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Small ubiquitin-like modifiers from the ATG8 family regulate autophagy initiation and progression in mammalian cells. Their interaction with LC3-interacting region (LIR) containing proteins promotes cargo sequestration, phagophore assembly, or even fusion between autophagosomes and lysosomes. Previously, we have shown that RabGAP proteins from the TBC family directly bind to LC3/GABARAP proteins. In the present study, we focus on the function of TBC1D2B. We show that TBC1D2B contains a functional canonical LIR motif and acts at an early stage of autophagy by binding to both LC3/GABARAP and ATG12 conjugation complexes. Subsequently, TBC1D2B is degraded by autophagy. TBC1D2B condensates into liquid droplets upon autophagy induction. Our study suggests that phase separation is an underlying mechanism of TBC1D2B-dependent autophagy induction.
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Autofagia , Proteínas Ativadoras de GTPase , Proteínas Associadas aos Microtúbulos , Humanos , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Células HeLa , Proteínas Reguladoras de Apoptose/metabolismo , Células HEK293 , Ligação Proteica , Separação de FasesRESUMO
Resumo Objetivo Compreender as Representações Sociais dos profissionais enfermeiros, médicos e odontólogos da Atenção Primária em Saúde (APS) sobre Cuidados Paliativos (CP) para a pessoa idosa. Método Pesquisa fundamentada na Teoria das Representações Sociais. Os dados foram obtidos por meio de entrevista semiestruturada a partir de questões fechadas (dados sociodemográficos e profissionais) e abertas (Fale qual a sua compreensão sobre Cuidado Paliativo para o idoso e Fale como você realiza o cuidado paliativo para os idosos que você cuida aqui da unidade). Para análise e organização dos dados, foi utilizada a técnica do Discurso do Sujeito Coletivo. Resultados Frente a questão sobre o que os profissionais compreendiam do CP para o idoso, resultaram quatro Ideias Centrais: diagnóstico incurável; cuidado biopsicossocial e humanizado para a pessoa idosa e família; qualidade de vida e educação em saúde. As cinco ideias centrais sobre como esse cuidado era realizado na unidade foram: visita domiciliar; atenção biopsicossocioespiritual a pessoa idosa e família; grupos de atividades; promoção da qualidade de vida e assistência no momento da morte. Conclusão Os dados obtidos permitiram identificar as representações sociais de profissionais de saúde da APS sobre o CP para a pessoa idosa, bem como sua execução. As compreensões sobre CP estão intimamente relacionadas com o preconizado pela Organização Mundial de Saúde, com exceção da educação em saúde que é um princípio e não um conceito. Essas compreensões permitiram, também, identificar ações de enfermeiros, médicos e odontólogos que demonstram como realizam o cuidado paliativo para a pessoa idosa.
Abstract Objective To comprehend the Social Representations of nurses, physicians, and dentists working in Primary Health Care (PHC) regarding Palliative Care (PC) for older adults. Method This research was grounded in the Theory of Social Representations. Data were obtained through semi-structured interviews comprising closed-ended questions (socio-demographic and professional data) and open-ended questions (Describe your understanding of Palliative Care for older adults and Explain how you provide palliative care for the older adults under your care at this unit). For data analysis and organization, the Collective Subject Discourse technique was employed. Results Regarding the question about what professionals understood about Palliative Care for older adults, four Central Ideas emerged: incurable diagnosis; biopsychosocial and humanized care for the older adult and family; quality of life; and health education. The five central ideas concerning how this care was conducted at the unit were: home visits; biopsychosocial and spiritual care for the older adult and family; activity groups; promotion of quality of life; and assistance at the moment of death. Conclusion The data obtained allowed for the identification of the social representations of PHC professionals regarding PC for older adults, as well as its implementation. The understandings of PC are closely related to those advocated by the World Health Organization, with the exception of health education, which is a principle rather than a concept. These understandings also allowed for the identification of actions by nurses, physicians, and dentists that demonstrate how they provide palliative care for older adults.
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To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Filogenia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Integrases/genética , Integrases/uso terapêutico , Mutação , Farmacorresistência Viral/genética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , PrevalênciaRESUMO
The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. Here, we show that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB, thereby coordinating the expression of lysosomal proteins and autophagy regulators. Importantly, both NPM1 and NPM1c bind to autophagy modifiers of the GABARAP subfamily through an atypical binding module preserved within its N terminus. The propensity of NPM1c to induce autophagy depends on this module, likely indicating that NPM1c exerts its pro-autophagic activity by direct engagement with GABARAPL1. Our data report a non-canonical binding mode of GABARAP family members that drives the pro-autophagic potential of NPM1c, potentially enabling therapeutic options.
