Delivery of SIRT1 by cancer-associated adipocyte-derived extracellular vesicles regulates immune response and tumorigenesis of ovarian cancer cells

Purpose This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells (AU)

Effects of Different Nursing Modes on Immune Function and Renal Function in Patients with Renal Calculus Undergoing Percutaneous Nephrolithotomy

Background: This study aimed to explore the effects of different nursing modes on immune function and renal function in patients with renal calculus and on percutaneous nephrolithotomy (PCNL). Methods: A total of 160 patients with kidney stone who were admitted to our hospital from January 2017 to January 2023 were retrospectively selected and equally divided into routine and comprehensive nursing groups. Both groups were treated with percutaneous nephrolithotomy, but the patients in the routine nursing group were treated with usual care, whereas the patients in the comprehensive nursing group were treated with comprehensive nursing. The levels of serum T lymphocyte subsets were detected by flow cytometry, the levels of serum immune indicators and renal function indicators in the two groups were measured and the incidence of postoperative complications and nursing satisfaction were recorded. Results: The levels of serum blood urea nitrogen, creatinine, kidney injury molecule and CD8+ cell subsets in the comprehensive nursing group were lower than those in the routine nursing group (p < 0.05), whereas the CD4+ cell subsets, CD4+:CD8+ ratio, and immunoglobulins (Ig)A, IgG and IgM levels were significantly higher than those in the routine nursing group (p < 0.05). The incidence of postoperative complications in the comprehensive nursing group was 2.50% (2/80), which was significantly lower than that in the routine nursing group (13.75%, 11/80), and the difference was statistically significant (χ2 = 6.782, p = 0.009). Nursing satisfaction in the comprehensive nursing group was 96.25% (77/80), which was significantly higher than that in the routine nursing group (85.00%, 68/80; χ2 = 5.959, p = 0.015) (AU)

Diferencias y similitudes entre la cefalea relacionada con la COVID-19 y la cefalea relacionada con la vacuna de la COVID-19. Un estudio de casos y controles / Differences and similarities between COVID-19 related-headache and COVID-19 vaccine related-headache. A case-control study

Introducción La cefalea es un síntoma frecuente en la fase aguda de la enfermedad por coronavirus 2019 (COVID-19) y también uno de los efectos adversos más comunes tras la vacunación. En ambos casos, la fisiopatología de la cefalea parece estar relacionada con la respuesta inmunitaria del huésped y podría presentar similitudes. Nuestro objetivo fue comparar el fenotipo clínico y la frecuencia de los síntomas asociados y los síntomas de inicio en pacientes con cefalea relacionada con la COVID-19 y cefalea relacionada con la vacuna de la COVID-19. Sujetos y métodos Se realizó un estudio de casos y controles. Se incluyó a pacientes con infección confirmada por COVID-19 y receptores de la vacuna de la COVID-19 que experimentaron un nuevo inicio de cefalea. Se administró un cuestionario estandarizado que incluyó variables demográficas, antecedentes previos de cefaleas, síntomas asociados y variables relacionadas con la cefalea. Ambos grupos se emparejaron por edad, sexo y antecedentes previos de cefaleas. Se realizó un análisis de regresión multivariante. Resultados Un total de 238 pacientes cumplieron con los criterios de elegibilidad (143 pacientes con cefalea relacionada con la COVID-19 y 95 sujetos con cefalea relacionada con la vacuna de la COVID-19). Los pacientes con cefalea relacionada con la COVID-19 presentaron una mayor frecuencia de artralgia, diarrea, disnea, dolor torácico, expectoración, anosmia, mialgia, odinofagia, rinorrea, tos y disgeusia. Además, los pacientes con cefalea relacionada con la COVID-19 experimentaron una duración diaria más prolongada de la cefalea y describieron la cefalea como la peor que habían experimentado. Los pacientes con cefalea relacionada con la vacuna de la COVID-19 experimentaron con más frecuencia dolor en la región parietal, fonofobia y empeoramiento de la cefalea por movimientos de la cabeza o de los ojos. Conclusión ... (AU)

INTRODUCTION Headache is a frequent symptom at the acute phase of coronavirus disease 2019 (COVID-19) and also one of the most frequent adverse effects following vaccination. In both cases, headache pathophysiology seems linked to the host immune response and could have similarities. We aimed to compare the clinical phenotype and the frequency and associated onset symptoms in patients with COVID-19 related-headache and COVID-19 vaccine related-headache. SUBJECTS AND METHODS A case-control study was conducted. Patients with confirmed COVID-19 infection and COVID-19-vaccine recipients who experienced new-onset headache were included. A standardised questionnaire was administered, including demographic variables, prior history of headaches, associated symptoms and headache-related variables. Both groups were matched for age, sex, and prior history of headache. A multivariate regression analysis was performed. RESULTS A total of 238 patients fulfilled eligibility criteria (143 patients with COVID-19 related-headache and 95 subjects experiencing COVID-19 vaccine related-headache). Patients with COVID-19 related-headache exhibited a higher frequency of arthralgia, diarrhoea, dyspnoea, chest pain, expectoration, anosmia, myalgia, odynophagia, rhinorrhoea, cough, and dysgeusia. Further, patients with COVID-19 related-headache had a more prolonged daily duration of headache and described the headache as the worst headache ever experienced. Patients with COVID-19 vaccine-related headache, experienced more frequently pain in the parietal region, phonophobia, and worsening of the headache by head movements or eye movements. CONCLUSION. Headache caused by SARS-CoV-2 infection and COVID-19 vaccination related-headache have more similarities than differences, supporting a shared pathophysiology, and the activation of the innate immune response. The main differences were related to associated symptoms. (AU)

Poor increase on HAV vaccination coverage among people living with HIV after an immunization-based intervention / Pobre incremento de la cobertura vacunal frente al VHA en personas que viven con el VIH, tras una intervención basada en la inmunización

