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1.
Cell ; 177(7): 1903-1914.e14, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31031007

RESUMO

Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc-/-, il2rga-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and visualized therapeutic responses using a four-color FUCCI cell-cycle fluorescent reporter. These experiments identified that combination treatment arrested rhabdomyosarcoma cells in the G2 cell cycle prior to induction of apoptosis. Finally, patient-derived xenografts could be engrafted into our model, opening new avenues for developing personalized therapeutic approaches in the future.


Assuntos
Animais Geneticamente Modificados/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Musculares , Rabdomiossarcoma , Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/imunologia , Feminino , Xenoenxertos , Humanos , Células K562 , Masculino , Neoplasias Musculares/tratamento farmacológico , Neoplasias Musculares/imunologia , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , Transplante de Neoplasias , Ftalazinas/farmacologia , Piperazinas/farmacologia , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma/patologia , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra/genética , Peixe-Zebra/imunologia
2.
Eur J Contracept Reprod Health Care ; 28(3): 163-167, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36961099

RESUMO

OBJECTIVE: We compared pain and the ease of insertion of two different types of intrauterine devices (IUDs; the levonorgestrel intrauterine systems 52 mg (LNG-IUS 52 mg) and the copper-bearing IUD [TCu380A]) among nulligravidas and parous women with and without caesarean delivery. METHODS: A cross-sectional study assessed pain referred by women and ease of insertion of the two IUDs models. We applied a visual analogue scale (VAS) to assess pain, while the ease of insertion was defined by healthcare professionals. RESULTS: We assessed 1076 women, including 334 nulligravidas and 566 parous women who had had at least one caesarean delivery and 176 women with history of only vaginal delivery. Regarding pain at IUD placement, 26 (2.5%) women reported no pain, 167 (16.4%) light pain, 319 (31.3%) moderate and 506 (49.7%) intense pain. The highest scores for pain were reported by nulligravidas (67.2%, p = 0.001), while the mean pain score was higher in the LNG-IUS 52 mg group. Difficulties reported by healthcare providers were more frequent in the nulligravidas (21.2%) and women with previous caesarean delivery (16.9%). CONCLUSIONS: Our findings suggested differences between the two IUDs tested, with higher pain associated with the LNG-IUS 52 mg, and highlights the need for pain management, mainly among nulligravida and women with history of caesarean delivery.SHORT CONDENSATIONIntense pain at insertion was more related to nulligravida than parous women and more pain with placement of LNG-IUS 52 mg IUDs than TCu380A IUDs. Nevertheless, our results confirmed that ease of IUD placement was between 80% to 90% of all insertions, being more common in parous women without previous caesarean delivery.


Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Gravidez , Feminino , Humanos , Masculino , Paridade , Dispositivos Intrauterinos Medicados/efeitos adversos , Medição da Dor , Estudos Transversais , Levanogestrel , Dispositivos Intrauterinos de Cobre/efeitos adversos , Dor/epidemiologia , Dor/etiologia
3.
J Obstet Gynaecol Res ; 43(11): 1732-1737, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28833891

RESUMO

AIM: Satisfaction with a contraceptive method constitutes an important factor in its acceptance and long-term use. The objective of this study was to assess the relationship between user satisfaction with the 20-µg/day levonorgestrel-releasing intrauterine system (LNG-IUS) and the bleeding patterns reported at two different time-points during follow-up. METHODS: A total of 251 LNG-IUS users aged 18-45 years were invited to answer a questionnaire on their return to the clinic for a routine follow-up visit and again 1 year later. Data were collected face-to-face. RESULTS: Twenty women discontinued prematurely; therefore, the analysis was performed on 231 women. Most users were either highly satisfied (66.6% and 66.2% at the first and second interviews, respectively) or satisfied (26.4% and 26.4% at the first and second interviews, respectively) with the LNG-IUS. Satisfaction was related to amenorrhea (P < 0.001) and duration of use (P < 0.001). Prolonged bleeding and spotting were the main causes of dissatisfaction with the device. CONCLUSION: Most LNG-IUS users in this sample were satisfied with the device. The only two factors associated with satisfaction were amenorrhea and duration of use, while prolonged bleeding and spotting were the main causes of dissatisfaction. These findings could be useful for health-care professionals and policy-makers when developing information material for women. The study provides insight into the profile of satisfied LNG-IUS users; however, this information is not suitable for counseling women who are considering using an LNG-IUS.


Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos Medicados , Levanogestrel , Distúrbios Menstruais , Satisfação do Paciente , Adolescente , Adulto , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Feminino , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Distúrbios Menstruais/induzido quimicamente , Distúrbios Menstruais/etiologia , Pessoa de Meia-Idade , Adulto Jovem
4.
Haematologica ; 101(10): 1228-1236, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27390356

RESUMO

The PML/RARA fusion protein occurs as a result of the t(15;17) translocation in the acute promyelocytic leukemia subtype of human acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia, including acute promyelocytic leukemia. We previously demonstrated that gain of chromosome 8-containing MYC is of central importance in trisomy 8, but the role of the nearby TRIB1 gene has not been experimentally addressed in this context. We have now tested the hypothesis that both MYC and TRIB1 have functional roles underlying leukemogenesis of trisomy 8 by using retroviral vectors to express MYC and TRIB1 in wild-type bone marrow and in marrow that expressed a PML/RARA transgene. Interestingly, although MYC and TRIB1 readily co-operated in leukemogenesis for wild-type bone marrow, TRIB1 provided no selective advantage to cells expressing PML/RARA. We hypothesized that this lack of co-operation between PML/RARA and TRIB1 reflected a common pathway for their effect: both proteins targeting the myeloid transcription factor C/EBPα. In support of this idea, TRIB1 expression abrogated the all-trans retinoic acid response of acute promyelocytic leukemia cells in vitro and in vivo Our data delineate the common and redundant inhibitory effects of TRIB1 and PML/RARA on C/EBPα providing a potential explanation for the lack of selection of TRIB1 in human acute promyelocytic leukemia, and highlighting the key role of C/EBPs in acute promyelocytic leukemia pathogenesis and therapeutic response. In addition, the co-operativity we observed between MYC and TRIB1 in the absence of PML/RARA show that, outside of acute promyelocytic leukemia, gain of both genes may drive selection for trisomy 8.


Assuntos
Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/patologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT/fisiologia , Cromossomos Humanos Par 8 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Leucemia Mieloide Aguda/etiologia , Leucemia Promielocítica Aguda/etiologia , Camundongos , Proteínas de Fusão Oncogênica , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas c-myc/fisiologia , Trissomia
5.
Int J Gynaecol Obstet ; 161(3): 1028-1032, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36527255

RESUMO

OBJECTIVES: To assess the occurrence of pregnancy in a cohort of women who received a copper intrauterine device (IUD), hormonal IUDs or an etonogestrel (ENG) contraceptive implant at a single-visit practice. METHODS: Prospective study conducted at the University of Campinas, Campinas, São Paulo, Brazil. We obtained data from four ongoing studies including both the date of the device placement, the first day of the last menstrual period, and the occurrence of pregnancy up to 3 months after device placement. RESULTS: We included 2479 device placements (413 TCu380A IUDs, 1476 hormonal IUD and 590 ENG implants). Almost half of the device placements (1113/2479; 44.9%) were performed within the first 5 days of the menstrual cycle. We observed three pregnancies: one in an ENG implant user who received the implant within days 1-5 of the menstrual cycle; one in a woman who received a hormonal IUD during days 6-10 of the menstrual cycle; and one in a copper IUD user with placement during days 21-25 of menstrual cycle. CONCLUSIONS: Single-visit long-acting reversible contraception placements are a good strategy with overall very low pregnancy rates. This strategy has a potential to reduce unintended pregnancies and to reduce costs and barriers to both women and the healthcare system.


Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos de Cobre , Contracepção Reversível de Longo Prazo , Gravidez , Feminino , Humanos , Levanogestrel , Taxa de Gravidez , Estudos Prospectivos , Brasil , Anticoncepção
6.
Rev Bras Ginecol Obstet ; 44(4): 391-397, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35623620

RESUMO

OBJECTIVE: To determine knowledge, attitude, and preventive (KAP) practices towards the SARS-CoV-2 (COVID-19) pandemic among women in reproductive age seeking to use copper or hormonal intrauterine devices (IUD/LNG-IUS). METHODS: We conducted a cross-sectional study in which we applied a questionnaire on 400 women about KAP practices on COVID-19 at the University of Campinas, Campinas, SP, Brazil, from May to August 2020. RESULTS: The mean (±SD) age of the women was 30.8 ± 7.9 years, and 72.8% of them reported being pregnant at least once. Most women (95%) had heard or read about COVID-19, and their main sources of information were television (91%) and government websites (53%). However, 53% of the women had doubts about the veracity of the information accessed. CONCLUSION: Women without a partner and with > 12 years of schooling had more information about COVID-19 and on its impact on new pregnancy, and those from high socioeconomic status had a higher chance of maintaining physical distance. Safety, effectiveness, comfort, and absence of hormone in the contraceptive method (in the case of TCu380A IUD) were the main reasons for the participants to seek the service during the pandemic, and the possibility to stop menstrual bleeding was the main reason to choose the LNG-IUS.


OBJETIVO: Determinar o conhecimento, atitude e práticas preventivas (CAP) em relação à pandemia de SARS-CoV-2 (Covid-19) entre mulheres em idade reprodutiva que buscam usar dispositivo intrauterino com cobre (DIU TCu 380) ou sistema intrauterino liberador de levonorgestrel (SIU-LNG). MéTODOS: Foi realizado um estudo transversal e um questionário foi aplicado a 400 mulheres para conhecer o CAP sobre o COVID-19 na Universidade Estadual de Campinas, Campinas, SP, Brasil, no período de maio a agosto de 2020. RESULTADOS: A média (±DP) de idade das mulheres foi de 30,8 ± 7,9 anos, e 72,8% delas relataram ter engravidado pelo menos uma vez. A maioria das mulheres (95%) tinha ouvido ou lido sobre a a Covid-19, e suas principais fontes de informação foram a televisão (91%) e sites do governo (53%). Porém, 53% das mulheres tinham dúvidas a respeito da veracidade das informações acessadas. CONCLUSãO: Mulheres sem companheiro e com mais de 12 anos de escolaridade tiveram mais informações sobre a COVID-19 e sobre o seu impacto em uma nova gravidez, e aquelas de nível socioeconômico alto tiveram maior chance de manter distância física. Segurança, eficácia, conforto e ausência de hormônio no método anticoncepcional (no caso do DIU TCu380A) foram os principais motivos para as participantes procurarem o serviço durante a pandemia, e a possibilidade de controlar o sangramento menstrual abundante foi o principal motivo para a escolha do SIU-LNG.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Anticoncepção , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pandemias/prevenção & controle , Gravidez , Adulto Jovem
7.
Contraception ; 105: 75-79, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34496300

RESUMO

OBJECTIVE: To compare the expulsion rates of the levonorgestrel (LNG) 52 mg intrauterine system (IUS) among women with heavy menstrual bleeding versus women using solely for contraception. STUDY DESIGN: We conducted an audit study of 548 (8.8%) women with heavy menstrual bleeding and 5655 (91.2%) users for contraception (comparison group) for 4 years in Campinas, Brazil. We retrieved sociodemographic data, expulsion rates, and variables associated to device placement. Among women with heavy menstrual bleeding, we placed the devices after the cessation of bleeding or after the reduction of menstrual flow. RESULTS: Thirty-one of 548 (5.6%) women with heavy menstrual bleeding and 315 of 5655 (5.6%) from the comparison group expelled the device. This constituted 7.8 expulsions/100 women-years in women with heavy menstrual bleeding and 10.3 expulsions/100 women-years from the comparison group (p = 0.94). Expulsion risk was associated with previous cesarean delivery in both groups (OR 1.93, 95% CI 1.36;2.74). CONCLUSIONS: Expulsion rates of the LNG IUS among women with heavy menstrual bleeding whose IUS was placed after the cessation or reduction of bleeding were similar to expulsion rates among users for contraception. Previous cesarean delivery was a risk factor for expulsion. IMPLICATIONS: We recommend the 52 mg LNG IUS placement after the cessation of bleeding or a reduction of menstrual flow among women with heavy menstrual bleeding because this strategy was associated with similar risk of expulsion when compared to users for contraception.


Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos Medicados , Menorragia , Anticoncepção , Feminino , Humanos , Levanogestrel , Menstruação , Gravidez
8.
Leukemia ; 36(6): 1533-1540, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35581375

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7R alone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally, we find that mutant IL7R collaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Animais , Animais Geneticamente Modificados , Carcinogênese/metabolismo , Criança , Humanos , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/metabolismo , Transdução de Sinais/genética , Linfócitos T/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
9.
Rev. bras. ginecol. obstet ; 44(4): 391-397, Apr. 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1387903

RESUMO

Abstract Objective To determine knowledge, attitude, and preventive (KAP) practices towards the SARS-CoV-2 (COVID-19) pandemic among women in reproductive age seeking to use copper or hormonal intrauterine devices (IUD/LNG-IUS). Methods We conducted a cross-sectional study in which we applied a questionnaire on 400 women about KAP practices on COVID-19 at the University of Campinas, Campinas, SP, Brazil, from May to August 2020. Results The mean (±SD) age of the women was 30.8±7.9 years, and 72.8% of them reported being pregnant at least once. Most women (95%) had heard or read about COVID-19, and their main sources of information were television (91%) and government websites (53%). However, 53% of the women had doubts about the veracity of the information accessed. Conclusion Women without a partner and with>12 years of schooling had more information about COVID-19 and on its impact on new pregnancy, and those from high socioeconomic status had a higher chance of maintaining physical distance. Safety, effectiveness, comfort, and absence of hormone in the contraceptive method (in the case of TCu380A IUD) were the main reasons for the participants to seek the service during the pandemic, and the possibility to stop menstrual bleeding was the main reason to choose the LNG-IUS.


Resumo Objetivo Determinar o conhecimento, atitude e práticas preventivas (CAP) em relação à pandemia de SARS-CoV-2 (Covid-19) entre mulheres em idade reprodutiva que buscam usar dispositivo intrauterino com cobre (DIU TCu 380) ou sistema intrauterino liberador de levonorgestrel (SIU-LNG). Métodos Foi realizado um estudo transversal e um questionário foi aplicado a 400 mulheres para conhecer o CAP sobre o COVID-19 na Universidade Estadual de Campinas, Campinas, SP, Brasil, no período de maio a agosto de 2020. Resultados A média (±DP) de idade das mulheres foi de 30,8±7,9 anos, e 72,8% delas relataram ter engravidado pelo menos uma vez. A maioria das mulheres (95%) tinha ouvido ou lido sobre a a Covid-19, e suas principais fontes de informação foram a televisão (91%) e sites do governo (53%). Porém, 53% das mulheres tinham dúvidas a respeito da veracidade das informações acessadas. Conclusão Mulheres sem companheiro e com mais de 12 anos de escolaridade tiveram mais informações sobre a COVID-19 e sobre o seu impacto em uma nova gravidez, e aquelas de nível socioeconômico alto tiveram maior chance de manter distância física. Segurança, eficácia, conforto e ausência de hormônio no método anticoncepcional (no caso do DIU TCu380A) foram os principais motivos para as participantes procurarem o serviço durante a pandemia, e a possibilidade de controlar o sangramento menstrual abundante foi o principal motivo para a escolha do SIU-LNG.


Assuntos
Humanos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Levanogestrel , COVID-19 , Fatores Sociodemográficos , Dispositivos Intrauterinos
10.
Nat Commun ; 7: 10358, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26790525

RESUMO

Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised rag2(E450fs) (casper) zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal dominance in T-cell acute lymphoblastic leukaemia and tumour evolution resulting in elevated growth and metastasis in BRAF(V600E)-driven melanoma. Cell transplantation approaches using optically clear immune-compromised zebrafish provide unique opportunities to uncover biology underlying cancer and to dynamically visualize cancer processes at single-cell resolution in vivo.


