Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases.

Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis and atrophy. Deletion of myogenin from adult mice diminishes expression of MuRF1 and atrogin-1 in denervated muscle and confers resistance to atrophy. Mice lacking histone deacetylases (HDACs) 4 and 5 in skeletal muscle fail to upregulate myogenin and also preserve muscle mass following denervation. Conversely, forced expression of myogenin in skeletal muscle of HDAC mutant mice restores muscle atrophy following denervation. Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder.

Regulation of lifespan by neural excitation and REST.

The mechanisms that extend lifespan in humans are poorly understood. Here we show that extended longevity in humans is associated with a distinct transcriptome signature in the cerebral cortex that is characterized by downregulation of genes related to neural excitation and synaptic function. In Caenorhabditis elegans, neural excitation increases with age and inhibition of excitation globally, or in glutamatergic or cholinergic neurons, increases longevity. Furthermore, longevity is dynamically regulated by the excitatory-inhibitory balance of neural circuits. The transcription factor REST is upregulated in humans with extended longevity and represses excitation-related genes. Notably, REST-deficient mice exhibit increased cortical activity and neuronal excitability during ageing. Similarly, loss-of-function mutations in the C. elegans REST orthologue genes spr-3 and spr-4 elevate neural excitation and reduce the lifespan of long-lived daf-2 mutants. In wild-type worms, overexpression of spr-4 suppresses excitation and extends lifespan. REST, SPR-3, SPR-4 and reduced excitation activate the longevity-associated transcription factors FOXO1 and DAF-16 in mammals and worms, respectively. These findings reveal a conserved mechanism of ageing that is mediated by neural circuit activity and regulated by REST.

Ret signaling in ureteric bud epithelial cells controls cell movements, cell clustering and bud formation.

Ret signaling promotes branching morphogenesis during kidney development, but the underlying cellular mechanisms remain unclear. While Ret-expressing progenitor cells proliferate at the ureteric bud tips, some of these cells exit the tips to generate the elongating collecting ducts, and in the process turn off Ret. Genetic ablation of Ret in tip cells promotes their exit, suggesting that Ret is required for cell rearrangements that maintain the tip compartments. Here, we examine the behaviors of ureteric bud cells that are genetically forced to maintain Ret expression. These cells move to the nascent tips, and remain there during many cycles of branching; this tip-seeking behavior may require positional signals from the mesenchyme, as it occurs in whole kidneys but not in epithelial ureteric bud organoids. In organoids, cells forced to express Ret display a striking self-organizing behavior, attracting each other to form dense clusters within the epithelium, which then evaginate to form new buds. The ability of forced Ret expression to promote these events suggests that similar Ret-dependent cell behaviors play an important role in normal branching morphogenesis.

AAV-mediated neuronal expression of an scFv antibody selective for Aß oligomers protects synapses and rescues memory in Alzheimer models.

The accumulation of soluble oligomers of the amyloid-ß peptide (AßOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AßOs and shows minimal reactivity to Aß monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AßOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AßO binding to neurons and AßO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AßOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AßO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.

Diet and physical activity behaviors: how are they related to illness perceptions, coping, and health-related quality of life in young people with hereditary cancer syndromes?

Individuals with inherited cancer syndromes, such as Li-Fraumeni syndrome (LFS), may be motivated to adopt health-protective behaviors, such as eating more fruits and vegetables and increasing physical activity. Examining these health behaviors among young people with high lifetime genetic cancer risk may provide important insights to guide future behavioral interventions that aim to improve health-related quality of life (HRQOL). We used a self-regulatory framework to investigate relationships among diet and physical activity behaviors and psychosocial constructs (e.g., illness perceptions, coping, HRQOL) in adolescents and young adults (AYAs; aged 15-39 years) with LFS. This longitudinal mixed-methods study included 57 AYAs aged 16-39 years at enrollment), 32 (56%) of whom had a history of one or more cancers. Participants completed one or two telephone interviews and/or an online survey. We thematically analyzed interview data and conducted regression analyses to evaluate relationships among variables. AYAs described adopting healthy diet and physical activity behaviors to assert some control over health and to protect HRQOL. More frequent use of active coping strategies was associated with greater reported daily fruit and vegetable intake. Greater reported physical activity was associated with better quality of psychological health. Healthy diet and physical activity behaviors may function as LFS coping strategies that confer mental health benefits. Clinicians might emphasize these potential benefits and support AYAs in adopting health behaviors that protect multiple domains of health. Future research could use these findings to develop behavioral interventions tailored to AYAs with high genetic cancer risk.

