Eosinophil-derived extracellular vesicles: isolation and classification techniques and implications for disease pathophysiology.

Eosinophils are leukocytes characterized by their ability to release granule content that is highly rich in enzymes and proteins. Besides the anti-helminthic, bactericidal, and antiviral properties of eosinophils and their secretory granules, these also play a prominent role in the pathophysiology of diseases like asthma, eosinophilic esophagitis, and other hypereosinophilic conditions by causing tissue damage and airway hyperresponsiveness. Although this cell was first recognized mainly for its capacity to release granule content, nowadays other capabilities such as cytokine secretion have been linked to its physiology, and research has found that eosinophils are not only involved in innate immunity, but also as orchestrators of immune responses. Nearly 10 years ago, eosinophil-derived extracellular vesicles (EVs) were first described; since then, the EV field has grown exponentially, revealing their vital roles in intracellular communication. In this review, we synthesize current knowledge on eosinophil-derived EVs, beginning with a description of what they are and what makes them important regulators of disease, followed by an account of the methodologies used to isolate and characterize EVs. We also summarize current understanding of eosinophil-derived vesicles functionality, especially in asthma, the disease in which eosinophil-derived EVs have been most widely studied, describing how they modulate the role of eosinophils themselves (through autocrine signaling) and the way they affect airway structural cells and airway remodeling. Deeper understanding of this cell type could lead to novel research in eosinophil biology, its role in other diseases, and possible use of eosinophil-derived EVs as therapeutic targets.

Patients Living With Arterial Hypertension in Mexico: First Insights of The Mexican Registry of Arterial Hypertension (RIHTA Study).

BACKGROUND: Arterial hypertension is a significant cause of morbidity and mortality in Mexico. However, there is limited evidence to understand blood pressure management and cardiometabolic profiles. Here, we aim to assess the prevalence of controlled and uncontrolled blood pressure, as well as the prevalence of cardiometabolic risk factors among patients from the Mexican Registry of Arterial Hypertension (RIHTA). METHODS: We conducted a cross-sectional analysis of participants living with arterial hypertension registered on RIHTA between December 2021 and April 2023. We used both the 2017 ACC/AHA and 2018 ESC/ESH thresholds to define controlled and uncontrolled arterial hypertension. We considered eleven cardiometabolic risk factors, which include overweight, obesity, central obesity, insulin resistance, diabetes, hypercholesterolemia, hypertriglyceridemia, low HDL-C, high LDL-C, low-eGFR, and high cardiovascular disease (CVD) risk. RESULTS: In a sample of 5,590 participants (female: 61%, n = 3,393; median age: 64 [IQR: 56-72] years), the prevalence of uncontrolled hypertension varied significantly, depending on the definition (2017 ACC/AHA: 59.9%, 95% CI: 58.6-61.2 and 2018 ESC/ESH: 20.1%, 95% CI: 19.0-21.2). In the sample, 40.43% exhibited at least 5-6 risk factors, and 32.4% had 3-4 risk factors, chiefly abdominal obesity (83.4%, 95% CI: 82.4-84.4), high LDL-C (59.6%, 95% CI: 58.3-60.9), high CVD risk (57.9%, 95% CI: 56.6-59.2), high triglycerides (56.2%, 95% CI: 54.9-57.5), and low HDL-C (42.2%, 95% CI: 40.9-43.5). CONCLUSIONS: There is a high prevalence of uncontrolled hypertension interlinked with a high burden of cardiometabolic comorbidities in Mexican adults living with arterial hypertension, underscoring the urgent need for targeted interventions and better healthcare policies to reduce the burden of the disease in our country.

Moderate-High Blood Eosinophilia Is Associated with Increased Hospitalization and Other Asthma Comorbidities.

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/µL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/µL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.

Strategies to prevent, diagnose and treat kidney disease related to systemic arterial hypertension: a narrative review from the Mexican Group of Experts on Arterial Hypertension.

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.

