Integração da doença crónica pediátrica na vida familiar: estudo preliminar da versão portuguesa do instrumento "Family Adaptation to Chronic Illness Questionnaire" / Integrating pediatric chronic illness into family life: preliminary study of the portuguese version of the instrument "Family Adaptation to Chronic Illness Questionnaire"

Existe um número crescente de famílias com crianças/adolescentes com o diagnóstico de uma doença crónica/perturbação, situação que desencadeia múltiplas mudanças no funcionamento familiar de forma a integrar a doença nas suas dinâmicas. Os enfermeiros encontram-se numa posição privilegiada para providenciar suporte e empoderar as famílias na vivência desta transição. No sentido de otimizar o cuidado à família, são necessários instrumentos de medida que sejam capazes de avaliar o processo de integração da doença crónica pediátrica por parte da família. A presente investigação visa adaptar culturalmente e fazer um estudo preliminar das propriedades da versão portuguesa do instrumento Family Adaptation to Chronic Illness Questionnaire (FAM-ACIQ). Tem ainda como objetivos avaliar os processos de integração da doença crónica pediátrica na vida familiar e analisar a associação entre os processos de integração da doença crónica pediátrica na vida familiar com a saúde auto-percebida dos pais, a perceção dos pais acerca da de saúde física e mental da criança/adolescente e a perceção acerca do suporte dado pelos enfermeiros. Este estudo insere-se no paradigma quantitativo, transversal e descritivo correlacional, integrando também uma componente de desenho metodológico. A amostra foi constituída por 135 pais de crianças/adolescentes com o diagnóstico de doença crónica/perturbação, acompanhados na consulta externa ou hospital de dia pediátrico de três instituições da região norte de Portugal. A colheita de dados foi realizada através da versão portuguesa do Family Adaptation to Chronic Illness Questionnaire (FAM-ACIQ) e do Iceland Family Perceived Support Questionnaire (ICE-FPSQ). Os resultados do estudo sugerem que a versão portuguesa da FAM-ACIQ é um instrumento válido e fidedigno. Na análise fatorial exploratória foram encontradas duas dimensões: uma relacionada com as barreiras e outra com as forças da família no processo de integração da doença crónica pediátrica, ambas com uma boa consistência interna (α=.707 e α=.869, respetivamente). Os participantes reportaram uma boa integração da doença crónica, no entanto, apenas a subescala relativa às barreiras da família apresenta uma associação positiva com a saúde auto-percebida dos pais e a perceção dos pais acerca da saúde física e mental da criança/adolescente. Por sua vez, os pais que manifestaram uma melhor integração da doença crónica, através da subescala das forças, apresentaram uma melhor perceção acerca do suporte emocional dado pelos enfermeiros. Conhecer o processo de integração da doença crónica pediátrica pela família e a sua perceção acerca do suporte fornecido pelos enfermeiros, permite uma avaliação e intervenção mais objetiva e centrada nas suas necessidades e dificuldades destas famílias.

There is a growing number of families with children/adolescents diagnosed with a chronic illness/disorder, situation that triggers multiple changes in family functioning to integrate the disease into family dynamics. Nurses are in a prime position to provide support and empower families through this transition. In order to optimize family care, instruments are needed to measure the family processes of integrating pediatric chronic illness. The present investigation aims to culturally adapt and carry out a preliminary study of the psychometric properties of the portuguese version of the instrument Family Adaptation to Chronic Illness Questionnaire (FAM-ACIQ). It also aims to evaluate the process of integrating chronic illness into family life and the association between the processes of integrating pediatric chronic illness into family life and the parents' self-perceived health, the parents' perception of their child/adolescent's physical and mental health and the perceived support from nurses. This is a quantitative, cross-sectional, descriptive correlational study, which integrates a methodological design component. The sample was composed by 135 parents of children/adolescents diagnosed with chronic illness/disorder, followed up in the pediatric outpatient clinic or day hospital of three hospital institutions, based in the north of Portugal. Data were collected using the portuguese version of the Family Adaptation to Chronic Illness Questionnaire (FAM-ACIQ) and the Iceland Family Perceived Support Questionnaire (ICE-FPSQ). The results of the study suggest that the portuguese version of the FAM-ACIQ is a valid and reliable instrument. In the exploratory factor analysis two dimensions emerged: one related to the barriers and the other to the family's strengths in the process of integrating pediatric chronic illness, both with good internal reliability (α=.707 e α=.869, respectively). Participants reported good integration of the chronic illness into family life, however, only the subscale related to the family "barriers" showed a positive association with the parents' self-perceived health and the parents' perception of their child/adolescent's physical and mental health. Parents who showed a good integration of their child's chronic illness, through the strength's subscale, presented a greater perceived emotional support from the nurses. Knowing the family's process in integrating pediatric chronic illness and their perceived support from nurses, indorses an appropriate assessment and intervention focused on the family needs and difficulties.

Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells.

During mitosis, chromatin condensation is accompanied by a global arrest of transcription. Recent studies suggest transcriptional reactivation upon mitotic exit occurs in temporally coordinated waves, but the underlying regulatory principles have yet to be elucidated. In particular, the contribution of sequence-specific transcription factors (TFs) remains poorly understood. Here we report that Brn2, an important regulator of neural stem cell identity, associates with condensed chromatin throughout cell division, as assessed by live-cell imaging of proliferating neural stem cells. In contrast, the neuronal fate determinant Ascl1 dissociates from mitotic chromosomes. ChIP-seq analysis reveals that Brn2 mitotic chromosome binding does not result in sequence-specific interactions prior to mitotic exit, relying mostly on electrostatic forces. Nevertheless, surveying active transcription using single-molecule RNA-FISH against immature transcripts reveals differential reactivation kinetics for key targets of Brn2 and Ascl1, with transcription onset detected in early (anaphase) versus late (early G1) phases, respectively. Moreover, by using a mitotic-specific dominant-negative approach, we show that competing with Brn2 binding during mitotic exit reduces the transcription of its target gene Nestin Our study shows an important role for differential binding of TFs to mitotic chromosomes, governed by their electrostatic properties, in defining the temporal order of transcriptional reactivation during mitosis-to-G1 transition.

Vulvar Hailey-Hailey disease treated with low-dose naltrexone: case report and literature review.

PURPOSE: To report a case of vulvar familial benign pemphigus, or Hailey-Hailey disease, treated successfully with low-dose naltrexone and to review the current literature. METHODS: We report a case of a 71-year-old white woman with vulvar Hailey-Hailey disease recalcitrant to topical corticosteroids. After treatment with low-dose naltrexone, 3 mg nightly was initiated, the lesions began to heal and 5 months later her skin showed no lesions. A literature review on the use of low-dose naltrexone for Hailey-Hailey disease was performed. We searched the PubMed/MEDLINE databases for previous case reports using the key words ''Pemphigus, Benign Familial'' and ''naltrexone". RESULTS: We found 35 more cases of Hailey-Hailey disease treated with naltrexone, showing promising results, reported until January 2020, with no major adverse effects. CONCLUSION: Low-dose naltrexone may represent a cost-effective and successful treatment modality in nongeneralized Hailey-Hailey disease without serious adverse effects. Future prospective studies are needed to investigate this interesting therapeutic option.

Zeb1 potentiates genome-wide gene transcription with Lef1 to promote glioblastoma cell invasion.

Glioblastoma is the most common and aggressive brain tumor, with a subpopulation of stem-like cells thought to mediate its recurring behavior and therapeutic resistance. The epithelial-mesenchymal transition (EMT) inducing factor Zeb1 was linked to tumor initiation, invasion, and resistance to therapy in glioblastoma, but how Zeb1 functions at molecular level and what genes it regulates remain poorly understood. Contrary to the common view that EMT factors act as transcriptional repressors, here we show that genome-wide binding of Zeb1 associates with both activation and repression of gene expression in glioblastoma stem-like cells. Transcriptional repression requires direct DNA binding of Zeb1, while indirect recruitment to regulatory regions by the Wnt pathway effector Lef1 results in gene activation, independently of Wnt signaling. Amongst glioblastoma genes activated by Zeb1 are predicted mediators of tumor cell migration and invasion, including the guanine nucleotide exchange factor Prex1, whose elevated expression is predictive of shorter glioblastoma patient survival. Prex1 promotes invasiveness of glioblastoma cells in vivo highlighting the importance of Zeb1/Lef1 gene regulatory mechanisms in gliomagenesis.

Identification of Novel Hemangioblast Genes in the Early Chick Embryo.

During early vertebrate embryogenesis, both hematopoietic and endothelial lineages derive from a common progenitor known as the hemangioblast. Hemangioblasts derive from mesodermal cells that migrate from the posterior primitive streak into the extraembryonic yolk sac. In addition to primitive hematopoietic cells, recent evidence revealed that yolk sac hemangioblasts also give rise to tissue-resident macrophages and to definitive hematopoietic stem/progenitor cells. In our previous work, we used a novel hemangioblast-specific reporter to isolate the population of chick yolk sac hemangioblasts and characterize its gene expression profile using microarrays. Here we report the microarray profile analysis and the identification of upregulated genes not yet described in hemangioblasts. These include the solute carrier transporters SLC15A1 and SCL32A1, the cytoskeletal protein RhoGap6, the serine protease CTSG, the transmembrane receptor MRC1, the transcription factors LHX8, CITED4 and PITX1, and the previously uncharacterized gene DIA1R. Expression analysis by in situ hybridization showed that chick DIA1R is expressed not only in yolk sac hemangioblasts but also in particular intraembryonic populations of hemogenic endothelial cells, suggesting a potential role in the hemangioblast-derived hemogenic lineage. Future research into the function of these newly identified genes may reveal novel important regulators of hemangioblast development.

Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism

Abstract Dyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.

Fixed drug eruption by etoricoxib confirmed by patch test.

Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis.

The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

Fixed drug eruption by etoricoxib confirmed by patch test

Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism.

Dyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.

[Allergic contact dermatitis to metals over a 20-year period in the Centre of Portugal: evaluation of the effects of the European directives]. / Alergia de contacto a metais num período de 20 anos no Centro de Portugal: implicações das directivas Europeias.

INTRODUCTION: Metals are a common cause of allergic contact dermatitis. After the introduction of the EU Nickel Directive (1994/27/CE; 2004/96/EC) and, more recently, the Cement Directive (2003/53/EC) there has been a significant decrease in sensitization to metals mainly in the Nordic countries. The applicability of these directives and their impact in the Portuguese population is unknown. MATERIAL AND METHODS: A retrospective study (1992-2011) was carried out in our patch test clinic to assess the temporal trend of metal sensitization (nickel [Ni], cobalt [Co] and chromium [Cr]) along the last 20 years, particularly considering age, sex and its relation with occupational activity. RESULTS: Out of 5 250 consecutively patch-tested patients, 1 626 (31%) were reactive to at least one metal (26.5% to Ni; 10.0% to Co and 7.9% to Cr). Women had a higher prevalence of sensitization to Ni (34.4% vs 8.9%) whereas men were more reactive to Cr (11.5% vs 5.0%). Nickel sensitization did not decrease significantly over the years, although in recent years among women sensitized to nickel the percentage of younger patients (16-30 years-old) is significantly lower (p < 0.001). Chromium sensitization significantly decreased, particularly in men (r = -0.535), and mainly in the construction workers (r = -0.639). Chromium reactivity associated with the shoe dermatitis has remained stable. DISCUSSION: We emphasize the higher and stable percentage of nickel sensitized individuals suggesting, so far, a low impact from the EU Ni directive, although a decreasing percentage in the the younger group among Ni sensitized women may suggest a beneficial effect is becoming evident is this age group. On the contrary, the impact of the directive regarding the modification of Cr in cement seems to be effective. There is now a need to regulate chromium content in leather products, namely in shoes. CONCLUSIONS: The regulation of interventional measures related either to the manufacture and trade of adornments or professional use will better protect the population of allergy to metals.

Introdução: Os metais são causa frequente de dermatite de contacto alérgica. Desde a introdução da Directiva Comunitária do Níquel (1994/27/CE; 2004/96/CE) e, mais recentemente, da Directiva do Cimento (2003/53/CE), nos países nórdicos tem havido uma diminuição da sensibilização aos metais. A aplicabilidade destas medidas e o seu impacto permanece por avaliar em Portugal. Material e Métodos: Foi realizado um estudo retrospectivo (1992-2011) na Consulta de Alergologia Cutânea com o principal objectivo de analisar a variação dos padrões de sensibilização aos metais (níquel [Ni], cobalto [Co] e crómio [Cr]) ao longo de 20 anos, em particular no que se refere ao género, grupo etário e relação com a actividade profissional. Resultados: Do total de 5 250 doentes estudados, em 1 626 (31%) observámos pelo menos um teste epicutâneo positivo a um metal (26,5% ao Ni; 10,0% ao Co e 7,0% ao Cr). A prevalência de sensibilização ao Ni era significativamente maior nas mulheres (34,4% versus 8,9%) e ao Cr nos homens (11,5% versus 5,0%). Não houve diminuição significativa da sensibilização ao Ni ao longo dos 20 anos, mas o contributo da faixa etária dos 16-30 anos no total de mulheres sensíveis a este metal decresceu de forma significativamente estatística ao longo dos anos (p < 0,001). A sensibilização ao Cr decresceu sobretudo nos homens (r = -0,535), muito particularmente nos casos relacionados com a construção civil (r = -0,639), enquanto a reatividade ao Cr relacionado com o uso de calçado se manteve estável. Discussão: A manutenção dos elevados níveis de sensibilização ao níquel denota ainda uma fraca implementação das Directivas comunitárias mas a redução da percentagem de mulheres jovens poderá significar já algum efeito positivo nesta faixa etária. Ao contrário, a Directiva referente à redução do Cr no cimento parece estar a ter os seus efeitos positivos. Há, contudo, necessidade de interferir com o conteúdo em Cr no couro natural utilizado no calçado. Conclusões: A regulamentação da implementação de medidas interventivas relacionadas quer com o fabrico e comércio de adornos quer a nível profissional permitirá uma melhor protecção da população da alergia aos metais.

Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients.

BACKGROUND: Although rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP.

Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients

BACKGROUND: aAlthough rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP. .