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1.
Adv Health Sci Educ Theory Pract ; 29(1): 217-243, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37382856

RESUMO

In 2019-2021, we engaged in a project aimed at developing, implementing, and evaluating an educational intervention actively involving patient-teachers in undergraduate medical education at Université Laval, Quebec, Canada. Patient-teachers were invited to participate in small group discussion workshops during which medical students deliberate on legal, ethical, and moral issues arising from medical practice. Patients were expected to bring other perspectives, based on their experience with illness and the healthcare system. Little is still known about patients' perspectives on their participation experience in such context. Informed by critical theory, our qualitative study aims to document,: (i) the motivating factors for patients' participation in our intervention; and (ii) what patients gained from the experience. Data collection was based on 10 semi-structured interviews with patient-teachers. A thematic analysis was conducted using NVivo software. Motivators for participation arose from: (i) perceived consistency between patients' individual characteristics and those of the project, and (ii) conceiving the project as a means to reach individual and social goals. What patients gained mainly refers to (1) the appreciation of a positive, enriching, motivating yet uncomfortable and destabilizing experience; (2) a deconstruction of biases against the medical field and critical thinking about their own experience; (3) new knowledge, with a potential impact on their future interactions with the healthcare system. Results reveal patients as non-neutral thinking and knowing subjects, engaged in the participation experience as active teachers and learners. They also highlight the empowering and emancipatory nature of the learning gained through patients' participation experience. These conclusions prompt us to promote transformative interventional approaches that question the pervasive power issues in medical teaching and value patients' specific knowledge in teaching and learning the Art of Medicine.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Humanos , Motivação , Pesquisa Qualitativa , Educação de Graduação em Medicina/métodos , Participação do Paciente , Ensino
2.
Can Med Educ J ; 14(4): 47-69, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37719397

RESUMO

Background: To train physicians who will respond to patients' evolving needs and expectations, medical schools must seek educational strategies to foster the development of non-technical competencies in students. This article aims to synthetize studies that focus on patient engagement in medical training as a promising strategy to foster the development of those competencies. Methods: We conducted a rapid review of the literature to synthetize primary quantitative, qualitative and mixed studies (January 2000-January 2022) describing patient engagement interventions in medical education and reporting non-technical learning outcomes. Studies were extracted from Medline and ERIC. Two independent reviewers were involved in study selection and data extraction. A narrative synthesis of results was performed. Results: Of the 3875 identified, 24 met the inclusion criteria and were retained. We found evidence of a range of non-technical educational outcomes (e. g. attitudinal changes, new knowledge and understanding). Studies also described various approaches regarding patient recruitment, preparation, and support and participation design (e.g., contact duration, learning environment, patient autonomy, and format). Some emerging practical suggestions are proposed. Conclusion: Our results suggest that patient engagement in medical education can be a valuable means to foster a range of non-technical competencies, as well as formative and critical reflexivity. They also suggest conditions under which patient engagement practices can be more efficient in fostering non-instrumental patient roles in different educational contexts. This supports a plea for sensible and responsive interventional approaches.


Contexte: Pour former des médecins aptes à répondre aux besoins et attentes évolutifs des patients, les facultés de médecine doivent trouver des stratégies éducatives pour stimuler le développement de compétences non techniques chez les étudiants. Cet article vise à synthétiser les études qui traitent de la participation des patients à la formation médicale comme stratégie prometteuse pour favoriser le développement de ces compétences. Méthodes: Nous avons effectué une revue rapide de la littérature pour synthétiser les études primaires quantitatives, qualitatives et mixtes (janvier 2000-janvier 2022) qui décrivent des interventions visant l'engagement des patients dans la formation médicale et qui font état de résultats d'apprentissage non technique. Les études ont été extraites de Medline et d'ERIC. Deux examinateurs indépendants ont participé à la sélection des études et à l'extraction des données. Une synthèse narrative des résultats est présentée. Résultats: Parmi les 3875 études recensées, 24 répondaient aux critères d'inclusion et ont été retenues. Ces études font état d'apprentissages non techniques (par exemple, des changements d'attitude, des compréhensions et connaissances nouvelles). Les études décrivent également diverses approches de recrutement et de préparation des patients, et diverses manières de concevoir leur participation (par exemple, la durée du contact, l'environnement d'apprentissage, l'autonomie du patient et le format) et le soutien pédagogique qui en découle. Quelques suggestions pratiques émergentes sont proposées. Conclusion: D'après nos résultats, l'engagement du patient dans l'éducation médicale constitue une avenue prometteuse pour favoriser le développement d'une panoplie de compétences non techniques, tout comme la réflexivité formative et critique des étudiants. Ils indiquent également certaines conditions et contextes éducatifs qui favorisent la participation non instrumentale des patients. Il s'agit d'un plaidoyer en faveur d'interventions éducatives centrées sur les besoins et préoccupations des acteurs impliqués et sur les particularités des contextes locaux.


