History of "Serve and Return" and a Synthesis of the Literature on Its Impacts on Children's Health and Development.

Parent/caregiver sensitivity and responsiveness are important for children's health and development. The "serve and return" metaphor was created to help providers and caregivers understand the importance of sensitive and responsive early caregiving. In this review, we explain the concept of "serve and return", outline historical and theoretical principles that culminated in this metaphor, highlight parent and child constructs associated with "serve and return" interactions, and synthesize literature on sensitive and responsive caregiving and children's health and developmental outcomes. Nurses and other healthcare professionals in public policy, clinical, community, education, and research roles need knowledge of "serve and return" interactions.

Research Summit V: Optimizing Transitions From Infancy to Early Adulthood in Children With Neuromotor Conditions.

PURPOSE: The purpose of this executive summary is to review the process and outcomes of the Academy of Pediatric Physical Therapy Research Summit V, "Optimizing transitions from infancy to young adulthood in children with neuromotor disabilities: biological and environmental factors to support functional independence." SUMMARY OF KEY POINTS: An interdisciplinary group of researchers, representatives from funding agencies, and individuals with neuromotor disabilities and their parents participated in an intensive 2.5-day summit to determine research priorities to optimize life transitions for children with neuromotor disabilities. Recommended priorities for research included (1) promoting self-determination and self-efficacy of individuals with neuromotor disabilities and their families, (2) best care at the right time: evidence-based best practice care, led and navigated by families seamlessly across the lifespan, (3) strengthening connections between developmental domains to enhance function and participation, and (4) optimal dosing and timing to support adaptive bone, muscle, and brain plasticity across the lifespan.

Neuro-pharmacological reinstatement of ovulation and associated neurobiology in a macaque model of functional hypothalamic amenorrhoea.

STUDY QUESTION: What is the underlying neuropathology in a cynomolgus macaque model of functional hypothalamic amenorrhoea (FHA) and can it be normalized to restore ovulation? SUMMARY ANSWER: Anovulatory monkeys exhibited increased hypothalamic norepinephrine (NE), kisspeptin and gonadotropin-releasing hormone (GnRH) in the early follicular phase, but administration of the NE reuptake inhibitor (NRI), reboxetine (REB), restored ovulation during stress and normalized NE, kisspeptin and GnRH. WHAT IS KNOWN ALREADY: Female cynomolgus macaques, like women, show individual reproductive sensitivity to modest psychosocial and metabolic stress. During stress, resilient females ovulate through two menstrual cycles whereas stress-sensitive (SS) macaques immediately cease ovulation. On Day 5 of a non-stressed menstrual cycle, resilient macaques have less NE synthesizing enzyme [dopamine ß-hydroxylase (DBH)], kisspeptin and GnRH innervation of the medial basal hypothalamus but more endogenous serotonin than SS macaques. Stress increased DBH/NE, kisspeptin and GnRH but did not alter serotonin. STUDY DESIGN, SIZE, DURATION: In a longitudinal design, 27 adult (7-13 years) female cynomolgus macaques (Macaca fascicularis) with three different levels of sensitivity to stress were monitored with daily vaginal swabs and frequent serum progesterone (P) measurements. Three 90-day experimental periods called 'Cycle Sets' were monitored. A Cycle Set consisted of one ovulatory menstrual cycle without stress, and two cycles, or 60 days, with modest stress. Each Cycle Set was followed by a rest period. During a Cycle Set, individuals were either untreated (placebo) or administered escitalopram (CIT) or REB. Ultimately, half of each sensitivity group was euthanized during stress with CIT or REB treatment and the hypothalamus was obtained. Neurobiological endpoints were compared between CIT and REB treatment groups in stress resilient and SS monkeys. PARTICIPANTS/MATERIALS, SETTING, METHODS: The monkeys were housed at the University of Pittsburgh primate facility for the duration of the experiments. Upon euthanasia, their brains and serum samples were shipped to the Oregon National Primate Research Center. The hypothalamus was examined with immunohistochemistry for the expression of DBH (a marker for NE axons), kisspeptin and GnRH. P was measured in the serum samples by radioimmunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: Daily administration of REB restored ovulation in 9 of 10 SS animals during stress. Of note, REB significantly increased P secretion during stress in the most sensitive group (P = 0.032), which indicates ovulation. CIT lacked efficacy. REB significantly reduced DBH/NE, kisspeptin and GnRH axon density in the hypothalamus relative to CIT treatment (P = 0.003. 0.018 and 0.0001, respectively) on Day 5 of the menstrual cycle in resilient and sensitive groups. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The US FDA has not approved REB for human use, although it is used in Europe for the treatment of depression/anxiety as EdronaxTR. Whether REB could be useful for the treatment of FHA in women has not been determined. WIDER IMPLICATIONS FOR THE FINDINGS: The use of an NRI to treat FHA is a novel approach and the potential reinstatement of ovulation could be straightforward compared to current treatment protocols. The underlying neurobiology provides a compelling case for treating the origin of the pathology, i.e. elevated NE, rather than circumventing the hypothalamus altogether with gonadotropins, which have associated risks such as hyperstimulation syndrome or multiple births. STUDY FUNDING/COMPETING INTEREST(S): Portions of this study were supported by NIH grant HD062864 to C.L.B., NIH grant HD62618 to J.L.C. and C.L.B. and 1P51 OD011092 for the operation of the Oregon National Primate Research Center. There were no competing interests.

