Thymic nurse cells exhibit epithelial progenitor phenotype and create unique extra-cytoplasmic membrane space for thymocyte selection.

Thymic nurse cells (TNCs) are epithelial cells in the thymic cortex that contain as many as 50 thymocytes within specialized cytoplasmic vacuoles. The function of this cell-in-cell interaction has created controversy since their discovery in 1980. Further, some skepticism exists about the idea that apoptotic thymocytes within the TNC complex result from negative selection, a process believed to occur exclusively within the medulla. In this report, we have microscopic evidence that defines a unique membranous environment wherein lipid raft aggregates around the alphabetaTCR expressed on captured thymocytes and class II MHC molecules expressed on TNCs. Further, immunohistological examination of thymic sections show TNCs located within the cortico-medullary junction to express cytokeratins five and eight (K5 and K8), and the transcription factor Trp-63, the phenotype defined elsewhere as the thymic epithelial progenitor subset. Our results suggest that the microenvironment provided by TNCs plays an important role in thymocyte selection as well as the potential for TNCs to be involved in the maintenance of thymic epithelia.

Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate their association with MHC restriction.

This study examines thymic nurse cell (TNC) function during T-cell development. It has been suggested that TNCs function in the removal of nonfunctional and/or apoptotic thymocytes and do not participate in major histocompatibility complex restriction. We analyzed TNCs isolated from both normal C57BL/6 mice and C57BL/6 TgN (TCRHY) mice (HY-TCR transgenic mice). Using confocal microscopic analyses of TNCs isolated from C57BL/6 animals, we showed that 75%-78% of the enclosed thymocyte subset was viable, and 87%-90% of these cells expressed both CD4 and CD8. CD4 and CD8 also were expressed on TNC thymocytes isolated from both male and female HY-TCR transgenic mice. The transgenic female thymus was shown to have 17 times more TNCs per milligram of thymus than the transgenic male thymus. TNCs from HY-TCR transgenic females were 8-10 microm larger than transgenic male TNCs, and the female TNCs contained five times more thymocytes within intracytoplasmic vacuoles, with less than 4% apoptosis. However, more than 42% of the thymocytes within transgenic male TNCs were apoptotic. The large number and size of TNCs containing viable thymocytes in the female transgenic thymus suggest that TNC function is not limited to the removal of apoptotic thymocytes. We believe that the selective uptake of viable double-positive thymocytes by TNCs in C57BL/6 and HY-TCR transgenic female mice provides evidence that this interaction occurs during the process of major histocompatibility complex restriction.

Características clínico-epidemiológicas de pacientes ingresados en un centro de aislamiento. Cienfuegos, 2021 / Clinical-epidemiological characteristics of patients admitted to an isolation center. Cienfuegos Province, March- 2021

RESUMEN Fundamento: la COVID-19 obligó a adoptar medidas y protocolos para el seguimiento a los enfermos y personas en riesgo de contraer la enfermedad. En Cienfuegos también hubo protocolos para el aislamiento de los contactos y sospechosos, con el propósito de contribuir a la contención de la epidemia. Objetivo: describir características clínico-epidemiológicas de pacientes en centro de aislamiento, al ingreso y durante el período de ingreso. Métodos: estudio observacional, descriptivo de corte transversal, de todos los pacientes que ingresaron en el mes de marzo del 2021 en el centro de aislamiento Filial de Ciencias Médicas, que fueron contactos de casos positivos. Se tuvieron en cuenta los datos generales y clínicos-epidemiológicos obtenidos de las historias clínicas individuales y el registro de pacientes ingresados. Resultados: hubo un total de 446 ingresos; predominaron las edades entre 40 y 59 años. Todos los municipios tuvieron representatividad, el de mayor número de ingresos fue Cienfuegos. El 38,8 % padecía de enfermedades no transmisibles, la HTA con mayor prevalencia. La mayoría de los pacientes estaban asintomáticos. Los síntomas mayormente reportados fueron ansiedad y/o depresión seguida de las cifras elevadas de presión arterial. Resultaron positivos 12 pacientes. Conclusiones: el aislamiento de los contactos de casos positivos es una medida que favorece no solo el tratamiento inmediato de los casos que resulten positivos, sino que previene las complicaciones asociadas a comorbilidades presentes en la población.