Objectives: To assess HAV serologic and vaccination status among people who live with HIV (PLWH), and to evaluate the impact of a vaccination-based strategy on HAV-negative patients in Seville, Spain. Methods: Study with two time-overlapping phases: (i) cross-sectional study of HAV immunity prevalence among PLWH followed at a Spanish hospital between August 2019 and March 2020. (ii) Patients seronegative for HAV, reliably unvaccinated were included in a before-and-after quasi-experimental study, with an intervention focused on HAV vaccination according to national recommendations in force. Results: Six hundred and fifty-six patients were included, of which 111 [17%, 95% confidence interval (95% CI) 14–20%] were seronegative for HAV. Of these, 48 [43% (95% CI, 34–53%)] individuals were MSM. The absence of HAV immunity was attributed in 69 [62% (95% CI, 52–71%)] patients to non-referral to vaccination, followed by lack of achievement of a correct vaccination scheme [n=26; 23% (95% CI, 16–32%)]. After the program implementation, 96 [15% (95% CI, 12–18%)] individuals were seronegative (17% vs. 15%, p=0.256), of whom 42 [41% (95% CI, 32–51%)] were MSM. The absence of immunity after the intervention was mainly attributed to: adherence failure in 23 [24.0% (95% CI, 15.8–33.7%)] patients, on-course immunization scheme in 34 [33% (95% CI, 24–43%)] individuals and pending appointment at the vaccine delivery unit in 20 [20.8% (95% CI, 13.2–30.3%)] patients. Conclusions: A sizeable proportion of PLWH remains susceptible for HAV infection in future outbreaks. A program based on referral to the vaccine delivery unit yields poor results, largely due to program adherence failures. New strategies are needed to increase HAV vaccination coverage.(AU)

Objetivos: Evaluar la prevalencia de inmunidad frente al VHA en personas que viven con VIH así como el impacto de una intervención basada en la vacunación de pacientes seronegativos frente al VHA. Métodos: Estudio con dos fases solapadas en el tiempo: 1) transversal de prevalencia de inmunidad frente al VHA en personas que viven con VIH seguidas en un hospital de tercer nivel, entre agosto de 2019 y el inicio de las medidas nacionales de contención de la epidemia por SARS-CoV-2, marzo de 2020. 2) Cuasiexperimental, con una intervención centrada en la vacunación frente a VHA de pacientes seronegativos, en la unidad responsable de esta. Resultados: Ciento once (17%, [95% IC, 14-20%]) de los 656 pacientes incluidos eran seronegativos frente al VHA. Las principales causas de la ausencia de inmunidad fueron: 69 (62% [95% IC, 52-71%]) individuos no derivados a la unidad responsable de la vacunación; 26 pacientes (23% [95% CI, 16-32%]) no completaron el esquema vacunal. Tras la intervención, 96 (15% [95% IC, 12-18%]) pacientes continuaron siendo seronegativos frente al VHA (comparada con la prevalencia basal, p=0,256), 42 (18% [95% IC, 13-23%]) eran HSH. Las principales causas de la ausencia de inmunidad fueron: 26 (23% [95% IC, 15-32%]) individuos presentaron fallos de adherencia al circuito vacunal; 34 (33% [95% IC, 24-43%]) pacientes habían recibido una sola dosis; 22 (22% [95% IC, 14-31%]) seguían sin una primera valoración por parte de la unidad responsable de la vacunación. Conclusiones: Una proporción considerable de personas que viven con VIH, particularmente HSH, sigue siendo susceptible a la infección por VHA. La derivación sistemática a la unidad responsable de la vacunación se traduce en modestos incrementos de la prevalencia de inmunidad. Son necesarias nuevas estrategias para aumentar la cobertura vacunal.(AU)

Inmunonutrición, evidencias y experiencias / Immunonutrition, evidence and experiences

La inmunonutrición es una ciencia que engloba aspectos relacionados con la nutrición, la inmunidad, la infección, la inflamación y el daño tisular. Las fórmulas inmunomoduladoras han demostrado beneficios en una amplia variedad de situaciones clínicas. El objetivo de este trabajo es revisar la evidencia disponible en inmunonutrición (IN). Para ello, se ha realizado una búsqueda bibliográfica con las palabras clave: inmunonutrición, arginina, glutamina, nucleótidos, ácidos grasos omega-3, ERAS, fast-track. Se han incluido ensayos clínicos, revisiones y guías de práctica clínica. La IN ha demostrado reducir las fístulas en el postoperatorio en pacientes con cáncer de cabeza y cuello. En pacientes con cáncer gástrico y cáncer de esófago, la IN se asocia a una disminución de las complicaciones infecciosas y la estancia hospitalaria. Otras situaciones clínicas que se benefician del uso de la IN son la cirugía del cáncer de páncreas, la cirugía del cáncer colorrectal y los grandes quemados. Son necesarios más estudios controlados, prospectivos y aleatorizados para confirmar los potenciales beneficios de la IN en otras situaciones clínicas como la cirugía torácica no esofágica, el cáncer vesical, la cirugía ginecológica, la fractura de cadera, la patología hepática y la COVID-19, entre otros. (AU)

Immunonutrition is a science that encompasses aspects related to nutrition, immunity, infection, inflammation and tissue damage. Immunomodulatory formulas have shown benefits in a wide variety of clinical situations.The objective of this work was to review the available evidence in immunonutrition (IN). For this, a bibliographic search has been carried outwith the keywords: immunonutrition, arginine, glutamine, nucleotides, omega-3 fatty acids, ERAS, fast-track. Clinical trials, reviews and clinicalpractice guidelines have been included.IN has been shown to reduce postoperative fistulae in head and neck cancer patients and in gastric and esophageal cancer patients, infectiouscomplications and hospital stay. Other clinical situations that benefit from the use of IN are pancreatic cancer surgery, colorectal cancer surgeryand major burns. More controlled, prospective, and randomized studies are necessary to confirm the potential benefits of IN in other clinical situations such as non-esophageal thoracic surgery, bladder cancer, gynecological surgery, hip fracture, liver pathology and COVID-19, among others. (AU)

