How we approach steroid-induced affective disorder in pediatric oncology.

High-dose corticosteroids are an essential component of treatment for pediatric cancers. Yet, these agents often cause psychiatric disturbances including sleep disruption, steroid-induced psychosis, and steroid-induced affective disorder (SIAD). SIAD, identified as a specific form of substance/medication-induced mental disorder, can present with various psychiatric symptoms, including mania, depression, irritability, and inconsolability. SIAD's varied presentation can lead to underdiagnosis and complicates clinical care, research, and identification of best practices. Here we highlight three pediatric oncology cases involving SIAD and discuss recommendations for supporting patients with SIAD, while introducing a tiered intervention framework (modified from Kazak) that stratifies responses based on symptom severity.

Developmental and adaptive functioning of very young children with solid tumors and brain tumors.

PURPOSE: Infancy/toddlerhood is a period of rapid development. All infants/toddlers (0-36 months-of-age) undergoing cancer-directed treatment at one hospital are offered developmental assessments and related services. Yet, literature comparing development of infants/toddlers with brain tumors to those with non-CNS solid tumors is sparse. DESIGN AND METHODS: Developmental assessment data were abstracted from electronic health records of infants/toddlers undergoing treatment for a brain tumor (n = 36; mean age = 21.83 ± 9.96 months) or a solid tumor (n = 40; mean age = 17.35 ± 8.50). Z-scores compared obtained data with age expectations. Chi-square analyses assessed whether a greater proportion of participants scored within the clinical range than normative expectations. Multivariate analysis of variance and chi-square analyses compared developmental outcomes between groups. RESULTS: Compared with age expectations, the overall group demonstrated significantly less well-developed skills. Infants/toddlers with solid tumors demonstrated clinical deficits at rates higher than expected for most domains; the rate of impairment for the solid tumor group did not differ significantly from that of the brain tumor group across most subtests. CONCLUSIONS: Like young patients with brain tumors, the developmental functioning of infants/toddlers with solid tumors should be studied across time to determine the trajectory of functioning for these young patients and to inform future developmental intervention studies. PRACTICE IMPLICATIONS: Infants/toddlers with a malignant solid tumor may be at increased risk for delayed development. These very young patients would likely benefit from developmental assessment, early intervention services during and after treatment, and ongoing monitoring of development across time.

Promoting Completion of Cranial Radiation Therapy Without Sedation in Young Patients With Brain Tumors: A Case Series Illustrating Flexible Application of Empirically Supported Intervention.

Repeated anesthesia poses risks to patients but is often utilized to immobilize young children undergoing cranial radiation therapy for brain tumors. To enable young patients to remain still during cranial radiation therapy and thereby avoid sedation, medical and psychosocial clinicians can use behavioral and other supportive interventions. This case series illustrates the utility of behavioral training for motion control in 3 children 6 years old or younger who were treated for brain tumors. We demonstrate the efficacy of flexible, individualized intervention approaches to accommodate patients with brain tumors in the context of emotional dysregulation, significant communication barriers, and profound sensory deficits.

Virtual Group Activities as a New Platform for Socialization in Children With Pediatric Cancer: A Case Series From the COVID-19 Pandemic.

Socialization with peers is essential for development yet reduced when children and adolescents are undergoing cancer treatment. Providing opportunity for social experiences is a key role for providers working in the pediatric oncology setting. Traditional in-person socialization activities were significantly impacted by coronavirus disease-2019 restrictions, and psychosocial providers were forced to adapt their practice. This case series illustrates four unique scenarios that highlight virtual social interactions as both feasible and beneficial. While virtual socialization groups were intended to be temporary, the experiences described suggest that ongoing video-based options for some socialization activities are likely prudent for some pediatric populations.

The Influence of Early Childhood Temperament on Later Social-Emotional Functioning in Youth with Cancer.

