Structure-Based Optimization of Selective and Brain Penetrant CK1δ Inhibitors for the Treatment of Circadian Disruptions.

Neuropsychiatric disorders such as major depressive disorders and schizophrenia are often associated with disruptions to the normal 24 h sleep wake cycle. Casein kinase 1 (CK1δ) is an integral part of the molecular machinery that regulates circadian rhythms. Starting from a cluster of bicyclic pyrazoles identified from a virtual screening effort, we utilized structure-based drug design to identify and reinforce a unique "hinge-flip" binding mode that provides a high degree of selectivity for CK1δ versus the kinome. Pharmacokinetics, brain exposure, and target engagement as measured by ex vivo autoradiography are described for advanced analogs.

In-Clinic vs. Online Recruitment of Women with a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post-hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes.

INTRODUCTION: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. METHODS: Participants were recruited from clinics within a university-based NCI-designated cancer center (n=87) and online nationally via Facebook (n=115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. RESULTS: Participants recruited online (vs. in-clinic) had higher educational attainment (p=.01) and health literacy (p=.003). They were more likely to have CIN vs. cancer, to be further from the time of diagnosis, and to have completed active treatment (p values<.001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1)=11.41, p<.001). There were no recruitment differences in self-reported (p=.90) or biochemically confirmed smoking abstinence (p=.18). CONCLUSIONS: Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (i.e., more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors to smoking cessation trials. IMPLICATIONS: People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN vs. cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12-months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

Changes in Cancer Screening Knowledge Among a Prospective Cohort of Spanish-Speaking Hispanic Community Outreach Event Participants in Florida and Puerto Rico.

The current study examined cancer prevention and early detection awareness (pre-workshop) and changes in knowledge (from pre- to post-workshop) among Hispanic/Latino (H/L) community members who participated in Spanish-language educational outreach events in Puerto Rico (PR) and Florida (FL). Spanish-language educational outreach events were comprised of an educational session lasting approximately 45-60 min and were delivered to groups in rural and urban community settings by a single trained community health educator (CHE). The research team assessed sociodemographic characteristics, personal and familial cancer health history, as well as awareness and knowledge (pre-test) of a range of cancer prevention and screening topics. Following the presentation, participants completed a post-test knowledge survey which also measured likelihood of engaging in cancer screening, cancer preventive behaviors, and cancer research as a result of information presented during the session. Change in the average knowledge score was evaluated using a paired samples t-test. Post-session likelihood of completing cancer screening and preventive behaviors and engaging in cancer research were examined using descriptive statistics and group/site comparisons. The percentage reporting awareness of screening procedures ranged from 33% (PSA test) to 79% (mammogram). H/L in PR reported higher percentage of stool blood test awareness when compared to H/L in FL (χ2(1)= 19.20, p<.001). The average knowledge score increased from 5.97 at pre-test to 7.09 at post-test (Cohen's d=0.69). The increase was significant across all participants (t(315)= 12.4, p<.001), as well as within the FL site (t(124)= 6.66, p<.001, d=0.59) and the PR site (t(190)=10.66, p<.001, d=0.77). Results from this study suggest that educational outreach events delivered to H/L community members by a CHE are valuable strategies to address challenges regarding cancer screening knowledge and engagement in multiple behaviors.

Longitudinal adherence to annual colorectal cancer screening among Black persons living in the United States enrolled in a community-based randomized trial.

BACKGROUND: This study examined repeat colorectal cancer screening rates at 12 and 24 months as part of a randomized intervention trial among Black persons living in the United States and factors associated with screening adherence. METHODS: Participants completed a survey assessing demographics and Preventive Health Model (PHM) factors (e.g., self efficacy, susceptibility) and received either a culturally targeted photonovella plus free fecal immunochemical test (FIT) kits (intervention group) or a standard educational brochure plus free FIT kits (comparison group). FIT return was assessed at 6, 12, and 24 months. Descriptive statistics summarized patterns of repeat screening. Logistic regression models assessed FIT uptake overtime, and demographic and PHM factors associated with screening adherence. RESULTS: Participants (N = 330) were U.S.-born (93%), non-Hispanic (97%), and male (52%). Initial FIT uptake within 6 months of enrollment was 86.6%, and subsequently dropped to 54.5% at 12 months and 36.6% at 24 months. Higher FIT return rates were observed for the brochure group at 24 months (51.5% vs 33.3% photonovella, p = .023). Multiple patterns of FIT kit return were observed: 37% completed FIT at all three time points (full adherence), 22% completed two of three (partial adherence), 29% completed one of three (partial adherence), and 12% did not return any FIT kits (complete nonadherence). Predictors of full adherence were higher levels of education and self-efficacy. CONCLUSIONS: Full adherence to repeat screening was suboptimal. Most participants had partial adherence (one or two of three) to annual FIT screening. Future studies should focus on strategies to support repeat FIT screening.

