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Rates of overweight and obesity are problematic among systematically marginalized youth; however, these youth and their families are a hard-to-reach research population. The purpose of our study was to identify facilitators and barriers for recruiting systematically marginalized families in youth weight-management intervention research. This study built upon existing evidence through involvement of youth, parents, community agency workers, and school nurses, and an exploration of both recruitment materials and processes. Seven focus groups were conducted with 48 participants from 4 stakeholder groups (youth, parents, school nurses, and community agency workers). A codebook approach to thematic analysis was used to identify key facilitator and barrier themes related to recruitment materials and processes across the stakeholder groups. Ecological systems theory was applied to contextualize the facilitators and barriers identified. Participants reported the need to actively recruit youth in the study through engaging, fun recruitment materials and processes. Participants reported greater interest in recruitment at community-based events, as compared to recruitment through health care providers, underscoring the depth of distrust that this sample group has for the health care system. Recommendations for recruitment materials and processes for weight-management intervention research with systematically marginalized families are proposed.
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Sobrepeso , Pais , Adolescente , Humanos , Sobrepeso/terapia , Projetos de Pesquisa , Grupos FocaisRESUMO
BACKGROUND: Type 2 diabetes (T2D) is a burgeoning epidemic in children and adolescents. Adult T2D doubles the risk of depression and mental health comorbidity, makes it more difficult to make the lifestyle, medication adherence and health behavior changes needed to optimize outcomes. There is limited research on the impact of depression and depressive symptoms on youth T2D. METHODS: A search of the literature in the last 10 years regarding youth with depression and T2D was conducted. Abstracts were screened by 2 randomly assigned authors for inclusion, and disagreement was resolved by a third author. Selected full-text articles were divided among all authors for review. RESULTS: 13 publications from 8 studies (N=2244, age 6-17) were included. 6 of 13 publications utilized Treatment Options for Type 2 Diabetes in Youth (TODAY) study data. While studies included evaluation of depressive symptoms, most did not formally assess for major depressive disorder (MDD) and excluded participants with a previous diagnosis of MDD. Depressive symptoms were common in this population and were associated with negative T2D outcomes. CONCLUSIONS: While there is a growing body of adult literature highlighting the extensive relationship between T2D and mental health, there is a dearth of data in youth. Future studies are needed that include, 1.) youth with diagnosed MDD, 2.) treatment studies of both T2D and MDD, 3.) larger, more racially diverse samples of youth with T2D, and 4.) studies that evaluate the impact of social determinants of health, including mental health comorbidity on outcomes of T2D.
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Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Criança , Adulto , Adolescente , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Saúde Mental , Comorbidade , Adesão à MedicaçãoRESUMO
BACKGROUND: As the number of people with heart failure and treatment complexity increases, many hospitals are implementing Advanced Heart Failure Intensive Care Units (AHFICU). However, little evidence concerning the clinical characteristics of people admitted to AHFICUs exists. Understanding the clinical characteristics of people admitted to the AHFICU will assist nurses with implementing tailored interventions to ensure high-quality care delivery. AIM: The purpose of this study was to describe the clinical characteristics of people who are admitted to and discharged from an AHFICU. STUDY DESIGN: Baseline data from a longitudinal descriptive study were collected on adults (N = 43) admitted to an AHFICU. Heart failure severity, self-management ability, cognition, sleep quality, and other clinical characteristics were assessed. RESULTS: Most study participants were New York Heart Association functional class IV (n = 24) or class III (n = 14), indicating poor functional capacity. Over half had mild cognitive impairment and poor sleep quality was prevalent (92.7%). Participants had adequate levels of heart failure knowledge, but low levels of heart failure self-management decision-making and ability. CONCLUSIONS: Interventions to address the unique clinical characteristics of AHFICU patients include sleep hygiene, integration of cognitive, sleep, and self-management assessments into the electronic medical record. Addressing the unique clinical needs of people with heart failure will lead to patient-centered, evidence-based, and safe care. RELEVANCE TO CLINICAL PRACTICE: Understanding characteristics of this population addresses this evidence gap and targeted clinical interventions to address unique discharge needs of this population are proposed. Sleep quality education should be done throughout hospitalization on sleep strategies and self-management coaching to facilitate adoption of new sleep routines. Healthcare providers should ensure each patient has care support upon discharge and take cognitive status into consideration during teaching. Addressing self-management readiness should include providing scenarios as part of discharge preparation. Providers must include addressing comorbidities and how they may affect heart failure self-management, such as teaching about sleep apnea device use and encouraging compliance.
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Although pheochromocytomas and paragangliomas (PPGLs) are usual low-grade neoplasms, the metastatic forms of these lesions are associated with high morbidity and mortality. Recent studies have discovered multiple aberrantly expressed long non-coding RNAs (lncRNAs) in cancers that may have regulatory roles in tumor pathogenesis and metastasis; however, the roles of some lncRNAs in PPGLs are still unknown. The expression levels of lncRNAs including metastasis-associated lung adenocarcinoma transcript (MALAT1), prostate cancer antigen 3 (PCA3), and HOX transcript antisense intergenic RNA (HOTAIR) in PPGLs were analyzed by in situ hybridization, using two tissue microarrays (TMAs). The pheochromocytoma (PCC) TMA consisted of normal adrenal medulla (N = 25), non-metastatic PCCs (N = 76) and metastatic PCCs (N = 5) while the paraganglioma (PGL) TMA had 73 non-metastatic PGLs and 5 metastatic PGLs. Immunohistochemical staining was performed on all samples with an anti-SDHB antibody. The correlations between lncRNA expression, loss of SDHB expression and clinical characteristics including tumor progression and disease prognosis were investigated. The expression levels of MALAT1 and PCA3 were significantly elevated (2.5-3.9 folds) in both non-metastatic and metastatic PCCs compared to normal adrenal medulla, although there were no significant differences between the non-metastatic and metastatic neoplasms. In contrast to non-metastatic PGLs, metastatic PGLs had significantly upregulated expression of MALAT1, PCA3, and HOTAIR. SDHB loss was more frequently observed in PGLs (25 of 78), especially in metastatic PGLs (5 of 5), compared to PCCs (2 of 81) and in 0 of 5 metastatic PCCs. Patients with SDHB loss, in contrast to SDHB retained, were younger at diagnosis, had higher rates of tumor recurrence, metastatic disease, and mortality. In addition, PGLs with SDHB loss had significantly increased expression of PCA3 compared to tumors with intact SDHB expression. Our findings suggest that specific lncRNAs may be involved in the SDHx signaling pathways in the tumorigenesis and in the development of PPGL.
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Paraganglioma , Feocromocitoma , RNA Longo não Codificante , Succinato Desidrogenase , Carcinogênese , Humanos , Mutação , Recidiva Local de Neoplasia , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/metabolismo , Paraganglioma/patologia , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/metabolismo , Feocromocitoma/patologia , Prognóstico , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Transdução de Sinais , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismoRESUMO
AIM: To conduct an integrative review of empirical studies examining factors affecting trust in the healthcare provider (HCP) relationship among adolescents. DESIGN: An integrative review was conducted. DATA SOURCES: The keywords adolescent, trust, healthcare provider and related words were searched in multiple online research databases. The results were limited to research published between 2004 and 2019. Seventeen primary sources were identified and synthesized in the final review. REVIEW METHOD: Guided by the Whittemore and Knafl integrative review method, a data-based convergent synthesis design was used to explore the key research question in both qualitative and quantitative research. RESULTS: This integrative review found that health care provider behaviours, such as confidentiality, honesty, respect, and empathy, promote adolescent's trust of the HCP. Notable gaps in the literature were also identified, including a lack of diversity among adolescent samples and HCP types and underdeveloped measures of adolescent trust of HCP. CONCLUSION: This integrative review informed the development of a new conceptual definition of adolescent trust of HCP, which embodies the key findings of the importance of HCP confidentiality, honesty, respect, and empathy. This definition can be used to develop instruments, interventions and policies that promote HCP trust among adolescents. Future research is needed to develop instruments to measure adolescents' trust of HCPs, evaluate trust of HCPs among diverse samples of adolescents and evaluate adolescent trust of HCPs with a variety of HCP types. IMPACT: The new conceptual definition of adolescent trust of HCP can be used to enhance nursing practice and design behavioural interventions to improve trust of HCP. To foster adolescent trust of HCP, policies should be enacted in healthcare institutions to explain confidentiality, provide notification of reporting mandates and formalize consent, assent and dissent for adolescents seeking health care.
