RESUMO
BACKGROUND: Although early intervention (EI) practitioners emphasise the importance of individualised family-centred services for families of children with developmental delay (DD), few empirical studies have evaluated whether EI can improve family quality of life (FQOL). This study aimed to investigate the trajectory of FQOL and its predictors among families of children with DD during the first 12 months of EI. METHODS: This study employed a prospective cohort design. Data were collected using structured questionnaires at the placement meeting before the commencement of EI, as well as 3, 6 and 12 months later. We recruited 142 primary caregivers of children with DD in northern Taiwan from March 2015 to August 2016. FQOL was measured using the Mandarin Chinese version of the Beach Centre FQOL Scale. Family resilience (FR) was measured using the Mandarin Chinese version of the FR Assessment Scale. Other independent variables included socio-demographics, type of DD and EI services. Generalised estimating equations were used to perform multivariate analysis. RESULTS: Family quality of life exhibited a significant quadratic trend in the 12 months surrounding EI. The score was the lowest before EI started (89.85), then increased to peak (94.87) at 6 months and then decreased slightly to 92.34 at 12 months. FR followed a significantly increased linear trend during the period. There were significant and positive correlations between FQOL and FR across all time points. Multivariate analysis showed that employed caregivers, FR, sufficient caregiving manpower and satisfaction with marital quality were positively associated with FQOL. Receiving more types of EI services and having fathers who were not Taiwanese nationals were negatively associated with FQOL. CONCLUSIONS: Family quality of life and FR increased significantly after receiving EI, revealing the latter's effectiveness. Unemployment, poor marital quality, father being an immigrant, low FR and insufficient family caregiving manpower were associated with lower FQOL, suggesting that these families require more assistance.
Assuntos
Deficiências do Desenvolvimento/terapia , Intervenção Médica Precoce , Família/psicologia , Qualidade de Vida/psicologia , Resiliência Psicológica , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pais , Estudos Prospectivos , Fatores Socioeconômicos , TaiwanRESUMO
BACKGROUND: Early intervention (EI) practitioners provide individualised family-centred services to enhance the quality of life (QOL) of families of children with developmental delay (DD). Family QOL (FQOL) could be an important outcome indictor for EI, but there is no measurement tool for FQOL in Mandarin Chinese. The purpose of this study was to translate the Beach Centre FQOL Scale (BCFQOL) into Mandarin Chinese and to examine the psychometric properties of the scale in families of children with DD. METHODS: Two independent translations were performed by two bilingual professors whose mother tongue was Mandarin, and two back-translations were performed by two bilingual professionals whose mother tongue was English. The translated and back-translated questionnaires were reviewed to revise the questionnaire. Five experts assessed the accuracy, equivalence and cultural appropriateness of the scale, and 10 parents of children with DD were interviewed to examine its readability, clarity and cultural appropriateness. From July to November 2014, we recruited 360 primary caregivers of children with DD who were receiving EI in northern Taiwan to validate the scale. The participants completed the BCFQOL as well as a one item overall ratings of their FQOL. RESULTS: Item analysis was performed to assess each item. Confirmatory factor analysis supported the following five-factor structure as in the original scale: family interaction, parenting, emotional well-being, physical/material well-being and disability-related support. The scale exhibited excellent internal consistency reliability (Cronbach's alpha = 0.96) and test-retest reliability at a 2-week interval (intra-class correlation coefficient = 0.92). Contrasted group validity was supported by significantly higher BCFQOL scores in the top quartile of the overall FQOL rating than the lowest quartile. The convergent validity was supported by the significant correlation between the FQOL item and the BCFQOL (r = 0.608, p < 0.01). CONCLUSIONS: This study showed that the Mandarin Chinese version of the BCFQOL is reliable and valid for Taiwanese families of children with DD. The instrument could be applied to assess FQOL in families of children with DD who are receiving EI in order to evaluate family services and supports.
Assuntos
Deficiências do Desenvolvimento/psicologia , Família/psicologia , Psicometria/métodos , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Reprodutibilidade dos Testes , Taiwan , TraduçõesRESUMO
Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.
Assuntos
Movimento Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Células CACO-2 , Antígeno Carcinoembrionário/sangue , Linhagem Celular Tumoral , Neoplasias Colorretais/sangue , Dinoprostona/genética , Progressão da Doença , Feminino , Células HCT116 , Células HT29 , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Molécula 1 de Interação EstromalRESUMO
Cellular senescence is a state of irreversible growth arrest; however, the metabolic processes of senescent cells remain active. Our previous studies have shown that radiation induces senescence of human breast cancer cells that display low expression of securin, a protein involved in control of the metaphase-anaphase transition and anaphase onset. In this study, the protein expression profile of senescent cells was resolved by two-dimensional gel electrophoresis to investigate associated metabolic alterations. We found that radiation induced the expression and activation of glyceraldehyde-3-phosphate dehydrogenase that has an important role in glycolysis. The activity of lactate dehydrogenase A, which is involved in the conversion of pyruvate to lactate, the release of lactate and the acidification of the extracellular environment, was also induced. Inhibition of glycolysis by dichloroacetate attenuated radiation-induced senescence. In addition, radiation also induced activation of the 5'-adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor kappa B (NF-κB) pathways to promote senescence. We also found that radiation increased the expression of monocarboxylate transporter 1 (MCT1) that facilitates the export of lactate into the extracellular environment. Inhibition of glycolysis or the AMPK/NF-κB signalling pathways reduced MCT1 expression and rescued the acidification of the extracellular environment. Interestingly, these metabolic-altering signalling pathways were also involved in radiation-induced invasion of the surrounding, non-irradiated breast cancer and normal endothelial cells. Taken together, radiation can induce the senescence of human breast cancer cells through metabolic alterations.