Amyloid ß Proteoforms Elucidated by Quantitative LC/MS in the 5xFAD Mouse Model of Alzheimer's Disease.

Numerous Aß proteoforms, identified in the human brain, possess differential neurotoxic and aggregation propensities. These proteoforms contribute in unknown ways to the conformations and resultant pathogenicity of oligomers, protofibrils, and fibrils in Alzheimer's disease (AD) manifestation owing to the lack of molecular-level specificity to the exact chemical composition of underlying protein products with widespread interrogating techniques, like immunoassays. We evaluated Aß proteoform flux using quantitative top-down mass spectrometry (TDMS) in a well-studied 5xFAD mouse model of age-dependent Aß-amyloidosis. Though the brain-derived Aß proteoform landscape is largely occupied by Aß1-42, 25 different forms of Aß with differential solubility were identified. These proteoforms fall into three natural groups defined by hierarchical clustering of expression levels in the context of mouse age and proteoform solubility, with each group sharing physiochemical properties associated with either N/C-terminal truncations or both. Overall, the TDMS workflow outlined may hold tremendous potential for investigating proteoform-level relationships between insoluble fibrils and soluble Aß, including low-molecular-weight oligomers hypothesized to serve as the key drivers of neurotoxicity. Similarly, the workflow may also help to validate the utility of AD-relevant animal models to recapitulate amyloidosis mechanisms or possibly explain disconnects observed in therapeutic efficacy in animal models vs humans.

Motivations to learn genomic information are not exceptional: Lessons from behavioral science.

Whether to undergo genome sequencing in a clinical or research context is generally a voluntary choice. Individuals are often motivated to learn genomic information even when clinical utility-the possibility that the test could inform medical recommendations or health outcomes-is low or absent. Motivations to seek one's genomic information can be cognitive, affective, social, or mixed (e.g., cognitive and affective) in nature. These motivations are based on the perceived value of the information, specifically, its clinical utility and personal utility. We suggest that motivations to learn genomic information are no different from motivations to learn other types of personal information, including one's health status and disease risk. Here, we review behavioral science relevant to motivations that may drive engagement with genome sequencing, both in the presence of varying degrees of clinical utility and in the absence of clinical utility. Specifically, we elucidate 10 motivations that are expected to underlie decisions to undergo genome sequencing. Recognizing these motivations to learn genomic information will guide future research and ultimately help clinicians to facilitate informed decision making among individuals as genome sequencing becomes increasingly available.

Which Intervention Strategies Promote the Adoption and Maintenance of Physical Activity? Evidence From Behavioral Trials With Cancer Survivors.

BACKGROUND/PURPOSE: We address four questions about interventions to promote physical activity in cancer survivors: (a) How often is both the adoption and maintenance of behavior change tested in trials? (b) How often do interventions generate adoption-plus-maintenance of behavior change? (c) Are intervention strategies specifically geared at promoting maintenance of behavior change deployed in trials? and (d) Which intervention strategies distinguish trials that promote both the adoption and maintenance of physical activity from trials that promote adoption-only or generate no behavioral changes? METHODS: Computerized literature searches identified 206 reports of randomized trials that measured physical activity in the wake of the intervention. RESULTS: Only 51 reports (24%) measured both behavioral adoption (postintervention) and behavioral maintenance (≥3 months follow-up). The 51 reports included 58 tests of interventions; 22% of tests observed both adoption and maintenance of physical activity, 26% reported adoption-only, and 52% found no change in behavior. Change techniques designed to promote behavioral maintenance were used much less frequently than adoption techniques or adoption and maintenance techniques. Interventions that aimed to improve quality of life, used supervised exercise sessions, were undertaken in community centers, and deployed fewer behavior change techniques were associated with adoption-plus-maintenance of physical activity in cancer survivors. CONCLUSIONS: The present findings offer new insights into the adoption and maintenance of physical activity and highlight the need to routinely assess these forms of behavior change in future trials. More extensive testing of intervention strategies specifically geared at maintenance of behavior change is warranted.

Cancer survivors need to not only adopt, but also maintain, physical activity to benefit their health and wellbeing. We undertook a systematic review of interventions to promote the adoption and maintenance of physical activity in cancer survivors. Out of 206 physical activity interventions for cancer survivors that we identified, only 51 (24%) measured both the adoption and maintenance of behavior change. Of these 51 intervention studies, only 22% were effective in promoting both the adoption and maintenance of physical activity. We developed a new classification of behavior change techniques used in interventions and discovered that techniques specifically designed to promote behavioral maintenance were used only rarely. We found that interventions that aimed to improve quality of life, used supervised exercise sessions, and were undertaken in community centers predicted adoption-plus-maintenance of physical activity in cancer survivors. These findings underscore the need for more trials that assess the adoption and maintenance of physical activity and for new research programs focused on evaluating the efficacy of maintenance techniques.

Activation Versus Change as a Principle Underlying Intervention Strategies to Promote Health Behaviors.

BACKGROUND AND PURPOSE: Interventions are effective in promoting health behavior change to the extent that (a) intervention strategies modify targets (i.e., mechanisms of action), and (b) modifying targets leads to changes in behavior. To complement taxonomies that characterize the variety of strategies used in behavioral interventions, we outline a new principle that specifies how strategies modify targets and thereby promote behavior change. We distinguish two dimensions of targets-value (positive vs. negative) and accessibility (activation level)-and show that intervention strategies operate either by altering the value of what people think, feel, or want (target change) or by heightening the accessibility of behavior-related thoughts, feelings, and goals (target activation). METHODS AND RESULTS: We review strategies designed to promote target activation and find that nudges, cue-reminders, goal priming, the question-behavior effect, and if-then planning are each effective in generating health behavior change, and that their effectiveness accrues from heightened accessibility of relevant targets. We also identify several other strategies that may operate, at least in part, via target activation (e.g., self-monitoring, message framing, anticipated regret inductions, and habits). CONCLUSIONS: The Activation Vs. Change Principle (AVCP) offers a theoretically grounded and parsimonious means of distinguishing among intervention strategies. By focusing on how strategies modify targets, the AVCP can aid interventionists in deciding which intervention strategies to deploy and how to combine different strategies in behavioral trials. We outline a research agenda that could serve to further enhance the design and delivery of interventions to promote target activation.

Future-oriented Emotions and Decisions to Receive Genomic Testing Results Among U.S. Adults of African Ancestry.

BACKGROUND: Future-oriented emotions are associated with consequential health decision-making, including genomic testing decisions. However, little is known about the relative role of various future-oriented emotions in such decisions. Moreover, most research on predictors of decision making regarding genomic testing is conducted with white participants. PURPOSE: This study examined the role of future-oriented emotions in decisions to receive genomic testing results in U.S. individuals of African descent. METHODS: We analyzed cross-sectional survey data from a genomic sequencing cohort (N = 408). All participants identified as African, African-American, or Afro-Caribbean (Mage = 56.3, 74.7% female). Participants completed measures assessing anticipatory affect (worry about genetic testing results), anticipated distress (feeling devastated if genetic testing showed an increased risk for fatal disease), and anticipated regret (regretting a decision not to learn results). Outcomes were intentions for learning actionable, nonactionable, and carrier results. RESULTS: Anticipated regret was robustly positively associated with intentions to receive actionable (b = 0.28, p < .001), nonactionable (b = 0.39, p < .001), and carrier (b = 0.30, p < .001) results. Anticipated distress was negatively associated with intentions to receive nonactionable results only (b = -0.16, p < .01). Anticipatory negative affect (worry) was not associated with intentions. At higher levels of anticipated regret, anticipated distress was less strongly associated with intentions to receive nonactionable results (b = 0.14, p = .02). CONCLUSIONS: Our results highlight the role of future-oriented emotions in genomic testing among participants who are typically underrepresented in genomic testing studies and behavioral medicine broadly. Future work should examine whether interventions targeting future-oriented emotions such as anticipated regret may have clinically meaningful effects in genetic counseling in similar cohorts.

Future-oriented emotions (emotions directed toward a future outcome, such as worrying about a future outcome, or expecting to feel distress or regret if a particular outcome occurs) are important predictors of health decisions, including decisions to seek and receive genomic testing results. Understanding how such factors relate to decisions to receive genetic testing results is particularly important in medically-underserved groups such as individuals of African ancestry, who are underrepresented in genomics and behavioral science research. We analyzed survey responses from a genomic sequencing cohort where all 408 participants identified as African, African-American, or Afro-Caribbean, and were asked about their level of worry, anticipated distress, and anticipated regret about results, plus their interest in receiving three types of genomic testing results from the study. We found that participants who expected that they would regret their decision to not learn the results had stronger intentions to receive all three types of results; those who expected to feel distressed by a genetic testing result that showed an increased risk for a fatal disease were less interested in nonactionable genetic testing results specifically. Our results highlight the differing roles of specific types of future-oriented emotions in genomic testing decisions, among participants who are typically underrepresented in this type of research.