Mejoría de la inmunidad y la esperanza de vida en ratones maduros, genéticamente deficientes en la síntesis de catecolaminas, tras convivir con controles durante dos meses / Improved immunity and mean lifespan in mature mice genetically deficient in catecholamine synthesis after living with wild type for two months

Introducción: Los ratones hemicigotos en la tirosina hidroxilasa (TH-HZ), enzima limitante en la síntesis de catecolaminas, muestran una inmunosenescencia prematura, que en hembras se asocia con menor esperanza de vida que los correspondientes controles (WT). La convivencia de los TH-HZ con WT permite, en la edad adulta, una normalización de la función inmunitaria tanto en machos como en hembras. Objetivo: Comprobar si la convivencia durante dos meses de machos maduros TH-HZ con WT produce una mejoría de la función inmunitaria de los primeros y si esto repercute en una mayor esperanza de vida media. Material y métodos: Ratones macho ICR-CD1 maduros (13 ± 1 meses) TH-HZ convivieron con WT (proporción 2:4 por jaula) dos meses. Al inicio, al mes y a los dos meses de convivencia se extrajeron los leucocitos peritoneales de los animales y se valoró la capacidad fagocítica de macrófagos, la quimiotaxis de macrófagos y linfocitos, la actividad antitumoral natural killer (NK) y la capacidad linfoproliferativa en respuesta a los mitógenos concanavalina A y lipopolisacarido. Los animales se mantuvieron en esas condiciones hasta su muerte natural. Resultados: Los TH-HZ parten, en general, con peor función inmunitaria y menor longevidad que los WT, observando una mejoría de esta tras la convivencia, alcanzándose valores similares a los controles. En la actividad NK esa mejoría se observó al mes de convivencia. Conclusión: La convivencia de los ratones macho TH-HZ con los WT durante dos meses, en la edad madura, permite mejorar la respuesta inmunitaria y la longevidad de esos animales genéticamente modificados. (AU)

Introduction: Mice hemizygous in tyrosine hydroxylase (TH-HZ), the limiting enzyme in catecholamine synthesis, show premature immunosenescence, which in females is associated with a shorter lifespan than the corresponding controls (WT). The coexistence of TH-Hz with WT improves the immune function in both males and females in adulthood. Objective: To test whether cohabitation for two months of mature male TH-HZ with WT improves the immune function of the former and whether this impacts the lifespan. Material and methods: Mature male ICR-CD1 mice (13 ± 1 months) TH-HZ coexisted with WT (2:4 ratio in each cage) for two months. Peritoneal leukocytes were extracted from all animals at baseline, one month, and two months after cohabitation, and macrophage phagocytic capacity, macrophage and lymphocyte chemotaxis, natural killer (NK) antitumor activity, and lymphoproliferative capacity in response to the mitogens concanavalin A and lipopolysaccharide (LPS) were assessed. The animals were maintained under these conditions until their natural death. Results: The TH-HZ, which start, in general, with lower values than the WT in the immune functions studied, improved them after two months of cohabitation, becoming similar to those of the controls. This improvement was already observed in NK activity after one month of cohabitation. The TH-HZ presented lower mean longevity than WT, but when they cohabited with WT, it was similar to the latter. Conclusion: The coexistence of TH-HZ male mice with WT mice for two months at mature age improves these genetically modified animals’ immune response and longevity. (AU)

Unique roles of aminophospholipid translocase Drs2p in governing efflux pump activity, ergosterol level, virulence traits, and host–pathogen interaction in Candida albicans / Roles únicos de la translocasa aminofosfolípida Drs2p en la actividad de la bomba de eflujo gobernante, el nivel de ergosterol, los rasgos de virulencia y la interacción huésped-patógeno en Candida albicans

Infections caused by Candida albicans are rising due to increment in drug resistance and a limited arsenal of conventional antifungal drugs. Thus, elucidating the novel antifungal targets still represent an alternative that could overcome the problem of multidrug resistance (MDR). In this study, we have uncovered the distinctive effect of aminophospholipid translocase (Drs2p) deletion on major MDR mechanisms of C. albicans. We determined that efflux activity was diminished in Δdrs2 mutant as revealed by extracellular rhodamine 6G (R6G) efflux and flow cytometry. Moreover, we further unveiled that Δdrs2 mutant displayed decreased ergosterol content and increased membrane fluidity. Furthermore, Drs2p deletion affects the virulence attributes and led to inhibited hyphal growth and reduced biofilm formation. Additionally, THP-1 cell lines’ mediated host–pathogen interaction studies revealed that Δdrs2 mutant displayed enhanced phagocytosis and altered cytokine production leading to increased IL-6 and decreased IL-10 production. Taken together, the present study demonstrates the relevance of Drs2p in C. albicans and consequently disrupting pathways known for mediating drug resistance and immune recognition. Comprehensive studies are further required to authenticate Drs2p as a novel antifungal drug target.(AU)

Análisis de las estrategias de vacunación frente a la COVID-19 en España y las bases científicas sobre las que se han sustentado (mayo 2022) / Analysis of vaccination strategy against COVID-19 in Spain. The scientific basics (may 2022)