Sharing and seeking information about skin cancer risk and prevention among Hispanic people from Florida and Puerto Rico.

Objective: To explore factors associated with communication and information-seeking after receipt of skin cancer prevention information among Hispanic individuals. Methods: Multivariable logistic regression was used to analyze existing data on demographics, personal experience, salience, and beliefs variables collected from Hispanic individuals to determine independent associations with sharing and seeking information about skin cancer prevention. Results: Of 578 participants, 53% reported any communication about skin cancer prevention behaviors or skin cancer genetic risk; and 31% and 21% sought additional information about preventive behaviors or genetic risk, respectively. Female sex, greater perceived severity, higher comparative chance of getting skin cancer, and lower health literacy were associated with greater communication, while having no idea of one's own skin cancer risk was related to less communication. Greater health numeracy and higher cancer worry were associated with information-seeking about prevention behaviors and genetic risk. Conclusion: Up to half of participants reported communication or information-seeking, although factors associated with specific activities differed. Future studies should evaluate how to promote communication behaviors in the Hispanic community and how sharing and seeking information influence an individual's network prevention practices. Innovation: Several factors related to communication behaviors among Hispanic people after obtaining skin cancer prevention information were identified.Trial registration: This trial was registered on clinicaltrials.gov (NCT03509467).

Skin cancer prevention behaviors, beliefs, distress, and worry among hispanics in Florida and Puerto Rico.

BACKGROUND: Incidence of skin cancer has been increasing among U.S. Hispanics, who often are diagnosed with larger lesions and at later stage disease. Behaviors to decrease exposure to ultraviolet radiation can reduce risk of skin cancer. We describe skin cancer prevention behaviors and psychosocial variables among Hispanic participants recruited into a skin cancer prevention trial. METHODS: Self-reported Hispanic participants from eight primary care clinics in Tampa, Florida and Ponce, Puerto Rico were recruited into a randomized controlled prevention trial. Information on demographics, sun-related behaviors, and psychosocial variables were collected before intervention materials were provided. Multivariable regression models were used to compare baseline sun-related behaviors and psychosocial variables across groups defined by geographic location and language preference. RESULTS: Participants reported low levels of intentional outdoor tanning, weekday and weekend sun exposure, and very low levels of indoor tanning. However, only a minority of participants practiced sun-protective behaviors often or always, and about 30% experienced a sunburn in the past year. Participants had low levels of recent worry and concern about skin cancer, modest levels of perceived risk and severity, and high levels of response efficacy and self-efficacy. When comparing across groups defined by geographic location and language preference, English-preferring Tampa residents (hereafter referred to as Tampeños) had the highest proportion who were sunburned (35.9%) and tended toward more risky behavior but also had higher protective behavior than did Spanish-preferring Tampeños or Puerto Ricans. Spanish-preferring Puerto Ricans had higher recent concern about skin cancer, comparative chance of getting skin cancer, and response efficacy compared to either English- or Spanish-preferring Tampeños. Spanish-preferring Tampeños had the highest levels of familism and recent distress about skin cancer. CONCLUSIONS: Our results mirror previous observations of low levels of sun-protective behavior among U.S. Hispanics compelling the need for culturally appropriate and translated awareness campaigns targeted to this population. Because Hispanics in Tampa and Puerto Rico reported modest levels of perceived risk and severity, and high levels of response efficacy and self-efficacy, interventions aiming to improve skin cancer prevention activities that are anchored in Protection Motivation Theory may be particularly effective in this population subgroup.

Predictors of correct recall of genetic risk information among Hispanic individuals in Florida and Puerto Rico.

