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Background: Although the health benefits of physical activity are well established, it remains challenging for people to adopt a more active lifestyle. Mobile health (mHealth) interventions can be effective tools to promote physical activity and reduce sedentary behavior. Promising results have been obtained by using gamification techniques as behavior change strategies, especially when they were tailored toward an individual's preferences and goals; yet, it remains unclear how goals could be personalized to effectively promote health behaviors., Objective: In this study, we aim to evaluate the impact of personalized goal setting in the context of gamified mHealth interventions. We hypothesize that interventions suggesting health goals that are tailored based on end users' (self-reported) current and desired capabilities will be more engaging than interventions with generic goals., Methods: The study was designed as a 2-arm randomized intervention trial. Participants were recruited among staff members of 7 governmental organizations. They participated in an 8-week digital health promotion campaign that was especially designed to promote walks, bike rides, and sports sessions. Using an mHealth app, participants could track their performance on two social leaderboards: a leaderboard displaying the individual scores of participants and a leaderboard displaying the average scores per organizational department. The mHealth app also provided a news feed that showed when other participants had scored points. Points could be collected by performing any of the 6 assigned tasks (eg, walk for at least 2000 m). The level of complexity of 3 of these 6 tasks was updated every 2 weeks by changing either the suggested task intensity or the suggested frequency of the task. The 2 intervention arms-with participants randomly assigned-consisted of a personalized treatment that tailored the complexity parameters based on participants' self-reported capabilities and goals and a control treatment where the complexity parameters were set generically based on national guidelines. Measures were collected from the mHealth app as well as from intake and posttest surveys and analyzed using hierarchical linear models., Results: The results indicated that engagement with the program inevitably dropped over time. However, engagement was higher for participants who had set themselves a goal in the intake survey. The impact of personalization was especially observed for frequency parameters because the personalization of sports session frequency did foster higher engagement levels, especially when participants set a goal to improve their capabilities. In addition, the personalization of suggested ride duration had a positive effect on self-perceived biking performance., Conclusions: Personalization seems particularly promising for promoting the frequency of physical activity (eg, promoting the number of suggested sports sessions per week), as opposed to the intensity of the physical activity (eg, distance or duration). Replications and variations of our study setup are critical for consolidating and explaining (or refuting) these effects., Trial Registration: ClinicalTrials.gov NCT05264155; https://clinicaltrials.gov/ct2/show/NCT05264155., (©Raoul Nuijten, Pieter Van Gorp, Alireza Khanshan, Pascale Le Blanc, Pauline van den Berg, Astrid Kemperman, Monique Simons. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 31.03.2022.)

In general, individuals with lower socioeconomic status (SES) are less physically active and adhere to poorer diets than higher SES individuals. To promote healthier lifestyles in lower SES populations, we hosted a digital health promotion program among male vocational students at a school in The Netherlands. In a pilot study, we evaluated whether this target audience could be engaged with an mHealth app using lottery-based incentives that trigger feelings of anticipated regret. Especially, we studied the social and interpersonal aspects of regret lotteries in a within-subject experimental design. In this design, subjects either participated in a social variant (i.e., with students competing against their peers for a chance at a regret lottery), or an individual variant (i.e., with subjects solely individually engaged in a lottery). Additionally, we studied the impact of different payout schedules in a between-subject experimental design. In this design, participants were assigned to either a short-term, low-value payout schedule, or a long-term, high-value payout schedule. From a population of 72 male students, only half voluntarily participated in our 10-week program. From interviews, we learned that the main reason for neglecting the program was not related to the lottery-based incentives, nor to the prizes that were awarded. Instead, non-enrolled subjects did not join the program, because their peers were not joining. Paradoxically, it was suggested that students withheld their active participation until a larger portion of the sample was actively participating. From the subjects that enrolled in the program ( N = 36, males, between 15 and 25 years of age), we found that a large proportion stopped interacting with the program over time (e.g., after roughly 4 weeks). Our results also indicated that students performed significantly more health-related activities when assigned to the social regret lottery, as opposed to the individual variant. This result was supported by interview responses from active participants: They mainly participated to compete against their peers, and not so much for the prizes. Hence, from this study, we obtained initial evidence on the impact of social and competitive aspects in lottery-based incentives to stimulate engagement levels in lower SES students with an mHealth app., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nuijten, Van Gorp, Hietbrink, Le Blanc, Kemperman, van den Berg and Simons.)

