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BACKGROUND: In recent years, researchers have made significant strides in understanding the heterogeneity of breast cancer and its various subtypes. However, the wealth of genomic and proteomic data available today necessitates efficient frameworks, instruments, and computational tools for meaningful analysis. Despite its success as a prognostic tool, the PAM50 gene signature's reliance on many genes presents challenges in terms of cost and complexity. Consequently, there is a need for more efficient methods to classify breast cancer subtypes using a reduced gene set accurately. RESULTS: This study explores the potential of achieving precise breast cancer subtype categorization using a reduced gene set derived from the PAM50 gene signature. By employing a "Few-Shot Genes Selection" method, we randomly select smaller subsets from PAM50 and evaluate their performance using metrics and a linear model, specifically the Support Vector Machine (SVM) classifier. In addition, we aim to assess whether a more compact gene set can maintain performance while simplifying the classification process. Our findings demonstrate that certain reduced gene subsets can perform comparable or superior to the full PAM50 gene signature. CONCLUSIONS: The identified gene subsets, with 36 genes, have the potential to contribute to the development of more cost-effective and streamlined diagnostic tools in breast cancer research and clinical settings.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Biomarcadores de Tumor/genética , Proteómica , Perfilación de la Expresión Génica/métodos , Técnicas GenéticasRESUMEN
AIM: To evaluate the role of regulatory T lymphocytes (Tregs) in the presence or absence of the synthetic ligand Pam3Cys during the progression of periapical lesion in wild-type (WT) and toll-like receptor 2 knockout (TLR2KO) mice. METHODOLOGY: A total of 130 C57BL/6 male WT and TLR2KO mice were allocated into control (n = 5) and experimental (periapical lesion induction) (n = 10) groups. In specific groups (WT+Pam3cys and TLR2KO+Pam3cys), the synthetic ligand Pam3cys was administered intraperitoneally every 7 days, according to the experimental period (14, 21 and 42 days). At the end of those periods, the animals were euthanized, and the mandible and the spleen were submitted to histotechnical processing. Mandible histological sections were analysed by haematoxylin and eosin, TRAP histoenzymology and immunohistochemistry (FOXP3, RANK, RANKL and OPG). Spleen sections were analysed by immunohistochemistry (FOXP3). RESULTS: The inflammatory infiltrate and bone resorption were more intense in the TLR2KO group compared to the WT group. The animals that received the Pam3cys had smaller periapical lesions when compared to the animals that did not receive the ligand (p < .05). TLR2KO animals showed a significant increase in the number of osteoclasts when compared to TLR2KO+Pam3cys group (p < .05). At 21 days, the WT+Pam3cys group had a lower number of osteoclasts when compared to the WT animals (p = .02). FOXP3 expression was more intense in the WT+Pam3cys groups when compared to the WT animals in the 42 days (p = .03). In the spleen analysis, the WT+Pam3cys group also had a higher expression of FOXP3 when compared to the WT animals at 14 and 42 days (p = .02). Concerning RANKL, there was a reduction in staining in the KOTLR2+Pam3cys groups at 21 and 42 days (p = .03) and a higher binding ratio between RANK/RANKL in animals that did not receive the ligand. CONCLUSION: Administration of the Pam3cys increased the proliferation of Tregs, showed by FOXP3 expression and prevented the progression of the periapical lesion in WT mice. On the other hand, in the TLR2KO animals, Treg expression was lower with larger areas of periapical lesions. Finally, systemic administration of the Pam3cys in KO animals was able to limit the deleterious effects of the absence of the TLR2 receptor.
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Osteoclastos , Receptor Toll-Like 2 , Ratones , Masculino , Animales , Osteoclastos/metabolismo , Receptor Toll-Like 2/metabolismo , Ligandos , Ratones Endogámicos C57BL , Ligando RANK/farmacología , Ligando RANK/metabolismo , Factores de Transcripción Forkhead/metabolismo , Ratones NoqueadosRESUMEN
Background: Breast cancer (BRCA) represents the most frequent diagnosed malignancy in women worldwide. Despite treatment advances, BRCAs eventually develop resistance to targeted therapies, resulting in poor prognosis. The identification of new biomarkers, like immune-related long non-coding RNAs (lncRNAs), could contribute to the clinical management of BRCA patients. In this report, we evaluated the LINC00426 expression in PAM50 BRCA subtypes from two clinical independent cohorts (BRCA-TCGA and GEO-GSE96058 datasets). Methods and results: Using Cox regression models and Kaplan-Meier survival analyses, we identified that LINC00426 expression was a consistent overall survival (OS) predictor in luminal B (LB) BRCA patients. Subsequently, differential gene expression and gene set enrichment analyses identified that LINC00426 expression was associated with different immune-related and cancer-related pathways and processes in LB BRCA. Additionally, the LINC00426 expression was correlated with the infiltration level of diverse immune cell populations, alongside immune checkpoint and cytolytic activity-related gene expression. Conclusion: This evidence suggests that LINC00426 is a potential biomarker of immune phenotype and an OS predictor in PAM50 LB BRCA.