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Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Leucemia Mieloide Aguda/metabolismo , Autofagia/fisiologia , Mutação/genética , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Reguladoras de Apoptose/metabolismoRESUMO
OBJECTIVES: to interpret the perception of graduates from the nursing technician program on the learning process developed during their education. METHODS: a qualitative study was conducted from March to September 2021, based on interviews with 20 graduates from a nursing technician program at a school in the Midwest of São Paulo, using thematic analysis and the NVivo tool. RESULTS: the following themes were identified: traditional teaching methods, active learning strategies, valuing proactivity and experiences in professional practice. FINAL CONSIDERATIONS: according to the graduates, the teaching process is essentially based on traditional methods, although there are initiatives to implement active strategies and recognition of the importance of advancing student proactivity and practical experience.
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Bacharelado em Enfermagem , Educação em Enfermagem , Estudantes de Enfermagem , Humanos , Brasil , Escolaridade , Aprendizagem Baseada em Problemas , Bacharelado em Enfermagem/métodos , Percepção , Educação em Enfermagem/métodosRESUMO
The endoplasmic reticulum (ER) undergoes continuous remodelling via a selective autophagy pathway, known as ER-phagy1. ER-phagy receptors have a central role in this process2, but the regulatory mechanism remains largely unknown. Here we report that ubiquitination of the ER-phagy receptor FAM134B within its reticulon homology domain (RHD) promotes receptor clustering and binding to lipidated LC3B, thereby stimulating ER-phagy. Molecular dynamics (MD) simulations showed how ubiquitination perturbs the RHD structure in model bilayers and enhances membrane curvature induction. Ubiquitin molecules on RHDs mediate interactions between neighbouring RHDs to form dense receptor clusters that facilitate the large-scale remodelling of lipid bilayers. Membrane remodelling was reconstituted in vitro with liposomes and ubiquitinated FAM134B. Using super-resolution microscopy, we discovered FAM134B nanoclusters and microclusters in cells. Quantitative image analysis revealed a ubiquitin-mediated increase in FAM134B oligomerization and cluster size. We found that the E3 ligase AMFR, within multimeric ER-phagy receptor clusters, catalyses FAM134B ubiquitination and regulates the dynamic flux of ER-phagy. Our results show that ubiquitination enhances RHD functions via receptor clustering, facilitates ER-phagy and controls ER remodelling in response to cellular demands.
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Autofagia , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Ubiquitinação , Autofagia/fisiologia , Retículo Endoplasmático/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ubiquitinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismoRESUMO
Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)1. Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons2. Here we report that ARL6IP1, another ER-shaping protein that contains a reticulon homology domain and is associated with sensory loss3, interacts with FAM134B and participates in the formation of heteromeric multi-protein clusters required for ER-phagy. Moreover, ubiquitination of ARL6IP1 promotes this process. Accordingly, disruption of Arl6ip1 in mice causes an expansion of ER sheets in sensory neurons that degenerate over time. Primary cells obtained from Arl6ip1-deficient mice or from patients display incomplete budding of ER membranes and severe impairment of ER-phagy flux. Therefore, we propose that the clustering of ubiquitinated ER-shaping proteins facilitates the dynamic remodelling of the ER during ER-phagy and is important for neuronal maintenance.
