Physical Pain Among Urban Native American Emerging Adults: Sociocultural Risk and Protective Factors.

OBJECTIVE: American Indian/Alaska Native (AI/AN) people have high rates of physical pain. Pain is understudied in urban-dwelling, AI/AN emerging adults, a group with unique sociocultural risk and protective factors. We explore associations between socioeconomic disadvantage, additional sociocultural factors, and pain among urban AI/AN emerging adults. METHODS: AI/AN participants aged 18-25 years ( N = 417) were recruited via social media. Regression models tested associations between socioeconomic disadvantage (income and ability to afford health care) and pain as well as additional sociocultural factors (discrimination, historical loss, cultural pride and belonging, visiting tribal lands) and pain. Multigroup regression models tested whether associations between sociocultural factors and pain differed between participants who were socioeconomically disadvantaged and those who were less disadvantaged. RESULTS: In the full sample, lower income ( b = 1.00-1.48, p < .05), inability to afford health care ( b = 1.00, p = .011), discrimination ( b = 0.12, p = .001), and historical loss ( b = 0.24, p = .006) were positively associated with pain, whereas visiting tribal lands was negatively associated with pain ( b = -0.86 to -0.42, p < .05). In the multigroup model, visiting tribal lands 31+ days was negatively associated with pain only among the less socioeconomically disadvantaged group ( b = -1.48, p < .001). CONCLUSIONS: Socioeconomic disadvantage may, in part, drive pain disparities among AI/AN emerging adults and act as a barrier to benefitting from visiting tribal lands. Results support a biopsychosocial approach to targeting pain in this population, including addressing socioeconomic challenges and developing culturally informed, strengths-based interventions.

Edge effects and social behavior in three platyrrhines.

Social behavior is a key adaptation for group-living primates. It is important to assess changes to social behavior in human-impacted landscape zones to better understand the impact of anthropogenic disturbance on primate species. We investigated social behavior rate and type in three species of platyrrhines across 100 m anthropogenic edge and interior zones of a fragmented forest in Costa Rica, La Suerte Biological Research Station (LSBRS). Following results from other sites, we predicted that spider monkeys (Ateles geoffroyi), capuchin monkeys (Cebus imitator) and howler monkeys (Alouatta palliata) would show lower rates and fewer types of social behavior in forest edge compared to interior. We collected 1341 h of instantaneous focal data from 2017 to 2023 across the three monkey species. We found mixed support for our predictions, with spider and capuchin monkeys modifying some but not all aspects of social behavior across forest zones at LSBRS. Spider monkeys had lower rates of social behavior and capuchin monkeys performed different types of social behaviors in forest edge compared to interior at LSBRS. In contrast, howler monkeys did not modify social behavior. Two out of three platyrrhine species altered their social behavior when in anthropogenic edges, indicating behavioral adjustment when in human-altered habitat areas at LSBRS.

Mixed Methods Evaluation of Satisfaction with Two Culturally Tailored Substance use Prevention Programs for American Indian/Alaska Native Emerging Adults.

American Indian/Alaska Native (AI/AN) communities are disproportionately affected by the opioid epidemic. AI/AN emerging adults (ages 18-25) in urban areas are at particularly high risk, with the overdose death rate among urban-dwelling AI/AN people 1.4 times higher than rural-dwelling AI/AN people. Despite these challenges, there are no evidence-based culturally tailored prevention or intervention programs to address opioid, alcohol and other drug use among urban AI/AN emerging adults. This study focused on understanding AI/AN emerging adults' experiences with two culturally tailored programs addressing opioid, cannabis, and alcohol use as part of the randomized controlled trial for Traditions and Connections for Urban Native Americans (TACUNA) in order to enhance feasibility of this intervention. Using a convergent mixed methods design at 3-month follow-up, we collected satisfaction and experience ratings and written narratives (total n = 162; intervention n = 77; control n = 85) from a sample of urban-dwelling AI/AN emerging adults who participated in both programs. We analyzed data through simultaneous examination of qualitative and quantitative data. The quantitative ratings show that both programs were rated highly. The qualitative data contextualized these ratings, illustrating pathways through which specific components were perceived to cause desired or observed behavioral change in participants. Among the elements that mattered most to these participants were the convenience of the virtual format, having a comfortable and safe space to share personal stories, and learning new information about their social networks. Negative comments focused on workshop length and inconvenient scheduling. This is one of the first studies to explore participant satisfaction and experience with culturally tailored substance use programming among a historically marginalized and understudied population. It is important to consider the voices of urban-dwelling AI/AN people in program development because hidden factors, such as limited financial resources, limited time, and misalignment with cultural values may prevent existing programs from being feasible.

