Riesgo de contagio por COVID-19 en función del tipo de contacto y de la renta familiar / Risk of contagion by COVID-19 depending on the type of contact and family income

Introducción: tras una segunda oleada de la pandemia COVID-19 en Zaragoza, se estudian los contactos estrechos con pacientes con COVID-19, con la finalidad de valorar el riesgo de infección tras exposición en función del paciente índice, adulto o niño, y la renta familiar. Material y métodos: se realiza un estudio descriptivo de todos los pacientes pediátricos que han tenido contacto con pacientes con COVID-19 en el centro de salud de Delicias Sur de Zaragoza entre los meses de julio y agosto de 2020 y se valora la aparición de síntomas, consultas en servicio de urgencias, realización de pruebas complementarias, contacto estrecho con adulto o con niño y la renta familiar. Resultados: un total de 292 pacientes fueron contacto estrecho con pacientes con COVID-19, de los cuales 128 fueron positivos para la PCR de SARS-CoV-2. Al analizar el tipo de contacto, se encontró que un 10,94% había mantenido contacto estrecho con un niño y un 89,06% con un adulto. El riesgo de contagio tras sufrir contacto con un niño positivo fue del 34,15%, mientras que, tras contacto con un adulto positivo, el riesgo fue del 45,78%. Asimismo, el riesgo de contagio entre las rentas inferiores a 18 000 € fue de 47,9 frente al 27,6% de aquellos pacientes con rentas superiores a 18 000 €. Conclusiones: el riesgo de contagio de COVID-19 es mayor cuando el contacto estrecho es con un adulto y cuando el nivel de renta familiar es inferior (AU)

Purpose: during the second wave of the COVID-19 pandemic in Zaragoza, we studied the paediatric contacts of COVID-19-positive patients to estimate the risk of infection after exposure to a positive child or adult and the risk of infection based on household income.Methods: we conducted a descriptive study of all paediatric patients that were close contacts of individuals with COVID-19 in the Delicias Sur Primary Care Centre (Zaragoza, Spain) between July and August 2020. We also analysed the most frequent symptoms, visits to the emergency department, diagnostic tests, contact with a child versus an adult with COVID-19 and household income.Results: a total of 292 patients had had close contact with individuals with COVID-19; 218 of them had positive SARS-CoV-2 PCR test results. When we analysed the close contacts, we found that 10.94% of patients that tested positive had been in close contact with a child with COVID-19 and 89.06% with an adult with COVID-19. The estimated risk of infection after exposure was 29.8% in the case of close contact with a child with COVID-19 compared to 46.53% when it came to close contact with an adult case. The risk of infection was higher in patients with an annual household income of less than €18000 (47.9%) compared to patients with a higher annual household income (27.6%).Conclusion: the risk of SARS-CoV-2 infection was higher in patients that had close contact with adult cases and with lower household incomes. (AU)

Effect of kinesio taping on calf pain after a half marathon: A pilot study / Efecto del vendaje neuromuscular sobre el dolor en las pantorrillas después de una media maratón: Un estudio piloto / Efeito da bandagem neuromuscular na dor na panturrilha após meia maratona: um estudo piloto

OBJECTIVE: The purpose of the present study was to examine the effect of kinesio taping on calf pain in healthy runners immediately after a half marathon. METHOD: A sample of 13 runner volunteers was recruited in a half marathon. Calf pain measurements were taken at baseline and 10-15 minutes after competition. Kinesio tape was applied to the calf of runners the evening before the competition, only on one leg, with the contralateral leg acting as a control. RESULTS: The results of the repeated measures ANOVA in the leg differences on pain values did not show statistically significant differences (p = 0.515). However, the effect size after the race could be an indication that kinesio tape might be useful (g = - 0.37) and that studies with the sample calculated would be necessary (n = 61). CONCLUSIONS: When kinesio tape was applied to healthy half marathon runners, the data did not disclose whether the tape could lead to control calf pain produced by the competition

