Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with ß3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly ß3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.

Human-centered designed communication tools for obesity prevention in early life.

Objective: How we communicate about obesity is critical as treatment paradigms shift upstream. We previously identified parental perceptions, concerns, beliefs, and communication preferences about early life obesity risk. We engaged parents of children 0 to 24 months of age and pediatricians from Indianapolis, Indiana, USA in the co-design of messages and tools that can be used to facilitate parent/provider conversations about early life obesity prevention. Methods: From April to June 2021, we conducted a series of co-design workshops with parents of children ages 0 to 24 months and pediatricians to identify their preferences for communicating obesity prevention in the setting of a pediatric well visit. Human-centered design techniques, including affinity diagraming and model building, were used to inform key elements of a communication model and communication strategy messages. These elements were combined and refined to create prototype tools that were subsequently refined using stakeholder feedback. Results: Parent participants included 11 mothers and 2 fathers: 8 white, 4 black, and 1 Asian; median age 33 years with 38% reporting annual household incomes less than $50,000. Pediatricians included 7 female and 6 male providers; 69% white. Through an iterative process of co-design, we created an exam room poster that addresses common misconceptions about infant feeding, sleep and exercise, and a behavior change plan to foster parent/provider collaboration focused on achieving children's healthy weight. Conclusions: Our hands-on, collaborative approach may ultimately improve uptake, acceptability and usability of early life obesity interventions by ensuring that parents remain at the center of prevention efforts.

Altered endosomal-lysosomal biogenesis in melanoma.

Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis. Herein, the involvement of the endosomal-lysosomal system in melanoma was examined by pooled secondary analysis of existing gene expression datasets. A set of differentially expressed endosomal-lysosomal genes was identified in melanoma, which were interconnected by biological function. To illustrate the protein expression of the dysregulated genes, immunohistochemistry was performed on samples from patients with cutaneous melanoma to reveal candidate markers. This study demonstrated the dysregulation of Syntenin-1, Sortilin and Rab25 may provide a differentiating feature between cutaneous melanoma and squamous cell carcinoma, while IGF2R may indicate malignant propensity in these skin cancers.

Development of a Family-Centered Communication Tool for Kidney Health in Premature Infants: Qualitative Focus Group Study Using Human-Centered Design Methodology.

BACKGROUND: Premature infants are at increased risk of kidney-related complications, including acute kidney injury (AKI) and chronic kidney disease (CKD). The risk of CKD in prematurely born infants is underrecognized by health care teams and caregivers. Understanding how to communicate the risk of CKD to caregivers is essential for longitudinal clinical follow-up and adherence. OBJECTIVE: This study aimed to determine family caregiver attitudes toward kidney health and risk communication during a neonatal intensive care admission. We also sought to understand caregiver preferences for the communication of information surrounding the risk of CKD in premature infants. METHODS: We augmented standard qualitative group sessions with human-centered design methods to assess parent preferences and clinician perspectives. Caregivers recruited had a prematurely born child who spent time in the neonatal intensive care unit at Riley Hospital for Children in Indianapolis, Indiana, and experienced AKI or another kidney complication, which put them at risk for future CKD. We used a variety of specific design methods in these sessions, including card sorting, projective methods, experience mapping, and constructive methods. RESULTS: A total of 7 clinicians and 8 caregivers participated in 3 group sessions. Caregivers and clinicians readily acknowledged barriers to and drivers of long-term kidney monitoring as well as opportunities for communication of the risk of long-term kidney disease. Caregivers' primary concerns were for both the type and depth of information conveyed as well as the time at which it was communicated. Participants emphasized the importance of collaboration between the hospital care team and the primary care provider. Participant input was synthesized into several prototype concepts and, ultimately, into a rough prototype of a website and an informational flyer. CONCLUSIONS: Caregivers of premature infants are open to communication about kidney health during their neonatal admission. The next phase of this work will translate caregivers' preferences into family-centered communication tools and test their efficacy in the neonatal intensive care unit.

Appl1, Sortilin and Syndecan-1 immunohistochemistry on intraductal carcinoma of the prostate provides evidence of retrograde spread.

