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.

The Long Behavioral Tail of the COVID-19 Pandemic-A Cancer Control Perspective.

This Viewpoint discusses the impact of the COVID-19 public health emergency on the trajectory of cancer deaths.

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.

Health Information in 2023 (and Beyond): Confronting Emergent Realities With Health Communication Science.

This Viewpoint describes how health communication science can be used to improve response to health challenges by providing credible health information to the public.

Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.

RATIONALE: Extracellular proteolytic activity plays an important role in memory formation and the preservation of cognitive function. Previous studies have shown increased levels of plasminogen activator inhibitor-1 (PAI-1) in the brain of mouse models of Alzheimer's disease (AD) and plasma of AD patients, associated with memory and cognitive decline; however, the exact function of PAI-1 in AD onset and progression is largely unclear. OBJECTIVE: In this study, we evaluated a novel PAI-1 inhibitor, TM5A15, on its ability to prevent or reverse memory deficits and decrease Aß levels and plaque deposition in APP/PS1 mice. METHODS: We administered TM5A15 mixed in a chow diet to 3-month and 9-month-old APP/PS1 mice before and after neuropathological changes were distinguishable. We then evaluated the effects of TM5A15 on memory function and neuropathology at 9 months and 18 months of age. RESULTS: In the younger mice, 6 months of TM5A15 treatment protected against recognition and short-term working memory impairment. TM5A15 also decreased oligomer levels and amyloid plaques, and increased mBDNF expression in APP/PS1 mice at 9 months of age. In aged mice, 9 months of TM5A15 treatment did not significantly improve memory function nor decrease amyloid plaques. However, TM5A15 treatment showed a trend in decreasing oligomer levels in APP/PS1 mice at 18 months of age. CONCLUSION: Our results suggest that PAI-1 inhibition could improve memory function and reduce the accumulation of amyloid levels in APP/PS1 mice. Such effects are more prominent when TM5A15 is administered before advanced AD pathology and memory deficits occur.

Genetic Testing and Other Healthcare Use by Black and White Individuals in a Genomic Sequencing Study.

INTRODUCTION: Early adopters play a critical role in the diffusion of medical innovations by spreading awareness, increasing acceptability, and driving demand. Understanding the role of race in the context of other characteristics of potential early adopters can shed light on disparities seen in the early implementation of genomic medicine. We aimed to understand the association between self-identified race and individual experience with genetic testing outside of the research context. METHODS: We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean ("Black") individuals. RESULTS: Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27-0.68], p < 0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests (e.g., echocardiogram, colonoscopy). Black and white individuals were similar on self-reported personality traits tied to early adoption but differed by sociodemographic and resource facilitators of early adoption. CONCLUSION: Persistent racial disparities among early adopters may represent especially-entrenched disparities in access to and knowledge of genomic technologies in clinical settings.

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.

Uncertainty: a neglected determinant of health behavior?

Health behaviors are critical determinants of the well-being of individuals and populations, and understanding the determinants of these behaviors has been a major focus of research. One important determinant that has received little direct attention in past health research is uncertainty: a complex phenomenon that pertains not only to scientific issues regarding the diagnosis, prognosis, prevention, and treatment of health problems, but also to personal issues regarding other important health-related concerns. Here, we make the case for greater attention to uncertainty in health behavior theory and research, and especially to personal uncertainties. We discuss three exemplary types of personal uncertainty-value uncertainty, capacity uncertainty, and motive uncertainty-which relate, respectively, to moral values, capacities to enact or change behaviors, and the motives and intentions of other persons or institutions. We argue that that personal uncertainties such as these influence health behaviors, but their influence has historically been obscured by a focus on other constructs such as self-efficacy and trust. Reconceptualizing and investigating health behavior as a problem of uncertainty can advance both our understanding of the determinants of healthy behaviors and our ability to promote them.

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.

Self assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades.