Enhancing sleep health in urban American Indian/Alaska Native adolescents: Implications for culturally tailored interventions.

BACKGROUND: Urban American Indian/Alaska Native (AI/AN) adolescents are vulnerable to sleep and other health-related disparities due to numerous social drivers, including historical trauma and relocation to urban areas. This study aims to identify strategies to increase protective factors and culturally tailor sleep health interventions for this population. METHODS: Using community-based participatory research, the NAYSHAW study conducted in-depth interviews with urban AI/AN adolescents aged 12-19 years to understand critical components needed for developing a culturally sensitive sleep health intervention. Data from two qualitative subsamples (N = 46) and parent surveys (N = 110) were analyzed, focusing on factors that affect sleep health behaviors, including parental involvement, technology, and traditional practices. RESULTS: Key findings include the detrimental impact of electronics use at night and protective effects of traditional practices on sleep. Parental involvement in sleep routines varied by adolescent's age. Adolescents desired sleep health education in interactive formats, whereas parents preferred workshops and digital applications for sleep health strategies. Findings suggest that interventions need to address electronics use and should also be culturally tailored to address the unique experiences of urban AI/AN adolescents. CONCLUSIONS: Results underscore the importance of utilizing community-based strategies to develop culturally tailored sleep interventions for underserved populations, specifically urban AI/AN adolescents. Integrating traditional practices with evidence-based sleep health strategies can provide a holistic approach to improving sleep and overall well-being. Parental education and involvement will be critical to the success of such interventions.

Caspase cleavage is not for everyone.

During apoptosis, caspases cleave cellular substrates to break down and package the apoptotic cell for removal. Reporting in Cell, Mahrus et al. (2008) and Dix et al. (2008) use new approaches that identify hundreds of previously unrecognized caspase substrates, many of which appear to produce polypeptide fragments with potentially new functional activities.

Assessing color cues of development, breeding status and reproductive condition in captive golden lion tamarins (Leontopithecus rosalia).

Color signals play an important role in intraspecific communication and are well studied in catarrhine primates, which exhibit uniform trichromatic vision that is well suited to detecting such signals. Platyrrhine primates exhibit polymorphic color vision with different individuals possessing different color vision types in most species. Intriguingly, some platyrrhine species exhibit bare faces, which are convergent with those of catarrhines. However, putative functions of bare-faced color signals in platyrrhines remain largely unexplored. We measured facial skin color of five captive golden lion tamarins (Leontopithecus rosalia) using color-calibrated digital photography and modeled these colors to the visual systems of the species. Our results show that facial coloration is different between infant and older adults and varies across reproductive condition, but not between breeding and nonbreeding adults. While preliminary, our study suggests that facial coloration may be involved in sociosexual signaling in golden lion tamarins, and provides intriguing evidence that we hope might stimulate more studies of bare-faced signaling in platyrrhines.

Culturally Responsive Opioid and Other Drug Prevention for American Indian/Alaska Native People: a Comparison of Reservation- and Urban-Based Approaches.