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Background: Cryptococcosis is a relevant invasive fungal infection that affects immunocompromised and immunocompetent individuals when caused by Cryptococcus gattii. Host innate and adaptive immune responses can be subverted by C. gattii, that blocks the differentiation of T helper (Th) 1 and Th17 cells, which are involved in the protection against cryptococcosis. Moreover, the macrophage polarization is modulated by C. gattii infection that requires a balance in the macrophage subsets to control the C. gattii infection. Toll-like receptor (TLR) 2 agonists are important immunomodulators favoring a pro-inflammatory response with potential fungicidal activity, and TLR2 agonists have been used as adjuvants in vaccines against infections caused by bacteria or viruses. Therefore, this work aimed to evaluate the immunomodulatory effect of the tripalmitoyl lipopeptide S-glycerol cysteine (Pam3CSK4 or P3C4), a TLR2 agonist, as an adjuvant in the vaccination against C. gattii infection. Methods and Results: C57BL/6 mice were immunized with 2 × 107 inactivated yeasts of C. gattii via intranasal route on day 1, 14 and 28 (Immunized group). Immunization was associated with 1µg or 10µg of adjuvant P3C4 (Immunized+P3C4-1µg or Immunized+P3C4-10 µg), followed by C. gattii infection on day 42 after the immunization protocol. Immunized+P3C4-1 µg group had reduced levels of IgG1, IgG2a and IgA and no significant difference in the IgG and IgM anti-GXM antibody titer was detected, compared to the Immunized group. High levels of IL-17 and IL-1ß in lung tissue of mice from the Immunized+P3C4-1µg group did not promote a predominance of Th17 cells, in contrast, the frequency of TLR2+ cells was increased in immunized mice that received 1 µg of P3C4. The reduction in the relative expression of T-bet and high levels of Foxp3 detected in the lungs of the Immunized+P3C4-1µg group suggest a prevalence of regulatory T cells in the tissue, which did not contribute to the control of C. gattii infection. The immunization protocol associated with 10 µg of adjuvant P3C4 induced high levels of IL-17 in the lung tissue, whereas the levels of pro-inflammatory cytokines were downregulated. To evaluate the effect of adjuvant P3C4 in the control of C. gattii infection, quantification of the fungal burden in the lungs was performed by the CFU assay, and the groups with adjuvant P3C4 showed a pulmonary C. gattii burden that was not significantly altered when compared with the immunized group. The mice that received 1 µg of adjuvant P3C4 had a lower percentage of inflammatory infiltrate in the lungs. Conclusion: The immunomodulatory effect of P3C4, associated with the immunization protocol, plays an imbalance between pro- and anti-inflammatory response in the lungs that did not favor a protection against C. gattii infection, which is related to the immune response characterized by a suppressive/regulatory profile in the pulmonary microenvironment after C. gattii infection.
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Criptococosis , Cryptococcus gattii , Animales , Ratones , Interleucina-17 , Receptor Toll-Like 2 , Ratones Endogámicos C57BL , Criptococosis/prevención & control , Inmunización , Vacunación , Adyuvantes Inmunológicos/farmacologíaRESUMEN
CRISPR-Cas systems are composed of repeated sequences separated by non-repeated sequences that are near genes coding for Cas proteins, which are involved in the function of these systems. Their function has been mostly related to "genetic immunity" against foreign genetic material, among other roles. Interest in them increased after their use in genetic manipulation was uncovered and surveys to find and classify them have been done in several bacterial groups. To determine the presence of these genetic elements in the Burkholderiaceae family members, a bioinformatic approach was followed. Attention in this family comes as it is formed by a great diversity of microorganisms that include opportunistic and true pathogens, and symbiotic and saprophytic organisms, among others. Results show that, in contrast to other bacterial groups, only 8.4% of family members harbor complete CRISPR-Cas systems and the rest either do not have one or have remains or sections of one. Analyses of the spacer sequences indicated that most of them have identity to sections of the same genomes they were found, while a few had identities with either plasmids or phages. The genus with the higher proportion of self-directed spacers is Ralstonia, and their possible roles are discussed. Most of the systems (60%) belong to the class I subtype I-E and a few to subtypes I-C (13.3%), I-F (18.3%), II-C (5%), IV-A (1.7%) and V-C (1.7%). To the best of our knowledge, this is the first study to uncover the CRISPR-Cas system for the whole Burkholderiaceae family.
