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Objetivo: conhecer as representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada na Estratégia Saúde da Família. Método: estudo qualitativo, orientado pela Teoria das Representações Sociais, realizado com 15 gestantes, entre abril e maio de 2019. Utilizou-se a entrevista semiestruturada. Os dados foram organizados por meio do Discurso do Sujeito Coletivo, com auxílio do software DSCsoft©. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultados: as representações sociais das mulheres em gravidez não planejada evidenciadas pelo Discurso do Sujeito Coletivo foram representadas por oito ideias centrais, a saber: "eu não me preveni, nem ele", "nós nos prevenimos", "eu comprava", "pegava no posto", "construir uma família", "ter esse acesso", "estou por fora" e "eu sei que é disponível". Conclusão: as representações sociais nos discursos das mulheres em gravidez não planejada estavam pautadas no desconhecimento acerca do planejamento reprodutivo, dos anticoncepcionais disponíveis e seu uso correto.
Objective: to understand the social representations of reproductive planning among women with unplanned pregnancies in the Family Health Strategy. Method: qualitative study, guided by the Theory of Social Representations, carried out with 15 pregnant women between April and May 2019. Semi-structured interviews were used. The data was organized using the Discourse of the Collective Subject, with the aid of DSCsoft© software. Research protocol approved by the Research Ethics Committee. Results: the social representations of women with unplanned pregnancies as evidenced by the Collective Subject Discourse were represented by eight central ideas, namely: "I didn't prevent myself, nor did he", "we prevented ourselves", "I would buy it", "I would get it at the health center", "build a family", "have this access", "I am not aware" and "I know it is available". Conclusion: the social representations in the women's speeches about unplanned pregnancies were based on a lack of knowledge about reproductive planning, the contraceptives available and their correct use.
Objetivo: conocer las representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado en la Estrategia Salud de la Familia. Método: estudio cualitativo, basado en la Teoría de las Representaciones Sociales, realizado con 15 mujeres embarazadas, entre abril y mayo de 2019. Se utilizaron entrevistas semiestructuradas. Los datos fueron organizados mediante el Discurso del Sujeto Colectivo, con ayuda del software DSCsoft©. El protocolo de investigación fue aprobado por el Comité de Ética en Investigación. Resultados: las representaciones sociales de las mujeres con embarazo no planificado reveladas por el Discurso del Sujeto Colectivo fueron representadas por ocho ideas centrales, a saber: "yo no me cuidé y él tampoco", "nos cuidamos", "yo los compraba", "los buscaba en el centro de salud", "construir una familia", "tener acceso", "no participo" y "sé que está disponible". Conclusión: las representaciones sociales en los discursos de las mujeres con embarazo no planificado se basaron en la falta de conocimiento sobre la planificación reproductiva, en los anticonceptivos disponibles y su uso correcto.
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We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD-DI) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD-DI without uneven late toxicities.
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BACKGROUND: Stilbenoid extracts, such as those originating from grapevine by-products (e.g. canes), are of interest for use as biopesticides in vineyard owing to their antimicrobial activities. However, stilbenoids are unstable in the environment, especially under light. This study aimed to chemically characterize the effect of UV light on stilbenoids present in a grapevine cane extract (CE), and to evaluate the antimicrobial activities against two major grapevine pathogens (Plasmopara viticola and Botrytis cinerea) of grapevine extracts exposed to UV. RESULTS: Treatment with UV (365 nm) on a grapevine CE led to degradation of stilbenoids (up to 71% after 1 h). The stilbenoid stability depended on their chemical structure: only those possessing CC, as trans-resveratrol and trans-ε-viniferin, were affected with first their isomerization and secondly their oxidation/cyclization. As a consequence, UV-exposed extracts (UV-CEs) showed reduced antimicrobial activities against the two pathogens (mycelium and spores). For instance, regarding P. viticola, an UV-CE exposed during 4 h showed an almost total loss of its activity on oomycete development and a 2.4-fold inhibition of zoospore mobility in comparison to CE. For B. cinerea, the inhibition capacity of the same UV-CE was reduced by only 1.1-fold on mycelial development and by 3.2-fold on conidial germination compared to CE. CONCLUSION: UV light triggered modifications on the structure of bioactive stilbenoids, resulting in losses of their antimicrobial activities. Photoprotection of stilbenoids has to be considered in the perspective of using them in vineyards as biopesticides. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Violence against women is defined as any act resulting from gender relations that cause death or physical, sexual, psychological, property and moral harm. Comprehensive care requires professionals understanding the support network to guide and refer women victims of violence to services and to value complaints/anxieties. The objective of this study was to identify the scientific production of comprehensive care for women victims of violence. This is an integrative literature review. Data collection was performed via a paired and independent search by two researchers in the Scopus, PubMed, CINAHL, Web of Science, LILACS, BDENF and SciELO databases between January and February 2023. After applying the eligibility criteria and descriptors in health sciences and medical subject headings, ten articles were retrieved. IRAMUTEQ software was used for data analyses. There are great challenges in implementing comprehensive care, and violence against women, as a serious social problem, demands health, education, social assistance and public security policies. The comprehensive actions taken in the care of women victims of violence demonstrate a strong link with the practices of reception and humanization, in addition to an interdisciplinary and intersectoral scope.