There are few substance use treatment and prevention programs for AI/AN people that integrate culturally based practices with evidence-based treatment and prevention. The National Institutes of Health's (NIH's) Helping to End Addiction Long-term (HEAL) Prevention Cooperative supports two projects focused on AI/AN populations. One focuses on youth ages 15 to 20 years living within the Cherokee Nation reservation, a multicultural rural area in northeastern Oklahoma, and the second focuses on emerging adults ages 18 to 25 years living in diverse urban areas. We provide a brief overview of the two prevention trials and a case comparison across approaches using the framework of promising practices for intervention science with Indigenous communities (Whitesell et al., 2020) related to (1) integration of Indigenous and academic perspectives to respond to community needs, (2) community partnership and engagement, (3) alignment with Indigenous cultural values and practices, (4) capacity building and empowerment, (5) implementation within complex cultural contexts, and (6) tribal oversight. Overall, these two projects highlight the importance of long-standing relationships with community partners, engaging the community at all levels to ensure that programming is culturally and developmentally appropriate, and having tribal and elder oversight. These practices are key to establishing trust and building confidence in research in these communities and ensuring that research can benefit AI/AN people. These studies showcase how strong partnerships can advance health and support the conduct of rigorous science to help pinpoint optimal health solutions by identifying efficacious, culturally grounded intervention strategies. Although the sovereign status of tribes demands this type of partnership, this research serves as a model for all community research that has a goal of improving health.

Including Community Partners in the Development and Adaptation of Intervention Strategies to Prevent Initiation or Escalation of Opioid Misuse.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

Changes in Sleep-Wake Patterns and Disturbances Before and During COVID-19 in Urban American Indian/ Alaska Native Adolescents.

BACKGROUND: COVID-19 has profoundly affected sleep, although little research has focused on high-risk populations for poor sleep health, including American Indian/Alaska Native (AI/AN) adolescents. METHODS: This is the first longitudinal study to examine changes in sleep with surveys completed before the pandemic and during the early months of COVID-19 in a sample of urban AI/AN adolescents (N = 118; mean age = 14 years at baseline; 63% female). We use a mixed-methods approach to explore how COVID-19 affected urban AI/AN adolescents' sleep, daily routines, and interactions with family and culture. Quantitative analysis examined whether pandemic-related sleep changes were significant and potential moderators of COVID-19's effect on sleep, including family and community cohesion and engagement in traditional practices. RESULTS: : Findings demonstrate changes in sleep, including increases in sleep duration, delays in bedtimes and waketimes, and increases in sleep-wake disturbances (p's <.001). Higher levels of family cohesion and higher levels of engagement in traditional practices moderated pandemic-related increases in weekday sleep duration. Qualitative analyses revealed changes in adolescents' sleep and daily behaviors, as well as strategies adolescents used to cope with pandemic-related disruptions in sleep and routines. CONCLUSION: Findings demonstrate positive and negative changes in sleep during COVID-19 stay-at-home orders, including simultaneous increases in sleep duration and sleep-wake disturbances. Results highlight the importance of considering multi-level influences on adolescent sleep, such as early school start times, family dynamics, and cultural factors. A multi-level approach may help guide prevention and intervention efforts to improve adolescent sleep health.

Novel amide and imidazole compounds as potent hematopoietic prostaglandin D2 synthase inhibitors.

In seeking novel and potent small molecule hematopoietic prostaglandin D2 synthase (H-PGDS) inhibitors as potential therapies for PGD2-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole "linker" between the pyrimidine or pyridine "core" ring and the "tail" ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD2 stimulation. Amide analogs show ten-fold greater shift in the thermal shift assay in the presence of glutathione (GSH) versus the same assay run in the absence of GSH. The imidazole analogs did not produce a significant change in thermal shift between the two assay conditions, suggesting a possible stabilization effect of the amide linker in the synthase-GSH-inhibitor complex. Imidazole analog 23, (KMN-010034) demonstrates superior potency across the in vitro assays and good in vitro metabolic stability in both human and guinea pig liver microsomes.

Recruitment and retention in randomized controlled trials with urban American Indian/Alaska Native adolescents: Challenges and lessons learned.