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Bacteriófagos , Burkholderiaceae , Sistemas CRISPR-Cas , Burkholderiaceae/genética , Plásmidos , Biología Computacional , Bacteriófagos/genética , Bacterias/genéticaRESUMEN
Resumen Esta investigación analizó las actitudes hacia la muerte expresadas por un grupo de adultos jóvenes en contexto COVID-19. Los participantes fueron 10 jóvenes residentes en la región de Tarapacá (60% mujeres, 40% hombres) entre 18 a 29 años. La metodología tuvo un enfoque mixto de preponderancia cualitativa y diseño secuencial. En la primera etapa, se administró el Perfil Revisado de Actitudes hacia la muerte [PAM-R] para medir cinco actitudes: Miedo a la muerte; Evitación de la muerte; Aceptación de acercamiento; Aceptación de escape; y Aceptación neutral. Posteriormente, se aplicaron entrevistas semiestructuradas que profundizaron los resultados, mediante la exploración de las percepciones, emociones y pensamientos de los participantes durante la pandemia. Finalmente, se triangularon los datos cuantitativos y cualitativos para obtener una mayor validez. Los resultados señalan a estas actitudes como un fenómeno contextual, cuya expresión depende de diversos elementos personales y del entorno, siendo los más importantes los miedos asociados a familiares. En jóvenes, la muerte fue comprendida como una realidad lejana. Esto influyó en una alta neutralidad y bajo miedo a la muerte propia. El contexto COVID-19 actuó como un factor influyente en las actitudes, particularmente en el miedo al contagio o a la posibilidad de morir. Si bien los jóvenes reconocieron la peligrosidad del virus, sus necesidades emocionales-afectivas se vislumbraron como problemas más urgentes. Por lo tanto, los miedos en contexto COVID-19 no evitaron la exposición al contagio en compañía de amigos. Estas conductas fueron significadas como medidas de autocuidado psicológico, particularmente en jóvenes con Aceptación de Escape.
Abstract This research analyzed the attitudes towards death expressed by a group of young adults in a COVID-19 context. The participants were 10 young residents in the Tarapacá region (60% women, 40% men) between 18 and 29 years old. The methodology had a mixed approach of qualitative preponderance and sequential design. First, the Death Attitude Profile-Revised [DAP-R] was administered to measure five attitudes: Fear of Death, Death Avoidance, Approach Acceptance, Escape Acceptance, and Neutral Acceptance. Subsequently, semi-structured interviews were applied that deepened the results, by exploring the perceptions, emotions and thoughts of the participants during the pandemic. Finally, the quantitative and qualitative data were triangulated to obtain greater validity. The results point to these attitudes as a contextual phenomenon, the expression of which depends on various personal and environmental elements, the most important being the fears associated with family members. In young people, death was understood as a distant reality. This influenced a high neutrality and low fear of own death. The COVID-19 context acted as an influencing factor in attitudes, particularly in fear of contagion or the possibility of dying. Although the young people recognized the dangerousness of the virus, their emotional-affective needs were seen as more urgent problems. Therefore, fears in the COVID-19 context did not prevent exposure to contagion in the company of friends. These behaviors were signified as measures of psychological self-care, particularly in young people with Escape Acceptance.
Resumo Este estudo teve como objetivo analisar as atitudes de um grupo de jovens adultos em relação a morte no contexto de COVID-19. Nela participaram 10 jovens que vivem na região de Tarapacá (60% mulheres, 40% homens) os quais tinham entre 18 e 29 anos. A metodologia da pesquisa teve uma abordagem mista de preponderância qualitativa e desenho de investigação sequencial. Na primeira etapa, foi administrado o Perfil Revisado de Atitudes em Relação a Morte [PAM-R] para medir cinco atitudes: Medo da morte; Evitar a morte; Aceitação de abordagem; Aceitação de fuga; e aceitação neutra. Posteriormente, foram aplicadas entrevistas semi-estruturadas que aprofundaram os resultados, explorando as percepções, emoções e pensamentos dos participantes durante a pandemia. Por fim, os dados quantitativos e qualitativos foram triangulados para obter maior validade. Os resultados apontam essas atitudes como um fenômeno contextual, cuja expressão depende de diversos elementos pessoais e do meio ambiente, sendo o mais importante deles, os medos associados aos parentes. Nos jovens, a morte era entendida como uma realidade distante. Isso influenciou uma alta neutralidade e pouco medo da propia morte. O contexto de COVID-19 atuou como um fator influente nas atitudes, particularmente no medo de contágio ou na possibilidade de morrer. Enquanto os jovens reconheciam o perigo do vírus, suas necessidades emotivas e afetivas eram vistas como problemas mais urgentes. Portanto, os temores no contexto de COVID-19 não impediram a exposição ao contágio na companhia de amigos. Esses comportamentos foram considerados como medidas de autocuidado psicológico, particularmente em jovens com Aceitação da Fuga da morte.