ABSTRACT Foundation: COVID-19 has forced the adoption of some measures and protocols to monitor patients and people at risk of contracting the disease. In Cuba and specifically in Cienfuegos, protocols are carried out for the isolation of contacts and suspects of the desease, in order to contribute to the containment of the epidemic. Objective To describe the clinical-epidemiological characteristics of the patients upon admission and during the isolation period. Methods: descriptive analysis of all patients who were admitted to the "Filial de Ciencias Médicas" isolation center in March, who were contacts of positive and asymptomatic cases. The general and clinical-epidemiological data obtained from individual medical records and the registry of patients admitted in that center were taken into account. Results: There was a total of 446 admissions, predominating ages between 40 and 59 years. All municipalities were representative, being Cienfuegos the one with the highest number of incomes. the38.8% suffered from non-communicable diseases, hypertension being the one with the highest prevalence. Most of the patients were asymptomatic. The most commonly reported symptoms were anxiety and / or depression followed by elevated blood pressure. Twelve patients were positive. Conclusions The isolation of the contacts of positive cases has been an effective strategy for the timely diagnosis of infections. This measure favors not only the immediate treatment of positive cases, but also prevents complications associated with comorbidities present in the population.

Esclerodermia cutánea localizada (Morfea): reporte de caso

RESUMEN La esclerodermia cutánea localizada es una enfermedad crónica del tejido conectivo, etiología desconocida, caracterizada por áreas de piel induradas. Existen varias formas. La Morfea es una enfermedad rara con incidencia de 0,3-3 casos por 100.000 habitantes / año. Más común en mujeres, proporción 4:1 mujer/hombre. Mujer, 21 años acude al Servicio de Dermatología del Hospital de Clínicas por cuadro de 3 años de evolución de mancha roja en cadera de lado derecho que luego se vuelve marrón, aparece luego otra lesión similar en muslo y rodilla derechos con misma evolución, sin desencadenante aparente ni síntomas acompañantes. Al examen físico se observa varias placas hipocrómicas algunas con bordes eritematosos, entre 2-3 cm, límites netos y bordes irregulares distribuidos en muslo derecho. Placas hipercrómicas induradas entre 1-6 cm de diámetro, límites netos, bordes regulares en cadera y muslo derechos, y brazo izquierdo. Piel difícil de plegar. Biopsia de piel compatible con Morfea. Recibe tratamiento con hidroxicloroquina, metotrexate, corticoides tópicos, vitamina A, C, E con respuesta y evolución favorable. Esclerodermia localizada aparece en adultos entre 40- 50 años, en comparación con paciente que afectó segunda década de vida. Tronco como localización más frecuente, característica de la paciente, además en miembros superiores e inferiores. Artralgias se presentan en 44% de casos, coincidentes con la paciente. Aumento del factor reumatoideo, eosinofilia, VSG guían hacia diagnóstico de Morfea en fase activa, no apreciables en el caso. Tratamiento con metotrexate como inmunosupresor es la terapéutica con evolución favorable, así como indican estudios, complementados con hidroxicloroquina y vitaminas A y E.

ABSTRACT Localized scleroderma is a chronic connective tissue disease, unknown etiology, characterized by areas of indurated skin. There are several types. It is a rare disease with an incidence of 0.3-3 cases per 100,000 inhabitants / year. More common in Caucasian women, with a 2-4:1 female/male ratio. Woman, 21 years of age goes to the Dermatology Department of the Hospital de Clínicas for the 3-year history of the red woman on the right who later turns brown, a similar lesion appears on the right leg, apparently not trigger or symptoms companions. On physical examination, several hypochromic plaques were observed, some with erythematous borders, between 2-3 cm, net boundaries and irregular borders distributed in the right thigh. Indurated hyperchromic plates between 1 and 6 cm in diameter, net boundaries, regular edges in red and right thighs, and left side. Skin difficult to fold. Skin biopsy compatible with Morphea. Treated with hydroxychloroquine, methotrexate, topical corticosteroids, vitamin A, C, E with response and favorable evolution. Localized scleroderma appears in adults between 40-50 years, in comparison with the patient who affected the second decade of life. The trunk as the most frequent location, found in the patient, also in the upper and lower limbs. Join pains are presented in 44% of cases. Increase of the rheumatoid factor, eosinophilia, VSG guide to the diagnosis of Morphea in active phase, not appreciable in the case. Treatment with methotrexate as an immunosuppressant is the appropriate therapy, as indicated by studies, supplemented with hydroxychloroquine and vitamins A and E.

