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.

Cellular mechanisms of oligoclonal vascular smooth muscle cell expansion in cardiovascular disease.

AIMS: Quiescent, differentiated adult vascular smooth muscle cells (VSMCs) can be induced to proliferate and switch phenotype. Such plasticity underlies blood vessel homeostasis and contributes to vascular disease development. Oligoclonal VSMC contribution is a hallmark of end-stage vascular disease. Here, we aim to understand cellular mechanisms underpinning generation of this VSMC oligoclonality. METHODS AND RESULTS: We investigate the dynamics of VSMC clone formation using confocal microscopy and single-cell transcriptomics in VSMC-lineage-traced animal models. We find that activation of medial VSMC proliferation occurs at low frequency after vascular injury and that only a subset of expanding clones migrate, which together drives formation of oligoclonal neointimal lesions. VSMC contribution in small atherosclerotic lesions is typically from one or two clones, similar to observations in mature lesions. Low frequency (<0.1%) of clonal VSMC proliferation is also observed in vitro. Single-cell RNA-sequencing revealed progressive cell state changes across a contiguous VSMC population at onset of injury-induced proliferation. Proliferating VSMCs mapped selectively to one of two distinct trajectories and were associated with cells showing extensive phenotypic switching. A proliferation-associated transitory state shared pronounced similarities with atypical SCA1+ VSMCs from uninjured mouse arteries and VSMCs in healthy human aorta. We show functionally that clonal expansion of SCA1+ VSMCs from healthy arteries occurs at higher rate and frequency compared with SCA1- cells. CONCLUSION: Our data suggest that activation of proliferation at low frequency is a general, cell-intrinsic feature of VSMCs. We show that rare VSMCs in healthy arteries display VSMC phenotypic switching akin to that observed in pathological vessel remodelling and that this is a conserved feature of mouse and human healthy arteries. The increased proliferation of modulated VSMCs from healthy arteries suggests that these cells respond more readily to disease-inducing cues and could drive oligoclonal VSMC expansion.

Occupational Therapy: An Essential Component of Support for Young Children With Cancer.

We established a multidisciplinary early childhood clinic to support infants and toddlers receiving cancer treatment. The access to occupational therapy (OT) in this population is unknown. To describe the access to OT for infants and toddlers with cancer. We retrospectively reviewed medical records to determine the frequency and characteristics of children with cancer who were referred to OT. Demographic data, medical information, and frequency of referrals were extracted from September 2015 to September 2018. Of the 134 patients, 112 (83.6%) received an OT evaluation: 88.4% were referred for hospital-based OT services; 42.0% were recommended for services upon returning home. Between-group comparisons revealed significant differences in referrals for home- or community-based OT services based on age and disease. OT is crucial to treatment plans that address the developmental needs of young pediatric oncology patients during hospitalization and thereafter. Recommendations for monitoring this vulnerable population are provided.

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.

Inaugural BMC Ecology and Evolution image competition: the winning images.

The inaugural BMC Ecology and Evolution image competition attracted entries from talented ecologists and evolutionary biologists worldwide. Together, these photos beautifully capture biodiversity, how it arose and why we should conserve it. This editorial celebrates the winning images as selected by the Editor of BMC Ecology and Evolution and senior members of the journal's editorial board.

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.

Pill-Swallowing Training in Very Young Children With Cancer: A Case Series and Developmental Considerations.

Pill-swallowing training (PST) is a promising behavioral intervention. However, previous studies of PST have largely reported outcomes only in children aged 6 years and older. In the pediatric oncology setting, younger children may benefit from learning to swallow pills, with motivators such as avoiding bad-tasting liquid medications, simplifying oral medication routines, and accessing trials for patients with poor prognoses. Here, we briefly describe the standard PST intervention protocol and report success with very young patients experiencing a variety of medical, emotional, behavioral, and developmental complications. The current case series illustrates the utility of traditional behavioral PST interventions with novel supplements, such as intervention to increase general compliance or decrease anxiety, in four young children with cancer. These cases highlight the effectiveness of PST and describe the positive impact reported by each family. Developmental considerations for using PST with young children with cancer are offered.

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.

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.

Beyond clinical practice in pediatric psychology: Illustrative experiences in influencing practice changes, public opinion, and governmental policies.

Consistent with the core underpinnings of advocacy within the field of pediatrics, the discipline of pediatric psychology places an emphasis on advocating for children through clinical and research efforts as well as through a systems approach of interdisciplinary collaboration and partnering with others. In the current article, the role of advocacy efforts for pediatric psychologists within children's hospitals are highlighted. Various forms and models of advocacy are discussed, particularly as they relate to individual and organizational advocacy within children's hospitals, as well as interdisciplinary collaboration and shared advocacy with other health care providers and leadership. Training of pediatric psychologists in advocacy is also addressed, including limitations in development and application of advocacy skills for pediatric psychologists. Examples of policy change at the hospital/institutional, state, and national levels are also provided. While pediatric psychologists are in unique positions to advocate for their patients within interdisciplinary health care settings, challenges in advocacy exist. Future directions for improving advocacy for pediatric psychologists are explored. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cognitive and Psychosocial Development in Young Children with Brain Tumors: Observations from a Clinical Sample.