Asunto(s)
Masculino , Femenino , Adolescente , Adulto , Virus , COVID-19 , MiedoRESUMEN
Esta investigación analizó las actitudes hacia la muerte expresadas por un grupo de adultos jóvenes en contexto COVID-19. Los participantes fueron 10 jóvenes residentes en la región de Tarapacá (60% mujeres, 40% hombres) entre 18 a 29 años. La metodología tuvo un enfoque mixto de preponderancia cualitativa y diseño secuencial. En la primera etapa, se administró el Perfil Revisado de Actitudes hacia la muerte [PAM-R] para medir cinco actitudes: Miedo a la muerte; Evitación de la muerte; Aceptación de acercamiento; Aceptación de escape; y Aceptación neutral. Posteriormente, se aplicaron entrevistas semiestructuradas que profundizaron los resultados, mediante la exploración de las percepciones, emociones y pensamientos de los participantes durante la pandemia. Finalmente, se triangularon los datos cuantitativos y cualitativos para obtener una mayor validez. Los resultados señalan a estas actitudes como un fenómeno contextual, cuya expresión depende de diversos elementos personales y del entorno, siendo los más importantes los miedos asociados a familiares. En jóvenes, la muerte fue comprendida como una realidad lejana. Esto influyó en una alta neutralidad y bajo miedo a la muerte propia. El contexto COVID-19 actuó como un factor influyente en las actitudes, particularmente en el miedo al contagio o a la posibilidad de morir. Si bien los jóvenes reconocieron la peligrosidad del virus, sus necesidades emocionales-afectivas se vislumbraron como problemas más urgentes. Por lo tanto, los miedos en contexto COVID-19 no evitaron la exposición al contagio en compañía de amigos. Estas conductas fueron significadas como medidas de autocuidado psicológico, particularmente en jóvenes con Aceptación de Escape.
This research analyzed the attitudes towards death expressed by a group of young adults in a COVID-19 context. The participants were 10 young residents in the Tarapacá region (60% women, 40% men) between 18 and 29 years old. The methodology had a mixed approach of qualitative preponderance and sequential design. First, the Death Attitude Profile-Revised [DAP-R] was administered to measure five attitudes: Fear of Death, Death Avoidance, Approach Acceptance, Escape Acceptance, and Neutral Acceptance. Subsequently, semi-structured interviews were applied that deepened the results, by exploring the perceptions, emotions and thoughts of the participants during the pandemic. Finally, the quantitative and qualitative data were triangulated to obtain greater validity. The results point to these attitudes as a contextual phenomenon, the expression of which depends on various personal and environmental elements, the most important being the fears associated with family members. In young people, death was understood as a distant reality. This influenced a high neutrality and low fear of own death. The COVID-19 context acted as an influencing factor in attitudes, particularly in fear of contagion or the possibility of dying. Although the young people recognized the dangerousness of the virus, their emotional-affective needs were seen as more urgent problems. Therefore, fears in the COVID-19 context did not prevent exposure to contagion in the company of friends. These behaviors were signified as measures of psychological self-care, particularly in young people with Escape Acceptance.
Este estudo teve como objetivo analisar as atitudes de um grupo de jovens adultos em relação a morte no contexto de COVID-19. Nela participaram 10 jovens que vivem na região de Tarapacá (60% mulheres, 40% homens) os quais tinham entre 18 e 29 anos. A metodologia da pesquisa teve uma abordagem mista de preponderância qualitativa e desenho de investigação sequencial. Na primeira etapa, foi administrado o Perfil Revisado de Atitudes em Relação a Morte [PAM-R] para medir cinco atitudes: Medo da morte; Evitar a morte; Aceitação de abordagem; Aceitação de fuga; e aceitação neutra. Posteriormente, foram aplicadas entrevistas semi-estruturadas que aprofundaram os resultados, explorando as percepções, emoções e pensamentos dos participantes durante a pandemia. Por fim, os dados quantitativos e qualitativos foram triangulados para obter maior validade. Os resultados apontam essas atitudes como um fenômeno contextual, cuja expressão depende de diversos elementos pessoais e do meio ambiente, sendo o mais importante deles, os medos associados aos parentes. Nos jovens, a morte era entendida como uma realidade distante. Isso influenciou uma alta neutralidade e pouco medo da propia morte. O contexto de COVID-19 atuou como um fator influente nas atitudes, particularmente no medo de contágio ou na possibilidade de morrer. Enquanto os jovens reconheciam o perigo do vírus, suas necessidades emotivas e afetivas eram vistas como problemas mais urgentes. Portanto, os temores no contexto de COVID-19 não impediram a exposição ao contágio na companhia de amigos. Esses comportamentos foram considerados como medidas de autocuidado psicológico, particularmente em jovens com Aceitação da Fuga da morte.
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Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).
