NOX2 control over energy metabolism plays a role in acute myeloid leukaemia prognosis and survival.

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, however the therapeutic approaches have hardly changed in the last decades. Metabolism rewiring and the enhanced production of reactive oxygen species (ROS) are hallmarks of cancer. A deeper understanding of these features could be instrumental for the development of specific AML-subtypes treatments. NADPH oxidases (NOX), the only cellular system specialised in ROS production, are also involved in leukemic metabolism control. NOX2 shows a variable expression in AML patients, so patients can be classified based on such difference. Here we have analysed whether NOX2 levels are important for AML metabolism control. The lack of NOX2 in AML cells slowdowns basal glycolysis and oxidative phosphorylation (OXPHOS), along with the accumulation of metabolites that feed such routes, and a sharp decrease of glutathione. In addition, we found changes in the expression of 725 genes. Among them, we have discovered a panel of 30 differentially expressed metabolic genes, whose relevance was validated in patients. This panel can segregate AML patients according to CYBB expression, and it can predict patient prognosis and survival. In summary, our data strongly support the relevance of NOX2 for AML metabolism, and highlights the potential of our discoveries in AML prognosis.

Sedation Quality and Cardiorespiratory, Echocardiographic, Radiographic and Electrocardiographic Effects of Intramuscular Alfaxalone and Butorphanol in Spanish Greyhound Dogs.

The quality of sedation and changes in cardiorespiratory variables after the intramuscular administration of alfaxalone and butorphanol in Spanish greyhound dogs were evaluated. Twenty-one adult dogs were included. The dogs received alfaxalone (2 mg/kg) and butorphanol (0.2 mg/kg) intramuscularly. Sedation scoring, cardiorespiratory parameters (including blood gas analysis), echocardiography, thoracic radiography and electrocardiography were performed before sedation and 30 min after drug administration. Moderate sedation was observed, and side effects, such as tremors, nystagmus and auditory hyperesthesia, were noticed. Statistically significant changes in heart rate, invasive blood pressure, pH, arterial saturation of O2 and partial pressure of O2 and CO2 were found. Echocardiographic variables, including end-diastolic volume, left ventricular diameter in diastole, aortic and pulmonic flow, diastolic transmitral flow and left atrial/aortic ratio, and electrocardiography parameters, including PQ interval and QT interval, showed statistically significant changes. In conclusion, the intramuscular administration of alfaxalone and butorphanol to healthy dogs produced moderate sedation with mild cardiorespiratory, echocardiographic and electrocardiographic changes, without alterations in cardiac size on radiographic images.

The Flp type IV pilus operon of Mycobacterium tuberculosis is expressed upon interaction with macrophages and alveolar epithelial cells.

The genome of Mycobacterium tuberculosis (Mtb) harbors the genetic machinery for assembly of the Fimbrial low-molecular-weight protein (Flp) type IV pilus. Presumably, the Flp pilus is essential for pathogenesis. However, it remains unclear whether the pili genes are transcribed in culture or during infection of host cells. This study aimed to shed light on the expression of the Flp pili-assembly genes (tadZ, tadA, tadB, tadC, flp, tadE, and tadF) in Mtb growing under different growth conditions (exponential phase, stationary phase, and dormancy NRP1 and NRP2 phases induced by hypoxia), during biofilm formation, and in contact with macrophages and alveolar epithelial cells. We found that expression of tad/flp genes was significantly higher in the stationary phase than in exponential or NRP1 or NRP2 phases suggesting that the bacteria do not require type IV pili during dormancy. Elevated gene expression levels were recorded when the bacilli were in contact for 4 h with macrophages or epithelial cells, compared to mycobacteria propagated alone in the cultured medium. An antibody raised against a 12-mer peptide derived from the Flp pilin subunit detected the presence of Flp pili on intra- and extracellular bacteria infecting eukaryotic cells. Altogether, these are compelling data showing that the Flp pili genes are expressed during the interaction of Mtb with host cells and highlight a role for Flp pili in colonization and invasion of the host, subsequently promoting bacterial survival during dormancy.

Clinical Characteristics of Coronavirus Disease (COVID-19) in Mexican Children and Adolescents.

