Estilos y enfoques de aprendizaje en estudiantes de Estomatología y relación con el rendimiento académico en Farmacología

Fundamento: los estilos y enfoques de aprendizaje permiten conocer cómo el estudiante enfrenta este proceso y el modo en que procesa la información que debe ser asimilada. Objetivo: identificar los estilos y enfoques de aprendizaje que utilizan estudiantes de Estomatología y su relación con el rendimiento académico en la disciplina Farmacología. Métodos: estudio descriptivo-transversal, con enfoque cualicuantitativo, realizado de noviembre 2021 a enero 2022. La muestra, no probabilística, fue de 28 estudiantes (90,3 %) de segundo año de la carrera de Estomatología impartida en la Facultad de Estomatología de La Habana. A los participantes se les aplicaron dos instrumentos: cuestionario Honey y Alonso sobre estilos de aprendizaje y cuestionario Enfoques e Inventario de Habilidades de Estudio de los Estudiantes. Las dimensiones del rendimiento académico fueron excelente, bueno, y regular. Resultados: predominó la preferencia muy alta/alta en el estilo teórico (67,86 %) y la preferencia moderada en el reflexivo (67,86 %). Se encontró relación significativa entre la cantidad de estilos de aprendizaje de preferencia muy alta/alta y el rendimiento académico (p=0,044), y entre el estilo reflexivo y el rendimiento académico (p=0,024). También, se encontró relación significativa entre el rendimiento académico y el enfoque de aprendizaje estratégico (p=0,008) y la preferencia por la transmisión de la información (p=0,028). Conclusiones: en los estudiantes existen estilos y enfoques de aprendizaje que se relacionan con el rendimiento académico en Farmacología; se muestran aspectos que se deben considerar para el mejoramiento del proceso docente de esta disciplina en Estomatología.

Foundation: the learning styles and approaches allow us to know how the student faces this process and the way in which they process the information that must be assimilated. Objective: to identify the learning styles and approaches used by Dentistry students and their relationship with academic performance in the Pharmacology discipline. Methods: a descriptive-cross-sectional study, with a qualitative-quantitative approach, carried out from November 2021 to January 2022. The non-probabilistic sample consisted of 28 students (90.3%) in the second year of the Dentistry course taught at the Havana Dentistry Faculty. Two instruments were applied to the participants: the Honey and Alonso questionnaire on learning styles and the Approaches and Inventory of Student Study Skills questionnaire. The dimensions of academic performance were excellent, good, and regular. Results: the very high/high preference predominated in the theoretical style (67.86%) and the moderate preference in the reflective style (67.86%). A significant relationship was found between the number of very high/high preference learning styles and academic performance (p=0.044), and between the reflective style and academic performance (p=0.024). Also, a significant relationship was found between academic performance and the strategic learning approach (p=0.008) and the preference for the transmission of information (p=0.028). Conclusions: there are learning styles and approaches among students that are related to academic performance in Pharmacology; Aspects that should be considered for the improvement of the teaching process of this discipline in Dentistry are shown.

Infección por SARS-CoV-2 y grupos sanguíneos en pacientes cubanos diagnosticados con la COVID-19 / SARS-Cov-2 Infection and Blood Groups in Cuban Patients Diagnosed with COVID-19

