The Value of Phenotypic Precision Medicine in Prostate Cancer.

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related death. For patients who develop metastatic disease, tissue-based and circulating-tumor-based molecular and genomic biomarkers have emerged as a means of improving outcomes through the application of precision medicine. However, the benefit is limited to a minority of patients. An additional approach to further characterize the biology of advanced prostate cancer is through the use of phenotypic precision medicine, or the identification and targeting of phenotypic features of an individual patient's cancer. In this review article, we will discuss the background, potential clinical benefits, and limitations of genomic and phenotypic precision medicine in prostate cancer. We will also highlight how the emergence of image-based phenotypic medicine may lead to greater characterization of advanced prostate cancer disease burden and more individualized treatment approaches in patients.

Co-activation of SAM and HPA responses to acute stress: A review of the literature and test of differential associations with preadolescents' internalizing and externalizing.

Understanding co-activation patterns of the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic adrenal medullary (SAM) during early adolescence may illuminate risk for development of internalizing and externalizing problems. The present study advances empirical work on the topic by examining SAM-HPA co-activation during both the reactivity and recovery phases of the stress response following acute stress exposure. Fourth and fifth grade boys and girls (N = 149) provided cortisol and alpha-amylase via saliva at seven times throughout a 95-min assessment in which they were administered the modified Trier Social Stress Test. Parents reported on adolescents' life stress, pubertal development, medication use, and externalizing problems. Adolescents reported their own internalizing symptoms. Multiple linear regressions tested both direct and interactive effects of SAM and HPA reactivity and recovery on internalizing and externalizing problems. Results from these analyses showed that whereas SAM and HPA reactivity interacted to predict internalizing symptoms, it was their interaction during the recovery phase that predicted externalizing. Concurrent high SAM and HPA reactivity scores predicted high levels of internalizing and concurrently low SAM and HPA recovery scores predicted high levels of externalizing. Implications of the findings for further study and clinical application are discussed.

Maternal parenting predicts infant biobehavioral regulation among women with a history of childhood maltreatment.

Early biobehavioral regulation, a major influence of later adaptation, develops through dyadic interactions with caregivers. Thus, identification of maternal characteristics that can ameliorate or exacerbate infants' innate vulnerabilities is key for infant well-being and long-term healthy development. The present study evaluated the influence of maternal parenting, postpartum psychopathology, history of childhood maltreatment, and demographic risk on infant behavioral and physiological (i.e., salivary cortisol) regulation using the still-face paradigm. Our sample included 153 women with high rates of childhood maltreatment experiences. Mother-infant dyads completed a multimethod assessment at 7 months of age. Structural equation modeling showed that maternal positive (i.e., sensitive, warm, engaged, and joyful) and negative (i.e., overcontrolling and hostile) behaviors during interactions were associated with concurrent maternal depressive symptoms, single parent status, and low family income. In turn, positive parenting predicted improved infant behavioral regulation (i.e., positive affect and social behaviors following the stressor) and decreased cortisol reactivity (i.e., posttask levels that were similar to or lower than baseline cortisol). These findings suggest increased risk for those women experiencing high levels of depressive symptoms postpartum and highlight the importance of maternal positive interactive behaviors during the first year for children's neurodevelopment.

Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.

BACKGROUND: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown. METHODS: We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status. RESULTS: Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups. CONCLUSIONS: Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.

Mother-infant bonding impairment across the first 6 months postpartum: the primacy of psychopathology in women with childhood abuse and neglect histories.

Our goal was to examine the trajectory of bonding impairment across the first 6 months postpartum in the context of maternal risk, including maternal history of childhood abuse and neglect and postpartum psychopathology, and to test the association between self-reported bonding impairment and observed positive parenting behaviors. In a sample of women with childhood abuse and neglect histories (CA+, n = 97) and a healthy control comparison group (CA-, n = 53), participants completed questionnaires related to bonding with their infants at 6 weeks, 4 months, and 6 months postpartum and psychopathology at 6 months postpartum. In addition, during a 6-month postpartum home visit, mothers and infants participated in a dyadic play interaction subsequently coded for positive parenting behaviors by blinded coders. We found that all women, independent of risk status, increased in bonding with their infant over the first 6 months postpartum; however, women with postpartum psychopathology (depression and posttraumatic stress disorder [PTSD]) showed consistently greater bonding impairment scores at all timepoints. Moreover, we found that, at the 6-month assessment, bonding impairment and observed parenting behaviors were significantly associated. These results highlight the adverse effects of maternal postpartum depression and PTSD on mother-infant bonding in early postpartum in women with child abuse and neglect histories. These findings also shed light on the critical need for early detection and effective treatment of postpartum mental illness in order to prevent problematic parenting and the development of disturbed mother-infant relationships. Results support the use of the Postpartum Bonding Questionnaire as a tool to assess parenting quality by its demonstrated association with observed parenting behaviors.