The presence of intraductal carcinoma of the prostate (IDCP) correlates with late-stage disease and poor outcomes for patients with prostatic adenocarcinoma, but the accurate and reliable staging of disease severity remains challenging. Immunohistochemistry (IHC) has been utilised to overcome problems in assessing IDCP morphology, but the current markers have only demonstrated limited utility in characterising the complex biology of this lesion. In a retrospective study of a cohort of patients who had been diagnosed with IDCP, we utilised IHC on radical prostatectomy sections with a biomarker panel of Appl1, Sortilin and Syndecan-1, to interpret different architectural patterns and to explore the theory that IDCP occurs from retrograde spread of high-grade invasive prostatic adenocarcinoma. Cribriform IDCP displayed strong Appl1, Sortilin and Syndecan-1 labelling patterns, while solid IDCP architecture had high intensity Appl1 and Syndecan-1 labelling, but minimal Sortilin labelling. Notably, the expression pattern of the biomarker panel in regions of IDCP was similar to that of adjacent invasive prostatic adenocarcinoma, and also comparable to prostate cancer showing perineural and vascular invasion. The Appl1, Sortilin, and Syndecan-1 biomarker panel in IDCP provides evidence for the model of retrograde spread of invasive prostatic carcinoma into ducts/acini, and supports the inclusion of IDCP into the five-tier Gleason grading system.

Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1.

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.

Building a prototype of a continence goal-selection tool for children with spina bifida: Patient, parental and urology provider recommendations.

INTRODUCTION: No tools exist to help children with spina bifida (SB) describe their incontinence concerns and to help their providers account for them when evaluating management success. Our aim was to understand patients', parents', and clinicians' preferences about how a SB continence goal-selection tool (MyGoal-C) should look and function, and to create a tool prototype. METHODS: We used a qualitative research approach integrated with human-centered design methods. We recruited children with SB (8-17 years old), parents ( ≥ 18 years old) of children with SB (8-17 years old) in clinic and online, and urology healthcare providers at our institution. We surveyed children and parents, and conducted parent and provider Zoom-based prototyping sessions to iteratively design the app. Design researchers analyzed online activities using affinity diagramming, group analysis and modeling activities. Provider sessions were analyzed with qualitative thematic analysis based on grounded theory. Recruitment continued until saturation was reached. RESULTS: Thirteen children with SB participated (median age: 10 years old, 4 female, 9 shunted, 10 using bladder catheterizations). Thirty-seven parents participated (33 mothers, median age: 43 years old). Children and parents unanimously recommended an app and their comments generated 6 major theme domains: goal-setting process, in-app content, working toward goals, urology provider check-in, app customization, and using big data to improve future functionality. Twenty-one of the parents participated in 3 prototyping sessions with 6 breakout groups. The remaining 16 parents and 13 children then completed the Prototype Testing Survey, leading to a refined prototype and a visual flow map of the app experience (Figure). Feedback from 11 urology healthcare providers (7 female, 6 advanced practice providers) generated 8 themes: patient engagement/autonomy, clearly displaying results, integration into clinic workflow, not increasing clinical staff burden, potential clinician bias, parental involvement, limitations of the app, and future app adaptation. These cumulative data allowed for a construction of a final app prototype. COMMENT: Findings of our study lay the foundation for creating a goal-selection app that meets preferences and needs of children, parents, and providers. Next steps involve building the app, testing its usability and assessing it prospectively in a clinical setting. CONCLUSIONS: Children with SB and parents preferred an app to help them set and track continence goals. All stakeholders, including urology providers, offered complementary and mutually reinforcing feedback to guide the creation of an app prototype that would ultimately be integrated into a clinic visit.

"Research Jam": Engaging patients and other stakeholders through human-centered design to improve translational research.

Effective stakeholder engagement increases research relevance and utility. Though published principles of community-based participatory research and patient-centered outcomes research offer guidance, few resources offer effective techniques to engage stakeholders and translate their engagement into improvements in research process and outcomes. The Indiana Clinical and Translational Sciences Institute (Indiana CTSI) is home to Research Jam (RJ), an interdisciplinary team of researchers, project management professionals, and design experts, that employs human-centered design (HCD) to engage stakeholders in the research process. Establishing HCD services at the Indiana CTSI has allowed for accessible and innovative stakeholder-engaged research. RJ offers services for stakeholder-informed study design, measurement, implementation, and dissemination. RJ's services are in demand to address research barriers pertaining to a diverse array of health topics and stakeholder groups. As a result, the RJ team has grown significantly with both institutional and extramural support. Researchers involved in RJ projects report that working with RJ helped them learn how to better engage with stakeholders in research and changed the way they approach working with stakeholders. RJ can serve as a potential model for effectively engaging stakeholders through HCD to improve translational research.

Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome.

