Environmental allergen reduction in asthma management: an overview

Asthma is a prevalent non-communicable disease that affects both children and adults. Many patients with severe, uncontrolled asthma could not achieve total control despite using anti-asthmatic drugs. There is increasing evidence that allergy to environmental allergens, including both indoor and outdoor allergens, is associated with asthma symptoms and severe asthma. Frequently reported sensitized allergens were dust mites, cockroaches, grass pollens, molds, pets, and rodents in allergic asthma patients, although the patterns of widespread allergens differed from each country. Allergen avoidance is the cornerstone of asthma management, especially in sensitized subjects. This review summarizes environmental allergen avoidance and clarifies their effects on asthma control. Despite contrasting results about the impact of allergen exposure reduction on asthma control, several studies supported the beneficial effects of reducing asthma-related symptoms or risk of exacerbations as a nondrug therapy. Identifying environmental allergens is helpful for asthma patients, and further studies on clinically effective avoidance methods are required

Интеллектуальная радиосеть с нечеткой конфигурацией

В статье обсуждаются возможности применения одноранговой радиосети стандарта IEEE 802.15.4 (ZigBee) диапазона 2,4 ГГц для работы системы, состоящей из группы малогабаритных мобильных роботов и одного командного пункта. Основная задача группы роботов – проведение разведки во время спасательных операций после техногенных и природных катастроф и аварий. Для сохранения управляемости отдельными роботами и системой в целом предлагается повысить «интеллект» системы связи за счет гибкой маршрутизации каналов между командным пунктом и конкретным мобильным роботом с тем, чтобы иметь систему с автоматическим, интеллектуальным восстановлением канала обмена данных.У статті обговорюються можливості застосування однорангової радіомережі стандарту ІЕЕ 802.15.4 (ZigBee) діапазону 2,4 Ггу для роботи системи, що складається з групи малогабаритних мобільних роботів та одного командного пункту. Основна задача групи роботів – проведення розвідки під час рятувальних операцій після техногенних та природних катастроф і аварій. Для збереження керованості окремими ротами та системою в цілому пропонується підвищити інтелект системи зв’язку за рахунок гнучкої маршрутитизації каналів між командним пунктом та конкретним мобільним роботом з тим, щоб мати систему з автоматичним, інтелектуальним відновлюванням каналу обміну даних.In the article the possibilities of application peer-to-peer radio networks of standard IEEE 802.15.4 (ZigBee) a range of 2,4 GHz for work of the system consisting of small-sized mobile robots group and one command point are discussed. The primary goal of group of robots – is carrying out of investigation during rescue operations after technogenic and natural accidents and failures. For controllability preservation by separate robots and system as a whole, it is offered to raise “intelligence” of a communication system at the expense of flexible routeing of channels between command point and the concrete mobile robot to have system with automatic, intellectual restoration of the channel of data exchange

ONE STEP SYNTHESIS OF WATER-DISPERSIBLE CoFe2O4 MAGNETIC NANOPARTICLES USING TRIETHYLENETETRAMINE AS SOLVENT AND STABILISING LIGAND

Magnetic CoFe2O4 nanoparticles were synthesised by one step synthetic method through thermal decomposition of Co and Fe precursors in triethylenetetramine solvent at high temperature. The advantage of this method is the ability to make monodisperse nanoparticles with high water-dispersibility and stability. The particle size can be tuned in the range of 7-11.3 nm by varying synthetic conditions. The obtained particles with small DLS size (less than 21 nm) are ready to disperse and stable in aqueous solution for weeks without any surface modification

Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis

Contains fulltext : 238107.pdf (Publisher’s version ) (Closed access)Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated phagocytosis (LAP) and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. In particular, we demonstrate that activation of LAP by the human fungal pathogen Aspergillus fumigatus depends on ERK1/2-mediated phosphorylation of p47phox subunit of NADPH oxidase. Physiologically, autocrine IL-6/JAK2/Ninein axis orchestrates microtubule organization and dynamics regulating ERK recruitment to the phagosome and LC3(+) phagosome (LAPosome) formation. In sepsis, loss of IL-6 signaling specifically abrogates microtubule-mediated trafficking of ERK, leading to defective activation of LAP and impaired killing of bacterial and fungal pathogens by monocytes/macrophages, which can be selectively restored by IL-6 supplementation. Our work uncovers a molecular pathway linking IL-6 signaling with LAP and provides insight into the mechanisms underlying immunoparalysis in sepsis

Leukocyte-Released Mediators in Response to Both Bacterial and Fungal Infections Trigger IFN Pathways, Independent of IL-1 and TNF-alpha, in Endothelial Cells

In sepsis, dysregulated immune responses to infections cause damage to the host. Previous studies have attempted to capture pathogen-induced leukocyte responses. However, the impact of mediators released after pathogen-leukocyte interaction on endothelial cells, and how endothelial cell responses vary depending on the pathogen-type is lacking. Here, we comprehensively characterized the transcriptomic responses of human leukocytes and endothelial cells to Gram negative-bacteria, Gram positive-bacteria, and fungi. We showed that whole pathogen lysates induced strong activation of leukocytes but not endothelial cells. Interestingly, the common response of leukocytes to various pathogens converges on endothelial activation. By exposing endothelial cells to leukocyte-released mediators, we observed a strong activation of endothelial cells at both transcription and protein levels. By adding IL-1RA and TNF-α antibody in leukocyte-released mediators before exposing to endothelial cells, we identified specific roles for IL-1 and TNF-α in driving the most, but not all, endothelial activation. We also showed for the first time, activation of interferon response by endothelial cells in response to leukocyte-released mediators, independently from IL-1 and TNF-α pathways. Our study therefore, not only provides pathogen-dependent transcriptional changes in leukocytes and endothelial cells during infections, but also reveals a role for IFN, together with IL1 and TNFα signaling, in mediating leukocyte-endothelial interaction in infections

Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma

Background: Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process. Methods: The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity. Results: Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators. Conclusions: The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs. Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1. NCT04919135. Registered June 9, 2021, https://www.clinicaltrials.gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1

Las políticas de reequilibro territorial e innovación institucional en Madrid, 2015-2019

Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional. El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia.Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional.El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead