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BACKGROUND: Type 2 diabetes has economic implications involving family income and out-of-pocket spending. OBJECTIVE: Determine family out-of-pocket expenditure for type 2 diabetes mellitus care and percentage of family income. MATERIAL AND METHODS: Study of family out-of-pocket spending in families with patients with type 2 diabetes treated at primary care level. Out-of-pocket expenses included expenses for transportation, food-drinks, and external medications. Family income corresponded to the total economic income contributed by family members. The percentage of out-of-pocket spending in relation to family income was identified with the relationship between these two variables. Statistical analysis included averages and percentages. RESULTS: The annual family out-of-pocket expenditure on transportation was $2,621.24, the family out-of-pocket expenditure on food and beverages was $1,075.67, and the family out-of-pocket expenditure on external medications was $722.08. The total annual family out-of-pocket expense was $4,418.89 and corresponds to 4.73% of family income. CONCLUSION: The family out-of-pocket expense in the family with a patient with diabetes mellitus 2 was $4,418.89 and represents 4.73% of the family income.
ANTECEDENTES: La diabetes tipo 2 tiene implicaciones económicas en el ingreso familiar y el gasto de bolsillo. OBJETIVO: Determinar el gasto de bolsillo familiar en la atención de la diabetes mellitus tipo 2 y el porcentaje que representa en el ingreso familiar. MATERIAL Y MÉTODOS: Estudio de gasto de bolsillo de las familias con pacientes con diabetes tipo 2 atendidos en el primer nivel de atención. El gasto de bolsillo familiar incluyó gasto en traslado, alimentos-bebidas y medicamentos externos. El ingreso familiar correspondió al total de ingresos económicos aportados por los miembros de la familia. El porcentaje del gasto de bolsillo con relación al ingreso familiar se identificó con la relación entre estas dos variables. El análisis estadístico incluyó promedios y porcentajes. RESULTADOS: El gasto de bolsillo familiar anual en transporte fue de $2621.24, en alimentos y bebidas fue de $1075.67 y en medicamentos externos fue de $722.08. El gasto familiar de bolsillo total anual fue de $4418.89 y correspondió a 4.73 % del ingreso familiar. CONCLUSIÓN: El gasto de bolsillo en las familias con un paciente con diabetes mellitus tipo 2 fue de $4418.89 y representó 4.73 % del ingreso familiar.
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Diabetes Mellitus Tipo 2 , Gastos em Saúde , Renda , Humanos , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/terapia , Gastos em Saúde/estatística & dados numéricos , Masculino , Feminino , Atenção Primária à Saúde/economia , Pessoa de Meia-Idade , Família , Efeitos Psicossociais da DoençaRESUMO
[This corrects the article on p. 1275 in vol. 12, PMID: 32355541.].
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The assessment of the strength and muscle mass of the hand-finger segment are reliable indicators of health and predictors of cardiometabolic risk in the adult population. However, there are no valid and reliable tests to assess the muscle power of this segment in healthy adolescents. The objective of this study was to determine the validity and inter-day reliability of a grip power test (GripW test) in healthy adolescents. Twenty-one adolescents (15.61 ± 2.20 years old) were part of the study. All participants were instructed to perform a grip with incremental load sets from 1-10 kg as fast as possible. The validity of the GripW test was determined with the load-power curve and linear regression equation. Inter-day reliability considered the coefficient of variation (CV), intra-class correlation coefficient (ICC), and standard error of the mean (SEM). The significance level for all statistical analyses was p < 0.05. The parabola in the load-power curve for both hands showed normality for the GripW test. In addition, the analysis showed a CV = 4.63% and ICC = 1.00 for the right hand, while the left hand showed a CV = 3.23% and ICC = 1.00. The GripW test proved to be valid and reliable for assessing gripping muscle power functionally and unilaterally in healthy adolescents.
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Força da Mão/fisiologia , Músculo Esquelético/fisiologia , Adolescente , Saúde do Adolescente , Feminino , Humanos , Masculino , Dinamômetro de Força Muscular , Equipamentos Ortopédicos , Reprodutibilidade dos TestesRESUMO
Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2-4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7-10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)-a secreted glycoprotein aberrantly abundant in different cancers-as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors.