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Autofagia , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Proteínas Ubiquitinadas , Ubiquitinação , Animais , Humanos , Camundongos , Autofagia/genética , Retículo Endoplasmático/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Ubiquitinadas/metabolismo , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/patologia , Membranas Intracelulares/metabolismoRESUMO
Huntington's disease (HD) is a disease characterized by the progressive degeneration of nerve cells in the brain. DNA damage has been implicated in many neurological disorders; however, the association between this damage and the impaired signaling related to neurodegeneration is still unclear. The transcription factor c-AMP-responsive element binding protein (CREB) has a relevant role in the neuronal plasticity process regulating the expression of several genes, including brain-derived neurotrophic factor (BDNF). Here we analyzed the direct link between DNA damage and the expression of genes involved in neuronal plasticity. The study was performed in model cell lines STHdhQ7 (wild type) and STHdhQ111 (HD model). Treatment with Etoposide (Eto) was used to induce double-strand breaks (DSBs) to evaluate the DNA damage response (DDR) and the expression of synaptic plasticity genes. Eto treatment induced phosphorylation of ATM (p-ATM) and H2AX (γH2AX), markers of DDR, in both cell lines. Interestingly, upon DNA damage, STHdhQ7 cells showed increased expression of activity-regulated cytoskeleton associated protein (Arc) and BDNF when compared to the HD cell line model. Additionally, Eto induced CREB activation with a differential localization of its co-activators in the cell types analyzed. These results suggest that DSBs impact differentially the gene expression patterns of plasticity genes in the normal cell line versus the HD model. This effect is mediated by the impaired localization of CREB-binding protein (CBP) and histone acetylation in the HD model. Our results highlight the role of epigenetics and DNA repair on HD and therefore we suggest that future studies should explore in depth the epigenetic landscape on neuronal pathologies with the goal to further understand molecular mechanisms and pinpoint therapeutic targets.
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Doença de Huntington , Humanos , Doença de Huntington/genética , Doença de Huntington/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Dano ao DNA , Transdução de Sinais , Plasticidade NeuronalRESUMO
Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency of pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion of intracellular vesicles and is important for vesicular secretion in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via regulation of the cargo of sEVs released by BMM-derived mesenchymal stromal cells (MSCs). PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, resulting in a more immature B-cell phenotype and an increased number/function of leukemia-initiating cells (LICs) via focal adhesion kinase and AKT signaling in B-ALL cells. Ex vivo pretreatment of LICs with sEVs derived from PLEKHM1-deficient MSCs led to a strong trend toward acceleration of murine and human BCR-ABL1+ B-ALL. In turn, inflammatory mediators such as recombinant or B-ALL cell-derived tumor necrosis factor α or interleukin-1ß condition murine and human MSCs in vitro, decreasing PLEKHM1, while increasing syntenin and syndecan-1 in MSCs, thereby perpetuating the sEV-associated circuit. Consistently, human trephine biopsies of patients with B-ALL showed a reduced percentage of PLEKHM1+ MSCs. In summary, our data reveal an important role of BMM-derived sEVs for driving specifically BCR-ABL1+ B-ALL, possibly contributing to its worse prognosis compared with BCR-ABL1- B-ALL, and suggest that secretion of inflammatory cytokines by cancer cells in general may similarly modulate the tumor microenvironment.
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Linfoma de Burkitt , Células-Tronco Mesenquimais , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Animais , Camundongos , Sindecana-1/metabolismo , Sinteninas/metabolismo , Comunicação Celular , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Linfoma de Burkitt/patologia , Células-Tronco Mesenquimais/metabolismo , Microambiente TumoralRESUMO
ABSTRACT Objectives: to interpret the perception of graduates from the nursing technician program on the learning process developed during their education. Methods: a qualitative study was conducted from March to September 2021, based on interviews with 20 graduates from a nursing technician program at a school in the Midwest of São Paulo, using thematic analysis and the NVivo tool. Results: the following themes were identified: traditional teaching methods, active learning strategies, valuing proactivity and experiences in professional practice. Final Considerations: according to the graduates, the teaching process is essentially based on traditional methods, although there are initiatives to implement active strategies and recognition of the importance of advancing student proactivity and practical experience.
RESUMEN Objetivos: interpretar la percepción de egresados del curso técnico de enfermería sobre el proceso de aprendizaje desarrollado durante su formación. Métodos: estudio cualitativo realizado en el periodo de marzo a septiembre de 2021, a partir de entrevistas con 20 egresados del curso técnico de enfermería de una escuela del Centro-Oeste paulista, mediante el análisis temático, utilizando la herramienta NVivo. Resultados: se identificaron los temas: método tradicional de enseñanza, estrategias activas de aprendizaje, atribución de valor a la proactividad y a las experiencias en la práctica profesional. Consideraciones Finales: para los egresados, el proceso de enseñanza se encuentra esencialmente basado en el método tradicional, aunque existen iniciativas de implantación de estrategias activas y reconocimiento de la importancia de avanzar en la proactividad del estudiante y acercamiento con la práctica.