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Pessoal de Saúde , Confiança , Adolescente , Empatia , Humanos , Inquéritos e QuestionáriosRESUMO
The purpose of this study was to evaluate associations among depressive symptoms, trust of healthcare provider, and health behavior in adolescents who live in a rural area. Two hundred twenty-four adolescents aged 14-19 years old attending public high school in the Midwestern United States were surveyed. Results showed a diagnosis of depression, trust of healthcare provider, health awareness, and stress management predicted depressive symptoms in adolescents living in a rural area. Healthcare providers should take extra care to promote trust in the healthcare provider-patient relationship with adolescents and to follow guidelines for annual screening of adolescents for depressive symptoms. Nursing implications include adolescent psychoeducation to improve health awareness and stress management.
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Depressão , Confiança , Adolescente , Depressão/diagnóstico , Pessoal de Saúde , Humanos , Meio-Oeste dos Estados Unidos , População RuralRESUMO
In situ hybridization (ISH) has become a common laboratory technique used for the analysis of gene expression and for the localization of specific DNA and RNA molecules in cells. Many different methods of performing ISH have been described. These techniques have evolved into important tools in basic scientific research and in clinical diagnoses. One of the goals of ISH is to localize gene sequences in situ and to visualize the products within cells while preserving cell integrity. This allows for meaningful anatomical and histological interpretation of the localized product(s) within heterogeneous tissues. Because of the possibility of false positive and false negative results that may occur with ISH assays, familiarity with the pathophysiology of the molecules that are analyzed and the cellular processes involved as well as with limitations of the assays can help to avoid erroneous diagnoses with clinical specimens.
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Perfilação da Expressão Gênica/métodos , Hibridização In Situ/métodos , HumanosRESUMO
Thyroid cancers are the most common endocrine malignancy and approximately 2% of thyroid cancers are anaplastic thyroid carcinoma (ATC), one of the most lethal and treatment resistant human cancers. Cancer stem-like cells (CSCs) may initiate tumorigenesis, induce resistance to chemotherapy and radiation therapy, have multipotent capability and may be responsible for recurrent and metastatic disease. The production of CSCs has been linked to epithelial-mesenchymal transition (EMT) and the acquisition of stemness. Exosomes are small (30-150 nm) membranous vesicles secreted by most cells that play a significant role in cell-to-cell communication. Many non-coding RNAs (ncRNA), such as long-non-coding RNAs (lncRNA), can initiate tumorigenesis and the EMT process. Exosomes carry ncRNAs to local and distant cell populations. This study examines secreted exosomes from two in vitro cell culture models; an EMT model and a CSC model. The EMT was induced in a papillary thyroid carcinoma (PTC) cell line by TGFß1 treatment. Exosomes from this model were isolated and cultured with naïve PTC cells and examined for EMT induction. In the CSC model, exosomes were isolated from a CSC clonal line, cultured with a normal thyroid cell line and examined for EMT induction. The EMT exosomes transferred the lncRNA MALAT1 and EMT effectors SLUG and SOX2; however, EMT was not induced in this model. The exosomes from the CSC model also transferred the lncRNA MALAT1 and the transcription factors SLUG and SOX2 but additionally transferred linc-ROR and induced EMT in the normal thyroid cells. Preliminary siRNA studies directed towards linc-ROR reduced invasion. We hypothesize that CSC exosomes transfer lncRNAs, importantly linc-ROR, to induce EMT and inculcate the local tumor microenvironment and the distant metastatic niche. Therapies directed towards CSCs, their exosomes and/or the lncRNAs they carry may reduce a tumor's metastatic capacity.
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Transição Epitelial-Mesenquimal/genética , Células-Tronco Neoplásicas/patologia , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Exossomos/genética , Exossomos/patologia , Humanos , Modelos Biológicos , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição da Família Snail/genética , Esferoides Celulares/patologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
The purpose of our study was to determine the extent to which individual characteristic variables predict trust of healthcare provider (HCP), lifestyle behaviors, and use of health services among adolescents attending public high school in rural Indiana. The sample included 224 individuals surveyed in 9th grade or 12th grade required courses. Trust of HCP and lifestyle behaviors were predicted using hierarchical multiple regression; number of HCP visits and emergency department (ED) visits in the past 12 months were predicted using negative binomial regression. This sample of adolescents living in a rural area reported riskier lifestyle behaviors than another sample of adolescents, lower trust of HCP than adults in general, and fewer HCP and ED visits than adolescents in general. Our study supports the need for school-based health services in rural areas and the opportunity for school nurses to act as care coordinators for marginalized youth.