Social Origins of Developmental Risk for Mental and Physical Illness.

Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution.

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

OBJECTIVES: Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. METHODS: In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). RESULTS: All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. CONCLUSIONS: Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.

Long-lasting effect of obesity on skeletal muscle transcriptome.

BACKGROUND: Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. RESULTS: Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitivity, the majority of WSD-induced (n = 457) and WSD-suppressed (n = 47) genes remained significantly dysregulated after caloric restriction (FDR ≤0.05). The MetacoreTM pathway analysis reveals that western-style diet induced the sustained activation of the transforming growth factor-ß gene network, associated with extracellular matrix remodeling, and the downregulation of genes involved in muscle structure development and nutritional processes. CONCLUSIONS: Western-style diet, in the absence of exercise, induced skeletal muscle transcriptional programing, which persisted even after insulin resistance and glucose intolerance were completely reversed with caloric restriction.

Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques.

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant PL is enriched in a subset of neural maturation (NM) genes compared to a nearby amygdala subregion; and 2) maternal deprivation would downregulate expression of NM transcripts (mRNA). mRNAs for bcl2, doublecortin, neuroD1, and tbr1-genes expressed in post-mitotic neurons-were enriched in the normal PL. Maternal deprivation at either 1 week or 1 month of age resulted in PL-specific downregulation of tbr1-a transcription factor necessary for directing neuroblasts to a glutamatergic phenotype. tbr1 expression also correlated with typical social behaviors. We conclude that maternal deprivation influences glutamatergic neuronal development in the PL, possibly influencing circuits mediating social learning.

Maturation time of new granule cells in the dentate gyrus of adult macaque monkeys exceeds six months.

We studied two groups of adult macaque monkeys to determine the time course of adult neurogenesis in the dentate gyrus of the hippocampus. In the first group, six adult monkeys (Macaca mulatta) received a single injection of the thymidine analog BrdU (75 mg/kg), which is incorporated into replicating DNA and serves as a marker for new cell birth. Brain tissue was collected 48 h, 2 wk, and 6 wk after BrdU injection to examine the initial stages of neurogenesis. Because mature neurons were not evident at 6 wk, we examined tissue collected over a longer time course in a second study. In this study, eight monkeys (Macaca fascicularis) who were subjects in a separate exercise study received 10 weekly injections of BrdU (75 mg/kg), and brain tissue was collected at 16 and 28 wk from the first injection. Based on the timing of expression of neuronal cell markers (ßIII-tubulin, doublecortin, NeuN), the extent of dendritic arborization, and acquisition of mature cell body morphology, we show that granule cell maturation in the dentate gyrus of a nonhuman primate is protracted over a minimum of a 6-mo time period, more than 6 times longer than in rodents. The lengthened time course for new cell maturation in nonhuman primates may be appropriate for preservation of neural plasticity over their longer life span and is relevant to our understanding of antidepressant and other therapies that have been linked to neurogenesis in humans.