Introducción: Diferentes estudios han propuesto la relación entre los grupos sanguíneos del sistema ABO y la susceptibilidad a la COVID-19 y su importancia en el curso de la enfermedad. Objetivo: Determinar la frecuencia fenotípica de grupos sanguíneos ABO y RhD en un grupo de pacientes con infección activa por SARS-CoV-2. Métodos: Se realizó un estudio descriptivo, transversal y caso control en el Hospital Docente Clínico Quirúrgico Freyre Andrade de La Habana, para determinar la frecuencia fenotípica ABO y RhD en un grupo de pacientes con enfermedad activa por la COVID-19. Se estudiaron 928 muestras de sangre de pacientes con diagnóstico de COVID-19 y 1050 muestras pertenecientes a individuos sanos como grupo control. El grupo sanguíneo ABO y RhD se determinó por método de aglutinación en tubo con sueros hemoclasificadores anti-A, anti-B, anti-A+B, yanti-D. Los resultados fueron expresados en frecuencias absolutas y relativas y se determinó la asociación del grupo sanguíneo con la gravedad de la enfermedad por medio de la prueba no paramétrica de χ2 con un nivel de significación de p ≤ 0,05. Resultados: Se observó predominio del fenotipo O (49,24 por ciento) seguido del A (35,79 por ciento), B (12,68 por ciento) y AB (2,27 por ciento) respectivamente. Los fenotipos O y B presentaron significación estadística para la ocurrencia de la COVID-19, con valores de p < 0,05. No se encontró significación estadística en cuanto al predominio de un fenotipo particular y la necesidad de cuidados intensivos. Conclusiones: La relación del grupo sanguíneo ABO en la infectividad por SARS-CoV-2 y la gravedad de la enfermedad por la COVID-19 requiere estudios adicionales ya que los actuales no son concluyentes(AU)

Introduction: Different studies have proposed the relationship between the blood groups of ABO system and the susceptibility to COVID-19 and its importance in the course of the disease. Objective: To determine the phenotypic frequency of ABO and RhD blood groups in a group of patients with active SARS-CoV-2 infection. Methods: A descriptive, cross-sectional, case-control study was conducted to determine the ABO and RhD phenotypic frequency in a group of patients with COVID-19 active disease. Nine hundred twenty eight blood samples and 1050 samples belonging to healthy individuals as control group were studied. The ABO and RhD blood group was determined by the tube agglutination method with anti-A, anti-B, anti-A+B, and anti-D blood classifying sera. The results were expressed in absolute and relative frequencies and the association of the blood group with the severity of the disease was determined by the non-parametric χ2 test with a significance level of p ≤ 0.05. Results: A predominance of phenotype O (49.24percent) was observed, followed by A (35.79percent), B (12.68percent) and AB (2.27percent) respectively. The O and B phenotypes showed statistical significance for the occurrence of COVID-19, with p values < 0.05. No statistical significance was found regarding the prevalence of a particular phenotype and the need for intensive care. Conclusions: The relationship of the ABO blood group in the infectivity of SARS-CoV-2 and the severity of the disease by COVID-19 requires additional studies, since the current ones are not conclusive(AU)

Alteraciones hematológicas en sangre periférica de pacientes con COVID-19 / Molecular study of leukemias: essential tool for the hematologist

Introducción: Los primeros casos con neumonía atípica de etiología desconocida fueron reportados en Wuhan, China en diciembre de 2019. En enero 2020 se describió como agente causal un nuevo tipo de virus de la familia Coronaviridae, denominado SARS-CoV-2. Objetivo: Evaluar la significación clínica de los cambios hematológicos y morfológicos en la sangre periférica de pacientes con COVID-19. Métodos: Se realizó un estudio descriptivo, observacional, transversal que incluyó a los pacientes con COVID-19 que ingresaron en el Hospital Clínico Quirúrgico Docente Freyre de Andrade desde el 1ro de junio hasta 31 de septiembre de 2021. Los pacientes fueron asignados a dos grupos según fueron admitidos, en las unidades de vigilancia intensiva o en la unidad de cuidados intensivos. Se les realizó hemograma completo y lámina periférica el día del ingreso para evaluar la significación clínica de estas variables en la evolución de estos pacientes. Resultados: El sexo femenino predominó en los pacientes ingresados en unidades de vigilancia intensiva (67,36 %) y el masculino en los ingresados en unidades de cuidados intensivos (63,26 %). La media de edad fue mayor en el grupo de pacientes en cuidados intensivos (65,83 años). La leucocitosis y el menor recuento de plaquetas predominaron en los pacientes ingresados en cuidados intensivos, seguido de linfopenia. Las macroplaquetas, las vacuolas citoplasmáticas y las granulaciones tóxicas fueron más frecuentes en el grupo de cuidados intensivos. Conclusiones: El hemograma y el frotis de sangre periférica son útiles para diagnosticar y predecir la evolución de los pacientes y permiten un mejor manejo de la infección.