Assuntos
Educação Médica , Participação do Paciente , Humanos , Escolaridade , Conhecimento , Aprendizagem
3.
Can J Occup Ther ; 90(4): 384-394, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36935619

RESUMO

Background. Current state of knowledge regarding occupational therapy's contribution to chronic pain (CP) management has evolved over the past decade. Yet, has this been transferred to clinical practice? Purpose. Describe the current state of practice of CP management-specific occupational therapy. Method. An online survey was sent to occupational therapists working with CP patients. Findings. Of the 90 respondents (11.9%), 42.2% worked in primary care and 52.2% in secondary care. They reported that their primary role aimed at enabling occupation and providing vocational rehabilitation. The Canadian Model of Occupational Performance and Engagement (CMOP-E) (87.8%), semi-structured interview (86.7%), and education on energy conservation (65.6%) and postural hygiene (60.0%) were the most frequently reported conceptual model, assessment, and intervention methods. Implications. Results illustrate the diversity of current occupational therapy practice in CP management and suggest opportunities for improvement to ensure best practices are adopted, by emphasizing an occupation-based vision of health and well-being.


Assuntos
Dor Crônica , Terapia Ocupacional , Humanos , Terapeutas Ocupacionais , Dor Crônica/terapia , Canadá , Reabilitação Vocacional
4.
J Geriatr Phys Ther ; 45(1): 34-49, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34928239

RESUMO

BACKGROUND AND PURPOSE: Musculoskeletal disorders (MSKDs) are the most common causes of disabilities for older adults. The aim of this systematic review and meta-analysis is to assess the effectiveness of multimodal interventions including exercise rehabilitation for older adults with chronic MSKDs. METHODS: A literature search was conducted up to February 2019 in 5 bibliographical databases to identify randomized controlled trials (RCTs) that compared multimodal interventions including exercise rehabilitation with usual medical care or no intervention. Randomized controlled trials were assessed with the Cochrane risk-of-bias tool. Meta-analyses were performed and pooled mean differences (MDs) or standardized mean differences (SMDs) were calculated. RESULTS: Sixteen RCTs (n = 2322 participants) were included. One RCT was considered at low risk of bias, 8 had some concerns of bias, and 7 had a high risk of bias. Participants suffered from hip or knee osteoarthritis (OA) (n = 12 RCTs), low back pain (LBP) (n = 2 RCTs) and generalized chronic pain (GCP) (n = 2 RCTs). Multimodal interventions were significantly more effective than usual care to decrease pain (visual analog scale, out of 10 points) in the short term, MD: -0.71 (95% confidence interval [CI] -1.08 to -0.34, n = 900), and in the long term: MD: -0.52 (95% CI -0.98 to -0.05, n = 575), but these differences are not considered clinically important. In terms of disabilities, multimodal interventions were also significantly more effective than usual care. The SMDs were -0.47 (95% CI -0.61 to -0.34, n = 903) and -0.29 (95% CI -0.46 to -0.13, n = 568) for OA trials in the short and long terms, respectively, and -0.47 (95% CI -0.81 to -0.12, n = 211) for LBP and GCP trials in the short term. The magnitude of these effects may be considered as small to moderate. CONCLUSION: Multimodal intervention including exercise rehabilitation combined with usual medical care is an efficacious therapeutic option to reduce disabilities in older adults with chronic MSKDs. A significant but not clinically important effect was observed for pain. The most beneficial component of the multimodal interventions in terms of education, exercises, or medication remains to be determined.