Comparison of Long-term Response and Remission to Omalizumab and Anti-IL-5/IL-5R Using Different Criteria in a Real-life Cohort of Severe Asthma Patients

Background: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission.ObjectivesTo ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission.MethodsA multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria.ResultsThe study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06–1.23; p<0.001), admissions at ICU (2.69; 1.30–5.56; p=0.01), high count of SAE (1.21; 1.03–1.42; p=0.02) before biologic treatment. High FEV1% (0.96; 0.95–0.98; p<0.001), a high ACT score (0.93; 0.88–0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29–0.91; p=0.02) showed strong associations with achieving clinical remission.ConclusionA substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons. (AU)

Comparison of Long-term Response and Remission to Omalizumab and Anti-IL-5/IL-5R Using Different Criteria in a Real-life Cohort of Severe Asthma Patients.

BACKGROUND: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission. OBJECTIVES: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission. METHODS: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria. RESULTS: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV1% (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission. CONCLUSION: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons.

Espacios cardioprotegidos en México: acciones para prevenir la muerte súbita cardiaca. Una postura de profesionales de la salud.

La muerte súbita cardiaca es un problema de salud pública a nivel mundial. Aunque su incidencia no es conocida, se estima que causa hasta 50% de la mortalidad de origen cardíaco y hasta 20% de la mortalidad total en los adultos. En México, estimaciones previas sugieren que causa en promedio 33 000 muertes al año; sin embargo, los datos no son precisos. La  mitad de los eventos por muerte súbita cardiaca se deben a un paro cardiaco súbito extrahospitalario que, de no ser atendido oportunamente, deriva en una muerte súbita cardiaca. Por tanto, la capacidad de responder pronta y adecuadamente a estos eventos con las maniobras y equipos necesarios mejora la sobrevida de las víctimas. Para atender este problema, en algunos estados del país se han creado espacios cardioprotegidos que permiten realizar maniobras de reanimación cardiopulmonar y desfibrilación cardiaca de acceso público oportunamente. Como objetivo, los profesionales de la salud establecen la importancia de implementar espacios cardioprotegidos y crear políticas públicas al respecto en todo el país.

The Val158Met Polymorphism in 8-Year-Old Boys and Girls Moderates the Influence of Parenting Styles on Proactive Aggression: Testing the Sensitivity to the Environment.

The aim of the study was to explore the possible vulnerability (diathesis-stress), susceptibility (differential susceptibility), or vantage (vantage sensitivity) properties of COMT gen Val158Met polymorphism to adverse and favorable parenting styles from both parents in relation to children's reactive and proactive aggressive behavior. Within 279 eight-year-old children (125 girls and 154 boys) from Spain, reactive and proactive aggressive behavior was measured through the "Reactive and Proactive Questionnaire" (RPQ). Saliva samples were collected to genotype for the COMT Val158Met polymorphism via real-time PCR. Finally, parenting styles were assessed using the "Parenting Styles and Dimensions Questionnaire" (PSDQ). The results revealed that for boys, the Met allele was a vulnerability factor for proactive aggression in response to low-authoritative parenting from the father. For girls, it was the Val allele, the vulnerability variable to the high authoritarian style of the father, and the susceptibility factor to the authoritative style of the mother over proactive aggression. The results are discussed, considering possible sex differences. Our results indicate that the COMT Val158Met polymorphism is a biological variable that confers greater sensitivity to the environment.

Chronic follicular pancreatitis: a space occupying lesion with spontaneous resolution.

Follicular pancreatitis (FP) is an extremely odd entity characterized by the presence of a pseudotumor that histologically presents lymphoid aggregates and germinal centers. The authors present the case of a 67-year-old woman with epigastric pain and jaundice. Endoscopic ultrasonography (EUS) was performed, revealing a 14x15 mm hypoechoic area with irregular edges in the head of the pancreas. The in situ cytological study showed polymorphic lymphoid cellularity, without atypia suggesting neoplasia. The cell block and the immunohistochemical study showed a polyclonal population with a pattern suggestive of FP. The patient presented spontaneous clinical improvement. The EUS follow up three months later shown pancreatic parenchyma with homogeneous echogenicity and no space occupying lesions were indentified. Since the diagnosis of FP has been reached after surgery in most cases, the treatment is not well established. However, no recurrences have been reported after surgery and spontaneous resolution has been observed in incomplete resections, which suggests the indication for conservative management. Diagnostic EUS has a fundamental role in the differential diagnosis between FP and pancreatic neoplasms, two entities with very different prognosis, and makes it possible to avoid, in the case of FP, unnecessary surgeries with the associated morbidity and mortality.

