Impaired immune function in children and adults with Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. PROCEDURE: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. RESULTS: Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4+ T cells were decreased (P = 0.022), while CD8+ T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8+ T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. CONCLUSIONS: Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development.

Disparities in Clinical Trial Participation: A Cross-Sectional Survey of Cancer Patients at a Midwest Academic Medical Center.

Research conducted on homogenous populations can lead to biased and misleading findings, impeding the development of effective interventions and treatments for diverse populations. Low participation among minority groups further leads to disparities in access to innovative cancer care and treatment outcomes associated with trial participation. To better understand cancer patients' attitudes and willingness to participate in clinical trials, solid tumor patients attending their clinic visits were invited to complete a survey. The survey included questions on demographics, previous trial participation, and future trial interest. Responses were analyzed with frequency tables and chi-square tests. Of 300 participants, only 96 (32%) were asked to participate in a clinical trial. Of these, 81 (84%) chose to participate and 15 (16%) did not. There were notable differences by race but not gender or education level. Of the 204 who had never been asked to participate, 70% indicated that they would be willing to participate in future, and there was a strong sex-race interaction. Non-White males were the most hesitant group. Of 204, 99% indicated that they would participate to access new treatments, and 57% would participate to contribute to research overall. This study shows that many solid tumor patients undergoing treatment are not offered clinical trials. Racial differences in attitudes toward trial participation are evident. Nonetheless, many patients are willing to participate in trials to access innovative treatments and to support research. Culturally relevant outreach to build trust with minority groups is needed to increase overall participation in clinical trials.

Cultural Insiders and Graphic Stories to Promote Research Readiness Among the South Asian Community: A Focus on Purpose, Protection, and Participation.

South Asians living in the United States are frequently underrepresented in health research. Their lack of participation limits the generalizability of research to them and keeps them from receiving the high-quality care and innovation that some studies may offer. "Research Ready" is a five-panel, community co-created graphic-style story that encourages discussion around the purpose of research, safety/protection while participating, and why diverse participation-including South Asians-improves study results and leads to more effective interventions/treatments. This study leveraged trained young adult "cultural insiders" to invite attendees of a Midwestern South Asian Cultural Festival to read the story aloud together as the characters in English or Hindi and used a decision guide to invite discussion. Post-discussion surveys (N = 104) were analyzed using descriptive statistics. Participants spanned from 10 to 79 years, with 42% < 18 years and more females (61%). Only 18.3% indicated having prior research participation. Adults 40+ years (60%) requested the story/discussion in Hindi, compared to 2.3% of adolescents and 6.7% of younger adults. After the discussion, participants indicated their willingness to consider participation, with most being open to participating in surveys/interviews (95.2%); only 52.9% would consider studies requiring the taking of medicines. Adolescents, females, and adults with higher education were more willing to participate in medication studies. Nearly all (97.1%) said they would feel safe participating in research, and 88.5% shared that the discussion would help them better decide about future participation. In conclusion, "Research Ready" discussions shared by cultural insiders effectively encourage South Asians to consider future research participation.

A Short-Term Evaluation of the Eat and Exercise to Win Program for Adults with Intellectual and Developmental Disabilities.

(1) Study Aim: Adults with intellectual and developmental disabilities (IDD) face a multitude of chronic health risks related to obesity, including diabetes and heart disease. Day adult service programs offer unique opportunities for improving and monitoring the health of this vulnerable group. To promote exercise and healthy eating habits among adults with IDD, the Eat and Exercise to Win Program (EE-2-Win) was offered weekly at two locations over 8-9 months. (2) Methods: Using daily logs, staff assessed outcomes of 26 program participants, including changes in knowledge, eating and exercise habits, and water consumption. Participants' weights were measured, and their lunches were photographed at baseline and 3 months. (3) Results: While participants' weights did not significantly differ at 3 months, assessing photographs indicated that participants' lunches included more fruits and vegetables. Staff surveys indicated that participants had greater knowledge of MyPlate and were consuming more water at three months. Survey responses indicated that staff perceived the program to be valuable overall, and challenges in learning and assessment were reported given differences in the cognitive abilities of adults with IDD. Staff also suggested engaging home caregivers in the program, as they often make dietary decisions. (4) Conclusions: Overall, results confirmed that the EE-2-Win Program positively impacted healthy eating and exercise. Future work, however, with both staff and caregivers is needed to further optimize the program.