Una vez transcurrido alrededor de un año y medio (en el momento de escribir estas líneas) desde el inicio de la campaña masiva de vacunación en la que, gracias a las altas coberturas alcanzadas en todos los grupos diana para vacunación, se ha conseguido reducir de manera muy significativa la morbimortalidad por la COVID-19, es importante revisar las bases científicas que han sustentado las recomendaciones implantadas hasta la fecha y aquellas que podrían adoptarse en un futuro próximo según la situación epidemiológica. El objetivo del presente artículo fue, por tanto, abordar los fundamentos de algunas de las decisiones técnicas propuestas desde la Ponencia de Programa y Registro de Vacunaciones y el Grupo de Trabajo Técnico de Vacunación frente a la COVID-19. A lo largo de once actualizaciones de la Estrategia de Vacunación frente a la COVID-19 en España, han sido objeto de intenso debate varias cuestiones relativas a los intervalos de vacunación entre dosis, la conveniencia del uso de diferentes tipos de vacunas, las combinaciones de las mismas, los beneficios de la inmunidad híbrida y el uso de una cuarta dosis (segunda dosis de recuerdo) para poblaciones seleccionadas. Todo ello sin olvidar aspectos esenciales de su seguridad. Este artículo se divide en los siguientes apartados: Intervalos de vacunación; Pauta heteróloga o mixta; Inmunidad híbrida (vacunación tras la infección e infección tras vacunación [breakthrough]); Segunda dosis de recuerdo.(AU)

After about a year and a half (at the moment these lines are being written) since the start of the massive vaccination campaign in which, thanks to the high coverage achieved in all groups eligible for vaccination, it has been possible to significantly reduce the morbidity and mortality due to COVID-19, it is important to review the scientific basics that have supported the recommendations implemented to date and those that could be adopted in the near future taking into consideration the epidemiological situation. The objective of this article is, therefore, to address the foundations of some of the technical decisions proposed by the Committee on Programme and Registry of Vaccinations (National Immunization Technical Advisory Group in Spain) and the Technical Working Group on Vaccination against COVID-19. Throughout the eleven updates of the Vaccination Strategy against COVID-19 in Spain, several issues pose intense debate as the vaccination intervals between doses, the convenience of using different types of vaccines, the use of heterologous schemes of vaccination, the benefits of hybrid immunity and the use of a fourth dose (second booster dose) for selected populations. All this without forgetting essential aspects of safety of vaccines. This article is divided into the following sections: Vaccination intervals; Heterologous or mixed scheme; Hybrid immunity (vaccination after infection and infection after vaccination[breakthrough]); Second booster dose.(AU)

Psychological stress in asthma: repercussions on epigenetics-genetics, immune responses, and pulmonary function in the pediatric population

In the assessment of childhood asthma, identifying the risk factors associated with exacerbations and broadening this view to understand psychological stress and its repercussions on the inflammatory process of asthma allow a different perspective on this biopsychosocial disease. Psychological stress, as a risk factor for the onset and noncontrol of asthma, has been increasingly evaluated from the perspective of the repercussions on the body of the stimulus generated in the hypothalamic-pituitary axis and adrenal glands, with cortisol release and immune system action. These processes trigger changes in T helper 2 cells, which polarize allergic processes, and dysfunctions in immune tolerance mechanisms, with a decrease in regulatory T cells. Genetic and epigenetic changes in β2-adrenergic and glucocorticoid receptors, with decreased response to these drugs, were also identified in studies, in addition to changes in respiratory function patterns, with worsening of obstruction and inflammation identified via decreased forced expiratory volume in one second and increased exhaled inflammatory gases in allergic asthma. Therefore, the present review sought to identify studies on the effect of personal and parental acute or chronic psychological stress, emphasizing the repercussions on genetics, epigenetics, and immune and pulmonary functional and inflammatory responses in the pediatric population (AU)

Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran / Inmunidad al virus de la hepatitis A en receptores de trasplante de hígado: un estudio poblacional en Irán

Background: Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation. To take appropriate preventive measures, it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection. To assess the need for immunization against hepatitis A, we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients. We also investigated the association between hepatitis A immune status and demographic factors such as age and sex, underlying liver disease, source of drinking water, geographical area of residence and socioeconomic status.Methods: This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz, Iran, between January 2017 and April 2017. The level of immunity was assessed using hepatitis A antibody detection kits.Results: The rate of immunity against hepatitis A was detected as 88.8% in our study population. In the multivariable logistic regression model, younger age (OR=1.175, P<0.001) and higher education level (OR=2.142, P=0.040) were the main determinants of non-immune status. However, hepatitis A immunity was independent of gender, monthly family income, water supply source, residential area and underlying liver disorder.Conclusion: Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A, a considerable proportion of younger patients and those with a higher level of education were non-immune. The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients.

Antecedentes: La hepatitis A aguda suele ser una enfermedad viral autolimitada, pero puede ser grave e incluso mortal en grupos especiales de pacientes, incluidos aquellos con enfermedad hepática crónica y los receptores de un trasplante de hígado. Para tomar las medidas preventivas adecuadas, es importante determinar el estado inmunológico frente al virus de la hepatitis A en pacientes con riesgo de sufrir resultados clínicos graves después de la infección. Para evaluar la necesidad de inmunización contra la hepatitis A, nuestro objetivo fue determinar el estado inmunológico contra la hepatitis A en una población de receptores de trasplante de hígado. También investigamos la asociación entre el estado inmunológico de la hepatitis A y factores demográficos como la edad y el sexo, la enfermedad hepática subyacente, la fuente de agua potable, el área geográfica de residencia y el nivel socioeconómico.Métodos: este estudio transversal se realizó en 242 receptores de trasplantes de hígado alogénicos en el hospital de trasplantes de órganos “Abu Ali Sina” en Shiraz, Irán, entre enero de 2017 y abril de 2017. El nivel de inmunidad se evaluó mediante kits de detección de anticuerpos contra la hepatitis A.Resultados: La tasa de inmunidad contra la hepatitis A se detectó como 88,8% en nuestra población de estudio. En el modelo de regresión logística multivariable, la edad más joven (OR=1,175, p<0,001) y el nivel de educación superior (OR=2,142, p=0,040) fueron los principales determinantes del estado no inmunitario. Sin embargo, la inmunidad contra la hepatitis A fue independiente del sexo, el ingreso familiar mensual, la fuente de suministro de agua, el área residencial y la enfermedad hepática subyacente.