OBJETIVO: El propósito del presente estudio fue examinar el efecto del vendaje neuromuscular sobre el dolor de la pantorrilla en corredores sanos inmediatamente después de una media maratón. MÉTODO: Una muestra de 13 corredores voluntarios fue reclutada en una media maratón. Las mediciones de dolor de las pantorrillas se tomaron al inicio y 10-15 minutos después de la competición. El vendaje neuromuscular se aplicó en la pantorrilla de los corredores la noche anterior a la competencia, sólo en una pierna, con la pierna contralateral actuando como control. RESULTADOS: Los resultados del ANOVA de medidas repetidas sobre las diferencias en los valores de dolor en las piernas no mostraron diferencias estadísticamente significativas (p = 0.515). Sin embargo, el tamaño del efecto después de la carrera podría ser un indicio de la utilidad del vendaje (g = - 0.37) y de que estudios con la muestra calculada son necesarios (n = 61). CONCLUSIONES: Cuando el vendaje neuromuscular se aplicó a los corredores de medio maratón sanos, los datos no revelaron si podría controlar el dolor de las pantorrillas producido por la competición

OBJETIVO: O objetivo do presente estudo foi examinar o efeito da bandagem neuromuscular na dor na panturrilha em corredores saudáveis ​​imediatamente após uma meia maratona. MÉTODO: Uma amostra de 13 corredores voluntários foi recrutada para uma meia maratona. As medições da dor na panturrilha foram feitas no início e 10-15 minutos após a competição. A bandagem neuromuscular foi aplicada na panturrilha dos corredores na noite anterior à competição, apenas em uma perna, com a perna contralateral atuando como controle. RESULTADOS: Os resultados da ANOVA de medidas repetidas sobre as diferenças nos valores de dor nas pernas não mostraram diferenças estatisticamente significativas (p = 0,515). Porém, o tamanho do efeito após a corrida pode ser um indicativo da utilidade da bandagem (g = - 0,37) e que estudos com a amostra calculada são necessários (n = 61). CONCLUSÕES: Quando a bandagem neuromuscular foi aplicada em corredores saudáveis ​​de meia maratona, os dados não revelaram se ela poderia controlar a dor na panturrilha produzida pela competição

Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.

In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused more by different parameterization and less by methods and indicates the need for further improvement of implicit solvent models parameterization. Within the same parameterization, various implicit methods give practically the same correlation with results obtained in explicit solvent model for ligands and proteins: e.g. correlation values of polar ligand solvation energies and the corresponding energies in the frame of explicit solvent were 0.953-0.966 for the APBS program, the GBNSR6 program and all models used in the DISOLV program. The DISOLV program proved to be on a par with the other used programs in the case of proteins and ligands solvation energy calculation. However, the solution of the Poisson-Boltzmann equation (APBS program) and Generalized Born method (implemented in the GBNSR6 program) proved to be the most accurate in calculating the desolvation energies of complexes.

Suicidio y cirugía bariátrica: un estudio de la evidencia / Suicide risk after bariatric surgery

Bariatric surgery is considered the most effective treatment for severe obesity and its benefits include improvement in medical comorbidities. However, a higher rate of suicides after this type of surgery has been reported. We performed a literature review on the subject, and concluded that the mentioned increase in suicide rates, compared to the general population, is probably caused by conditions that the patient had before surgery, especially psychiatric disorders such as depression or eating disorders. These are risk factors for suicide, and are more common in the population with indication for bariatric surgery. Therefore, it is necessary to thoroughly evaluate these patients before surgery searching for suicide risk factors, deriving them to a mental health professional if necessary and follow their mental health after surgery. Considering that the literature on the topic is inconsistent, further research is needed.

[Suicide risk after bariatric surgery]. / Suicidio y cirugía bariátrica: un estudio de la evidencia.