Assuntos
Dor Crônica , Dor Lombar , Dor Musculoesquelética , Idoso , Dor Crônica/terapia , Terapia por Exercício , Humanos , Dor Lombar/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Eur J Cancer ; 145: 221-229, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33516050

RESUMO

BACKGROUND: The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. METHODS: This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). RESULTS: Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28-0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25-0.64). Median PFS was 13.0 months (95% CI: 5.0-not reached) with high-TIL versus 2.2 months (95% CI: 1.7-3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2-not reached) versus 8.4 months (95% CI: 5.0-11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P < .0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9-6.7) and 11.7 months (95% CI: 9.3-13.0), respectively, with no association with TILs. CONCLUSIONS: High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos do Interstício Tumoral/imunologia , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , França , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Imunoterapia/mortalidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo
6.
MedEdPublish (2016) ; 10: 103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-38486589

RESUMO

This article was migrated. The article was marked as recommended. Epistemic injustices are defined as power inequalities in the access, recognition and production of knowledge. Their persistence in medical education, especially to the detriment of patients and their specific knowledge, has been documented by several authors. Patient engagement is a new paradigm that involves fostering meaningful patient collaboration at different levels of the healthcare system. Since it is fundamentally based on the recognition of the value and relevance of patients' experiential knowledge, patient engagement in medical education is generally recognized as a desirable strategy to address epistemic injustices in the field. Patient engagement is challenged in the context of COVID-19 where most Canadian medical schools have had to quickly modify their teaching models, stop in-person classes and redirect most activities online. This article presents a critical reflection on the issues raised by COVID-constrained teaching strategies and their impact on epistemic injustices in medical education. It also suggests strategies to favour epistemic justice in medical education despite the pandemic turmoil and online shift. It therefore adds an epistemic perspective to the reflection on the effects of the pandemic on medical education and training, which has been little discussed so far.

7.
Int J Equity Health ; 19(1): 94, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522215

RESUMO

BACKGROUND: There are shortcomings in medical practitioners' capacity to adapt to the particular needs of people experiencing circumstances of social vulnerability. Clinical traineeships create opportunities for the acquisition of knowledge, competencies, attitudes, and behaviors. However, some authors question the learnings to be made through classical clinical training pathways. This article explores the learnings gained from a traineeship experience within a community-based clinical setting intended for patients experiencing social vulnerability and operating under an alternative paradigm of care. To our knowledge, there is little research intended to identify and understand what medical trainees gain from their experience in such contexts. METHODS: This exploratory qualitative study is based on twelve interviews with practicing physicians who completed a traineeship at La Maison Bleue (Montreal, Canada) and three interviews conducted with key informants involved in traineeship management. Based on Mezirow's theory of transformational learning, data were analyzed according to L'Écuyer's principles of qualitative content analysis. NVivo software was used. RESULTS: The main learnings gained through the traineeship are related to (1) greater awareness of beliefs, assumptions and biases through prejudice deconstruction, cultural humility and critical reflection on own limitations, power and privileges; (2) the development of critical perspectives regarding the health care system; (3) a renewed vision of medical practice involving a less stigmatizing approach, advocacy, empowerment, interdisciplinarity and intersectorality; and (4) strengthened professional identity and future practice orientation including confirmation of interest for community-based practice, the identification of criteria for choosing a future practice setting, and commitment to becoming an actor of social change. Certain characteristics of the setting, the patients and the learner's individual profile are shown to be factors that promote these learnings. CONCLUSIONS: This article highlights how a traineeship experience within a clinical setting intended for a clientele experiencing circumstances of social vulnerability and operating under an alternative paradigm presents an opportunity for transformative learning and health practice transformation toward renewed values of health equity and social justice. Our findings suggest medical traineeships in community-based clinical settings are a promising lead to foster the development of fundamental learnings that are conducive to acceptable and equitable care for people experiencing social vulnerability.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Currículo , Educação Médica/organização & administração , Equidade em Saúde , Disparidades em Assistência à Saúde , Médicos/psicologia , Apoio ao Desenvolvimento de Recursos Humanos/organização & administração , Adulto , Canadá , Feminino , Humanos , Masculino , Pesquisa Qualitativa
8.
Mod Pathol ; 33(6): 1041-1055, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31857685