BACKGROUND: We analyzed the demographic, clinical, and diagnostic data of children and adolescents in Mexico, from the first case of coronavirus disease (COVID-19) to 28 February 2022. METHODS: Using the open databases of the Ministry of Health and a tertiary pediatric hospital, we obtained demographic and clinical data from the beginning of the COVID-19 pandemic until 28 February 2022. In addition, quantitative reverse-transcription polymerase chain reaction outputs were used to determine the viral load, and structural protein-based serology was performed to evaluate IgG antibody levels. RESULTS: Of the total 437,832 children and adolescents with COVID-19, 1187 died. Of these patients, 1349 were admitted to the Hospital Infantil de Mexico Federico Gómez, and 11 died. Obesity, asthma, and immunosuppression were the main comorbidities, and fever, cough, and headache were the main symptoms. In this population, many patients have a low viral load and IgG antibody levels. CONCLUSION: During the first 2 years of the COVID-19 pandemic in Mexico, children and adolescents had low incidence and mortality. They are a heterogeneous population, but many patients had comorbidities such as obesity, asthma, and immunosuppression; symptoms such as fever, cough, and headache; and low viral load and IgG antibodies.

The antecedents of entrepreneurial behaviour in the creation of platform economy initiatives: An analysis based on the decomposed theory of planned behaviour.

The platform economy (PE) has experienced its strongest period of growth since the emergence of the sharing economy (SE). Much work has been put into understanding the effects and antecedents of the PE, with particular emphasis on peers and consumer motivation, yet few studies have analysed the motivations of the service providers and even fewer its impact on individual and collective wellbeing. The aim of this paper is provide a better understanding of the decomposed beliefs that inform the attitudinal, social-normative and control factors that make up pro-PE behavioural intention (the intention to develop a PE initiative) in the context of digitisation and wellbeing, while making the platform the focus of analysis. In this study we adapt and extend the Decomposed Theory of Planned Behaviour (DTPB) and use partial least squares regression (PLS), a structural equation modelling technique, to analyse valid data collected from 127 PE organisations operating in Spain. The empirical results obtained demonstrate that the three antecedents for behavioural intention (perceived control, attitude and the subjective norm) have a positive effect on the intention to develop a PE initiative. The study also shows that PE micro-entrepreneurs are motivated by individual and collective wellbeing and not just financial gain. This contributes substantially to reconciling the PE with its origins, rooted in pro-solidarity and social concerns, and to framing wellbeing in a broader paradigm consisting of psychological and social factors, going beyond the economic considerations and interests contained in previous paradigms.

Natural killer cell exhaustion in SARS-CoV-2 infection.

At the end of 2019, an outbreak of a severe respiratory disease occurred in Wuhan China, and an increase in cases of unknown pneumonia was alerted. In January 2020, a new coronavirus named SARS-CoV-2 was identified as the cause. The virus spreads primarily through the respiratory tract, and lymphopenia and cytokine storms have been observed in severely ill patients. This suggests the existence of an immune dysregulation as an accompanying event during a serious illness caused by this virus. Natural killer (NK) cells are innate immune responders, critical for virus shedding and immunomodulation. Despite its importance in viral infections, the contribution of NK cells in the fight against SARS-CoV-2 has yet to be deciphered. Different studies in patients with COVID-19 suggest a significant reduction in the number and function of NK cells due to their exhaustion. In this review, we summarize the current understanding of how NK cells respond to SARS-CoV-2 infection.

Liver Transplantation: Analysis of Preservation Solutions in the Andalusian Registry.

BACKGROUND: The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. METHODS: A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. RESULTS: Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P < .005) with donors older than 47.6 and 47.5 years, respectively. CONCLUSIONS: Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours.

Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents). Keywords: Obstructive sleep apnea Diagnosis Treatment

Leyes de eutanasia en España y en el mundo: aspectos médicos / Euthanasia laws in Spain and in the world: Medical aspects

