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OBJECTIVE: Limited research has characterized cancer-related stress (CRS) among families of childhood cancer survivors. We examined the prevalence of CRS among survivors and caregivers, as well as its association with health risk perceptions (i.e., prognosis, risk for diminished quality of life) and views of survivor quality of life (QoL). METHODS: At five years post-diagnosis or relapse, survivors (n = 100; Mage = 15.84 years; 89% White), mothers (n = 127), and fathers (n = 59) reported their CRS. Perceived prognosis and risk for diminished QoL were rated on a 0%-100% visual analogue scale, while the PedsQL assessed QoL. RESULTS: CRS was low (M = 1.6-1.8, scale: 1-4); mothers reported greater stress than survivors, p = 0.038, d = 0.25. There was an indirect effect of survivors' perceived prognosis on their QoL through CRS, CI = 0.04 to 0.25, R2 = 0.32. Among mothers, there was an indirect effect of perceived prognosis/risk for diminished QoL on their reports of survivor QoL through CRS, CI = 0.03 to 0.23 and -0.15 to -0.03, R2 = 0.28 and 0.32, respectively. There were no indirect effects among fathers. CONCLUSIONS: CRS may be an important, modifiable factor that could improve survivors' QoL. Research is needed to examine how CRS changes over time to assess the utility of interventions among female survivors, mothers, and those with lower prognosis estimates.
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Supervivientes de Cáncer , Neoplasias , Humanos , Femenino , Niño , Adolescente , Calidad de Vida , Neoplasias/epidemiología , Prevalencia , SobrevivientesRESUMEN
OBJECTIVE: Parents of children who died of a medical condition experience a range of psychosocial outcomes. The current scoping review aims to summarize the outcomes assessed, methodology, and sample characteristics of recent psychosocial research conducted with this population. METHODS: Included studies were limited to peer-reviewed, psychosocial outcomes research published between August 2011 and August 2022, written in English, and including caregiver study participants of children who died of a medical condition. Data sources were scholarly journal articles from 9 electronic databases, including Scopus, Web of Science, Academic Search Primer, ProQuest Research Library, PubMed, Embase, PsycINFO, Psychology & Behavioral Sciences Collection, and Health Source: Nursing/Academic Edition. The Mixed Methods Appraisal Tool-2018 evaluated methodological quality. RESULTS: The study sample included 106 studies, most of which were either qualitative (60%) or quantitative (29%). Mixed-methods studies (8%) and randomized clinical trials (2%) were also identified. Study quality was variable, but most studies met all quality criteria (73%). Studies primarily represented cancer populations (58%), White participants (71%), and mothers (66%). Risk-based psychosocial outcomes (e.g., grief) were more commonly assessed than resilience-based outcomes. CONCLUSIONS: The current scoping review revealed that recent research assessing the psychosocial outcomes of bereaved parents is limited in the representation of diverse populations, primarily qualitative, of broadly strong methodological quality, and oriented to psychosocial risk. To enhance the state of the science and inform evidence-based psychosocial services, future research should consider varied methodologies to comprehensively assess processes of risk and resilience with demographically and medically diverse populations.
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Neoplasias , Resiliencia Psicológica , Femenino , Humanos , Niño , Padres/psicología , Neoplasias/psicología , Cuidadores/psicología , MadresRESUMEN
OBJECTIVE: Illness intrusiveness refers to the subjective cognitive appraisal of a chronic health condition interfering in daily, valued activities and may be highly relevant for parents of children with atypical genital appearance due to differences of sex development (DSD). However, a measure of illness intrusiveness has not been validated for this population. The current study aimed to evaluate the factor structure of the Illness Intrusiveness Scale for Parents (IIS-P) and examine convergent validity. METHODS: Participants included 102 parents (Mage = 33.39 years, SD = 6.48; 58% mothers) of 65 children (<2 years old) diagnosed with DSD participating in a larger, longitudinal study. Parents completed the IIS-P as well as self-report measures of stigma, and anxious and depressive symptoms. An exploratory factor analysis (EFA) was conducted. RESULTS: EFA results supported a 1-factor intrusiveness solution (α = .93), as well as a 2-factor solution measuring intrusiveness on daily living (α = .92) and community connectedness (α = .85). The 1-factor solution and both factors of the 2-factor solution demonstrated significant convergent validity with stigma as well as anxious and depressive symptoms. CONCLUSIONS: Support emerged for both 1- and 2-factor solutions of the IIS-P in parents of children with DSD. The decision to evaluate illness intrusiveness as a total score or to examine the subscales of daily living and community connectedness should be tailored to the unique aims of researchers and clinicians. Future research should conduct a confirmatory factor analysis with both 1- and 2-factor models with larger, more diverse samples of caregivers.