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Antineoplásicos/uso terapêutico , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Lipocalina-2/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/patologia , Lipocalina-2/genética , Células MCF-7 , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêuticoRESUMO
Objective: To compare prenatal attachment in women hospitalised due to high-risk pregnancy with prenatal attachment in non-hospitalised patients. To describe the impact of social support, socio-demographic factors and the nature of the pregnancy on prenatal attachment, anxiety and depression. Study Design: An exploratory, cross-sectional and descriptive study utilising the Maternal Antenatal Attachment Scale, the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. The sample comprised 80 hospitalised and 88 non-hospitalised patients. Result: No difference in prenatal attachment was found between the two groups. The hospitalised group presented higher levels of depressive symptomatology and anxiety. Social support had a significant effect on the hospitalised group, improving attachment quality. Conclusion: Incorporation of members of the patient's support network may help to improve quality of prenatal attachment during hospitalisation. Detection and treatment of anxiety and/or depression in hospitalised patients is recommended given their impact on the mental health of mother and baby.
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Depressão Pós-Parto/diagnóstico , Hospitalização , Relações Mãe-Filho/psicologia , Apego ao Objeto , Gravidez de Alto Risco/psicologia , Adolescente , Adulto , Ansiedade/diagnóstico , Ansiedade/psicologia , Estudos Transversais , Depressão/complicações , Depressão/diagnóstico , Depressão Pós-Parto/complicações , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Escalas de Graduação Psiquiátrica , Apoio Social , Adulto JovemRESUMO
Lipocalin-2 (LCN2) is a secreted glycoprotein linked to several physiological roles, including transporting hydrophobic ligands across cell membranes, modulating immune responses, maintaining iron homeostasis, and promoting epithelial cell differentiation. Although LNC2 is expressed at low levels in most human tissues, it is abundant in aggressive subtypes of cancer, including breast, pancreas, thyroid, ovarian, colon, and bile duct cancers. High levels of LCN2 have been associated with increased cell proliferation, angiogenesis, cell invasion, and metastasis. Moreover, LCN2 modulates the degradation, allosteric events, and enzymatic activity of matrix metalloprotease-9, a metalloprotease that promotes tumor cell invasion and metastasis. Hence, LCN2 has emerged as a potential therapeutic target against many cancer types. This review summarizes the most relevant findings regarding the expression, biological roles, and regulation of LCN2, as well as the proteins LCN2 interacts with in cancer. We also discuss the approaches to targeting LCN2 for cancer treatment that are currently under investigation, including the use of interference RNAs, antibodies, and gene editing.
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Lipocalina-2/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias/metabolismo , Regulação para Cima , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Proliferação de Células , Edição de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipocalina-2/antagonistas & inibidores , Terapia de Alvo Molecular , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/tratamento farmacológico , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Regulação para Cima/efeitos dos fármacosRESUMO
INTRODUCTION: Glioblastoma (GBM) is the most common and lethal of the central nervous system (CNS) malignancies. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Thus, targeting dysregulated miRNAs with RNA oligonucleotides (RNA interference, RNAi) has been proposed for GBM treatment. Despite promising results in the laboratory, RNA oligonucleotides have clinical limitations that include poor RNA stability and off-target effects. RNAi therapies against GBM confront an additional obstacle, as they need to cross the blood-brain barrier (BBB). METHODS: Here, we developed gold-liposome nanoparticles conjugated with the brain targeting peptides apolipoprotein E (ApoE) and rabies virus glycoprotein (RVG). First, we functionalized gold nanoparticles with oligonucleotide miRNA inhibitors (OMIs), creating spherical nucleic acids (SNAs). Next, we encapsulated SNAs into ApoE, or RVG-conjugated liposomes, to obtain SNA-Liposome-ApoE and SNA-Liposome-RVG, respectively. We characterized each nanoparticle in terms of their size, charge, encapsulation efficiency, and delivery efficiency into U87 GBM cells in vitro. Then, they were administered intravenously (iv) in GBM syngeneic mice to evaluate their delivery efficiency to brain tumor tissue. RESULTS: SNA-Liposomes of about 30-50 nm in diameter internalized U87 GBM cells and inhibited the expression of miRNA-92b, an aberrantly overexpressed miRNA in GBM cell lines and GBM tumors. Conjugating SNA-Liposomes with ApoE or RVG peptides increased their systemic delivery to the brain tumors of GBM syngeneic mice. SNA-Liposome-ApoE demonstrated to accumulate at higher extension in brain tumor tissues, when compared with non-treated controls, SNA-Liposomes, or SNA-Liposome-RVG. DISCUSSION: SNA-Liposome-ApoE has the potential to advance the translation of miRNA-based therapies for GBM as well as other CNS disorders.
