date (2022), on occasion of the 50 Years Anniversary of EFSUMB. A publication of the European Federation of Societies for Ultrasound In Medicine and Biology (EFSUMB), designed to record the historical development of medical ultrasound.

The history of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) is closely related to the general history of ultrasound. In the presented paper the physical background and history of technologies including A-mode, Time motion or M-mode, 2D Imaging (B-mode) are summarized. In addition, ultrasound tissue characterization, Doppler ultrasound, 3D and 4D ultrasound, intracavitary and endoscopic ultrasound, interventional ultrasound, ultrasonic therapy, contrast enhanced ultrasound (CEUS) and key developments in echocardiography are discussed.

Motivation in Team Exergames: Testing the Köhler Discrepancy Effect with a Software-Generated Partner During Plank Exercise.

Objective: The Köhler effect is a social-psychological group motivation gain phenomenon that has been successfully adapted to video-based exercise games (exergames) using human partners. This research then shifted to using software-generated partners (SGPs), providing greater flexibility and adaptability to manipulate the game environment to be most motivating for the user. However, recent SGP-based experiments have demonstrated a diminished motivation gain effect. Extending previous work with human-human partners, this experiment varied the perceived exercise ability of the SGP as a potential motivation gain effect moderator on the participant's exercise persistence. Materials and Methods: Male and female college students (n = 176; mean age, 21.5 years) completed two series of abdominal plank exercises using an exergame developed specifically for a previous Köhler study. Participants completed the exercises individually and, after a rest, were randomly assigned to complete the same exercises again alone or with one of three SGPs: low ability discrepancy partner (LP), moderate ability discrepancy partner (MP), and high ability discrepancy partner (HP). Results: A 2 (sex) × 4 (condition) analysis of covariance main effect for Condition was not significant after controlling for Block 1 times (P = 0.093). However, contrast estimates of plank persistence times between the MP condition and individual no-partner control were significant, P = 0.014, 95% confidence interval [4.34-37.68]. There were no other significant condition persistence differences. Conclusions: A moderate discrepancy between the participant and the superior nonhuman partner is more motivating in a conjunctive task paradigm than exercising alone or with an SGP that is low or high in ability discrepancy.

P-Curve Analysis of the Köhler Motivation Gain Effect in Exercise Settings: A Demonstration of a Novel Technique to Estimate Evidential Value Across Multiple Studies.

BACKGROUND: Practitioners and researchers may not always be able to adequately evaluate the evidential value of findings from a series of independent studies. This is partially due to the possibility of inflated effect size estimates for these findings as a result of researcher manipulation or selective reporting of analyses (i.e., p-hacking). In light of the possible overestimation of effect sizes in the literature, the p-curve analysis has been proposed as a worthwhile tool that may help identify bias across a series of studies focused on a single effect. The p-curve analysis provides a measure of the evidential value in the published literature and might highlight p-hacking practices. PURPOSE: Therefore, the purpose of this paper is to introduce the mechanics of the p-curve analysis to individuals researching phenomena in the psychosocial aspects of behavior and provide a substantive example of a p-curve analysis using findings from a series of studies examining a group dynamic motivation gain paradigm. METHODS: We performed a p-curve analysis on a sample of 13 studies that examined the Köhler motivation gain effect in exercise settings as a means to instruct readers how to conduct such an analysis on their own. RESULTS: The p-curve for studies examining the Köhler effect demonstrated evidential value and that this motivation effect is likely not a byproduct of p-hacking. The p-curve analysis is explained, as well as potential limitations of the analysis, interpretation of the results, and other uses where a p-curve analysis could be implemented.

Can Simulated Partners Boost Workout Effort in Long-Term Exercise?

Feltz, DL, Hill, CR, Samendinger, S, Myers, ND, Pivarnik, JM, Winn, B, Ede, A, and Ploutz-Snyder, L. Can simulated partners boost workout effort in long-term exercise? J Strength Cond Res 34(9): 2434-2442, 2020-We tested whether exercising with a stronger simulated (i.e., software-generated) partner leads to greater work effort compared to exercising alone, to help those seeking to maintain or improve fitness levels with long-term high-intensity training, but who find it necessary or practical to exercise in social isolation. Forty-one middle-aged adults, who participated in at least 30 minutes of vigorous exercise 3x·wk, trained on a cycle ergometer 6 days per week for 24 weeks in an alternating regimen of moderate-intensity 30-minute continuous and 3 types of high-intensity interval sessions (8 × 30-second sprints, 6 × 2-minute ladders, and 4 × 4-minute intervals). They were assigned either no partner (control), an always superior partner, or a not always superior partner. Participants varied cycle power output to increase or decrease session intensity during the repeated moderate-intensity sessions (30-minute continuous) and 1 of the 3 high-intensity sessions (4 × 4-minute intervals). Changes in intensity were used as a measure of effort motivation over time. Nested multilevel models of effort trajectory were developed and alpha was set to 0.05. For continuous and interval sessions, effort trajectory was positive and significant for those with an always superior partner, but not significantly different from control. Within interval sessions, those with an always superior partner significantly increased effort in the fourth interval compared to control (p = 0.02). Exercising with an always superior partner leads to greater work efforts during the hardest interval training compared to exercising alone.