BACKGROUND: Although the majority of American Indians/Alaska Natives reside in urban areas, there are very few randomized controlled trials analyzing culturally centered substance use prevention interventions for this population. METHODS: We describe methods employed to recruit and retain urban American Indian/Alaska Native adolescents into a randomized controlled trial, which was focused on testing the potential benefits of a substance use prevention intervention for this population. We also report challenges encountered in recruitment and retention of participants and strategies employed addressing these challenges. Data collection occurred from August 2014 to October 2017. RESULTS: We partnered with two community-based organizations in different cities in California. We utilized American Indian/Alaska Native recruiters from communities, placed flyers in community-based organizations, and asked organizations to post flyers on their web and social media sites. We also offered gift cards for participants. Our initial recruitment and retention model was moderately successful; however, we encountered five main challenges: (1) transportation, (2) increasing trust and interest, (3) adding research sites, (4) getting the word out about the project, and (5) getting youth to complete follow-up surveys. Strategies employed to overcome transportation challenges included shortening the number of sessions, offering sessions on both weekends and weekdays, and increasing bus tokens and transportation options. We hired more staff from American Indian/Alaska Native communities, added more research sites from our previously established relationships, and were more proactive in getting the word out on the project in American Indian/Alaska Native communities. We also utilized more field tracking and emailed and mailed survey invitations to reach more participants for their follow-up surveys. Because of our efforts, we were nearly able to reach our initial recruitment and retention goals. CONCLUSION: Although our research team had previously established relationships with various urban American Indian/Alaska Native communities, we encountered various recruitment and retention challenges in our study. However, by identifying challenges and employing culturally appropriate strategies, we were able to collect valuable data on the potential effectiveness of a substance use prevention intervention for urban American Indian/Alaska Native adolescents. Findings from this study assist toward the development of potentially successful strategies to successfully recruit and retain urban American Indian/Alaska Native adolescents in randomized controlled trials.

Unveiling an 'invisible population': health, substance use, sexual behavior, culture, and discrimination among urban American Indian/Alaska Native adolescents in California.

Objectives: There are limited public health data on urban American Indian/Alaska Native (AI/AN) populations, particularly adolescents. The current study attempted to address gaps by providing descriptive information on experiences of urban AI/AN adolescents across northern, central, and southern California.Design: We describe demographics and several behavioral health and cultural domains, including: alcohol and other drug (AOD) use, risky sexual behavior, mental and physical health, discrimination experiences, involvement in traditional practices, and cultural pride and belonging. We recruited 185 urban AI/AN adolescents across northern, central, and southern California from 2014 to 2017 who completed a baseline survey as part of a randomized controlled intervention trial.Results: Average age was 15.6 years; 51% female; 59% of adolescents that indicated AI/AN descent also endorsed another race or ethnicity. Rates of AOD use in this urban AI/AN sample were similar to rates for Monitoring the Future. About one-third of adolescents reported ever having sexual intercourse, with 15% reporting using alcohol or drugs before sex. Most reported good mental and physical health. Most urban AI/AN adolescents participated in traditional practices, such as attending Pow Wows and learning their tribal history. Adolescents also reported discrimination experiences, including being a victim of racial slurs and discrimination by law enforcement.Conclusions: This study describes a select sample of California urban AI/AN adolescents across several behavioral health and cultural domains. Although these adolescents reported numerous discrimination experiences and other stressors, findings suggest that this sample of urban AI/AN teens may be particularly resilient with regard to behavioral health.

Mental Health, Physical Health, and Cultural Characteristics Among American Indians/Alaska Natives Seeking Substance Use Treatment in an Urban Setting: A Descriptive Study.