Bariatric surgery is considered the most effective treatment for severe obesity and its benefits include improvement in medical comorbidities. However, a higher rate of suicides after this type of surgery has been reported. We performed a literature review on the subject, and concluded that the mentioned increase in suicide rates, compared to the general population, is probably caused by conditions that the patient had before surgery, especially psychiatric disorders such as depression or eating disorders. These are risk factors for suicide, and are more common in the population with indication for bariatric surgery. Therefore, it is necessary to thoroughly evaluate these patients before surgery searching for suicide risk factors, deriving them to a mental health professional if necessary and follow their mental health after surgery. Considering that the literature on the topic is inconsistent, further research is needed.

Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis.

Transforming growth factor-ß-induced protein (TGFBIp) is an extracellular matrix protein that has a role in a wide range of pathological conditions. However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood. The purpose of this study was therefore to analyze the effects of TGFBIp on lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is important for the metastasis of tumor cells. TGFBIp increased adhesion, migration, and morphologic differentiation of human lymphatic endothelial cells (LECs), consistent with an increase in lymphatic vessel sprouting in a three-dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced lymphatic vessel sprouting was inhibited by addition of anti-integrin ß3 antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased both CCL21 expression in LECs, a chemokine that actively recruits tumor cells expressing the cognate chemokine receptors to lymphatic vessels and LEC permeability by inducing the dissociation of VE-cadherin junctions between LECs via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in SW620 cancer cells dramatically reduced tumor lymphangiogenesis and metastasis. Collectively, our findings demonstrate that TGFBIp is a lymphangiogenic factor contributing to tumor dissemination and represents a potential target to inhibit metastasis.

Quaternary origin and genetic divergence of the endemic cactus Mammillaria pectinifera in a changing landscape in the Tehuacán Valley, Mexico.

The endemic Mexican cactus, Mammillaria pectinifera, shows low dispersal capabilities and isolated populations within the highly dissected landscape of Tehuacán Valley. These characteristics can restrict gene flow and act upon the genetic divergence and speciation in arid plants. We conducted a phylogeographic study to determine if the origin, current distribution, and genetic structure of M. pectinifera were driven by Quaternary geomorphic processes. Sequences of the plastids psbA-trnH and trnT-trnL obtained from 66 individuals from seven populations were used to estimate genetic diversity. Population differentiation was assessed by an analysis of molecular variance. We applied a stepwise phylogenetic calibration test to determine whether species origin and genetic divergence among haplotypes were temporally concordant with recognizable episodes of geomorphic evolution. The combination of plastid markers yielded six haplotypes, with high levels of haplotype diversity (h = 0.622) and low nucleotide diversity (π = 0.00085). The populations were found to be genetically structured (F(ST) = 0.682; P < 0.00001), indicating that geographic isolation and limited dispersal were the primary causes of genetic population differentiation. The estimated origin and divergence time among haplotypes were 0.017-2.39 and 0.019-1.237 mya, respectively, which correlates with Pleistocene tectonics and erosion events, supporting a hypothesis of geomorphically-driven geographical isolation. Based on a Bayesian skyline plot, these populations showed long term demographic stability, indicating that persistence in confined habitats has been the main response of this species to landscape changes. We conclude that the origin and haplotype divergence of M. pectinifera were a response to local Quaternary geomorphic evolution.

Comparación de valores de temperatura obtenidos con termómetro ótico digital y con termómetros axilar y rectal de mercurio en menores de 5 años / Comparison of body temperature measurements obtained with otic digital thermometer and mercury axillary and rectal thermometers in children under the age of five