Determining interchromophore effects for energy transport in molecular networks using machine-learning algorithms.

Nature uses chromophore networks, with highly optimized structural and energetic characteristics, to perform important chemical functions. Due to its modularity, predictable aggregation characteristics, and established synthetic protocols, structural DNA nanotechnology is a promising medium for arranging chromophore networks with analogous structural and energetic controls. However, this high level of control creates a greater need to know how to optimize the systems precisely. This study uses the system's modularity to produce variations of a coupled 14-Site chromophore network. It uses machine-learning algorithms and spectroscopy measurements to reveal the energy-transport roles of these Sites, paying particular attention to the cooperative and inhibitive effects they impose on each other for transport across the network. The physical significance of these patterns is contextualized, using molecular dynamics simulations and energy-transport modeling. This analysis yields insights about how energy transfers across the Donor-Relay and Relay-Acceptor interfaces, as well as the energy-transport pathways through the homogeneous Relay segment. Overall, this report establishes an approach that uses machine-learning methods to understand, in fine detail, the role that each Site plays in an optoelectronic molecular network.

Perceptions and tolerance of uncertainty: relationship to trust in COVID-19 health information and vaccine hesitancy.

The COVID-19 crisis has exposed the public to considerable scientific uncertainty, which may promote vaccine hesitancy among individuals with lower tolerance of uncertainty. In a national sample of US adults in May-June 2020, we examined how both perceptions of uncertainty about COVID-19 and trait-level differences in tolerance of uncertainty arising from various sources (risk, ambiguity, and complexity) are related to vaccine hesitancy-related outcomes, including trust in COVID-19 information, COVID-19 vaccine intentions, and beliefs that COVID-19 vaccines should undergo a longer testing period before being released to the public. Overall, perceptions of COVID-19 uncertainty were not associated with trust in information, vaccine intentions, or beliefs about vaccine testing. However, higher tolerance of risk was associated with lower intentions to get vaccinated, and lower tolerance of ambiguity was associated with lower intentions to get vaccinated and preferring a longer period of vaccine testing. Critically, perceptions of COVID-19 uncertainty and trait-level tolerance for uncertainty also interacted as predicted, such that greater perceived COVID-19 uncertainty was more negatively associated with trust in COVID-19 information among individuals with lower tolerance for risk and ambiguity. Thus, although perceptions of uncertainty regarding COVID-19 may not reduce trust and vaccine hesitancy for all individuals, trait-level tolerance of uncertainty arising from various sources may have both direct and moderating effects on these outcomes. These findings can inform public health communication or other interventions to increase COVID-19 vaccination uptake.

Early intraneuronal amyloid triggers neuron-derived inflammatory signaling in APP transgenic rats and human brain.

Chronic inflammation during Alzheimer's disease (AD) is most often attributed to sustained microglial activation in response to amyloid-ß (Aß) plaque deposits and cell death. However, cytokine release and microgliosis are consistently observed in AD transgenic animal models devoid of such pathologies, bringing into question the underlying processes that may be at play during the earliest AD-related immune response. We propose that this plaque-independent inflammatory reaction originates from neurons burdened with increasing levels of soluble and oligomeric Aß, which are known to be the most toxic amyloid species within the brain. Laser microdissected neurons extracted from preplaque amyloid precursor protein (APP) transgenic rats were found to produce a variety of potent immune factors, both at the transcript and protein levels. Neuron-derived cytokines correlated with the extent of microglial activation and mobilization, even in the absence of extracellular plaques and cell death. Importantly, we identified an inflammatory profile unique to Aß-burdened neurons, since neighboring glial cells did not express similar molecules. Moreover, we demonstrate within disease-vulnerable regions of the human brain that a neuron-specific inflammatory response may precede insoluble Aß plaque and tau tangle formation. Thus, we reveal the Aß-burdened neuron as a primary proinflammatory agent, implicating the intraneuronal accumulation of Aß as a significant immunological component in the AD pathogenesis.