A violência direcionada à mulher é definida como todo ato resultante das relações de gênero que cause morte, dano físico, sexual, psicológico, patrimonial e moral. O cuidado integral possibilita que o profissional conheça a rede de apoio, a fim de orientá-las e encaminhá-las aos serviços, e valorize queixas/anseios. Objetivou-se identificar a produção científica acerca do cuidado integral às mulheres vítimas de violência. Trata-se de uma revisão integrativa da literatura. A coleta de dados ocorreu com busca pareada e independente de duas pesquisadoras, nos bancos Scopus, PubMed, CINAHL, Web of Science, LILACS, BDENF e SciELO, no período de janeiro e fevereiro de 2023. Foram utilizados critérios de elegibilidade, Descritores em Ciências da Saúde e Medical Subject Headings, totalizando dez artigos. Na análise dos dados, utilizou-se o software Iramuteq. Verificou-se grandes desafios para o cuidado integral, e que a violência contra a mulher, por ser uma problemática social grave, demanda políticas de saúde, educação, assistência social e segurança pública. Conclui-se que as ações integrais no cuidado à mulher vítima de violência demonstram forte vínculo com as práticas de acolhimento, humanização, além de perpassarem o âmbito interdisciplinar e intersetorial.
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Atención Integral de Salud , Violencia de Género , Humanos , Femenino , Atención Integral de Salud/organización & administración , Víctimas de Crimen/psicologíaRESUMEN
Despite the global vaccination campaigns, certain patient groups remain highly vulnerable to SARS-CoV-2 and are at high risk for unfavorable COVID-19 outcomes. As previously shown by our group and a more recent report by Chang Su and coworkers, patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT) represent one of such high-risk populations. This is due to the underlying disease-related immunodeficiency, suboptimal response to vaccines, heavy exposure to dexamethasone, and the use of high-dose melphalan prior to the ASCT procedure. Contracting SARS-CoV-2 and developing COVID-19 during the ASCT procedure remain high-risk events for these patients. It is then crucial to maintain and implement all appropriate strategies to prevent COVID-19 breakthroughs in this clinical setting. This might include targeted pre- and post-exposure prophylaxis with monoclonal antibodies, based on the circulation and prevalence of different SARS-CoV-2 variants/subvariants, and the prompt use of antivirals if, despite prophylaxis, MM patients develop COVID-19 during the transplantation procedure. We emphasize the importance of regularly monitoring MM patients for SARS-CoV-2 infection at all stages of the ASCT procedure. This is crucial to promptly implement measures to reduce the risk of unfavorable COVID-19 outcomes during the current post-pandemic phase.
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BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.
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Aterosclerosis , Modelos Animales de Enfermedad , Hígado , Ratones Noqueados para ApoE , Receptores de LDL , Animales , Receptores de LDL/genética , Receptores de LDL/deficiencia , Aterosclerosis/prevención & control , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/etiología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Factores de Tiempo , Ayuno/sangre , Ratones , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Hipercolesterolemia/complicaciones , Dieta Aterogénica , Aumento de Peso , Ratones Noqueados , Enfermedades de la Aorta/prevención & control , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/metabolismo , Lípidos/sangre , Apolipoproteínas ERESUMEN
Enterococcus faecalis is a resident of the human gut, though upon translocation to the blood or body tissues, it can be pathogenic. Here we discover and characterize two peptide-based quorum-sensing systems that transcriptionally modulate de novo purine biosynthesis in E. faecalis . Using a comparative genomic analysis, we find that most enterococcal species do not encode this system; E. moraviensis , E. haemoperoxidus and E. caccae , three species that are closely related to E. faecalis , encode one of the two systems, and only E. faecalis encodes both systems. We show that these systems are important for the intracellular survival of E. faecalis within macrophages and for the fitness of E. faecalis in a murine wound infection model. Taken together, we combine comparative genomics, microbiological, bacterial genetics, transcriptomics, targeted proteomics and animal model experiments to describe a paired quorum sensing mechanism that directly influences central metabolism and impacts the pathogenicity of E. faecalis .
