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1.
EMBO J ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420093

RESUMO

Triple-negative breast cancer (TNBC) metabolism and cell growth uniquely rely on glutamine uptake by the transporter ASCT2. Despite previous data reporting cell growth inhibition after ASCT2 knockdown, we here show that ASCT2 CRISPR knockout is tolerated by TNBC cell lines. Despite the loss of a glutamine transporter and low rate of glutamine uptake, intracellular glutamine steady-state levels were increased in ASCT2 knockout compared to control cells. Proteomics analysis revealed upregulation of macropinocytosis, reduction in glutamine efflux and increased glutamine synthesis in ASCT2 knockout cells. Deletion of ASCT2 in the TNBC cell line HCC1806 induced a strong increase in macropinocytosis across five ASCT2 knockout clones, compared to a modest increase in ASCT2 knockdown. In contrast, ASCT2 knockout impaired cell proliferation in the non-macropinocytic HCC1569 breast cancer cells. These data identify macropinocytosis as a critical secondary glutamine acquisition pathway in TNBC and a novel resistance mechanism to strategies targeting glutamine uptake alone. Despite this adaptation, TNBC cells continue to rely on glutamine metabolism for their growth, providing a rationale for targeting of more downstream glutamine metabolism components.

2.
Nature ; 598(7879): 65-71, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616057

RESUMO

The human eye can distinguish as many as 10,000 different colours but is far less sensitive to variations in intensity1, meaning that colour is highly desirable when interpreting images. However, most biological samples are essentially transparent, and nearly invisible when viewed using a standard optical microscope2. It is therefore highly desirable to be able to produce coloured images without needing to add any stains or dyes, which can alter the sample properties. Here we demonstrate that colorimetric histology images can be generated using full-sized plasmonically active microscope slides. These slides translate subtle changes in the dielectric constant into striking colour contrast when samples are placed upon them. We demonstrate the biomedical potential of this technique, which we term histoplasmonics, by distinguishing neoplastic cells from normal breast epithelium during the earliest stages of tumorigenesis in the mouse MMTV-PyMT mammary tumour model. We then apply this method to human diagnostic tissue and validate its utility in distinguishing normal epithelium, usual ductal hyperplasia, and early-stage breast cancer (ductal carcinoma in situ). The colorimetric output of the image pixels is compared to conventional histopathology. The results we report here support the hypothesis that histoplasmonics can be used as a novel alternative or adjunct to general staining. The widespread availability of this technique and its incorporation into standard laboratory workflows may prove transformative for applications extending well beyond tissue diagnostics. This work also highlights opportunities for improvements to digital pathology that have yet to be explored.


Assuntos
Colorimetria/instrumentação , Colorimetria/métodos , Técnicas Histológicas/instrumentação , Microscopia/instrumentação , Animais , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Humanos , Antígeno Ki-67/análise , Camundongos , Camundongos Endogâmicos C57BL
3.
J Pathol ; 262(4): 480-494, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38300122

RESUMO

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias da Mama , Fibroadenoma , Tumor Filoide , Humanos , Feminino , Tumor Filoide/diagnóstico , Tumor Filoide/genética , Tumor Filoide/patologia , Metilação de DNA , Fibroadenoma/diagnóstico , Fibroadenoma/genética , Fibroadenoma/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mama/patologia
4.
EMBO J ; 39(19): e104063, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32790115

RESUMO

The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states: the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.


Assuntos
Neoplasias de Mama Triplo Negativas/imunologia , Evasão Tumoral , Matriz Extracelular/imunologia , Matriz Extracelular/patologia , Feminino , Humanos , RNA-Seq , Células Estromais/imunologia , Células Estromais/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Neoplasias de Mama Triplo Negativas/patologia
5.
Appetite ; 195: 107204, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38219831

RESUMO

Food insecurity in rich countries is a growing problem with far reaching consequences but how it impacts parents, particularly their food parenting practices, is under researched. Food parenting practices play a critical role in the development of children's eating and may be a mechanism in the link between food insecurity and children's health outcomes; this study aims to illuminate their potential role. Twenty-one parents participated in a qualitative interview study. Their household food security was very low (18/21) or low (3/21). Reflexive Thematic Analysis generated three themes. Challenges of food insecurity: parents shielded children from hunger by eating less themselves, relying on free school meals and turning to family and food banks when in crisis. They perceived a conflict between giving children food of high nutritional quality and its cost. Practical impact of food insecurity: although motivated to provide children with healthy food, finances meant parents struggled to achieve this goal. Parents used a range of food parenting practices but their use of some that are known to be effective may have been compromised by their food insecurity. Emotional impact of food insecurity: parents described feelings of failure, despair, helplessness and shame. Food insecurity adversely effects both children and parents, and non-stigmatising services that mitigate its impact and facilitate children's exposure to food parenting practices known to be effective are needed.


