Poly(ADP-ribose) polymerase activity and inhibition in cancer.

Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination. Five PARP inhibitors are now in late-stage development in clinical trials that are seeking to expand the understanding of targeted therapies and DNA repair defects in human cancer. This review examines the cell biology of PARP, the discovery of synthetic lethality with HR deficiency, the clinical development of PARP inhibitors, and the role of PARP inhibitors in ongoing clinical trials and clinical practice.

An Age-Friendly University (AFU) assists with technology learning and social engagement among older adults and individuals with developmental disabilities.

As an Age-Friendly University (AFU), University of Akron is striving to support lifelong learning. A collaborative research effort developed between aging researchers at the university and a government-sponsored pilot program aimed to provide learning opportunities for older adults (OA) and engagement for individuals with developmental disabilities (IDD). The present study assessed the success of a pilot program to increase comfort with technology and community engagement. OA and IDD participants met twice a month for 9 months to discuss how to use technology (e.g., an IPad). We assessed satisfaction, perceived changes in comfort with technology, perceived changes in connection with others, and motivations for participating with questionnaires and a structured interview. On average, participants reported very high satisfaction with the group, and moderate increases in comfort with technology and how connected they feel to others as a result of participating in the group. The most common motivations for participation were related to values, strengthening social ties, seeking to learn, and bringing joy to others. These findings suggest that the pilot was successful at improving community engagement. The involvement of the university in the assessment of this pilot program situates the university as an age-friendly partner for community efforts to support lifelong learning.

Violent Death Reporting in Maryland: Demographic Variability in Data Completeness.

OBJECTIVES: To analyze the completeness of precipitating circumstance information recorded in the Maryland Violent Death Reporting System and identify limitations that could affect the system's utility. METHODS: We reviewed all violent deaths among Maryland residents for the years 2003 through 2014 (n = 19 161). We assessed the presence of precipitating circumstance data (abstracted from medical examiner and police reports) by manner of death and demographic characteristics. We further evaluated homicide records with multivariable regression. RESULTS: Demographic variation in circumstance reporting was most pronounced for homicide. Circumstances were known for 53.2% of homicide cases, and this percentage was lower among non-Latino Blacks (48.2%), males (50.7%), those aged 18 to 25 years (47.9%), those residing in jurisdictions with higher-than-average homicide rates (46.1%), and those who died outside in a public place (43.4%) or in a correctional facility (48.9%). With the exception of male gender, these factors were significantly associated with circumstance reporting when we controlled for demographic and situational variables. CONCLUSIONS: Circumstance reporting was least likely among groups most at risk for homicide in Maryland. Collection of circumstance data for the most affected groups should be strengthened to help develop better prevention strategies.

PARP1 and phospho-p65 protein expression is increased in human HER2-positive breast cancers.

Previous studies have shown that basal breast cancers, which may have an inherent "BRCAness" phenotype and sensitivity to inhibitors of poly (ADP-Ribose) polymerase (PARP), express elevated levels of PARP1. Our lab recently reported that HER2+ breast cancers also exhibit sensitivity to PARP inhibitors (PARPi) by attenuating the NF-κB pathway. In this study, we assessed PARP1 and phospho-p65, a marker of activated NF-κB levels in human breast cancer tissues. PARP1 and PARP2 copy number, mRNA, and protein expression was assessed by interrogating the PAM-50 defined breast cancer patient set from the TCGA using cBioPortal. PARP1 and phospho-p65 immunohistochemistry and correlation to clinical parameters was conducted using 307 primary breast cancer specimens (132 basal, 82 luminal, 93 HER2+) through univariate and multivariate analyses. In the PAM50 breast cancer data set, PARP1 and 2 expression was altered in 24/58 (41 %) HER2+, 32/81 (40 %) basal, and 75/324 (23 %) luminal A/B breast cancer patients. This correlated with a statistically significant increase in PARP1 protein levels in HER2+ and basal but not luminal breast cancers (p = 0.003, p = 0.027, p = 0.289, respectively). No change in PARP2 protein level was observed. Interestingly, using breast cancer specimens from 307 patients, HER2 positivity correlated with elevated PARP1 expression (p < 0.0001) and was three times more likely than HER2 negative breast cancers to exhibit high PARP1 levels. No significant differences were noted between race, ER status, or PR status for PARP1 expression. Additionally, we found a significant correlation between HER2 status and phospho-p65 expression (p < 0.0001). Lastly, a direct correlation between PARP1 and phospho-p65 (p < 0.0001) was noted. These results indicate a potential connection between HER2, PARP1, and phospho-p65. Furthermore, these data suggest that the PARPi sensitivity we previously observed in HER2+ breast cancer cells may be due to elevated PARP1 expression.