Differential susceptibility to parenting influences on reactive and proactive aggression: The role of testosterone and cortisol in children.

This study explored whether cortisol and testosterone moderate the effect of parenting style on children's aggressive behavior, in accordance with the diathesis-stress or differential susceptibility theory; i.e., whether children are vulnerable to negative parenting styles (diathesis-stress) or, in addition to this vulnerability, also benefit more from positive parenting (differential susceptibility). The sample group comprised 279 eight-year-old children (154 boys and 125 girls) from Spain. Aggressive behavior was assessed using the "Reactive and Proactive Questionnaire" (RPQ) and parenting styles were measured using the "Parenting Styles and Dimensions Questionnaire" (PSDQ). Additionally, three saliva samples were collected to measure testosterone and cortisol levels, which were analyzed using ELISA. The results revealed that girls' high testosterone levels moderated the association between mothers' authoritarian parenting style and reactive aggression. This result can be explained by the differential susceptibility model. None of the interactions were statistically significant in boys' proactive aggression. The study emphasizes the importance of investigating biological and social factors that may influence aggressive behavior.

Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age.

BACKGROUND: Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age. METHODS: Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed. RESULTS: A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025). CONCLUSIONS: Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

Jejunal varix with a high transfusion requirement: therapy with cyanoacrylate with radiological control by double-balloon enteroscopy.

A jejunal varix with high transfusion requirement is treated by double-balloon enteroscopy with cyanoacrylate/ lipiodol with radiological control. The patient had not gastrointestinal hemorrhage or transfusion requeriment after 8 months follow up. Our recent previous article in Rev Esp Enferm Dig on advanced therapeutics by enteroscopy is referenced, providing this new therapeutic possibility.

Food insecurity profile according to habits and lifestyles in workers with subsistence jobs, Medellín-Colombia 2016.

Introduction: Although the informal economy absorbs a considerable portion of the population, there is still little evidence that contributes to identify the lifestyles and eating habits that outline food insecurity in workers with subsistence jobs. Objectives: To determine the profile of food insecurity according to habits and lifestyles in workers with subsistence jobs. Methods: Cross-sectional study with primary sources of information, obtained through an assisted survey, to a census of 686 workers in 2016. The results of the nutritional component of a doctoral thesis approved by the Institutional Ethics Committee of the CES University, Medellín, Colombia, are presented. Results: In this working population, 52.6% were 50 years or old; however, 86.1% reported being the main household provider, and 33.3% did not have a permit to work in public areas. Moreover, 56.8% reported being sedentary/little active, and the highest consumption of alcohol and tobacco was recorded in men, who also ate their food alone. Conversely, women considered that mood affected their appetite, and they consumed their food while serving customers and handling money. In general, less than 50.0% of workers had a set time to consume their food. Food insecurity in workers' households was explained by alcohol consumption (prevalence ratio = 1.62; confidence interval = 1.05;2.38) and having exclusive hours to consume food (prevalence ratio = 1.40; confidence interval = 1.00;1.96). Their food insecurity is defined by not consuming alcoholic beverages, considering that their mood affects their appetite, consuming one or two meals a day, without a defined schedule, not having permission to work, presenting moderate/severe food insecurity, and being a woman. Conclusions: The conditions that explain and outline food insecurity in this working population contribute to their socio-environmental and labor vulnerability, however, these conditions can be reversed.

