Janus kinase inhibitors modify the fatty acid profile of extracellular vesicles and modulate the immune response.

Background: Janus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication. Jakinibs can modify the content of EVs and enable them to modulate the activity of different components of the immune response. Objective: to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. Methods: EVs were isolated from monocytes (M) and lymphocytes (L) of healthy individuals, as well as from U937 (U) and Jurkat (J) cells exposed to non-cytotoxic concentrations of BARI, ITA, and dimethyl sulfoxide (DMSO; vehicle control). The binding to and engulfment of EVs by peripheral blood leukocytes of healthy individuals were analyzed by flow cytometry using CFSE-stained EVs and anti-CD45-PeCy7 mAb-labeled whole blood. The effect of EVs on respiratory burst, T-cell activation and proliferation, cytokine synthesis, and platelet aggregation was evaluated. Respiratory burst was assessed in PMA-stimulated neutrophils by the dihydrorhodamine (DHR) test and flow cytometry. T-cell activation and proliferation and cytokine production were assessed in CFSE-stained PBMC cultures stimulated with PHA; expression of the T-cell activation markers CD25 and CD69 and T-cell proliferation were analyzed by flow cytometry, and the cytokine levels were quantified in culture supernatants by Luminex assays. Platelet aggregation was analyzed in platelet-rich plasma (PRP) samples by light transmission aggregometry. The EVs' fatty acid (FA) profile was analyzed using methyl ester derivatization followed by gas chromatography. Results: ITA exposure during the generation of EVs modified the size of the EVs released; however, treatment with DMSO and BARI did not alter the size of EVs generated from U937 and Jurkat cells. Circulating neutrophils, lymphocytes, and monocytes showed a 2-fold greater tendency to internalize ITA-U-EVs than their respective DMSO control. The neutrophil respiratory burst was attenuated in greater extent by M-EVs than by L-EVs. Autologous ITA-M-EVs reduced T-cell proliferation by decreasing IL-2 levels and CD25 expression independently of CD69. A higher accumulation of pro-inflammatory cytokines was observed in PHA-stimulated PBMC cultures exposed to M-EVs than to L-EVs; this difference may be related to the higher myristate content of M-EVs. Platelet aggregation increased in the presence of ITA-L/M-EVs by a mechanism presumably dependent on the high arachidonic acid content of the vesicles. Conclusions: Cellular origin and jakinib exposure modify the FA profile of EVs, enabling them, in turn, to modulate neutrophil respiratory burst, T-cell proliferation, and platelet aggregation. The increased T-cell proliferation induced by BARI-L/M-EVs could explain the lymphocytosis observed in patients treated with BARI. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

B cell-targeted polylactic acid nanoparticles as platform for encapsulating jakinibs: potential therapeutic strategy for systemic lupus erythematosus.

Background: B cells are pivotal in systemic lupus erythematosus and autoimmune disease pathogenesis. Materials & methods: To address this, Nile Red-labeled polylactic acid nanoparticles (NR-PLA NPs) loaded with the JAK inhibitor baricitinib (BARI), specifically targeting JAK1 and JAK2 in B cells, were developed. Results: Physicochemical characterization confirmed NP stability over 30 days. NR-PLA NPs were selectively bound and internalized by CD19+ B cells, sparing other leukocytes. In contrast to NR-PLA NPs, BARI-NR-PLA NPs significantly dampened B-cell activation, proliferation and plasma cell differentiation in healthy controls. They also inhibited key cytokine production. These effects often surpassed those of equimolar-free BARI. Conclusion: This study underscores the potential of PLA NPs to regulate autoreactive B cells, offering a novel therapeutic avenue for autoimmune diseases.