Epithelial Barrier: Protector and Trigger of Allergic Disorders

The epithelial barrier has classically been considered as the only first line of defense against irritants, pathogens, and allergens. However,it is now known to play an essential role in the immune response to exogenous agents. In fact, recent reports postulate the epithelialbarrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases.The epithelial barrier preserves the isolation of internal tissues from potential external threats. Moreover, a coordinated interaction betweenepithelial and immune cells ensures the unique immune response taking place in mucosal tissues, which is reported to be dysregulatedin allergic diseases.We and others have demonstrated that in severe allergic phenotypes, the epithelial barrier undergoes several histological modifications,with increased infiltration of immune cells, leading to dysfunction. This is common in atopic dermatitis, asthma, and food allergy. However,the precise role of the epithelial barrier in mucosal biology during progression of allergic diseases is not well understood.In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelialbarrier and to shed light on the role of this compartment in the onset and progression of allergic diseases (AU)

La barrera epitelial se ha considerado clásicamente sólo como la primera línea de defensa contra los irritantes, patógenos y alérgenos,pero ahora sabemos que el epitelio también desempeña un papel esencial en la respuesta inmunológica frente los agentes exógenos.De hecho, informes recientes postulan la hipótesis de la barrera epitelial como una posible explicación de la creciente incidencia y lagravedad de las enfermedades alérgicas.La barrera epitelial preserva el aislamiento de los tejidos internos de las posibles amenazas exteriores. Se sabe que las células epiteliales,además de un papel meramente protector, también tienen una función esencial en el desarrollo de la respuesta inmune en las mucosas,favoreciendo un ambiente tolerogénico. Sin embargo, en enfermedades alérgicas, estas características se ven afectadas como demuestrauna repuesta exagerada ante antígenos inocuos. De hecho, en los fenotipos alérgicos graves, la barrera epitelial experimenta variasmodificaciones histológicas que se asocian con pérdida de integridad y aumento de los infiltrados celulares, lo que conduce a una disfunciónde la misma. Este proceso es común en la dermatitis atópica, el asma y/o la alergia alimentaria. Aunque todavía no se conoce bien lafunción exacta de la barrera epitelial en la biología de la mucosa durante las enfermedades alérgicas.En esta revisión, pretendemos recopilar los conocimientos recientes sobre la estructura histológica y la función inmunológica de la barreraepitelial, y arrojar luz sobre el papel de este compartimento en la aparición y la progresión de las enfermedades alérgicas (AU)

Genetics and Epigenetics of Nasal Polyposis: A Systematic Review

Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses that is often associated with nasal polyposis (CRSwNP) in the most severe cases. As in other complex diseases, genetic factors are thought to play an important role in the risk and development of the disease. Environment may also modulate the epigenetic signature in affected patients. In the present systematic review, we aimed to compile all published data on genetic and epigenetic variations in CRSwNP since 2000. We found 104 articles, 24 of which were related to epigenetic studies. We identified more than 150 genetic variants in 99 genes involved in the pathogenesis of nasal polyposis. These were clustered into 8 main networks, linking genes involved in inflammation and immune response (eg, MHC), cytokine genes (eg, TNF), leukotriene metabolism, and the extracellular matrix. A total of 89 miRNAs were also identified; these are associated mainly with biological functions such as the cell cycle, inflammation, and the immune response. We propose a potential relationship between genes and the miRNAs identified that may open new lines of investigation. An in-depth knowledge of gene variants and epigenetic traits could help us to design more tailored treatment for patients with CRSwNP (AU)

COVID-19 y la esperanza de la inmunidad / COVID-19 and the hope for immunity

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Situación inmunitaria respecto a la rubéola de las mujeres en edad fértil del Área de Gestión Sanitaria de Osuna / Immune situation regarding rubéola of women in fertile age, belonging Osuna Sanitary Management Area

OBJETIVO: Conocer la situación de inmunidad a la rubéola en mujeres en edad fértil asociada a las variables de paridad, edad y localidad de procedencia pertenecientes al área de gestión sanitaria de Osuna, según recomendación del Plan Nacional de Eliminación del Sarampión y la Rubéola, y valorar la necesidad de intervención al respecto. METODOLOGÍA: Estudio observacional, descriptivo y transversal de mujeres que tuvieron parto en el Hospital de la Merced de Osuna durante 2016. Se recogieron datos de los resultados de serología de rubéola de las historias clínicas. RESULTADOS: El 82,51% de las mujeres atendidas eran inmunes. Por paridad, todos los grupos presentaron tasas de inmunidad inferiores al 85%. Por grupos de edad, destaca que las mujeres menores de 35 años tuvieron tasas de inmunidad inferiores (<80%) que las mayores de esa edad, de forma estadísticamente significativa. CONCLUSIONES: La tasa de mujeres inmunes a la rubéola, atendidas en el hospital del estudio, es inferior a la recomendada. Estos resultados podrían explicarse por varios factores, como un criterio analítico demasiado sensible para determinar inmunidad o no, la existencia de mujeres inmigrantes procedentes de países con baja cobertura vacunal, y la falta de cumplimiento de las indicaciones recomendadas, que son la serología preconcepcional y la vacunación posparto en casos identificados

OBJECTIVE: Know the rubella immunity situation in women of child-bearing age associated with the variables of parity, age and locality of origin belonging to the health management area of Osuna, according to the recommendation of the National Measles and Rubella Elimination Plan, and assess the Need for intervention in this regard. METHODOLOGY: Observational, descriptive and cross-sectional study of women who had birth in Hospital de la Merced de Osuna during 2016. Data were collected on the results of rubella serology from the medical records. RESULTS: 82.51% of women treated were immune. For parity, all groups offered immunity rates below 85%. By age groups, it is noteworthy that those under 35 had lower immunity rates (<80%) than those over that age, in a statistically significant way. CONCLUSIONS: The rate of women immune to rubella, treated in the hospital of this study, is lower than recommended. These results could be explained by several factors, such as an analytical criterion that is too sensitive to determine immunity or not, the existence of immigrant women from countries with low vaccination coverage, and the lack of compliance with the recommended indications, which are preconceptional serology and vaccination postpartum in identified cases