Introduction: The first cases of atypical pneumonia of unknown etiology were reported in Wuhan, China in December 2019. In January 2020 a new virus from Coronaviridae family was described as causal agent and was named SARS-COV-2. Objectives: To evaluate the clinical significance of numerical values of complete blood count (CBC) and morphologic changes on peripheral blood on patients with COVID-19. Methods: A descriptive, observational, transversal study included patients with diagnosis of COVID-19 admitted in Freyre de Andrade Hospital in Havana, between June 1st and September 31st of 2022 was carried out. Patients were assigned to two groups according to their admission in intensive vigilance ward or intensive care unit. CBC test and peripheral blood smear were performed on admission day to evaluate the significance on clinical evolution. Results: Female sex predominated on intensive vigilance group (67,36 %) and male in intensive care group (63,26 %). Media of age was superior in intensive care group (67,83 years). Leukocytosis and low level of platelets count were significantly more common in more severe group followed by lymphopenia. The presence of big platelets, cytoplasmic vacuoles and toxic granules were more common in intensive care unit group. Conclusions: The CBC and peripheral blood smear are useful tools to diagnose and predict clinical evolution and allow a better management of infection.

Electroforesis de isoenzimas de fosfatasa alcalina: utilidad diagnóstica en pacientes con enfermedad de células falciformes / Alkaline phosphatase isoenzyme electrophoresis: diagnostic utility in patients with sickle cell disease

Introducción: Las fosfatasas alcalinas (FAL) humanas son indicadores enzimáticos de daño de órganos. Las complicaciones de la drepanocitosis incluyen lesión de órganos debido a la reperfusión, la vasculopatía proliferativa y la anemia hemolítica. Objetivo: Demostrar la utilidad de la determinación de la actividad enzimática de la FAL y la movilidad electroforética de las isoenzimas séricas de FAL en pacientes con drepanocitosis en estado basal y durante las crisis. Métodos: Estudio descriptivo, longitudinal, prospectivo en 85 individuos adultos, 25 controles sanos y 60 pacientes, entre enero y diciembre/2018. Variables estudiadas: genotipos (SS/Sβo, SC/Sβ+), edad, sexo, actividad de FAL e isoenzimas por electroforesis en gel de agarosa con y sin lectina: hepática 1 (H1) y (H2); placenta 1(P1), ósea, intestinales 1, 2, 3 (I1.2.3) en estado basal y crisis. Resultados: La actividad de la FAL fue significativamente mayor en los pacientes que en los controles. Hubo diferencias significativas en la actividad de la FAL y de la fracción H1+P1/1 de pacientes en estado basal en relación con el grupo control. La actividad de la enzima y las isoenzimas no mostró diferencias significativas entre los genotipos. Igual comportamiento se observó en la actividad de las enzimas e isoenzimas durante las crisis vasoclusivas dolorosas y hepáticas. Se encontraron diferencias significativas en la actividad de la fracción hepática H1+P1/1 entre los grupos de 20-29 y 40-49 años Conclusiones: La determinación de la FAL en los pacientes con drepanocitosis es útil y permite establecer un perfil isoenzimático personalizado, con importancia pronóstica como un marcador biológico de alarma(AU)