RESUMO

Adenoid cystic carcinoma (ACC) of the breast with a predominant solid pattern is difficult to diagnose with certainty and differentiate from more common triple-negative breast cancers (TNBCs) of basal-phenotype. To better characterize solid ACC, we performed a clinical, morphological, immunohistochemical, and molecular comparative analysis of 33 ACCs of the breast comprising 17 solid variant ACCs and 16 conventional ACCs. Solid ACCs displayed basaloid morphology with an exclusive or predominant epithelial cell population associated with decreased myoepithelial differentiation, while demonstrating MYB protein overexpression similar to the more common type of ACC. Strong and diffuse MYB expression by immunochemistry was observed in 14/17 (82%) of solid ACCs while MYB rearrangements were detected by break apart fluorescence in situ hybridization (FISH) in only 3/16 (19%) of solid ACCs. Conversely, weak MYB immunohistochemical expression was observed in only 7/204 (3%) of TNBC. Solid ACCs displayed a transcriptomic profile distinct from conventional ACCs with 549 genes showing a highly significant differential expression between conventional and solid ACC [false discovery rate (FDR) < 0.01; log2FC > |1|]. EnrichR and Kegg Pathway analyses identified PI3K-Akt and focal adhesion signaling pathways as significantly overexpressed in conventional ACCs compared with solid ACCs which significantly overexpressed the nitrogen metabolism pathway. CREBBP mutations and NOTCH activating gene mutations were only present in solid ACCs, concerning 5/16 (31%) of cases for each gene. Tumors with NOTCH activating mutations displayed a strong diffuse nuclear NICD1 staining, an established marker of Notch pathway activation. Solid ACCs also differed from basal-type TNBC, with fewer TP53 mutations and a more stable genomic profile on array comparative genomic hybridization (CGH). In summary, solid-type ACC of the breast is a distinct molecular entity within the ACC family and is different from common basal-type TNBC. MYB is a diagnostically useful biomarker of solid ACC and NOTCH could be a novel potential therapeutic target in 30% of cases.


Assuntos
Neoplasias da Mama/genética , Proteína de Ligação a CREB/genética , Carcinoma Adenoide Cístico/genética , Receptores Notch/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteína de Ligação a CREB/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Receptores Notch/metabolismo , Estudos Retrospectivos
9.
Pain Res Manag ; 2018: 5378451, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30538795

RESUMO

Occupational therapy (OT) makes a unique contribution to chronic pain (CP) management due to its overarching focus on occupation. The aim of this scoping review was to describe current knowledge about this contribution by documenting OT roles, models, assessments, and intervention methods used with adults living with CP. A systematic search exploring 10 databases and gray literature from 2006 to 2017 was conducted. Fifty-two sources were retained and analysed. Results bring forward the main role of OT being improving activities and participation (76.9 %), the Canadian Model of Occupational Performance (9.6 %), and the Canadian Occupational Performance Measure (21.2 %). Within the 30 reported interventions, 73.3% related directly to the person, 20% pertained to occupation (activities and participation), and 6.7% addressed environmental factors. The distinction and complementarity between the bottom-up and the top-down approaches to OT intervention were discussed. This review highlights OT specificity in adult CP management.


Assuntos
Dor Crônica/terapia , Terapia Ocupacional/métodos , Manejo da Dor , Humanos
10.
Diagn Pathol ; 11: 23, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26926447

RESUMO

BACKGROUND: Patients with non-dysplastic Barrett's esophagus (ND-BE) and low-grade dysplasia (LGD) are typically monitored by periodic endoscopic surveillance, while those with high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) are usually treated by more aggressive interventions like endoscopic mucosal resection, ablation or surgery. Therefore, the accurate grading of dysplasia in Barrett's esophagus (BE) is essential for proper patient care. However, there is significant interobserver and intraobserver variability in the histologic grading of BE dysplasia. The objective of this study was to create an immunohistochemical (IHC) panel that facilitates the grading of BE dysplasia and can be used as an adjunct to histology in challenging cases. METHODS: 100 BE biopsies were re-graded for dysplasia independently by 3 subspecialized gastrointestinal pathologists. IHC staining for CDX2, p120ctn, c-Myc and Jagged1 proteins was then performed and assessed by two separate methods of semi-quantitative scoring. Scores were integrated using a principal component analysis (PCA) and receiver operating characteristic (ROC) curve. RESULTS: Principal component analysis demonstrated the ability of this panel of proteins to segregate ND-BE/LGD and HGD/EAC, as the expression of the four proteins is significantly altered between the two subsets. Analysis of the receiver operating characteristic curve showed that this panel has the potential to aid in the grading of dysplasia in these two subcategories with both high sensitivity and specificity. While not able to discriminate between ND-BE and LGD, this panel of four proteins may be used as an adjunct to help discriminate subsets of ND-BE/LGD from HGD/EAC. CONCLUSIONS: We propose that the maximum utility of this IHC panel of CDX2, p120ctn, c-Myc, and Jagged1 proteins would be to distinguish between LGD and HGD in histologically challenging cases, given the aggressive interventions still used for HGD in many institutions, and hence may aid in the optimal patient management. The results of this initial study are promising, though further validation is needed before this panel can be used clinically, including future randomized prospective studies with larger patient cohorts from diverse locations.