OBJECTIVE: To identify predictors of genetic risk recall and examine whether recall influences adoption of skin cancer preventive behaviors among Hispanic individuals. METHODS: Hispanic participants randomized to intervention arms (n = 463) of a precision prevention trial were provided MC1R risk information (average, higher) and asked to recall their risk after 3 and 9 months. Predictors of recall (correct versus did not recall/misremembered) were determined by backwards stepwise logistic regression. Intervention effects on preventive behaviors were estimated within strata of 3-month recall. RESULTS: Age inversely predicted correct recall in both risk groups (average: OR3-months(3)= 0.97, 95%CI:0.94-1.01, OR9-months(9)= 0.96, 95%CI:0.93-0.99; higher: OR3 = 0.98, 95%CI:0.95-1.01, OR9 = 0.98, 95%CI:0.95-1.00). Education positively predicted recall among participants at average risk (OR3 =1.64, 95%CI:1.06-2.63, OR9 =1.73, 95%CI:1.12-2.81). Darker untanned skin color inversely predicted recall among participants at higher risk (OR3 =0.68, 95%CI:0.45-0.99, OR9 =0.74, 95%CI:0.50-1.09). Intervention effects for routine sunscreen use and undergoing a clinical skin exam were stronger among participants at higher risk who correctly recalled at 3 months than those who did not recall/misremembered. CONCLUSIONS: Younger age, higher education, and lighter untanned skin color predicted correct recall. Better recall may improve skin cancer prevention outcomes. PRACTICE IMPLICATIONS: Additional strategies are needed to boost recall among Hispanic individuals who are older, less educated, and darker-skinned.

Associations of Germline Genetic Variants With Depression and Fatigue Among Hematologic Cancer Patients Treated With Allogeneic Hematopoietic Cell Transplantation.

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT). METHODS: Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05. RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ). CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.

Effects of Digestion, Cell Culture Media, and Mucous on the Physical Properties, Cellular Effects, and Translocation of Polystyrene and Polymethacrylate Nanoparticles.

The discovery of plastic and metal nanoparticles in organisms, foods, and beverages has generated numerous studies on the effects of these particles on the barrier cells and their subsequent absorption into the body. Following ingestion, nanoparticles travel down the gastrointestinal tract (GIT), and their physicochemical characteristics change in response to the change in proteins and pH during their digestion. We measured the translocation of digested nanoparticles across a co-culture monolayer of Caco-2 and various combinations (1:9, 5:5, and 9:1) of HT29-MTX-E12. The in vitro model of the intestine was used to determine the translocation of digested 20 nm polymethacrylate (PMA) particles and the accompanying monolayer barrier effects after a 72 h exposure. The in vitro digestion increased the agglomeration and hydrodynamic diameters and decreased the surface charge of the nanoparticles. For NH2-functionalized polymethacrylate nanoparticles (PMA-NH2), the diameters increased from 57 nm (water) to 3800 nm (media), or 2660 nm (chyme). These nanoparticles compromised the integrity of the monolayer (trans-epithelial electrical resistance, Lucifer yellow translocation) and translocated across all the cell ratio configurations. Digestion can have a large effect on nanoparticle agglomeration and surface charge. Excess mucous was not seen as a barrier to the translocation of PMA-NH2.

Enhancing long-term smoking abstinence among individuals with a history of cervical intraepithelial neoplasia or cervical cancer (Project ACCESS): protocol for a randomized clinical trial.