Introducción: En los últimos años han aparecido nuevos métodos para medir la temperatura en niños, como el termómetro digital ótico. Siendo este un método más rápido para medir la temperatura y por lo tanto ideal para el servicio de urgencias, es necesario conocer su confiabilidad. Objetivo: Comparar los valores de temperatura corporal que entrega el termómetro ótico digital con los termómetros de mercurio axilar y rectal. Pacientes y Método: Se efectuó la medición de la temperatura en 50 pacientes menores de 5 años elegidos al azar, que consultaron en el Servicio de Urgencia del Hospital de Niños y Cunas de Viña del Mar. Se les midió la temperatura con un termómetro digital ótico al lado izquierdo y derecho, y las temperaturas axilar derecha y rectal con termómetros de mercurio. EL análisis de los resultados se efectuó en el grupo estudiado, separado en dos grupos, menores y mayores de 6 meses. Resultados: Los resultados entre ambos subgrupos fueron los mismos. La temperatura media rectal obtenida fue 0,414°C más alta que la media ótica derecha (p < 0,001) y 0,438°C más alta que la temperatura media ótica izquierda (p < 0,001). Conclusión: El termómetro ótico digital entrega una temperatura significativamente más baja que la que entregan los termómetros de mercurio axilar y rectal.

Background: In recent years, otic thermometers to measure body temperature in children have become increasingly popular as they reflect changes in body temperature sooner than other thermometers. The have become valuable assets in hospital emergency rooms; however, their accuracy and reliability need further studies. Objective: To compare corporal temperature readings between an otic thermometer and mercury axillary and rectal thermometers. Patients and Method: 50 patients under the age of 5, who were treated at the emergency room of our hospital, were randomly chosen to participate in this study. Temperature was measured on their right and left ears using an otic thermometer, and their rectal and right axillary temperature was taken using mercury thermometers. Patients were separated into 2 subgroups for comparison, children under and over 6 months old. Results: The results between the 2 subgroups were very similar. The average temperature obtained by rectal thermometers was 0.414°C higher than the average right-ear temperature (p < 0.001) and 0.438°c higher than the average left-ear temperature (p < 0.001). Conclusion: The otic thermometer's reading is significantly lower than the one obtained using mercury rectal and axillary thermometers.

Factores asociados a multidrogorresistencia en pacientes con tuberculosis en el departamento de Lambayeque / Factors associated with multidrug resistance in patients with tuberculosis in the department of Lambayeque

Objetivo: Determinar los factores asociados a Multidrogoresistencia en pacientes con Tuberculosis. Materiales y métodos: Estudio analítico, retrospectivo y transversal de casos y controles realizado en 41 pacientes Multidrogorresistentes (casos) y 3 controles por cada caso (Tuberculosis Pulmonar no MDR). Se recolectaron los datos directamente de las historias clínicas y de las fichas empleadas por la DIRESA de Lambayeque. Se realizó el análisis a través del programa estadístico SPSS 13. Resultados: Se encontró que la irregularidad en el tratamiento es un factor de riesgo con OR = 6,857 (IC: 95%, [2,480 - 18,961]). La presencia de comorbilidad mostró un OR = 3,068 (IC: 95%, [1,439 - 6,541]), mientras que el contacto con TB tuvo un OR = 2,119 (IC: 95%, [1,004 -4,472]) y el desempleo un OR = 2,143 (IC: 95%, [1,035 - 4,439]). Conclusiones: La mayor fuerza de asociación para el desarrollo de Multidrogorresistencia corresponde a la irregularidad en el Tratamiento. Además, el desempleo, el contacto con TB y, la presencia de comorbilidad son también factores de riesgo en paciente con TB para desarrollar TB-MD

Trastorno esquizoafectivo: ¿Cuánto de esquizofrenia? ¿Cuánto de bipolar? / Schizoaffective disorder: How much belongs to schizophrenia? How much belongs to bipolar disorder?

Introduction: Schizoaffective Disorder represents a controversial clinical entity, in regard to nosology and classification criteria. It has been considered as a variant of Schizophrenia, as a mixed entity between Schizophrenia and Bipolar Disorder and as a Bipolar Disorder subtype Method: Classificatory, clinical issues, neuropsychology and genetics research contributions are reviewed. Discussion and Conclusion: Schizoaffective Disorder concept at present time, differs from its original description, maintaining lack of definitive clarity with respect to its nosology. Considering neurocognitive impairment within its course, Schizoaffective Disorder looks much closer to affective psychosis than to Schizophrenia. From genetic research field emerges data that challenge the classic dichotomist distinction between affective psychosis and Schizophrenia established by E. Kraepelin, raising again the question about thinking in psychosis as a continuum in which Schizoaffective Disorder could represent an intermediate state...