Assuntos
Rastreamento de Células/métodos , Melanoma/química , Melanoma/imunologia , Animais , Rastreamento de Células/instrumentação , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Hospedeiro Imunocomprometido , Melanoma/genética , Melanoma/patologia , Metástase Neoplásica , Transplante de Neoplasias , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/imunologia
11.
J Exp Med ; 213(12): 2575-2589, 2016 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-27810924

RESUMO

Cell transplantation into immunodeficient mice has revolutionized our understanding of regeneration, stem cell self-renewal, and cancer; yet models for direct imaging of engrafted cells has been limited. Here, we characterize zebrafish with mutations in recombination activating gene 2 (rag2), DNA-dependent protein kinase (prkdc), and janus kinase 3 (jak3). Histology, RNA sequencing, and single-cell transcriptional profiling of blood showed that rag2 hypomorphic mutant zebrafish lack T cells, whereas prkdc deficiency results in loss of mature T and B cells and jak3 in T and putative Natural Killer cells. Although all mutant lines engraft fluorescently labeled normal and malignant cells, only the prkdc mutant fish reproduced as homozygotes and also survived injury after cell transplantation. Engraftment into optically clear casper, prkdc-mutant zebrafish facilitated dynamic live cell imaging of muscle regeneration, repopulation of muscle stem cells within their endogenous niche, and muscle fiber fusion at single-cell resolution. Serial imaging approaches also uncovered stochasticity in fluorescently labeled leukemia regrowth after competitive cell transplantation into prkdc mutant fish, providing refined models to assess clonal dominance and progression in the zebrafish. Our experiments provide an optimized and facile transplantation model, the casper, prkdc mutant zebrafish, for efficient engraftment and direct visualization of fluorescently labeled normal and malignant cells at single-cell resolution.


Assuntos
Proteína Quinase Ativada por DNA/deficiência , Imageamento Tridimensional/métodos , Transplante de Neoplasias , Fenômenos Ópticos , Análise de Célula Única/métodos , Peixe-Zebra/metabolismo , Anemia/patologia , Animais , Sequência de Bases , Células Clonais , Proteína Quinase Ativada por DNA/metabolismo , Modelos Animais de Doenças , Raios gama , Homozigoto , Humanos , Hospedeiro Imunocomprometido/efeitos da radiação , Proteínas Luminescentes/metabolismo , Células Musculares/patologia , Células Musculares/efeitos da radiação , Mutação/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Regeneração/efeitos da radiação , Transplante Homólogo , Recombinação V(D)J/genética , Proteínas de Peixe-Zebra/metabolismo , Proteína Vermelha Fluorescente
12.
J Exp Med ; 213(6): 979-92, 2016 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-27139488

RESUMO

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4(+) cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2(E450fs) mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4(+) cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2(E450fs) mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4(+)/CD8(+) cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia.


Assuntos
Hematopoese/imunologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Neoplásicas/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Transcrição Gênica/imunologia , Peixe-Zebra/imunologia , Substituição de Aminoácidos , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Hematopoese/genética , Células-Tronco Hematopoéticas/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Mutação de Sentido Incorreto , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Transcrição Gênica/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/imunologia
15.
Hig. aliment ; 31(264/265): 132-137, 27/02/2017.
Artigo em Português | LILACS | ID: biblio-833127