BACKGROUND: The prevalence of smoking among cervical cancer survivors is high and evidence-based smoking cessation interventions are critically needed. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial (RCT) designed to evaluate the efficacy of a novel, personally tailored SMS-delivered text-based digital treatment adjuvant designed to enhance the long-term efficacy of a "Motivation And Problem-Solving" (MAPS) approach for smoking cessation among individuals with a history of cervical intraepithelial neoplasia (CIN) or cervical cancer. MAPS is a phone counseling approach designed to facilitate long-term abstinence that comprises 6 counseling calls over 12 months. The current trial is evaluating the efficacy of MAPS+, which comprises all MAPS components plus a 24-month digital treatment adjuvant. This trial represents a logical extension of our previous RCT, which compared the efficacy of MAPS to a quitline control condition and found that MAPS resulted in greater than a 2-fold increase in smoking abstinence at 12 months (i.e., 26.4% vs. 11.9%). This treatment effect was no longer significant at 18 months, suggesting that efficacy dissipated as time from the end of treatment increased. The primary aim of the current trial is to compare the efficacy of MAPS + and ST in facilitating long-term abstinence. METHODS: Individuals who smoke and have a history of cervical cancer or CIN (N = 340) are recruited throughout Florida and randomly assigned to Standard Treatment [ST] or MAPS+. ST participants are electronically connected with the Florida Quitline. MAPS + consists of 6 proactive MAPS-based counseling calls over 12 months plus the novel, personally tailored, text message-based treatment adjuvant delivered over 24 months. All participants receive 12 weeks of combination nicotine replacement therapy (patch and lozenge) and are followed for 24 months. Participant recruitment commenced in December 2022 and is ongoing. DISCUSSION: This study builds on promising results from our recent trial which found that MAPS was associated with substantially higher abstinence from smoking at the end of the 12-month treatment period. Finding that this low-burden, personally tailored digital treatment adjuvant improves the long-term efficacy of MAPS would have important clinical and public health implications. TRIAL REGISTRATION: Clinical Trials Registry NCT05645146; https://clinicaltrials.gov/ct2/show/NCT05645146 ; Registered on December 9, 2022.

Ending Tobacco Use Through Interactive Tailored Messaging for Cambodian People With HIV (Project EndIT): Protocol for a Randomized Controlled Trial.

BACKGROUND: The prevalence of smoking remains high in many low- and middle-income countries (LMICs), including the Southeast Asian nation of Cambodia. Smoking is especially hazardous for people with HIV. In Cambodia, approximately 43%-65% of men with HIV and 3%-5% of women with HIV smoke cigarettes. Thus, there is a critical need for cost-effective smoking cessation interventions for Cambodian people with HIV. This paper describes the design, methods, and data analysis plans for a randomized controlled trial assessing the efficacy of a theory-based mobile health smoking cessation intervention in Cambodian people with HIV. OBJECTIVE: This 2-group randomized controlled trial compares the efficacy of a mobile health-based automated messaging (AM) intervention versus standard care (SC) in facilitating smoking cessation among Cambodian people with HIV. METHODS: Cambodian people with HIV who currently smoke and are receiving antiretroviral treatment (target, N=800) will be randomized to (1) SC or (2) the AM intervention. SC participants will receive brief advice to quit smoking, written self-help materials, nicotine patches, and will complete weekly app-delivered dietary assessments for 26 weeks. AM participants will receive all SC components (but will complete smoking-related weekly assessments instead of dietary assessments), in addition to a fully automated tailored messaging program driven by the weekly assessments to facilitate smoking cessation. In the Phase-Based Model of smoking cessation, the cessation process is partitioned into 4 phases: motivation, preparation (precessation), cessation (quit date to 2 weeks post quit), and maintenance (up to 6 months post quit). Our AM program targets processes within these phases, including increasing motivation to quit, enhancing self-efficacy, obtaining social support, skills to cope with nicotine withdrawal symptoms and stress, and skills to maintain abstinence. All participants will complete baseline and 3-, 6-, and 12-month in-person follow-up assessments. The primary outcome is biochemically confirmed abstinence at 12 months, with 3- and 6-month abstinence as secondary outcomes. Potential mediators and moderators underlying treatment effects will be explored, and cost-effectiveness will be assessed. RESULTS: This study was approved by all relevant domestic and international institutional and ethical review boards. Participant recruitment commenced in January 2023. Data collection is expected to conclude by the end of 2025. CONCLUSIONS: By demonstrating the greater efficacy and cost-effectiveness of AM relative to SC, this study has the potential to transform HIV care in Cambodia and prevent tobacco-related diseases. Furthermore, it may be adapted for use in other Cambodian populations and in other low- and middle-income countries. Ultimately, the AM approach to smoking cessation could greatly improve public health in the developing world and beyond. TRIAL REGISTRATION: ClinicalTrials.gov NCT05746442; https://clinicaltrials.gov/ct2/show/NCT05746442. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48923.