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Trastornos del Desarrollo Sexual , Padres , Humanos , Masculino , Femenino , Padres/psicología , Adulto , Análisis Factorial , Trastornos del Desarrollo Sexual/psicología , Estudios Longitudinales , Estigma Social , Depresión/psicología , Psicometría , Ansiedad/psicología , Preescolar , Lactante , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Culture and diversity-related training is critical to the development of competent pediatric psychologists. Evaluation of training efforts have been conducted at the program level, yet evaluation of trainee experiences in culture and diversity-related training remains unassessed. This trainee-led study was the first formal assessment of pediatric psychology trainee experiences of culture and diversity-related training and the impact of training on their own cultural humility. METHODS: Study overview and a survey link was distributed across 2 listservs associated with the American Psychological Association (Division 53, Division 54) and sent directly to directors of graduate, internship, and fellowship training programs with a request to share with trainees. Surveys assessing integration of cultural training and trainee cultural humility were completed. Trainees also provided qualitative feedback regarding their multicultural training and development. RESULTS: Pediatric psychology trainees (N = 90) reported inconsistent integration of culture and diversity topics into their training. Of the 34 training areas assessed, 10 were perceived as thoroughly integrated into formal training by at least half of the respondents. Trainees often sought independent cultural training outside of their programs, and no relationship was detected between perceived integration of cultural training and trainee cultural competence. DISCUSSION: Results indicate room for improvement regarding integration of cultural training and a need to better understand driving forces behind trainees independently seeking training outside of their formal training programs. Moreover, understanding the aspects of training that are most contributory to trainee development is needed given that no relationship between training and development emerged in the current study.
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CNOT1 is a member of the CCR4-NOT complex, which is a master regulator, orchestrating gene expression, RNA deadenylation, and protein ubiquitination. We report on 39 individuals with heterozygous de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development.
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Discapacidades del Desarrollo/genética , Expresión Génica/genética , Trastornos del Neurodesarrollo/genética , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , ARN/genética , Receptores CCR4/genética , Factores de Transcripción/genética , Alelos , Femenino , Variación Genética/genética , Haploinsuficiencia/genética , Heterocigoto , Humanos , Masculino , Malformaciones del Sistema Nervioso/genética , Fenotipo , Estabilidad ProteicaRESUMEN
OBJECTIVE: Differences/disorders of sex development (DSDs) are rare, congenital conditions involving discordance between chromosomes, gonads, and phenotypic sex and are often diagnosed in infancy. A key subset of parents of children newly diagnosed with a DSD experience clinically elevated distress. The present study examines the relationship between perinatal factors (i.e., gestational age, delivery method) and trajectories of parental adjustment. METHODS: Parent participants (mothers = 37; fathers = 27) completed measures at baseline, 6- and 12-month follow-up. Multilevel linear regression controlled for clustering of the data at three levels (i.e., time point, parent, and family) and examined the relationship between perinatal factors and trajectories of depressive and anxious symptoms. Two-way interactions between perinatal factors and parent type were evaluated. RESULTS: Overall depressive and anxious symptoms decreased over time. There were significant interactions between gestational age and parent type for depressive and anxious symptoms, with younger gestational age having a stronger negative effect on mothers vs. fathers. There was a significant interaction between time and gestational age for depressive symptoms, with 36 weeks' gestational age demonstrating a higher overall trajectory of depressive symptoms across time compared to 38 and 40 weeks. Findings for the delivery method were not significant. CONCLUSIONS: Findings uniquely demonstrated younger gestational age was associated with increased depressive symptoms, particularly for mothers compared to fathers. Thus, a more premature birth may predispose parents of infants with DSD to distress. Psychosocial providers should contextualize early diagnosis-related discussions within stressful birth experiences when providing support.
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Madres , Padres , Femenino , Lactante , Niño , Embarazo , Humanos , Masculino , Padres/psicología , Madres/psicología , Edad Gestacional , Desarrollo Sexual , Genitales , Padre/psicología , Depresión/psicologíaRESUMEN
ABSTRACT: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein-Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy.
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Infecciones por Virus de Epstein-Barr , Infecciones por VIH , Síndromes de Inmunodeficiencia , Linfoma de Células B , Trastornos Linfoproliferativos , Lesiones Precancerosas , Humanos , Metotrexato/efectos adversos , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4 , Úlcera/patología , Infecciones por VIH/complicaciones , Linfoma de Células B/tratamiento farmacológico , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/diagnóstico , Lesiones Precancerosas/tratamiento farmacológico , Enfermedad IatrogénicaRESUMEN
Emerging adults with a chronic medical condition (CMC) are at increased risk for developing health anxiety (HA). Adverse childhood experiences (ACEs) have been linked to developing HA. CMCs and ACEs frequently co-occur among emerging adults. However, no known research has examined ACEs and HA within this critical developmental period. Further, increased negative illness appraisals (e.g., uncertainty, intrusivness) may partially explain the relation between ACEs and HA. The present study examined the following mediation model: ACEs â illness appraisals â HA. Emerging adults (N = 121) with a CMC completed self-report measures of demographics, ACEs, illness appraisals, and HA. Regression analyses were conducted to test each illness appraisal as a mediator between ACEs and HA. Results demonstrated significant indirect effects for both illness appraisals. Findings demonstrate greater ACEs may increase negative illness appraisals which heightens overall HA. Thus, these associations support trauma-informed care approaches to support emerging adults.
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Experiencias Adversas de la Infancia , Adulto , Humanos , Ansiedad/epidemiología , Trastornos de Ansiedad , Enfermedad Crónica , AutoinformeRESUMEN
A conceptual framework towards understanding biological condensed phases is emerging, derived from biological, biomimetic, and synthetic sequences. However, de novo peptide condensate design remains a challenge due to an incomplete understanding of the structural and interactive complexity. We designed peptide modules based on a simple repeat motif composed of tripeptide spacers (GSG, SGS, GLG) interspersed with adhesive amino acids (R/H and Y). We show, using sequence editing and a combination of computation and experiment, that nâπ* interactions in GLG backbones are a dominant factor in providing sufficient backbone structure, which in turn regulates the water interface, collectively promoting liquid droplet formation. Moreover, these R(GLG)Y and H(GLG)Y condensates unexpectedly display sequence-dependent emission that is a consequence of their non-covalent network interactions, and readily observable by confocal microscopy.