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Comportamento do Adolescente/psicologia , Serviços de Saúde do Adolescente/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Serviços de Saúde Escolar/estatística & dados numéricos , Confiança/psicologia , Adolescente , Atitude Frente a Saúde , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Assunção de Riscos , Estados UnidosRESUMO
The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.
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Células-Tronco Neoplásicas , Neoplasias da Glândula Tireoide , Animais , Transição Epitelial-Mesenquimal , Humanos , Camundongos , MicroRNAs , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/fisiopatologiaRESUMO
Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies.
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Células-Tronco Neoplásicas/efeitos dos fármacos , Estilbenos/farmacologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Ácido Valproico/farmacologia , Animais , Antioxidantes/farmacologia , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Reação em Cadeia da Polimerase em Tempo Real , ResveratrolRESUMO
BACKGROUND: A better understanding of the optimal "dose" of behavioral interventions to affect change in weight-related outcomes is a critical topic for childhood obesity intervention research. The objective of this review was to quantify the relationship between dose and outcome in behavioral trials targeting childhood obesity to guide future intervention development. METHODS: A systematic review and meta-regression included randomized controlled trials published between 1990 and June 2017 that tested a behavioral intervention for obesity among children 2-18 years old. Searches were conducted among PubMed (Web-based), Cumulative Index to Nursing and Allied Health Literature (EBSCO platform), PsycINFO (Ovid platform) and EMBASE (Ovid Platform). Two coders independently reviewed and abstracted each included study. Dose was extracted as intended intervention duration, number of sessions, and length of sessions. Standardized effect sizes were calculated from change in weight-related outcome (e.g., BMI-Z score). RESULTS: Of the 258 studies identified, 133 had sufficient data to be included in the meta-regression. Average intended total contact (# sessions x length of sessions) was 27.7 (SD 32.2) hours and average duration was 26.0 (SD 23.4) weeks. When controlling for study covariates, a random-effects meta-regression revealed no significant association between contact hours, intended duration or their interaction and effect size. CONCLUSIONS: This systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity, but was unable to detect a clear relationship between dose and weight-related outcomes. There is insufficient evidence to provide quantitative guidance for future intervention development. One limitation of this review was the ability to uniformly quantify dose due to a wide range of reporting strategies. Future trials should report dose intended, delivered, and received to facilitate quantitative evaluation of optimal dose. TRIAL REGISTRATIONS: The protocol was registered on PROSPERO (Registration # CRD42016036124 ).
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Comportamentos Relacionados com a Saúde , Obesidade Infantil/prevenção & controle , Obesidade Infantil/terapia , Adolescente , Criança , Pré-Escolar , Dieta , Exercício Físico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The PI3K/AKT/mTOR signaling pathway controls major cellular processes such as cell growth, proliferation and survival. Stimulation of this pathway leads to AKT phosphorylation and activation, resulting in phosphorylation of mTOR and myriad other targets. AKT upregulation has been implicated in thyroid cancer pathogenesis and is a candidate treatment target for patients with advanced disease that has not responded to traditional therapies. Here we evaluate a large series of benign and malignant thyroid tumors for AKT activity and intracellular distribution. We also deplete AKT from multiple thyroid cancer cell lines, including putative cancer stem cell lines, and measure the effect on proliferation and invasion in vitro. We show that active AKT has a predominantly nuclear distribution and its expression is highest in anaplastic thyroid carcinomas and papillary thyroid carcinomas, including encapsulated and invasive follicular variants. Depletion of AKT in thyroid carcinoma cell lines led to greatly reduced proliferative capacity and resulted in a reduction of invasive potential. A reduction in invasion was also observed in the cancer stem cell compartment. Targeting AKT activity in the clinical setting may slow the growth and spread of aggressive thyroid neoplasms, and target the tumor stem cell compartment.