This study tests organizational trust as the psychosocial mechanism that explains how healthy organizational practices and team resources predict multilevel performance in organizations and teams, respectively. In our methodology, we collect data in a sample of 890 employees from 177 teams and their immediate supervisors from 31 Spanish companies. Our results from the multilevel analysis show two independent processes predicting organizational performance (return on assets, ROA) and performance ratings by immediate supervisors, operating at the organizational and team levels, respectively. We have found evidence for a theoretical and functional quasi-isomorphism. First, based on social exchange theory, we found evidence for our prediction that when organizations implement healthy practices and teams provide resources, employees trust their top managers (vertical trust) and coworkers (horizontal trust) and try to reciprocate these benefits by improving their performance. Second, (relationships among) constructs are similar at different levels of analysis, which may inform HRM officers and managers about which type of practices and resources can help to enhance trust and improve performance in organizations. The present study contributes to the scarce research on the role of trust at collective (i.e., organizational and team) levels as a psychological mechanism that explains how organizational practices and team resources are linked to organizational performance.

Background: Overall, health-related correlates of job demands and job resources are well-known. However, in today's working life, personal resources are considered to be of increasing importance. Beyond general mental ability, knowledge regarding personal resources remains limited. This is particularly so among women working in the welfare sector, a sector mainly employing women and with the work typically involving clients., Objective: This study investigated the importance of job demands, job resources, and personal resources for health-related outcomes, as well as the mitigating effects of resources, among women working within the Swedish welfare sector., Methods: Self-reports from 372 women employed within the welfare sector were analyzed using hierarchical multiple regression., Results: Overall, increasing job demands were associated with poorer health outcomes while increasing job resources and personal resources were associated with better health. Additionally, lower control aggravated the effects of quantitative job demands on health outcomes while lower feedback mitigated the effect of qualitative demands. However, personal resources had no moderating effect., Conclusions: Job resources seem more pertinent to health than personal resources, at least among women working within the welfare sector in Sweden.

Speech is a complex sensorimotor skill, and vocal learning involves both the basal ganglia and the cerebellum. These subcortical structures interact indirectly through their respective loops with thalamo-cortical and brainstem networks, and directly via subcortical pathways, but the role of their interaction during sensorimotor learning remains undetermined. While songbirds and their song-dedicated basal ganglia-thalamo-cortical circuitry offer a unique opportunity to study subcortical circuits involved in vocal learning, the cerebellar contribution to avian song learning remains unknown. We demonstrate that the cerebellum provides a strong input to the song-related basal ganglia nucleus in zebra finches. Cerebellar signals are transmitted to the basal ganglia via a disynaptic connection through the thalamus and then conveyed to their cortical target and to the premotor nucleus controlling song production. Finally, cerebellar lesions impair juvenile song learning, opening new opportunities to investigate how subcortical interactions between the cerebellum and basal ganglia contribute to sensorimotor learning., Competing Interests: LP, PL, CL, AL No competing interests declared, (© 2018, Pidoux et al.)

There is a multitude of mHealth applications that aim to solve societal health problems by stimulating specific types of physical activities via gamification. However, physical health activities cover just one of the three World Health Organization (WHO) dimensions of health. This paper introduces the novel notion of Unified Health Gamification (UHG), which covers besides physical health also social and cognitive health and well-being. Instead of rewarding activities in the three WHO dimensions using different mHealth competitions, UHG combines the scores for such activities on unified leaderboards and lets people interact in social circles beyond personal interests. This approach is promising in corporate environments since UHG can connect the employees with intrinsic motivation for physical health with those who have quite different interests. In order to evaluate this approach, we realized an app prototype and we evaluated it in two corporate pilot studies. In total, eighteen pilot users participated voluntarily for six weeks. Half of the participants were recruited from an occupational health setting and the other half from a treatment setting. Our results suggest that the UHG principles are worth more investigation: various positive health effects were found based on a validated survey. The mean mental health improved significantly at one pilot location and at the level of individual pilot participants, multiple other effects were found to be significant: among others, significant mental health improvements were found for 28% of the participants. Most participants intended to use the app beyond the pilot, especially if it would be further developed.