Heme b (iron protoporphyrin IX) plays important roles in biology as a metallocofactor and signaling molecule. However, the targets of heme signaling and the network of proteins that mediate the exchange of heme from sites of synthesis or uptake to heme dependent or regulated proteins are poorly understood. Herein, we describe a quantitative mass spectrometry (MS)-based chemoproteomics strategy to identify exchange labile hemoproteins in human embryonic kidney HEK293 cells that may be relevant to heme signaling and trafficking. The strategy involves depleting endogenous heme with the heme biosynthetic inhibitor succinylacetone (SA), leaving putative heme-binding proteins in their apo-state, followed by the capture of those proteins using hemin-agarose resin, and finally elution and identification by MS. By identifying only those proteins that interact with high specificity to hemin-agarose relative to control beaded agarose in an SA-dependent manner, we have expanded the number of proteins and ontologies that may be involved in binding and buffering labile heme or are targets of heme signaling. Notably, these include proteins involved in chromatin remodeling, DNA damage response, RNA splicing, cytoskeletal organization, and vesicular trafficking, many of which have been associated with heme through complementary studies published recently. Taken together, these results provide support for the emerging role of heme in an expanded set of cellular processes from genome integrity to protein trafficking and beyond.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

A patient- and parent-centered approach to urinary and fecal incontinence in children and adolescents with spina bifida: understanding experiences in the context of other competing care issues.

INTRODUCTION: Despite significant and known challenges to urinary and fecal incontinence (UI and FI, respectively) among children with spina bifida (SB) and their families, few studies have identified patient-centered measures and approaches to assessing them. This study represents the first stage of a larger study to develop a patient-centered goal-setting tool to guide incontinence management (Figure). Our aim was to understand patient experiences of UI and FI, and what goals should be included in the tool. METHODS: We used a qualitative research approach integrated with human-centered design methods. We recruited, in clinic and online, children with SB (8-17 years old) and parents (>=18 years old) of children with SB (8-17 years old). Online activities were analyzed by four experienced design researchers using affinity diagramming, group analysis and modeling activities (mind maps, challenge maps, experience maps). Recruitment and thematic qualitative analysis continued until saturation was reached. RESULTS: Seventeen children with SB participated (9 female, 12 shunted, 13 using bladder catheterizations, 6 using Malone antegrade continence enema, median age: 15 years old). Fifteen parents participated (13 mothers/2 fathers, median age: 42 years old), including six mother-child dyads. Five major themes each were identified for UI and FI experiences: (1) negative emotional impact of incontinence, (2) unpredictability of incontinence, (3) challenging/unpleasant incontinence management, (4) inconvenient/unreliable incontinence management, (5) UI management having unpleasant complications and FI putting much responsibility on parents. We identified six UI goal domains and five FI goal domains. Four overlapping domains included: accidents, independence, interruptions at school and social/friends. Unique domains were: urinary tract infections (UI), catheterizations (UI) and enemas (FI). COMMENT: Findings of our study improve our understanding of children's and parents' experiences associated with incontinence in SB and potential continence goals. CONCLUSIONS: Children with SB experience incontinence as distressing and unpredictable. Incontinence management can be challenging and unreliable. Patient-centered continence goals cluster in domains, indicating how incontinence intermeshes with other life areas and offering potential approaches to structure continence goals in a goals-selection tool.

A human-centered designed outreach strategy for a youth contraception navigator program.

Objective: To identify key elements of an outreach strategy for a youth contraception navigator program designed to help young people overcome barriers to contraception access. Methods: A human-centered design approach was used to engage adolescents aged 15-17 in co-design sessions. Human-centered design techniques, such as affinity diagramming and model building were used to inform key elements of the communication model and the final outreach strategy messages. Results: Messages focused on the individual, normalizing talking about birth control, acknowledging the challenges to obtaining birth control, explaining how the navigator program works resonate with young people. Having images of diverse participants, offering information about birth control, and showing images of reputable sources will enhance trust. Conclusions: A name (IN Control) and key elements of an outreach strategy were determined for the navigator program. It is important to work with key stakeholders and co-design the optimal strategy and messages to assure that the intended audience is reached, and the desired behavior change is achieved. Innovation: Human-centered design techniques can be used to provide insight into programmatic outreach strategies for a contraception navigator program to increase their impact and ultimate success.

Investigating the conservatism-disgust paradox in reactions to the COVID-19 pandemic: A reexamination of the interrelations among political ideology, disgust sensitivity, and pandemic response.

Research has documented robust associations between greater disgust sensitivity and (1) concerns about disease, and (2) political conservatism. However, the COVID-19 disease pandemic raised challenging questions about these associations. In particular, why have conservatives-despite their greater disgust sensitivity-exhibited less concern about the pandemic? Here, we investigate this "conservatism-disgust paradox" and address several outstanding theoretical questions regarding the interrelations among disgust sensitivity, ideology, and pandemic response. In four studies (N = 1,764), we identify several methodological and conceptual factors-in particular, an overreliance on self-report measures-that may have inflated the apparent associations among these constructs. Using non-self-report measures, we find evidence that disgust sensitivity may be a less potent predictor of disease avoidance than is typically assumed, and that ideological differences in disgust sensitivity may be amplified by self-report measures. These findings suggest that the true pattern of interrelations among these factors may be less "paradoxical" than is typically believed.