Assuntos
Adenocarcinoma/química , Esôfago de Barrett/metabolismo , Biomarcadores Tumorais/análise , Proteínas de Ligação ao Cálcio/análise , Cateninas/análise , Neoplasias Esofágicas/química , Esôfago/química , Proteínas de Homeodomínio/análise , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteínas de Membrana/análise , Proteínas Proto-Oncogênicas c-myc/análise , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Esôfago de Barrett/patologia , Biópsia , Fator de Transcrição CDX2 , Consenso , Diagnóstico Diferencial , Neoplasias Esofágicas/patologia , Esôfago/patologia , Feminino , Humanos , Proteína Jagged-1 , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Variações Dependentes do Observador , Valor Preditivo dos Testes , Análise de Componente Principal , Curva ROC , Reprodutibilidade dos Testes , Proteínas Serrate-Jagged , Índice de Gravidade de Doença , Estados Unidos , delta Catenina
11.
Exp Cell Res ; 317(13): 1922-34, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21570965

RESUMO

The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.


Assuntos
Proteínas de Transporte/metabolismo , Diferenciação Celular , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Camundongos , Proteínas do Tecido Nervoso/genética
12.
Exp Cell Res ; 316(7): 1190-201, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20219459

RESUMO

Toti- or pluripotent cells proliferation and/or differentiation have been shown to be strongly related to nuclear chromatin organization and structure over the last past years. We have recently identified ZFPIP/Zfp462 as a zinc finger nuclear factor necessary for correct cell division during early embryonic developmental steps of vertebrates. We thus questioned whether this factor was playing a general role during cell division or if it was somehow involved in embryonic cell fate or differentiation. To achieve this goal, we performed a knock-down experiment in the pluripotent P19 and differentiated 3T3 cell lines, both expressing endogenous ZFPIP/Zfp462. Using specific shRNA directed against ZFPIP/Zfp462 transcripts, we demonstrated that depletion of this protein induced cell death in P19 but had no effect in 3T3 cells. In addition, in the absence of the protein, the P19 cells exhibited a complete destructuration of pericentromeric domains associated with a redistribution of the HP1alpha proteins and an increase in DNA satellites transcribed RNAs level. These data suggested an instrumental role of ZFPIP/Zfp462 in maintaining the chromatin structure of pluripotent cells.


Assuntos
Proteínas de Transporte/fisiologia , Cromatina/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Células-Tronco Pluripotentes/fisiologia , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Células COS , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Chlorocebus aethiops , Cromatina/química , Cromatina/genética , Instabilidade Cromossômica/genética , Instabilidade Cromossômica/fisiologia , Proteínas de Ligação a DNA , Embrião de Mamíferos , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo , RNA Interferente Pequeno/farmacologia
13.
Dev Growth Differ ; 51(8): 699-706, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19737294

RESUMO

ZFPIP/Zfp462 has been recently identified as a new vertebrate zinc finger encoding gene whose product interacts with Pbx1. Previous work indicates that ZFPIP is maternally expressed in Xenopus laevis oocytes and plays a key role during the cleavage phase of embryogenesis. This early expression is followed by a zygotic expression which overlaps with the neural Pbx1 expression pattern, suggesting an interaction between these two partners during Xenopus neurogenesis. In order to test the physiological interaction between ZFPIP and Pbx1, we carried out a dominant negative assay in which the Pbx1 interacting domain of ZFPIP (ZFPIPp) was overexpressed in Xenopus laevis embryos. We observed that ZFPIPp ectopic expression led to abnormal en2 and N-cam expression patterns, whereas krox-20 expression was not affected. Furthermore, we showed that while ZFPIPp alone was localized in the nucleus of Cos-7 cells, additional expression of Pbx1 induced a location of ZFPIPp at the perinuclear region of the cells. These overall data suggest that ZFPIP and Pbx1 could be partners and cooperate in the regulation of essential neural genes during Xenopus development.