Although approximately 70% of American Indians/Alaska Natives (AI/ANs) reside in urban areas, our knowledge of risk and protective factors among AI/ANs seeking substance use treatment within urban areas is limited. We analyze substance and commercialized cigarette use, AI/AN cultural identity and involvement, physical health and cognitive functioning, and mental health symptoms among 63 AI/AN adults seeking substance use treatment within an urban area in California. Alcohol (37%), marijuana (27%), and methamphetamine (22%) were the most commonly reported substances. Sixty-two percent used commercialized tobacco use. The majority of AI/AN adults (78%) engaged in at least one traditional practice during the past month and endorsed high levels of spiritual connectedness. Those who engaged in traditional practices demonstrated significantly less depression (p = 0.007) and anxiety (p = 0.04). Medical and mental health issues were not prominent, although participants revealed high levels of cognitive impairment. Results highlight the importance of utilizing AI/AN traditional practices for AI/AN adults seeking substance use treatment within urban areas. Clinical Trials Registry Number NCT01356667.

Identifying as American Indian/Alaska Native in Urban Areas: Implications for Adolescent Behavioral Health and Well-Being.

American Indian and Alaska Native (AI/AN) youth exhibit multiple health disparities, including high rates of alcohol and other drug (AOD) use, violence and delinquency, and mental health problems. Approximately 70% of AI/AN youth reside in urban areas, where negative outcomes on behavioral health and well-being are often high. Identity development may be particularly complex in urban settings, where youth may face more fragmented and lower density AI/AN communities, as well as mixed racial-ethnic ancestry and decreased familiarity with AI/AN lifeways. This study examines racial-ethnic and cultural identity among AI/AN adolescents and associations with behavioral health and well-being by analyzing quantitative data collected from a baseline assessment of 185 AI/AN urban adolescents from California who were part of a substance use intervention study. Adolescents who identified as AI/AN on their survey reported better mental health, less alcohol and marijuana use, lower rates of delinquency, and increased happiness and spiritual health.

Mantled Howler Monkeys (Alouatta palliata) in a Costa Rican Forest Fragment Do Not Modify Activity Budgets or Spatial Cohesion in Response to Anthropogenic Edges.

Forest fragmentation increases forest edge relative to forest interior, with lower vegetation quality common for primates in edge zones. Because most primates live in human-modified tropical forests within 1 km of their edges, it is critical to understand how primates cope with edge effects. Few studies have investigated how primates inhabiting a fragment alter their behaviour across forest edge and interior zones. Here we investigate how anthropogenic edges affect the activity and spatial cohesion of mantled howler monkeys (Alouatta palliata) at the La Suerte Biological Research Station (LSBRS), a Costa Rican forest fragment. We predicted the monkeys would spend greater proportions of their activity budget feeding and resting and a lower proportion travelling in edge compared to forest interior to compensate for lower resource availability in the edge. We also predicted that spatial cohesion would be lower in the edge to mitigate feeding competition. We collected data on activity and spatial cohesion (nearest neighbour distance; number of individuals within 5 m) in forest edge and interior zones via instantaneous sampling of focal animals. Contrary to predictions, the monkeys spent equal proportions of time feeding, resting and travelling in forest edge and interior. Similarly, there were no biologically meaningful differences in the number of individuals or the distance between nearest neighbours in the edge (1.0 individuals; 1.56 m) versus the interior (0.8 individuals; 1.73 m). Our results indicate that A. palliata at LSBRS do not adjust their activity or spatial cohesion patterns in response to anthropogenic edge effects, suggesting that the monkeys here exhibit less behavioural flexibility than A. palliata at some other sites. To develop effective primate conservation plans, it is therefore crucial to study primate species' responses to fragmentation across their geographic range.

Risk and Resilience Factors in Urban American Indian and Alaska Native Youth during the Coronavirus Pandemic.

American Indians and Alaska Natives suffer disproportionately from poverty and other inequities and are vulnerable to adverse health and socioeconomic effects of COVID-19. Using surveys and interviews (May - July 2020), we examined urban American Indian/Alaska Native adolescents' (N=50) health and behaviors, family dynamics, community cohesion, and traditional practice participation during COVID-19. About 20% of teens reported clinically significant anxiety and depression, 25% reported food insecurity, and 40% reported poor sleep. Teens also reported high family and community cohesion, and many engaged in traditional practices during this time. Although many teens reported problems, they also emphasized resilience strategies.