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BACKGROUND: HER2-positive breast cancer is an aggressive tumor subtype and it is usually associated with worse clinical outcomes. Given the advances in HER2-targeted therapies, we hypothesized that HER2 amplification is no longer a marker of poor prognosis. METHODS: We conducted a population-based observational study employing two independent cohorts of patients with breast cancer. Samples from the METABRIC cohort were collected before clinical availability of HER2-targeted therapies, whereas samples from the SCAN-B cohort were collected afterward. The primary endpoint was overall survival (OS). RESULTS: A total of 5121 patients were included in the analyses. In both cohorts, HER2-positive tumors were more likely to be node-positive (P < .05) and high grade (P < .001). Before HER2-targeted agents, HER2 patients had a significantly worse 5-year OS than hormone receptor-positive (HR+) patients (63.4% vs. 83.0%, HR = 2.49, P < .001). In contrast, after HER2-targeted agents entered clinical practice, 5-year OS no longer differed (88.3% vs. 90.4%, HR = 1.24, P = .17). Additionally, in an exploratory analysis using PAM50 subtypes, we identified that, after HER2-targeted therapies were implemented, patients clinically HER2-negative but PAM50-HER2-enriched have a lower OS (HR = 1.99, P = .009) than those who are both HER2-positive and PAM50-HER2-enriched, since they have not benefitted from HER2-targeted therapies. CONCLUSIONS: HER2-targeted therapies dramatically altered the natural history of HER2-positive breast cancer, with overall survival approaching those of luminal subtype. HER2 positivity is no longer a marker of poor prognosis if access to HER2-targeted therapies is granted. Future trials should assess whether HER2-negative PAM50-HER2-enriched patients may also benefit from such therapies.
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Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Femenino , Humanos , Pronóstico , Receptor ErbB-2RESUMEN
This study focuses on a Lyngbya cf. aestuarii dominated mat community from the intertidal zone of the Laguna Ojo de Liebre, Baja California Sur. In this environment, the mat is desiccated for several days between spring tides. While the mats were desiccated, photosynthetic activity was absent but recovered rapidly (~3 h) upon rehydration. It has been shown previously that the rate of photosynthetic recovery is dependent on both light intensity and salinity. In the current study, photosynthetic recovery was measured based on chlorophyll a fluorescence using pulse amplitude modulated (PAM) fluorometry. Upon the addition of water, photosystem II (PSII) complexes recovered the capacity for reaction centre excitation. However, these functional centres were initially closed. Respiratory activity early in recovery probably reduced the plastoquinone pool through the shared use of part of the photosynthetic transport chain, thus temporarily blocking electron transport downstream of PSII. The time that PSII complexes remained closed increased with light intensities above saturation. This condition is potentially damaging to the cyanobacteria since the exposure of closed PSII centres to high light intensities can lead to the production of singlet oxygen. After this initial lag period, PSII centres opened rapidly indicating an increase in the flow of electrons from PSII to PSI. The rate of photosynthetic recovery appeared to be limited primarily by the relatively slow return of functional PSII. Photosynthetic recovery rates were slower in salinities greater than those that naturally occur in the intertidal zone.
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Clorofila , Cianobacterias , Clorofila A , Fluidoterapia , Fluorescencia , Luz , México , Fotosíntesis , SalinidadRESUMEN
Objetivo: analisar a influência da pandemia nas consultas preventivas da Saúde da Mulher na atenção primária, descrevendo a percepção das mulheres quanto à assistência de enfermagem e orientação prestada durante o período da pandemia e avaliando sobre o retorno da paciente para busca do resultado. Método: estudo de qualitativa e exploratório que utilizou os princípios de Gil. Entre março e dezembro de 2020, foram entrevistadas 11 mulheres com idade entre 18 e 23 anos, que responderam questões referentes ao exame Papanicolau realizado durante a pandemia e suas experiências. Resultados: Após a transcrição e análise das entrevistas, surgiram quatro categorias temáticas, a ser: motivos para realização do papanicolau; sobre a realização do papanicolau durante a pandemia; orientações sobre a covid-19 e sobre o exame papanicolau por parte da equipe durante a pandemia; e orientação sobre a importância da busca do resultado. Conclusão: As entrevistas evidenciaram que as mulheres se sentiram inseguras em realizar o exame, bem como a dificuldade em acessar os serviços de saúde durante a pandemia. Além da necessidade do fortalecimento de ações de educação em saúde que visem a realização, orientação e importância do retorno para busca do resultado
Objective: to assess the influence of the pandemic on preventive consultations in Women's Health, describing the perception of women in relation to the nursing care provided during the pandemic and evaluating the patient's return to search for the result. Method: qualitative and exploratory study that used Gil's principles. Between March and December 2020, 11 women aged between 18 and 23 years were interviewed, who answered questions regarding the Pap smear test performed during the pandemic and their experiences. Results: After the transcription and analysis of the interviews, four thematic categories appeared: reasons for performing the pap smear; on the performance of the pap smear during the pandemic; guidelines on covid-19 and the pap smear by the team during the pandemic; and guidance on the importance of the search for the result. Conclusion: The interviews showed that women felt insecure about taking the exam and had difficulty in accessing health services during the pandemic. In addition to the need to strengthen health education actions aimed at the achievement, guidance and importance of the return to search for the result.