In this study, a new approach to treating autoimmune diseases, particularly systemic lupus erythematosus, was investigated by focusing on a type of immune cell called B cells. Special nanoparticles (NPs) labeled with Nile Red (NR) and made from polylactic acid (PLA) were created. These NPs were loaded with a drug called baricitinib (BARI), which targets specific proteins (JAK1 and JAK2) in B cells. This was done to determine if these NPs could help control the behavior of B cells, which are important in autoimmune diseases. First, these NPs remained stable for a long time (30 days). The NR-labeled PLA NPs (NR-PLA NPs) were also good at attaching to and entering a specific type of B cell called CD19⁺ B cells while leaving other types of immune cells alone. The use of NR-PLA NPs loaded with BARI produced exciting results. These NPs were better at reducing the activity, growth and transformation of B cells into plasma cells compared with the drug BARI by itself. They also stopped the production of certain immune system signals called cytokines, which are usually overactive in autoimmune diseases. This work suggests that PLA NPs could be a promising way to control overactive B cells that contribute to autoimmune diseases like systemic lupus erythematosus. This could open a new and exciting path for developing treatments for these conditions.

Electrochemical determination of Saccharomyces cerevisiae sp using glassy carbon electrodes modified with oxidized multi-walled carbon nanotubes dispersed in water -Nafion®.

The electrochemical behavior of Saccharomyces cerevisiae sp was studied using a glassy carbon electrode (GCE) modified with Nafion-dispersed oxidized multi-walled carbon nanotubes (OMWCNT). The morphology was studied using scanning electron microscopy (SEM), showing that the yeast sticks to the carbon nanotube surface instead of the glassy carbon surface. The redox couple Fe(CN)6 4-/Fe(CN)6 3- was used to determine the electroactive area and the heterogeneous transfer constant, which increased 80.5% and 108% respectively by the presence of nanotubes. The studies of the pH effect showed that the anodic potential decreases at alkaline pH and that the highest current intensity occurs at a pH value of 7.00. Studies of the scan rate effect have shown that yeast oxidation is an irreversible mixed control process in which two electrons participate. The relationship between yeast concentration and the anodic current density was studied using different electrochemical techniques obtaining the best analytical parameters through chronoamperometry. The linear range was between 3.36 and 6.52 g L-1, the limit of detection (LOD) and the limit of quantification (LOQ) were 0.98 g L-1 and 3.36 g L-1 respectively, and the sensibility obtained was 0.086 µA L g-1 mm-2. These results show that the multi-walled carbon nanotubes in water and Nafion® allow obtaining an anodic signal corresponding to the yeast, which facilitates its quantification through electrochemical methodologies, favoring the reduction of analysis times and costs compared with other techniques.

Beliefs of parents of children with mental disorders in a university hospital out-patient clinic in Colombia.

OBJECTIVE: Describe the beliefs of parents about the mental disorders of their children who attended a paediatric outpatient clinic at a university hospital. METHODS: This was a descriptive study with parents of children with mental disorders seen from January to May of 2018 at a high complexity hospital in Medellin, Colombia. Ninety-eight (98) parents of children and adolescents attending their first outpatient consultation with Paediatric Psychiatry were studied. An instrument designed by the investigators was applied to obtain demographic variables and beliefs about the origin of their child's mental disorder, treatment and adjuvants. RESULTS: 49.9% of the 98 parents believed that their child had a mental disorder. 43.9% believed the disorder was inherited and 41.8% believed its cause was organic. 95.9% of the parents believed the child needed treatment, including psychotherapy (90.4%) and medication (58.51%). Among the alternative treatments the parents believed the child needed, healing was the most commonly cited by 27.5% of the parents. Of the adjuvant methods, the most commonly cited were reinforcing positive behaviour (82.7%) and correcting with words and setting a good example (72.4%). CONCLUSIONS: Nearly half of the parents believed their child had a mental disorder, the treatment that was most commonly considered was psychotherapy above medication, and the best adjuvant methods cited by parents were reinforcing positive behaviour, correcting with words and setting a good example.