Qualitative assessment of uptake retention and evaluation of prevention materials for skin cancer among Hispanics.

OBJECTIVE: Examine retention and evaluation of incorporating melanocortin-1 receptor genetic risk information materials in a skin cancer prevention intervention conducted in Hispanics living near Tampa, Florida and Ponce, Puerto Rico. METHODS: Two researchers applied thematic content analysis to identify major themes of open-ended responses (n = 1689) from 489 participants. RESULTS: Five major thematic categories emerged: 1) intervention comments; 2) tips and tricks; 3) cancer prevention; 4) general information; and 5) risk factors and genetics. Responses captured under intervention comments (e.g., information was clear, easy to understand) and tips and tricks for sun protection (e.g., using sunscreen, wearing protective clothing) were most frequent. Participants noted the importance of conducting skin exams professionally or at home. English-preferring Tampa residents stated their individual risk factors, especially race and/or ethnicity, more frequently than Ponce residents and Spanish-preferring Tampa residents. Ponce residents were more likely to comment on wanting to share intervention materials with family and friends. CONCLUSION: Findings suggest Hispanic participants implemented sun safety activities.

Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS: There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION: MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

Pilot randomized controlled trial of mindfulness-based relapse prevention vs cognitive behavioral therapy for smoking and alcohol use.

BACKGROUND: The combined use of cigarettes and alcohol is associated with a synergistic increase in the risk of morbidity and mortality. Continued alcohol use during a smoking quit attempt is a considerable risk factor for smoking relapse. As such, there is a need for interventions that address both behaviors concurrently. Mindfulness-based interventions hold much promise for simultaneously addressing tobacco and alcohol use. METHOD: This pilot study evaluated the feasibility and acceptability of a mindfulness-based intervention using a two-arm randomized controlled trial of Mindfulness-Based Relapse Prevention for Smoking and Alcohol (MBRP-SA) vs Cognitive Behavioral Therapy (CBT). Interventions were delivered via telehealth in a group setting; all participants received a 6-week supply of the nicotine patch. Participants (N = 69) were adults who smoked cigarettes who reported binge drinking and were motivated to both quit smoking and change their alcohol use. Primary outcomes were feasibility and acceptability of MBRP-SA compared to CBT. Changes in tobacco and alcohol use are also presented. RESULTS: Participants in MBRP-SA and CBT indicated that the treatments were highly acceptable, meeting a priori benchmarks. Feasibility was mixed with some outcomes meeting benchmarks (e.g., recruitment) and others falling below (e.g., retention). Participants in both conditions demonstrated significant reductions in tobacco and alcohol use at the end of treatment. CONCLUSIONS: In sum, MBRP-SA had comparable outcomes to CBT on all metrics measured. Future research should evaluate the efficacy of MBRP-SA on smoking abstinence and drinking reductions in a large-scale, fully powered trial. This study was registered on clinicaltrials.gov (NCT03734666).

Predictors of genetic risk recall among the participants of a randomized controlled precision prevention trial against melanoma.

PURPOSE: Inherited variation in MC1R imparts low to moderate risk of melanoma. Research on genetic risk recall, factors predicting recall, and whether recall influences adoption of preventive behaviors is limited. METHODS: Participants (n = 447) enrolled in a melanoma precision prevention trial were provided with MC1R risk information (average or higher) and after 6 and 12 months, were asked to recall their genetic risk. Predictors of recall were identified using backward stepwise selection. Intervention effects were reassessed after stratifying by recall. RESULTS: Participants at higher risk were 2 to 3 times more likely to misremember or not recall than participants with average risk. Misremembering was almost exclusively observed among participants at higher risk. Among the participants with average risk, lower health numeracy and not completing the telephone follow-up were associated with not recalling or misremembering. Among the participants at higher risk, lower education was associated with not recalling and lower perceived comparative chance of developing melanoma was associated with misremembering. In general, participants at higher risk who correctly recalled had modestly stronger intervention effects on sun protection behaviors than those who misremembered or did not recall. CONCLUSION: Future studies should examine different strategies to increase genetic risk recall, which may result in improved behavioral outcomes, especially among participants with lower education and health numeracy.

Identification and characterization of select oxysterols as ligands for GPR17.