Activity of CEP-9722, a poly (ADP-ribose) polymerase inhibitor, in urothelial carcinoma correlates inversely with homologous recombination repair response to DNA damage.

As loss of DNA-repair proteins is common in urothelial carcinoma (UC), a rationale can be made to evaluate the activity of poly (ADP-ribose) polymerase (PARP) inhibitors to exploit synthetic lethality. We aimed to preclinically evaluate a PARP inhibitor, CEP-9722, and its active metabolite, CEP-8983, in UC. The activity of CEP-8983 was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay against human UC cell lines. Flow cytometry, COMET assay, and western blot were performed to assess apoptosis, DNA damage, and DNA-repair proteins, respectively. RT4 xenografts received placebo or CEP-9722 (100 or 200 mg/kg/day) orally. Xenografts were subjected to immunohistochemistry for apoptosis [cleaved caspase (cc)-3] and angiogenesis (CD31). CEP-8983 (1 µmol/l) reduced the viability of RT4 and T24 cells by 20%, but did not reduce the viability of 5637 and TCC-SUP cells. Apoptosis and necrosis occurred in 9.7 and 9.1% of RT4 and 5637 cells, respectively. RT4 cells showed greater DNA damage compared with 5637 cells. Increased DNA damage occurred with combination versus CEP-8983 or cisplatin alone in RT4 and 5637 cells. T24 and RT4 showed the least RAD51 foci 8 h following radiation, whereas TCC-SUP and 5637 robustly induced RAD51 foci. CEP-9722 showed dose-dependent antitumor activity in RT4 xenografts; 200 mg/kg daily was better than control (P=0.04) and 100 mg/kg was not (P=0.26). Immunohistochemistry of xenografts showed a significant increase in cc-3 and decrease in CD31 with both doses (P<0.05). Biomarker-driven evaluation of PARP inhibitors in UC is justified as the activity of CEP-9722 correlated inversely with homologous recombination repair response to DNA damage.

A novel video-based paradigm to study the mechanisms underlying age- and falls risk-related differences in gaze behaviour during walking.

PURPOSE: The current study aimed to quantitatively assess differences in gaze behaviour between participants grouped on the basis of their age and measures of functional mobility during a virtual walking paradigm. METHODS: The gaze behaviour of nine young adults, seven older adults with a relatively low risk of falling and seven older adults with a relatively higher risk of falling was measured while they watched five first-person perspective movies representing the viewpoint of a pedestrian walking through various environments. Participants also completed a number of cognitive tests: Stroop task, visual search, trail making task, Mini Mental Status Examination, and reaction time, visual tests (visual acuity and contrast sensitivity) and assessments of balance (Activities Balance Confidence Scale and Berg Balance Scale) to aid in the interpretation of differences in gaze behaviour. RESULTS: The high risk older adult group spent significantly more time fixating aspects of the travel path than the low risk and young adult groups. High risk older adults were also significantly slower in performing a number of the cognitive tasks than young adults. Correlations were conducted to compare the extent to which travel path fixation durations co-varied with scores on the tests of visual search, motor, and cognitive function. A positive significant correlation was found between the speed of response to the incongruent Stroop task and travel path fixation duration r21  = 0.44, p < 0.05. CONCLUSIONS: The results indicate that our movie-viewing paradigm can identify differences in gaze behaviour between participants grouped on the basis of their age and measures of functional mobility and that these differences are associated with cognitive decline.

The impact of co-occurring mental health problems on referral to and initiation of treatment among youth under probation supervision: Findings from a cluster randomized trial.