Increasing Receptivity to COVID-19 Public Health Messages with Self-Affirmation and Self vs. Other Framing.

There remains an urgent need for effective communication about the importance of widespread adherence to behavioral recommendations to control the COVID-19 pandemic that will also reduce resistance to such guidance. We examined two strategies for COVID-19 communication- (1) self-affirmation (reflecting on a personal value in order to boost self-integrity and reduce defensiveness to potentially threatening information); and (2) manipulating self/other message framing - and moderation of these strategies by COVID-19 risk. 600 participants (Mage = 32.55, 51% female) were recruited for an online study and, after assessment of risk factors for severe COVID-19 infection, were exposed to the experimental manipulations. Three classes of defensive responses were considered as outcomes of interest: reactance, attitudinal responses, and behavioral responses. We found that participants derogated the self-focused message more than the other-focused message. Further, other-focused messaging and/or self-affirmation were more likely to elicit positive responses among individuals at higher risk for COVID-19 complications. Our findings suggest having individuals affirm values prior to viewing COVID-19 messages, and framing messages in terms of the importance of protecting others, may be beneficial strategies for encouraging responsiveness - particularly if the targets of such messages are at risk of COVID-19 complications themselves.

Determining the Cytosolic Stability of Small DNA Nanostructures In Cellula.

DNA nanostructures have proven potential in biomedicine. However, their intracellular interactions─especially cytosolic stability─remain mostly unknown and attempts to discern this are confounded by the complexities of endocytic uptake and entrapment. Here, we bypass the endocytic uptake and evaluate the DNA structural stability directly in live cells. Commonly used DNA structures─crosshairs and a tetrahedron─were labeled with a multistep Förster resonance energy transfer dye cascade and microinjected into the cytosol of transformed and primary cells. Energy transfer loss, as monitored by fluorescence microscopy, reported the structure's direct time-resolved breakdown in cellula. The results showed rapid degradation of the DNA crosshair within 20 min, while the tetrahedron remained consistently intact for at least 1 h postinjection. Nuclease assays in conjunction with a current understanding of the tetrahedron's torsional rigidity confirmed its higher stability. Such studies can inform design parameters for future DNA nanostructures where programmable degradation rates may be required.

Optimal Integration of Behavioral Medicine into Clinical Genetics and Genomics.

Clinical genetics and genomics will exert their greatest population impact by leveraging the rich knowledge of human behavior that is central to the discipline of behavioral medicine. We contend that more concerted efforts are needed to integrate these fields synergistically, and accordingly, we consider barriers and potential actions to hasten such integration.

Uptake and timing of bilateral and contralateral risk-reducing mastectomy in women with Li-Fraumeni syndrome.

PURPOSE: Women with Li-Fraumeni Syndrome (LFS) often consider risk-reducing mastectomy (RRM) due to extremely high risk of breast cancer at early ages. Data on uptake of RRM in LFS are scarce, and are inferred from experience in women with pathogenic variants (PVs) in BRCA1/2, despite differences in cancer risks. This study evaluated RRM uptake in a cohort of women with LFS. METHODS: Women (n = 205) with LFS enrolled in NCI's LFS study reported lifetime cancer diagnoses and mastectomies and completed questionnaires regarding reproductive history, cancer worry and risk perceptions. A subset of women participating in an annual cancer screening study received counseling regarding RRM. RESULTS: 65% (n = 71) of women diagnosed with presumed unilateral breast cancer (n = 109) underwent contralateral RRM over their lifetime. Nearly half (49%, n = 25) of the women who did not complete contralateral RRM within one year of their breast cancer diagnosis (n = 51) developed contralateral breast cancer (median interval = 6 years). Only 18.5% (n = 15) of women without breast cancer history (n = 81) underwent bilateral RRM. Median age at bilateral RRM of 39 years was sub-optimal for breast cancer risk reduction. Contralateral RRM was associated with early genetic diagnosis, participation in the screening study, and fewer prior cancers. Bilateral RRM uptake was associated with having had children, having breastfed, and high cancer worry. CONCLUSION: Uptake of contralateral RRM is high in women with LFS. The frequency of contralateral breast cancer necessitates active discussion of benefits of contralateral RRM and counseling regarding bilateral RRM should be tailored to the early age at risk of breast cancer onset in LFS. There is a need for research into the survival and long-term benefits of RRM in LFS.

Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease.

