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Las enfermedades causadas por amebas de vida libre son infecciones oportunistas que pueden tener un curso fatal. Pueden producir afecciones diseminadas graves con compromiso del sistema nervioso central, como la encefalitis amebiana granulomatosa. Esta infección es cada vez más frecuente en América Latina, aunque se reconocen tardíamente debido a la similitud con otras patologías o porque es inusual incluirla en el diagnóstico diferencial. Comunicamos un caso fatal de una encefalitis amebiana granulomatosa por Balamuthia mandrillaris en una niña de 10 años. Destacamos la gravedad de la afectación cerebral y la falta de esquemas antimicrobianos validados para su tratamiento. Hoy en el mundo esta infección es considerada una enfermedad emergente, influenciada por el cambio climático, lo que llama a estar atentos a su presencia.
Diseases caused by free-living amoebae are opportunistic infections that can have a fatal course. They can cause very serious disseminated conditions with involvement of the central nervous system such as granulomatous amoebic encephalitis. This infection has become more common in Latin America, although its recognition is late due to the similarity with other pathological conditions or because it is unusual to include it in the differential diagnosis. We report a fatal case of granulomatous amoebic encephalitis due to Balamuthia mandrillaris in a 10-year-old girl. We highlight the severity of the brain involvement and the lack of validated schemes for its treatment. Today in the world this infection is considered an emerging disease, influenced by climate change, which calls for being attentive to its presence.
Assuntos
Humanos , Feminino , Criança , Encefalite Infecciosa/diagnóstico , Amebíase/diagnóstico , Tomografia Computadorizada por Raios X , Análise de Sequência de DNA , Evolução Fatal , Balamuthia mandrillaris/isolamento & purificação , Balamuthia mandrillaris/genética , Encefalite Infecciosa/diagnóstico por imagem , Amebíase/diagnóstico por imagemRESUMO
Introducción: el diagnóstico y tratamiento del cáncer de pulmón representa un desafío para la sociedad en tiempos de pandemia de COVID-19. Objetivo: analizar el impacto del diagnóstico y tratamiento de pacientes con cáncer de pulmón durante dieciocho meses de COVID-19 en Matanzas. Materiales y métodos: se realizó un estudio analítico, prospectivo y longitudinal. El universo lo constituyeron los 135 pacientes inscritos en el Servicio Provincial de Oncología, de Matanzas, entre el 1 de marzo de 2020 y el 31 de agosto de 2021. Los datos se obtuvieron de las historias clínicas y se analizaron con el paquete estadístico SPSS v. 23. Resultados: los meses con más diagnóstico fueron septiembre, octubre y noviembre. La edad de mayor incidencia fue la comprendida entre 60 y 69 años, con predominio del sexo masculino. Con relación al hábito tabáquico, la incidencia más alta estuvo representada por los fumadores (59,2 %), y la menor por los no fumadores (17,8 %). Respecto al tipo histológico, el carcinoma de células escamosas fue el más frecuente, y al estado general de los pacientes, el grupo 1 de la escala del Easter Cooperative Oncology Group, el de mayor prevalencia. La etapa clínica al diagnóstico predominante fue la IV, y las modalidades de tratamiento más usadas fueron la quimioterapia y la inmunoterapia. Conclusiones: el impacto del diagnóstico oportuno y el tratamiento adecuado del cáncer de pulmón en los primeros dieciocho meses de COVID-19 en Matanzas, fue negativo.
Introduction: the diagnosis and treatment of lung cancer represents a challenge for society in times of COVID-1 pandemics. Objective: to analyze the impact of the diagnosis and treatment of lung cancer patients during 18 months of COVID-19 pandemics in Matanzas. Matertials and methods: an analytical, prospective and longitudinal study was carried out. The universe were 135 patients registered in the Oncology Provincial Service of Matanzas between March 1st 2020 and August 31st 2021. Data were obtained from the clinical records and analyzed with SPSS v.23 statistical packet. Results: the months with higher quantity of diagnosis were September, October and November. The age with the highest incidence was from 60 to 69 years, with predominance of male sex. In relation to smoking, the highest incidence was represented by smokers (59.2%), and the lowest by non-smokers. Respecting the histological type, the squamous cell carcinoma was the most frequent, and respecting the general status of the patient, the group 1 of the Easter Cooperative Oncology Group was the one with highest prevalence. IV stage was the predominant clinical stage at diagnosis, and chemotherapy and immunotherapy were the most used treatment modalities. Conclusions: the impact of lung cancer opportune diagnosis and adequate treatment in the first eighteen months of COVID-19 in Matanzas was negative.
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Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53.
Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Melanoma/mortalidade , MicroRNAs/genética , Interferência de RNA , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Humanos , Melanoma/patologia , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
RESUMEN En los adultos mayores existen múltiples enfermedades que afectan su calidad de vida y el logro de una longevidad satisfactoria. Una de ellas es la osteoporosis, enfermedad de elevada incidencia a nivel mundial, lo cual también se refleja en Cuba. Siendo una afección que conlleva a un alto grado de discapacidad, constituye un problema en el campo de la salud y de magnitud epidémica, más aún cuando la supervivencia de la humanidad tiende al aumento. Con el objetivo de estructurar los referentes teóricos sobre la osteoporosis, que contribuyan a la capacitación de médicos y estudiantes de Medicina como promotores de salud en prevención primaria de esta enfermedad, se realizó el siguiente artículo científico. Los factores que predisponen la aparición de la enfermedad son diversos, algunos modificables. Se señaló la importancia de su prevención, diagnóstico y tratamiento, así como formas de actuar sobre la misma, para modificar estilos de vida en la comunidad (AU).
ABSTRACT There are many diseases affecting life quality and the achievement of a satisfactory longevity in elder people; osteoporosis, a disease of high incidence around the world that also strikes in Cuba, is found among them. It is an affection leading to a high disability level, being a problem in the health field with an epidemic magnitude, even more when the human kind survival tends to increase. The current scientific article was written with the objective of structuring the theoretical referents on osteoporosis contributing to train Medicine doctors and students as health promoters in the primary prevention of this disease. The factors predisposing the disease's appearance are different, some of them modifiable. It is also stated the importance of its prevention, diagnosis and treatment, and also forms and ways of working on it to modify life styles in the community (AU).
Assuntos
Humanos , Masculino , Feminino , Idoso , Osteoporose/epidemiologia , Idoso/fisiologia , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/prevenção & controle , Osteoporose/terapia , Qualidade de Vida , Pessoas com Deficiência/reabilitação , Estilo de VidaRESUMO
RESUMEN La dimensión científica educativa constituye uno de los aportes más sólidos de la obra de Carlos de la Torre y Huerta. Su extensa obra investigativa se nutre de las asignaturas que impartió en la Universidad de la Habana entre las que se desatacan Paleontología, Arqueología, Antropología, Zoología, Geología, Biología y Entomología. Estos estudios favorecieron el descubrimiento de la gran riqueza existente en el país, destacándose una trayectoria ejemplar cuyos cimientos se insertan en la malacología. El descubrimiento de las Polymitas lo llevan a describir una diversidad de subespecies que lo insertan en el escenario internacional aclamado como un referente de obligatoria consulta para los especialistas. La divulgación sistemática de su obra lo conducen a la formación de una escuela cubana de naturalistas en la que los discípulos marcaron impronta en el quehacer científico nacional al apropiarse de las herramientas que le permiten hacer ciencia utilizando medios de enseñanza, imágenes proyectadas, láminas, dibujos y ejemplares autóctonos del país (AU).
ABSTRACT The educational scientific dimension is one of the strongest contributions of the work of Carlos de la Torre and Huerta. His extensive research work draws on the subjects he taught at the University of Havana, including Paleontology, Archeology, Anthropology, Zoology, Geology, Biology and Entomology. These studies favored the discovery of the great wealth existing in the country, highlighting an exemplary trajectory whose foundations are inserted in malacology. The discovery of the Polymites leads him to describe a diversity of subspecies that insert him in the acclaimed international scenario as a mandatory reference for specialists. The systematic dissemination of his work lead him to the formation of a Cuban school of naturalists in which the disciples marked imprint on the national scientific work by appropriating the tools that allow him to do science using teaching means, projected images, prints, drawings and native copies of the country (AU).
Assuntos
Humanos , Masculino , Pesquisadores/história , Docentes , Disciplinas das Ciências Naturais/educação , Disciplinas das Ciências Naturais/história , Prática Profissional/ética , Universidades , Domínios CientíficosRESUMO
INTRODUCTION: The aim of this article was to evaluate the effectiveness of the Gleason grade groups (GGG) system on a group of Argentinian patients with prostate cancer (PC) who underwent radical prostatectomy (RP). MATERIAL AND METHODS: We retrospectively studied 262 patients who underwent RP between 1996 and 2014. To determine the performance and validity of the GGG system, a Kaplan-Meier analysis and multivariate analysis with Cox proportional method were performed to evaluate biochemical recurrence, distance metastases and specific cancer mortality. The area under the curve (AUC) was calculated to compare new groups of degrees of the GGG system with the classical scheme of stratification into 3 groups. RESULTS: The median follow-up was 84 months. As the groups ascend, there is less confined organ disease (p <0.001) and greater extraprostatic extension (p <0.001), greater invasion of seminal vesicles (p <0.001) and greater lymph node involvement (p <0.001). The biochemical recurrence-free survival at 5 years was 68%, 55%, 22%, 9%, 0% of the 1-5 groups, respectively. Ten-years cancer-specific survival was 96%, 95%, 78%, 64%, 25% for group 1-5, respectively. In the multivariate analysis, the GGG system is presented as the only independent predictor of biochemical recurrence and specific cancer mortality. The AUC indicates that the GGG system has a higher prognostic discrimination compared to the classic 3-group system (6, 7, ≥8). CONCLUSIONS: The International Society of Urological Pathology (ISUP) GGG system is an independent predictor of biochemical recurrence and mortality from prostate cancer in patients treated with RP. The classification into 5 groups shows greater discrimination in the prognosis than the traditional Gleason classification.