INTRODUCTION: Many youth under community supervision have substance use and co-occurring mental health issues. Yet, access to treatment is limited, and many programs cannot address co-occurring disorders. This study examines how co-occurring symptoms among youth on probation affect referral to and initiation of treatment. We hypothesize that both referral and initiation rates will be lower for youth with any co-occurring indicators. METHODS: This study collected administrative data from 14 sites in three states between March 2014 and November 2017 using JJ-TRIALS, a cluster randomized trial. Among 8552 youth in need of treatment (screened as having a substance use problem, drug possession arrest, positive drug test, etc.), 2069 received a referral to treatment and 1630 initiated treatment among those referred. A co-occurring indicator (n = 2828) was based on symptoms of an internalizing and/or externalizing issue. Descriptive analyses compared referral and initiation by behavioral health status. Two-level mixed effects logistic regression models estimated effects of site-level variables. RESULTS: Among youth in need with co-occurring internal, external, or both indicators, only 16 %, 18 %, and 20 % were referred to treatment and of those referred, 63 %, 69 %, and 57 % initiated treatment, respectively. Comparatively, 27 % and 83 % of youth with a substance use only indicator were referred and initiated treatment respectively. Multi-level multivariate models found that, contrary to our hypothesis, co-occurring-both (p = 0.00, OR 1.44) and co-occurring-internal indicators (p = 0.06, OR 1.25) predicted higher referral but there were no differences in initiation rates. However, there was substantial site-level variation. CONCLUSIONS: Youth on probation in need of substance use treatment with co-occurring issues have low referral rates. Behavioral health status may influence youth referral to treatment depending on where a youth is located. Depending on the site, there may be a lack of community programs that can adequately treat youth with co-occurring issues and reduce unmet service needs.

Elaborating on the construct validity of the Triarchic Psychopathy Measure in a criminal offender sample.

Patrick, Fowles, and Krueger (2009) developed the triarchic conceptualization of psychopathy in an effort to integrate historical theories and contemporary measurement models. The model proposes 3 phenotypic domains of boldness, meanness, and disinhibition. Patrick (2010) developed the Triarchic Psychopathy Measure (TriPM), a 58-item self-report measure, to index these 3 domains. This study examined the construct validity of the TriPM in a sample of incarcerated offenders (N = 141) and found evidence of good construct validity in that the scales were related to conceptually relevant normal-range and dysfunctional personality trait criteria, as well as narcissism and deficits in empathy.

Reducing psychiatric illness in the perinatal period: A review and commentary.

This brief overview highlights the global crisis of perinatal psychiatric illness (PPI). PPI is a major contributor to many adverse pregnancy, childbirth, and childhood development outcomes. It contributes to billions of dollars in spending worldwide each year and has a significant impact on the individual, their family, and their community. It is also highly preventable. Current recommendations for intervention and management of PPI are limited and vary considerably from country to country. Furthermore, there are several significant challenges asso-ciated with implementation of these recommendations. These challenges are magnified in number and consequence among women of color and/or minority populations, who experience persistent and negative health disparities during pregnancy and the postpartum period. This paper aims to provide a broad overview of the current state of recommendations and implementation challenges for PPI and layout a framework for overcoming these challenges. An equity-informed model of care that provides universal intervention for pregnant women may be one solution to address the preventable consequences of PPI on child and maternal health. Uniquely, this model emphasizes the importance of managing and eliminating known barriers to traditional health care models. Culturally and contextually specific challenges must be overcome to fully realize the impact of improved management of PPI.

Monounsaturated and Diunsaturated Fatty Acids Sensitize Cervical Cancer to Radiation Therapy.

Obesity induces numerous physiological changes that can impact cancer risk and patient response to therapy. Obese patients with cervical cancer have been reported to have superior outcomes following chemoradiotherapy, suggesting that free fatty acids (FFA) might enhance response to radiotherapy. Here, using preclinical models, we show that monounsaturated and diunsaturated FFAs (uFFA) radiosensitize cervical cancer through a novel p53-dependent mechanism. UFFAs signaled through PPARγ and p53 to promote lipid uptake, storage, and metabolism after radiotherapy. Stable isotope labeling confirmed that cervical cancer cells increase both catabolic and anabolic oleate metabolism in response to radiotherapy, with associated increases in dependence on mitochondrial fatty acid oxidation for survival. In vivo, supplementation with exogenous oleate suppressed tumor growth in xenografts after radiotherapy, an effect that could be partially mimicked in tumors from high fat diet-induced obese mice. These results suggest that supplementation with uFFAs may improve tumor responses to radiotherapy, particularly in p53 wild-type tumors. SIGNIFICANCE: Metabolism of monounsaturated and diunsaturated fatty acids improves the efficacy of radiotherapy in cancer through modulation of p53 activity. See related commentary by Jungles and Green, p. 4513.

Phase I Trial of Stereotactic MRI-Guided Online Adaptive Radiation Therapy (SMART) for the Treatment of Oligometastatic Ovarian Cancer.

PURPOSE: Stereotactic body radiation therapy is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative stereotactic body radiation therapy dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs at risk. A novel radiation delivery method, stereotactic magnetic-resonance-guided online-adaptive radiation therapy (SMART), may improve the therapeutic index of stereotactic body radiation therapy through enhanced soft-tissue visualization, real-time nonionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy-free intervals. This phase I trial assessed feasibility, safety, and dosimetric advantage of SMART to treat ovarian oligometastases. METHODS AND MATERIALS: Ten patients with recurrent oligometastatic ovarian cancer underwent SMART for oligometastasis ablation. Initial plans prescribed 35 Gy/5 fractions with goal 95% planning target volume coverage by 95% of prescription, with dose escalation permitted, subject to strict organ-at-risk dose constraints. Daily adaptive planning was used to protect organs-at-risk and/or increase target dose. Feasibility (successful delivery of >80% of fractions in the first on-table attempt) and safety of this approach was evaluated, in addition to efficacy, survival metrics, quality-of-life, prospective timing and dosimetric outcomes. RESULTS: Ten women with seventeen ovarian oligometastases were treated with SMART, and 100% of treatment fractions were successfully delivered. Online adaptive plans were selected at time of treatment for 58% of fractions, due to initial plan violation of organs-at-risk constraints (84% of adapted fractions) or observed opportunity for planning target volume dose escalation (16% of adapted fractions), with a median on-table time of 64 minutes. A single Grade ≥3 acute (within 6 months of SMART) treatment-related toxicity (duodenal ulcer) was observed. Local control at 3 months was 94%; median progression-free survival was 10.9 months. Median Kaplan-Meier estimated systemic-therapy-free survival after radiation completion was 11.5 months, with concomitant quality-of-life improvements. CONCLUSIONS: SMART is feasible and safe for high-dose radiation therapy ablation of ovarian oligometastases of the abdomen, pelvis, and central thorax with minimal toxicity, high rates of local control, and prolonged systemic-therapy-free survival translating into improved quality-of-life.

Health ranking of the largest US counties using the Community Health Status Indicators peer strata and database.

OBJECTIVE: Using the structure of the Community Health Status Indicators (CHSI) report, we embarked on analysis of population health data with the aim to validate the CHSI modules as overarching themes and to rank county health within peer strata. DESIGN, SETTING, PARTICIPANTS: Ranking was conducted for the largest (>100 000), nonfrontier counties (county aggregates) (N = 508) in the United States for many aspects of population health. Factor analysis was used to assess CHSI modularity and analyses of variance confirmed peer strata homogeneity. MAIN OUTCOME MEASURES: Ten factors were identified. They were life stage, injury, cancer, adult behaviors, preventive services, environment-food, and health care access. Because they did not contribute to a factor, 4 CHSI summary health measures (all-cause mortality, average life expectancy, health status, and unhealthy days) were also ranked. RESULTS: No single factor emerged as reflecting overall county health. CONCLUSIONS: Further summary of county health will be challenging. We present the ranks for CHSI peer strata #1, local jurisdictions of 1 million or greater population. County factor content and data availability may differ when counties of smaller size are considered. Ranking may be utilized by community leaders for community health assessment and local priority setting, and ultimately incorporated into CHSI Web-based reports.

Holding on to pieces of the past: Daily reports of nostalgia in a life-span sample.

Nostalgia, the fond remembrance of one's past, is a common experience hypothesized to increase across the life span. Yet data on the specific features of nostalgia, such as daily frequency and associated affect, are scarce. This study sought to address this limitation by assessing the daily experience of nostalgia using experience-sampling methods. A life-span sample of 108 participants (47 young, 31 middle-aged, and 30 older adults) completed a 2-week, twice-daily experience-sampling study that yielded data describing the frequency and emotions of everyday nostalgia. Multilevel logistic regression analyses supported increased nostalgia frequency at every life stage: Young adults were 60% less likely to report nostalgia compared with middle-aged adults (odds ratio [OR] = .40), whereas older adults were 3 times more likely than middle-aged adults to report nostalgia (OR = 3.05). Additionally, the experience of nostalgia was associated with significant heterogeneity in positive and negative affect. Approximately 72% of participants experienced an increase in positive affect, and 51% experienced an increase in negative affect. For young and middle-aged adults, a change in positive affect was associated with a 2-times-larger increase in nostalgia likelihood, whereas a change in negative affect was more strongly associated with a nostalgia experience in older adults. The current study provides increased evidence for the affectively mixed nature of nostalgia and how the affective pattern differs for adults of different ages. Greater nostalgia frequency may be instrumental during life review when individuals make meaning of their lives, fulfilling developmental goals of late adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introducing a Face Sort Paradigm to Evaluate Age Differences in Emotion Perception.