Assuntos
Poder Familiar , Pais , Criança , Humanos , Poder Familiar/psicologia , Pais/psicologia , Refeições , Insegurança Alimentar , Pesquisa Qualitativa , Comportamento Alimentar/psicologia
6.
Behav Cogn Psychother ; 52(3): 243-261, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37840150

RESUMO

BACKGROUND: Cognitive behavioural therapy (CBT) including exposure and response prevention (ERP) is an effective treatment for preadolescent children with obsessive compulsive disorder (OCD); however, there is a need to increase access to this treatment for affected children. AIMS: This study is a preliminary evaluation of the efficacy and acceptability of a brief therapist-guided, parent-led CBT intervention for pre-adolescent children (5-12 years old) with OCD using a non-concurrent multiple baseline approach. METHOD: Parents of 10 children with OCD were randomly allocated to no-treatment baselines of 3, 4 or 5 weeks before receiving six to eight individual treatment sessions with a Psychological Wellbeing Practitioner. Diagnostic measures were completed prior to the baseline, 1-week post-treatment, and at a 1-month follow-up, and parents completed weekly measures of children's OCD symptoms/impairment. RESULTS: Seventy percent of children were 'responders' and/or 'remitters' on diagnostic measures at post-treatment, and 60% at the 1-month follow-up. At least 50% of children showed reliable improvements on parent-reported OCD symptoms/impairment from pre- to post-treatment, and from pre-treatment to 1-month follow-up. Crucially, the intervention was acceptable to parents. CONCLUSIONS: Brief therapist-guided, parent-led CBT has the potential to be an effective, acceptable and accessible first-line treatment for pre-adolescent children with OCD, subject to the findings of further evaluations.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Criança , Humanos , Adolescente , Pré-Escolar , Transtorno Obsessivo-Compulsivo/terapia , Resultado do Tratamento , Pais
7.
Br J Clin Psychol ; 62(1): 53-69, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36214425

RESUMO

OBJECTIVES: Childhood social anxiety disorder (SAD) is a common and disabling condition. General forms of cognitive behavioural treatments have demonstrated poorer efficacy for childhood SAD when compared to other childhood anxiety disorders and further understanding of the psychological factors that contribute to the maintenance of childhood SAD is warranted. Examining the social experiences of children with SAD may help to identify relevant psychological factors and increase our understanding of what keeps childhood SAD going. METHODS: The current study used reflexive thematic analysis to analyse the transcripts of interviews with 12 children aged 8-12 years with SAD who had been interviewed about their 'in the moment' social experiences during a social stress induction task. The interview topic guide included factors hypothesized to maintain SAD in adult cognitive models of the disorder. RESULTS: The interviews revealed both variety and commonalities in the experiences and interpretations of social events in children with SAD, captured in three related main themes: (i) Discomfort being the centre of attention, (ii) (Lack of) awareness of cognitions and (iii) Managing social fears. Findings indicated likely developmental influences on which maintenance mechanisms apply at which point in time. CONCLUSIONS: There is variation in the psychological mechanisms that children with SAD endorse and developmental factors are likely to influence when specific mechanisms are relevant. We now need further studies that take a developmentally informed approach to understand the nature of the association between the factors identified in this study and social anxiety in childhood to inform the development of more effective interventions for childhood SAD.