Adjuvants in allergen-specific immunotherapy: modulating and enhancing the immune response

Allergen-specific immunotherapy (AIT) is the only treatment that can affect the natural course of allergic diseases such as allergic asthma, allergic rhinitis, and IgE-mediated food allergy. Adjuvants are used to induce a quicker, more potent, and longer-lasting immune response. Only 4 compounds are used as adjuvants in currently marketed AIT products: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL). The first 3 adjuvants are delivery systems with a depot effect, although they may also have immunomodulatory properties. These first-generation adjuvants are still widely used, especially aluminum hydroxide. However, aluminum is subject to limitations. MCT is the depot formulation of L-tyrosine; it enhances IgG production without inducing a significant increase in IgE, is biodegradable, and has good local and systemic tolerability. In turn, MPL is an immunostimulatory agent that is the only second-generation adjuvant currently used for AIT. In addition, multiple adjuvants are currently being studied, including immunostimulatory sequences (ISSs), nanoparticles (liposomes, virus-like particles, and biodegradable polymers), and phosphatidylserine derivatives. In a murine model of allergic bronchial inflammation by sensitization to olive pollen, the specific IgE level was significantly higher in sensitized mice treated with olive pollen and aluminum hydroxide. However, specific IgE levels were significantly reduced and bronchial hyperreactivity significantly improved in sensitized mice treated with olive pollen and bacterial derivatives (MPL or ISSs)

La inmunoterapia específica con alérgenos (ITE) es el único tratamiento con potencial para modificar la evolución natural de enfermedades alérgicas como el asma alérgica, la rinitis alérgica y la alergia a alimentos mediada por IgE. Los adyuvantes se usan para provocar una respuesta inmune más rápida, más potente y de mayor duración. Hasta ahora, solo cuatro compuestos se usan como adyuvantes en los productos de ITE comercializados actualmente: hidróxido de aluminio, fosfato cálcico, tirosina microcristalina (MCT) y monofosforil lípido A (MPL). Los tres primeros son sistemas de liberación retardada (efecto depot), aunque también podrían tener propiedades inmunomoduladoras. Estos adyuvantes de primera generación todavía se usan ampliamente, sobre todo el hidróxido de aluminio. Sin embargo, el aluminio tiene algunas limitaciones. MCT es la formulación de liberación retardada de la L-tirosina; aumenta la producción de IgG sin provocar un incremento significativo de IgE, es biodegradable y tiene una buena tolerabilidad local y sistémica. A su vez, MPL es un inmunoestimulador y es el único adyuvante de segunda generación usado actualmente en ITE. Además, hay múltiples adyuvantes en investigación, como las secuencias inmunoestimuladoras (SIE), nanopartículas (liposomas, partículas similares a virus y polímeros biodegradables) y derivados de la fosfatidilserina.En un modelo múrido de inflamación bronquial alérgica por sensibilización al polen de olivo, el nivel de IgE específica fue significativamente mayor en los animales sensibilizados tratados con polen de olivo e hidróxido de aluminio. Sin embargo, en los animales sensibilizados tratados con polen de olivo y derivados bacterianos (MPL o SIE) se observó una disminución significativa del nivel de IgE específica y una mejoría significativa de la hiperreactividad bronquial

Interrelationship between lymphocytes and leptin in fat depots of obese mice revealed by changes in nutritional status

The mechanisms underlying the relationships between nutritional status and immunity remain to be fully characterized. The present study was undertaken to analyze by flow cytometry, in the context of diet-induced obesity, the status of immune cells in subcutaneous, and epididymal fat depots in wild-type and immunodeficient Rag2−/− mice submitted to nutritional challenge, i.e., 48-h fasting and 1-week refeeding. In parallel, the responsiveness of mature adipocytes and immune cells in bone marrow, lymph node, and liver were also analyzed. The results show that fasting in obese wild-type mice induces a prominent lipolysis in epididymal AT and immunosuppression restricted to both subcutaneous and epididymal AT, characterized by reduced number of CD4+ T and B lymphocytes and M1/M2 macrophages associated with reduced leptin and increased FGF21 expression in mature adipocytes. One-week refeeding was sufficient to reverse the fasting-induced effects. Obese immunodeficient mice under nutritional challenge exhibited no changes in adipocyte leptin expression and no marked trafficking of AT macrophages or NK cells, while the fasted-induced upregulation of FGF21 expression was maintained as well as the lipolytic responses. The present results demonstrate that, in a context of diet-induced obesity, fasting-induced immunosuppression is restricted to fat depots in immunocompetent mice. Lack of adipocyte leptin regulation and fasting-induced immunosuppression in obese immunodeficient mice strongly suggests that lymphocytes are involved in the modulation of adipocyte leptin expression on one hand and on the other that leptin is involved in the immune changes in AT according to nutritional status

Immunonutrition: methodology and applications / Inmunonutrición: metodología y aplicaciones

Immunonutrition is an emergent and interdisciplinary subject, since it comprises several aspects related to Nutrition, Immunity, Infection, Inflammation, and Injury or tissue damage, what is known as Nutrition and 4 'Is'. Within these interactions the endocrine, nervous and immune systems are involved, microbiota being a part of the last one. Nowadays, gut microbiota has been shown to play an essential role, not only in the gastrointestinal tract but also into the nervous system, because of its bilateral connection. There are several methods to study Immunonutrition, which allow measuring different immunological biomarkers to provide information about the nutritional status. However, it should be taken into account that there is not a single gold standard parameter to evaluate the cause-effect relationship between nutrition and the immune system. On the contrary, a combination of biomarkers have to be assessed depending on the different nutritional situations. Since Immunonutrition is a multidisciplinary matter as mentioned above, the study on the interactions between nutrition and the immune system has not been exclusively focused as such, but bearing in mind other systems of the organisms as well as a wide range of confounding factors and determinants coming from idiosyncratic features, genes and lifestyle of each individual. Therefore, Immunonutrition allows to study the following research fields: 1) Evaluation of nutritional status in presumably healthy people with risk of malnutrition (children, adolescents, adults, pregnant women, elderly, and sportspeople); 2) Assessment of the evolution and progress of patients with nutrition and immune-related diseases, such as food allergies, eating and metabolic disorders; 3) Evaluation of the effects of nutrients, bioactive compounds and both conventional and functional foods on the immune system; 4) Evaluation of impact of lifestyle determinants on the immune system, such as diet, food behaviour, physical activity, sedentariness, sleep quality and quantity, and as a key factor, stress (AU)

La Inmunonutrición es una materia emergente e interdisciplinar, ya que abarca distintos aspectos relacionados con la Nutrición, la Inmunidad, la Infección, la Inflamación y la Injuria o daño tisular, lo que se ha denominado como la Nutrición y las 4 'Ies'. En estas interacciones se encuentran implicados los sistemas endocrino, nervioso e inmune, formando parte la microbiota de este último. Actualmente la microbiota intestinal tiene un papel fundamental no solo a nivel del tracto gastrointestinal sino que presenta además un eje de conexión bilateral con el sistema nervioso Para el estudio de la Inmunonutrición existen diferentes biomarcadores del sistema inmune que proporcionan información acerca del estado nutricional del individuo. Sin embargo, se debe tener en cuenta que no existe un solo parámetro para evaluar la relación causa-efecto de la nutrición sobre el sistema inmunitario, sino que es un conjunto de biomarcadores a tener en cuenta dependiendo de los distintas situaciones nutricionales. Si bien está claro que se trata de una materia multidisciplinar, no solo se deben focalizar los estudios sobre las interacciones entre la nutrición y el sistema inmune de manera aislada, sino sobre otros sistemas del organismo teniendo en cuenta un gran abanico de factores de confusión y determinantes derivados de las condiciones idiosincrásicas de cada individuo, su genética y su estilo de vida. Por todo ello, la Inmunonutrición permite llevar a cabo una serie de estudios basados fundamentalmente en cuatro líneas de investigación: 1) Evaluación de poblaciones supuestamente sanas pero con riesgo de malnutrición (niños, adolescentes, adultos, gestantes, lactantes, personas mayores y deportistas), 2) Estudio de la evolución de pacientes con enfermedades relacionadas con la nutrición y el sistema inmunitario, 3) Estudio de los efectos de nutrientes, compuestos bioactivos y alimentos convencionales y funcionales sobre el sistema inmunitario; 4) Estudio del impacto del estilo de vida sobre el comportamiento del sistema inmunitario, teniendo como determinantes principales la dieta, el comportamiento alimentario, la actividad física, el sedentarismo, la calidad y cantidad de sueño, y como factor clave, el estrés (AU)

Autoimmune flares. The hows, whens, and whys of killing / Cómo, cuando y por qué matar durante los brotes en las enfermedades autoinmunes

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Enfermedades inflamatorias mediadas por inmunidad y otras comorbilidades en pacientes con psoriasis. Características basales de la cohorte de pacientes con psoriasis del estudio AQUILES / Immune-Mediated Inflammatory Diseases and Other Comorbidities in Patients With Psoriasis: Baseline Characteristics of Patients in the AQUILES Study

Introducción y objetivos: Los pacientes con psoriasis presentan con frecuencia comorbilidades, incluyendo otras enfermedades inflamatorias mediadas por inmunidad (EIMI) y factores de riesgo cardiovascular (FRCV). El objetivo de este trabajo es describir la prevalencia basal de otras EIMI y comorbilidades en una cohorte de pacientes con psoriasis. Pacientes y métodos: AQUILES es un estudio observacional prospectivo multicéntrico de 3 cohortes de pacientes (psoriasis, espondiloartritis y enfermedad inflamatoria intestinal [EII]), para evaluar la coexistencia de EIMI y otras comorbilidades. En la cohorte con psoriasis se incluyeron pacientes ≥ 18 años atendidos en consultas hospitalarias de dermatología. Se recogió información sobre datos demográficos y clínicos de acuerdo a un protocolo preespecificado. Resultados: Se incluyeron 528 pacientes con psoriasis (edad media: 46,7 años; 60,2% hombres; 39,8% mujeres; 89,8% psoriasis en placas; mediana de PASI 3,2 [1,5-7,4]). Presentaron otra EIMI 82 pacientes (15,5% [IC 95%: 12,7-18,9]). El 14,0% (IC 95%: 11,3-17,2) presentó espondiloartritis (la mayoría de estos artritis psoriásica [prevalencia 13,1%, IC 95%: 10,5-16,2), el 1,3% EII (IC 95%: 0,6-2,7) y el 0,2% uveítis (IC 95%: 0,1-1,4). La presencia de artritis psoriásica se asoció al sexo masculino (OR: 1,75 [0,98-2,98]) y a la duración de la psoriasis > 8 años (OR: 4,17; [1,84- 9,44]) respecto a < 4 años. El 73,1% presentó al menos un FRCV: tabaquismo (40,5%); obesidad (26,0%); dislipidemia (24,8%); hipertensión arterial (24,3%) y diabetes mellitus (12,3%). Conclusión: Los pacientes con psoriasis presentaron una prevalencia del 15,5% de otras EIMI, discretamente superior a la de población general. Casi tres cuartas partes tuvieron al menos un FRCV (AU)