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Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.
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Vacunas contra el Cáncer , Células Dendríticas , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Células Dendríticas/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Terapia Combinada , Animales , Inmunoterapia/métodos , Vacunación/métodosRESUMEN
Fragile X syndrome (FXS) is a monogenic neurodevelopmental disorder with manifestations spanning molecular, neuroanatomical, and behavioral changes. Astrocytes contribute to FXS pathogenesis and show hundreds of dysregulated genes and proteins; targeting upstream pathways mediating astrocyte changes in FXS could therefore be a point of intervention. To address this, we focused on the bone morphogenetic protein (BMP) pathway, which is upregulated in FXS astrocytes. We generated a conditional KO (cKO) of Smad4 in astrocytes to suppress BMP signaling, and found this lessens audiogenic seizure severity in FXS mice. To ask how this occurs on a molecular level, we performed in vivo transcriptomic and proteomic profiling of cortical astrocytes, finding upregulation of metabolic pathways, and downregulation of secretory machinery and secreted proteins in FXS astrocytes, with these alterations no longer present when BMP signaling is suppressed. Functionally, astrocyte Smad4 cKO restores deficits in inhibitory synapses present in FXS auditory cortex. Thus, astrocytes contribute to FXS molecular and functional phenotypes, and targeting astrocytes can mitigate FXS symptoms.
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: A educação em enfermagem caracteriza-se por discussões constantes sobre as abordagens pedagógicas utilizadas nos cursos de graduação em enfermagem, visando introduzir mudanças curriculares que possibilitem experiências de aprendizagem cada vez mais significativas. Nesse contexto, o objetivo deste estudo foi analisar a percepção dos estudantes sobre as práticas pedagógicas de um curso de graduação em enfermagem. Esta pesquisa adota abordagem qualitativa com ênfase crítico-reflexiva. Participaram do estudo quinze estudantes de enfermagem do oitavo semestre matriculados no curso Tópicos Especiais em Cuidados de Enfermagem de uma universidade pública do Nordeste do Brasil. A coleta de dados ocorreu no segundo semestre de 2019 por meio da análise de portfólios que expressavam significativamente o conteúdo abordado e o aprendizado adquirido. Após a transcrição dos textos, as informações obtidas foram analisadas com base na análise de conteúdo categorial temática. Emergiram três categorias: trabalho em equipe como ferramenta eficaz na construção do conhecimento; o processo de ensino-aprendizagem como parte integrante da produção de conhecimento significativo; e motivação e engajamento decorrentes de experiências positivas no curso. Essas categorias destacaram a importância do trabalho em equipe, do desenvolvimento de uma aprendizagem significativa e de experiências positivas decorrentes do uso desses métodos. Consequentemente, os estudantes indicaram que as práticas empregadas no curso os prepararam efetivamente para os desafios da prática profissional, permitindo-lhes desenvolver habilidades como pensamento crítico, tomada de decisões e trabalho em equipe.
O ensino de enfermagem é marcado por constantes discussões frente às propostas pedagógicas em uso nos cursos de graduação em enfermagem, a fim de introduzir mudanças curriculares, que viabilizam um aprendizado cada vez mais significativo. Diante do exposto, objetivou-se analisar a percepção dos discentes sobre as práticas pedagógicas em um curso de graduação em enfermagem. Trata-se de uma pesquisa de abordagem qualitativa, com ênfase crítica-reflexiva. Participaram 15 estudantes, do oitavo período de enfermagem, matriculados na disciplina Tópicos Especiais do Cuidado de Enfermagem, pertencentes a uma universidade pública do Nordeste brasileiro. A coleta foi realizada no segundo semestre de 2019, por meio da análise de um portfólio que expressa de forma significativa os conteúdos competitivos, bem como o aprendizado adquirido. Após a transcrição dos textos, as informações obtidas foram exploradas com base na análise de conteúdo do tipo categorial temático. Revela-se três categorias: Trabalho em equipe como ferramenta eficaz na construção do conhecimento; O processo de ensino-aprendizagem como parte integrante na produção de um saber significativo; Motivação e engajamento através de experiências positivas na disciplina imersas respectivamente na importância do trabalho em equipe, desenvolvimento de um aprendizado significativo, além de experiências positivas frente à utilização desses métodos. Assim, os estudantes evidenciaram que as práticas usadas na disciplina os prepararam de forma eficaz para os desafios das práticas profissionais permitindo-lhes desenvolver habilidades como pensamento crítico, tomada de decisão e trabalho em equipe.