Introduction: Human alkaline phosphatases (ALP) are enzymatic indicators of organ damage. Complications of sickle cell disease include injury to organs due to reperfusion injury, proliferative vascular disease, and hemolytic anemia. Objective: To demonstrate the usefulness of determing ALP activity and the electrophoretic mobility of the serum ALP isoenzymes in patients with sickle cell disease at base line and during the crises. Methods: A descriptive, longitudinal, prospective study was carried out in 85 adult individuals, 25 healthy controls and 60 patients, between January and December/2018. Studied variables: genotypes (SS/SβO, SC/Sβ+), age, sex, ALP activity and isoenzymes by agarose gel electrophoresis with and without lectin: hepatic 1 (H1) and (H2); placenta 1 (P1), bone, intestinal 1, 2, 3 (I1.2.3) in basal state and crisis. Results: ALP activity was significantly higher in patients than in controls. Significant differences were found in the activity of the ALP and fraction H1+P1/1 of patients in basal state in relation to the control group. The activity of the enzyme and the isoenzymes showed no significant differences between genotypes. The same behavior was observed in the activity of enzymes and isoenzymes during painful and liver vasooclusive crises. Significant differences were found in the activity of the liver fraction H1+P1/1 between the groups of 20-29 and 40-49 years. Conclusions: The determination of the ALP in patients with sickle cell disease is useful and allows to establish a personalized isoenzimatic profile, with prognostic importance as a biological alarm marker(AU)

Influencia de la carga alélica del JAK2V617F en pacientes cubanos con trombocitemia esencial y mielofibrosis primaria / Influence of JAK2V617F allelic burden in Cuban patients with essential thrombocythemia and primary myelofibrosis

Introducción: La frecuencia de la mutación JAK2V617F se estima entre el 50 y 60 por ciento en pacientes con trombocitemia esencial y mielofibrosis primaria. El 30 por ciento de los pacientes con policitemia vera y mielofibrosis primaria. Entre 2-4 por ciento de los pacientes con trombocitemia esencial presentan pérdida de heterocigosidad. Objetivos: Evaluar la influencia de la carga alélica de la mutación JAK2V617F y su relación con variables clínico-hematológicas en el diagnóstico de estas enfermedades en pacientes cubanos. Métodos: Se realizó un estudio retrospectivo, descriptivo y longitudinal en el Instituto de Hematología e Inmunología entre 2010 y 2020. Se incluyeron todos los pacientes con sospecha de trombocitemia esencial y mielofibrosis primaria con muestras de ADN válidas. Se les cuantificó la carga alélica de la mutación por PCR en tiempo real. Resultados: Se detectó la mutación en 66,7 por ciento de los diagnosticados con trombocitemia esencial y mielofibrosis primaria. El 62,5 por ciento de los pacientes con mielofibrosis primaria fueron homocigotos a la mutación, mientras que en la trombocitemia esencial solo el 20,8 por ciento. La diferencia de medias de cargas alélicas entre ambas enfermedades fue estadísticamente significativa. No se encontraron diferencias significativas en la comparación de las variables clínicas y hematológicas en estas enfermedades ni asociación con la carga alélica con excepción de las plaquetas en la mielofibrosis primaria. Conclusiones: El estudio estuvo limitado por la escasa muestra de pacientes, pero se corresponde con otras investigaciones que sostienen el concepto de que la presentación fenotípica de las neoplasias mieloproliferativasestá influenciada por la carga mutacional del JAK2V617F(AU)

Introduction: The frequency of the JAK2V617F mutation is estimated to be between 50 percent and 60 percent in patients with essential thrombocythemia and primary myelofibrosis. 30 percent of patients with polycythemia vera and primary myelofibrosis and 2-4 percent of patients with essential thrombocythemia show loss of heterozygosity. Objectives: To evaluate the influence of the allelic load of the JAK2V617F mutation in the diagnosis of these diseases in Cuban patients and its relationship with clinical-hematological variables. Methodology: A retrospective, descriptive and longitudinal study was carried out at the Institute of Hematology and Immunology between 2010 and 2020. All patients with suspected essential thrombocythemia and primary myelofibrosis with valid DNA samples were included. The allelic load of the mutation was quantified by real-time PCR. Results: The mutation was detected in 66.7 percent of those diagnosed with essential thrombocythemia and primary myelofibrosis. 62.5 percent of the patients with primary myelofibrosis were homozygous for the mutation, while in essential thrombocythemia only 20.8 percent. The difference in mean allelic loads between both diseases was statistically significant. No significant differences were found in the comparison of clinical and hematological variables in these diseases or association with allelic load, with the exception of platelets in primary myelofibrosis. Conclusions: The study was limited by the small sample of patients, but it corresponds to other investigations that support the concept that the phenotypic presentation of myeloproliferative neoplasms is influenced by the mutational load of JAK2V617F(AU)

Biomarkers of sequela in adult patients convalescing from COVID-19.

