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1.
Qual Life Res ; 33(1): 219-227, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37582819

ABSTRACT

PURPOSE: This study aimed to evaluate the association of oral health literacy (OHL) and oral health-related quality of life (OHRQoL) of pregnant women. METHODS: This cross-sectional study evaluated a representative sample of pregnant women assisted in public health services in southern Brazil. Demographic, socioeconomic, psychosocial and behavioural data were collected through structured questionnaires. The Oral Health Impact Profile (OHIP-14) questionnaire was used to evaluate the OHRQoL. The Brazilian Rapid Estimate of Adult Literacy in Dentistry (BREALD-30) was used to measure OHL. Dental caries and gingival bleeding were evaluated by clinical examinations. Adjusted multilevel Poisson regression models with a hierarchical approach were used to assess the associations. The results are presented as rate ratio (RR) and 95% confidence interval (95% CI). RESULTS: A total of 520 pregnant women were evaluated. Pregnant women with lower levels of OHL presented overall OHIP-14 scores 14% higher (RR 1.14; 95% CI 1.07-1.22) than their counterparts. High household income and high education level were related to low overall OHIP-14 scores. Furthermore, less dental attendance, low social support, untreated dental caries and gingival bleeding were also associated with high overall OHIP-14 scores. CONCLUSION: Our findings reinforce that health literacy levels influence patient-reported outcomes. Pregnant women with lower OHL were more likely to present poorer OHRQoL.


Subject(s)
Dental Caries , Health Literacy , Adult , Humans , Female , Pregnancy , Oral Health , Pregnant Women , Quality of Life/psychology , Cross-Sectional Studies , Surveys and Questionnaires , Brazil
2.
Sci Rep ; 12(1): 12172, 2022 07 16.
Article in English | MEDLINE | ID: mdl-35842494

ABSTRACT

Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained by a complex cytoskeleton, which becomes disrupted in glomerular disease resulting in defective filtration and albuminuria. Lack of endogenous thymosin ß4 (TB4), an actin sequestering peptide, exacerbates glomerular injury and disrupts the organisation of the podocyte actin cytoskeleton, however, the potential of exogenous TB4 therapy to improve podocyte injury is unknown. Here, we have used Adriamycin (ADR), a toxin which injures podocytes and damages the glomerular filtration barrier leading to albuminuria in mice. Through interrogating single-cell RNA-sequencing data of isolated glomeruli we demonstrate that ADR injury results in reduced levels of podocyte TB4. Administration of an adeno-associated viral vector encoding TB4 increased the circulating level of TB4 and prevented ADR-induced podocyte loss and albuminuria. ADR injury was associated with disorganisation of the podocyte actin cytoskeleton in vitro, which was ameliorated by treatment with exogenous TB4. Collectively, we propose that systemic gene therapy with TB4 prevents podocyte injury and maintains glomerular filtration via protection of the podocyte cytoskeleton thus presenting a novel treatment strategy for glomerular disease.


Subject(s)
Kidney Diseases , Podocytes , Albuminuria , Animals , Cells, Cultured , Doxorubicin , Genetic Therapy , Kidney Glomerulus , Mice , Thymosin
3.
J Am Soc Nephrol ; 30(1): 33-49, 2019 01.
Article in English | MEDLINE | ID: mdl-30530834

ABSTRACT

BACKGROUND: During kidney fibrosis, a hallmark and promoter of CKD (regardless of the underlying renal disorder leading to CKD), the extracellular-regulated kinase 1/2 (ERK1/2) pathway, is activated and has been implicated in the detrimental differentiation and expansion of kidney fibroblasts. An ERK1/2 pathway inhibitor, trametinib, is currently used in the treatment of melanoma, but its efficacy in the setting of CKD and renal fibrosis has not been explored. METHODS: We investigated whether trametinib has antifibrotic effects in two mouse models of renal fibrosis-mice subjected to unilateral ureteral obstruction (UUO) or fed an adenine-rich diet-as well as in cultured primary human fibroblasts. We also used immunoblot analysis, immunohistochemical staining, and other tools to study underlying molecular mechanisms for antifibrotic effects. RESULTS: Trametinib significantly attenuated collagen deposition and myofibroblast differentiation and expansion in UUO and adenine-fed mice. We also discovered that in injured kidneys, inhibition of the ERK1/2 pathway by trametinib ameliorated mammalian target of rapamycin complex 1 (mTORC1) activation, another key profibrotic signaling pathway. Trametinib also inhibited the ERK1/2 pathway in cultured primary human renal fibroblasts stimulated by application of TGF-ß1, the major profibrotic cytokine, thereby suppressing downstream mTORC1 pathway activation. Additionally, trametinib reduced the expression of myofibroblast marker α-smooth muscle actin and the proliferation of renal fibroblasts, corroborating our in vivo data. Crucially, trametinib also significantly ameliorated renal fibrosis progression when administered to animals subsequent to myofibroblast activation. CONCLUSIONS: Further study of trametinib as a potential candidate for the treatment of chronic renal fibrotic diseases of diverse etiologies is warranted.