Objetivo: Comparar la ley española de eutanasia y suicidio asistido con las que existen en otros países.DiseñoRevisión sistemática de la bibliografía.Fuentes de datosSe buscaron en Medline/PubMed, EMBASE y Biblioteca Cochrane los estudios que contuvieran en su título o resumen los descriptores «eutanasia» o «suicidio asistido» y además «legislación» o «ley», entre 2002 y final de 2020.Selección de estudios La búsqueda encontró 1.647 estudios y tras su cribado se valoraron 663, de los cuales 30 se incluyeron en la revisión. Se rechazaron estudios en los que solo constaran opiniones o no aportaran datos sobre la eutanasia/suicidio asistido en los países que los tienen regulados.Extracción de datosSe registraron los criterios que regulan la aceptación o rechazo de una petición de eutanasia o suicidio asistido en España y en los demás países en que están despenalizados.ResultadosLas regulaciones de la eutanasia en el mundo pueden agruparse en tres: leyes que permiten la eutanasia y el suicidio asistido (Países Bajos, Bélgica, Canadá, algunos estados de Australia, Nueva Zelanda, España), en las que la ley solo permite el suicidio asistido (EE.UU.) y en las que se admite únicamente el suicidio asistido y en base a sentencias judiciales, sin legislación específica (Suiza, Alemania).ConclusionesAunque hay diferencias, las leyes a las que más se asemeja la ley española de eutanasia son las de Países Bajos y Bélgica, por lo que es previsible que la casuística de eutanasia y sus cifras en España se parezcan en el futuro a las de estos países.

Objective: To compare the Spanish law on euthanasia and assisted suicide with those that exist in other countries.DesignSystematic review of the bibliography.Data sourcesMedline/PubMed, EMBASE and the Cochrane Library were searched for studies that contained in their title or abstract the descriptors «euthanasia» or «assisted suicide» and also «legislation» or «law», between 2002 and the end of 2020.Study selectionThe search found 1647 studies and after screening 663 were assessed, of which 30 were included in the review. Studies that only contained opinions or did not provide data on euthanasia/assisted suicide in the countries that have them regulated were rejected.Data extractionWe registered the criteria that regulate the acceptance or rejection of a request for euthanasia or assisted suicide in Spain and in the other countries where they are decriminalized.ResultsThe euthanasia regulations in the world can be grouped into three groups: laws that allow euthanasia and assisted suicide (Netherlands, Belgium, some states of Australia, New Zealand, Spain), those in which the law only allows assisted suicide (USA) and those in which only assisted suicide is admitted and based on court decisions, without specific legislation (Switzerland, Germany).ConclusionsAlthough there are differences, the laws that the Spanish euthanasia law most closely resembles are those of the Netherlands and Belgium, so it is foreseeable that the casuistry of euthanasia and its figures in Spain will resemble that of those countries in the future.

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

[Euthanasia laws in Spain and in the world: Medical aspects]. / Leyes de eutanasia en España y en el mundo: aspectos médicos.

OBJECTIVE: To compare the Spanish law on euthanasia and assisted suicide with those that exist in other countries. DESIGN: Systematic review of the bibliography. DATA SOURCES: Medline/PubMed, EMBASE and the Cochrane Library were searched for studies that contained in their title or abstract the descriptors «euthanasia¼ or «assisted suicide¼ and also «legislation¼ or «law¼, between 2002 and the end of 2020. STUDY SELECTION: The search found 1647 studies and after screening 663 were assessed, of which 30 were included in the review. Studies that only contained opinions or did not provide data on euthanasia/assisted suicide in the countries that have them regulated were rejected. DATA EXTRACTION: We registered the criteria that regulate the acceptance or rejection of a request for euthanasia or assisted suicide in Spain and in the other countries where they are decriminalized. RESULTS: The euthanasia regulations in the world can be grouped into three groups: laws that allow euthanasia and assisted suicide (Netherlands, Belgium, some states of Australia, New Zealand, Spain), those in which the law only allows assisted suicide (USA) and those in which only assisted suicide is admitted and based on court decisions, without specific legislation (Switzerland, Germany). CONCLUSIONS: Although there are differences, the laws that the Spanish euthanasia law most closely resembles are those of the Netherlands and Belgium, so it is foreseeable that the casuistry of euthanasia and its figures in Spain will resemble that of those countries in the future.

Relevance of TMPRSS2, CD163/CD206, and CD33 in clinical severity stratification of COVID-19.