Introducción: El Trastorno Esquizoafectivo constituye un área de controversias respecto a su nosología y criterios para su clasificación. Ha sido considerado como una variante de la Esquizofrenia, un cuadro mixto en el cual coexisten la Esquizofrenia y el Trastorno Bipolar y como un subtipo del Trastorno Bipolar. Método: Se revisan aspectos diagnósticos, clasificatorios y características psicopatológicas del trastorno en su concepción actual y aportes desde la perspectiva de la investigación neuropsicológica y la genética. Discusión y Conclusiones: El concepto actual de Trastorno Esquizoafectivo, difiere de su descripción original manteniéndose la falta de claridad definitiva respecto a su nosología. Tomando en consideración las alteraciones neurocognitivas que acompañan su evolución, el Trastorno Esquizoafectivo guardaría una mayor afinidad con las psicosis afectivas que con la Esquizofrenia. Desde la investigación genética surgen datos que cuestionan la distinción dicotómica clásica entre las psicosis afectivas y la Esquizofrenia establecida por E. Kraepelin, replanteándose la formulación de la psicosis en un continuum del cual el Trastorno Esquizoafectivo podría representar un estadio intermedio...

Tétanos generalizado: caso clínico y revisión del tema / Generalized tetanus: clinical case report and review of the literature

Tetanus is a severe and potentially mortal disease, which affects the Nervous System, caused by the bacteria Clostridium tetani. It's endemic in developing countries, presenting in Chile with a rate of 0,02 cases per 100.000 habitants, but the antitetanic vaccine has reduced its incidence in developed countries. We present here a case report of a patient with generalized tetanus from our hospital. The clinical presentation was characterized by generalized increased muscle tone and trismus, and the patient was hospitalized in the Intensive Care Unit. The neurologic manifestations were important for a period of 3 weeks, but then they started decreasing until the patient was discharged, without complications and being able to sit and walk with assistance. In relation to this case, we will review the actualizations in the subject of Tetanus. The recommended treatment includes support therapy, prevention of complications, antibiotics, muscle relaxants and anti-tetanospasmin immunoglobulin; all therapies that our patient received partially. The disease has a mortality that reaches the 50 percent in some series, but the ones who survive have a good prognosis and full recovery. This is why the presentation of this case is important, being an infrequent disease that must be diagnosed timely and be treated adequately.

Introducción: El tétanos es una enfermedad grave y potencialmente mortal, que afecta al sistema nervioso y causada por la bacteria Clostridium tetani. Es endémica en países en desarrollo, teniendo en Chile el año 2007 una tasa de 0,02 casos por cien mil habitantes. La vacuna con el toxoide antitetánico ha disminuido ostensiblemente su incidencia en países desarrollados. Caso clínico: Se presenta el caso clínico de un paciente de 18 años con tétanos generalizado ingresado a nuestro hospital. Clínicamente se manifestó con un aumento del tono muscular generalizado y trismo. Se hospitalizó en la Unidad de Cuidados Intensivos. Los síntomas y signos neurológicos tuvieron una máxima intensidad de aproximadamente cuatro semanas; posteriormente fueron disminuyendo sin presentar complicaciones severas. Al alta el enfermo lograba sentarse y caminar con ayuda. Discusión: A propósito de este caso se hace una revisión de la literatura y actualización de esta grave enfermedad. El tratamiento recomendado incluye terapia de soporte, prevención de complicaciones, antibioterapia, relajantes musculares e inmunoglobulina antitetánica; terapias que este paciente recibió. Si bien esta enfermedad tiene una letalidad promedio de un 50 por ciento, los pacientes que sobreviven tienen buen pronóstico y recuperación completa. Por ello, la presentación de este caso clínico es importante, sobre todo siendo una condición poco frecuente, que debe diagnosticarse con prontitud y, así, recibir el tratamiento adecuado.