Assuntos
Neoplasias da Mama/metabolismo , Efeito Espectador , Senescência Celular/efeitos da radiação , Glicólise/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos da radiação , Eletroforese em Gel Bidimensional , Ativação Enzimática , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Transportadores de Ácidos Monocarboxílicos/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica , Proteômica/métodos , Interferência de RNA , Securina/genética , Securina/metabolismo , Transdução de Sinais/efeitos da radiação , Simportadores/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial-mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.
Assuntos
Neoplasias da Mama/patologia , Quitosana/farmacologia , Ablação por Ultrassom Focalizado de Alta Intensidade , Animais , Biomarcadores Tumorais/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Diagnóstico por Imagem , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Genes Reporter , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , TransfecçãoRESUMO
BACKGROUND: We isolated several Madin-Darby canine kidney (MDCK) subclones that exhibit different degrees of branching tubulogenesis in lower concentrations of collagen gel. The M634 clone formed cell aggregates in 0.3% collagen gel, but developed branching tubules vigorously in 0.1% collagen gel. In contrast, the Y224 clone formed cysts in 0.3% collagen gel and displayed fewer branching structures in 0.1% collagen gel. Morphologically, M634 cells exhibited higher levels of cell scattering as well as collagen-induced cell migration than Y224. We conducted this study to delineate the underlying mechanism of branching tubulogenesis in M634 cells. METHODS: Components of the focal contact machinery were analyzed in both cell lines, including the extracellular matrix glycoproteins fibronectin, laminin, and vitronectin; cytoskeleton-associated elements alpha-actinin, talin, and vinculin; and receptors for extracellular matrix and alpha(2), alpha(3), alpha(5), alpha(v), beta(1), and beta(3) integrins. Furthermore, we established several stable transfectants of alpha(3) integrin antisense RNA in M634 cells to examine the role of alpha(3)beta(1) integrin in branching morphogenesis directly. RESULTS: There were no obvious differences in levels of the focal adhesion complex proteins between M634 and Y224 cells, except that the content of the alpha(3) and beta1 integrins were 1.2- and 0.6-fold higher in M634 cells, respectively. The expression of alpha(3) integrin antisense RNA significantly lowered the levels of alpha(3) integrin mRNA and protein. The potential of cell scattering, migration, and branching tubulogenesis in M634 cells was inhibited according to the decrease in alpha(3) integrin expression. CONCLUSION: Our data indicate that expression of alpha(3)beta(1) integrin regulates cell scattering, migration, and branching tubulogenesis of MDCK cells, possibly via adhesion to or serving as a signaling molecule for type I collagen.
Assuntos
Integrinas/fisiologia , Túbulos Renais/crescimento & desenvolvimento , Animais , Antígenos CD/genética , Antígenos CD/fisiologia , Sequência de Bases , Linhagem Celular , Colágeno , Meios de Cultura , Primers do DNA/genética , DNA Complementar/genética , Cães , Géis , Humanos , Integrina alfa3 , Integrina alfa3beta1 , Integrinas/antagonistas & inibidores , Integrinas/genética , Túbulos Renais/metabolismo , Camundongos , Dados de Sequência Molecular , RNA Antissenso/genética , Homologia de Sequência do Ácido Nucleico , TransfecçãoRESUMO
We explore the extending application of Potts encoding to the task of independent component analysis, which primarily deals with the problem of minimizing the Kullback-Leibler divergence between the joint distribution and the product of all marginal distributions of output components. The competitive mechanism of Potts neurons is used to encode the overlapping projections from observations to output components. Based on these projections, the marginal distributions and the entropy of output components are made tractable for computation and the adaptation of the de-mixing matrix toward independent output components is obtained. The Potts model for ICA is well formulated by an objective function subject to a set of constraints, which leads to a novel energy function. A hybrid of the mean field annealing and the gradient descent method is applied to the energy function. Our approach to independent component analysis presents a new criterion for ICA. The performance of the Potts model for ICA given by our numerical simulations is encouraging.
RESUMO
Rats receiving intracerebroventricular administration of 10 nanomoles of L-BMAA (beta-N-methylamino-L-alanine) were found to grow more slowly and contain less brain L-(3H) glutamate binding sites than rats receiving injection of phosphate-buffered saline (PBS). It was also noticed that rats receiving L-BMAA injection inevitably developed a characteristic behavioral pattern, including loss of mobility and keeping their heads in a tilted position with occasional side to side movement. This unique behavioral pattern was not observed in rats receiving injection of PBS. Rats receiving injection of beta-N-oxalylamino-L-alanine, another toxic plant amino acid, showed a decrease in brain L-(3H) glutamate binding sites, however, without the characteristic behavioral change as induced by L-BMAA. It was further found that rats receiving injection of L-BMAA plus 2-amino-5-phosphonovalerate were similar to those injected with PBS with respect to their L-(3H) glutamate binding activity and behavioral pattern. Results obtained here show that L-BMAA at nanomole level is able to elicit neurotoxic effects on rats and that these toxic effects are mediated by N-methyl-D-asparate-subtype L-glutamate receptors. The results also show that a decrease in glutamate receptor number results from L-BMAA treatment, suggesting an involvement of altered glutamate receptor level in the manifestation of L-BMAA neurotoxicity.