Objetivo: evaluar la influencia de la pandemia en las consultas preventivas en salud de la mujer, describiendo la percepción de las mujeres en relación a los cuidados de enfermería brindados durante la pandemia y evaluando el retorno de la paciente para buscar el resultado. Método: estudio cualitativo y exploratorio que utilizó los principios de Gil. Entre marzo y diciembre de 2020 se entrevistó a 11 mujeres de entre 18 y 23 años, quienes respondieron preguntas sobre la prueba de Papanicolaou realizada durante la pandemia y sus experiencias. Resultados: Tras la transcripción y análisis de las entrevistas, aparecieron cuatro categorías temáticas: motivos para realizar la prueba de Papanicolaou; sobre la realización de la prueba de Papanicolaou durante la pandemia; directrices sobre covid-19 y la prueba de Papanicolaou por parte del equipo durante la pandemia; y orientación sobre la importancia de la búsqueda del resultado. Conclusión: Las entrevistas mostraron que las mujeres se sentían inseguras sobre la realización del examen y tenían dificultades para acceder a los servicios de salud durante la pandemia. Además de la necesidad de fortalecer las acciones de educación en salud orientadas al logro, orientación e importancia del retorno para la búsqueda del resultado.
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Femenino , Salud de la Mujer , Atención Primaria de Salud , Pandemias , Prueba de PapanicolaouRESUMEN
BACKGROUND: The macrophage lineage is characterized by plasticity due to the acquisition of distinct functional phenotypes, and two major subsets are evaluated; classical M1 activation (strong microbicidal activity) and alternative M2 activation (immunoregulatory functions). The M1 subset expresses inducible nitric oxide synthase (iNOS), which is a primary marker to identify these cells, whereas M2 macrophages are characterized by expression of Arginase-1, found in inflammatory zone 1 (Fizz1), chitinase-like molecule (Ym-1), and CD206. The micro-environmental stimuli and signals in tissues are critical in the macrophage polarization. Toll-like receptors (TLR) ligands, such as lipopolysaccharide (LPS), palmitoyl-3-cysteine-serine-lysine-4 (Pam3CSK4), and ArtinM (mannose-binding lectin) are inductors of M1 subset. The impact of TLR2 and TLR4 signals to fight against Cryptococcus gattii infection is unknown, which is a fungal pathogen that preferentially infects the lung of immunocompetent individuals. The macrophages initiate an immune response to combat the C. gattii, then we evaluated in RAW 264.7 cell the effect of TLR2 and TLR4 agonists on the macrophage polarization dynamic and the impact on the growth of C. gattii. METHODS AND RESULTS: We demonstrated that P3C4, LPS, and ArtinM induced an increase in the levels of iNOS transcripts in RAW 264.7 cells, whereas the relative expression of arginase-1, Ym-1, and Fizz1 was significantly increased in the presence of IL-4 alone. The effects of TLR2 and TLR4 agonists on repolarization from the M2 to M1 subset was evaluated, and the first stimulus was composed of IL-4 and, after 24 h of incubation, the cells were submitted to a second stimulus of P3C4, LPS, ArtinM, or Medium. These TLR agonists induced the production of TNF-α in polarized RAW 264.7 cells to the M2 subset, moreover the measurement of M1/M2 markers using qRT-PCR demonstrated that a second stimulus with LPS for 24 h induced a significant augmentation of levels of iNOS mRNA. This impact of TLR2 and TLR4 agonists in the activation of the RAW 264.7 macrophage was assayed in the presence of C. gattii, the macrophages stimulated with TLR2 and TLR4 agonists for 24 h and co-cultured with C. gattii, as a second stimulus, reached high levels of TNF-α even after incubation with different concentrations of C. gattii. The activation of RAW 264.7 cells induced by TLR2 and TLR4 agonists favored the phagocytosis of C. gattii and inhibited the growth of yeast in the early period of infection. However, RAW 264.7 cells incubated with C. gattii in the presence of TLR2 and TLR4 agonists did not result a significant difference in the colony forming unit (CFU) assay in the early period of C. gattii infection, compared to negative control. CONCLUSION: Polarized RAW 264.7 cells to the M1 subset with TLR2 and TLR4 agonists did not inhibit the growth of C. gattii, whereas robust immunity was identified that could dysregulate host tolerance to this pathogen.
