Germline ATM Mutations Detected by Somatic DNA Sequencing in Lethal Prostate Cancer

DNA damage response; PARP inhibition; Prostate cancerRespuesta al daño del ADN; Inhibición de PARP; Cáncer de próstataResposta al dany de l'ADN; Inhibició de PARP; Càncer de pròstataBackground Germline mutations in the ataxia telangiectasia mutated (ATM) gene occur in 0.5–1% of the overall population and are associated with tumour predisposition. The clinical and pathological features of ATM-mutated prostate cancer (PC) are poorly defined but have been associated with lethal PC. Objective To report on the clinical characteristics including family history and clinical outcomes of a cohort of patients with advanced metastatic castration-resistant PC (CRPC) who were found to have germline ATM mutations after mutation detection by initial tumour DNA sequencing. Design, setting, and participants We acquired germline ATM mutation data by saliva next-generation sequencing from patients with ATM mutations in PC biopsies sequenced between January 2014 and January 2022. Demographics, family history, and clinical data were collected retrospectively. Outcome measurements and statistical analysis Outcome endpoints were based on overall survival (OS) and time from diagnosis to CRPC. Data were analysed using R version 3.6.2 (R Foundation for Statistical Computing, Vienna, Austria). Results and limitations Overall, seven patients (n = 7/1217; 0.6%) had germline ATM mutations detected, with five of them having a family history of malignancies, including breast, prostate, pancreas, and gastric cancer; leukaemia; and lymphoma. Two patients had concomitant somatic mutations in tumour biopsies in genes other than ATM, while two patients were found to carry more than one ATM pathogenic mutation. Five tumours in germline ATM variant carriers had loss of ATM by immunohistochemistry. The median OS from diagnosis was 7.1 yr (range 2.9–14 yr) and the median OS from CRPC was 5.3 yr (range 2.2–7.3 yr). When comparing these data with PC patients sequenced by The Cancer Genome Atlas, we found that the spatial localisation of mutations was similar, with distribution of alterations occurring on similar positions in the ATM gene. Interestingly, these include a mutation within the FRAP-ATM-TRRAP (FAT) domain, suggesting that this represents a mutational hotspot for ATM. Conclusions Germline ATM mutations are rare in patients with lethal PC but occur at mutational hotspots; further research is warranted to better characterise the family histories of these men and PC clinical course

Comparison of visual and auditory modalities for Upper-Alpha EEG-Neurofeedback

Electroencephalography (EEG) neurofeedback (NF) training has been shown to produce long-lasting effects on the improvement of cognitive function as well as the normalization of aberrant brain activity in disease. However, the impact of the sensory modality used as the NF reinforcement signal on training effectiveness has not been systematically investigated. In this work, an EEG-based NF training system was developed targeting the individual upper alpha (UA) band and using either a visual or an auditory reinforcement signal, so as to compare the effects of the two sensory modalities. Sixteen healthy volunteers were randomly assigned to the Visual or Auditory group, where a radius varying sphere or a volume-varying sound, respectively, reflected the relative amplitude of UA measured at EEG electrode Cz. Each participant underwent a total of four NF sessions, of approximately 40 min each, on consecutive days. Both groups showed significant increases in UA at Cz within sessions, and also across sessions. Effects subsequent to NF training were also found beyond the target frequency UA and scalp location Cz, namely in the lower-alpha and theta bands and in posterior brain regions, respectively. Only small differences were found on the EEG between the Visual and Auditory groups, suggesting that auditory reinforcement signals may be as effective as the more commonly used visual signals. The use of auditory NF may potentiate training protocols conducted under mobile conditions, which are now possible due to the increasing availability of wireless EEG systems.info:eu-repo/semantics/publishedVersio

O funcionamento familiar em famílias com filhos adultos com deficiência: estudo descritivo-correlacional