RESUMO

Os queijos minas frescal e ricota são alimentos derivados do leite, muito nutritivos e muito consumidos pela população em geral. Por ser um veículo frequente de patógenos, a contaminação microbiológica dos queijos gera um grande risco de surtos de doenças de origem alimentar aos consumidores. O objetivo do trabalho foi verificar a qualidade microbiológica de queijos minas frescal e ricota comercializados na região metropolitana de Campinas/SP. Foram analisadas 20 amostras (5 queijo minas frescal caseiro, 5 queijo minas frescal industrializados, 5 queijo frescal ultrafiltrados e 5 ricotas) para quantificação de coliformes a 35ºC e 45ºC, E. coli, aeróbios mesófilos totais, bolores e leveduras, estafilococos, Salmonella sp e Listeria monocytogenes. As amostras apresentaram contagens de coliformes 35ºC (13 amostras ­ até >1,1x10³NMP/ mL), coliformes a 45ºC (5 amostras ­ até >1,1x10³NMP/mL), E. coli (12 amostras ­ até >1,1x10³ UFC/g), aeróbios mesófilos totais (13 amostras acima de 106 UFC/g), bolores e leveduras (7 amostras acima de 106 UFC/g) e Staphylococcus aureus (10 amostras acima de 5x10² UFC/g). Em nenhuma das amostras foi detectada Salmonella sp. e L. monocytogenes. 11 amostras estiveram em desacordo com a legislação RDC nº 12/2001 por causa da alta contagem de S. aureus e coliformes a 45ºC. O processo de ultrafiltração do queijo reduziu a contagem microbiológica para todas as amostras exceto uma, mostrando que mesmo após o processo é preciso ter boas práticas para evitar a recontaminação. A alta contagem de micro-organismos indica falhas na higiene durante as etapas de fabricação, manipulação e transporte do produto. Assim boas práticas de fabricação devem ser aplicadas aos queijos minas frescal caseiros e industriais, para se adequar a legislação e não oferecer riscos à saúde pública.


Assuntos
Humanos , Contaminação de Alimentos/análise , Queijo/microbiologia , Microbiologia de Alimentos , Amostras de Alimentos , Coliformes , Fungos/isolamento & purificação
16.
Rev. medica electron ; 37(6): 579-588, oct.-dic. 2015.
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-769489

RESUMO

Introducción: la Organización Mundial de la Salud reporta al tabaquismo como la principal causa prevenible de enfermedad, discapacidad y muerte prematura, y ha señalado que mueren aproximadamente 14 000 personas al día, por alguna de las enfermedades atribuibles a este. Objetivo: caracterizar el comportamiento del tabaquismo en adolescentes. Materiales y métodos: la investigación fue observacional, descriptiva, transversal, en un universo de 51 adolescentes de los consultorios 24, 25 y 26 del Policlínico Universitario “Héroes del Moncada”, de Cárdenas, que cumplieron los siguientes criterios de inclusión: tener edad comprendida entre 10 y 19 años, ser fumador activo, independientemente del tiempo con el hábito, la cantidad de cigarrillos que fume, y con consentimiento asistido por los padres de participar en el estudio durante el período de enero a junio de 2013. Resultados: el 11,4 % de los adolescentes son fumadores, y del sexo masculino 78,4 %. Predominó el grupo de 17 a 19 años, con un 58,8 %. El 92,2 % comenzó a fumar a los 12 años, el 56,9 % lo hace diariamente, y compran personalmente el cigarro en las tiendas el 43,8 %. Todos fuman públicamente, y en casa lo hace el 62,7 %. Conclusiones: predominaron los fumadores varones entre 17 y 19 años de edad. La mayoría de los adolescentes fuman diariamente en lugares públicos, compran personalmente los cigarros en las tiendas y comenzaron a fumar con más de 12 años de edad.


Background: the World Health Organization reports smoking as the main preventable cause of disease, disability and premature death, and has pointed out that around 14 000 persons per day die due to any of the diseases attributed to it. Aim: characterizing smoking behavior in teenagers. Material and Methods: the research was observational, descriptive, cross-sectional, in a universe of 51 teenagers belonging to the family physician consultations 24, 25 and 26 of the Teaching Policlinic “Heroes del Moncada”, of Cardenas, fulfilling the following inclusion criteria: aged 10-19 years, being active smokers without taking into account the time they have being smoking, the quantity of cigarettes they smoke, and having their relatives´ informed consent for participating in the research in the period from January to June 2013. Outcomes: 11.4 % of the teenagers were smokers, and 78.4 % were male. There it was a predominance of the 17-19 years-old group, for 58.8 %. 92.2 % of them began smoking at the age of 12, 56.9 percent smokes every day, and 43.8 % buys cigarettes in the stores by themselves. All of them smoke in public, and 62.7 % smokes at home. Conclusions: there it is a predominance of male teenagers aged 17-19 years. Most of the teenagers smoke every day in public places, buy personally cigarettes in the stores and began smoking when they were more than 12 years old.

17.
Rev. paul. pediatr ; 28(3): 276-282, set. 2010. graf, tab
Artigo em Português | LILACS | ID: lil-566339

RESUMO

OBJETIVO: Descrever os resultados do programa de oxigenoterapia domiciliar, com uso de concentrador de oxigênio, utilizado por crianças egressas de uma unidade neonatal ao longo de seus primeiros dez anos. MÉTODOS: Estudo de corte transversal com componente analítico para avaliar o programa de oxigenoterapia domiciliar de uma unidade neonatal de um hospital público universitário do interior do Estado de São Paulo durante o período de novembro de 1996 a dezembro de 2006. RESULTADOS: Foram identificadas 160 crianças com indicação de oxigenoterapia domiciliar, das quais 63,3 por cento apresentavam displasia broncopulmonar. Em média, 3,0 por cento de todos os pacientes internados e 8,6 por cento dos recém-nascidos com peso inferior a 1500g ao nascer receberam alta em oxigenoterapia. A duração média do uso de O2 no domicílio foi de 42,3±54,0 dias. Na comparação das características demográficas da população e do tempo de uso de O2 domiciliar, não se observaram diferenças significativas entre os anos. Não houve correlação entre o tempo de ventilação mecânica e a duração da terapia domiciliar. Houve necessidade de cuidados especiais, além do uso de O2 e medicações, em 22,3 por cento dos casos. Nos primeiros dois anos de vida, a taxa de morbidade e de mortalidade foram, respectivamente, 40,1 e 14,1 por cento. CONCLUSÕES: O uso de oxigênio domiciliar, com sistema de concentrador de oxigênio, é uma alternativa terapêutica factível em nosso meio, merecendo mais atenção dos profissionais de saúde e maior investimento das instituições de saúde. São necessários mais estudos nacionais para se aprimorar a qualidade do atendimento e a segurança destes programas para a população neonatal.


OBJECTIVE: To describe the results of a home oxygen therapy program consisting of the use oxygen concentrator by children discharged from a neonatal unit during their first 10 years of the program. METHODS: Cross-sectional analytical study with data collection from November 1996 to December 2006. All infants that needed home oxygen therapy after discharge from the neonatal unit of a public university hospital in the state of São Paulo, Brazil, were studied. RESULTS: We identified 160 infants who used home oxygen therapy during the period and 63.3 percent of them had bronchopulmonary dysplasia. A mean of 3.0 percent of all hospitalized patients and 8.6 percent of very low birth weight newborns were discharged on oxygen. The mean duration of home oxygen therapy was 42.3±54.0 days. Significant differences were not found when comparing demographic characteristics of the population and duration of home oxygen therapy. There was no correlation between the duration of mechanical ventilation and the duration of home oxygen therapy. In addition to the use of oxygen and medications, 22.3 percent of the infants needed special care. In the first 2 years of life, the infants' morbidity and mortality rates were, respectively, 40.1 percent and 14.1 percent. CONCLUSIONS: The use of an oxygen concentrator at home is a feasible therapeutic alternative in Brazil; therefore, it deserves more attention from health professionals and greater investments from health institutions. Further national studies are needed to improve the quality of care and the safety of these programs intended for the neonatal population.


Assuntos
Humanos , Recém-Nascido , Neonatologia , Oxigenoterapia/tendências , Recém-Nascido Prematuro , Serviços Hospitalares de Assistência Domiciliar , Displasia Broncopulmonar
18.
J. Health Sci. Inst ; 26(3): 289-293, jul.-set. 2008. graf, tab
Artigo em Português | LILACS | ID: lil-646005

RESUMO

Introdução - Embora a morte seja um evento bastante presente no cotidiano dos profissionais de enfermagem, observa-se uma grande dificuldade destes, não apenas em aceitar, mas também de como enfrentar de modo saudável a situação, sobretudo quando envolve o recém-nascido e sua família. Este estudo objetiva verificar a percepção e os sentimentos dos profissionais perante a morte neonatal. Material e Métodos - Trata-se de pesquisa quantitativa, exploratória, com coleta de dados por questionário estruturado. A população é de 52 profissionais de enfermagem da UTI neonatal de um hospital de médio porte do interior de São Paulo, com amostra de 42 (80,8%). Resultados - Os dados foram analisados de forma descritiva, seguida de um estudo observacional, no qual 62% julgaram ter recebido informações suficientes sobre o tema na formação, 57% referiram não ter recebido subsídios no treinamento; 76% pontuaram não saber abordar uma família enlutada, porém 94% gostariam de saber; 95% gostariam de receber apoio da instituição; pontuaram como "necessários" para melhor enfrentar a morte: 90% preparo na formação; 92% preparo específico na unidade; 69% apoio psicológico periódico; 85% atualização de conhecimentos. Frente a situações de morte: 62% agiram naturalmente; 58% conseguiram dar suporte à família; 95% conseguiram realizar os procedimentos com o corpo; 78% ficaram pensando no acontecimento em casa e 92% não sonharam; nos depoimentos, 26% relataram tristeza. Conclusão - O profissional de enfermagem sente-se inseguro já que precisa além de conhecimentos técnicos, competência na dimensão física, emocional em situação de morte. Assim, seu preparo profissional deveria abranger conteúdos para melhor ajudar pacientes sem condições de tratamento e suas famílias.


Introduction - Although death is an often presence on a nursing professional working day, great difficulties have been observed, not only in accepting it but also in knowing how to deal with the situation in a healthy way; specially when it involves a new born baby and it's family. This project focuses on verifying how professionals deal with and how are their feelings towards neonatal death. Material and Methods - This is a quantitative research, exploratory, with data collection by structured questionnaire. Population is formed by 52 nursing professionals at a neonatal ICU located in a medium sized hospital in the suburbs of São Paulo. Utilizing 42 sample (80,8%). Results - Data was analyzed through observational studies, in descriptive format, in which we can verify that in situation of death 62% of the subjects admitted having received enough information while still in school, 57% implied not having received enough information during training; 76% admitted not knowing how to approach a family in a death situation, although 94% would like to have that knowledge. 95% would like to have institutional support. Subjects claimed as necessary to better deal with death: 90% - school education on the subject, 92% - specialized training in work unit; 69% periodical psychological support; 85% updated information knowledgebase. Of all subjects studied, 62% acted naturally, 58% were able to give family support; 95% were able to perform all body procedures; 78% had thoughts about it at home and 92% did not have dreams about it. During survey, 26% admitted sadness. Conclusion - The nursing professional feels insecure due to the need of technical knowledge, physical, emotional and competency on death situations. For that reason, their professional training should involve data to better assist patients without treatment conditions and their families


Assuntos
Humanos , Masculino , Feminino , Adulto , Luto , Unidades de Terapia Intensiva Neonatal , Papel do Profissional de Enfermagem , Morte Perinatal , Cuidados de Enfermagem
19.
Rev. méd. HEC/FEMPAR ; 3(1): 44-53, jan.-jun. 1988. ilus
Artigo em Português | LILACS | ID: lil-60434

RESUMO

Os autores descrevem um caso de sirenomelia - "simpus apus" -: um feto de 37 semanas nascido vivo de multíparas de 26 anos, sadia, com outros filhos normais, sem antecedentes de diabete e que apresentara oligoidrâmnio. Além da característica fusäo dos membros inferiores vêem severas malformaçöes, entre as quais: facies de Potter, fenda labial e palatina, completa ausência de ânus e genitália externa, agenesia de aparelho urinário. Discutem as malformaçöes essenciais e as várias teorias de sua gênese. Revisam exaustivamente os casos apresentados na literatura


Assuntos
Humanos , Ectromelia , Ectromelia/patologia , Ectromelia
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