Different biomarkers for SARS-CoV-2 have been linked to detection, diagnosis, treatment, disease progression, and development of new drugs and vaccines. The objective of this research was to evaluate various hematological, biochemicals, immunological, radiological and spirometric parameters in 20 adult patients convalescing from COVID-19 and their possible relationship with the clinical course of the disease. The frequencies of categorical variables were compared using the chi-square and Fisher's exact test. The levels of statistical significance were denoted in each figure legend. Two-dimensional clustering analysis was performed using MeV software from TIGR. The tests with P value of ≤ 0.05 were considered statistically significant. Most of the patients studied presented alterations in dissimilar laboratory, radiological and spirometric parameters, which were related to the clinical evolution of the disease. The results obtained show that certain hematological, biochemical, immunological and radiological parameters can be considered as biomarkers of sequela in adult COVID-19 patients, which allows their stratification, according to the degree of involvement or sequela, into three groups: I (mild degree of involvement or sequela), without lung lesions on computerized axial tomography (CT scan) and high values of IgG, C3 and hemoglobin, II (moderate degree of involvement or sequel), without lung lesions on CT scan, characterized by high levels of CD3+/CD4+ T lymphocytes and the rest of the variables with low values and III (severe degree of involvement or sequela), with lung lesions on CT scan and high values of erythrocyte sedimentation rate, monocytes and neutrophils, associated with lymphopenia and decreased concentrations of IgG and C3.

Persistently positive PCR SARS-CoV-2 at low cycle threshold in an immunosuppressed patient.

We describe the very prolonged course of the disease in an immunosuppressed patient with persistently positive PCR against SARS-CoV-2 with low cycle threshold for at least 114 days.

Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice.

Oncolytic viruses (OVs) encoding a variety of transgenes have been evaluated as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-modified T cells in the solid tumor microenvironment (TME). Here, using systemically delivered OVs and CAR T cells in immunocompetent mouse models, we have defined a mechanism by which OVs can potentiate CAR T cell efficacy against solid tumor models of melanoma and glioma. We show that stimulation of the native T cell receptor (TCR) with viral or virally encoded epitopes gives rise to enhanced proliferation, CAR-directed antitumor function, and distinct memory phenotypes. In vivo expansion of dual-specific (DS) CAR T cells was leveraged by in vitro preloading with oncolytic vesicular stomatitis virus (VSV) or reovirus, allowing for a further in vivo expansion and reactivation of T cells by homologous boosting. This treatment led to prolonged survival of mice with subcutaneous melanoma and intracranial glioma tumors. Human CD19 CAR T cells could also be expanded in vitro with TCR reactivity against viral or virally encoded antigens and was associated with greater CAR-directed cytokine production. Our data highlight the utility of combining OV and CAR T cell therapy and show that stimulation of the native TCR can be exploited to enhance CAR T cell activity and efficacy in mice.

Morbilidad y mortalidad de 599 pacientes con drepanocitosis en el Instituto de Hematología e Inmunología / Morbidity and mortality of 599 sickle cell disease patients in the Institute of Hematology and Immunology