Background: Approximately 13.8% and 6.1% of coronavirus disease 2019 (COVID-19) patients require hospitalization and sometimes intensive care unit (ICU) admission, respectively. There is no biomarker to predict which of these patients will develop an aggressive stage that we could improve their quality of life and healthcare management. Our main goal is to include new markers for the classification of COVID-19 patients. Methods: Two tubes of peripheral blood were collected from a total of 66 (n = 34 mild and n = 32 severe) samples (mean age 52 years). Cytometry analysis was performed using a 15-parameter panel included in the Maxpar® Human Monocyte/Macrophage Phenotyping Panel Kit. Cytometry by time-of-flight mass spectrometry (CyTOF) panel was performed in combination with genetic analysis using TaqMan® probes for ACE2 (rs2285666), MX1 (rs469390), and TMPRSS2 (rs2070788) variants. GemStone™ and OMIQ software were used for cytometry analysis. Results: The frequency of CD163+/CD206- population of transitional monocytes (T-Mo) was decreased in the mild group compared to that of the severe one, while T-Mo CD163-/CD206- were increased in the mild group compared to that of the severe one. In addition, we also found differences in CD11b expression in CD14dim monocytes in the severe group, with decreased levels in the female group (p = 0.0412). When comparing mild and severe disease, we also found that CD45- [p = 0.014; odds ratio (OR) = 0.286, 95% CI 0.104-0.787] and CD14dim/CD33+ (p = 0.014; OR = 0.286, 95% CI 0.104-0.787) monocytes were the best options as biomarkers to discriminate between these patient groups. CD33 was also indicated as a good biomarker for patient stratification by the analysis of GemStone™ software. Among genetic markers, we found that G carriers of TMPRSS2 (rs2070788) have an increased risk (p = 0.02; OR = 3.37, 95% CI 1.18-9.60) of severe COVID-19 compared to those with A/A genotype. This strength is further increased when combined with CD45-, T-Mo CD163+/CD206-, and C14dim/CD33+. Conclusions: Here, we report the interesting role of TMPRSS2, CD45-, CD163/CD206, and CD33 in COVID-19 aggressiveness. This strength is reinforced for aggressiveness biomarkers when TMPRSS2 and CD45-, TMPRSS2 and CD163/CD206, and TMPRSS2 and CD14dim/CD33+ are combined.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Role of Toll-like receptors in natural killer cell function in acute lymphoblastic leukemia.

Natural killer (NK) cells are specialized lymphocytes primarily involved in the response to infection and tumors. NK cells are characterized by the presence of specific surface molecules, as well as a wide repertoire of receptors that impart microenvironment-dependent effector functions. Among these receptors, Toll-like receptors (TLRs) can be activated to condition the NK response to either a cytotoxic or immunoregulatory phenotype. However, cellular function is frequently impaired during disorders such as cancer. In the last decade, it has become increasingly evident that the stimulation of NK cells is a requirement for their increased cytotoxic activity. TLR activation has been suggested as an alternative route for reestablishing the antitumor activity of NK cells. The present review summarizes the characteristics of NK cells, their receptors, the expression and function of NK cell TLRs, and their functional status in cancer, primarily acute lymphoblastic leukemia.

NK Cell Subpopulation Is Altered and the Expression of TLR1 and TLR9 Is Decreased in Patients with Acute Lymphoblastic Leukemia.

NK cells represent a heterogeneous subpopulation of lymphocytes of the innate immune system, which possess powerful antitumor activity. NK cells exhibit their function through a complex collection of receptors that act synergistically to recognize, regulate, or amplify the immune response. TLRs allow cells to detect PAMPs, MAMPs, or DAMPs, which are essential for the initiation of the immune response. Studies on the different subpopulations of NK cells and their expression profile of innate immune receptors in hematological cancers are limited. In this study, the specific subpopulations of NK cells in pediatric patients with acute lymphoblastic leukemia (ALL) and the repertoire and level of expression of TLRs in cytotoxic NK cells were assessed. The results suggested that pediatric patients with ALL exhibited a significant decrease in NK cells in peripheral blood and bone marrow, in addition to alterations in the distribution of the subpopulations of cells. Regulatory and cytotoxic NK cells were diminished, whereas dysfunctional phenotype was considerably increased. Cytotoxic NK cells from children with ALL expressed all 10 TLRs, and expression of TLR1 and TLR9 was decreased compared with the controls. Interestingly, cytotoxic NK cells exhibited a higher expression of TLR1 in the bone marrow than in the peripheral blood of patients with ALL. The present study is the first to show that TLR10 was expressed in the cytotoxic NK cells and the first to assess the profile and levels of the 10 known TLRs in cytotoxic NK cells from patients with ALL. The alterations in expression levels and cellular distribution may be involved in the immune response.