Creencias de los padres acerca de los trastornos mentales de sus hijos en una consulta universitaria en Colombia / Beliefs of parents of children with mental disorders in a university hospital out-patient clinic in Colombia

RESUMEN Objetivo: Describir las creencias de los padres acerca de los trastornos mentales de sus hijos que asistieron a consulta externa infantil en una clínica universitaria. Métodos: Estudio descriptivo transversal realizado en padres de niños con trastornos mentales de una clínica de cuarto nivel de Medellín, Colombia, durante el periodo comprendido entre enero y mayo del 2018. Se estudió a 98 padres de niños y adolescentes que consultaron por primera vez a Psiquiatría Infantil. Se aplicó un instrumento elaborado por los investigadores con variables demográficas y de creencias sobre: el origen del trastorno mental, del tratamiento y sus coadyuvantes. Resultados: El 49,9% de los 98 padres evaluados creyeron que su hijo tenía un trastorno mental; en cuanto al origen de este, el 43,9% creía que era heredado y 41,8% por causas orgánicas. El 95,9% de los padres creía que sus hijos necesitaban tratamiento, de ellos, el 90,4% estimó la psicoterapia y el 58,51%, la medicación. Entre los tratamientos alternativos el más frecuente fue la sanación, con un 27,5%. De los métodos coadyuvantes en el tratamiento, los más frecuentes fueron estimular comportamientos positivos con el 82,7%, y corregir con palabras y dar buen ejemplo con el 72,4%. Conclusiones: En este estudio casi la mitad de los padres pensaba que sus hijos tenían una enfermedad mental. El tratamiento más considerado por los participantes fue la psicoterapia, por encima del uso de psicofármacos. En cuanto a los métodos coadyuvantes, los padres consideraron principalmente el estimular comportamientos positivos, corregir con palabras y dar buen ejemplo.

ABSTRACT Objective: Describe the beliefs of parents about the mental disorders of their children who attended a paediatric outpatient clinic at a university hospital. Methods: This was a descriptive study with parents of children with mental disorders seen from January to May of 2018 at a high complexity hospital in Medellin, Colombia. Ninety-eight (98) parents of children and adolescents attending their first outpatient consultation with Paediatric Psychiatry were studied. An instrument designed by the investigators was applied to obtain demographic variables and beliefs about the origin of their child's mental disorder, treatment and adjuvants. Results: 49.9% of the 98 parents believed that their child had a mental disorder. 43.9% believed the disorder was inherited and 41.8% believed its cause was organic. 95.9% of the parents believed the child needed treatment, including psychotherapy (90.4%) and medication (58.51%). Among the alternative treatments the parents believed the child needed, healing was the most commonly cited by 27.5% of the parents. Of the adjuvant methods, the most commonly cited were reinforcing positive behaviour (82.7%) and correcting with words and setting a good example (72.4%). Conclusions: Nearly half of the parents believed their child had a mental disorder, the treatment that was most commonly considered was psychotherapy above medication, and the best adjuvant methods cited by parents were reinforcing positive behaviour, correcting with words and setting a good example.

Beliefs of parents of children with mental disorders in a university hospital out-patient clinic in Colombia. / Creencias de los padres acerca de los trastornos mentales de sus hijos en una consulta universitaria en Colombia.

OBJECTIVE: Describe the beliefs of parents about the mental disorders of their children who attended a paediatric outpatient clinic at a university hospital. METHODS: This was a descriptive study with parents of children with mental disorders seen from January to May of 2018 at a high complexity hospital in Medellin, Colombia. Ninety-eight (98) parents of children and adolescents attending their first outpatient consultation with Paediatric Psychiatry were studied. An instrument designed by the investigators was applied to obtain demographic variables and beliefs about the origin of their child's mental disorder, treatment and adjuvants. RESULTS: 49.9% of the 98 parents believed that their child had a mental disorder. 43.9% believed the disorder was inherited and 41.8% believed its cause was organic. 95.9% of the parents believed the child needed treatment, including psychotherapy (90.4%) and medication (58.51%). Among the alternative treatments the parents believed the child needed, healing was the most commonly cited by 27.5% of the parents. Of the adjuvant methods, the most commonly cited were reinforcing positive behaviour (82.7%) and correcting with words and setting a good example (72.4%). CONCLUSIONS: Nearly half of the parents believed their child had a mental disorder, the treatment that was most commonly considered was psychotherapy above medication, and the best adjuvant methods cited by parents were reinforcing positive behaviour, correcting with words and setting a good example.