Background: the presence of a child with a disability is an overwhelming challenge. Each family is unique, with its own needs, and promoting healthy family functioning is essential for the individual and collective health of its members. Objectives: characterize families with an adult child with disabilities and understand their family functioning. Methodology: correlational descriptive study, non-probabilistic convenience sample, of forty families whose children attend an institution in the district of Guarda. Data collected through a questionnaire, subject to descriptive and inferential statistics (Nonparametric Mann-Whitney and Kruskal-Wallis U tests). Results: the majority of the sample consists of children aged between 31 and 45 years, similarly distributed by sex. Most families have balanced levels of family functioning. The female gender positively influences the cohesion and communication subscale and the male gender the dismembered and chaotic subscale. Families with younger children are related to higheraverages on the tangled subscale, as well as those with physical disabilities. Conclusion: the existence of a disability interferes with family functioning, with differences regarding the sex and age of the disabled child. The family nurse, a decisive element in the diagnostic approach, develops strategies and creates multidisciplinary programs aimed at these families.Marco contextual: la presencia de un niño con una discapacidad es un desafío abrumador. Cada familia es única, con sus propias necesidades, y promover un funcionamiento familiar saludable es fundamental para la salud individual y colectiva de sus miembros. Objetivos: caracterizar familias con un hijo adulto con discapacidad y comprender su funcionamiento familiar. Metodología: estudio descriptivo correlacional, muestra no probabilística por conveniencia, de cuarenta familias cuyos hijos asisten a una institución del distrito de Guarda. Datos recolectados a través de un cuestionario, sujeto a estadística descriptiva e inferencial (pruebas U no paramétricas de Mann-Whitney y Kruskal-Wallis). Resultados: la mayoría de la muestra está compuesta por niños con edades comprendidas entre 31 y 45 años, igualmente distribuidos por sexo. La mayoría de las familias tienen niveles equilibrados de funcionamiento familiar. El género femenino influye positivamente en la subescala cohesión y comunicación y el género masculino en la subescala desmembrado y caótico. Las familias con niños más pequeños se relacionan con promedios más altos en la subescala de enredados, así como aquellas con discapacidades físicas. Conclusión: la existencia de una discapacidad interfiere en el funcionamiento familiar, existiendo diferencias en cuanto al sexo y edad del hijo discapacitado. La enfermera de familia, elemento decisivo en el abordaje diagnóstico, desarrolla estrategias y crea programas multidisciplinares dirigidos a estas familias.Enquadramento: a presença de um filho com deficiência é um desafio avassalador. Cada família é única, com necessidades próprias e promover um funcionamento familiar saudável é essencial para a saúde individual e coletiva dos seus membros. Objetivos: caraterizar as famílias com filho adulto com deficiência e compreender o funcionamento familiar das mesmas. Metodologia: estudo descritivo correlacional, amostra não probabilística por conveniência, de quarenta famílias cujos filhos frequentam uma instituição do distrito da Guarda. Dados recolhidos através de questionário, sujeitos a estatística descritiva e inferencial (testes não paramétricos U de Mann-Whitney e Kruskal-Wallis). Resultados: a generalidade da amostra é constituída por filhos com idades entre 31 e 45 anos, semelhantemente distribuídas por sexo. A maioria das famílias apresenta níveis de funcionamento familiar equilibrados. O sexo feminino influencia positivamente a subescala coesão e comunicação e o masculino a desmembrada e caótica. Às famílias com filhos mais novos estão relacionadas a médias superiores na subescala emaranhada, bem como nos que apresentam deficiência física. Conclusão: a existência de uma deficiência interfere no funcionamento familiar, com diferenças quanto ao sexo e idade do filho com deficiência. O enfermeiro de família, elemento decisivo na abordagem diagnóstica, elabora estratégias e cria programas multidisciplinares direcionados a estas famílias

Phenotypic diversity of circulating tumour cells in patients with metastatic castration‐resistant prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/1/bju13631_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/2/bju13631.pd

Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.

Abstract Background Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression. Objective To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS). Design, setting, and participants CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients). Outcome measurements and statistical analysis CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined. Results and limitations Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19–184 vs 9, 2–64; Mann-Whitney test p Conclusions Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported. Patient summary Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use

Interdisciplinaridade e Intersetorialidade: Desafios nos Processos de Formação e Trabalho Profissional

Interdisciplinaridade eIntersetorialidade: Desafios nos Processosde Formação e Trabalho Profissiona

description of the methodological approach

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Estudos Artísticos

Nesta procura continuada de reunir escritos de artistas sobre outros criadores se reuniram neste número da Revista Croma dezasseis artigos que têm em comum a determinação interventiva e emancipada. Provoca-se o inconformismo, ensaia-se o pensamento. A intervenção advém do estatuto, do capital simbólico associado à autoria. O estatuto político da arte centra o artista e tona-o vocal. A sua perspetiva, a sua síntese, a sua fantasia, são agora meios para uma mediação junto de todos, em direção a uma transformação fundamental e construtora de um dos pontos essenciais da cultura: a arte emancipada. Com a emancipação da arte, criou-se uma nova referencialidade, um novo descentramento, um olhar exterior, um olhar do homem sobre o homem, um olhar político mediado pelas formas pensadas.info:eu-repo/semantics/publishedVersio