Factores genéticos del huésped y respuesta terapéutica en la hepatitis C / No disponible

No disponible

Phyllodes tumor of the prostate.

A 67-year-old man presented with gross hematuria. Magnetic resonance imaging showed a 900-mL cystic mass, in continuity to the basal left side of the prostate, that laterally compressed the bladder. The patient underwent tumor resection, and the histologic diagnosis was benign cystic Phyllodes tumor of the prostate. Phyllodes tumor of the prostate is a rare tumor composed of hyperplastic and neoplastic glandular-stromal proliferation. The tumor grade has an effect on the prognosis, although if not completely resected, even low-grade tumors can recur, metastasize, or differentiate into sarcoma.

Análisis bibliométrico de los trabajos de grado del área organizacional de la Facultad de Psicología de la Universidad Santo Tomás / Bibliometric research of the works of degree into the organizational area in the Faculty of Psychology at the Santo Tomas University

El propósito de esta investigación fue realizar un análisis bibliométrico de los trabajos de grado del área organizacional de la Facultad de Psicología de la Universidad Santo Tomás. Primero, se hizo una revisión todos los trabajos de grado de Psicología (1307 tesis) de los cuales se seleccionaron 247 del área producidos durante 26 años, cerca del 19%, -período comprendido entre 1985-2005-. Luego, se diseñó una base de datos y de acuerdo con las variables previamente establecidas se sistematizaron los datos. El estudio fue de tipo descriptivo y se realizan dos tipos de análisis, uno de carácter descriptivo bibliométrico y el segundo, corresponde al análisis de datos textuales. Se encontró que de los 247 trabajos revisados se revelo que 1995 fue el año en el que se desarrollaron mayor número de tesis (50 trabajos); los enfoques teóricos de abordaje de las tesis son de: enfoque sistémico (51 trabajos) seguidos por el enfoque cognitivo comportamental (26). Por último, se presento un valioso aporte metodológico, y es la inclusión del análisis de datos textual a la bibliometría, el cual revelo en primer lugar la relación entre la Psicología social y la Psicología organizacional; en segundo lugar se evidenciaron dos periodos donde las temáticas giran en torno a una visión clásica de la psicología organizacional y en últimos 10 años un énfasis en una perspectiva critica de la psicología de las organizaciones.

The aim of this research was to make a bibliometric analysis of the works of works of degree into the organizational area in the faculty of psychology at the Santo Tomas University. First, a general overhaul of the works of degree of Psychology was made (1307 theses) of which were selected 247 of the organizational area produced during 26 years (close to the 19%) of history of the Faculty - period between 1985-2005-. Then, a data base was designed and in agreement with the variables previously established (author, year, thematic, director, juries, approach, methodology, design, type of statistical analysis and references) the data were systematized. This study was a descriptive one and tow types of analysis were made, one is a bibliometric descriptive and the second, corresponds to the analysis of textual data. It was find that into the 247 works revised, in 1995 were the year in which more number of thesis were developed (50 works): the theorist perspectives more used in that works were: systemic (51 works), followed by cognitive-behaviorist (26). Finally, a worth methodology contribution is presented, and it is the inclusion of the textual data analysis in the bibliometric study, which revels the relation between Social and Organizational Psychology. In a second place, it was evident two periods: one characterized by a classic vision of organizational psychology, and other, in the last 10 years, whit an emphasis in a psychological critical perspective in the organizations.

Transgene-enforced co-stimulation of CD4+ T cells leads to enhanced and sustained anti-tumor effector functioning.