OBJECTIVE: One of the peak incidences of childhood cancer is during the early childhood years. This is also an important time for psychosocial and personality development, and it is well known that early childhood temperament influences later psychosocial functioning. However, this association has not been examined in young children with cancer. METHODS: Parents of children with cancer (N = 39) and healthy comparisons (N = 35) completed an indicator of temperament (Children's Behavior Questionnaire) when children were young (Mage=4.99 ± 1.05 years). Five years later, parents and youth completed measures of psychosocial functioning (Mage=10.15 ± 1.10 years; Behavior Assessment Scale for Children, 2nd edition and Social Emotional Assets and Resilience Scale). RESULTS: Parents of healthy comparisons reported that their children demonstrated greater surgency than youth with cancer; there were no differences in negative affect or effortful control. Children with cancer and healthy comparisons were rated similarly on measures of psychosocial functioning. Health status was not a significant predictor of later functioning, but socioeconomic status and temperament were. The influence of temperament was stronger for strengths-based functioning (e.g., social competence, adaptive functioning) versus distress (internalizing and externalizing problems). CONCLUSIONS: Early childhood temperament is a strong predictor of later psychosocial functioning, regardless of health status. Findings highlight the need to consider temperament in the clinical assessment of psychosocial functioning in children with cancer. Additional research is needed to specifically assess how a diagnosis of cancer in early childhood influences temperament over time.

Social-Emotional Functioning in Preschool-Aged Children With Cancer: Comparisons Between Children With Brain and Non-CNS Solid Tumors.

OBJECTIVES: The preschool years (ages 4-6) are essential for the development of social-emotional skills, such as problem solving, emotion regulation, and conflict resolution. For children with cancer treated during this period, especially those with brain tumors, there are questions regarding the consequences of missed normative social experiences. The objective of this pilot study was to explore the social-emotional functioning of young children with brain tumors, as compared to those with non-CNS solid tumors, who have recently completed treatment. METHODS: Children with brain (n = 23) or solid tumors (n = 20) 4-6 years of age (5.42 ± 0.73 years; 60.5% male, 65.1% white) who were 8.21 (SD = 2.42) months post-treatment completed objective measures (Challenging Situations Task, NEPSY-II) of social functioning while a caregiver completed questionnaires (e.g., BASC-3, NIH Toolbox Emotion Measures). RESULTS: A large portion of the sample (brain tumor: 65.2%, solid tumor: 44.4%) fell in the clinical range on parent-report measures of peer interaction. There were no statistically significant differences between patient groups across measures, but effect sizes suggest youth with brain tumors potentially experienced more difficulties on some indices. All children were more likely to choose prosocial responses when presented with a challenging social situation where they were physically provoked (e.g., hit) versus socially provoked (e.g., left out). CONCLUSIONS: Preschool-aged children with cancer may experience weaknesses in social functioning shortly after treatment, with youth with brain tumors potentially demonstrating greater concerns. Emphasizing social interaction is critical to ensure young children have the opportunity to develop critical social-emotional skills.

Compersion: When Jealousy-Inducing Situations Don't (Just) Induce Jealousy.

Emotional reactions to a partner's extradyadic romantic interests are assumed to be negative and characterized by jealousy, an emotional state that arises over a perceived threat to one's relationship. Yet, reactions may also be positive, and involve compersion, or taking joy in one's partner's pleasure in other sexual and relational encounters. Although some have argued that compersion is the opposite of jealousy, research suggests that compersion and jealousy may not be opposing constructs, despite being treated this way in both theoretical and empirical research. Using a convenience sample of polyamorous (N = 3530) and monogamous (N = 1358) individuals, we draw on theories of jealousy, emotional ambivalence, and emotional forecasting to examine people's anticipated affective responses to hypothetical situations involving a partner's extradyadic relations and assess whether experience with having a partner engage in extradyadic relations was associated with anticipating less jealousy and more compersion. Results suggest that people in polyamorous relationships report less jealousy and more compersion with their partners, and that personal experience involving a partner's extradyadic romantic interests predicted more compersion and less jealousy, with experience predicting greater increases in compersion among monogamous than polyamorous participants. Finally, while anticipated compersion was associated with greater relationship satisfaction, neither jealousy nor ambivalence was associated with relationship satisfaction. These results further demonstrate that individuals can experience both positive and negative reactions to a partner's extradyadic relations, both based on actual experience and projection of responses to future events, and that real-life experiences are important in anticipating these emotions.

Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation.

Jmjd2 H3K9 demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we reveal that Jmjd2c facilitates this process by stabilising the assembly of mediator-cohesin complexes at lineage-specific enhancers. Functionally, we show that Jmjd2c is required in ESCs to initiate appropriate gene expression programs upon somatic multi-lineage differentiation. In the absence of Jmjd2c, differentiation is stalled at an early post-implantation epiblast-like stage, while Jmjd2c-knockout ESCs remain capable of forming extra-embryonic endoderm derivatives. Dissection of the underlying molecular basis revealed that Jmjd2c is re-distributed to lineage-specific enhancers during ESC priming for differentiation. Interestingly, Jmjd2c-bound enhancers are co-occupied by the H3K9-methyltransferase G9a (also known as Ehmt2), independently of its H3K9-modifying activity. Loss of Jmjd2c abrogates G9a recruitment and further destabilises loading of the mediator and cohesin components Med1 and Smc1a at newly activated and poised enhancers in ESC-derived epiblast-like cells. These findings unveil Jmjd2c and G9a as novel enhancer-associated factors, and implicate Jmjd2c as a molecular scaffold for the assembly of essential enhancer-protein complexes with an impact on timely gene activation.

Epigenetic Regulation of Vascular Smooth Muscle Cells by Histone H3 Lysine 9 Dimethylation Attenuates Target Gene-Induction by Inflammatory Signaling.

OBJECTIVE: Vascular inflammation underlies cardiovascular disease. Vascular smooth muscle cells (VSMCs) upregulate selective genes, including MMPs (matrix metalloproteinases) and proinflammatory cytokines upon local inflammation, which directly contribute to vascular disease and adverse clinical outcome. Identification of factors controlling VSMC responses to inflammation is therefore of considerable therapeutic importance. Here, we determine the role of Histone H3 lysine 9 di-methylation (H3K9me2), a repressive epigenetic mark that is reduced in atherosclerotic lesions, in regulating the VSMC inflammatory response. Approach and Results: We used VSMC-lineage tracing to reveal reduced H3K9me2 levels in VSMCs of arteries after injury and in atherosclerotic lesions compared with control vessels. Intriguingly, chromatin immunoprecipitation showed H3K9me2 enrichment at a subset of inflammation-responsive gene promoters, including MMP3, MMP9, MMP12, and IL6, in mouse and human VSMCs. Inhibition of G9A/GLP (G9A-like protein), the primary enzymes responsible for H3K9me2, significantly potentiated inflammation-induced gene induction in vitro and in vivo without altering NFκB (nuclear factor kappa-light-chain-enhancer of activated B cell) and MAPK (mitogen-activated protein kinase) signaling. Rather, reduced G9A/GLP activity enhanced inflammation-induced binding of transcription factors NFκB-p65 and cJUN to H3K9me2 target gene promoters MMP3 and IL6. Taken together, these results suggest that promoter-associated H3K9me2 directly attenuates the induction of target genes in response to inflammation in human VSMCs. CONCLUSIONS: This study implicates H3K9me2 in regulating the proinflammatory VSMC phenotype. Our findings suggest that reduced H3K9me2 in disease enhance binding of NFκB and AP-1 (activator protein-1) transcription factors at specific inflammation-responsive genes to augment proinflammatory stimuli in VSMC. Therefore, H3K9me2-regulation could be targeted clinically to limit expression of MMPs and IL6, which are induced in vascular disease.