Group dynamics motivation to increase exercise intensity with a virtual partner.

BACKGROUND: The effect of the Köhler group dynamics paradigm (i.e., working together with a more capable partner where one's performance is indispensable to the team outcome) has been shown to increase motivation to exercise longer at a strength task in partnered exercise video games (exergames) using a software-generated partner (SGP). However, the effect on exercise intensity with an SGP has not been investigated. The purpose of this study was to examine the motivation to maintain or increase exercise intensity among healthy, physically active middle-aged adults using an SGP in an aerobic exergame. METHODS: Participants (n = 85, mean age = 44.9 years) exercised with an SGP in a 6-day cycle ergometer protocol, randomly assigned to either (a) no partner control, (b) superior SGP who was not a teammate, or (c) superior SGP as a teammate (team score was dependent on the inferior member). The protocol alternated between 30-min continuous and 4-min interval high-intensity session days, during which participants could change cycle power output (watts) from target intensity to alter distance and speed. RESULTS: Mean change in watts from a targeted intensity (75% and 90% maximum heart rate) was the primary dependent variable reflecting motivational effort. Increases in performance over baseline were demonstrated without significant differences between conditions. Self-efficacy and enjoyment were significantly related to effort in the more intense interval sessions. CONCLUSION: Under these conditions, no Köhler effect was observed. Exercise performance during the higher-intensity interval format is more closely related to enjoyment and self-efficacy beliefs compared to the continuous sessions.

Why Residuals Are Important in the Self-Efficacy-Performance Relationship Analysis: A Study Across 12 Cycling Sessions.

Background: The positive role of self-efficacy in directing a wide range of health-related interventions has been well documented, including those targeting an increase in physical activity. However, rarely do researchers control the influence of past performance and past self-efficacy perception ratings when exploring the interaction of self-efficacy and performance, allowing for a refined understanding of this relationship and the unique contribution of each factor. Methods: A residualized past performance, residualized self-efficacy hierarchical regression model was used to examine the effect of prior past performance and pre-exercise self-efficacy on performance with a health-related task (12 aerobic exercise cycling sessions). Results: The previous day's residualized performance was a significant predictor of performance, as was same-day residualized self-efficacy (P < .001). However, residualized self-efficacy became a stronger predictor over time. Conclusions: While maintaining a consistent level of moderate-vigorous physical activity over 12 exercise sessions, participants increased their ratings of task self-efficacy, explaining an increasing portion of the variance in the self-efficacy-performance relationship days 9 to 12.

Within-person relationship between self-efficacy and performance across trials: effect of task objective and task type.

BACKGROUND: Self-efficacy has been shown to be a consistent, positive predictor of between-persons performance in sport. However, there have been equivocal results regarding the influence of self-efficacy on a person's performance over time. This study investigated the influence of self-efficacy on motor skill performance across trials with respect to two different task objectives and task types. METHODS: Participants (N.=84) performed 4 blocks of 10 trials of a dart throwing (closed skill) and a hitting (open skill) task under 2 different task objectives: competitive and goal-striving. For the goal-striving condition, success was defined as reaching a predetermined performance level. The competitive condition involved competing against an opponent. RESULTS: Hierarchical linear modeling was used to examine the influence of past performance and self-efficacy on the within-person performance across multiple trials. Previous performance was negatively related with subsequent performance on all conditions. Self-efficacy was not a significant predictor of performance on any of the conditions. CONCLUSIONS: While task objective and task type did not moderate the efficacy-performance relationship in the current study, it is important to consider the role of other moderators in future research.

Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma.

INTRODUCTION: Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology. METHODS: A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤ 18 years receiving cyclophosphamide (250 mg/m(2)), were used to characterise a population pharmacokinetic model. Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed. RESULTS: A two-compartment model provided the best fit of the population analysis. The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 (1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m(2), respectively; mean ± standard deviation from empirical Bayes estimates; P < 0.001). The presence of at least one CYP2B6*6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 (1.54 ± 0.11 L/h/m(2) versus 2.20 ± 0.31 L/h/m(2), P = 0.033) and dose 5 (3.12 ± 0.17 L/h/m(2) versus 4.35 ± 0.37 L/h/m(2), P = 0.0028), as compared to homozygous wild-type patients. No pharmacokinetic parameters investigated were shown to have a significant influence on progression free survival. CONCLUSION: The results do not support previous findings of a link between cyclophosphamide pharmacokinetics or metabolism and disease recurrence in childhood B-cell NHL. While CYP2B6 genotype was shown to influence pharmacokinetics, there was no clear impact on clinical outcome.