Assuntos
Terapia Cognitivo-Comportamental , Fobia Social , Adulto , Humanos , Criança , Fobia Social/psicologia , Transtornos de Ansiedade/terapia , Medo , Estresse Psicológico/psicologia
8.
Appetite ; 182: 106447, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623774

RESUMO

Vegetable consumption in young children in the UK is well below the recommended five child-sized portions per day. Effective and practical strategies are therefore needed to encourage vegetable consumption in young children. In this exploratory study, we examine the effects of visual familiarization to foods via See & Eat ebooks, which show vegetables on their journey from 'field to fork'. As part of a larger study, in which 242 British families completed a range of measures about their family's eating habits, child's food preferences and potential parent and child predictors of these (Masento et al., 2022), parents were invited to download a See & Eat ebook about a vegetable their child did not eat. Thirty-six families participated in the intervention, looking at the ebook with their child for two weeks and reporting on their child's willingness to taste, intake and liking of the vegetable targeted by the ebook and a matched control vegetable before and after the intervention period. Results showed significant increases in parental ratings of children's acceptance of the target vegetable. Willingness to taste and intake ratings improved for the target vegetable, but not the control vegetable, while liking was reported to increase for both vegetables. These results corroborate previous research demonstrating the benefits of familiarising children with vegetables before they are offered at mealtimes and suggest that ebooks can be added to the set of tools parents can use to support children's vegetable consumption.


Assuntos
Dieta , Verduras , Humanos , Pré-Escolar , Preferências Alimentares , Comportamento Alimentar , Pais
9.
Eur Child Adolesc Psychiatry ; 32(4): 661-673, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34746976

RESUMO

Computerized treatments have been shown to be effective in young people with anxiety disorders. However, there has been limited investigation into the experiences of adolescents in undertaking this treatment. This qualitative study explored adolescents' experiences of being treated for an anxiety disorder, using an online intervention with therapist support, as part of a randomised controlled trial. Individual semi-structured interviews were conducted with thirteen adolescents aged between 13 and 17 years, who had received the online intervention. Data were analysed using reflexive thematic analysis. Two cross-cutting themes were identified: (i) Usability of the program, and (ii) Putting techniques into practice. Although the convenience of online sessions was recognised as positive, many of the adolescents expressed a preference for face-to-face sessions. The length of sessions and the large amount of reading involved was highlighted by most participants. The transdiagnostic nature of the content meant some elements of the programme were seen as less relevant. While many participants appreciated the 'fun' aspect of the program, others felt that certain aspects of the program were not suitable for their age group. Exposure, psychoeducation and cognitive restructuring were generally received positively, whereas responses to the use of relaxation and rewards were much more mixed. Our findings highlight the potential utility for online treatments delivered with therapist support. However, they also highlight how issues with both the format and treatment components can impact the acceptability of a program. As such, further work is warranted to improve the acceptability of online treatments for adolescents with anxiety disorders.


Assuntos
Terapia Cognitivo-Comportamental , Intervenção Baseada em Internet , Humanos , Adolescente , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Internet
10.
Breast Cancer Res ; 24(1): 63, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153537

RESUMO

BACKGROUND: Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDXs) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions. RESULTS: Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60 × coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance. CSMD1, previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers. CONCLUSIONS: Our WGS data provides a comprehensive genome sequencing resource of these models.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/genética , Modelos Animais de Doenças , Feminino , Genômica/métodos , Xenoenxertos , Humanos , Células MCF-7 , Nucleotídeos , Sequenciamento Completo do Genoma
11.
Br J Surg ; 109(6): 530-538, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35576373

RESUMO

BACKGROUND: Prepectoral breast reconstruction (PPBR) has recently been introduced to reduce postoperative pain and improve cosmetic outcomes in women having implant-based procedures. High-quality evidence to support the practice of PPBR, however, is lacking. Pre-BRA is an IDEAL stage 2a/2b study that aimed to establish the safety, effectiveness, and stability of PPBR before definitive evaluation in an RCT. The short-term safety endpoints at 3 months after surgery are reported here. METHODS: Consecutive patients electing to undergo immediate PPBR at participating UK centres between July 2019 and December 2020 were invited to participate. Demographic, operative, oncology, and complication data were collected. The primary outcome was implant loss at 3 months. Other outcomes of interest included readmission, reoperation, and infection. RESULTS: Some 347 women underwent 424 immediate implant-based reconstructions at 40 centres. Most were single-stage direct-to-implant (357, 84.2 per cent) biological mesh-assisted (341, 80.4 per cent) procedures. Conversion to subpectoral reconstruction was necessary in four patients (0.9 per cent) owing to poor skin-flap quality. Of the 343 women who underwent PPBR, 144 (42.0 per cent) experienced at least one postoperative complication. Implant loss occurred in 28 women (8.2 per cent), 67 (19.5 per cent) experienced an infection, 60 (17.5 per cent) were readmitted for a complication, and 55 (16.0 per cent) required reoperation within 3 months of reconstruction. CONCLUSION: Complication rates following PPBR are high and implant loss is comparable to that associated with subpectoral mesh-assisted implant-based techniques. These findings support the need for a well-designed RCT comparing prepectoral and subpectoral reconstruction to establish best practice for implant-based breast reconstruction.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Mastectomia/métodos , Estudos Prospectivos , Estudos Retrospectivos
12.
BMC Public Health ; 22(1): 636, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365107