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Proliferação de Células/genética , Invasividade Neoplásica/genética , Proteína Oncogênica v-akt/genética , Neoplasias da Glândula Tireoide/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are well-recognized post-transcriptional regulators of gene expression. This study examines the expression of microRNA-21 (miR-21) and lncRNA MALAT1 in medullary thyroid carcinomas (MTCs) and their effects on tumor behavior. METHODS: Tissue microarrays (TMAs) were constructed using normal thyroid (n=39), primary tumors (N=39) and metastatic MTCs (N=18) from a total of 42 MTC cases diagnosed between 1987 and 2016. In situ hybridization with probes for miR-21 and MALAT1 was performed. PCR quantification of expression was performed in a subset of normal thyroid (N=10) and primary MTCs (N=32). An MTC-derived cell line (MZ-CRC-1) was transfected with small interfering RNAs (siRNAs) targeting miR-21 and MALAT1 to determine the effects on cell proliferation and invasion. RESULTS: In situ hybridization (ISH) showed strong (2+ to 3+) expression of miR-21 in 17 (44%) primary MTCs and strong MALAT1 expression in 37 (95%) primary MTCs. Real-time PCR expression of miR-21 (P<0.001) and MALAT1 (P=0.038) in primary MTCs were significantly higher than in normal thyroid, supporting the ISH findings. Experiments with siRNAs showed inhibition of miR-21 and MALAT1 expression in the MTC-derived cell line, leading to significant decreases in cell proliferation (P<0.05) and invasion (P<0.05). CONCLUSION: There is increased expression of miR-21 and MALAT1 in MTCs. This study also showed an in vitro pro-oncogenic effect of MALAT1 and miR-21 in MTCs. The results suggest that overexpression of miR-21 and MALAT1 may regulate MTC progression.
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Biomarcadores Tumorais/genética , Carcinoma Medular/secundário , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinogênese , Carcinoma Medular/genética , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Células Tumorais Cultivadas , Adulto JovemRESUMO
Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-ß1-induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-ß1-induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression.
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Carcinoma/patologia , Transição Epitelial-Mesenquimal/fisiologia , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/patologia , Animais , Western Blotting , Carcinoma Papilar , Linhagem Celular Tumoral , Progressão da Doença , Citometria de Fluxo , Imunofluorescência , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Câncer Papilífero da Tireoide , Análise Serial de Tecidos , Transfecção , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
This article describes the implementation and evaluation of the chronic-disease self-management (CDSM) program, developed by Stanford University, among Chinese older adults in a metro area of a large Southeastern City of the U.S. The method of Practical Participatory Evaluation through an academic-community partnership between university researchers and local Chinese communities was used to develop the program and assess its applicability in the population. Results suggested that language proficiency, communication, social network and culture of the population were the most influential factors for U.S. Chinese immigrants to attend the CDSM program. The program increased participants' knowledge, skills and confidence in CDSM, whereas its capability in addressing culture differences needed improvement. Knowledge learned in this project was instrumental in implementing similar projects among immigrants.
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Doença Crônica/terapia , Autocuidado , Idoso , China/etnologia , Humanos , Avaliação de Programas e Projetos de Saúde , Estados UnidosRESUMO
Epithelial-mesenchymal transition is an important mechanism of epithelial tumor progression, local invasion and metastasis. The E-cadherin (CDH1) repressor SLUG (SNAI2) and the basic helix-loop-helix transcription factor TWIST1 inhibit CDH1 expression in poorly differentiated malignancies as inducers of epithelial-mesenchymal transition. Epithelial-mesenchymal transition has been implicated in progression from well to poorly differentiated/anaplastic thyroid carcinoma but the expression of SNAI2 and TWIST1 proteins and their phenotypic association in human thyroid cancers has not been extensively studied. We examined the expression of SNAI2, TWIST1 and CDH1 by immunohistochemistry in a panel of well-differentiated and anaplastic thyroid cancers and by qRT-PCR in thyroid cell lines. Ten normal thyroids, 33 follicular adenomas, 56 papillary thyroid carcinomas including 28 follicular variants, 27 follicular carcinomas and 10 anaplastic thyroid carcinomas were assembled on a tissue microarray and immunostained for SNAI2, TWIST1 and CDH1. Most (8/10) anaplastic thyroid carcinomas demonstrated strong nuclear immunoreactivity for SNAI2 with associated absence of CDH1 in 6/8 cases (75%). TWIST1 was expressed in 5/10 anaplastic thyroid carcinomas with absence of CDH1 in 3/5 (60%) cases. These findings were confirmed in whole sections of all anaplastic thyroid carcinomas and in a separate validation set of 10 additional anaplastic thyroid carcinomas. All normal thyroids, follicular adenomas, papillary and follicular thyroid carcinomas were negative for SNAI2 and TWIST1 (P<0.0001) and all showed strong diffuse immunoreactivity for CDH1 (P=0.026). Expression of SNAI2, TWIST1 and CDH1 mRNA varied in a normal thyroid, papillary carcinoma and two anaplastic thyroid carcinoma cell lines tested, but the highest levels of CDH1 mRNA were detected in the normal thyroid cell line while the anaplastic thyroid carcinoma cell line demonstrated the highest levels of SNAI2 and TWIST1 mRNA. Our findings support the role of epithelial-mesenchymal transition in the development of anaplastic thyroid carcinoma.