OBJECTIVES: Previous research has uncovered age-related differences in emotion perception. To date, studies have relied heavily on forced-choice methods that stipulate possible responses. These constrained methods limit discovery of variation in emotion perception, which may be due to subtle differences in underlying concepts for emotion. METHOD: We employed a face sort paradigm in which young (N = 42) and older adult (N = 43) participants were given 120 photographs portraying six target emotions (anger, disgust, fear, happiness, sadness, and neutral) and were instructed to create and label piles, such that individuals in each pile were feeling the same way. RESULTS: There were no age differences in number of piles created, nor in how well labels mapped onto the target emotion categories. However, older adults demonstrated lower consistency in sorting, such that fewer photographs in a given pile belonged to the same target emotion category. At the same time, older adults labeled piles using emotion words that were acquired later in development, and thus are considered more semantically complex. DISCUSSION: These findings partially support the hypothesis that older adults' concepts for emotions and emotional expressions are more complex than those of young adults, demonstrate the utility of incorporating less constrained experimental methods into the investigation of age-related differences in emotion perception, and are consistent with existing evidence of increased cognitive and emotional complexity in adulthood.

Age similarities in matching pro- and contra-hedonic emotional strategies to everyday scenarios.

Older adults are motivated to maximize positive affect in the present. Young adults will purposely feel negative and high arousal emotions in order to achieve a goal. However, this type of contra-hedonic emotional alignment has not been extensively studied with older adults. We expected older adults are less likely than young adults to select high arousal and negative emotions within specific scenarios where those states could be useful. In two studies, participants selected the emotion they preferred in hypothetical problems that varied on the arousal and valence best suited for goal achievement. Young and older adults were equally likely to endorse affective strategies that matched both pro and contra-hedonic scenarios. While older adults may be generally motivated to avoid negative and high-arousing emotions, they are just as likely as young adults to indicate that these states could be helpful in certain situations.

An Emergency Preparedness Response to Opioid-Prescribing Enforcement Actions in Maryland, 2018-2019.

Federal and state enforcement authorities have increasingly intervened on the criminal overprescribing of opioids. However, little is known about the health effects these enforcement actions have on patients experiencing disrupted access to prescription opioids or medication-assisted treatment/medication for opioid use disorder. Simultaneously, opioid death rates have increased. In response, the Maryland Department of Health (MDH) has worked to coordinate mitigation strategies with enforcement partners (defined as any federal, state, or local enforcement authority or other governmental investigative authority). One strategy is a standardized protocol to implement emergency response functions, including rapidly identifying health hazards with real-time data access, deploying resources locally, and providing credible messages to partners and the public. From January 2018 through October 2019, MDH used the protocol in response to 12 enforcement actions targeting 34 medical professionals. A total of 9624 patients received Schedule II-V controlled substance prescriptions from affected prescribers under investigation in the 6 months before the respective enforcement action; 9270 (96%) patients were residents of Maryland. Preliminary data indicate fatal overdose events and potential loss of follow-up care among the patient population experiencing disrupted health care as a result of an enforcement action. The success of the strategy hinged on endorsement by leadership; the establishment of federal, state, and local roles and responsibilities; and data sharing. MDH's approach, data sources, and lessons learned may support health departments across the country that are interested in conducting similar activities on the front lines of the opioid crisis.

Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 inhibitor palbociclib on HPVU cancer cell lines. Patients with HPVU CC tumors had worse progression-free and overall survival outcomes compared to HPV+ patients. TP53, ARID1A, PTEN, ARID5B, CTNNB1, CTCF, and CCND1 were identified as significantly mutated genes (SMGs) enriched in HPVU tumors, with converging functional roles in cell cycle progression. In vitro HPVU, but not HPV+, cancer cell lines with wild type RB1 were sensitive to palbociclib monotherapy. These results indicate that HPVU status can be translated into the clinic as a predictive biomarker of poor patient response to standard of care treatments. We suggest primary cervix tumors be routinely tested for HPV prior to treatment to identify patients who will benefit from more aggressive precision-driven therapy. Our results identify palbociclib as a lead candidate as an alternative treatment strategy for HPVU CC patients.