Actividad lúpica en paciente con enfermedad renal terminal: reporte de caso / Lupus activity in a patient with end-stage renal disease: a case report

RESUMEN El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que afecta múltiples órganos; el compromiso renal se encuentra en el 50% de los pacientes y es variable de acuerdo con el grupo racial y étnico. Se estima que el 10% de los pacientes con nefritis lúpica (NL) desarrollan enfermedad renal terminal (ERT) y, una vez que se da la progresión, el 80% de los pacientes negativizan los marcadores de actividad. Sin embargo, aunque es inusual, la reactivación de la enfermedad puede presentarse en compromiso renal avanzado y es importante diagnosticarla oportunamente para definir la causa, tratarla y evitar complicaciones. Presentamos el caso clínico de una paciente de 45 arios, con ERT en diálisis peritoneal, que se encontraba en remisión de la enfermedad y posteriormente desarrolló actividad lúpica.

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, and renal involvement is found in 50% of patients and is variable according to racial and ethnic group. It is estimated that 10% of patients with lupus nephritis (NL) develop end-stage renal disease (ERT), and once progression occurs, 80% of patients are negative for activity markers. However, although it is rare, the reactivation of the disease can occur in advanced renal involvement, and it is important to diagnose it in a timely manner to define the cause and treat it, avoiding complications.

Caracterización de pacientes con artritis indiferenciada y evolución a otras enfermedades inflamatorias en una cohorte del noroccidente colombiano: Estudio observacional / Characterization of patients with undifferentiated arthritis and evolution to other inflammatory diseases in a Colombian northwestern cohort: An observational study

RESUMEN Objetivo: La artritis indiferenciada es una artropatía inflamatoria que no cumple con los criterios de enfermedades reumatológicas específicas y cuyos síntomas persisten durante un año. Estos individuos pueden remitir espontáneamente o evolucionar a otra artropatía definida, especialmente artritis reumatoide. El objetivo de este estudio fue describir las características clínicas y de laboratorio, tanto basales como de seguimiento, de pacientes con artritis indiferenciada en un centro de referencia. Materiales y métodos: Se realizó un estudio descriptivo retrospectivo con pacientes con artritis indiferenciada por criterio de reumatólogo. Se analizaron variables sociodemográficas, clínicas y terapéuticas. Las variables cualitativas se expresaron como frecuencias absolutas y relativas, y las cuantitativas con mediana y rango intercuartílico. Resultados: Se incluyeron 66 pacientes; la mediana de edad fue 46,3 años (RIC: 37,5-51,8); diez (15,2 %) sujetos tenían antecedente familiar de artritis reumatoide. Cuarenta (60,6 %) individuos tuvieron compromiso articular en interfalángicas proximales; el principal síntoma fue la rigidez matinal en 29 pacientes (44 %). El compromiso extraarticular más frecuente fue el cutáneo (n=14; 21,2 %). Los antiinflamatorios no esteroideos (n=18; 27,2 %) y los esteroides (n=15; 22,7 %) fueron los tratamientos más frecuentes. De 43 pacientes, 22 (51,2 %) permanecieron con diagnóstico de artritis indiferenciada, 18 (41,9 %) progresaron a otras enfermedades, siendo la más frecuente artritis reumatoide, y en tres (7 %) hubo remisión. Conclusiones: En una cohorte de pacientes con artritis indiferenciada del noroccidente colombiano, luego de 12 meses, la mayoría, persiste con este diagnóstico; fue llamativa la frecuencia importante de antecedente familiar de artritis reumatoide y de baja remisión espontánea.

ABSTRACT Introduction: Undifferentiated arthritis is an inflammatory arthropathy that does not meet the criteria of specific rheumatological diseases and whose symptoms persist for one year. These individuals may spontaneously remit or evolve to another defined arthropathy, especially rheumatoid arthritis. The aim of this study was to describe the clinical and laboratory characteristics, both baseline and follow-up, of patients with undifferentiated arthritis in a reference center. Materials and methods: A retrospective descriptive study was conducted with patients with undifferentiated arthritis defined by rheumatologist criteria. Sociodemographic, clinical and therapeutic variables were analyzed. The qualitative variables were expressed as absolute and relative frequencies and the quantitative variables with median and interquartile range. Results: 66 patients were included; the median age was 46.3 years (IQR: 37.5-51.8); 10 subjects (15.2 %) had a family history of rheumatoid arthritis. Forty individuals (60.6 %) had involvement in proximal interphalangeal joints; the main symptom was morning stiffness in 29 patients (44 %). The most frequent extra-articular involvement was cutaneous (n = 14, 21.2 %). Non-steroidal anti-inflammatory drugs (n=18; 27.2%) and steroids (n=15; 22.7 %) were the most frequent treatments. Of 43 patients, 22 (51.2 %) remained with a diagnosis of undifferentiated arthritis, 18 (41.9 %) progressed to other diseases, the most frequent being rheumatoid arthritis, and in three (7 %) there was disease remission. Conclusions: In a cohort of patients with undifferentiated arthritis from northwestern Colombia, after 12 months, most of them persist with this diagnosis; it was striking the important frequency of a family history of rheumatoid arthritis and a low spontaneous remission.

Effect of the desiccation tolerance and cryopreservation methods on the viability of Citrus limon L. Burm cv. Eureka seeds.

Cryopreservation of the germplasm for long-term periods is of great importance to maintain the genetic resource. Argentina is one of the world's highest lemon producing country. The performance of different cooling/warming rates in the cryopreservation method of Citrus limon L. Burm cv. Eureka seeds and their influence on the interval of optimal moisture content in the desiccation stage were analyzed. Water sorption isotherm was determined and modeled using D'Arcy & Watt equation; it provided important information concerning the amounts of water associated to strong, weak and multimolecular binding sites along the sorption isotherm. Seeds tolerated a wide range of desiccation conditions (0.180%), however desiccation to 0.0526 g H2O g-1 d.b. (aw = 0.0901) produced a significant loss of viability. Differential Scanning Calorimetry was used to identify the thermal transitions of lipids and water in the seed; enthalpies were used to calculate the unfrozen water fraction (0.19 g H2O g-1 d.b. corresponding to aw = 0.64). Two cooling/warming rates were tested on desiccated seeds (0.110.64 corresponding to the unfrozen water fraction. The use of higher cooling/warming rates enables a wider range of desiccation conditions (0.33

Multiple software based 3D modeling protocol for printing anatomical structures / Protocolo de impresión 3D de estructuras anatómicas basados en la utilización de software múltiple

With the increasing number of medical programs, research for new teaching methods has also emerged. Computer software and diagnostic images have been used for anatomy teaching as an alternative to cadaver dissection, which means students cannot develop a mental image of the human body without compromising spatial reasoning. Also the cadavers present flaws such as color, texture and smell. This paper explains in details the protocol used to reconstruct 3D models for rapid prototyping as an overcome to these difficulties. Online Computerized Tomography scans were obtained in DICOM format from OsiriX and InVesalius. Reconstruction of 3D models from aortic and superior tracheobronchial tract structures were created, InVesalius and Rhinoceros software were used. 3D models of a heart with its aorta, superior tracheobronchial tract and an aneurysm at the aortic bifurcation were obtained for rapid prototyping. The superior tracheobronchial tract model was printed. It is possible to produce printed models from CT scans using different softwares for 3D modeling and rapid prototyping. These models could allow the student to develop a three dimensional mental image of the human body according to literature.