RESUMO

BACKGROUND: From a public health perspective there is growing interest in children's play, including play involving risk and adventure, in relation to children's physical and mental health. Regarding mental health, it is theorised that adventurous play, where children experience thrilling, exciting emotions, offers important learning opportunities that prepare children for dealing with uncertainty and help prevent anxiety. Despite these benefits, adventurous play has decreased substantially within a generation. Parents have a key role in facilitating or limiting children's opportunities for adventurous play, but research identifying the barriers and facilitators parents perceive in relation to adventurous play is scarce. The present study therefore examined the barriers to and facilitators of adventurous play as perceived by parents of school-aged children in Britain. METHODS: This study analysed data from a subsample of parents in Britain (n = 377) who participated in the nationally representative British Children's Play Survey. Parents responded to two open-ended questions pertaining to the barriers to and facilitators of children's adventurous play. Responses were analysed using a qualitative Framework Analysis, an approach suitable for managing large datasets with specific research questions. RESULTS: Four framework categories were identified: Social Environment; Physical Environment; Risk of Injury; Child Factors. Social Environment included barriers and facilitators related to parents, family and peers, as well as community and society. Dominant themes within the Social Environment related to perceptions about the certainty of child safety, such as supervision and the safety of society. Beliefs about the benefits of adventurous play for development and well-being were also important in the Social Environment. Physical Environment factors focused on safety and practical issues. Risk of Injury captured concerns about children being injured during play. Child Factors included child attributes, such as play preference, developmental ability and trait-like characteristics. CONCLUSIONS: Improved understanding of what influences parent perceptions of adventurous play can inform public health interventions designed to improve children's opportunities for and engagement in adventurous play, with a view to promote children's physical and mental health.


Assuntos
Pais , Recreação , Criança , Família , Humanos , Pais/psicologia , Jogos e Brinquedos , Reino Unido
13.
Appetite ; 178: 106259, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35985496

RESUMO

Emotional child temperament has consistently been found to be related to food fussiness. One factor that may exacerbate or reduce the risk conferred by children's emotionality is parent feeding practices during mealtimes. Specifically, the use of controlling feeding practices aimed at increasing food consumption may particularly affect children with an emotional temperament. The primary aim of this study was to investigate whether the association between child food fussiness and higher emotionality found in previous studies is moderated by maternal use of controlling feeding practices, namely verbal pressure, physical prompts and food rewards. Sixty-seven mother-child dyads were video-recorded during a meal in their home and mothers' use of controlling feeding practices during this meal were coded. Mothers completed a questionnaire assessing child temperament. Moderation analyses revealed that maternal use of verbal pressure and physical prompts moderated the relationship between higher emotionality and food fussiness, but maternal use of food rewards did not. These results indicate that the use of verbal pressure and physical prompts may have a particularly negative influence on fussy eating for children higher in emotionality.


Assuntos
Seletividade Alimentar , Criança , Comportamento Infantil/psicologia , Pré-Escolar , Comportamento Alimentar/psicologia , Feminino , Preferências Alimentares/psicologia , Humanos , Refeições , Relações Mãe-Filho , Mães/psicologia , Poder Familiar/psicologia , Inquéritos e Questionários
14.
Appetite ; 157: 104991, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049340

RESUMO

Low consumption of vegetables in children is a concern around the world, hence approaches aimed at increasing intake are highly relevant. Previous studies have shown that repeated taste exposure is an effective strategy to increase vegetable acceptance. However, few studies have examined the effect of repeated taste exposure on children varying in bitter taste sensitivity. This study investigated the influence of taste genotypes and phenotypes on the effects of repeated taste exposure to a Brassica vegetable. 172 preschool children aged 3-5 years were recruited into this study. Turnip was selected as the target vegetable and parents completed a questionnaire to ensure unfamiliarity. During the intervention, children were exposed to steamed-pureed turnip for 10 days (once/day). Intake and liking were measured before, during and after the intervention, and a follow-up was done 3 months post-intervention. Taste genotypes (TAS2R38 and gustin (CA6) genotypes) and taste phenotypes (PROP taster status and fungiform papillae density) were determined. There was a significant effect of exposure shown by significant increases in intake (p < 0.001) and liking (p = 0.008) post-intervention; however, there were no significant effects of taste genotypes or phenotypes on intake and liking. In summary, repeated taste exposure is confirmed to be a good strategy to increase vegetable acceptance in children, regardless of bitter taste sensitivity.