Inteligencia emocional asociada a niveles de ansiedad y depresión en estudiantes de Medicina de una Universidad pública / Emotional intelligence associated with levels of anxiety and depression in medical students of a public University

Introducción: La carrera que siguen es el principal factor para depresión o ansiedad en estudiantes de ciencias de salud, quiénes presentan elevados índices de depresión y de ansiedad. Sin embargo, aquellos estudiantes con buena inteligencia emocional muestran menos síntomas físicos, de ansiedad y depresión. Objetivos: determinar la asociación entre inteligencia emocional y niveles de ansiedad y depresión en estudiantes de Medicina. Materiales y métodos: estudio observacional analítico, transversal, retrospectivo, no probabilístico por conveniencia. La investigación incluyó a 276 estudiantes, quienes fueron evaluados con el test TMMS-24, Beck's Depression Inventory ­ second version (BD-II )y con la Generalised Anxiety Disorder Assessment (GAD-7). Se utilizó estadística descriptiva para todas las variables. Para buscar asociaciones entre variables categóricas se utilizó la prueba de chi cuadrado. Para determinar correlación entre variables se utilizó el coeficiente de correlación de Pearson, consideró una p<0,05 como significativa en todos los casos. Resultados: el 65,5 % de la muestra era del sexo femenino, con edades comprendidas entre 18 a 31 años (21,79±2,66). Se encontró 61,4 % de los participantes con síntomas de depresión y 67,7 % con síntomas de ansiedad. Se halló significancia con relación al sexo y la inteligencia emocional (atención y reparación de emociones), así como entre la inteligencia emocional (claridad y reparación de emociones) con los promedios de depresión y ansiedad. Se presentó mayor riesgo relativo en el sexo femenino asociado a ansiedad y depresión. Conclusión: en estudiantes de Medicina se encuentra una tendencia elevada de depresión y ansiedad, las cuales presentan relación con la inteligencia emocional.

Introduction: The course of studies they choose is the main factor for depression or anxiety in health sciences students, who have high rates of these disorders. Nevertheless, those students with good emotional intelligence show fewer physical symptoms, or symptoms of anxiety and depression. Objectives: We aimed to determine the association between emotional intelligence and levels of anxiety and depression in medical students. Materials and methods: analytical, cross-sectional, retrospective, non-probabilistic observational study, of convenience sampling. The research included 276 students, who were evaluated with the TMMS-24 test, the Beck Depression Inventory ­ second version (BD-II) and the Generalised Anxiety Disorder Assessment (GAD-7). Descriptive statistics were used for all variables. The chi-square test was used to search for associations between categorical variables. To determine correlation between variables, Pearson's correlation coefficient was used, considering p <0.05 as significant in all cases. Results: 65.5% of the sample was female, aged between 18 and 31 years (21.79 ± 2.66). 61.4% of the participants had symptoms of depression and 67.7% symptoms of anxiety. Significance was found in relation to sex and emotional intelligence (attention and repair of emotions), as well as between emotional intelligence (clarity and repair of emotions) with the average levels of depression and anxiety. Females had a higher relative risk for anxiety and depression. Conclusion: In medical students there is a high tendency to develop symptoms of depression and anxiety, which are related to emotional intelligence.

Factores psicosociales influyentes en la actitud de estudiantes de medicina paraguayos hacia la donación de órganos / Influential psychosocial factors in the attitude of Paraguayan medical students towards organ donation

INTRODUCCIÓN: el trasplante de órganos es considerado el avance más significativo de la medicina moderna. Paraguay es uno de los países con las tasas más bajas de donación de órganos, alcanzando 7 donaciones por millón de personas. OBJETIVO: determinar los factores psicosociales que influyen en la actitud de estudiantes de Medicina paraguayos de una universidad pública hacia la donación de órganos. MATERIALES Y MÉTODOS: el estudio fue observacional analítico de corte transversal y muestreo no probabilístico por conveniencia entre abril a junio del 2017 en la Universidad Nacional de Asunción (Paraguay). RESULTADOS: los factores más frecuentes e influyentes fueron, un 37,6% (105) que manifestó informarse mediante Internet; consideran escasa la información sobre trasplantes en 61,6% (172); conscientes de la falta de órganos en 87,8% (245); aprobación de la donación pero sin estar registrados en las instituciones vinculadas por 86,37% (241). Asociación de estado civil, concepto de muerte encefálica y autopsia con la experiencia previa/favor/contra de la donación, alcanzaron valores significativos (p<0,05). CONCLUSIÓN: el estado civil, concepto de muerte encefálica y autopsia son factores influyentes y favorables en las actitudes sobre la donación en estudiantes de Medicina del Paraguay.