The multifactorial causes impacting the risk of developing sporadic forms of Alzheimer's disease (AD) remain to date poorly understood. Epidemiologic studies in humans and research in rodents have suggested that hypothyroidism could participate in the etiology of AD. Recently, we reported that adult-onset hypothyroidism in rats favors β-amyloid peptide production in the hippocampus. Here, using the same hypothyroidism model with the antithyroid molecule propythiouracyl (PTU), we further explored AD-related features, dysfunctional cell-signaling mechanisms and hippocampal-dependent learning and memory. In vivo MRI revealed a progressive decrease in cerebral volume of PTU-treated rats. In the hippocampus, hypothyroidism resulted in tau hyperphosphorylation and increases in several proinflammatory cytokines. These modifications were associated with impaired spatial memory and reduced hippocampal expression of signaling molecules important for synaptic plasticity and memory, including neurogranin, CaMKII, ERK, GSK3β, CREB, and expression of the transcription factor EGR1/Zif268. These data strengthen the idea that hypothyroidism represents an important factor influencing the risk of developing sporadic forms of AD., (Copyright © 2014 Wiley Periodicals, Inc.)

Melatonin receptor expression exhibits profound developmental changes through poorly understood mechanisms. In mammals, a current model suggests that pubertal reactivation of gonadotrophin-releasing hormone (GnRH) secretion down-regulates MT1 melatonin receptors in pituitary gonadotroph cells, via the induction of early growth response factor-1 (EGR-1). Here we have examined this model by testing the hypotheses that inhibition of Mt1 expression by GnRH occurs directly in gonadotroph cells, can be reversed in adulthood by blockade of GnRH receptors, and requires EGR-1. We first confirmed the endogenous expression of Mt1 mRNA in the αT3-1 gonadotroph cell line. Stimulation of these cells with a GnRH agonist resulted in a rapid increase of Egr-1 mRNA expression, which peaked after 30-60 minutes, and a more prolonged elevation of nuclear EGR-1 immunoreactivity. Moreover, the GnRH agonist significantly decreased Mt1 mRNA. We then treated adult male rats with the GnRH antagonist cetrorelix or saline. After 4 weeks of daily injections, cetrorelix significantly reduced serum LH concentration and testis weight, with histological analysis confirming absence of spermatogenesis. Despite the successful inhibition of GnRH signalling, pituitary Mt1 expression was unchanged. Next we studied the proximal region of the rat Mt1 promoter. Consistent with previous work, over-expression of the transcription factor PITX-1 increased Mt1-luciferase reporter activity; this effect was dependent on the presence of consensus PITX-1 promoter binding regions. Over-expression of EGR-1 inhibited PITX-1-stimulated activity, even following mutation of the consensus EGR-1 binding site. Finally, we studied Egr1-/- mice and observed no difference in pituitary Mt1 expression between Egr1-/- and wild-type litter mates. This work demonstrates that GnRH receptor activation directly down-regulates Mt1 expression in gonadotroph cells. However, pituitary Mt1 expression in adults is unaltered by blockade of GnRH signalling or absence of EGR-1. Our data therefore suggest that melatonin receptor regulation by GnRH is not reversible in adulthood and doesn't require EGR-1.

Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.

Dystrophin, the protein responsible for X-linked Duchenne muscular dystrophy (DMD), is normally expressed in both muscle and brain, which explains that its loss also leads to cognitive deficits. The utrophin protein, an autosomal homolog, is a natural candidate for dystrophin replacement in patients. Pharmacological upregulation of endogenous utrophin improves muscle physiology in dystrophin-deficient mdx mice, and represents a potential therapeutic tool that has the advantage of allowing delivery to various organs following peripheral injections. Whether this could alleviate cognitive deficits, however, has not been explored. Here, we first investigated basal expression of all utrophins and dystrophins in the brain of mdx mice and found no evidence for spontaneous compensation by utrophins. Then, we show that systemic chronic, spaced injections of arginine butyrate (AB) alleviate muscle alterations and upregulate utrophin expression in the adult brain of mdx mice. AB selectively upregulated brain utrophin Up395, while reducing expression of Up113 and Up71. This, however, was not associated with a significant improvement of behavioral functions typically affected in mdx mice, which include exploration, emotional reactivity, spatial and fear memories. We suggest that AB did not overcome behavioral and cognitive dysfunctions because the regional and cellular expression of utrophins did not coincide with dystrophin expression in untreated mice, nor did it in AB-treated mice. While treatments based on the modulation of utrophin may alleviate DMD phenotypes in certain organs and tissues that coexpress dystrophins and utrophins in the same cells, improvement of cognitive functions would likely require acting on specific dystrophin-dependent mechanisms.