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The occurrence of pesticides and their mixtures in the environment can alter the ecological relationships between aquatic food chains. Since fipronil and 2,4-dichlorophenoxyacetic acid (2,4-D) are commonly found together in Brazilian water bodies, the present study aimed to investigate through an integrative approach the toxicity mechanisms of environmentally relevant concentrations of pesticides Regent® 800 WG (active ingredient - a.i. fipronil), DMA® 806 BR (a.i. 2,4-D) isolated and in mixtures on the green alga Raphidocelis subcapitata using multiple parameters: physiological (growth rate and chlorophyll a fluorescence), morphological (cell complexity and size), biochemical (composition of lipid classes) and related to the photosynthetic activity (variable fluorescence, the maximum quantum yield of the photosystem II - PSII - and the efficiency of the oxygen evolving complex - OEC - of PSII). The results indicated that fipronil significantly inhibited algal population growth, increased the chlorophyll a content (observed by fluorescence), cell size and lipid class content of triacylglycerol (TAG), free fatty acid (FFA) and acetone mobile polar lipid (AMPL) and, on the other hand, decreased variable fluorescence of algae. The tested concentrations of 2,4-D increased the chlorophyll a fluorescence, the cell size and the lipid classes TAG and FFA. The pesticide mixtures have had more effects on algae than isolated compounds, causing alterations in all parameters analyzed, including photosynthetic activity (maximum quantum yield and efficiency of the oxygen evolving complex of the PSII), in which no alterations were observed for the toxicity of the single pesticides. The results suggest that these analyses are important to evaluate pesticide toxicity mechanisms in ecological risk assessments of tropical regions. Thus, here we demonstrate the importance of using multiple parameters in ecotoxicological studies to obtain a better understanding of the toxicity of these compounds for phytoplankton.
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Ácido 2,4-Diclorofenoxiacético/toxicidad , Chlorophyceae/fisiología , Pirazoles/toxicidad , Contaminantes Químicos del Agua/toxicidad , Brasil , Clorofila/metabolismo , Clorofila A , Ecotoxicología , Herbicidas/análisis , Plaguicidas/toxicidad , Fotosíntesis/efectos de los fármacos , Complejo de Proteína del Fotosistema II , Fitoplancton/metabolismoRESUMEN
Breast cancer is a disease that exhibits heterogeneity that goes from the genomic to the clinical levels. This heterogeneity is thought to be captured (at least partially) by the so-called breast cancer molecular subtypes. These molecular subtypes were initially defined based on the unsupervised clustering of gene expression and its correlate with histological, morphological, phenotypic and clinical features already known. Later, a 50-gene signature, PAM50, was defined in order to identify the biological subtype of a given sample within the clinical setting. The PAM50 signature was obtained by the use of unsupervised statistical methods, and therefore no limitation was set on the biological relevance (or lack of) of the selected genes beyond its predictive capacity. An open question that remains is what are the regulatory elements that drive the various expression behaviors of this set of genes in the different molecular subtypes. This question becomes more relevant as the measurement of more biological layers of regulation becomes accessible. In this work, we analyzed the gene expression regulation of the 50 genes in the PAM50 signature, in terms of (a) gene co-expression, (b) transcription factors, (c) micro-RNAs, and (d) methylation. Using data from the Cancer Genome Atlas (TCGA) for the Luminal A and B, Basal, and HER2-enriched molecular subtypes as well as normal tumor adjacent tissue, we identified predictors for gene expression through the use of an elastic net model. We compare and contrast the sets of identified regulators for the gene signature in each molecular subtype, and systematically compare them to current literature. We also identified a unique set of predictors for the expression of genes in the PAM50 signature associated with each of the molecular subtypes. Most selected predictors are exclusive for a PAM50 gene and predictors are not shared across subtypes. There are only 13 coding transcripts and 2 miRNAs selected for the four subtypes. MiR-21 and miR-10b connect almost all the PAM50 genes in all the subtypes and normal tissue, but do it in an exclusive manner, suggesting a cancer switch from miR-10b coordination in normal tissue to miR-21. The PAM50 gene sets of selected predictors that enrich for a function across subtypes, support that different regulatory molecular mechanisms are taking place. With this study we aim to a wider understanding of the regulatory mechanisms that differentiate the expression of the PAM50 signature, which in turn could perhaps help understand the molecular basis of the differences between the molecular subtypes.
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In the present work, we performed a complementary quantum mechanical (QM) study to describe the mechanism by which deprotonated pralidoxime (2-PAM) could reactivate human (Homo sapiens sapiens) acetylcholinesterase (HssAChE) inhibited by the nerve agent VX. Such a reaction is proposed to occur in subsequent addition-elimination steps, starting with a nucleophile bimolecular substitution (SN2) mechanism through the formation of a trigonal bipyramidal transition state (TS). A near attack conformation (NAC), obtained in a former study using molecular mechanics (MM) calculations, was taken as a starting point for this project, where we described the possible formation of the TS. Together, this combined QM/MM study on AChE reactivation shows the feasibility of the reactivation occurring via attack of the deprotonated form of 2-PAM against the Ser203-VX adduct of HssAChE.