Introducción: La drepanocitosis es la anemia hemolítica congénita más común del mundo. Entre el 5 y 15 por ciento de la población mundial es portadora de la hemoglobina S y en Cuba, la frecuencia es de 3,08 por ciento, lo que representa un problema de salud pública. Objetivo: Caracterizar el cuadro clínico, el perfil hematológico y la probabilidad de supervivencia de los pacientes con drepanocitosis en el Instituto de Hematología e Inmunología. Método: Se realizó estudio descriptivo, longitudinal y retrospectivo, que incluyó todos los enfermos seguidos, al menos dos años, en la institución, entre enero de 1973 y diciembre del 2009. Resultados: Se incluyeron 599 pacientes (285 masculinos), 439 SS/Sβ0tal y 160 SC/Sβ+tal. El seguimiento medio fue de 17,6±9,5 años. Predominaron los pacientes entre 20 y 59 años. Los eventos clínicos más frecuentes fueron las crisis vasoclusivas dolorosas, las infecciones, el síndrome torácico agudo y las complicaciones hepáticas. Los valores de reticulocitos, plaquetas, leucocitos y hemoglobina fetal fueron significativamente mayores en los pacientes SS/Sβ0tal; no así la hemoglobina total que fue mayor en los SC/Sβ+tal. La probabilidad de supervivencia global de los pacientes a los 45 años fue de 69 por ciento. Los accidentes vasculares encefálicos (17,5 por ciento), las complicaciones hepáticas (17,5 por ciento) y las cardíacas (14,28 por ciento) fueron las principales causas de muerte. Conclusiones: La distribución demográfica y por hemoglobinopatías, el cuadro clínico, y el perfil hematológico fueron similares a los encontrados en pacientes de otras regiones geográficas, excepto la frecuencia de complicaciones hepáticas que fue mayor. La probabilidad de supervivencia fue similar con los mejores centros de atención en el mundo(AU)

Introduction: Sickle cell disease is the most common congenital hemolytic anemia in the world. Between 5 to 15 percent of the world population is a carrier of hemoglobin S and in Cuba, the frequency is 3.08 percent, which represents a public health problem. Objective: To characterize the clinical picture, the hematological profile, and the probability of survival of patients with sickle cell disease at the Institute of Hematology and Immunology. Method: A descriptive, longitudinal and retrospective study was carried out, which included all patients followed up for at least two years at the institution between January 1973 and December 2009. Results: 599 patients (285 male), 439 SS/Sβ0tal and 160 SC/Sβ+tal, were included. The mean follow-up was 17.6±9.5 years. Patients between 20 and 59 years old predominated. The most frequent clinical events were painful vasocclusive crises, infections, acute chest syndrome, and liver complications. The reticulocytes, platelets, leukocytes and fetal hemoglobin values ​​were significantly higher in the SS/Sβ0tal patients, but not the total hemoglobin, which was higher in the SC/Sβ+tal. The overall survival probability of patients at 45 years was 70 percent. Stroke (17.5 percent), liver complications (17.5 percent), and cardiac complications (14.28 percent) were the main causes of death. Conclusions: The demographic distribution and by hemoglobinopathies, the clinical events, and the hematological profile were similar to those found in patients from other geographic regions, except the frequency of liver complications, which was higher. The probability of survival was comparable with the best care centers in the world(AU)

Persistently positive PCR SARS-CoV-2 at low cycle threshold in an immunosuppressed patient

ABSTRACT We describe the very prolonged course of the disease in an immunosuppressed patient with persistently positive PCR against SARS-CoV-2 with low cycle threshold for at least 114 days.

Quality of Life in Hidradenitis Suppurativa: validation of the HSQoL-24.

To date, there are no disease-specific instruments in Spanish to assess quality of life of patients with hidradenitis suppurativa. A multicentre study was previously carried out in Spain between 2016 and 2017 to develop the Hidradenitis Suppurativa Quality of Life-24 (HSQoL-24), a disease-specific questionnaire to assess quality of life in patients with hidradenitis suppurativa. The objectiv-es of this study are to revalidate the HSQoL-24 in Spanish with a larger sample of patients, and to present the English version. In this multi-centre study in Spain, patients with hidradenitis suppurativa completed the HSQoL-24, the Dermatology Life Quality Index and the Skindex-29. The Hurley staging system was used to assess the severity of the disease. Validation of the questionnaire was carried out in 130 patients, of whom 75 (57.7%) were women. This study demonstrates adequate values of reliability and validity of the HSQoL-24, confirming the previous test re-test validation and making this questionnaire one of wide clinical validity in terms of results perceiv-ed by patients.

Development and validation of IMMUNO-COV™: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2.