AIMS: An obstacle to developing new treatment strategies for Alzheimer's disease (AD) has been the inadequate translation of findings in current AD transgenic rodent models to the prediction of clinical outcomes. By contrast, nonhuman primates (NHPs) share a close neurobiology with humans in virtually all aspects relevant to developing a translational AD model. The present investigation used African green monkeys (AGMs) to refine an inducible NHP model of AD based on the administration of amyloid-beta oligomers (AßOs), a key upstream initiator of AD pathology. METHODS: AßOs or vehicle were repeatedly delivered over 4 weeks to age-matched young adult AGMs by intracerebroventricular (ICV) or intrathecal (IT) injections. Induction of AD-like pathology was assessed in subregions of the medial temporal lobe (MTL) by quantitative immunohistochemistry (IHC) using the AT8 antibody to detect hyperphosphorylated tau. Hippocampal volume was measured by magnetic resonance imaging (MRI) scans prior to, and after, intrathecal injections. RESULTS: IT administration of AßOs in young adult AGMs revealed an elevation of tau phosphorylation in the MTL cortical memory circuit compared with controls. The largest increases were detected in the entorhinal cortex that persisted for at least 12 weeks after dosing. MRI scans showed a reduction in hippocampal volume following AßO injections. CONCLUSIONS: Repeated IT delivery of AßOs in young adult AGMs led to an accelerated AD-like neuropathology in MTL, similar to human AD, supporting the value of this translational model to de-risk the clinical trial of diagnostic and therapeutic strategies.

Information Avoidance, Self-affirmation, and Intentions to Receive Genomic Sequencing Results Among Members of an African Descent Cohort.

BACKGROUND: Information avoidance tendencies have been found to be associated with lower intentions to pursue medically actionable genomic sequencing results, but less so among individuals who engage more in spontaneous self-affirmation. Yet these results were obtained with a largely non-Hispanic White, high-SES cohort. PURPOSE: To assess these variables, their magnitude, and their associations in an African-descent cohort as part of the same ClinSeq® exome sequencing program. METHODS: Participants reported levels of spontaneous self-affirmation, information avoidance, and intentions to receive three types of results - medically actionable, non-medically actionable, and carrier status as part of a baseline survey. RESULTS: Relative to the original, non-Hispanic White cohort, those in the African-descent cohort had higher levels of spontaneous self-affirmation and lower intentions of learning about carrier genomic results; they reported comparable levels of information avoidance and intentions to receive other results. Information avoidance was negatively associated with intention to receive non-actionable results in the African-descent cohort, as found in the initial cohort, with no moderating effect of spontaneous self-affirmation. Information avoidance, spontaneous self-affirmation, and their interaction were not associated with intentions to receive actionable results (contrary to findings in the initial cohort), or carrier results. CONCLUSIONS: Individuals of African descent may engage in relatively more spontaneous self-affirmation, and do not appear to engage in more information avoidance. Their information avoidance tendencies were associated with pursuit of non-actionable sequencing results, with no moderating effect of self-affirmation, and were not associated with pursuit of actionable results or carrier results.

The role of future-oriented affect in engagement with genomic testing results.

Future-oriented emotions such as anticipatory affect (i.e., current affect experienced regarding a potential future outcome) and anticipated affect (i.e., expectations about potential future affect), are uniquely associated with health decision-making (e.g., electing to receive results of genomic testing). This study investigated the degree to which negative anticipated and anticipatory emotions predict health decision making over time, and whether such emotions predict social, emotional, and behavioral responses to anticipated information (e.g., genomic testing results). 461 participants (M age = 63.9, SD = 5.61, 46% female) in a genomic sequencing cohort who elected to receive genomic sequencing (carrier) results were included in the current study. Anticipated and anticipatory affect about sequencing results were assessed at baseline. Psychological and behavioral responses to sequencing results, including participants' reported anxiety, decisional conflict, and distress about sequencing results, whether they shared results with family members, and their intentions to continue learning results in the future, were collected immediately, one month, and/or six months after receiving results. More negative anticipated and anticipatory affect at baseline was significantly and independently associated with lower intentions to continue learning results in the future, as well as higher levels of anxiety and uncertainty at multiple time points after receiving results. Anticipated negative affect was also associated with greater decisional conflict, and anticipatory negative affect was also associated with greater distress after receiving results. Future-oriented emotions may play an important role in decisions that unfold over time, with implications for genomic testing, behavioral medicine, and health decision-making broadly.