Introducción: Aunque la economía informal ocupe una gran parte de la población, todavía existen pocas evidencias que ayuden a identificar los estilos de vida y hábitos alimentarios que definen la inseguridad alimentaria entre los trabajadores con empleos de subsistencia. Objetivos: Determinar el perfil de inseguridad alimentaria según hábitos y estilos de vida en trabajadores con empleos de subsistencia. Métodos: Estudio transversal con fuentes primarias de información, realizado a través de encuesta asistida, con un censo de 686 trabajadores en 2016. Los resultados del componente nutricional de una tesis doctoral aprobada por el Comité de Ética Institucional de la Universidad CES, en Medellín, Colombia, son presentados. Resultados: De esta población trabajadora, el 52,6% tenía más de 50 años, sin embargo, el 86,1% reportó ser la persona que más aportaba en el hogar y al 33,3% no se le permitía trabajar en los espacios públicos. El 56,8% refirió ser sedentario/poco activo, registrándose el mayor consumo de bebidas alcohólicas y cigarrillos en los hombres, quienes también comían solos. Por su parte, las mujeres consideraban que el estado de ánimo afectaba al apetito y, cuando comían, simultáneamente atendían a los clientes y manejaban dinero. En general, menos del 50,0% tenía un tiempo definido para consumir sus alimentos. Explicaron inseguridad alimentaria en sus hogares, consumo de bebidas alcohólicas (RP = 1,62. IC = 1,05;2,38) e horarios exclusivos para consumir alimentos (RP = 1,40. IC = 1,00;1,96). Perfilan su inseguridad alimentaria no consumir bebidas alcohólicas, considerar que el estado de ánimo afectaba al apetito, consumir una o dos comidas al día, sin horario definido, no tener permiso para trabajar, presentar inseguridad alimentaria moderada/grave y ser mujer. Conclusiones: Las condiciones que explican y perfilan la inseguridad alimentaria de esta población trabajadora contribuyen a configurar su vulnerabilidad socioambiental y laboral, sin embargo, pueden ser revertidas.

Fog Computing for Control of Cyber-Physical Systems in Industry Using BCI.

Brain-computer interfaces use signals from the brain, such as EEG, to determine brain states, which in turn can be used to issue commands, for example, to control industrial machinery. While Cloud computing can aid in the creation and operation of industrial multi-user BCI systems, the vast amount of data generated from EEG signals can lead to slow response time and bandwidth problems. Fog computing reduces latency in high-demand computation networks. Hence, this paper introduces a fog computing solution for BCI processing. The solution consists in using fog nodes that incorporate machine learning algorithms to convert EEG signals into commands to control a cyber-physical system. The machine learning module uses a deep learning encoder to generate feature images from EEG signals that are subsequently classified into commands by a random forest. The classification scheme is compared using various classifiers, being the random forest the one that obtained the best performance. Additionally, a comparison was made between the fog computing approach and using only cloud computing through the use of a fog computing simulator. The results indicate that the fog computing method resulted in less latency compared to the solely cloud computing approach.

How reliably can algorithms identify eosinophilic asthma phenotypes using non-invasive biomarkers?

Background and Aims: Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non-invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely-eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset. Materials and Methods: We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity. Results: No correlation was found between both classifications 0.025 (CI = 0.013-0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population. Discussion and Conclusion: In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation.

Detection of COVID-19 Lung Lesions in Computed Tomography Images Using Deep Learning / Detección de lesiones pulmonares por COVID-19 en imágenes de tomografía computarizada mediante aprendizaje profundo

ABSTRACT The novel coronavirus (COVID-19) is a disease that mainly affects the lung tissue. The detection of lesions caused by this disease can help to provide an adequate treatment and monitoring its evolution. This research focuses on the bi- nary classification of lung lesions caused by COVID-19 in images of computed tomography (CT) using deep learning. The database used in the experiments comes from two independent repositories, which contains tomographic scans of patients with a positive diagnosis of COVID-19. The output layers of four pre-trained convolutional networks were adapted to the proposed task and re-trained using the fine-tuning technique. The models were validated with test images from the two database's repositories. The model VGG19, considering one of the repositories, showed the best performance with 88% and 90.2% of accuracy and recall, respectively. The model combination using the soft voting technique presented the highest accuracy (84.4%), with a recall of 94.4% employing the data from the other repository. The area under the receiver operating characteristic curve was 0.92 at best. The proposed method based on deep learning represents a valuable tool to automatically classify COVID-19 lesions on CT images and could also be used to assess the extent of lung infection.