We here describe the development and validation of IMMUNO-COV™, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-Δ19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-Δ19CT infection was blocked by monoclonal α-SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of α-SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNT EC50 values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV™ assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.

Oncolytic Viruses: Priming Time for Cancer Immunotherapy.

New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates.

Respuesta al tratamiento radioterápico en pacientes con tumores malignos de cabeza y cuello / Response to radiotherapy treatment in patients with head and neck malignant tumors

Introducción: La radioterapia es una de las variantes de tratamiento más antiguas con que contamos hoy día para curar los pacientes afectos de neoplasias malignas, pero debe ser cuidadosamente seleccionada en pacientes pediátricos. Objetivo: Evaluar la respuesta al tratamiento radiante en niños con tumores de cabeza y cuello. Métodos: Se realizó un estudio descriptivo, retrospectivo lineal, donde se incluyeron 26 pacientes ingresados en el Servicio de Oncocirugía del hospital William Soler desde enero de 2000 a enero de 2013, con diferentes tipos de tumores malignos de cabeza y cuello y edades comprendidas entre 1 y 18 años. Se tuvieron en cuenta los efectos tóxicos a largo plazo del tratamiento radiante, asociado o no a tratamiento quimioterápico adyuvante o concurrente y a la cirugía. Resultados: Todos los pacientes recibieron radioterapia corporal externa, el 73,1 por ciento de los casos recibió quimioterapia adyuvante en su mayoría con diagnóstico de linfomas y 7,7 por ciento recibió quimioterapia concurrente. Esta última en dos pacientes: uno con sarcoma facial y otro con carcinoma de parótida. Cinco pacientes (19,2 por ciento) solo recibieron cirugía y radioterapia como tratamiento: dos casos con neuroblastoma, un caso con sarcoma facial y dos con hemangiopericitomas. Conclusión: El estudio demostró la gran utilidad del empleo de la radioterapia en el control de las enfermedades malignas de la infancia localizadas en cabeza y cuello(AU)

Introduction: Radiotherapy is one of the oldest treatments used nowadays for curing patients suffering from malignant neoplasias, but it must be carefully selected in pediatric patients. Objective: To evaluate the response of radiotherapy treatments in children with head and neck tumors. Methods: A descriptive, lineal retrospective study was carried out, in which were included 26 patients admitted in the Service of Oncosurgery of William Soler Hospital from January, 2000 to January, 2013. These patients presented different kinds of head and neck malignant tumors; their ages were among 1 and 18 years. The long term toxic effects of radiotherapy were taken into account, being those associated or not to concurrent or adyuvant chemotherapy, and to surgery. Results: All the patients received physical external radiotherapy. 73,1 percent of the cases (most of them with a diagnosis of lymphoma) received adyuvant chemotherapy and 7,7 percent had concurrent chemotherapy. This last one in two patients: one with facial sarcoma and the other one with parotid carcinoma. Just five patients (19.2 percent) had surgery and radiotherapy as treatment: two cases with neuroblastoma, one case with facial sarcoma, and two cases of hemangiopericytomas. Conclusions: This study has demonstrated the usefulness of radiotherapy in the control of head and neck malignant diseases in children(AU)

Preclinical Development of Oncolytic Immunovirotherapy for Treatment of HPVPOS Cancers.

Immunotherapy for HPVPOS malignancies is attractive because well-defined, viral, non-self tumor antigens exist as targets. Several approaches to vaccinate therapeutically against HPV E6 and E7 antigens have been adopted, including viral platforms such as VSV. A major advantage of VSV expressing these antigens is that VSV also acts as an oncolytic virus, leading to direct tumor cell killing and induction of effective anti-E6 and anti-E7 T cell responses. We have also shown that addition of immune adjuvant genes, such as IFNß, further enhances safety and/or efficacy of VSV-based oncolytic immunovirotherapies. However, multiple designs of the viral vector are possible-with respect to levels of immunogen expression and method of virus attenuation-and optimal designs have not previously been tested head-to-head. Here, we tested three different VSV engineered to express a non-oncogenic HPV16 E7/6 fusion protein for their immunotherapeutic and oncolytic properties. We assessed their profiles of efficacy and toxicity against HPVPOS and HPVNEG murine tumor models and determined the optimal route of administration. Our data show that VSV is an excellent platform for the oncolytic immunovirotherapy of tumors expressing HPV target antigens, combining a balance of efficacy and safety suitable for evaluation in a first-in-human clinical trial.