The fanconi anemia pathway limits human papillomavirus replication.

High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.

Opportunities to Improve HPV Vaccination Among Pediatric, Adolescent, and Young Adult Cancer Survivors by Engaging both Oncology and Primary Care Teams.

The incidence of second primary cancers is rising particularly among pediatric, adolescent, and young adult (PAYA) cancer survivors. While human papillomavirus (HPV)-associated cancers can be prevented by vaccination, their uptake is lower and delayed in this group. Because a recommendation from a health care provider is the strongest predictor of HPV vaccination, there are great opportunities for PAYA cancer care providers to positively impact HPV vaccination rates. Prioritizing PAYA cancer care provider education as well as improving the education of and coordination with primary care providers are viewed as opportunities to encourage HPV vaccine uptake and prevent future cancers. See related article by Garcia et al., p. 581.

Promoting Community Health and Understanding of Science Topics by Reading Graphic-Style Stories Aloud Together.

Limited health literacy and access to engaging, relevant, understandable health promotion and disease prevention materials are barriers to achieving and maintaining health. The We-Engage-4-Health program co-created the graphic-style story "Foamy Soap Fun" with community members to reinforce the importance of the primary preventive strategy-handwashing-in limiting spread of COVID-19. Pre/postsurveys were administered, and a modified focus group was conducted to learn community participants' preferences for reading stories (aloud together and/or silently to themselves), versus reading typical health promotion information sheets. Three themes were identified related to reading the story aloud: increased enthusiasm, increased attentiveness, and improved interpretation skills, vocabulary, and information processing skills. Educational constructs included: empathy with the story's characters, engagement with previous health experiences, enthusiasm with sharing health information, and explanation of complex health topics. This study supports the value of graphic-style stories in helping communities to better understand the science behind health topics.

Environmental Health Knowledge Does Not Necessarily Translate to Action in Youth.

Environmental challenges pose serious health problems, especially for children, and lay public action is lacking. This study sought to characterize the relationship between environmental health knowledge and behavior in youth. A cross-sectional, descriptive survey with quantitative and qualitative questions was conducted. Open-ended questions were coded to generate themes/subthemes. Subscales' scores were presented as mean ± SD or median and interquartile range (IQR). T- and Mann-Whitney tests were used to compare groups, and correlations were used to evaluate covariation. A total of 452 children were surveyed. Youth verbalized concerns about their environments and their impact on health. Air pollution was the most concerning issue. Participants had moderate knowledge scores. Few described the three health domains; even fewer included environment. Behavior scores were low and weakly correlated with knowledge, but were moderately correlated with attitude and self-efficacy. Participation in environmental classes, activities, and clubs was associated with higher scores. We found variable environmental health knowledge, limited understanding of the local environment's impact on health, and a weak association between youth's knowledge and behavior. Focused formal and non-formal educational experiences were associated with improved scores, indicating the value of targeted youth educational programming to increase environmental health knowledge and action.

The Eyewitness Community Survey: An Engaging Citizen Science Tool to Capture Reliable Data while Improving Community Participants' Environmental Health Knowledge and Attitudes.