Assuntos
Carcinoma/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Proteínas Nucleares/biossíntese , Neoplasias da Glândula Tireoide/metabolismo , Fatores de Transcrição/biossíntese , Proteína 1 Relacionada a Twist/biossíntese , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição da Família Snail , Neoplasias da Glândula Tireoide/patologia , Análise Serial de Tecidos , Fatores de Transcrição/análise , Proteína 1 Relacionada a Twist/análise , Adulto JovemRESUMO
In this study, we evaluated sleep quality changes in persons with advanced heart failure (HF) who were admitted to the intensive care unit. Sleep quality was assessed at admission, during hospitalization, and post-discharge. Statistical tests compared within subject mean sleep quality over time (n = 22). Poor quality sleep was reported by 96% of participants at admission, 96% during hospitalization, and 86% post-discharge. Significant differences were found between timepoints in global sleep quality, subject sleep quality, sleep duration, and habitual sleep efficiency. A greater proportion of these participants had poor global sleep quality during hospitalization than previously reported. Participants reported better sleep post-discharge than admission and during hospitalization. Interventions enhancing hospital sleep, along with home sleep self-management education, would improve HF outcomes. Implementation science methods are warranted to integrate efficacious interventions in this population.
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Insuficiência Cardíaca , Distúrbios do Início e da Manutenção do Sono , Humanos , Qualidade do Sono , Alta do Paciente , Assistência ao Convalescente , Sono , Unidades de Terapia Intensiva , Insuficiência Cardíaca/terapiaRESUMO
AIMS: Social determinants of health (SDOH) influence cardiovascular health in the general population; however, the degree to which this occurs in individuals with type 1 diabetes (T1D) is not well understood. We evaluated associations among socioeconomic deprivation and cardiometabolic risk factors (hemoglobin A1c, low-density lipoprotein, blood pressure, body mass index, physical activity) in individuals with T1D from the T1D Clinic Exchange Registry. METHODS: We evaluated the association between the social deprivation index (SDI) and cardiometabolic risk factors using multivariable and logistic regression among 18,754 participants ages 13 - 90 years (mean 29.2 ± 17) in the T1D Exchange clinic registry from 6,320 zip code tabulation areas (2007-2017). RESULTS: SDI was associated with multiple cardiometabolic risk factors even after adjusting for covariates (age, biological sex, T1D duration, and race/ethnicity) in the multivariable linear regression models. Those in the highest socially deprived areas had 1.69 (unadjusted) and 1.78 (adjusted) times odds of a triple concomitant risk burden of poor glycemia, dyslipidemia, and hypertension. CONCLUSIONS: Persistent SDOH differences could account for a substantial degree of poor achievement of cardiometabolic targets in individuals with T1D. Our results suggest the need for a broader framework to understand the association between T1D and adverse cardiometabolic outcomes.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Fatores de Risco Cardiometabólico , Fatores Socioeconômicos , Sistema de Registros , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Fatores de RiscoRESUMO
The purpose of this study was to identify facilitators and barriers for engaging youth and families from a historically and systematically marginalized community in high-tech research. Adapting community-based participatory research principles, 4 focus groups were conducted with 13 youth and 12 parents. Using codebook thematic analysis, 5 facilitator themes (develop skills, ensure health, build understanding, promote safety, and help others, youth-initiated interest) and 4 barrier themes (anxiety and fear, skepticism, confusion, and unfamiliar/unknown experience) were identified. Youth and parent responses informed proposed guidelines for recruiting and engaging families in research using high-tech methods, particularly those from historically and systematically marginalized communities.