Subject(s)
Extracellular Signal-Regulated MAP Kinases/drug effects , Mechanistic Target of Rapamycin Complex 1/drug effects , Pyridones/pharmacology , Pyrimidinones/pharmacology , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/pathology , Signal Transduction/drug effects , Animals , Biopsy, Needle , Cells, Cultured , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/genetics , Fibroblasts/drug effects , Fibrosis/drug therapy , Fibrosis/pathology , Immunohistochemistry , Mechanistic Target of Rapamycin Complex 1/genetics , Mice , Molecular Targeted Therapy/methods , Random Allocation , Reference Values , Renal Insufficiency, Chronic/genetics , Signal Transduction/genetics
4.
J Pathol ; 246(4): 485-496, 2018 12.
Article in English | MEDLINE | ID: mdl-30125361

ABSTRACT

Planar cell polarity (PCP) pathways control the orientation and alignment of epithelial cells within tissues. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the normal differentiation of kidney glomeruli and tubules. Vangl2 has also been implicated in modifying the course of acquired glomerular disease, and here, we further explored how Vangl2 impacts on glomerular pathobiology in this context. Targeted genetic deletion of Vangl2 in mouse glomerular epithelial podocytes enhanced the severity of not only irreversible accelerated nephrotoxic nephritis but also lipopolysaccharide-induced reversible glomerular damage. In each proteinuric model, genetic deletion of Vangl2 in podocytes was associated with an increased ratio of active-MMP9 to inactive MMP9, an enzyme involved in tissue remodelling. In addition, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in the glomeruli of individuals with focal segmental glomerulosclerosis, suggesting that the molecule may also be involved in certain human glomerular diseases. These observations support the conclusion that Vangl2 modulates glomerular injury, at least in part by acting as a brake on MMP9, a potentially harmful endogenous enzyme. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Subject(s)
Cell Polarity , Glomerulosclerosis, Focal Segmental/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Kidney Glomerulus/metabolism , Membrane Proteins/metabolism , Nephrosis, Lipoid/metabolism , Nerve Tissue Proteins/metabolism , Podocytes/metabolism , Adult , Animals , Case-Control Studies , Cells, Cultured , Disease Models, Animal , Enzyme Activation , Female , Glomerulosclerosis, Focal Segmental/genetics , Glomerulosclerosis, Focal Segmental/pathology , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Intracellular Signaling Peptides and Proteins/genetics , Kidney Glomerulus/pathology , Kidney Glomerulus/physiopathology , Male , Matrix Metalloproteinase 9/metabolism , Membrane Proteins/genetics , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Nephrosis, Lipoid/genetics , Nephrosis, Lipoid/pathology , Nephrosis, Lipoid/physiopathology , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/genetics , Podocytes/pathology , Signal Transduction , Young Adult
5.
Ciênc. cogn ; 14(2): 166-193, jul. 2009. ilus
Article in Portuguese | Index Psychology - journals | ID: psi-53716

ABSTRACT

A existência de poucos relatos de tentativas de promoção da aprendizagem significativa de Ausubel na Educação Tecnológica e a busca de uma formação cidadã integrada à de um técnico motivaram o projeto apresentado neste trabalho. Para tentar alcançar estes objetivos foram usadas duas ferramentas baseadas na teoria de Ausubel: mapas conceituais e diagramas V. Os mapas conceituais foram utilizados como organizadores de conhecimento e para avaliação das aprendizagens e os diagramas V para potencializar as aulas de laboratório didático. O projeto ocorreu com alunos do campus Araranguá do Instituto Federal de Educação, Ciência e Tecnologia de Santa Catarina em um curso da área do vestuário de nível pós-médio. Para acompanhar o desempenho dos alunos, e o quanto eles alcançavam a aprendizagem significativa, foram desenvolvidos protocolos de avaliação de mapas conceituais e diagramas V, que, junto com a explicação dos alunos, constituíam no instrumento de avaliação do projeto. Os resultados apontam que enquanto tomavam contato com as ferramentas, seus mapas conceituais e diagramas V fizeram crer em uma evolução gradual na estrutura cognitiva dos alunos em direção à aprendizagem significativa dos temas discutidos. Como asserção de valor deste estudo, podemos expor que a expectativa expressa na missão do IF-SC, de formar indivíduos capazes de exercer sua cidadania além de sua profissão, pode ser alcançada através da aprendizagem significativa, com o auxílio das ferramentas construídas para isso: os mapas conceituais e os diagramas V(AU)