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The adverse environmental conditions found in the periodontium during periodontitis pathogenesis stimulate local autophagy responses, mainly due to a continuous inflammatory response against the dysbiotic subgingival microbiome. The junctional epithelium represents the main site of the initial interaction between the host and the dysbiotic biofilm. Here, we investigated the role of autophagy in junctional epithelium keratinocytes (JEKs) in response to Aggregatibacter actinomycetemcomitans or its purified lipopolysaccharides (LPS). Immunofluorescence confocal analysis revealed an extensive nuclear translocation of transcription factor EB (TFEB) and consequently, an increase in autophagy markers and LC3-turnover assessed by immunoblotting and qRT-PCR. Correspondingly, challenged JEKs showed a punctuate cytosolic profile of LC3 protein contrasting with the diffuse distribution observed in untreated controls. Three-dimensional reconstructions of confocal images displayed a close association between intracellular bacteria and LC3-positive vesicles. Similarly, a close association between autophagic vesicles and the protein p62 was observed in challenged JEKs, indicating that p62 is the main adapter protein recruited during A. actinomycetemcomitans infection. Finally, the pharmacological inhibition of autophagy significantly increased the number of bacteria-infected cells as well as their death, similar to treatment with LPS. Our results indicate that A. actinomycetemcomitans infection induces autophagy in JEKs, and this homeostatic process has a cytoprotective effect on the host cells during the early stages of infection.
Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Autofagia , Inserção Epitelial/patologia , Queratinócitos/microbiologia , Queratinócitos/patologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Biomarcadores/metabolismo , Contagem de Células , Linhagem Celular , Núcleo Celular/metabolismo , Sobrevivência Celular , Humanos , Imageamento Tridimensional , Lipopolissacarídeos/isolamento & purificação , Modelos Biológicos , Transporte Proteico , Proteína Sequestossoma-1/metabolismoRESUMO
Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors. T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP). Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82. Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion. Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP. Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor. SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association. Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus. This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
Assuntos
Doença de Chagas/patologia , Sinais Direcionadores de Proteínas/genética , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/patogenicidade , Glicoproteínas Variantes de Superfície de Trypanosoma/metabolismo , Fatores de Virulência/metabolismo , Doença de Chagas/parasitologia , Retículo Endoplasmático/metabolismo , Células HeLa , Humanos , Mutagênese Sítio-Dirigida , Proteínas de Protozoários/genética , Alinhamento de Sequência , Relação Estrutura-Atividade , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Glicoproteínas Variantes de Superfície de Trypanosoma/genética , Fatores de Virulência/genéticaRESUMO
Trypanosoma cruzi is the etiologic agent of Chagas' disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo. Extracellular amastigotes (EAs) have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb) 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9. We demonstrated that the carbohydrate epitope recognized by mAb1D9 could promote host cell invasion by EAs. Although infectious EAs express lower amounts of Ssp-4 compared with less-infectious EAs (at the mRNA and protein levels), it is the glycosylation of Ssp-4 (identified by mAb1D9 staining only in infectious strains and recognized by galectin-3 on host cells) that is the determinant of EA invasion of host cells. Furthermore, Ssp-4 is secreted by EAs, either free or associated with parasite vesicles, and can participate in host-cell interactions. The results presented here describe the possible role of a carbohydrate moiety of T. cruzi surface glycoproteins in host cell invasion by EA forms, highlighting the potential of these moieties as therapeutic and vaccine targets for the treatment of Chagas' disease.
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INTRODUCTION: The aim of this study was to describe the prognostic impact of microvascular invasion (MVI) in patients with non-metastatic renal cell cancer. MATERIAL AND METHODS: We carried out a retrospective, descriptive and analytical study of patients with non-metastatic renal cell carcinoma who had undergone a radical or partial nephrectomy. Patients were divided according to the presence of MVI. In each group, clinical and pathological characteristics were evaluated. Metastasis-free and cancer-specific survival was evaluated by the Kaplan Meier method. The multivariate analysis was performed with Cox proportional method in order to predict risk factors of metastasis and cancer-specific mortality. RESULTS: A total of 221 patients with a median of 40-month long follow-up were evaluated. Patients with MVI+ were 40 (18%) while those with MVI - were 181 (82%). In the univariate analysis, the presence of MVI had a strong correlation with symptomatic tumors (OR 3.56; p 0.0003), tumor size (OR 12.08; p <0.0001), nuclear grade (OR 6.99; p <0.0001), pathological stage (OR 35.8; p <0.0001), distance metastasis (OR 4.16; p 0.0001), and death by cancer (OR 4.7; p 0.0004). However, in the multivariate analysis it is not presented as an independent predictor of metastasis (HR 0.45; p 0.11) or cancer-specific mortality (HR 0.93; p 0.91). CONCLUSIONS: In our series, MVI is associated with unfavorable tumors characteristics. In spite of this, it does not seem to be an independent predictor for metastasis and death by non-metastatic renal cancer.