Characterisation of the clinical pharmacokinetics of actinomycin D and the influence of ABCB1 pharmacogenetic variation on actinomycin D disposition in children with cancer.

BACKGROUND AND OBJECTIVE: Despite its important role in cancer treatment, there is currently very limited available information concerning the clinical pharmacology of actinomycin D (Act D). The study was designed to characterise Act D pharmacokinetics and investigate the impact of pharmacogenetic variation on Act D disposition in children with cancer. METHODS: A total of 650 plasma samples collected over an 8 year period from 117 patients ≤21 years receiving Act D (0.4-1.6 mg/m(2)) were used to characterise a population pharmacokinetic model. Polymorphisms in ABCB1 were analysed in 140 patients. RESULTS: A 3-compartment model provided a good fit to the data. Median values for Act D clearance and volume of distribution in the central compartment (V 1) obtained from the model were 5.3 L/h and 1.9 L (13.9 L/h/70 kg and 7.5 L/70 kg), respectively. There was substantial inter-subject variation in all pharmacokinetic parameters (coefficients of variation 53-81 % for non-normalised values). Body weight was a major determinant of Act D clearance, such that dose capping at 2 mg in larger children at a protocol dose of 1.5 mg/m(2) resulted in significantly lower area under the plasma concentration-time curves (mean AUC values: 9.3 versus 12.8 mg·min/L; P < 0.0001). No significant relationships were found between ABCB1 genetic variants and Act D pharmacokinetic parameters, nor between CL, V 1 or dose and incidence of grade 3 or 4 toxicity. CONCLUSION: We have defined the pharmacokinetics of Act D in a paediatric patient population, providing robust estimates of key pharmacokinetic parameters. Pharmacokinetic data bring into question the current clinical practice of dose capping at 2 mg in larger patients. Pharmacogenetic variation in candidate drug transporter genes identified from preclinical studies does not significantly impact on Act D exposure in a clinical setting.

Characterisation of the roles of ABCB1, ABCC1, ABCC2 and ABCG2 in the transport and pharmacokinetics of actinomycin D in vitro and in vivo.

Actinomycin D plays a key role in the successful treatment of Wilms tumour. However, associated liver toxicities remain a drawback to potentially curative treatment. We have used MDCKII cells over-expressing ABCB1, ABCC1, ABCC2 and ABCG2, alongside knockout mouse models to characterise actinomycin D transport and its impact on pharmacokinetics. Growth inhibition, intracellular accumulation and cellular efflux assays were utilised. A 59-fold difference in GI(50) was observed between MDCKII-WT and MDCKII-ABCB1 cells (12.7 nM vs. 745 nM, p<0.0001). Reduced sensitivity was also seen in MDCKII-ABCC1 and ABCC2 cells (GI(50) 25.7 and 40.4 nM respectively, p<0.0001). Lower intracellular accumulation of actinomycin D was observed in MDCKII-ABCB1 cells as compared to MDCKII-WT (0.98 nM vs. 0.1 nM, p<0.0001), which was reversed upon ABCB1 inhibition. Lower accumulation was also seen in MDCKII-ABCC1 and ABCC2 cells. Actinomycin D efflux over 2 h was most pronounced in MDCKII-ABCB1 cells, with 5.5-fold lower intracellular levels compared to WT. In vivo studies showed that actinomycin D plasma concentrations were significantly higher in Abcb1a/1b(-/-) as compared to WT mice following administration of 0.5 mg/kg actinomycin D (AUC(0-6 h) 242 vs. 152 µg/Lh respectively). While comparable actinomycin D concentrations were observed in the kidneys and livers of Abcb1a/1b(-/-) and Abcc2(-/-) mice, concentrations in the brain were significantly higher at 6h following drug administration in Abcb1a/1b(-/-) mice compared to WT. Results confirm actinomycin D as a substrate for ABCB1, ABCC1 and ABCC2, and indicate that Abcb1a/1b and Abcc2 can influence the in vivo disposition of actinomycin D. These data have implications for ongoing clinical pharmacology trials involving children treated with actinomycin D.

PATTERN CLADISTICS OR EVOLUTIONARY CLADISTICS?

We can also put it like this. The introduction of an auxiliary hypothesis should always be regarded as an attempt to construct a new system; and this new system should then always be judged on the issue of whether it would, if adopted, constitute a real advance in our knowledge of the world-K. R. Popper.