Relapsing-Remitting Multiple Sclerosis Is Characterized by a T Follicular Cell Pro-Inflammatory Shift, Reverted by Dimethyl Fumarate Treatment.

Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing-remitting MS (RRMS) patients whose mechanism of action is not completely understood. The aim of our study was to compare cTfh subpopulations between RRMS patients and healthy subjects and evaluate the impact of DMF treatment on these subpopulations, relating them to changes in B cells and humoral response. We analyzed, by flow cytometry, the distribution of cTfh1 (CXCR3+CCR6-), cTfh2 (CXCR3-CCR6-), cTfh17 (CXCR3-CCR6+), and the recently described cTfh17.1 (CXCR3+CCR6+) subpopulations of CD4+ Tfh (CD45RA-CXCR5+) cells in a cohort of 29 untreated RRMS compared to healthy subjects. CD4+ non-follicular T helper (Th) cells (CD45RA-CXCR5-) were also studied. We also evaluated the effect of DMF treatment on these subpopulations after 6 and 12 months treatment. Untreated RRMS patients presented higher percentages of cTfh17.1 cells and lower percentages of cTfh2 cells consistent with a pro-inflammatory bias compared to healthy subjects. DMF treatment induced a progressive increase in cTfh2 cells, accompanied by a decrease in cTfh1 and the pathogenic cTfh17.1 cells. A similar decrease of non-follicular Th1 and Th17.1 cells in addition to an increase in the anti-inflammatory Th2 subpopulation were also detected upon DMF treatment, accompanied by an increase in naïve B cells and a decrease in switched memory B cells and serum levels of IgA, IgG2, and IgG3. Interestingly, this effect was not observed in three patients in whom DMF had to be discontinued due to an absence of clinical response. Our results demonstrate a possibly pathogenic cTfh pro-inflammatory profile in RRMS patients, defined by high cTfh17.1 and low cTfh2 subpopulations that is reverted by DMF treatment. Monitoring cTfh subsets during treatment may become a biological marker of DMF effectiveness.

Mala conducta científica en la publicación / Scientific misconduct in the publication

La publicación en revistas científicas constituye la forma más aceptada para validar una investigación debido a que pasa por un riguroso proceso de revisión por expertos, que deciden entre lo publicable y lo no publicable con vista a garantizar la calidad de los trabajos. A pesar de esto con frecuencia aparecen prácticas incorrectas relacionadas con la ética durante la publicación, que se conocen como mala conducta científica. Las manifestaciones de mala conducta científica van desde el fraude científico hasta una variedad de faltas que se cometen en el proceso de publicación. El fraude científico incluye la invención, la falsificación y el plagio. Las faltas en el proceso de publicación incluyen la autoría ficticia, la autoría fantasma, la publicación duplicada, la publicación fragmentada o publicación salami, la publicación inflada, el autoplagio, la incorrección de citas bibliográficas, los sesgos de publicación y la publicación anticipada.

The publication in scientific journals is the most accepted way to validate an investigation because it undergoes a rigorous process of review by experts, who decide between the publishable and the non-publishable in order to guarantee the quality of the works. In spite of this, misconceptions about ethics are frequently encountered during publication, which are known as scientific misconduct. The manifestations of scientific misconduct range from scientific fraud to a variety of misconduct that are committed in the publishing process. Scientific fraud includes invention, counterfeiting and plagiarism. Faults in the publishing process include fictitious authorship, ghostwriting, duplicate publication, fragmented publication or salami publication, inflated publication, self-plagiarism, incorrect bibliographic citations, publication biases, and early publication.

Direct oral anticoagulants: An update. / Anticoagulantes orales directos: puesta al día.

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs.