Preparing Children for Invasive Medical Cancer Treatment with "My Logbook": Preliminary Results of a Pilot Study.

Pediatric cancer is one of the most burdensome chronic diseases, necessitating a variety of severe medical interventions. As a result, the disease and its treatment cause numerous acute and long-term medical, psychological, and socioeconomic strains for young patients and their families. Therefore, psychosocial care using evidence-based interventions (EBIs) before, during, and after medical treatments is essential to ensure that patients receive adequate information and to minimize the adverse emotional and psychosocial impacts such as insecurity, fear, and shame. The present study reports the first promising results of applying cancer-specific psychosocial methods developed in the quality improvement project "My Logbook." The four assessed tools are specifically designed to adequately prepare pediatric cancer patients for surgery, chemotherapy, radiotherapy, and stem cell transplantation. Self and proxy ratings were used to assess the patients' subjective knowledge and emotional well-being before and after each intervention session. The results showed that patient-centered interventions using various creative and developmentally adapted methodologies (e.g., psychoeducation, crafting, games) have the potential to effectively enhance patient health literacy (V = 120.5, p < .001, r = 0.33) and well-being as manifested in more positive (slope = 0.121, p = .016) and less negative (slope = - 0.350, p < .001) or neutral emotions (slope = - 0.202, p = .002). These findings highlight the importance of developing and implementing psychosocial tools in pediatric oncology to prevent psychological overload and negative emotions and to increase subjective control beliefs, autonomy, and empowerment. Moreover, the effective application and systematic evaluation of evidence-based psychosocial tools can facilitate the establishment of standardized guidelines for psychosocial care in pediatric oncology. Thereby, the final goal is to ensure the quality of care and to use education to increase the quality of life for all pediatric cancer patients.Trial registration: ClinicalTrials.gov Identifier: NCT04474678 (July 17, 2020).

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies.

BACKGROUND: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). PATIENTS AND METHODS: Following surgery, patients (0-36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. RESULTS: We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001-.019; d = 0.79-1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. CONCLUSION: Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.

The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.

Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.

RADX interacts with single-stranded DNA to promote replication fork stability.

Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.

Evaluation of the Good Start Program: a healthy eating and physical activity intervention for Maori and Pacific Islander children living in Queensland, Australia.

BACKGROUND: Reducing the prevalence of obesity and chronic disease are important priorities. Maori and Pacific Islander communities living in Australia have higher rates of obesity and chronic disease than the wider Australian population. This study aims to assess the effectiveness of the Good Start program, which aims to improve knowledge, attitudes and practices related to healthy eating and physical activity amongst Maori and Pacific Islander communities living in Queensland. METHODS: The intervention was delivered to children aged 6-19 years (N = 375) in schools by multicultural health workers. Class activities focused on one message each term related to healthy eating and physical activity using methods such as cooking sessions and cultural dance. The evaluation approach was a quantitative uncontrolled pre-post design. Data were collected each term pre- and post-intervention using a short questionnaire. RESULTS: There were significant increases in knowledge of correct servings of fruit and vegetables, knowledge of sugar and caffeine content of common sugar-sweetened drinks, recognition of the consequences of marketing and upsizing, and the importance of controlling portion size (all P < 0.05). There was also increases in knowledge of physical activity recommendations (P < 0.001), as well as the importance of physical activity for preventing heart disease (P < 0.001) and improving self-esteem (P < 0.001). In terms of attitudes, there were significant improvements in some attitudes to vegetables (P = 0.02), and sugar-sweetened drinks (P < 0.05). In terms of practices and behaviours, although the reported intake of vegetables increased significantly (P < 0.001), the proportion of children eating discretionary foods regularly did not change significantly, suggesting that modifying the program with an increased emphasis on reducing intake of junk food may be beneficial. CONCLUSION: The study has shown that the Good Start Program was effective in engaging children from Maori and Pacific Island backgrounds and in improving knowledge, and some attitudes and practices, related to healthy eating and physical activity. The evaluation contributes valuable information about components and impacts of this type of intervention, and considerations relevant to this population in order to successfully change behaviours and reduce the burden of chronic disease.