Access to efficient enzymatic channeling is desired for improving all manner of designer biocatalysis. We demonstrate that enzymes constituting a multistep cascade can self-assemble with nanoparticle scaffolds into nanoclusters that access substrate channeling and improve catalytic flux by orders of magnitude. Utilizing saccharification and glycolytic enzymes with quantum dots (QDs) as a model system, nanoclustered-cascades incorporating from 4 to 10 enzymatic steps are prototyped. Along with confirming channeling using classical experiments, its efficiency is enhanced several fold more by optimizing enzymatic stoichiometry with numerical simulations, switching from spherical QDs to 2-D planar nanoplatelets, and by ordering the enzyme assembly. Detailed analyses characterize assembly formation and clarify structure-function properties. For extended cascades with unfavorable kinetics, channeled activity is maintained by splitting at a critical step, purifying end-product from the upstream sub-cascade, and feeding it as a concentrated substrate to the downstream sub-cascade. Generalized applicability is verified by extending to assemblies incorporating other hard and soft nanoparticles. Such self-assembled biocatalytic nanoclusters offer many benefits towards enabling minimalist cell-free synthetic biology.

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.

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.

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.

Do Beliefs about Alcohol and Cancer Risk Vary by Alcoholic Beverage Type and Heart Disease Risk Beliefs?

BACKGROUND: Alcohol is a leading risk factor for cancer, yet awareness of the alcohol-cancer link is low. Awareness may be influenced by perceptions of potential health benefits of alcohol consumption or certain alcoholic beverage types. The purpose of this study was to estimate awareness of the alcohol-cancer link by beverage type and to examine the relationship between this awareness and concomitant beliefs about alcohol and heart disease risk. METHODS: We analyzed data from the 2020 Health Information National Trends Survey 5 Cycle 4, a nationally representative survey of U.S. adults. RESULTS: Awareness of the alcohol-cancer link was highest for liquor (31.2%), followed by beer (24.9%) and wine (20.3%). More U.S. adults believed wine (10.3%) decreased cancer risk, compared with beer (2.2%) and liquor (1.7%). Most U.S. adults (>50%) reported not knowing how these beverages affected cancer risk. U.S. adults believing alcoholic beverages increased heart disease risk had higher adjusted predicted probabilities of being aware of the alcohol-cancer link (wine: 58.6%; beer: 52.4%; liquor: 59.4%) compared with those unsure (wine: 6.0%; beer: 8.6%; liquor: 13.2%), or believing alcoholic beverages reduced (wine: 16.2%; beer: 21.6%; liquor: 23.8%) or had no effect on heart disease risk (wine: 10.2%; beer: 12.0%; liquor: 16.9%). CONCLUSIONS: Awareness of the alcohol-cancer link was low, varied by beverage type, and was higher among those recognizing that alcohol use increased heart disease risk. IMPACT: These findings underscore the need to educate U.S. adults about the alcohol-cancer link, including raising awareness that drinking all alcoholic beverage types increases cancer risk. See related commentary by Hay et al., p. 9.

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.

Awareness of Alcohol and Cancer Risk and the California Proposition 65 Warning Sign Updates: A Natural Experiment.

In 1986, California enacted Proposition 65 (P65), requiring businesses to display warning signs informing consumers that specific chemicals and alcohol exposure increase the risk of cancer and reproductive harm. In 2018, the P65 alcohol warning signs were updated to include an informational P65 website link, and the update was associated with media coverage and increased enforcement of warning requirements. This study examines knowledge of the association between alcohol use and cancer risk in California compared to the rest of the US before and after the 2018 P65 update. We analyzed state-level data on alcohol and cancer knowledge from the Health Information National Trends Survey from 2017 (n = 3285), 2019 (n = 5438), and 2020 (n = 3865). We performed multinomial logistic regressions to examine knowledge levels by survey year and location (California vs. all other states) and reported the predicted marginals of knowledge by survey year and location. The adjusted prevalence of respondents who reported an association between alcohol and cancer risk was higher in California (41.6%) than the remaining states (34.1%) (p = 0.04). However, knowledge levels decreased significantly over survey years, and there was no evidence for an effect of the P65 update on knowledge in California compared to other states based on the testing of an interaction between state and year (p = 0.32). The 1986 warning signs may have had an enduring effect on awareness, though the update, so far, has not. Further efforts are needed to determine how to increase alcohol and cancer knowledge to address the burden of alcohol-attributable cancers.