Foreign accent syndrome as a heralding manifestation of transformation to small cell neuroendocrine prostate cancer.

A man in his 50s with metastatic hormone-sensitive prostate cancer, receiving androgen deprivation therapy and abiraterone acetate/prednisone, presented with an uncontrollable 'Irish brogue' accent despite no Irish background, consistent with foreign accent syndrome (FAS). He had no neurological examination abnormalities, psychiatric history or MRI of the brain abnormalities at symptom onset. Imaging revealed progression of his prostate cancer, despite undetectable prostate-specific antigen levels. Biopsy confirmed transformation to small cell neuroendocrine prostate cancer (NEPC). Despite chemotherapy, his NEPC progressed resulting in multifocal brain metastases and a likely paraneoplastic ascending paralysis leading to his death. We report FAS as the presenting manifestation of transformation to small cell NEPC, a previously undescribed phenomenon. His presentation was most consistent with an underlying paraneoplastic neurological disorder (PND), despite a negative serum paraneoplastic panel. This report enhances the minimal existing literature on FAS and PNDs associated with transformed NEPC.

A Quality Improvement Initiative To Improve Postdischarge Antimicrobial Adherence.

OBJECTIVES: Bedside delivery of discharge medications improves caregiver understanding and experience. Less is known about its impact on medication adherence. We aimed to improve antimicrobial adherence by increasing on-time first home doses for patients discharged from the pediatric hospital medicine service from 33% to 80% over 1 year via creation of a discharge medication delivery and counseling "Meds to Beds" (M2B) program. METHODS: Using sequential plan-do-study-act cycles, an interprofessional workgroup implemented M2B on select pediatric hospital medicine units at our quaternary children's hospital from October 2017 through December 2018. Scripted telephone surveys were conducted with caregivers of patients prescribed antimicrobial agents at discharge. The primary outcome measure was on-time administration of the first home antimicrobial dose, defined as a dose given within the time of the inpatient dose equivalent plus 25%. Process measures primarily assessed caregiver report of barriers to adherence. Run charts, statistical process control charts, and inferential statistics were used for data analysis. RESULTS: Caregiver survey response rate was 35% (207 of 585). Median on-time first home antimicrobial doses increased from 33% to 67% (P < .001). Forty percent of M2B prescriptions were adjusted before discharge because of financial or insurance barriers. M2B participants reported significantly less difficulty in obtaining medications compared with nonparticipants (1% vs 17%, P < .001). CONCLUSIONS: The M2B program successfully increased parental report of timely administration of first home antimicrobial doses, a component of overall adherence. The program enabled providers to identify and resolve prescription problems before discharge. Importantly, caregivers reported reduced barriers to medication adherence.

What is "neuromarketing"? A discussion and agenda for future research.

Recent years have seen advances in neuroimaging to such an extent that neuroscientists are able to directly study the frequency, location, and timing of neuronal activity to an unprecedented degree. However, marketing science has remained largely unaware of such advances and their huge potential. In fact, the application of neuroimaging to market research--what has come to be called "neuromarketing"--has caused considerable controversy within neuroscience circles in recent times. This paper is an attempt to widen the scope of neuromarketing beyond commercial brand and consumer behaviour applications, to include a wider conceptualisation of marketing science. Drawing from general neuroscience and neuroeconomics, neuromarketing as a field of study is defined, and some future research directions are suggested.

Perspectives on trauma-informed care from mothers with a history of childhood maltreatment: a qualitative study.

Women who experienced abuse or neglect as children are more likely to have health problems during pregnancy and postpartum, but can be reluctant to seek help due to a lack of trauma-informed services. As part of a larger mixed method study, this component aimed to obtain qualitative data from trauma-exposed new mothers about their health care preferences during the perinatal period with the ultimate goal to design personalized, supportive interventions. Fifty-two trauma-exposed mothers completed a semi-structured interview at seven months postpartum about health care preferences including ideas for programs that promote wellness, thoughts about the influences of being a new mother and possible names for a program serving trauma-exposed mothers. Interviews were transcribed and coded using N-Vivo. Participants described ambivalence about seeking help but also a sincere desire for healing, coupled with hope for the future. This tension was apparent in the discussions highlighting the importance of access to experienced, nonjudgmental, and knowledgeable health and social care staff and volunteers, the wish for both formal, integrated physical and mental health services, and for informal opportunities to meet other trauma-exposed mothers in a non-stigmatizing, child-friendly setting. Finally, positive relationship-building, respect, and safety were identified as key elements of services critical to counteract trauma-related shame and mistrust in others. Services for trauma-exposed mothers should acknowledge the normal ambivalence surrounding seeking help, but promote hope-affirming practices in a family-centered, safe, non-clinical setting that involves children, builds social support, and provides peer interaction. Program names should reflect optimism and healing rather than trauma.