The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages

Introduction: Macrophages significantly contribute to the regulation of vessel formation under physiological and pathological conditions. Although the angiogenesis-regulating role of alternatively polarized macrophages is quite controversial, a growing number of evidence shows that they can participate in the later phases of angiogenesis, including vessel sprouting and remodeling or regression. However, the epigenetic and transcriptional regulatory mechanisms controlling this angiogenesis-modulating program are not fully understood. Results: Here we show that IL-4 can coordinately regulate the VEGFA-VEGFR1 (FLT1) axis via simultaneously inhibiting the proangiogenic Vegfa and inducing the antiangiogenic Flt1 expression in murine bone marrow-derived macrophages, which leads to the attenuated proangiogenic activity of alternatively polarized macrophages. The IL-4-activated STAT6 and IL-4-STAT6 signaling pathway-induced EGR2 transcription factors play a direct role in the transcriptional regulation of the Vegfa-Flt1 axis. We demonstrated that this phenomenon is not restricted to the murine bone marrow-derived macrophages, but can also be observed in different murine tissue-resident macrophages ex vivo and parasites-elicited macrophages in vivo with minor cell type-specific differences. Furthermore, IL-4 exposure can modulate the hypoxic response of genes in both murine and human macrophages leading to a blunted Vegfa/VEGFA and synergistically induced Flt1/FLT1 expression. Discussion: Our findings establish that the IL-4-activated epigenetic and transcriptional program can determine angiogenesis-regulating properties in alternatively polarized macrophages under normoxic and hypoxic conditions

The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages

Introduction: Macrophages significantly contribute to the regulation of vessel formation under physiological and pathological conditions. Although the angiogenesis-regulating role of alternatively polarized macrophages is quite controversial, a growing number of evidence shows that they can participate in the later phases of angiogenesis, including vessel sprouting and remodeling or regression. However, the epigenetic and transcriptional regulatory mechanisms controlling this angiogenesis-modulating program are not fully understood. Results: Here we show that IL-4 can coordinately regulate the VEGFA-VEGFR1 (FLT1) axis via simultaneously inhibiting the proangiogenic Vegfa and inducing the antiangiogenic Flt1 expression in murine bone marrow-derived macrophages, which leads to the attenuated proangiogenic activity of alternatively polarized macrophages. The IL-4-activated STAT6 and IL-4-STAT6 signaling pathway-induced EGR2 transcription factors play a direct role in the transcriptional regulation of the Vegfa-Flt1 axis. We demonstrated that this phenomenon is not restricted to the murine bone marrow-derived macrophages, but can also be observed in different murine tissue-resident macrophages ex vivo and parasites-elicited macrophages in vivo with minor cell type-specific differences. Furthermore, IL-4 exposure can modulate the hypoxic response of genes in both murine and human macrophages leading to a blunted Vegfa/VEGFA and synergistically induced Flt1/FLT1 expression. Discussion: Our findings establish that the IL-4-activated epigenetic and transcriptional program can determine angiogenesis-regulating properties in alternatively polarized macrophages under normoxic and hypoxic conditions

Influence of the Cumulative Incidence of COVID-19 Cases on the Mental Health of the Spanish Out-of-Hospital Professionals

This study aimed to analyze the psychological affectation of health professionals (HPs) of Spanish Emergency Medical Services (EMSs) according to the cumulative incidence (CI) of COVID19 cases in the regions in which they worked. A cross-sectional descriptive study was designed, including all HPs working in any EMS of the Spanish geography between 1 February 2021 and 30 April 2021. Their level of stress, anxiety and depression (DASS-21) and the perception of self-efficacy (GSES) were the study’s main results. A 2-factor analysis of covariance was used to determine if the CI regions of COVID-19 cases determined the psychological impact on each of the studied variables. A total of 1710 HPs were included. A third presented psychological impairment classified as severe. The interaction of CI regions with the studied variables did not influence their levels of stress, anxiety, depression or self-efficacy. Women, younger HPs or those with less EMS work experience, emergency medical technicians (EMT), workers who had to modify their working conditions or those who lived with minors or dependents suffered a greater impact from the COVID-19 pandemic in certain regions. These HPs have shown high levels of stress, anxiety, depression and medium levels of self-efficacy, with similar data in the different geographical areas. Psychological support is essential to mitigate their suffering and teach them to react to adverse events.This research was funded by Fundación ASISA and Sociedad Española de Urgencias y Emergencias (SEMES)

Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.Estas recomendações baseadas na evidência detalham o uso da enteroscopia assistida por dispositivo no manejo clínico das doenças do intestino delgado. Um conjunto de Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta técnica, o seu papel nos algoritmos de manejo de cada indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero ([removed]2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16–0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26–0·57; p[removed]11 página

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Desempeño y formación docente en competencias digitales en clases no presenciales durante la pandemia COVID-19

The spread of COVID 19 has caused an unprecedented impact on multidimensional development in the population of all nations. This has resulted in governments speaking out in favour of adopting and implementing emergency sanitary and social isolation measures to prevent the spread of the virus. In Paraguay, the Ministry of Public Health and Social Welfare and the Ministry of Education and Science decreed the suspension of face-to-face educational activities at all levels. This brought, as an alternative solution, the implementation of a distance learning modality involving the adaptation of approaches orientated to the use of New Information Communication Technologies (NTICs). This raised questions from the perspective of the teacher about the preparation and prior knowledge in the use of digital tools and the ways in which the teachinglearning activity is being developed within the non-contact modality. The objective of the study was to evaluate the skill performance of teachers in schools in the city of Piribebuy in Paraguay during the COVID-19 pandemic. The study was a non-experimental descriptive trans-sectional one with a sample of teachers from 7 schools in the city of Piribebuy, Paraguay. A non-probability sampling for convenience was used using a predesigned questionnaire through the Google Forms platform. Most of the teachers described the fact of suddenly assuming non-contact classes as an inescapable professional commitment, partially adapting the regular plan to the current needs. They found the collapse of the platform gave the most difficulty. Texting first and social media second were the means of communication. They considered that they frequently tried to replicate the experience of the face-to-face class. Regarding the support of the parents in the development of the activities, they thought that it was regularly active. The role of teachers has been essential in the development of the distance learning experience in the midst of the health crisis. It is imperative to facilitate collaborative training and career guidance work for teachers, and to provide stable digital media access so that they can overcome technological and connectivity barriers.La propagación del COVID 19 ha causado un impacto sin precedentes en el desarrollo multidimensional en la población en todas las naciones. Esto trajo como consecuencia que los gobiernos se pronunciaran a favor de adoptar e implantar medidas de emergencia sanitaria y aislamiento social para evitar la propagación del virus. En Paraguay el Ministerio de Salud Pública y Bienestar Social y el Ministerio de Educación y Ciencias decretaron suspensión de las actividades presenciales educativas en todos los niveles. Esto trajo como alternativa de solución la implantación de la modalidad a distancia implicando la adaptación de enfoques orientados al uso de las Nuevas Tecnologías de la Información Comunicación (NTIC), surgiendo interrogantes desde la perspectiva del docente sobre la preparación y el conocimiento previo en el uso de herramientas digitales y las formas en que se está desarrollando la actividad de enseñanza aprendizaje bajo la modalidad no presencial. El estudio planteó como objetivo evaluar el desempeño competencial de los docentes de las escuelas de la ciudad de Piribebuy en Paraguay durante la pandemia de COVID-19. Fue un estudio no experimental descriptivo transeccional con una muestra de docentes de 7 escuelas de la ciudad de Piribebuy del Paraguay. Se utilizó un muestreo no probabilístico por conveniencia empleando un cuestionario prediseñado a través de la plataforma Google Forms. La mayoría de los docentes calificó el hecho de asumir repentinamente las clases no presenciales como un compromiso profesional ineludible, adecuando parcialmente el plan regular a las necesidades actuales, encontrando como mayor dificultad el colapso de la plataforma. Los mensajes de texto en primer lugar y las redes sociales en segundo lugar fueron los medios señalados para la comunicación. Consideraron que intentaban frecuentemente replicar la experiencia de la clase presencial. Respecto al acompañamiento de los padres en el desarrollo de las actividades opinaron que era regularmente activo. El papel de los docentes ha sido esencial para en el desarrollo de la experiencia de aprendizaje a distancia en medio de la crisis sanitaria. Es imperante facilitar un trabajo colaborativo de entrenamiento y orientación profesional a los docentes, y proporcionar acceso medios digitales estables a fin de que puedan superar las barreras tecnológicas y de conectividad