The present study investigated temporal perception in a Huntington disease transgenic rat model using a temporal bisection procedure. After initial discrimination training in which animals learned to press one lever after a 2-s tone duration, and the other lever after a 8-s tone duration for food reward, the bisection procedure was implemented in which intermediate durations with no available reinforcement were interspersed with trials with the anchor durations. Bisection tests were repeated in a longitudinal design from 4 to 8 months of age. The results showed that response latencies evolved from a monotonic step-function to an inverted U-shaped function with repeated testing, a precursor of non-responding on trials with intermediate durations. We inferred that temporal sensitivity and incentive motivation combined to control the transformation of the bisection task from a two-choice task at the outset of testing to a three-choice task with repeated testing. Changes in the structure of the task and/or continued training were accompanied by improvement in temporal sensitivity. In sum, the present data highlight the possible joint roles of temporal and non-temporal factors in the temporal bisection task, and suggested that non-temporal factors may compensate for deficits in temporal processing.

Objectives: To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors., Design: Cross-sectional., Setting: Chronic Renal Insufficiency Cohort Study., Participants: Eight hundred twenty-five adults aged 55 and older with CKD., Measurements: Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean)., Results: Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59)., Conclusion: In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

Aims of the Study: This paper presents the results of a validation study of the so-called well-being of intensive care nurses (WEBIC)-questionnaire that is designed to perform a detailed job analysis of intensive care unit (ICU) nurses' jobs., Background: The WEBIC-questionnaire is based on modern sociotechnical systems theory, and distinguishes four integrated task categories: (1) operational, (2) organizing, (3) preparatory, and (4) supportive tasks. For each task, the WEBIC assesses (1) how demanding this task is, and (2) how satisfying the performance of this task is. Using the WEBIC, information is gathered about ICU nurses' qualitative workload, and typical job-related risks for ICU nurses' well-being at work can be mapped., Methods: A cross-sectional survey on work and well-being of almost 2000 ICU-nurses in 13 different European areas was conducted. Exploratory factor analyses were performed to study the validity of the factorial structure of the WEBIC-questionnaire. The construct validity of the WEBIC-questionnaire was studied by performing hierarchical multiple regression analyses of the WEBIC-factors on two types of job-related well-being, i.e. burnout and general job satisfaction., Results: Results of the exploratory factor analyses showed that the hypothesized four-factor structure of the WEBIC is confirmed by our data. Internal consistencies of the different factors varied from 0.77 to 0.91. Intensive care unit nurses' most central (operational) tasks turned out to pose the greatest demands, but also seemed to drive their satisfaction. With respect to the relationships between the four WEBIC-factors, and burnout and general job satisfaction, it was found that, especially for the satisfying tasks, significant relationships with these outcomes were found., Conclusion: The reliability and construct validity of the WEBIC-questionnaire can be considered satisfactory. Furthermore, the questionnaire provides a systematical and detailed coverage of ICU nurses' tasks. In relation to this, the questionnaire is not only useful for scientific purposes but also for practical use.

This research examined burnout (i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment) among 2 samples of Dutch teachers as a function of inequity and experienced job stress in 3 different exchange relationships (with students, colleagues, and the school). It was hypothesized that inequity would be linked to burnout through the stress resulting from this inequity. Analysis of a cross-sectional sample (N = 271) revealed that this was indeed the case. Findings were replicated longitudinally using an independent sample of 940 teachers. It is concluded that the often-reported effect of inequity on burnout can partly be interpreted in terms of elevated levels of job stress. Implications of the findings are discussed.