Introduction and objectives: Patients with psoriasis often have comorbidities, including other immune-mediated inflammatory diseases (IMIDs), and cardiovascular risk factors. In this article we describe the baseline prevalence of comorbidities----including other IMIDs----in a cohort of patients with psoriasis. Patients and methods: AQUILES was a prospective observational multicenter study of 3 patient cohorts (patients with psoriasis, spondyloarthritis, or inflammatory bowel disease) undertaken to investigate the prevalence of comorbidities, including other IMIDs, in these settings. The psoriasis cohort comprised patients aged at least 18 years who were seen in hospital dermatology clinics. A predefined protocol was used to collect demographic and clinical data. Results: The study enrolled 528 patients with psoriasis (60.2% men and 39.8% women). Mean age was 46.7 years; 89.8% of the participants had plaque psoriasis, and the median Psoriasis Area Severity Index score (PASI) was 3.2 (1.5-7.4). Comorbid IMIDs were present in 82 (15.5%) of the patients (CI 95%, 12.7%-18.9%). Spondyloarthritis was observed in 14% of patients (95% CI, 11.3%-17.2%), mostly in the form of psoriatic arthritis, for which the overall prevalence was 13.1% (95% CI, 10.5%-16.2%). Inflammatory bowel disease was present in 1.3% (95% CI, 0.6%-2.7%) and uveitis in .2% (95% CI, 0.1%-1.4%). Psoriatic arthritis was associated with male sex (odds ratio, 1.75 [.98-2.98]) and a disease duration of over 8 years (OR, 4.17 [1.84-9.44] vs a duration of < 4 years). In 73.1%, at least 1 cardiovascular risk factor was identified: smoking (40.5%), obesity (26.0%), dyslipidemia (24.8%), hypertension (24.3%), and diabetes mellitus (12.3%). Conclusion: In patients with psoriasis the prevalence of other IMIDs was 15.5%, a level slightly higher than that found in the general population. Nearly three-quarters of these patients had at least 1 cardiovascular risk factor (AU)

Inmunonutrición: metodología y aplicaciones / Immunonutrition: methodology and applications

La Inmunonutrición es una materia emergente e interdisciplinar, ya que abarca distintos aspectos relacionados con la Nutrición, la Inmunidad, la Infección, la Inflamación y la Injuria o daño tisular, lo que se ha denominado como la Nutrición y las 4 'Ies'. En estas interacciones se encuentran implicados los sistemas endocrino, nervioso e inmune, formando parte la microbiota de este último. Actualmente la microbiota intestinal tiene un papel fundamental no solo a nivel del tracto gastrointestinal sino que presenta además un eje de conexión bilateral con el sistema nervioso. Para el estudio de la Inmunonutrición existen diferentes biomarcadores del sistema inmune que proporcionan información acerca del estado nutricional del individuo. Sin embargo, se debe tener en cuenta que no existe un solo parámetro para evaluar la relación causa-efecto de la nutrición sobre el sistema inmunitario, sino que es un conjunto de biomarcadores a tener en cuenta dependiendo de las distintas situaciones nutricionales. Si bien está claro que se trata de una materia multidisciplinar, no solo se deben focalizar los estudios sobre las interacciones entre la nutrición y el sistema inmune de manera aislada, sino sobre otros sistemas del organismo teniendo en cuenta un gran abanico de factores de confusión y determinantes derivados de las condiciones idiosincrásicas de cada individuo, su genética y su estilo de vida. Por todo ello, la Inmunonutrición permite llevar a cabo una serie de estudios basados fundamentalmente en cuatro líneas de investigación: 1) Evaluación de poblaciones supuestamente sanas pero con riesgo de malnutrición (niños, adolescentes, adultos, gestantes, lactantes, personas mayores y deportistas), 2) Estudio de la evolución de pacientes con enfermedades relacionadas con la nutrición y el sistema inmunitario, 3) Estudio de los efectos de nutrientes, compuestos bioactivos y alimentos convencionales y funcionales sobre el sistema inmunitario; 4) Estudio del impacto del estilo de vida sobre el comportamiento del sistema inmunitario, teniendo como determinantes principales la dieta, el comportamiento alimentario, la actividad física, el sedentarismo, la calidad y cantidad de sueño, y como factor clave, el estrés (AU)

Immunonutrition is an emergent and interdisciplinary subject, since it comprises several aspects related to Nutrition, Immunity, Infection, Inflammation, and Injury or tissue damage, what is known as Nutrition and 4 'Is'. Within these interactions the endocrine, nervous and immune systems are involved, microbiota being a part of the last one. Nowadays, gut microbiota has been shown to play an essential role, not only in the gastrointestinal tract but also into the nervous system, because of its bilateral connection. There are several methods to study Immunonutrition, which allow measuring different immunological biomarkers to provide information about the nutritional status. However, it should be taken into account that there is not a single gold standard parameter to evaluate the cause-effect relationship between nutrition and the immune system. On the contrary, a combination of biomarkers have to be assessed depending on the different nutritional situations. Since Immunonutrition is a multidisciplinary matter as mentioned above, the study on the interactions between nutrition and the immune system has not been exclusively focused as such, but bearing in mind other systems of the organisms as well as a wide range of confounding factors and determinants coming from idiosyncratic features, genes and lifestyle of each individual. Therefore, Immunonutrition allows to study the following research fields: 1) Evaluation of nutritional status in presumably healthy people with risk of malnutrition (children, adolescents, adults, pregnant women, elderly, and sportspeople); 2) Assessment of the evolution and progress of patients with nutrition and immune-related diseases, such as food allergies, eating and metabolic disorders; 3) Evaluation of the effects of nutrients, bioactive compounds and both conventional and functional foods on the immune system; 4) Evaluation of impact of lifestyle determinants on the immune system, such as diet, food behaviour, physical activity, sedentariness, sleep quality and quantity, and as a key factor, stress (AU)