High expression of Toll-like receptor 7 is a survival factor in pediatric medulloblastoma.

PURPOSE: Medulloblastoma is an embryonal brain tumor that predominantly occurs in childhood with a wide histological and molecular variability. Our aim was to investigate the expression of Toll-like receptors (TLRs), their association with the infiltration of immune cells and with the histological subgroups, and, also, with the overall survival of patients. METHODS: Fifty-six paraffin-preserved biopsies from children with medulloblastoma of the classic, desmoplastic, and anaplastic subtypes were included. Microarrays of tissues were performed, and the infiltration of T and NK cells was quantified, as well as the expression of TLR7, TLR8, and TLR9. For all statistical analyses, significance was p < 0.05. RESULTS: CD4 + and CD8 + T lymphocytes and NK cells were found infiltrating the tumor. The infiltration of NK and CD4 + cells was greater in the classic and desmoplastic subtypes than in anaplastic. We found an important expression of TLRs in all medulloblastomas, but TLR7 and TLR8 were considerably higher in classic and desmoplastic subtypes than in anaplastic. Importantly, we observed that TLR7 was a prognostic factor for survival. CONCLUSIONS: Medulloblastomas present cellular infiltration and a differential expression of TLRs depending on the histological subtype. TLR7 is a prognostic factor of survival that is dependent on treatment and age.

Granuloma Formation in a Cyba-Deficient Model of Chronic Granulomatous Disease Is Associated with Myeloid Hyperplasia and the Exhaustion of B-Cell Lineage.

Haematopoiesis is a paradigm of cell differentiation because of the wide variety and overwhelming number of mature blood cells produced daily. Under stress conditions, the organism must adapt to a boosted demand for blood cells. Chronic granulomatous disease (CGD) is a genetic disease caused by inactivating mutations that affect the phagocyte oxidase. Besides a defective innate immune system, CGD patients suffer from recurrent hyper-inflammation episodes, circumstances upon which they must face emergency haematopoiesis. The targeting of Cybb and Ncf1 genes have produced CGD animal models that are a useful surrogate when studying the pathophysiology and treatment of this disease. Here, we show that Cyba-/- mice spontaneously develop granuloma and, therefore, constitute a CGD animal model to complement the existing Cybb-/- and Ncf1-/- models. More importantly, we have analysed haematopoiesis in granuloma-bearing Cyba-/- mice. These animals showed a significant loss of weight, developed remarkable splenomegaly, bone marrow myeloid hyperplasia, and signs of anaemia. Haematological analyses showed a sharped decrease of B-cells and a striking development of myeloid cells in all compartments. Collectively, our results show that granuloma inflammatory lesions dramatically change haematopoiesis homeostasis. Consequently, we suggest that besides their defective innate immunity, the alteration of haematopoiesis homeostasis upon granuloma may contribute to the dismal outcome of CGD.

Neutrophils: Many Ways to Die.

Neutrophils or polymorphonuclear leukocytes (PMN) are key participants in the innate immune response for their ability to execute different effector functions. These cells express a vast array of membrane receptors that allow them to recognize and eliminate infectious agents effectively and respond appropriately to microenvironmental stimuli that regulate neutrophil functions, such as activation, migration, generation of reactive oxygen species, formation of neutrophil extracellular traps, and mediator secretion, among others. Currently, it has been realized that activated neutrophils can accomplish their effector functions and simultaneously activate mechanisms of cell death in response to different intracellular or extracellular factors. Although several studies have revealed similarities between the mechanisms of cell death of neutrophils and other cell types, neutrophils have distinctive properties, such as a high production of reactive oxygen species (ROS) and nitrogen species (RNS), that are important for their effector function in infections and pathologies such as cancer, autoimmune diseases, and immunodeficiencies, influencing their cell death mechanisms. The present work offers a synthesis of the conditions and molecules implicated in the regulation and activation of the processes of neutrophil death: apoptosis, autophagy, pyroptosis, necroptosis, NETosis, and necrosis. This information allows to understand the duality encountered by PMNs upon activation. The effector functions are carried out to eliminate invading pathogens, but in several instances, these functions involve activation of signaling cascades that culminate in the death of the neutrophil. This process guarantees the correct elimination of pathogenic agents, damaged or senescent cells, and the timely resolution of the inflammation that is essential for the maintenance of homeostasis in the organism. In addition, they alert the organism when the immunological system is being deregulated, promoting the activation of other cells of the immune system, such as B and T lymphocytes, which produce cytokines that potentiate the microbicide functions.