Assuntos
Brassica napus , Brassica rapa , Brassica , Pré-Escolar , Preferências Alimentares , Humanos , Paladar , Verduras
15.
Aging Ment Health ; 25(6): 999-1007, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252544

RESUMO

OBJECTIVES: This study aimed to evaluate the feasibility of a 14-session programme of individual Cognitive Stimulation Therapy (iCST) for people with dementia (PWD). It addressed potential limitations in previous literature of iCST and evaluated possible impact on cognition, quality of life (QoL) and positive psychology. METHOD: The 14-session iCST programme was developed using existing manuals for group and individual CST and consultation with experts in the field. Thirty-three PWD were recruited from care homes and randomly assigned to iCST (14, 45-min sessions) or treatment as usual (TAU) over seven weeks. Outcomes measures were assessed at baseline and follow-up after the intervention. RESULTS: The intervention appeared feasible with high attendance to sessions, minimal levels of attrition, and ease of recruitment. Analysis of covariance indicated significant improvements in cognition (Alzheimer's Disease Assessment Scale-Cognitive subscale) for PWD receiving iCST compared to TAU. There were no significant differences between groups on follow-up scores on the standardised Mini Mental State Examination, measures of positive psychology or self- and proxy- reported QoL. CONCLUSION: A 14-session programme of iCST delivered by professionals was feasible and acceptable to PWD and may provide benefits to cognition. A larger randomised control trial would be necessary to fully evaluate intervention impact on cognition, as well as QoL and positive psychology.


Assuntos
Demência , Qualidade de Vida , Cognição , Demência/terapia , Estudos de Viabilidade , Humanos , Psicologia Positiva
16.
J Pathol ; 247(2): 214-227, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30350370

RESUMO

Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5-year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology - the biological basis and clinical relevance of its seven sub-categories are currently unclear. By establishing the Asia-Pacific MBC (AP-MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan-cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for 'mixed' MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis-1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed-type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan-cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Mutação , Neoplasias Complexas Mistas/genética , Antígenos CD/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Caderinas/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos Transversais , Transição Epitelial-Mesenquimal , Receptores ErbB/análise , Feminino , Predisposição Genética para Doença , Humanos , Queratinas/análise , Metaplasia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/classificação , Neoplasias Complexas Mistas/patologia , Neurofibromina 1/genética , PTEN Fosfo-Hidrolase/genética , Fenótipo , Carga Tumoral , Proteína Supressora de Tumor p53/genética
17.
Appetite ; 154: 104796, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712195

RESUMO

Food fussiness is the rejection of familiar and novel foods leading to consumption that is insufficient and/or inadequately varied. Its importance to children's nutrition and the development of food preferences means it has been the focus of extensive research. To measure food fussiness, research has predominantly relied on parent-report, though parents' reporting of their child's eating behaviour can be reliable, responses may also be subject to bias. Utilising data from video-recordings of sixty-seven mother-child dyads during a meal in the home environment, this study aimed to validate the most widely used parent-report questionnaire measuring food fussiness against independent observations of children's eating behaviour and, in so doing, determine its accuracy. Maternal reported food fussiness, assessed using the Food Fussiness subscale of the Children's Eating Behaviour Questionnaire (CEBQ; Wardle, Guthrie, Sanderson, & Rapoport, 2001) was compared to children's observed food rejection and acceptance behaviours. Bootstrapped Pearson's correlations revealed that maternal reports of food fussiness were significantly positively related to food rejection behaviours and significantly negatively related to food acceptance behaviours. Maternal reports of food fussiness were also found to be significantly negatively related to the proportion of familiar/appealing of familiar foods consumed by the child. There was no significant association between maternal reported food fussiness and the proportion of familiar/unappealing, unfamiliar/appealing and unfamiliar/unappealing foods consumed by the child or the meal duration. These findings support the CEBQ FF as a valid measure of food fussiness.