BACKGROUND: organ transplantation is considered the most significant advance in modern medicine. Paraguay is one of the countries with the lowest rates of organ donation, reaching 7 donators per million people. AIM: to determine the psychosocial factors that influence the attitude of Paraguayan medical students of a public university towards organ donation. METHODS: the study was cross-sectional analytical observational and non-probabilistic convenience sampling between April and June 2017 at the National University of Asunción (Paraguay). p<0.05 was considered as significant. RESULTS: 279 cases were analyzed; age rank between 18 and 30 years old (21.75 ± 2.12); female participation was greater 70.3% (196). The most frequent and influential factors were 37.6% (105) who reported being informed using the internet; 61.6% (172) consider information about organ transplant insufficient; they are aware of the lack of organ donators in 87.8% (245); they approve the organ donation, despite of being unregistered in the related institutions, about 86.37% (241). There is an association of marital status, concept of brain death and autopsy with previous experience / being in favor / being against donation (p<0.05). CONCLUSION: marital status, concept of brain death and autopsy are influential and favorable factors in attitudes about donation in medical students of Paraguay.

Impaired mitochondrial function protects against free radical-mediated cell death.

Free radical damage can have fatal consequences. Mitochondria carry out essential cellular functions and produce high levels of reactive oxygen species (ROS). Many agents also generate ROS. Using the yeast Saccharomyces cerevisiae as a eukaryotic model, the role of functional mitochondria in surviving free radical damage was investigated. Respiratory-deficient cells lacking mitochondrial DNA (rho(0)) were up to 100-fold more resistant than isogenic rho(+) cells to killing by ROS generated by the bleomycin-phleomycin family of oxidative agents. Up to approximately 90% of the survivors of high oxidative stress lost mitochondrial function and became "petites." The selective advantage of respiratory deficiency was studied in several strains, including DNA repair-deficient rad52/rad52 and blm5/blm5 diploid strains. These mutant strains are hypersensitive to lethal effects of free radicals and accumulate more DNA damage than related wild-type strains. Losses in mitochondrial function were dose-dependent, and mutational alteration of the RAD52 or BLM5 gene did not affect the resistance of surviving cells lacking mitochondrial function. The results indicate that inactivation of mitochondrial function protects cells against lethal effects of oxygen free radicals.

The Antigenic Determinant That Defines Thymic Nurse Cells Is Expressed by Thymic Epithelial Progenitor Cells.

Stromal thymic epithelial cells with the multicellular structure unique to thymic nurse cells (TNCs) express the pH91 antigen on their cell surfaces. The multicellular TNC-complexes develop through an intimate association between αßTCR+CD4+CD8+ thymocytes and pH91-expressing cortical epithelial cells. TNCs participate in MHC-restriction and exhibit epithelial cell progenitor characteristics. In this report, we show that as early as E11.5 stage of thymus development, the pH91 antigen is expressed in association with K8, K5, Foxn1 and p63. The expression of these epithelial progenitor markers along with the pH91 antigen persists throughout thymic development in the murine thymus. At E13.5, pH91+ cells express relatively low levels of MHC class II. After E17.5, the first multicellular TNC complexes are recognizable along with increased cell surface expression of MHC class II. Our data suggest that epithelial cells bearing the "progenitor phenotype" develop into the multicellular TNCs.

The identification of thymic nurse cells in vivo and the role of cytoskeletal proteins in thymocyte internalization.

Much debate has been generated about the existence of thymic nurse cells within the thymus. Until now, the authenticity of an epithelial cell capable of internalizing developing thymocytes within the thymic cortex has been in question. Here, we use the thymic nurse cell-specific monoclonal antibody, ph91, to define the in vivo location of thymic nurse cells. For the first time, thymic nurse cells enclosing several thymocytes were detected in the subcapsular region of the thymic cortex in a "honeycomb-like" configuration. In vitro studies show the internalization process using digitalized time-lapse microscopy. Internalized thymocytes have also been reported to interact with macrophages within the TNC complex. The cytoplasmic interaction between thymocytes and macrophages was detected using time-lapse microscopy. Using fluorescence microscopy, we show polymerization of actin within macrophages at the contact point with thymocytes, which is indicative of an immunological synapse. Microfilaments and microtubules within TNCs were shown to be associated with thymocyte binding and internalization, but neither interacted with macrophages. Also, we provide data to show that thymocytes are actively involved in the internalization process. These experiments show for the first time the existence of thymic nurse cells within the thymic microenvironment. They provide a visual documentation of thymocyte uptake by thymic nurse cells, and define an interaction between thymocytes and macrophages within the TNC complex.