Many youths and young adults have variable environmental health knowledge, limited understanding of their local environment's impact on their health, and poor environmentally friendly behaviors. We sought to develop and test a tool to reliably capture data, increase environmental health knowledge, and engage youths as citizen scientists to examine and take action on their community's challenges. The Eyewitness Community Survey (ECS) was developed through several iterations of co-design. Herein, we tested its performance. In Phase I, seven youths audited five 360° photographs. In Phase II, 27 participants works as pairs/trios and audited five locations, typically 7 days apart. Inter-rater and intra-rater reliability were determined. Changes in participants' knowledge, attitudes, behaviors, and self-efficacy were surveyed. Feedback was obtained via focus groups. Intra-rater reliability was in the substantial/near-perfect range, with Phase II having greater consistency. Inter-rater reliability was high, with 42% and 63% of Phase I and II Kappa, respectively, in the substantial/near-perfect range. Knowledge scores improved after making observations (p ≤ 0.032). Participants (85%) reported the tool to be easy/very easy to use, with 70% willing to use it again. Thus, the ECS is a mutually beneficial citizen science tool that rigorously captures environmental data and provides engaging experiential learning opportunities.

Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema.

BACKGROUND: Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial protein associated with allergic inflammation in mice that has not been evaluated in human atopic diseases. OBJECTIVE: To determine whether single-nucleotide polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the phenotype of childhood eczema combined with asthma. METHODS: Genotyping for SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4 years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR; N = 1152; ages 5-10 years). Eczema and eczema plus asthma were clinical outcomes based on parental report and clinician's diagnosis. Genetic analyses were restricted to whites and adjusted for sex in both cohorts and adjusted for environmental covariates in CCAAPS. RESULTS: Variants in SPRR2B were not significantly associated with eczema in either cohort after Bonferroni adjustment. Children from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4 times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence interval, 1.5-10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95% confidence interval, 1.8-9.1; P < .001 in the GCPCR), however. SNPs in SPRR2B were not in strong linkage disequilibrium with the R501X and del2282 FLG mutations, and these findings were independent of FLG. CONCLUSIONS: An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. SPRR2B polymorphisms may serve as important predictive markers for the combined eczema plus asthma phenotype.

Leveraging Stories to Promote Health and Prevent Cancer.

Many challenges are associated with communicating health messages to promote healthy behaviors and prevent cancer including limited health literacy levels, varied life experiences, and different learning styles. In this issue of Cancer Prevention Research, Chen and colleagues codeveloped personal, audiovisual digital stories using community-engaged, Digital Storytelling. Their goal was to improve the attitudes of and vaccination intention for human papillomavirus among Vietnamese American mothers of unvaccinated children ages 11-14. This spotlight discusses the implications of their results and further the broader use of stories as tools to promote health and prevent cancer-particularly in underserved minority and immigrant populations. See related article, p. 465.

Shared Purpose: Leveraging a Community-Academic Partnership to Increase Local Environmental Health Awareness via Community Science.

Environmental factors can lead to disease and health disparities when the places where people live, learn, work, play and pray are burdened by social inequities. Non-formal programs that explicitly connect local environmental exposures and human health could be of great value to communities at greatest risk. The purpose of this work was to co-create relevant and engaging education with youth and community stakeholders of all ages that more explicitly emphasizes the link between the local environment and community members' health through a hands-on community science experience. Our experiences helped strengthen our community-academic partnership and establish a route to create and tailor informal programming to meet local needs and engage people in community science with academic partners. We generated two distinctly different community science neighborhood audit tools designed to differently engage our community partners and inform community participants of their local environments and its role on their health. Through community meetings, we garnered critical insight from our stakeholders. While neither of the tools and accompanying data collected were deemed to be scientifically generalizable, our ongoing and future work has benefited from important lessons learned from their creation and sharing.

Co-Designing a Program to Lower Cardiovascular Disease Risk in Midlife Black Women.