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Aminoácidos , Péptidos , Fluorescencia , Péptidos/química , Aminoácidos/químicaRESUMEN
KEY POINTS: Adipocyte enlargement is a key feature of obesity and associated with insulin resistance and metabolic disease The cause and consequences of adipocyte enlargement have remained hard to study in vitro due to a lack of human cell models with representative morphology This paper provides an easily set up spheroid culture method, HUVAS (human unilocular vascularized adipocyte spheroids), for the differentiation and culturing of human adipocytes with a more unilocular morphology We show that providing adipocyte progenitors with a vascular differentiation niche is key for achieving in vitro differentiated adipocytes with large lipid droplets Lipid treatment of the HUVAS spheroids can further adipocyte enlargement and induce cellular dysfunction, mimicking the in vivo effects of weight gain The model will allow a wider research community to perform mechanistic studies of the factors impacting on human adipocyte differentiation and growth, increasing our understanding of how obesity develops and why it has such detrimental consequences on whole body metabolism ABSTRACT: The rise in obesity prevalence has created an urgent need for new and improved methods to study human adipocytes and the pathogenic effects of weight gain in vitro. Despite the proven advantage of culturing adipocyte progenitors as 3D structures, the majority of studies continue to use traditional 2D cultures which result in small, multilocular adipocytes with poor representability. We hypothesized that providing differentiating pre-adipocytes with a vascular growth niche would mimic in vivo adipogenesis and improve the differentiation into unilocular adipocytes. Here we present HUVAS (human unilocular vascularized adipocyte spheroids), a simple, easily applicable culture protocol that allows for the differentiation of human adipocytes with a more unilocular morphology and larger lipid droplets than previous protocols. Moreover, we offer a protocol for inducing adipocyte enlargement in vitro, resulting in larger lipid droplets and development of several key features of adipocyte dysfunction, including altered adipokine secretion, impaired lipolysis and insulin resistance. Taken together, our HUVAS model offers an improved culture system for studying the cellular and molecular mechanisms causing metabolic dysfunction and inflammation in human adipose tissue during weight gain.
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Adipocitos , Tejido Adiposo , Adipocitos/metabolismo , Adipogénesis , Tejido Adiposo/metabolismo , Diferenciación Celular , Humanos , Aumento de PesoRESUMEN
Supramolecular self-assembly of fibrous components and liquid-liquid phase separation are at the extremes of the order-to-disorder spectrum. They collectively play key roles in cellular organization. It is still a major challenge to design systems where both highly ordered nanostructures and liquid-liquid phase-separated domains can coexist. We present a three-component assembly approach that generates fibrous domains that exclusively form inside globally disordered, liquid condensates. This is achieved by creating amphiphilic peptides that combine the features of fibrillar assembly (the amyloid domain LVFFA) and complex coacervation (oligo-arginine and adenosine triphosphate (ATP)) in one peptide, namely, LVFFAR9. When this hybrid peptide is mixed in different ratios with R9 and ATP, we find that conditions can be created where fibrous assembly is exclusively observed inside liquid coacervates. Through fluorescence and atomic force microscopy characterization, we investigate the dynamic evolution of ordered and disordered features over time. It was observed that the fibers nucleate and mature inside the droplets and that these fiber-containing liquid droplets can also undergo fusion, showing that the droplets remain liquid-like. Our work thus generates opportunities for the design of ordered structures within the confined environment of biomolecular condensates, which may be useful to create supramolecular materials in defined compartments and as model systems that can enhance understanding of ordering principles in biology.
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Nanoestructuras , Péptidos , Adenosina Trifosfato , Amiloide , Proteínas Amiloidogénicas , Nanoestructuras/químicaRESUMEN
OBJECTIVE: Adolescents and young adults in the college setting often report poor sleep hygiene and quality. These sleep difficulties may be related to emotion dysregulation, which is highly relevant to broader adjustment. The current study aimed to empirically identify latent groups of healthy college students with distinct subjective sleep patterns and examine differences in emotion dysregulation between subgroups. METHODS: College students (N = 476; Mage=19.38) completed the Adolescent Sleep-Wake Scale-Revised, Adolescent Sleep Hygiene Scale-Revised, and Difficulties in Emotion Dysregulation Scale. Most participants were White (78%), non-Hispanic/Latinx (85%), and female (77%). Latent profile analysis identified patterns of sleep with maximum likelihood estimation. Bolck-Croon-Hagenaars procedure evaluated differences in emotion dysregulation by class. RESULTS: A three-class model had optimal fit, Bayesian information criterion = 11,577.001, Bootstrapped Parametric Likelihood Ratio Test = -5,763.042, p < .001, entropy = .815. The three profiles identified were good sleep (overall high sleep quality and hygiene; n = 219), moderate sleep (low sleep quality with mix of low and high sleep hygiene; n = 221), and poor sleep (very low sleep quality and hygiene; n = 36). Those in the good sleep group (M = 68.06, SE = 1.5) reported significantly less emotion dysregulation than the moderate sleep group (M = 92.12, SE = 1.67; X2(2) = 98.34, p = .001) and the poor sleep group (M = 99.51, SE = 4.10; p < .001). The moderate and poor sleep groups did not significantly differ, X2(2) = 2.60, p = .11. CONCLUSIONS: Emotion dysregulation differed across three sleep profiles, with participants classified in the good sleep group reporting, on average, the lowest emotion dysregulation, compared to the moderate and poor sleep groups. These findings highlight contextual factors of sleep that may be clinically targeted to promote emotion regulation.