RESUMO Objetivos: interpretar a percepção de egressos do curso técnico de enfermagem sobre o processo de aprendizagem desenvolvido durante sua formação. Métodos: estudo qualitativo realizado no período de março a setembro de 2021, a partir de entrevistas com 20 egressos do curso técnico de enfermagem de uma escola do Centro-Oeste paulista, por meio da análise temática, utilizando a ferramenta NVivo. Resultados: foram identificados os temas: método tradicional de ensino, estratégias ativas de aprendizagem, atribuição de valor à proatividade e às vivências na prática profissional. Considerações Finais: para os egressos, o processo de ensino encontra-se essencialmente pautado no método tradicional, embora existam iniciativas de implantação de estratégias ativas e reconhecimento da importância de avançar na proatividade do estudante e aproximação com a prática.
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In this pilot clinical trial, we evaluated rates of residual replication in persons without lamivudine resistance-associated mutations in proviral DNA population sequencing who switched to dolutegravir plus lamivudine. After 144 weeks, there was no signal of changes in residual viremia based on qualitative detection methods, irrespective of past lamivudine resistance. Clinical Trials Registration. NCT03539224.
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BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.
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Fármacos Anti-HIV , COVID-19 , Infecções por HIV , HIV-1 , Adulto , Humanos , Lamivudina/farmacologia , Fármacos Anti-HIV/efeitos adversos , Pandemias , HIV-1/genética , Antirretrovirais/uso terapêuticoRESUMO
Gene expression in pathogenic protozoans of the family Trypanosomatidae has several novel features, including multiple eIF4F-like complexes involved in protein synthesis. The eukaryotic eIF4F complex, formed mainly by eIF4E and eIF4G subunits, is responsible for the canonical selection of mRNAs required for the initiation of mRNA translation. The best-known complexes implicated in translation in trypanosomatids are based on two related pairs of eIF4E and eIF4G subunits (EIF4E3/EIF4G4 and EIF4E4/EIF4G3), whose functional distinctions remain to be fully described. Here, to define interactomes associated with both complexes in Trypanosoma brucei procyclic forms, we performed parallel immunoprecipitation experiments followed by identification of proteins co-precipitated with the four tagged eIF4E and eIF4G subunits. A number of different protein partners, including RNA binding proteins and helicases, specifically co-precipitate with each complex. Highlights with the EIF4E4/EIF4G3 pair include RBP23, PABP1, EIF4AI and the CRK1 kinase. Co-precipitated partners with the EIF4E3/EIF4G4 pair are more diverse and include DRBD2, PABP2 and different zinc-finger proteins and RNA helicases. EIF4E3/EIF4G4 are essential for viability and to better define their role, we further investigated their phenotypes after knockdown. Depletion of either EIF4E3/EIF4G4 mRNAs lead to aberrant morphology with a more direct impact on events associated with cytokinesis. We also sought to identify those mRNAs differentially associated with each complex through CLIP-seq with the two eIF4E subunits. Predominant among EIF4E4-bound transcripts are those encoding ribosomal proteins, absent from those found with EIF4E3, which are generally more diverse. RNAi mediated depletion of EIF4E4, which does not affect proliferation, does not lead to changes in mRNAs or proteins associated with EIF4E3, confirming a lack of redundancy and distinct roles for the two complexes.
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The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in the adult organism is associated with the development of various cancers. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. Therefore, the present study investigated the role of protein patched homolog 1 (PTCH1), a component of the Hh signaling pathway, and changes in the promoter methylation status of the corresponding gene in a cohort of low(LGSC) and highgrade serous ovarian carcinomas (HGSC) and HGSC cell lines (OVCAR8 and OVSAHO). PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples and immunofluorescence and western blotting in cell lines. DNA methylation patterns of the PTCH1 gene were analyzed using methylationspecific PCR. PTCH1 protein expression was significantly higher in HGSCs and LGSCs compared with controls (healthy ovaries and fallopian tubes). Similarly, ovarian cancer cell lines exhibited significantly higher PTCH1 protein expression compared with a normal fallopian tube nonciliated epithelial cell line (FNE1). PTCH1 protein fragments of different molecular weights were detected in all cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble Nterminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was exclusively detected in a proportion of HGSC (13.5%) but did not correlate with protein expression. PTCH1 protein was highly expressed in serous ovarian carcinoma tissues and cell lines, while PTCH1 promoter methylation was only detected in HGSC. Further investigation is required to elucidate the possible mechanisms of PTCH1 activation in serous ovarian carcinomas.