The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review.

OBJECTIVE: To provide a comprehensive synthesis of the effects of Zn supplementation on childhood body composition and adiposity-related hormone levels. DESIGN: Five electronic databases were searched for randomized controlled trials of Zn supplementation studies published before 28 February 2015. No statistical pooling of results was carried out due to diversity in study designs. SETTING: Community- or hospital-based, from fourteen developing and developed countries. SUBJECTS: Children and adolescents aged 0 to 10 years. RESULTS: Seven of the fourteen studies reported an overall or subgroup effect of Zn supplementation on at least one parameter of body composition, when determined by anthropometric measurements (increased mid upper-arm circumference, triceps skinfold, subscapular skinfold and mid upper-arm muscle area, and decreased BMI). Three out of the fourteen studies reported increased mean value of total body water estimated by bio-impedance analysis and increased fat-free mass estimated by dual energy X-ray absorptiometry and by total body water. Zn supplementation was associated with increased fat-free mass among stunted children. One study found supplementation decreased leptin and insulin concentrations. CONCLUSIONS: Due to the use of anthropometry when determining body composition, a majority of the studies could not accurately address whether alterations in the fat and/or fat-free mass components of the body were responsible for the observed changes in body composition. The effect of Zn supplementation on body composition is not consistent but may modify fat-free mass among children with pre-existing growth failure.

Breastfeeding experiences of Aboriginal and Torres Strait Islander mothers in an urban setting in Brisbane.

STUDY AIM: This study examined urban Aboriginal and Torres Strait Islander mothers' breastfeeding experiences to inform support for mothers and their families. STUDY DESIGN: The research took a strengths approach, using qualitative methodology. Twenty semi-structured in-depth face-to-face interviews were conducted and analysed thematically. SETTING AND PARTICIPANTS: Indigenous mothers of infants 3 to 12 months were recruited through a Brisbane Indigenous health service. KEY FINDINGS: All mothers recounted considerable physical and emotional energy invested in breastfeeding. Although early introduction of formula made sense for some mothers under stressful circumstances, timely pro-breastfeeding support from family and health professionals facilitated continued breastfeeding. Professional and social/family contacts play key roles in steering infant feeding outcomes. CONCLUSIONS: Mothers' experiences strongly influence infant feeding strategies. Aboriginal and Torres Strait Islander community strengths are underutilised in supporting breastfeeding mothers. FUTURE IMPLICATIONS: Indigenous mothers, family and community strengths present points for engagement in future breastfeeding promotion and support initiatives.

A T cell-specific enhancer of the human CD40 ligand gene.

We observed that the human CD40 ligand (CD40L) gene 5'-flanking region conferred weak promoter activity in activated CD4 T cells, suggesting that additional regions are required for optimal CD40L gene transcription. We therefore examined a 3'-flanking segment of the CD40L gene, which contained a putative NF-kappaB/Rel cis-element, for its ability to enhance CD40L promoter function. This segment augmented CD40L promoter activity in an orientation-independent manner in CD4 T-lineage cells but not in human B cell or monocyte cell lines. Mapping of CD4 T-lineage cell nuclei identified a DNase I-hypersensitive site in the flanking region near the NF-kappaB/Rel sequence, suggesting a transcriptional regulatory role. This was further supported by truncation analysis and site-directed mutagenesis, which indicated that the CD40L 3'-flanking NF-kappaB/Rel cis-element was critical for enhancer function. Electrophoretic mobility shift assays showed that the cis-element preferentially bound the p50 form of the NF-kappaB1 gene contained in human T cell nuclear protein extracts. This binding also appeared to occur in vivo in CD4 T cells based on chromatin immunoprecipitation assays using NF-kappaB p50-specific antiserum. Together, these results suggest that the CD40L gene 3'-flanking region acts as a T cell-specific classical transcriptional enhancer by a NF-kappaB p50-dependent mechanism.