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Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Adolescente , Teorema de Bayes , Emociones , Femenino , Humanos , Sueño , Trastornos del Sueño-Vigilia/psicología , Universidades , Adulto JovenRESUMEN
PURPOSE: Pediatric cancer survivors may have lower quality of life (QoL), but most research has assessed outcomes either in treatment or long-term survivorship. We focused on early survivorship (i.e., 3 and 5 years post-diagnosis), examining the impact of CNS-directed treatment on child QoL, as well as sex and age at diagnosis as potential moderators. METHODS: Families of children with cancer (ages 5-17) were recruited at diagnosis or relapse (N = 336). Survivors completed the PedsQL at 3 (n = 96) and 5 years (n = 108), along with mothers (101 and 105, respectively) and fathers (45 and 53, respectively). The impact of CNS treatment, sex, and age at diagnosis on child QoL was examined over both time since diagnosis and time since last treatment using mixed model analyses. RESULTS: Parent-report of the child's total QoL was in the normative range and stable between 3 and 5 years when examining time since diagnosis, while child reported QoL improved over time (p = 0.04). In terms of time since last treatment, mother and child both reported the child's QoL improved over time (p = 0.0002 and p = 0.0006, respectively). Based on parent-report, males with CNS-directed treatment had lower total QoL than females and males who did not receive CNS-directed treatment. Age at diagnosis did not moderate the impact of treatment type on total QoL. CONCLUSIONS: Quality of life (QoL) in early survivorship may be low among males who received CNS-directed treatment. However, this was only evident on parent-report. Interventions to improve child QoL should focus on male survivors who received CNS-directed treatment, as well as females regardless of treatment type.
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Supervivientes de Cáncer , Neoplasias , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Calidad de Vida/psicología , Encuestas y Cuestionarios , Sobrevivientes , SupervivenciaRESUMEN
BACKGROUND: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL. AIMS: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL. METHODS: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland. RESULTS: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group. CONCLUSIONS: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL.
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Leucemia Linfocítica Crónica de Células B , Melanoma , Neoplasias Cutáneas , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/epidemiología , Estudios de Cohortes , Recurrencia Local de Neoplasia , Melanoma/complicaciones , Melanoma/epidemiología , Melanoma/patología , Neoplasias Cutáneas/patologíaRESUMEN
The aim of this study was to examine the impact of end-of-life (EoL) circumstances on grief and internalizing symptoms among bereaved siblings. Bereaved families (N = 88) were recruited from three sites 3-12 months (M = 11.57, SD = 3.48) after their child's death from cancer. One sibling per family aged 8-17 years (M = 12.41, SD = 2.64) was randomly selected to participate. Families completed measures of siblings' grief and internalizing symptoms, as well as a structured interview about circumstances surrounding the death. Mother and sibling reports of EoL circumstances were generally concordant, except there was a discrepancy between mothers and children about whether or not children expected their sibling's death (t(75) = 1.52, p = .018). Mother reports of sibling internalizing symptoms were above the normative mean (t(83) = 4.44, p ≤ .001 (M = 56.01 ± 12.48), with 39% (n = 33) in the borderline/clinical range. Sibling opportunity to say goodbye was associated with greater grief-related growth (t(79) = - 1.95, p = .05). Presence at the death and wishing they had done something differently were both associated with greater grief (t(80) = - 2.08, p = .04 and t(80) = - 2.24, p = .028, respectively) and grief-related growth (t(80) = - 2.01, p = .048 and t(80) = - 2.31, p = .024, respectively). However, findings were primarily unique to sibling report, with few mother-reported effects. The adjustment of bereaved siblings may be affected by certain modifiable circumstances surrounding the death of their brother or sister. A proportion of bereaved siblings had elevated internalizing symptoms irrespective of circumstances at EoL. Further work is needed to understand predictors of adjustment among bereaved siblings to provide better support and optimize their outcomes.