Emerging Roles for Neuropilin-2 in Cardiovascular Disease.

Cardiovascular disease, the leading cause of death worldwide, is predominantly associated with atherosclerosis. Atherosclerosis is a chronic inflammatory disease characterised by the narrowing of large to medium-sized arteries due to a build-up of plaque. Atherosclerotic plaque is comprised of lipids, extracellular matrix, and several cell types, including endothelial, immune, and vascular smooth muscle cells. Such narrowing of the blood vessels can itself restrict blood flow to vital organs but most severe clinical complications, including heart attacks and strokes, occur when lesions rupture, triggering the blood to clot and obstructing blood flow further down the vascular tree. To circumvent such obstructions, percutaneous coronary intervention or bypass grafts are often required; however, re-occlusion of the treated artery frequently occurs. Neuropilins (NRPs), a multifunctional family of cell surface co-receptors, are expressed by endothelial, immune, and vascular smooth muscle cells and are regulators of numerous signalling pathways within the vasculature. Here, we review recent studies implicating NRP2 in the development of occlusive vascular diseases and discuss how NRP2 could be targeted for therapeutic intervention.

Early Cognitive and Adaptive Functioning of Clinically Referred Infants and Toddlers with Cancer.

Many children with cancer are diagnosed during infancy and toddlerhood (< 3 years of age), potentially resulting in disrupted and/or missed developmental opportunities. Our objective was to describe the functioning of infants and toddlers with cancer who were clinically referred for evaluation at a hospital-based psychology clinic. Data from 29 very young children with cancer (Mage = 23.62 ± 6.6 months; 55.2% male) who completed clinically referred assessments from 2010 to 2015 were abstracted. Children were 11.3 months post-diagnosis (SD = 7.77, range 1-29 months) with just over half off-therapy at the time of assessment (55.2%). Overall, developmental functioning was significantly below expectations [t(22) = - 8.99, p < .001]. Adaptive functioning [t(25) = - 6.41, p < .001] was also significantly below expectations. Infants and toddlers with cancer appear to be at significant risk for weaknesses in early cognitive and adaptive functioning. The margin of deficits found in this study warrant the need for further investigation and consideration of this young population to ensure optimal functional development.

Comparing Relationship Quality Across Different Types of Romantic Partners in Polyamorous and Monogamous Relationships.

Polyamory is the practice of having multiple emotionally close relationships that may or may not be sexual. Research concerning polyamory has just begun to determine how relationships among partners in polyamorous arrangements may vary. Most of the research assessing perceptions of polyamorous partners has focused on primary-secondary configurations; however, non-hierarchical configurations exist and can involve having multiple primary partners or having only non-primary partners. The current research is the first to examine perceptions of partners and relationship quality in various polyamorous configurations and compares results for each configuration to monogamous partners. Results from online convenience samples suggest that co-primary and non-primary configurations are common among polyamorous participants, with approximately 38% identifying with one of these configurations in 2013 and 55% in 2017. Furthermore, our results suggest that while relationships with partners in co-primary and non-primary structures still differ in some ways (e.g., investment, acceptance, secrecy, time spent having sex), they are closer to their ideals on several psychologically meaningful indicators of relationship quality (e.g., commitment and satisfaction). In other words, despite rejecting hierarchical primary-secondary labels, many of the same relationship qualities differ systematically among partners in non-hierarchical relationships. Furthermore, pseudo-primary partners and primary partners in these relationships are more comparable to monogamous partners than they are to secondary partners. We discuss how these results inform our understanding of polyamorous and monogamous relationships and suggest future directions based on these findings.

Extensive Proliferation of a Subset of Differentiated, yet Plastic, Medial Vascular Smooth Muscle Cells Contributes to Neointimal Formation in Mouse Injury and Atherosclerosis Models.