Using peer review to improve research and promote collaboration.

OBJECTIVE: The declining success rate of National Institutes of Health (NIH) grant applications highlights the need for interdisciplinary work within a large, diverse department to improve chances of federal funding success. The authors demonstrate how systematic peer review promotes two goals: enhancing the quality of research proposals and cultivating a collaborative departmental culture. METHODS: Changes to the Research Review Committee (RRC) in the Department of Psychiatry at the University of Pittsburgh were instituted to accommodate the increasingly interdisciplinary nature of grant applications, integrate revisions to NIH grant application processes, and incorporate advances in computer technology. RESULTS: The internal peer review process is associated with success in obtaining research support and with significant levels of collaborative scientific work reflected in both grant applications and peer-reviewed publications. CONCLUSIONS: A rich collaborative environment promoted through a rigorous internal peer review system has many benefits for both the quality of scholarly work and the collegiality of the research environment.

Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea.

A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5 days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly higher in HSR than SS animals (p<0.04). There was no change in either group after 5 days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity×stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertility. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE.

Gene transcripts associated with BMI in the motor cortex and caudate nucleus of calorie restricted rhesus monkeys.

Obesity affects over 500 million people worldwide, and has far reaching negative health effects. Given that high body mass index (BMI) and insulin resistance are associated with alterations in many regions of brain and that physical activity can decrease obesity, we hypothesized that in Rhesus monkeys (Macaca mulatta) fed a high fat diet and who subsequently received reduced calories BMI would be associated with a unique gene expression signature in motor regions of the brain implicated in neurodegenerative disorders. In the motor cortex with increased BMI we saw the upregulation of genes involved in apoptosis, altered gene expression in metabolic pathways, and the downregulation of pERK1/2 (MAPK1), a protein involved in cellular survival. In the caudate nucleus with increased BMI we saw the upregulation of known obesity related genes (the insulin receptor (INSR) and the glucagon-like peptide-2 receptor (GLP2R)), apoptosis related genes, and altered expression of genes involved in various metabolic processes. These studies suggest that the effects of high BMI on the brain transcriptome persist regardless of two months of calorie restriction. We hypothesize that active lifestyles with low BMIs together create a brain homeostasis more conducive to brain resiliency and neuronal survival.

Recruitment and Retention Strategies for Parents Experiencing Vulnerability: Lessons from an Online Parenting Program.

BACKGROUND: Supportive parenting programs can promote parent-child interactions and children's development. However, families experiencing vulnerability (e.g., low socioeconomic status) report barriers (e.g., transportation, distrust of researchers) to research participation, and attrition rates of 40% and higher have been reported in parenting research. In response, we conducted a longitudinal evaluation of a digital parenting program in a major metropolitan centre in western Canada and retained 99% of our sample. AIM: Review recruitment and retention strategies employed in the First Pathways study and evaluate associations between sociodemographic (e.g., income) and psychosocial (e.g., parental depression) factors with recruitment and retention strategies. METHODS AND FINDINGS: In collaboration with community agencies, we commenced recruitment of 100 families experiencing vulnerability (e.g., low-income) in June 2021. We utilized strategies to engage staff (e.g., presentations, gift cards, updates) and employed snowball sampling. Families recruited through community agencies were significantly more likely to experience vulnerability (e.g., low income and education, high adverse experiences) compared to families in the snowball sample. We incorporated strategies to minimize participant burden (e.g., choice of online or in-person meetings), promoted rapport (e.g., holiday texts, nonjudgmental environment), incorporated trauma-informed practices (e.g., sensitive inquiry), and demonstrated appreciation for participants' contributions (i.e., honorarium). Family experiences of vulnerability (i.e., low income, depressive symptoms, adversity) were correlated with higher participant rescheduling. CONCLUSION: Nurses need knowledge of strategies to promote equitable access to research for families experiencing vulnerability. Digital programs with protocols designed to establish rapport, include trauma-informed practices, and minimize participant burden will likely optimize participation and retention.