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Acetilcolinesterasa/efectos de los fármacos , Compuestos Organotiofosforados/farmacología , Compuestos de Pralidoxima/farmacología , Acetilcolinesterasa/química , Dominio Catalítico , Humanos , Conformación Molecular , Simulación de Dinámica Molecular , Compuestos de Pralidoxima/química , Protones , Teoría Cuántica , Serina/químicaRESUMEN
Vinasse is a waste from the alcohol industry that can support microalgal growth because of its mineral and organic contents. Growing microalgae on waste can be a means of its remediation and decrease culture costs. The physiological knowledge of microalgae on waste can generate subsidies to increase biomass productivity. However, few studies have explored the photosynthetic metabolism of microalgae on complex matrices such as vinasse. In the present research, we investigated some physiological aspects related to photosynthesis and growth of several microalgae in centrifuged and diluted vinasse. The species investigated were Chlamydomonas sp., Chlorella sorokiniana, Chlorella vulgaris, Desmodesmus spinosus, Haematococcus pluvialis, Monoraphidium sp., Scenedesmus quadricauda and Tetraselmis gracilis. Daily cell density, in vivo chlorophyll a and final cellular biovolumes (96 h) were monitored to infer about population growth. Maximum and operational photosynthetic yields (ÏM and Ï'M), photochemical (qP) and non-photochemical (NPQ) quenchings, light saturation curves and related parameters (α, rETRm and EK), as well as theoretical carbon fixation were evaluated using pulse amplitude modulated fluorometry (PAM). The results showed that chlorophyll a, photochemical (qP) and non-photochemical (NPQ) quenchings were not affected in vinasse, but photosynthetic yields, light curves parameters and autotrophic carbon fixation decreased. Connecting these results to the increase in productivities in vinasse lead us to the rationale that mixotrophic metabolism was supporting microalgae growth on the waste. This study offers important insights into the understanding of microalgal photosynthetic physiology on complex organic wastes, generating subsidies for optimization of biotechnological use of vinasse related to microalgae production.
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Carbono/metabolismo , Residuos Industriales/análisis , Microalgas/crecimiento & desarrollo , Biodegradación Ambiental , Biomasa , Ciclo del Carbono , Clorofila A/metabolismo , Microalgas/metabolismo , FotosíntesisRESUMEN
Studying tissue-independent components of cancer and defining pan-cancer subtypes could be addressed using tissue-specific molecular signatures if classification errors are controlled. Since PAM50 is a well-known, United States Food and Drug Administration (FDA)-approved and commercially available breast cancer signature, we applied it with uncertainty assessment to classify tumor samples from over 33 cancer types, discarded unassigned samples, and studied the emerging tumor-agnostic molecular patterns. The percentage of unassigned samples ranged between 55.5% and 86.9% in non-breast tissues, and gene set analysis suggested that the remaining samples could be grouped into two classes (named C1 and C2) regardless of the tissue. The C2 class was more dedifferentiated, more proliferative, with higher centrosome amplification, and potentially more TP53 and RB1 mutations. We identified 28 gene sets and 95 genes mainly associated with cell-cycle progression, cell-cycle checkpoints, and DNA damage that were consistently exacerbated in the C2 class. In some cancer types, the C1/C2 classification was associated with survival and drug sensitivity, and modulated the prognostic meaning of the immune infiltrate. Our results suggest that PAM50 could be repurposed for a pan-cancer context when paired with uncertainty assessment, resulting in two classes with molecular, biological, and clinical implications.
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Biomarcadores de Tumor/metabolismo , Puntos de Control del Ciclo Celular/genética , Diferenciación Celular/genética , Daño del ADN/genética , Células Madre Embrionarias/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias/clasificación , Neoplasias/metabolismo , Algoritmos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Centrosoma/metabolismo , Estudios de Cohortes , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Humanos , Concentración 50 Inhibidora , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Neoplasias/genética , Neoplasias/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas de Unión a Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4+ and CD8+ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis.
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Antígenos de Protozoos/inmunología , Leishmania/inmunología , Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis Visceral/inmunología , Lipopéptidos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Administración Intranasal , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/administración & dosificación , Citocinas/sangre , Femenino , Vacunas contra la Leishmaniasis/administración & dosificación , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/prevención & control , Lipopéptidos/administración & dosificación , Hígado/metabolismo , Hígado/parasitología , Linfocitos/inmunología , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Bazo/metabolismo , Bazo/parasitología , VacunaciónRESUMEN
PURPOSE: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. PATIENTS AND METHODS: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. RESULTS: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. CONCLUSION: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer. TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7-11, 2016, Copenhagen, Denmark (oral presentation).
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Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/inmunología , Recuento de Linfocitos , Neutrófilos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Naegleria fowleri is a pathogenic amoeboflagellate most prominently known for its role as the etiological agent of the Primary Amoebic Meningoencephalitis (PAM), a disease that afflicts the central nervous system and is fatal in more than 95% of the reported cases. Although being fatal and with potential risks for an increase in the occurrence of the pathogen in populated areas, the organism receives little public health attention. A great underestimation in the number of PAM cases reported is assumed, taking into account the difficulty in obtaining an accurate diagnosis. In this review, we summarize different techniques and methods used in the identification of the protozoan in clinical and environmental samples. Since it remains unclear whether the protozoan infection can be successfully treated with the currently available drugs, we proceed to discuss the current PAM therapeutic strategies and its effectiveness. Finally, novel compounds for potential treatments are discussed as well as research on vaccine development against PAM.