Assuntos
Seletividade Alimentar , Criança , Comportamento Infantil , Comportamento Alimentar , Preferências Alimentares , Humanos , Refeições , Pais , Inquéritos e Questionários
18.
Eur Child Adolesc Psychiatry ; 29(5): 649-664, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31410579

RESUMO

There is a lack of current data on help-seeking, and barriers to accessing professional support for child anxiety disorders. This study aimed to provide current data on the frequency and type of parental help-seeking, professional support received, and parent-reported barriers/facilitators in the context of child anxiety, and to explore factors associated with help-seeking, and parent-reported barriers among help-seekers and non help-seekers. We conducted a survey of help-seeking in parents of 222 children (aged 7-11) with elevated anxiety symptoms identified through screening in schools, 138 children of whom met diagnostic criteria for an anxiety disorder. Almost two-thirds (64.5%) of parents of children with an anxiety disorder reported seeking help from a professional; in 38.4% of cases parents reported that their child had received support from a professional to help manage and overcome their anxiety difficulties, and < 3% had received evidence-based treatment (CBT). Frequently reported parental barriers related to difficulties differentiating between developmentally appropriate and clinically significant anxiety, a lack of help-seeking knowledge, perceived negative consequences of help-seeking, and limited service provision. Non-help seekers were more likely than help seekers to report barriers related to thinking a child's anxiety may improve without professional support, and the absence of professional recognition. Findings identify the need for (i) tools for parents and primary school staff to help identify children who may benefit from professional support to overcome difficulties with anxiety; and (ii) increased evidence-based provision for child anxiety disorders, including delivery within schools and direct support for parents.


Assuntos
Transtornos de Ansiedade/terapia , Saúde da Criança/normas , Criança , Feminino , Humanos , Masculino
19.
Eur Child Adolesc Psychiatry ; 29(4): 489-499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31270605

RESUMO

Anhedonia (or loss of interest and pleasure) is a core symptom of depression and may predict poor treatment outcome. However, little is known about the subjective experience of anhedonia, and it is rarely targeted in psychological treatment for depression. The aim of this study is to examine how young people experience anhedonia in the context of depression. Semi-structured interviews were conducted with 34 adolescents with a primary diagnosis of depression (N = 12) or elevated depressive symptoms (N = 22). Thematic analysis was used to identify important aspects of adolescents' experiences. Four main themes were identified: (1) experiencing a loss of joy and a flattening of emotion; (2) struggling with motivation and active engagement; (3) losing a sense of connection and belonging; and (4) questioning sense of self, purpose, and the bigger picture. The results challenge the framing of anhedonia as simply the loss of interest and pleasure. Adolescents reported a range of experiences that mapped closely onto the cluster of negative symptoms associated with schizophrenia and were similar to the sense of 'apathy' characteristic in Parkinson's disease. This highlights the potential benefit of taking a trans-diagnostic approach to understanding and treating reward deficits associated with mental health problems.


Assuntos
Anedonia/fisiologia , Depressão/psicologia , Prazer/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Resultado do Tratamento
20.
Arch Dis Child Educ Pract Ed ; 105(2): 117-121, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073035

RESUMO

Research is vital to paediatrics; however, many trainees feel there is a deficit in their opportunities, experience and exposure in this area. Three training regions in the UK, the West Midlands, Wales and Peninsula, have recently started region-wide, trainee-led research and governance collaboratives aimed at improving trainee access and education in research, undertaking good quality, multicentre audit, quality improvement and pilot projects in collaboration across the regions and implementing change. We report on the experiences, benefits and challenges of these trainee collaboratives (Paediatric Research Across the Midlands, Wales Research and Education Network and Peninsula Trainee Research Audit and Innovation Network) including a trainee survey looking at how these initiatives have improved skills in conducting multicentre prospective studies, team working skills, leadership, understanding of statistics and manuscripts and presentation skills. We also describe how collaboration with colleagues and participation in projects can benefit trainees in a wider sense of purpose and help to encourage morale, as well as what can be learnt as paediatric training moves forward.


Assuntos
Saúde da Criança , Governança Clínica/organização & administração , Pediatria/educação , Medicina Estatal , Humanos , Reino Unido
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