Background The role of co-stimulation in CD4+ T cell activation by professional APC is well established, while less is known of the role co-stimulation plays when CD4+ T cells interact directly with tumor cells. Methods Through genetic engineering of human CD4+ T cells, we tested the hypothesis that integration of co-stimulatory signaling domains within a tumor-targeting chimeric Ag receptor (CAR), the IL-13Ralpha2-specific IL-13-zetakine (IL13zeta), would enhance CD4+ T cell mediated responses against tumors that fail to express ligands for co-stimulatory receptors. Results Compared with CD3zeta-mediated activation alone, CD4+ effector T cells expressing the IL13-CD28-41BBzeta CAR exhibited augmented/sustained MAPK and AKT activity, up-regulated Th1 cytokine production, and enhanced cytolytic potency against tumor targets. Moreover, upon recursive stimulation with tumor, the IL13-CD28-41BBzeta+ cells retained/recycled their lytic function, whereas IL-13zeta+ CD4+ cells became anergic/exhausted. These in vitro observations correlated with enhanced in vivo control of established orthotopic CNS glioma xenografts in immunodeficient mice mediated by adoptively transferred ex vivo-expanded CD4+ T cells expressing the co-stimulatory CAR. Discussion Together these studies demonstrate the importance of integrating co-stimulation with CD3zeta signaling events to activate fully CD4+ anti-tumor effector cells for sustained function in the tumor microenvironment.

Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor.

Adoptive transfer of ex vivo expanded tumor-specific T cells is a promising therapeutic modality for promoting or augmenting antitumor immunity. Several groups, including ours, are developing antigen receptor gene transfer strategies as a means of generating effector cells for adoptive therapy. Chimeric antigen receptors (CARs) have been described that use single-chain antibodies or cytokine ligands as tumor targeting domains. Here, we describe the capacity of a tumor-binding peptide identified by phage display combinatorial library screening to serve as a CAR targeting domain. A phage library-selected high-affinity 12-mer peptide (Bpep) specific for alpha(v) beta(6) integrin (alpha v beta6) was chosen for these studies. Primary human T cells were genetically modified to express the Bpep-CAR consisting of an alpha v beta6-specific peptide and human IgG4 hinge-Fc extracellular domain fused to the cytoplasmic tail of CD3-zeta. T cell expression of the Bpep-CAR was assessed by Western blot analysis, and trafficking of the Bpep-CAR to the cell surface was demonstrated by flow cytometry. Functionally, Bpep-CAR redirected cytotoxic T lymphocytes specifically kill integrin alpha v beta6+ ovarian tumor targets, and are activated for interferon gamma secretion. Our data suggest that large new repertoires of tumor-specific T cell antigen receptor transgenes might be available through merging combinatorial peptide libraries with CAR construct design.

The treatment of mice with Lactobacillus casei induces protection against Babesia microti infection.

In this study, we report that administration of Lactobacillus casei confers protection to mice against the intracellular protozoan Babesia microti. Mice treated with L. casei orally or intraperitoneally were inoculated 7 days later with an infectious dose of B. microti. Mice treated with lactobacilli showed significant reduction in the percentage of parasitized erythrocytes (PPE) compared to untreated mice. When mice were inoculated intraperitoneally with L. casei 3 or 0 days before challenge with B. microti, the PPE was significantly lower compared to untreated mice and there were no differences between treated mice and mice immune to B. microti infection. When mice treated with live or dead L. casei were compared to mice inoculated with Freund Complete Adjuvant before a B. microti infection, a significant reduction of PPE was observed. These results show the protective effect of L. casei administered to mice against a B. microti infection and suggest that it might act by stimulating the innate immune system.

Differences in the incidence of apoptosis between in vivo and in vitro produced blastocysts of farm animal species: a comparative study.