Implicaciones clínicas del uso de la triple terapia en combinación de dosis fija en EPOC: del ensayo al paciente / The Clinical Implications of Triple Therapy in Fixed-Dose Combination in COPD: From the Trial to the Patient

La aparición de la denominada triple terapia inhalada mediante la combinación de un agonista ß2 de acción prolongada (LABA), un anticolinérgico de acción prolongada (LAMA) y un corticoide inhalado (ICS) en una combinación a dosis fijas (CDF) en un solo dispositivo de inhalación ha supuesto un cambio en el uso de este tratamiento. A pesar de que los ensayos clínicos nos aportan una idea de la eficacia y la seguridad de estas CDF, su aplicación a la clínica diaria puede presentar retos para el clínico sobre dos escenarios concretos. En pacientes que ya están recibiendo una triple terapia en dispositivos distintos el cambio a una CDF podría suponer beneficios en cuanto a disminución de errores críticos en el manejo de los inhaladores, mayor adherencia al tratamiento y menor coste, manteniendo la misma eficacia clínica. En pacientes que no están recibiendo una triple terapia en dispositivos distintos y que necesiten un cambio en el tratamiento, la CDF de triple terapia presenta beneficios mostrados en los ensayos clínicos. Aunque las diferencias metodológicas entre ensayos desaconsejan comparaciones directas, los resultados clínicos muestran una buena eficacia, pero también una considerable variabilidad y un número de resultados clínicos aún por explorar. En el futuro deberán desarrollarse ensayos que completen los datos de eficacia clínica, estudios en vida real que informen de su efectividad y trabajos encaminados a descubrir el perfil de paciente que presenta una mayor respuesta terapéutica a cada CDF, con el objeto de avanzar en el tratamiento personalizado

The emergence of a fixed-dose combination (FDC) of a long-acting ß2-agonists (LABAS), a long-acting anticholinergic agent (LAMA), and an inhaled corticosteroid (ICS) in a single inhalation device has changed the approach to inhaled therapy. Although clinical trials describe the efficacy and safety of these FDCs, their use in daily clinical practice can present challenges for the clinician in two specific scenarios. In patients who are already receiving triple therapy via different devices, switching to FDCs could confer benefits by reducing critical errors in the management of inhalers, improving therapeutic adherence, and lowering costs, while maintaining the same clinical efficacy. In patients who are not receiving triple therapy in different devices and who require a change in treatment, triple therapy FDC has shown benefits in clinical trials. Although methodological differences among the trials advise against direct comparison, clinical results show good efficacy, but also considerable variability, and a number of clinical outcomes have yet to be explored. In the future, trials must be developed to complete clinical efficacy data. Real-world efficacy trials are needed, and studies must be designed to determine the profile of patients who present a greater therapeutic response to each FDC in order to pave to way towards more personalized treatment

Understanding the Determinants for the Adoption of Mobile Market Research: An Empirical Study in the Spanish Market Research Industry.

The aim of this study is to investigate the determinants for the intention to adopt mobile technology as a data collection methodology in market research projects. A conceptual framework was developed using the technology-organization-environment (TOE) model to identify technological factors (perceived benefits and limitations), organizational factors (open attitude toward change, professional competence, satisfaction with traditional systems, and firm size), and environmental factors (industry pressure, client pressure, and participant pressure) affecting adoption. The empirical study was performed with data from 67 firms in the Spanish market research industry, which were analyzed using partial least squares (PLS). The results suggest that only organizational and environmental factors have a significant influence on adoption. Key factors include professional competence, organizational openness, satisfaction with traditional and online methodologies, and pressure from industry, clients and survey participants. The findings reveal that technological characteristics are no longer a driver, as firms are starting to adopt mobile marketing research based on its greater convenience for participants, and as an element of strategic differentiation.