A realist review of digitally delivered child development assessment and screening tools: Psychometrics and considerations for future use.

BACKGROUND: Developmental screening improves the detection of developmental concerns, yet numerous children are not screened/assessed. Remote child developmental tool administration has been utilized to increase screening and assessment accessibility. METHOD: We conducted a realist review to: (1) identify existing multi-domain child development assessment and screening tools for children 0-5 years; (2) review psychometric data on their digital (i.e., only administered remotely) administration; and (3) explore contextual factors relevant to their digital administration. We searched APA PsycInfo, MEDLINE, CINAHL, and ERIC to identify tools and papers on their psychometrics. We reference-searched included articles and searched Google for relevant grey literature. RESULTS: Of 33 multi-domain child development tools identified in objective one, five tools (in five studies) were delivered digitally and compared to traditional (e.g., paper) delivery (i.e., objective two). Studies evaluated within-group equivalence reliability (k = 2) and between-group equivalence (k = 3). Within-group equivalence reliability was established for the Vineland Adaptive Behavior Scales, and domains (e.g., gross motor) of the Ages and Stages Questionnaires 2nd edition (ASQ-2) and Revised Prescreening Denver Questionnaire (R-PDQ). Between group equivalence was demonstrated for Developmental Neuropsychological Assessment, 2nd Edition (NEPSY-II) subtests and Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3) items. In another between group evaluation, web-based and paper versions of the ASQ-2 were deemed generally equivalent. Digital Bayley-3 inter-observer reliability ranged from 0.82 to 1.0. Examiner support, time, tool modifications, family resources, and comfort promotion supported digital administration. CONCLUSION: Digitally delivered ASQ-2, R-PDQ, Vineland, and Bayley-3 and NEPSY-II components show promise for equivalence with traditional administration.

Immature neurons in the primate amygdala: changes with early development and disrupted early environment.

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL’s potential for cellular growth during development, we compared PL cells in 1) infant and adolescent macaques (control, maternally-reared), and in 2) infant macaques that experienced separation from their mother in the first month of life. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. tbr-1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al, 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between tbr1mRNA and mature neuron numbers across animals.

Immature neurons in the primate amygdala: Changes with early development and disrupted early environment.

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL's potential for cellular growth during development, we compared PL neurons in (1) infant and adolescent macaques (control, maternally-reared), and in (2) infant macaques that experienced separation from their mother in the first month of life compared to control maternally-reared infants. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. TBR1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al., 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between TBR1 mRNA and mature neuron numbers across animals.

Impacts of Parental Technoference on Parent-Child Relationships and Child Health and Developmental Outcomes: A Scoping Review.

Parental technological immersion during parenting activities has been shown to alter parent-child interactions. This concept, referred to as parental technoference, has the potential to affect parent-child relationships and children's health and development. This scoping review utilized the Joanna Briggs Institute (JBI) methodology to identify, describe, and summarize: (a) evidence of parental technoference on parent-child relationships, and children's health and development; (b) definitions and measurements of parental technoference; (c) research designs and methodologies used to investigate parental technoference; and (d) literature gaps. We searched MEDLINE, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database for Systematic Reviews, JBI EBP Database, Embase, CINAHL, and Scopus, as well as the reference lists of included studies for literature on parental technology use during parenting and parent-child interactions and its effects on parent-child relationships, and children's health and development. Sixty-four studies, found in 61 publications, met the review criteria. The effect of parental technoference on parent-child relationships was most studied, and findings demonstrated that parents recognized, and researchers observed, changes in parents' and children's behaviors. Adolescent self-reported mental health concerns and maladaptive technological behaviors (e.g., cyberbullying) were associated with more parental technoference, and findings highlighted safety concerns for children. Other aspects of children's development, although less studied, were also negatively impacted by parental technoference. No significant associations were found between parental technoference and children's medical and physiological health, yet these associations were the least studied. Additional research is needed to understand these associations and evaluate interventions designed to mitigate technoference harms.