BACKGROUND AND PURPOSE: G-protein coupled receptor 17 (GPR17) is an orphan receptor involved in the process of myelination, due to its ability to inhibit the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Despite multiple claims that the biological ligand has been identified, it remains an orphan receptor. EXPERIMENTAL APPROACH: Seventy-seven oxysterols were screened in a cell-free [35 S]GTPγS binding assay using membranes from cells expressing GPR17. The positive hits were characterized using adenosine 3',5' cyclic monophosphate (cAMP), inositol monophosphate (IP1) and calcium mobilization assays, with results confirmed in rat primary oligodendrocytes. Rat and pig brain extracts were separated by high-performance liquid chromatography (HPLC) and endogenous activator(s) were identified in receptor activation assays. Gene expression studies of GPR17, and CYP46A1 (cytochrome P450 family 46 subfamily A member 1) enzymes responsible for the conversion of cholesterol into specific oxysterols, were performed using quantitative real-time PCR. KEY RESULTS: Five oxysterols were able to stimulate GPR17 activity, including the brain cholesterol, 24(S)-hydroxycholesterol (24S-HC). A specific brain fraction from rat and pig extracts containing 24S-HC activates GPR17 in vitro. Expression of Gpr17 during mouse brain development correlates with the expression of Cyp46a1 and the levels of 24S-HC itself. Other active oxysterols have low brain concentrations below effective ranges. CONCLUSIONS AND IMPLICATIONS: Oxysterols, including but not limited to 24S-HC, could be physiological activators for GPR17 and thus potentially regulate OPC differentiation and myelination through activation of the receptor.

A Just-In-Time Adaptive intervention (JITAI) for smoking cessation: Feasibility and acceptability findings.

Smoking cessation treatments that are easily accessible and deliver intervention content at vulnerable moments (e.g., high negative affect) have great potential to impact tobacco abstinence. The current study examined the feasibility and acceptability of a multi-component Just-In-Time Adaptive Intervention (JITAI) for smoking cessation. Daily smokers interested in quitting were consented to participate in a 6-week cessation study. Visit 1 occurred 4 days pre-quit, Visit 2 was on the quit day, Visit 3 occurred 3 days post-quit, Visit 4 was 10 days post-quit, and Visit 5 was 28 days post-quit. During the first 2 weeks (Visits 1-4), the JITAI delivered brief mindfulness/motivational strategies via smartphone in real-time based on negative affect or smoking behavior detected by wearable sensors. Participants also attended 5 in-person visits, where brief cessation counseling (Visits 1-4) and nicotine replacement therapy (Visits 2-5) were provided. Outcomes were feasibility and acceptability; biochemically-confirmed abstinence was also measured. Participants (N = 43) were 58.1 % female (AgeMean = 49.1, mean cigarettes per day = 15.4). Retention through follow-up was high (83.7 %). For participants with available data (n = 38), 24 (63 %) met the benchmark for sensor wearing, among whom 16 (67 %) completed at least 60 % of strategies. Perceived ease of wearing sensors (Mean = 5.1 out of 6) and treatment satisfaction (Mean = 3.6 out of 4) were high. Biochemically-confirmed abstinence was 34 % at Visit 4 and 21 % at Visit 5. Overall, the feasibility of this novel multi-component intervention for smoking cessation was mixed but acceptability was high. Future studies with improved technology will decrease participant burden and better detect key intervention moments.

Augmented reality as a novel approach for addiction treatment: development of a smoking cessation app.