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Aflicción , Neoplasias , Adolescente , Niño , Muerte , Pesar , Humanos , Masculino , HermanosRESUMEN
PURPOSE: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority. METHODS: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC. RESULTS: Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype-phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts. CONCLUSION: Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism.
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Discapacidad Intelectual , Trastornos del Neurodesarrollo , Actinas/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Humanos , Discapacidad Intelectual/genética , Trastornos del Neurodesarrollo/genética , ConvulsionesRESUMEN
BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors' increased risk for adverse health outcomes could be mitigated through consuming a balanced diet. Nonetheless, >70% of adult survivors do not meet survivorship dietary recommendations. ALL treatment may amplify risk for restricted dietary preferences (picky eating) and poor self-regulation of food intake that could contribute to suboptimal diets in survivorship. This study aims to: (a) characterize differences in picky eating and self-regulation of food intake between survivors and peer controls; and (b) examine the associations between these eating behaviors and dietary quality in ALL survivors relative to peer controls. METHODS: Participants were children (5-13 years) with (n = 32) and without (n = 32) a history of ALL and their caregivers. Children's dietary quality (Healthy Eating Index-2015) was calculated from 24-h dietary recalls. Caregivers completed the Child Eating Behavior Questionnaire-Food Fussiness subscale and the Child Self-Regulation in Eating Questionnaire. RESULTS: Independent samples t-tests revealed survivors exhibited greater picky eating than peer controls but comparable self-regulation of food intake. Bootstrapped grouped multivariate regression results showed that for ALL survivors, greater picky eating was associated with worse dietary quality (controlling for age and self-regulation of food intake). For peer controls, worse self-regulation of food intake was associated with poorer dietary quality (controlling for picky eating and age). CONCLUSIONS: Results provide preliminary support that different eating behaviors contribute to poor dietary quality in children with and without an ALL history. These findings suggest that interventions to improve ALL survivors' dietary quality may benefit targeting picky eating.
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Supervivientes de Cáncer , Conducta Alimentaria , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Niño , Preescolar , Dieta , Ingestión de Alimentos , Femenino , Calidad de los Alimentos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
OBJECTIVE: Despite calls to increase prognosis communication for adolescents with cancer, limited research has examined their perceptions of prognosis as compared with their parents. We assessed adolescents' understanding of their prognosis relative to parents and oncologists. METHODS: Families of adolescents (aged 10-17) were recruited at two pediatric institutions following a new diagnosis or relapse. Seventy-four adolescents, 68 mothers, and 40 fathers participated at enrollment; 76 adolescents, 69 mothers, and 35 fathers participated one year later. The adolescent's primary oncologist reported on prognosis only at enrollment. Participants rated the likelihood of the adolescent's survival in five years, as well as reporting prognosis communication and sources of information. RESULTS: Most oncologists (65%) and fathers (63%) discussed prognosis in numerical terms with the adolescent at baseline, which was greater than mother report (49%) of discussions of numerical prognosis with adolescents. Adolescents reported a better prognosis than oncologists, but comparable with mothers at diagnosis and one year. Adolescents' prognosis estimates were stable over time (P > .05). At diagnosis, adolescent-father (P = 0.025) and adolescent-oncologist (P < 0.001) discrepancies were larger for youth with advanced than non-advanced cancer. Adolescents whose parents received numerical prognosis estimates from the oncologist, and whose fathers reported providing numerical prognosis estimates had more accurate understandings of prognosis (P < 0.05). CONCLUSIONS: Adolescent prognosis estimates were comparable with those of parents at diagnosis and one year but more favorable than that of oncologists. Although additional research is needed, results suggest discrepancies in prognosis estimates between family members and oncologists, particularly for adolescents with advanced cancer.