"We" Before "Me": Differences in Usage of Collectivistic and Individualistic Language Influence Judgments of Electability and Performance.

OBJECTIVES: Older adults are often judged to be warm, but not competent, which contradicts their representation in positions of authority. This study sought to extend evidence of age differences in more individualistic (e.g., "I") and collectivistic (e.g., "we") language and explore their impact on judgments of performance and electability. METHOD: Speeches from young and older adults who campaigned for a fictitious position were analyzed using Linguistic and Inquiry Word Count Software. Words fitting specified categories (e.g., pronouns, affect) were compared to outcome judgments obtained from trained coders on the dimensions of performance and electability. RESULTS: Older adults used significantly more "we"-language. Young adults used more "I"-language, and more positive affect, achievement, and power language. Language choices and coder judgments were associated such that the more "I"-language that was used during the speech, the less electable the candidate was judged. This relationship was not found for "we"-language. DISCUSSION: This study found no evidence for collectivistic language enhancing ratings of electability or performance; however, an age-invariable, negative relationship was obtained between increased individualistic language and reduced coder judgments of electability. This suggests that speakers should minimize "I"-statements to promote electability, a characteristic that is reflected more in older adults' speeches than young.

Tumor Microenvironment as a Regulator of Radiation Therapy: New Insights into Stromal-Mediated Radioresistance.

: A tumor is a complex "organ" composed of malignant cancer cells harboring genetic aberrations surrounded by a stroma comprised of non-malignant cells and an extracellular matrix. Considerable evidence has demonstrated that components of the genetically "normal" tumor stroma contribute to tumor progression and resistance to a wide array of treatment modalities, including radiotherapy. Cancer-associated fibroblasts can promote radioresistance through their secreted factors, contact-mediated signaling, downstream pro-survival signaling pathways, immunomodulatory effects, and cancer stem cell-generating role. The extracellular matrix can govern radiation responsiveness by influencing oxygen availability and controlling the stability and bioavailability of growth factors and cytokines. Immune status regarding the presence of pro- and anti-tumor immune cells can regulate how tumors respond to radiation therapy. Furthermore, stromal cells including endothelial cells and adipocytes can modulate radiosensitivity through their roles in angiogenesis and vasculogenesis, and their secreted adipokines, respectively. Thus, to successfully eradicate cancers, it is important to consider how tumor stroma components interact with and regulate the response to radiation. Detailed knowledge of these interactions will help build a preclinical rationale to support the use of stromal-targeting agents in combination with radiotherapy to increase radiosensitivity.

Age Differences in Preferences for Fear-Enhancing Vs. Fear-Reducing News in a Disease Outbreak.

Older adults (OA) prefer positive over negative information in a lab setting, compared to young adults (YA; i.e., positivity effects). The extent to which OA avoid negative events or information relevant for their health and safety is not clear. We first investigated age differences in preferences for fear-enhancing vs. fear-reducing news articles during the Ebola Outbreak of 2014. We were able to collect data from 15 YA and 13 OA during this acute health event. Compared to YA, OA were more likely to read the fear-enhancing article, select hand-sanitizer over lip balm, and reported greater fear of Ebola. We further investigated our research question during the COVID-19 pandemic with 164 YA (18-30 years) and 171 OA (60-80 years). Participants responded to an online survey about the COVID-19 pandemic across 13 days during the initial peak of the pandemic in the United States (U.S.). Both YA and OA preferred to read positive over negative news about the coronavirus, but OA were even more likely than YA to prefer the positive news article. No age differences in the fear of contraction were found, but OA engaged in more health-protective behaviors compared to YA. Although OA may not always report greater fear than YA or seek out negative information related to a health concern, they still engage in protective health behaviors. Thus, although positivity effects were observed in attention and emotional reports (in the COVID-19 study), OA still modified their behaviors more than YA (giveaway in both studies, and health-protective behavior change in the COVID-19 study), suggesting that positivity effects did not hamper OA ability to respond to a health crisis.