Assuntos
Proteínas de Transporte/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas do Tecido Nervoso/genética , Neurogênese/genética , Fatores de Transcrição/genética , Proteínas de Xenopus/genética , Xenopus laevis/genética , Animais , Western Blotting , Células COS , Proteínas de Transporte/metabolismo , Células Cultivadas , Chlorocebus aethiops , Embrião não Mamífero , Desenvolvimento Embrionário/genética , Proteínas de Homeodomínio/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Proteínas do Tecido Nervoso/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Dedos de Zinco
14.
Int J Dev Biol ; 53(2-3): 411-24, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19412895

RESUMO

The mammalian female reproductive tract develops from the Mullerian ducts which differentiate, in a cranial to caudal direction, into oviducts, uterine horns, cervix and the anterior vagina. The developmental processes taking place during this organogenesis are notably under the control of steroid hormones, such as members of the Wnt and Hox families, which regulate key developmental genes. At later stages, steroid hormones also participate in the development of the female genital tract. Chemical compounds homologous to steroids can thus act as agonists or antagonists in fetuses exposed to them. These so-called endocrine disruptors are nowadays found in increasing amounts in the environment and may therefore have a particular impact on such developing organs. Epidemiological studies have revealed that endocrine disruptors have had drastic effects on female health and fertility during the last decades. Furthermore, these adverse effects might be transmitted to subsequent generations through epigenetic modifications. Given the potential hazard of inherited epigenetic marks altering reproduction and/or human health, such molecular mechanisms must be urgently investigated. This review aims to summarize the cellular and molecular mechanisms involved in female genital tract development, to highlight key genes involved in this process and to present epigenetic mechanisms triggered by endocrine disruptors and their consequences in regard to female reproductive tract development.


Assuntos
Desenvolvimento Fetal/fisiologia , Genitália Feminina/embriologia , Ductos Paramesonéfricos/embriologia , Animais , Epigênese Genética , Feminino , Desenvolvimento Fetal/genética , Regulação da Expressão Gênica no Desenvolvimento , Genitália Feminina/citologia , Genitália Feminina/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Humanos , Modelos Biológicos , Ductos Paramesonéfricos/citologia , Ductos Paramesonéfricos/metabolismo
15.
Dev Biol ; 327(1): 169-76, 2009 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19111535

RESUMO

ZFPIP (Zinc Finger Pbx1 Interacting Protein) has been recently identified in our laboratory in a yeast two hybrid screen using an embryonic mouse cDNA library and PBX1 as a bait. This gene encodes a large protein (250 kDa) that contains a bipartite NLS, numerous C2H2 zinc fingers and is highly conserved amongst vertebrates. In order to address the role of ZFPIP during embryonic development, we analysed the expression pattern of the gene and performed morpholinos injections into Xenopus laevis embryos. We first showed that the ZFPIP protein was maternally present in oocytes. Then, ZFPIP was detected from morula to neurula stages in the nucleus of the cells, with a gradient from animal to vegetal pole. By injection of ZFPIP morpholinos, we showed that morphant embryos were unable to undergo proper gastrulation and subsequently exhibited a persistent opened blastopore. Analysis of molecular and cellular events that were altered in morphant embryos highlighted an impairment of cell division processes as illustrated by atypical mitosis with aberrant metaphase, anaphase or telophase, incomplete chromosome segregation or conjointed nuclei. The overall data presented here demonstrated that ZFPIP was a major developing gene that acts in the very first steps of embryonic development of Xenopus laevis.


Assuntos
Proteínas de Transporte/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Proteínas de Xenopus/fisiologia , Xenopus laevis/crescimento & desenvolvimento , Animais , Divisão Celular , Proteínas de Ligação a DNA , Embrião não Mamífero , Desenvolvimento Embrionário , Feminino , Camundongos , Organismos Geneticamente Modificados , Xenopus laevis/embriologia
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