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Comunicación , Neoplasias/patología , Neoplasias/psicología , Oncólogos/psicología , Padres/psicología , Adolescente , Niño , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Neoplasias/terapia , Pronóstico , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To identify coping trajectories from diagnosis through survivorship and test whether particular trajectories exhibit better health-related quality of life (HRQOL) at 5 years post-diagnosis. METHODS: Families of children with cancer (ages 5-17; M = 10.48, SD = 4.03) were recruited following a new diagnosis of cancer (N = 248). Three follow-up assessments occurred at 1-year (N = 185), 3-years (N = 101), and 5-years (N = 110). Mothers reported on children's coping using the Responses to Stress Questionnaire for Pediatric Cancer. Survivor HRQOL was measured at 5-year follow-up using self-report on the PedsQL 4.0. Longitudinal patterns of coping were derived using Latent Class Growth Analysis and mean-levels of survivor-report HRQOL were compared across classes. RESULTS: Two primary control coping trajectories emerged, "Moderate and Stable" (50%) and "Low-moderate and Decreasing" (50%), with no significant differences in HRQOL across trajectories. Three secondary control coping trajectories emerged, "Moderate-high and Increasing" (54%), "Moderate and Stable" (40%), and "High and Increasing" (6%), with survivors in the last trajectory showing better HRQOL. Two disengagement coping trajectories emerged, "Low and Stable" (85%) and "Low and Variable" (15%), with no significant differences in HRQOL across trajectories. CONCLUSIONS: Coping trajectories were relatively stable from diagnosis to 5 years. A small group of survivors with high and increasing secondary control coping over time, per mother-report, reported better HRQOL. Future research should consider tailoring coping interventions to children with cancer to improve survivors' HRQOL.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Adaptación Psicológica , Adolescente , Niño , Preescolar , Femenino , Humanos , Calidad de Vida , SobrevivientesRESUMEN
PURPOSE: The transition to college is associated with numerous stressors, including environmental changes, increased academic expectations, and changes in social support, all of which may be exacerbated by the added responsibility of managing a chronic medical condition. Huang (2019) proposed a model examining the relationships between coping styles, transition readiness, and health anxiety, and suggested that greater transition readiness is associated with adaptive coping strategies and less health anxiety. However, there are limited findings as to how poor transition readiness relates to health anxiety. Therefore, the current study tested a serial mediation model (i.e., poor transition readiness â avoidance coping â illness uncertainty â health anxiety). DESIGN AND METHODS: College students (N = 194) with a chronic medical condition completed self-report questionnaires. RESULTS: Results indicated several direct effects among the modeled variables and a significant poor transition readiness â avoidance coping â illness uncertainty â health anxiety serial mediation (path a1d21b2 = 0.438, 95% CI = 0.153 to 0.913). CONCLUSIONS: Worse transition readiness was associated with increased avoidance as a coping mechanism, which in turn is associated with increased illness uncertainty, and ultimately health anxiety. The current findings identified possible drivers of health anxiety in college students with a chronic medical condition. PRACTICE IMPLICATIONS: These findings highlight that good transition readiness skills may buffer against maladaptive avoidance, illness uncertainty, and health anxiety. Modules aimed at improving healthcare management, avoidance, and illness uncertainty may be beneficial additions to interventions to reduce health anxiety.