Considering the very small amount of narrated attempts to promote meaningful learning, as Ausubel defined, this study aims to determine whether it is possible to implement, in technical high school courses from IF-SC (Campus Araranguá), strategies that facilitate this kind of learning. This study aims to determine whether it is possible to implement, in technical highschool courses from IF-SC (Campus-Araranguá), strategies that facilitate meaningful learning, as Ausubel defined it. The methodology employed was to use two well known tools which try to make this kind of learning viable: concepual maps and V diagram. The first one is used in order to organize knowledge and assessment of students and the second to boost the classes of laboratory teaching. The project involved students from a technical highschool course in clothing from IF-SC. Results indicate that as the students get in touch with these tools, their analysis suggest a gradual evolution in their cognitive structure towards meaningful learning of the issues discussed. As the value proposition of this study, we can point out that the expectation expressed in the mission of IF-SC, which is to train individuals capable of exercising their citizenship in addition to their profession, can be provided through meaningful learning, which in turn can be implemented through two tools built to achieve this type of learning: conceptual maps and V diagram(AU)

6.
Cienc. cogn ; 14(2): 166-193, jul. 31, 2009. ilus
Article in Portuguese | Index Psychology - journals | ID: psi-58884

ABSTRACT

A existência de poucos relatos de tentativas de promoção da aprendizagem significativa de Ausubel na Educação Tecnológica e a busca de uma formação cidadã integrada à de um técnico motivaram o projeto apresentado neste trabalho. Para tentar alcançar estes objetivos foram usadas duas ferramentas baseadas na teoria de Ausubel: mapas conceituais e diagramas V. Os mapas conceituais foram utilizados como organizadores de conhecimento e para avaliação das aprendizagens e os diagramas V para potencializar as aulas de laboratório didático. O projeto ocorreu com alunos do campus Araranguá do Instituto Federal de Educação, Ciência e Tecnologia de Santa Catarina em um curso da área do vestuário de nível pós-médio. Para acompanhar o desempenho dos alunos, e o quanto eles alcançavam a aprendizagem significativa, foram desenvolvidos protocolos de avaliação de mapas conceituais e diagramas V, que, junto com a explicação dos alunos, constituíam no instrumento de avaliação do projeto. Os resultados apontam que enquanto tomavam contato com as ferramentas, seus mapas conceituais e diagramas V fizeram crer em uma evolução gradual na estrutura cognitiva dos alunos em direção à aprendizagem significativa dos temas discutidos. Como asserção de valor deste estudo, podemos expor que a expectativa expressa na missão do IF-SC, de formar indivíduos capazes de exercer sua cidadania além de sua profissão, pode ser alcançada através da aprendizagem significativa, com o auxílio das ferramentas construídas para isso: os mapas conceituais e os diagramas V.


Subject(s)
Cognition
7.
BMC Genomics ; 8: 19, 2007 Jan 17.
Article in English | MEDLINE | ID: mdl-17233888

ABSTRACT

BACKGROUND: Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. Defects in them and their associated proteins cause a range of neuromuscular disorders. Members of this superfamily have been discovered in a relatively serendipitous way; we set out to compile a comprehensive description of dystrophin- and dystrobrevin-related sequences from available metazoan genome sequences, validated in representative organisms by RT-PCR, or acquired de novo from key species. RESULTS: Features of the superfamily revealed by our survey include: a) Dystrotelin, an entirely novel branch of the superfamily, present in most vertebrates examined. Dystrotelin is expressed in the central nervous system, and is a possible orthologue of Drosophila DAH. We describe the preliminary characterisation of its function, evolution and expression. b) A novel vertebrate member of the dystrobrevin family, gamma-dystrobrevin, an ancient branch now extant only in fish, but probably present in our own ancestors. Like dystrophin, zebrafish gamma-dystrobrevin mRNA is localised to myosepta. c) The extent of conservation of alternative splicing and alternative promoter use in the dystrophin and dystrobrevin genes; alternative splicing of dystrophin exons 73 and 78 and alpha-dystrobrevin exon 13 are conserved across vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C-terminally truncated common ancestor of dystrophin and utrophin in cyclostomes. f) A severely restricted repertoire of dystrophin complex components in ascidians. CONCLUSION: We have refined our understanding of the evolutionary history and isoform diversity of the five previously reported vertebrate superfamily members and describe two novel members, dystrotelin and gamma-dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally related to each other. Vertebrates therefore have a repertoire of seven superfamily members (three dystrophins, three dystrobevins, and one dystrotelin), with one lost in tetrapods. Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology.


Subject(s)
Drosophila Proteins/chemistry , Dystrophin-Associated Proteins/chemistry , Dystrophin/chemistry , Membrane Proteins/chemistry , Protein Isoforms , Amino Acid Sequence , Animals , Drosophila , Dystrophin/genetics , Expressed Sequence Tags , Humans , Mice , Molecular Sequence Data , Multigene Family , Promoter Regions, Genetic , Sequence Homology, Amino Acid , Zebrafish
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