A gateway conspiracy? Belief in COVID-19 conspiracy theories prospectively predicts greater conspiracist ideation.

A primary focus of research on conspiracy theories has been understanding the psychological characteristics that predict people's level of conspiracist ideation. However, the dynamics of conspiracist ideation-i.e., how such tendencies change over time-are not well understood. To help fill this gap in the literature, we used data from two longitudinal studies (Study 1 N = 107; Study 2 N = 1,037) conducted during the COVID-19 pandemic. We find that greater belief in COVID-19 conspiracy theories at baseline predicts both greater endorsement of a novel real-world conspiracy theory involving voter fraud in the 2020 American Presidential election (Study 1) and increases in generic conspiracist ideation over a period of several months (Studies 1 and 2). Thus, engaging with real-world conspiracy theories appears to act as a gateway, leading to more general increases in conspiracist ideation. Beyond enhancing our knowledge of conspiracist ideation, this work highlights the importance of fighting the spread of conspiracy theories.

Dual Protection Messaging for Adolescents and Young Adults in the Setting of Over-the-Counter Hormonal Contraception: A Human-Centered Design Approach.

STUDY OBJECTIVE: To use human-centered design approaches to engage adolescents and young adults in the creation of messages focused on dual method use in the setting of over-the-counter hormonal contraception access DESIGN: Baseline survey and self-directed workbooks with human-centered design activities were completed. The workbooks were transcribed and analyzed using qualitative methods to determine elements of the communication model, including sender, receiver, message, media, and environment. SETTING: Indiana and Georgia PARTICIPANTS: People aged 14-21 years in Indiana and Georgia INTERVENTIONS: Self-directed workbooks MAIN OUTCOME MEASURES: Elements of the communication model, including sender, receiver, message, media, and environment RESULTS: We analyzed 54 workbooks, with approximately half from each state. Stakeholders self-identified as female (60.5%), white (50.9%), Hispanic (10.0%), sexually active (69.8%), and heterosexual (79.2%), with a mean age of 18 years. Most strongly agreed (75.5%) that they knew how to get condoms, but only 30.2% expressed the same sentiment about hormonal contraception. Exploration of the elements of the communication model indicated the importance of crafting tailored messages to intended receivers. Alternative terminology for dual protection, such as "Condom+____," was created. CONCLUSION: There is a need for multiple and diverse messaging strategies about dual method use in the context of over-the-counter hormonal contraception to address the various pertinent audiences as this discussion transitions outside of traditional clinical encounters. Human-centered design approaches can be used for novel message development.

Communicating Risk for Obesity in Early Life: Engaging Parents Using Human-Centered Design Methodologies.

Objective: Pediatricians are well positioned to discuss early life obesity risk, but optimal methods of communication should account for parent preferences. To help inform communication strategies focused on early life obesity prevention, we employed human-centered design methodologies to identify parental perceptions, concerns, beliefs, and communication preferences about early life obesity risk. Methods: We conducted a series of virtual human-centered design research sessions with 31 parents of infants <24 months old. Parents were recruited with a human intelligence task posted on Amazon's Mechanical Turk, via social media postings on Facebook and Reddit, and from local community organizations. Human-centered design techniques included individual short-answer activities derived from personas and empathy maps as well as group discussion. Results: Parents welcomed a conversation about infant weight and obesity risk, but concerns about health were expressed in relation to the future. Tone, context, and collaboration emerged as important for obesity prevention discussions. Framing the conversation around healthy changes for the entire family to prevent adverse impacts of excess weight may be more effective than focusing on weight loss. Conclusions: Our human-centered design approach provides a model for developing and refining messages and materials aimed at increasing parent/provider communication about early life obesity prevention. Motivating families to engage in obesity prevention may require pediatricians and other health professionals to frame the conversation within the context of other developmental milestones, involve the entire family, and provide practical strategies for behavioral change.

Developing a Youth Contraception Navigator Program: A Human-Centered Design Approach.

PURPOSE: To determine key elements of a contraception navigator program that provides a personalized approach to overcoming patient-specific barriers by a trained navigator in central Indiana. METHODS: A human-centered design approach was used to engage adolescents and community stakeholders in co-design sessions. Sessions incorporated techniques, such as divergent brainwriting and journey maps, which led to the exploration of various themes that were ultimately used to inform key elements of the contraception navigator program. RESULTS: Adolescents aged 15-17 years (N = 35) and community stakeholders (N = 11) participated in co-design sessions. Analysis verified that the process of obtaining contraception for pregnancy prevention could be intimidating for young people. The importance of language, the presence of stigma, and the knowledge of side effects were all discussed. Essential elements of a contraceptive navigator program included building trust to ultimately co-create a plan that can overcome patient-specific barriers. Having a variety of communication methods available, as well as contraceptive side-effect support, will be essential. DISCUSSION: Using human-centered design techniques to engage adolescent and community stakeholders can help inform the development of a contraceptive navigator program. A trusted navigator that can address patient-specific barriers to contraception access both before and after contraception is obtained is a key element identified by stakeholders.

A novel qualitative approach for identifying effective communication for recruitment of minority women to a breast cancer prevention study.

Ensuring that racial and ethnic minority women are involved in breast cancer research is important to address well-documented current disparities in cancer incidence, stages of diagnosis, and mortality rates. This study used a novel interactive focus group method to identify innovative communication strategies for recruiting women from two minority groups-Latinas and Asian Americans-into the Komen Tissue Bank, a specific breast cancer biobank clinical trial. Through activities that employed visual interactive tools to facilitate group discussion and self-reflection, the authors examined perspectives and motivations for Asian American women (N = 17) and Latinas (N = 14) toward donating their healthy breast tissue. Findings included three themes that, while common to both groups, were unique in how they were expressed: lack of knowledge concerning breast cancer risks and participation in clinical research, cultural influences in BC risk thinking, and how altruism relates to perceived personal connection to breast cancer. More significantly, this study illuminated the importance of using innovative methods to encourage deeper, more enlightened participation among underrepresented populations that may not arise in a traditional focus group format. The findings from this study will inform future health communication efforts to recruit women from these groups into clinical research projects like the Komen Tissue Bank.

EatWellNow: Formative Development of a Place-Based Behavioral "Nudge" Technology Intervention to Promote Healthier Food Purchases among Army Soldiers.

Approximately 17% of military service members are obese. Research involving army soldiers suggests a lack of awareness of healthy foods on post. Innovative approaches are needed to change interactions with the military food environment. Two complementary technological methods to raise awareness are geofencing (deliver banner ads with website links) and Bluetooth beacons (real-time geotargeted messages to mobile phones that enter a designated space). There is little published literature regarding the feasibility of this approach to promote healthy behaviors in retail food environments. Thus, we conducted a formative feasibility study of a military post to understand the development, interest in, and implementation of EatWellNow, a multi-layered interactive food environment approach using contextual messaging to improve food purchasing decisions within the military food environment. We measured success based on outcomes of a formative evaluation, including process, resources, management, and scientific assessment. We also report data on interest in the approach from a Fort Bragg community health assessment survey (n = 3281). Most respondents agreed that they were interested in receiving push notifications on their phone about healthy options on post (64.5%) and that receiving these messages would help them eat healthier (68.3%). EatWellNow was successfully developed through cross-sector collaboration and was well received in this military environment, suggesting feasibility in this setting. Future work should examine the impact of EatWellNow on military service food purchases and dietary behaviors.

Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells.

Heme oxygenases (HOs) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin and excreted. Humans express two isoforms of HO: the inducible HO-1, which is upregulated in response to excess heme and other stressors, and the constitutive HO-2. Much is known about the regulation and physiological function of HO-1, whereas comparatively little is known about the role of HO-2 in regulating heme homeostasis. The biochemical necessity for expressing constitutive HO-2 is dependent on whether heme is sufficiently abundant and accessible as a substrate under conditions in which HO-1 is not induced. By measuring labile heme, total heme, and bilirubin in human embryonic kidney HEK293 cells with silenced or overexpressed HO-2, as well as various HO-2 mutant alleles, we found that endogenous heme is too limiting a substrate to observe HO-2-dependent heme degradation. Rather, we discovered a novel role for HO-2 in the binding and buffering of heme. Taken together, in the absence of excess heme, we propose that HO-2 regulates heme homeostasis by acting as a heme buffering factor that controls heme bioavailability. When heme is in excess, HO-1 is induced, and both HO-2 and HO-1 can provide protection from heme toxicity via enzymatic degradation. Our results explain why catalytically inactive mutants of HO-2 are cytoprotective against oxidative stress. Moreover, the change in bioavailable heme due to HO-2 overexpression, which selectively binds ferric over ferrous heme, is consistent with labile heme being oxidized, thereby providing new insights into heme trafficking and signaling.