OBJECTIVE: Augmented reality (AR) is a rapidly developing technology that has substantial potential as a novel approach for addiction treatment, including tobacco use. AR can facilitate the delivery of cue exposure therapy (CET) such that individuals can experience the treatment in their natural environments as viewed via a smartphone screen, addressing the limited generalizbility of extinction learning. Previously, our team developed a basic AR app for smoking cessation and demonstrated the necessary mechanisms for CET. Specifically, we showed that the AR smoking cues, compared to neutral cues, elicited substantial cue reactivity (i.e. increased urge) and that repeated exposure to the AR smoking cues reduced urge (i.e. extinction) in a laboratory setting. Here we report the next step in the systematic development of the AR app, in which we assessed the usability and acceptability of the app among daily smokers in their natural environments. METHOD: Daily smokers (N = 23, 78.3% female, Mean Age = 43.4, Mean Cigarettes/Day = 14.9), not actively quitting, were instructed to use the AR app in locations and situations where they smoke (e.g. home, bar) at least 5 times per day over one week. The study is registered in clinicaltrials.gov (NCT04101422). RESULTS: Results indicated high usability and acceptability. Most of the participants (73.9%) used the AR app on at least 5 days. Participants found the AR cues realistic and well-integrated in their natural environments. The AR app was perceived as easy to use (Mean = 4.1/5) and learn (mean of 2 days to learn). Overall satisfaction with the app was also high. Secondary analyses found that 56.5% reported reduced smoking, with an average 26% reduction in cigarettes per day at follow-up. CONCLUSIONS: These findings set the stage for a randomized controlled trial testing the AR app as an adjuvant therapy for treating tobacco dependence, with potential applicability to other substances. KEY MESSAGEThis study found that the augmented reality (AR) smartphone application that utlized cue exposure treatment for smoking cessation was perceived as easy to use and learn in the natural, day-to-day environment of daily smokers. Findings set the stage for a larger clinical trial testing the AR app as an adjuvant therapy for treating tobacco dependence, with potential applicability to other addictive behaviors.

Training cancer caregiver navigators: experiences from implementing the eSNAP and caregiver navigator intervention.

Patient navigation is increasingly common in cancer care. While navigation programs often involve informal family caregivers, few navigation interventions specifically target the family caregiver. We developed the eSNAP and Caregiver Navigator Intervention to help cancer family caregivers identify and capitalize on informal and formal social support resources. While the skill set for patient navigators may be adequate for supporting caregivers, other skills and areas of knowledge expertise are needed. In addition, sparse documentation of navigator training best practices creates further challenges for dissemination and implementation. Our goal is to describe the education and training of cancer caregiver navigators within key competencies used to prepare and support navigators to deliver our manualized intervention. Nationally recognized navigation competencies, related to developing a sensitivity to ethical, cultural, and professional issues, knowledge development, skills development, and practice-based learning, were identified and adapted. Performance goals were identified within each competency. Training activities were selected to support competency development. Based on adult learning theories, we emphasize multiple learning strategies, including experiential learning and critical reflection. Two caregiver navigators engaged in initial training between December, 2019 and February, 2020. Initial training was supervised by study leadership, who coordinated with experts and stakeholders. Navigators completed initial training. We describe lessons learned. To ensure that navigators are well-equipped to provide effective services, evidence-based training programs that include navigation and protocol-specific competencies are needed. Given the lack of detailed training programs in the literature, we created a flexible, multimodal learning approach that other teams may adopt.

Spiritual well-being, distress and quality of life in Hispanic women diagnosed with cancer undergoing treatment with chemotherapy.

OBJECTIVE: Previous studies have examined whether spiritual well-being is associated with cancer outcomes, but minority populations are under-represented. This study examines associations of baseline spiritual well-being and change in spiritual well-being with change in distress and quality of life, and explores potential factors associated with changes in spiritual well-being among Hispanic women undergoing chemotherapy. METHODS: Participants completed measures examining spiritual well-being, distress, and quality of life prior to beginning chemotherapy and at weeks 7 and 13. Participants' acculturation and sociodemographic data were collected prior to treatment. Mixed models were used to examine the association of baseline spiritual well-being and change in spiritual well-being during treatment with change in distress and quality of life, and to explore whether sociodemographic factors, acculturation and clinical variables were associated with change in spiritual well-being. RESULTS: A total of 242 participants provided data. Greater baseline spiritual well-being was associated with less concurrent distress and better quality of life (p < 0.001), as well as with greater emotional and functional well-being over time (p values < 0.01). Increases in spiritual well-being were associated with improved social well-being during treatment, whereas decreases in spiritual well-being were associated with worsened social well-being (p < 0.01). Married participants reported greater spiritual well-being at baseline relative to non-married participants (p < 0.001). CONCLUSIONS: Greater spiritual well-being is associated with less concurrent distress and better quality of life, as well as with greater emotional, functional, and social well-being over time among Hispanic women undergoing chemotherapy. Future work could include developing culturally targeted spiritual interventions to improve survivors' well-being.