Midlife Black women suffer disproportionately from heart disease and stroke in comparison to White women of similar age and demographic. Risk for cardiovascular disease (CVD) and stroke is largely considered to be modifiable yet CVD prevention and awareness campaigns have been less effective among Black women. Decreased awareness of personal CVD risk is associated with delays in the presentation of women to the emergency room or health care providers for symptoms of myocardial infarction. The Midlife Black Women's Stress and Wellness (B-SWELL) program was designed to increase awareness about CVD risk factors, stress, and healthy lifestyle behaviors among midlife Black women. In partnership with an existing Community Research Advisory Board (C-RAB), materials were developed and culturally adapted for the B-SWELL program. Following successful development of the B-SWELL materials, a trial of the B-SWELL program was conducted with a sample of midlife Black women recruited from the community. The program was co-facilitated by members of the C-RAB. We outline the strategies used to successfully co-create and trial the B-SWELL program materials and reflect on the strengths and challenges associated with the development of a culturally tailored heart disease prevention program using community participatory methods.

A randomized feasibility trial of the Midlife Black Women's Stress and Wellness intervention (B-SWELL); a community participatory intervention to increase adoption of Life's Simple 7 healthy lifestyle behaviors.

BACKGROUND: Black women have a disproportionately higher incidence of cardiovascular disease-related mortality than other groups, yet they are less likely to receive culturally proficient education and competent preventive care. PURPOSE: The purpose of this study was to determine feasibility of the Midlife Black Women's Stress and Wellness intervention (B-SWELL); a culturally adapted, 8-week group intervention leveraging stress reduction and goal setting to increase awareness and adoption of Life's Simple 7 (LS7) healthy lifestyle behaviors. METHODS: A randomized feasibility trial was conducted. Participants (N = 48, mean age = 55 years) were randomized to the B-SWELL or a group wellness (WE) intervention that lacked stress reduction and goal setting instruction. We hypothesized that B-SWELL participants would achieve a lower perceived stress, greater self-efficacy, improved LS7 scores, fewer symptoms (depression and unhealthy days), and greater perceived general health compared to WE participants. Survey data were collected at three timepoints: baseline, 8 weeks, and 12 weeks. RESULTS: Both B-SWELL and WE groups had low attrition and navigated the online platform well. Further, both groups experienced lower perceived stress, improved LS7 scores, reduced depressive symptoms, and greater perceived general health from baseline to 8 weeks. Based on data trends, participants in the B-SWELL had more improvement in perceived stress, self-efficacy, and mental and physical unhealthy days compared to WE participants. CONCLUSION: The B-SWELL is a feasible intervention for midlife Black women. Positive data trends were found for both B-SWELL and WE groups. Based on observations from the feasibility study, a larger outcomes-based study is planned.

Midlife Black women have a greater chance of dying from heart disease compared to other groups. However, Black women are less likely to receive the education and health care needed to affect this difference. The purpose of this study was to compare a new program, the Midlife Black Women's Stress and Wellness intervention (B-SWELL) to a wellness program (WE). The B-SWELL program uses education, stress reduction, and goal setting to improve healthy lifestyle behaviors in midlife Black women. The WE program provided health education in a group setting but did not offer information about stress or goal setting. We enrolled 48 midlife Black women ages 40­64 years old into the study. The women were randomly assigned to either the B-SWELL or WE program. We proposed that women in the B-SWELL program would have lower stress, improved healthy lifestyle scores, less depression, and fewer symptoms compared to women in the WE program. Both groups experienced lower stress, improved healthy lifestyle scores, and less depression. Women in the B-SWELL had greater improvement in stress and symptoms. In conclusion, the B-SWELL program is practical for midlife Black women. A larger study is planned.

COVID-19 Vaccine Hesitancy: A Critical Time Period Analysis.

The COVID-19 pandemic has been a devastating, global public health crisis. Public health systems in the United States heavily focused on getting people to adhere to preventive behaviors, and later, to get vaccinated. January through May of 2021 was a critical and volatile time period for COVID-19 cases, deaths, and expanding vaccination programs coinciding with important political and social events which will have a lasting impact on how the public views science, places trust in our government, and views individual rights. Having collected almost 1400 surveys, our goal was to assess vaccine behavior, explore attitudes toward receiving the vaccine, and identify trusted information sources. More than 83% of our survey respondents said they were at least partially vaccinated. Of 246 unvaccinated, 31.3% were somewhat or extremely likely to get vaccinated when available. Their two most common concerns were vaccine effectiveness (41.1%) and safety (40.2%). Significant differences were observed between respondents who were likely to be vaccinated in the future and those who were hesitant on three of five demographic variables. Our data provide unique insight into the history of behavior and motivations related to COVID-19 vaccines-what will be seen as a "wicked problem" for years to come.