Two designs of an outlet stator for the Nimbus axial flow left ventricular assist device (LVAD) are analyzed at nominal operating conditions. The original stator assembly (Design 1) has significant flow separation and reversal. A second stator assembly (Design 2) replaces the original tubular outer housing with a converging-diverging throat section with the intention of locally improving the fluid dynamics. Both stator designs are analyzed using computational fluid dynamics (CFD) analysis and experimental particle imaging flow visualization (PIFV). The computational and experimental methods indicate: 1) persistent regions of flow separation in Design 1 and improved fluid dynamics in Design 2; 2) blade-toblade velocity fields that are well organized at the blade tip yet chaotic at the blade hub for both designs; and 3) a moderate decrease in pressure recovery for Design 2 as compared with Design 1. The CFD analysis provides the necessary insight to identify a subtle, localized flow acceleration responsible for the decreased hydraulic efficiency of Design 2. In addition, the curiously low thrombogenicity of Design 1 is explained by the existence of a three-dimensional unsteady vortical flow structure that enhances boundary advection.

Nimbus Inc. (Rancho Cordova, CA) and the University of Pittsburgh have completed the second year of development of a totally implanted axial flow blood pump under the National Institutes of Health Innovative Ventricular Assist System Program. The focus this year has been on completing pump hydraulic development and addressing the development of the other key system components. Having demonstrated satisfactory pump hydraulic and biocompatibility performance, pump development has focused on design features that improve pump manufacturability. A controller featuring full redundancy has been designed and is in the breadboard test phase. Initial printed circuit layout of this circuit has shown it to be appropriately sized at 5 x 6 cm to be compatible with implantation. A completely implantable system requires the use of a transcutaneous energy transformer system (TETS) and a diagnostic telemetry system. The TETS power circuitry has been redesigned incorporating an improved, more reliable operating topography. A telemetry circuit is undergoing characterization testing. Closed loop speed control algorithms are being tested in vitro and in vivo with good success. Eleven in vivo tests were conducted with durations from 1 to 195 days. Endurance pumps have passed the 6 month interval with minimal bearing wear. All aspects of the program continue to function under formal quality assurance.

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

The process of adipose differentiation uniquely endows fat cells to accrue triacylglycerols under conditions of nutrient energy surfeit and to release fatty acids during energy deprivation. The object of this investigation was to study influences on this process in perirenal preadipocytes, grown in primary culture or first subculture and derived from male Sprague-Dawley rats, 180-200 g. Supplementation of the culture medium with 1-methyl-3-isobutylxanthine, corticosterone, and insulin induced differentiation in practically all perirenal preadipocytes, as indicated morphologically and by rising glycerophosphate dehydrogenase activity. Appreciable differentiation was induced even in the absence of methylisobutylxanthine. Transforming growth factor beta (1-1000 pM), cachectin (tumour necrosis factor alpha) (1-1000 pM), and basic fibroblast growth factor (0.063-63 nM) inhibited adipose differentiation significantly, almost completely at the higher concentrations. Direct inhibition, rather than a persisting mitogenic effect of fibroblast growth factor, was confirmed using demecolcine (Colcemid). The fact that transforming growth factor beta and cachectin inhibit differentiation in preadipocytes from postpubertal rats suggests that this effect probably also occurs in vivo, thus diverting energy from adipose depots in certain neoplastic and inflammatory states. We propose that the anterior pituitary, through fibroblast growth factor(s), modulates the pool of preadipocytes and other mesenchymal cells. The mitogenic effect would be complemented by a concerted function, inhibition of adipose differentiation, resulting in the retention of a greater number of potentially replicative cells. Then, depending on the subject's nutritional and endocrine status, extrapituitary factors would regulate the specific process of differentiation.

Heart rate, stroke volume, cardiac output, its distribution and organ blood flows were measured, using the microsphere technique (15 micron in diameter microspheres), in 5, 12 and 24 months old conscious male rats. Each rat was then infused with isoproterenol (0.2 microgram/kg.min) and the measurements were repeated. It was found that resting cardiovascular values do not change within the age range studied, with the exception of the renal blood flow. After infusion of isoproterenol, the heart rate and cardiac output increased in the youngest group while only smaller increase in heart rate and no significant changes in cardiac output were found in the oldest group. Similarly, organ blood flow increased after isoproterenol in all organs studied in the 5 months group, with significance levels reached in the case of blood supply to the right and left ventricles, total heart, skin and carcass. In contrast, infusion of the same dose of isoproterenol in the 24 months old animals did not elicit any significant changes in the regional blood flow. Thus, the response to beta-adrenergic stimulation is depressed with advancing age. This finding of decreased in vivo response to beta-adrenergic stimulation may be a mechanism for the altered cardiovascular performance during stress seen in aged animals and man.