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Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Lipossomos/administração & dosagem , Interferência de RNA , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Técnicas de Transferência de Genes , Glioblastoma/genética , Glioblastoma/patologia , Ouro/química , Humanos , Lipossomos/química , Masculino , Nanopartículas Metálicas/química , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Ácidos Nucleicos/química , Oligonucleotídeos/química , Oligonucleotídeos/genética , Oligonucleotídeos/farmacocinética , Proteínas do Envelope Viral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop a platinum-resistant disease with a poor overall prognosis. The molecular events leading to the cisplatin resistance of ovarian cancer cells are not fully understood. Here, we performed a proteomic analysis to identify protein candidates deregulated in a cisplatin-resistant ovarian cancer cell line (A2780CP20) in comparison to their sensitive counterpart (A2780). Forty-eight proteins were differentially abundant in A2780CP20, as compared with A2780, cells. Enolase-1 (ENO1) was significantly decreased in cisplatin-resistant ovarian cancer cells. Western blots and RT-PCR confirmed our findings. Ectopic ENO1 expression increased the sensitivity of ovarian cancer cells to cisplatin treatment. In contrast, small-interfering (siRNA)-based ENO1 silencing in A2780 cells reduced the sensitivity of these cells to cisplatin treatment. Whereas glucose consumption was lower, intracellular levels were higher in cisplatin-resistant ovarian cancer cells as compared with their cisplatin-sensitive counterparts. Senescence-associated ß-galactosidase (ß-Gal) levels were higher in cisplatin-resistant ovarian cancer cells as compared with cisplatin-sensitive ovarian cancer cells. ß-Gal levels were decreased in ENO1 overexpressed clones. Protein levels of the cell cycle regulators and senescence markers p21 and p53 showed opposite expression patterns in cisplatin-resistant compared with cisplatin sensitive cells. Our studies suggest that decreased expression of ENO1 promotes glucose accumulation, induces senescence, and leads to cisplatin resistance of ovarian cancer cells.
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Cumulating evidence indicates that dysregulation of microRNAs (miRNAs) plays a central role in the initiation, progression, and drug resistance of cancer cells. However, the specific miRNAs contributing to drug resistance in ovarian cancer cells have not been fully elucidated. Aimed to identify potential miRNAs involved in platinum resistance, we performed a miRNA expression profile in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells, and we found several differentially abundant miRNAs in the pair of cell lines. Notably, miR-18a-5p (miR-18a), a member of the oncogenic associated miR-17-92 cluster, was decreased in cisplatin-resistant as compared with cisplatin-sensitive cells. Real-time PCR analysis confirmed these findings. We then studied the biological, molecular, and therapeutic consequences of increasing the miR-18a levels with oligonucleotide microRNA mimics (OMM). Compared with a negative control OMM, transient transfection of a miR-18a-OMM reduced cell growth, cell proliferation, and cell invasion. Intraperitoneal injections of miR-18a-OMM-loaded folate-conjugated liposomes significantly reduced the tumor weight and the number of nodules in ovarian cancer-bearing mice when compared with a control-OMM group. Survival analysis using the Kaplan-Meier plotter database showed that ovarian cancer patients with high miR-18a levels live longer in comparison to patients with lower miR-18a levels. Bioinformatic analyses, real-time-PCR, Western blots, and luciferase reporter assays revealed that Matrix Metalloproteinase-3 (MMP-3) is a direct target of miR-18a. Small-interfering RNA (siRNA)-mediated silencing of MMP-3 reduced cell viability, cell growth, and the invasiveness potential of cisplatin-resistant ovarian cancer cells. Our study suggests that targeting miR-18a is a plausible therapeutic strategy for cisplatin-resistant ovarian cancer.
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Background Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.