Development of Food Literacy Assessment Tool Targeting Adults With Low Income.

OBJECTIVE: Develop and test validity and reliability of the Food Literacy Assessment Tool (FLitT) in adults with low income. DESIGN: Face validity was tested using cognitive interviews, content validity using expert review, and internal consistency reliability and test-retest reliability based on 2 administrations of the survey. SETTING: Urban choice food pantry in Cincinnati, OH. PARTICIPANTS: There were 10 and 98 adults with low income for the cognitive interview and survey, respectively VARIABLES MEASURED: Knowledge, self-efficacy, and behavior required to plan and manage, select, prepare, and eat in relation to food. ANALYSIS: Cronbach α and Kuder-Richardson Formula 20 for internal consistency reliability and intraclass correlation coefficient (ICC) for test-retest reliability. RESULTS: Cognitive interviews and expert feedback suggested modifications to improve the clarity of FLitT and offer more response options. Testing shows acceptable internal consistency in self-efficacy (Cronbach α = 0.92) and behavior (Cronbach α = 0.90) but not in knowledge (Kuder-Richardson Formula 20 = 0.51). The FLitT shows acceptable test-retest reliability for knowledge (ICC = 0.84), self-efficacy (ICC = 0.70), and behavior (ICC = 0.93). CONCLUSIONS AND IMPLICATIONS: The FLitT was developed and tested for face and content validity and internal and test-retest reliability in adults with low income. Additional research is needed to conduct a second round of face validity and test construct validity using factor analysis with a larger size.

Attitudes About COVID-19 and Health (ATTACH): Online Survey and Mixed Methods Study.

BACKGROUND: Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. OBJECTIVE: In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. METHODS: The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll questions related to COVID-19 2 times daily and a monthly survey assessing mental health, social isolation, physical health, and quality of life. Poll question responses were graphed using 95% Clopper-Pearson (exact) tests with 95% CIs. Pearson correlations, hierarchical linear regression analyses, and generalized linear models assessed relationships, predictors of self-reported outcomes, and group differences, respectively. RESULTS: By October 31, 2020, 1405, 80, and 90 participants had consented to participate in the UK, United States, and Mexico, respectively. Descriptive data for the UK daily poll questions indicated that participants generally followed social distancing measures, but worry and negative impacts on families increased as the pandemic progressed. Although participants generally reported feeling that the reasons for current measures had been made clear, there was low trust that the government was doing everything in its power to meet public needs. In the UK, 1282 participants also completed a monthly survey (94.99% [1326/1396] White, 72.22% [1014/1404] female, and 20.12% [277/1377] key or essential workers); 18.88% (242/1282) of UK participants reported a preexisting mental health disorder, 31.36% (402/1282) reported a preexisting chronic medical illness, and 35.11% (493/1404) were aged over 65; 57.72% (740/1282) of participants reported being more sedentary since the pandemic began, and 41.89% (537/1282) reported reduced access to medical care. Those with poorer mental health outcomes lived in more deprived neighborhoods, in larger households (Ps<.05), had more preexisting mental health disorders and medical conditions, and were younger than 65 years (all Ps<.001). CONCLUSIONS: Communities who have been exposed to additional harm during the COVID-19 pandemic were experiencing worse mental outcomes. Factors including having a medical condition, or living in a deprived neighborhood or larger household were associated with heightened risk. Future longitudinal studies should investigate the link between COVID-19 exposure, mental health, and sociodemographic and residential characteristics.

Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia.

High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96-11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.