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Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Adulto , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/patologia , Feminino , Proteínas Hedgehog , Humanos , Neoplasias Ovarianas/patologia , Receptor Patched-1/genéticaRESUMO
INTRODUCTION: Despite the growing evidence supporting the use of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in cervical and ovarian malignant tumours, data on vulvar and vaginal cancer is sparse. Our aim was to assess the role of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in patients with vulvar and vaginal cancer. MATERIAL AND METHODS: A retrospective study was conducted on a cohort of 20 patients with biopsy-proven vulvar (n = 17) and vaginal (n = 3) cancer who performed 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography, between January 2013 and April 2018. We collected the clinical data of all patients, as well as the indication for 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography, its results, and the main lesion maximum standard uptake value (SUVmax). In addition, we correlated the results of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography with other diagnostic modalities, namely histological findings, computed tomography and magnetic resonance imaging. Patients were divided into two groups, one with newly diagnosed disease and another with recurrent disease. RESULTS: Six patients had newly diagnosed disease and 14 had recurrent disease. The main lesion was detected by 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in five out of six patients with newly diagnosed disease and in all 14 patients with recurrent disease. Additional sites of 2-[F-18]-fluor-2-desoxi-D-glucose uptake were identified in inguinal and iliac lymph nodes and in distant lesions. Magnetic resonance imaging and computed tomography were performed in 12 cases. In four patients with recurrent disease, abnormalities (main lesion/ metastatic lymph nodes) identified by 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography were not detected as suspicious by computed tomography. DISCUSSION: In our study, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography identified abnormalities more often than conventional computed tomography scans in recurrent disease. In comparison with histology, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography had a sensitivity of 95% and a positive predictive value of 100% in identifying the primary tumour and the recurrent main lesion. Little data is available regarding the usefulness of 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography in the management of vulvar and vaginal cancers. The existing evidence supports a high accuracy in detecting lymph node metastases and a change of 36.0% - 61.5% in patient management. Our findings reinforce the usefulness of this technique in vulvar and vaginal cancer. Limitations of our study include its retrospective nature and the rareness of both vulvar and vaginal cancer, which leads to a small sample size and few comparative imaging tests. CONCLUSION: In this preliminary study, 2-[F-18]-fluor-2-desoxi-D-glucose positron emission tomography/computed tomography demonstrated it can be a useful method in patients with vulvar and vaginal cancers, namely in defining the extent of disease and contributing to accurate staging and restaging.
Introdução: Apesar da crescente evidência que suporta o uso da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose em tumores malignos do colo do útero e do ovário, os dados sobre o carcinoma da vulva e da vagina são escassos. O nosso objetivo foi avaliar o papel da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose em doentes com carcinoma da vulva e da vagina. Material e Métodos: Entre janeiro de 2013 e abril de 2018 foi realizado um estudo retrospetivo numa coorte de 20 doentes com carcinoma da vulva (n = 17) e da vagina (n = 3), comprovados por biópsia, que efetuaram tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose. Recolheram-se os dados clínicos de todos os doentes, bem como a indicação clínica para a realização da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose, os seus resultados e o valor de captação padronizado máximo da lesão principal (SUVmax). Para além disso, correlacionaram-se os resultados da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose com os de outras modalidades diagnósticas, nomeadamente com os achados histológicos, a tomografia computadorizada e a ressonância magnética. Os doentes foram divididos em dois grupos, um com doença recém diagnosticada e outro com doença recorrente. Resultados: Seis doentes tinham doença recém diagnosticada e 14 tinham doença recorrente. A lesão principal foi detetada em cinco dos seis doentes com doença recém diagnosticada e nos 14 com doença recorrente. Foram identificados outros locais de captação de 2-[F-18]-fluor-2-desoxi-D-glucose, nomeadamente gânglios linfáticos ilíacos e inguinais, e lesões à distância. Em 12 casos foram