Making the Invisible Visible: Identifying and Articulating Culture in Practice-Based Evidence.

This study describes a conceptual tool, labeled the "culture cube," developed to identify and articulate the cultural underpinnings of prevention and early intervention projects in five priority populations (i.e., African American, Asian Pacific Islander, Latino, Native American, and Lesbian, Gay, Bisexual, Transgender, Queer, and Questioning), participating in the California Reducing Disparities Project Phase 2 (CRDP Phase 2). The culture cube was developed for evaluation of these practice-based evidence services (PBEs) for three purposes: (a) to focus attention on revealing and articulating more fully the operative worldview and culturally grounded frameworks underlying PBEs, explicitly identifying the links between cultural beliefs and values, community needs, and intervention design; (b) to guide the methods used to assess and evaluate PBEs so that the outcome indicators and process measures are conceptually consistent, community defined, and culturally centered; and (c) to invite communities to use their own indigenous epistemological frameworks to establish credible evidence. After reviewing the literature in this area and describing the theoretical framework for the culture cube, we describe its development, application, and the response to its use in the initial stages of the California Reducing Disparities Project-Phase 2.

Chemotherapy-induced peripheral neuropathy: a review of recent findings.

PURPOSE OF REVIEW: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN. RECENT FINDINGS: A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN. SUMMARY: Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation.

Psychometric Study of the Pain Drawing.

PURPOSE: The objectives of the study were to (1) assess the extent to which interrater reliability of pain drawing location and dispersion scoring methods are similar across pain disciplines in a sample of patients with cancer treatment-induced neuropathic pain (N = 56) and (2) investigate indicators of validity of the pain drawing in this unique sample. METHODS: Patients undergoing cancer therapy completed the Brief Pain Inventory Body Map, the MD Anderson Symptom Inventory, and the McGill Pain Questionnaire. RESULTS: Intraclass correlation coefficients among medical and psychology professionals ranged from .93-.99. Correlations between pain drawing score and symptom burden severity ranged from .29-.39; correlations between pain drawing score and symptom burden interference ranged from .28-.34. Patients who endorsed pain in the hands and feet more often described their pain as electric, numb, and shooting than patients without pain in the hands and feet. They also endorsed significantly more descriptors of neuropathic pain. CONCLUSIONS: Results suggest a similar understanding among members of a multidisciplinary pain team as to the location and dispersion of pain as represented by patients' pain drawings. In addition, pain drawing scores were related to symptom burden severity and interference and descriptors of neuropathic pain in expected ways.

Rsk-mediated phosphorylation and 14-3-3ɛ binding of Apaf-1 suppresses cytochrome c-induced apoptosis.

Many pro-apoptotic signals trigger mitochondrial cytochrome c release, leading to caspase activation and ultimate cellular breakdown. Cell survival pathways, including the mitogen-activated protein kinase (MAPK) cascade, promote cell viability by impeding mitochondrial cytochrome c release and by inhibiting subsequent caspase activation. Here, we describe a mechanism for the inhibition of cytochrome c-induced caspase activation by MAPK signalling, identifying a novel mode of apoptotic regulation exerted through Apaf-1 phosphorylation by the 90-kDa ribosomal S6 kinase (Rsk). Recruitment of 14-3-3ɛ to phosphorylated Ser268 impedes the ability of cytochrome c to nucleate apoptosome formation and activate downstream caspases. High endogenous levels of Rsk in PC3 prostate cancer cells or Rsk activation in other cell types promoted 14-3-3ɛ binding to Apaf-1 and rendered the cells insensitive to cytochrome c, suggesting a potential role for Rsk signalling in apoptotic resistance of prostate cancers and other cancers with elevated Rsk activity. Collectively, these results identify a novel locus of apoptosomal regulation wherein MAPK signalling promotes Rsk-catalysed Apaf-1 phosphorylation and consequent binding of 14-3-3ɛ, resulting in decreased cellular responsiveness to cytochrome c.