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Meningitis is the infection of the meninges, which are connective tissue membranes covering the brain, and it most commonly affects the leptomeninges. Clinically, meningitis may present with fever, neck stiffness, altered mental status, headache, vomiting, and neurological deficits. Encephalitis is an infection of the brain, which usually presents with fever, altered mental status, neurological deficits, and seizure. Meningitis and encephalitis are serious conditions which could also coexist, with high morbidity and mortality, thus requiring prompt diagnosis and treatment. Imaging plays an important role in the clinical management of these conditions, especially Magnetic Resonance Imaging. It is indicated to exclude mimics and evaluate the presence of complications. The aim of this review is to depict imaging findings of the most common meningitis and encephalitis.
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Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.
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Adipocitos , Dieta Alta en Grasa , Inflamación , Resistencia a la Insulina , Factor 3 Regulador del Interferón , Ratones Noqueados , Obesidad , Animales , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/genética , Masculino , Obesidad/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Adipocitos/metabolismo , Ratones Endogámicos C57BL , Glucosa/metabolismo , Células 3T3-L1RESUMEN
Dendritic cells (DCs) are major antigen-presenting cells that connect innate and adaptive immunity. Hepatic DCs are less activated and contribute to maintain the tolerogenic environment of the liver under steady state. Several studies indicated DCs in metabolic dysfunction-associated steatohepatitis (MASH), representing a substantial burden on healthcare systems due to its association with liver-related morbidity and mortality. Studies highlighted the potential disease-promoting role of liver DCs in the development of MASH while other experimental systems suggested their protective role. This review discusses this controversy and the current understanding of how DCs affect the pathogenesis of MASH.
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Células Dendríticas , Células Dendríticas/inmunología , Humanos , Animales , Hígado/inmunología , Hígado Graso/inmunologíaRESUMEN
Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration.
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Ceramidas , Receptores de Adiponectina , Retina , Animales , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/genética , Ratones , Ceramidas/metabolismo , Retina/metabolismo , Retina/patología , Ratones Noqueados , Ácidos Grasos Insaturados/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Degeneración Macular/metabolismo , Degeneración Macular/patología , Degeneración Macular/genéticaRESUMEN
Lipid synthesis increases during the cell cycle to ensure sufficient membrane mass, but how insufficient synthesis restricts cell-cycle entry is not understood. Here, we identify a lipid checkpoint in G1 phase of the mammalian cell cycle by using live single-cell imaging, lipidome, and transcriptome analysis of a non-transformed cell. We show that synthesis of fatty acids in G1 not only increases lipid mass but extensively shifts the lipid composition to unsaturated phospholipids and neutral lipids. Strikingly, acute lowering of lipid synthesis rapidly activates the PERK/ATF4 endoplasmic reticulum (ER) stress pathway that blocks cell-cycle entry by increasing p21 levels, decreasing Cyclin D levels, and suppressing Retinoblastoma protein phosphorylation. Together, our study identifies a rapid anticipatory ER lipid checkpoint in G1 that prevents cells from starting the cell cycle as long as lipid synthesis is low, thereby preventing mitotic defects, which are triggered by low lipid synthesis much later in mitosis.
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Lípidos , Mitosis , Animales , Ciclo Celular , Fase G1 , Fosforilación , MamíferosRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. The recognition of BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift toward CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combinations of treatments with other anti-leukemic drugs. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy.