RATIONALE: Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved. In particular, it is not known whether all VSMCs proliferate and display plasticity or whether individual cells can switch to multiple phenotypes. OBJECTIVE: To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells. METHODS AND RESULTS: Using multicolor lineage labeling, we demonstrate that VSMCs in injury-induced neointimal lesions and in atherosclerotic plaques are oligoclonal, derived from few expanding cells. Lineage tracing also revealed that the progeny of individual VSMCs contributes to both alpha smooth muscle actin (aSma)-positive fibrous cap and Mac3-expressing macrophage-like plaque core cells. Costaining for phenotypic markers further identified a double-positive aSma+ Mac3+ cell population, which is specific to VSMC-derived plaque cells. In contrast, VSMC-derived cells generating the neointima after vascular injury generally retained the expression of VSMC markers and the upregulation of Mac3 was less pronounced. Monochromatic regions in atherosclerotic plaques and injury-induced neointima did not contain VSMC-derived cells expressing a different fluorescent reporter protein, suggesting that proliferation-independent VSMC migration does not make a major contribution to VSMC accumulation in vascular disease. CONCLUSIONS: We demonstrate that extensive proliferation of a low proportion of highly plastic VSMCs results in the observed VSMC accumulation after injury and in atherosclerotic plaques. Therapeutic targeting of these hyperproliferating VSMCs might effectively reduce vascular disease without affecting vascular integrity.

Early intervention for infants and toddlers: Applications for pediatric oncology.

Young children (<3 years) with cancer are at risk for delays in development due to their disease and its required treatments and restrictions. In the United States, Part C of the Individuals with Disabilities Education Act describes a system of early intervention (EI) services for young children with delays or the potential for delays in development. Children with cancer may be eligible for EI but are rarely referred. Our objectives are to describe the critical impact of early childhood development on long-term outcomes, review current considerations for EI, and advocate for the referral to EI for young children with cancer.

"Love me, parents!": impact evaluation of a national social and behavioral change communication campaign on maternal health outcomes in Tanzania.

BACKGROUND: Despite marked improvements over the last few decades, maternal mortality in Tanzania remains among the world's highest at 454 maternal deaths per 100,000 live births. Many factors contribute to this disparity, such as a lack of attendance at antenatal care (ANC) services and low rates of delivery at a health facility with a skilled provider. The Wazazi Nipendeni (Love me, parents) social and behavioral change communication campaign was launched in Tanzania in 2012 to improve a range of maternal health outcomes, including individual birth planning, timely ANC attendance, and giving birth in a healthcare facility. METHODS: An evaluation to determine the impact of the national Wazazi Nipendeni campaign was conducted in five purposively selected regions of Tanzania using exit interviews with pregnant and post-natal women attending ANC clinics. A total of 1708 women were interviewed regarding campaign exposure, ANC attendance, and individual birth planning. RESULTS: Over one third of interviewed women (35.1%) reported exposure to the campaign in the last month. The more sources from which women reported hearing the Wazazi Nipendeni message, the more they planned for the birth of their child (ß = 0.08, p = .001). Greater numbers of types of exposure to the Wazazi Nipendeni message was associated with an increase in ANC visits (ß = 0.05, p = .004). Intervention exposure did not significantly predict the timing of the first ANC visit or HIV testing in the adjusted model, however, findings showed that exposure did predict whether women delivered at a health care facility (or not) and whether they tested for HIV with a partner in the unadjusted models. CONCLUSIONS: The Wazazi Nipendeni campaign shows promise that such a behavior change communication intervention could lead to better pregnancy and childbirth outcomes for women in low resource settings. For outcomes such as HIV testing, message exposure showed some promising effects, but demographic variables such as age and socioeconomic status appear to be important as well.

Understanding the experiences and needs of female commercial sex workers in Kathmandu, Nepal.

Through this exploratory study, we sought to better understand Nepali female commercial sex workers' (FCSWs') experiences in order to inform HIV prevention and health promotion interventions for this vulnerable and hard-to-reach population. Data were collected through phenomenological interviews with eight FCSWs. Through analysis we reveal promising intervention points to enhance FCSW health, empowerment, and overall well-being. Researchers suggest a combination of structural and individual programs is essential to improving the circumstances of Nepali FCSWs and preventing the spread of HIV. Given Nepal's limited resources and complex environment, it is imperative future prevention programs are focused and guided by FCSWs' lived experiences.

Unveiling the silence: women's sexual health and experiences in Nepal.

Rising rates of HIV in Nepal signal an impending epidemic. In order to develop culturally appropriate and effective actions and programmes to reduce HIV transmission, it is necessary to understand attitudes, behaviours and norms surrounding sexual networking and safer-sex practices in Nepal. Nepali women are thought to be at increased risk of sexually transmitted infections (STIs) and HIV, sexual violence and exploitation and other sexual health disparities due to cultural scripts limiting access to education, ability to control sexual relationships and acceptability in discussing sex and sexual health. The present study comprises a series of interviews with 25 women living in Kathmandu (13 individual interviews and 2 focus-group discussions) about their knowledge and experiences related to sex and sexual health. Interviews were translated and transcribed and two independent coders conducted a thematic analysis. Overall, the women described sex as primarily a male domain. Sex and sexual health were viewed as taboo discussion topics and formal sex education was perceived as minimally available and far from comprehensive in its scope. This formative study can inform future interventions aimed at reducing the spread of STIs/HIV in Nepal and empowering women on issues of sexual health and well-being.

Nature, extent and implications of belief in Kikombe cha babu and other herbal HIV cures in Tanzania.

This study's objective was to describe awareness of, access to, belief in, and utilization of the healing tea Kikombe cha babu and other alternative treatments for HIV in Tanzania. Associations with HIV testing, treatment, and prevention behaviors are also explored. A survey with questions about alternative medicine was administered to a sample in Tanzania using a stratified, multistage random selection method. Adults were interviewed face-to-face. Items concerning alternative HIV treatments addressed awareness, access, beliefs, and treatment-seeking behaviors. Questions about HIV prevention and treatment were also asked. Results showed participants indicated a high awareness of alternative treatments available in Tanzania, with 95.3% of 2313 adults having heard of these treatments. Of those, 6.0% had actually sought the treatment, and 46.8% had an acquaintance seek it. However, 81.0% indicated these treatments were not easily accessible. There is a high level of belief in the ability of these alternative treatments to cure HIV, with 44.0% of people who had heard of these treatments indicating they believe such treatments can cure HIV. Additionally, many people indicated having these alternative treatments available would result in decreased condom use (15.6%), no need to use condoms (94.9%), and no need to take antiretroviral therapy (81.7%). However, 57.4% indicated they would be more likely to get tested for HIV if alternative treatments were available. Belief in the ability of alternative treatments to cure HIV in Tanzania is high and should be further explored due to its implications for potentially sidelining HIV prevention and treatment initiatives.

Evaluation of the "let's talk" safer sex intervention in Nepal.

This study is an evaluation of a pilot of the Let's Talk Intervention for Nepali women for effectiveness in increasing sexual health communication between women and the men in their lives. The intervention included 88 women in Kathmandu and spanned three 2-hour group sessions. Baseline, posttest, and follow-up knowledge, attitude, and behavior surveys were completed. Results showed women at posttest and follow-up spoke with more women and men about sex than they had at baseline. Attitudes regarding gender norms about sex improved as a result of the intervention, and shame about sex and sexuality for women decreased after intervention. Women also reported greater comfort discussing sex after the intervention. HIV knowledge scores increased after intervention but dropped again at follow-up, likely because of time constraints in addressing this topic in sufficient detail. This is the first program in Nepal that addresses communication about sexual health while focusing on education and prevention for HIV/STIs for women.