Survivors of pediatric brain tumor (BT) are known to be at risk for developing cognitive and psychosocial late effects. Young age at treatment (≤6 years) is typically considered to put patients at increased risk. However, there is limited research specifically exploring functioning in these young patients. Cognitive and psychosocial data were retrospectively abstracted from medical charts for 79 young patients (54.4% male) treated for BT with a variety of treatment modalities (e.g., surgery, radiation therapy, chemotherapy). Children were clinically assessed at 4.52 years of age (range = 1.48-5.98) and most were off-therapy (74.4%). Mean performances on developmental (68.3 ± 10.02), cognitive (88.09 ± 18.38), and pre-academic (86.84 ± 19.75) measures were all below average. Parent report of adaptive functioning was also below average (82.10 ± 16.21), but psychosocial functioning was generally within normal limits. Most patients had impaired functioning (scores <10th percentile) in at least one domain assessed. Exploratory analyses revealed that many patients (27.3-60.6%) exhibited a significant discrepancy between domains of cognitive functioning (e.g., verbal and spatial). Young children treated for BT experienced high rates of impairment in cognitive, pre-academic, and adaptive domains. Future work is needed to focus on serial longitudinal assessment of these young patients, as well as dedicated intervention and prevention efforts.

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.

The role of smooth muscle cells in plaque stability: Therapeutic targeting potential.

Events responsible for cardiovascular mortality and morbidity are predominantly caused by rupture of "vulnerable" atherosclerotic lesions. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and have historically been considered beneficial for plaque stability. VSMCs constitute the main cellular component of the protective fibrous cap within lesions and are responsible for synthesising strength-giving extracellular matrix components. However, lineage-tracing experiments in mouse models of atherosclerosis have shown that, in addition to the fibrous cap, VSMCs also give rise to many of the cell types found within the plaque core. In particular, VSMCs generate a substantial fraction of lipid-laden foam cells, and VSMC-derived cells expressing markers of macrophages, osteochondrocyte, and mesenchymal stem cells have been observed within lesions. Here, we review recent studies that have changed our perspective on VSMC function in atherosclerosis and discuss how VSMCs could be targeted to increase plaque stability.

Psychosocial Functioning of Young Children Treated for Cancer: Findings From a Clinical Sample.

OBJECTIVES: Many pediatric cancers are diagnosed in early childhood, a time of significant growth and development that lays the foundations for overall adjustment and functioning. The objective of this article was to characterize the psychosocial functioning of young children with cancer. METHOD: Data from a sample of young children with cancer ( N = 92) who completed a psychological evaluation that included the Behavior Assessment Scale for Children-second edition (BASC-2) parent report were abstracted from the medical record. Patients were primarily White (70.7%), male (54.3%), and 4.81 ± 0.89 years old at evaluation. Most were treated for brain tumors (64.1%). RESULTS: Overall group means on each of the BASC-2 subscales were within normal limits, though significantly more patients than expected had elevated scores on the Internalizing and Behavioral Symptoms indexes. Patients who were on-treatment had higher mean overall Internalizing Problems scores, as well as greater Anxiety and Somatization scores, than those who were off-treatment (Wilks's λ = 0.75, p < .001). Patients treated for brain tumors had lower mean Activities of Daily Living scores than those with other diagnoses ( F = 15.81, p < .001). CONCLUSIONS: Findings from this clinically referred sample indicate that while most young children with cancer are doing well psychosocially, approximately 20% to 30% demonstrated difficulties in at least one area. Findings support the need for monitoring of young children with cancer as well as appropriate intervention services.

Parent-reported executive functioning in young children treated for cancer.

It is well known that children treated for cancer are at risk for cognitive and functional impairments. Such research is largely based on studies of late effects in school-aged or older children. However, far less is known about executive function weaknesses in preschool-aged children treated for cancer. Thus, the aim of this study was to examine executive functioning in a clinically referred sample of young oncology patients, and its association with broader domains of functioning. Data from 61 young children with cancer, who were referred for clinical cognitive evaluations, were abstracted and included in this study. Patients were 5.00 years of age (SD = 0.72) at assessment, 54.1% male, and two-thirds (63.9%) had been treated for brain tumors. Most executive functions were significantly discrepant from the mean, with 47.5% of preschoolers having parent-reported working memory concerns within the clinically significant range. There were no differences in executive functioning based on diagnosis or treatment status. Parent-reported executive functioning was strongly correlated with global intelligence and adaptive functioning, with some indices also associated with nonverbal problem solving and pre-academic skills. Ultimately, results indicate the presence of emerging weaknesses in executive functioning in young children with cancer, and add to a growing body of literature highlighting the potential cognitive and behavioral risks associated with a cancer diagnosis in early childhood.

Provision of Adequate Pain Management to a Young Adult Oncology Patient Presenting with Aberrant Opioid-Associated Behavior: A Case Study.

Pain and emotional distress are relevant risk factors as clinicians assess for aberrant opioid-associated behavior and provide adequate and responsible pain relief to patients who engage in behaviors that may be interpreted as drug seeking in nature. The present case illustrates how undertreated pain and treatment-related anxiety affected the opioid use of a young adult with cancer. Because these risk factors were identified during the initial consult, the treatment team was able to implement a multimodal and multidisciplinary treatment approach that provided the patient with better analgesia and coping skills for anxiety.

Publisher Correction: Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels.

The original version of this Article contained errors in the author affiliations.Martin R. Bennett was incorrectly associated with Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, Phoebe Oldach was incorrectly associated with Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.This has now been corrected in the HTML version of the Article. The PDF version of the Article was correct at the time of publication.