realizadas ressonância magnética e tomografia computadorizada. Em quatro casos com doença recorrente, as anomalias (lesão principal /gânglios linfáticos metastáticos) identificadas na tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose não haviam sido descritas como suspeitas pela tomografia computadorizada. Discussão: No nosso estudo, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose identificou mais anomalias que a tomografia computadorizada na doença recorrente. Comparando com os resultados histológicos, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose apresentou sensibilidade de 95% e um valor preditivo positivo de 100% na identificação do tumor primário/ lesão principal recorrente. Poucos dados estão disponíveis sobre a utilidade da tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose no seguimento de carcinomas da vulva e da vagina. As evidências atuais sugerem uma elevada exatidão na deteção de metástases ganglionares e uma mudança de 36,0% - 61,5% no tratamento destes doentes. Os nossos achados reforçam a utilidade desta técnica no carcinoma da vulva e da vagina. As limitações do nosso estudo decorrem da sua natureza retrospetiva e da raridade das patologias estudadas, o que condiciona o tamanho da amostra e a quantidade de exames de imagem comparativos. Conclusão: Neste estudo preliminar, a tomografia por emissão de positrões/ tomografia computadorizada com 2-[F-18]-fluor-2-desoxi-D-glucose demonstrou poder ser um método útil em doentes com carcinoma da vulva e da vagina, nomeadamente na definição da extensão da doença e na contribuição para o estadiamento e restadiamento precisos.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Vaginais , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: We aim to investigate the infection rate, the clinical characteristics and outcomes of COVID-19-disease in a cohort of people living with HIV in Madrid (Spain), during the first year of pandemics. SETTING: Observational single-center study, in which we included all HIV-infected patients (aged ≥ 18 years) with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as of February 28, 2021, at the Hospital Universitario 12 de Octubre. METHODS: Confirmed disease was defined as any patient with a positive antigen test, reverse transcriptase polymerase chain reaction, or serology for SARS-CoV-2. We compared the characteristics of patients with mild disease (asymptomatic included) with those with moderate or severe disease (requiring admission). RESULTS: Of 2344 HIV-infected patients, 158 (82.9% male; median age, 46.5 years) were diagnosed with SARS-CoV-2 (infection rate, 6.74%; 95% confidence interval, 5.79 to 7.83). Thirty-nine individuals (24.7%) had moderate or severe disease, 43.7% had mild disease, and 31.6% were asymptomatic. Hypertension (23.4%) and obesity (15.8%) were the most prevalent comorbidities; 12.7% had at least 2 comorbidities. One hundred forty-five patients (97.3%) had RNA-HIV viral load of <50 copies per milliliter, and only 3 had CD4 cell count of <200 cells per cubic millimeter before infection. Of those admitted to hospital, 59% required oxygen support and 15.4%, invasive mechanical ventilation. Five patients died. None of the patient taking tenofovir-disoproxil-fumarate required admission. In the multivariate analysis, age remained as the only independent factor for moderate-severe disease (odds ratio, 1.09; 95% confidence interval 1.04 to 1.14; P < 0.001). CONCLUSIONS: People living with HIV are at risk of severe SARS-CoV-2 infection. Age was the only variable with an independent association with moderate-severe disease, after adjusting by comorbidities and other factors.
Assuntos
COVID-19 , Infecções por HIV , COVID-19/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
Esta pesquisa buscou investigar as práticas do pré-natal odontológico sob a perspectiva das gestantes do município de Itacoatiara, Amazonas. Utilizou-se um instrumento composto por 14 questões objetivas aplicado a 146 gestantes, maiores de 18 anos, acompanhadas em sete unidades de saúde da família do município de Itacoatiara, Amazonas. Os dados foram analisados descritivamente por meio de frequências absolutas e relativas sendo utilizado o teste qui-quadrado (p<0,05). Do total das participantes, 49,32% relataram não ter ido à consulta com dentista durante a gestação, sendo que dentre as que compareceram,47,30% foram apenas uma vez, e em 31,08% dos casos quem marcou a consulta foi profissional de enfermagem. Em relação a atividades de educação em saúde, 91,78% não participaram de nenhuma atividade e 54,11% não tiveram orientação de higiene oral. Sendo o acompanhamento e assistência odontológica durante a gestação fundamental para minimizar alterações bucais que possam afetar a saúde da mãe e do bebê, ressalta-se a importância de fortalecer ações pelas equipes de saúde bucal na sensibilização das gestantes acerca da importância do pré-natal odontológico, colaborando com maior adesão destas ao acompanhamento de suas condições de saúde bucal.