The occurrence of pregnancies and births after embryo transfer (ET) of in vivo produced embryos is generally more successful compared to that of embryos produced in vitro. This difference in ET success has been observed when embryos of morphological equal (high) quality were used. The incidence of apoptosis has been suggested as an additional criterion to morphological embryo evaluation in order to assess embryo quality and effectively predict embryo viability. In this study, equine, porcine, ovine, caprine and bovine in vivo and in vitro produced morphologically selected high quality (grade-I) blastocysts were compared for the occurrence of apoptosis in blastomeres. The total number of cells per embryo and the number of cells with damaged plasma membranes, fragmented DNA and fragmented nuclei per embryo were assessed in selected blastocysts by combining Ethidium homodimer (EthD-1), terminal dUTP nick end labeling (TUNEL) and Hoechst 33342 staining. In general, the level of blastomere apoptosis was low. A higher level of apoptosis was observed in in vitro produced equine, porcine and bovine blastocysts compared to their in vivo counterparts. Interestingly, 4 of the initially selected 29 bovine in vitro produced blastocysts exhibited extensive signs of apoptosis affecting the inner cell mass (ICM), which is not compatible with a viable conceptus. Repeated occurrence of this observation may explain the lower ET outcome of in vitro produced bovine embryos compared to in vivo produced embryos. It is concluded that, although in morphologically high quality blastocysts of several farm animal species a significant difference exists in the percentages of apoptotic cells between in vivo and in vitro produced embryos, the incidence of apoptosis at the blastocyst stage is at such a low level that it cannot reflect the substantial differences in embryo viability that have been described between in vivo and in vitro produced blastocysts following ET.

Ultrastructural characteristics of fresh and frozen-thawed ovine embryos using two cryoprotectants.

Cryopreservation of sheep embryos with ethylene glycol as a protectant appears to be more effective than glycerol, particularly at the morula stage, as has been demonstrated on the basis of in vitro and in vivo development rates after thawing. In this study we compare the ultrastructure of fresh morulae, thawed morulae, and blastocysts cryopreserved with either ethylene glycol or glycerol at the electron microscopic level, to look for cellular damage that could be responsible for proven differences in embryo survival after transfer. Embryos cryopreserved with glycerol showed unequal degrees of conservation even among blastomeres within a single embryo. In morulae, inner blastomeres were completely damaged, whereas external ones appeared to be intact. Both morulae and blastocysts cryopreserved with ethylene glycol showed a higher uniformity in blastomere conservation than embryos with glycerol. The most remarkable features in this experimental group were the presence of desmosomes following tight junctions between blastomeres and the presence of many microvilli on the outer surface of external blastomeres. These characteristics are similar in fresh embryos of the control group. Our results show that ethylene glycol protects membrane and cytoplasmic structures of embryonic cells from cryoinjury much better than glycerol. In vivo survival of embryos confirmed the ultrastructural observations. A limited permeability of glycerol would explain the observed ultrastructural differences in blastomere integrity, which depends on blastomere location and the differences between morulae and blastocysts. We conclude that the low reproductive yield after cryopreservation using glycerol can be attributed to the lack of protection of inner cells.

Binding of a surface protein of Staphylococcus aureus to cultured ovine mammary gland epithelial cells.

Staphylococcus aureus is the most persistent pathogen causing ovine mastitis. This study investigated S. aureus binding to cultured epithelial cells obtained from the mammary gland. A staphylococcal 145kDa cell wall adhesin, originally isolated from a bovine mastitis strain, was detected in lysostaphin-solubilized ovine mastitis strains and in the encapsulated strain A. This adhesin was able to bind to cultured ovine mammary gland epithelial cells (MGEC) and to a rat intestinal epithelial cell line (RIE-1), exhibiting different electrophoretic mobilities that could be attributable to protein polymorphism. Inhibition assays using antibodies against 145kDa adhesin and against whole bacteria showed the specificity of the binding to cells. The role of this protein in adherence was assessed by adherence inhibition tests carried out in vitro with radiolabeled bacteria and cultured epithelial cells. Preincubation of bacteria with antibodies against adhesin 145kDa or against strain c195 resulted in a statistically significant decrease of adherence. These experiments suggest that adherence of S. aureus to MGEC may be critical for colonization.