Mechanisms by Which Cultural-Centric Narrative Influences Interest in ADRD Research Among African American Adults.

BACKGROUND AND OBJECTIVES: Insufficient ethnoracial diversity is a pervasive challenge in Alzheimer's disease (AD) research. The Recruitment Innovations for Diversity Enhancement (RIDE) is grounded in the premise that culturally informed narratives of research participation can inspire individuals from a given culture-sharing group to consider research enrollment. This study examines factors associated with interest in AD research among Black or African American adults following exposure to RIDE narrative campaign materials. RESEARCH DESIGN AND METHODS: A community-based sample of 500 Black or African American adults viewed RIDE narrative materials online and completed a survey of perceptions about research, AD risk, and likelihood of enrolling in AD research. Logistic regression examined predictors and mediators of self-reported likelihood of participating in AD research. RESULTS: Most (72%) participants reported interest in being contacted for AD research opportunities. After controlling for key variables, prior experience with clinical research and trust in medical researchers emerged as independent predictors of likelihood of enrolling in AD research. Perceived burden of AD research partially mediated the effects of prior research experience and trust on likelihood of enrollment. Perceived benefits of AD research also played a mediating role, accounting for over one third of the effect of trust on likelihood of enrollment. DISCUSSION AND IMPLICATIONS: This study advances the field's understanding of how narrative may function to enhance diversity in AD research. Findings suggest that participant narratives should address experiences regarding the burdens and potential benefits of AD research participation as these factors may influence decisions leading to subsequent research enrollment.

Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P < 0.0001) and follicle-stimulating hormone levels (P < 0.0001), consistent with the estrogenic action of the compound. GSK232802A treatment produced a small but sustained weight loss (4.6 ± 1.0%, P < 0.0001) and reduced adiposity (P < 0.0001), which was due at least in part to a suppression of food intake (3.6 ± 3.7%, P < 0.0001). Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

Physical activity is linked to ceruloplasmin in the striatum of intact but not MPTP-treated primates.

Ceruloplasmin is a protective ferroxidase. Although some studies suggest that plasma ceruloplasmin levels are raised by exercise, the impact of exercise on brain ceruloplasmin is unknown. We have examined whether striatal ceruloplasmin is raised with treadmill exercise and/or is correlated with spontaneous physical activity in rhesus monkeys. Parkinson's disease is characterized by a loss in ceruloplasmin and, similarly, Parkinson's models lead to a loss in antioxidant defenses. Exercise might protect against Parkinson's disease and is known to prevent antioxidant loss in experimental models. We have therefore examined whether treadmill exercise prevents ceruloplasmin loss in monkeys treated unilaterally with the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). We found that exercise raised ceruloplasmin expression in the caudate and accumbens but not the putamen of intact monkeys. However, putamen ceruloplasmin was correlated with spontaneous activity in a home pen. MPTP alone did not cause unilateral loss of ceruloplasmin but blocked the impact of exercise on ceruloplasmin. Similarly, the correlation between putamen ceruloplasmin and activity was also lost with MPTP. MPTP elicited loss of tyrosine hydroxylase in the treated hemisphere; the remaining tyrosine hydroxylase was correlated with overall daily activity (spontaneous activity plus that induced by the treadmill). Thus, treadmill activity can raise ceruloplasmin but this impact and the link with spontaneous activity are both diminished in Parkinsonian primates. Furthermore, low overall physical activity predicts greater loss of dopaminergic phenotype in MPTP-treated primates. These data have implications for the maintenance of active lifestyles in both healthy and neurodegenerative conditions.