This study sought to investigate the practices of prenatal dental care from the perspective of pregnant women in the city of Itacoatiara, Amazonas. An instrument composed of 14 objective questions was used, applied to 146 pregnant women, over 18 years of age, followed up in seven family health units in the city of Itacoatiara, Amazonas. The data were descriptively analyzed using absolute and relative frequencies, using the chi-squared test (p<0.05). Of the total number of participants, 49.32% reported not having gone to a dentist appointment during pregnancy, and among those who did, 47.30% went only once, and in 31.08% of the cases the appointment was made by a nursing professional. Regarding health education activities, 91.78% did not participate in any activity and 54.11% did not receive oral hygiene guidance. As the follow-up and dental care during pregnancy are essential to minimize oral changes that may affect the health of the mother and baby, the importance of strengthening actions by oral health teams in raising awareness among pregnant women about the importance of prenatal dental care is highlighted, contributing to a greater adherence to the monitoring of their oral health conditions.
RESUMO
Objetivo:Avaliar a relação do SOC com índice Ceo-d e o SOC com as condições socioeconômicas familiares com a cárie dentária em pré-escolares (3-5 anos) do município de Manaus, capital do Estado do Amazonas. Métodos: O estudo contou com uma amostra de 89 pais e 89 crianças. Para avaliação da cárie dentária foi utilizado o índice ceo-d; o índice significativo de cárie (SiC Index) foi utilizado para avaliar a desigualdade de cárie na amostra do estudo; para avaliar o SOC materno foi utilizado o questionário (versão curta); e para avaliar as condições socioeconômicas foram utilizadas as questões do Levantamento Nacional SB Brasil 2010. Resultados: Houve uma média do ceo-d de 1,50 com maior ocorrência de cárie dentária nos participantes do gênero masculino, assim como índice SiC que se apresentou maior no gênero masculino em média 4,38. A média do senso de coerência materno foi maior entre as crianças de 5 anos de idade com um valor de 39,33 em média e no que tange às condições socioeconômicas, observaram-se que a maior parte dos participantes, 42,33 em média vive com uma renda familiar de R$1.501 a R$2.500 reais, e uma amostra considerável de 35,40 em média sobrevive com uma renda familiar de R$ 250 reais. Conclusão: Não houve uma correlação significativa entre as condições socioeconômicas e o SOC materno com o índice ceo-d.
Aim: To evaluate the relationship between SOC with the Ceo-d index and SOC with family socioeconomic conditions with dental caries in preschoolers (3-5 years) in the municipality of Manaus, capital of the State of Amazonas, Brazil. Methods: This study included a sample of 89 parents and 89 children. To evaluate dental caries, the ceo-d index was used; the significant caries index (SiC Index) was used to evaluate the inequality of caries in the study sample; to evaluate the maternal SOC, the questionnaire (short version) was applied; and to evaluate the socioeconomic conditions, the SB Brazil 2010: National Research on Oral Health was used. Results: An average ceo-d of 1.50 was found, with a higher occurrence of dental caries in male participants, as well as an SiC index that proved to be higher in males, on average by 4.38 fold. The average sense of maternal coherence was higher among 5-year-old children, with a value of 39.33 on average. As regards socioeconomic conditions, it was observed that most participants, 42.33 on average, live with a monthly family income of R$1,501 to R$2,500 reais, and a considerable sample of 35.40 on average survives on a monthly family income of R$250 reais. Conclusion: No significant correlation was found between socioeconomic conditions and maternal SOC with the ceo-d index.
Assuntos
Classe Social , Pré-Escolar , Cárie Dentária , Senso de CoerênciaRESUMO
OBJECTIVE: To characterize the points and counterpoints in the development of interdisciplinarity in the nursing technical training. METHOD: This is an exploratory-descriptive study with a qualitative approach conducted through interviews with 30 teachers and coordinators of nursing technical courses from 12 different regions of the state of São Paulo. Data analysis was performed through theme-based content analysis. RESULTS: Regarding the theme of institutional orientation, it was found that, although there are initiatives to promote interdisciplinarity, since there is teacher training and definition of goals for articulation with other courses and for the joint work among the teachers of the disciplines, these are still vague and ineffective. As for the theme, the implementation of interdisciplinarity by the teachers, it is observed that they seek different forms of integration, but they come across the curricular structure, the form of teacher hiring, and the resistance to changes. With respect to the comprehension of the concept, relevant aspects of its meaning are recognized; however, they admit the existence of limits. CONCLUSION: The institution defines a trajectory aiming at interdisciplinarity, the teachers try to follow the path for its implementation; however, they find structural obstacles, little comprehension of the concept, and resistance to changes. It appears that efforts are needed to advance the curricular implementation with the logics of interdisciplinarity.