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Neoplasias Hematológicas , Subunidad alfa del Receptor de Interleucina-3 , Trastornos Mieloproliferativos , Humanos , Células Dendríticas , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/patología , Subunidad alfa del Receptor de Interleucina-3/efectos de los fármacos , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Trasplante de Células MadreAsunto(s)
Antineoplásicos , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Antineoplásicos/uso terapéutico , Agammaglobulinemia Tirosina Quinasa , Italia , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
BACKGROUND: When feeding on a vertebrate host, ticks secrete saliva, which is a complex mixture of proteins, lipids, and other molecules. Tick saliva assists the vector in modulating host hemostasis, immunity, and tissue repair mechanisms. While helping the vector to feed, its saliva modifies the site where pathogens are inoculated and often facilitates the infection process. The objective of this study is to uncover the variation in protein composition of Rhipicephalus microplus saliva during blood feeding. METHODS: Ticks were fed on calves, and adult females were collected, weighed, and divided in nine weight groups, representing the slow and rapid feeding phases of blood feeding. Tick saliva was collected, and mass spectrometry analyses were used to identify differentially secreted proteins. Bioinformatic tools were employed to predict the structural and functional features of the salivary proteins. Reciprocal best hit analyses were used to identify conserved families of salivary proteins secreted by other tick species. RESULTS: Changes in the protein secretion profiles of R. microplus adult female saliva during the blood feeding were observed, characterizing the phenomenon known as "sialome switching." This observation validates the idea that the switch in protein expression may serve as a mechanism for evading host responses against tick feeding. Cattle tick saliva is predominantly rich in heme-binding proteins, secreted conserved proteins, lipocalins, and protease inhibitors, many of which are conserved and present in the saliva of other tick species. Additionally, another remarkable observation was the identification of host-derived proteins as a component of tick saliva. CONCLUSIONS: Overall, this study brings new insights to understanding the dynamics of the proteomic profile of tick saliva, which is an important component of tick feeding biology. The results presented here, along with the disclosed sequences, contribute to our understanding of tick feeding biology and might aid in the identification of new targets for the development of novel anti-tick methods.
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Rhipicephalus , Animales , Femenino , Bovinos , Rhipicephalus/fisiología , Saliva/química , Proteómica , Proteínas de Artrópodos/metabolismo , Proteínas y Péptidos Salivales/metabolismoRESUMEN
RESUMO: Objetivo: analisar a abordagem dos conteúdos relacionados ao empreendedorismo nas dimensões ético-políticas em documentos curriculares dos cursos de graduação em Enfermagem. Método: pesquisa documental, com abordagem mista e natureza descritiva, de junho de 2021 a agosto de 2022, com verificação no site do Ministério da Educação, das instituições que ofertam cursos em Enfermagem na região Nordeste do Brasil. Avaliação de conteúdo e quantitativa pelo teste-T. Resultados: a maioria das IES oferecia cursos presenciais (94,1%) e pertencia a instituições privadas (64,7%). As disciplinas abordavam principalmente temas teóricos (94,1%), destacando a importância do empreendedorismo na formação de enfermeiros. A análise lexicográfica e de similitude destacou a forte ligação entre as palavras "Empreendedor" e "Saúde", evidenciando a relevância desses conceitos na formação dos enfermeiros. Conclusão: os documentos curriculares destacam a importância de formar enfermeiros em seu papel profissional e empreendedor com competência, levando em consideração os princípios da Bioética, Moral, Ciência e Filosofia.
ABSTRACT Objective: to analyze the approach to content related to entrepreneurship in the ethical-political dimensions in curricular documents of undergraduate nursing courses. Method: documentary research, with a mixed approach and descriptive nature, from June 2021 to August 2022, with inspection of the Ministry of Education's website, of the institutions offering Nursing courses in the Northeast region of Brazil. Content and quantitative evaluation using the T-test. Results: the majority of HEIs offered face-to-face courses (94.1%) and belonged to private institutions (64.7%). The subjects mainly covered theoretical topics (94.1%), highlighting the importance of entrepreneurship in the training of nurses. The lexicographic and similarity analysis highlighted the strong link between the words "Entrepreneur" and "Health", highlighting the relevance of these concepts in the training of nurses. Conclusion: The curriculum documents highlight the importance of training nurses in their professional and entrepreneurial roles with competence, taking into account the principles of Bioethics, Morals, Science, and Philosophy.
RESUMEN: Objetivo: analizar el abordaje de contenidos relacionados con el emprendimiento en dimensiones ético-políticas en documentos curriculares de cursos de graduación en Enfermería. Método: investigación documental, de enfoque mixto y de carácter descriptivo, de junio de 2021 a agosto de 2022, con verificación en el sitio web del Ministerio de Educación de las instituciones que ofrecen cursos de Enfermería en la región Noreste de Brasil. Evaluación de contenidos y cuantitativa mediante la prueba T. Resultados: la mayoría de las IES ofrecían carreras presenciales (94,1%) y pertenecían a instituciones privadas (64,7%). Los temas abordaron principalmente temas teóricos (94,1%), destacando la importancia del emprendimiento en la formación del enfermero. El análisis lexicográfico y de similitud destacó la fuerte conexión entre las palabras "Emprendedor" y "Salud", destacando la relevancia de esos conceptos en la formación de enfermeros. Conclusión: los documentos curriculares resaltan la importancia de formar enfermeros en su rol profesional y empresarial con competencia, teniendo en cuenta los principios de la Bioética, la Moral, la Ciencia y la Filosofía.