Con el incremento en el número de programas médicos, la búsqueda por nuevos métodos de enseñanza también ha emergido. Software computarizado e imágenes diagnósticas han sido utilizados en la enseñanza de anatomía como una alternativa a la disección cadavérica, lo que conlleva a que los estudiantes no puedan desarrollar una imagen mental del cuerpo humano sin comprometer el raciocinio espacial. También los cadáveres presentan desventajas como color, textura y olor. Este artículo explica en detalle el protocolo usado para la reconstrucción de modelos 3D para prototipado rápido como un recurso para superar estas dificultades. Tomografías computarizadas online fueron obtenidas en formato DICOM de OsiriX e InVesalius. La reconstrucción en 3D de modelos de estructuras aórticas y del ducto traqueobronquial fueron creadas con los software InVesalius y Rhinoceros. Modelos 3D de corazón y aorta, el ducto traqueobronquial y un aneurisma aórtico abdominal en su bifurcación fueron obtenidos para la prototipado rápido. El modelo de ducto traqueobronquial fue impreso. Es posible producir modelos de TC usando diferentes programas de modelado 3D. Estos modelos podrían permitir a los estudiantes desarrollar una imagen metal tridimensional del cuerpo humano según la literatura.

Zosteriform cutaneous leishmaniasis due to Leishmania ( Viannia ) panamensis and Leishmania ( Viannia ) braziliensis: report of three cases.

In Colombia, zosteriform leishmaniasis is a little-known and infrequent clinical variant of cutaneous leishmaniasis. Its clinical features include one or more plaques made up of papules and pseudo-vesicles, which conform to a lineal pattern, as well as satellite lesions that affect one or more dermatomes, without crossing the median line. We present three zosteriform cutaneous leishmaniasis cases in which Leishmania panamensis and Leishmania braziliensis were identified as the infective species. In light of the fact that the disease occurs infrequently, diagnosis was reached by taking into account epidemiological and clinical suspicion.

Zosteriform cutaneous leishmaniasis due to Leishmania ( Viannia ) panamensis and Leishmania ( Viannia ) braziliensis: Report of three cases / Leishmaniasis cutánea zosteriforme causada por Leishmania ( Viannia) panamensis y Leishmania ( Viannia ) braziliensis: reporte de tres casos

In Colombia, zosteriform leishmaniasis is a little-known and infrequent clinical variant of cutaneous leishmaniasis. Its clinical features include one or more plaques made up of papules and pseudo-vesicles, which conform to a lineal pattern, as well as satellite lesions that affect one or more dermatomes, without crossing the median line. We present three zosteriform cutaneous leishmaniasis cases in which Leishmania panamensis and Leishmania braziliensis were identified as the infective species. In light of the fact that the disease occurs infrequently, diagnosis was reached by taking into account epidemiological and clinical suspicion.

La leishmaniasis zosteriforme es una variante clínica de la leishmaniasis cutánea, infrecuente y poco conocida en Colombia. Clínicamente se caracteriza por una o varias placas conformadas por pápulas y pseudovesículas que siguen un patrón lineal, y por lesiones satelitales que comprometen uno o varios dermatomas sin sobrepasar la línea media. Se presentan tres casos de leishmaniasis cutánea zosteriforme en los que se identificaron Leishmania panamensis y Leishmania braziliensis como especies infectantes. La sospecha epidemiológica derivada de la procedencia de los pacientes, así como la sospecha clínica a partir del reconocimiento de una presentación infrecuente de la enfermedad, permitieron hacer el diagnóstico.