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Magnetic anisotropy and magnetic exchange interactions are crucial parameters that characterize the hybrid metal-organic interface, a key component of an organic spintronic device. It is shown that the incorporation of 4f RE atoms to hybrid metal-organic interfaces of CuPc/REAu2 type (RE = Gd, Ho) constitutes a feasible approach toward on-demand magnetic properties and functionalities. The GdAu2 and HoAu2 substrates differ in their magnetic anisotropy behavior. Remarkably, the HoAu2 surface promotes the inherent out-of-plane anisotropy of CuPc, owing to the match between the anisotropy axis of substrate and molecule. Furthermore, the presence of RE atoms leads to a spontaneous antiferromagnetic exchange coupling at the interface, induced by the 3d-4f superexchange interaction between the unpaired 3d electron of CuPc and the 4f electrons of the RE atoms. It is shown that 4f RE atoms with unquenched quantum orbital momentum ( L $L$ ), as it is the case of Ho, induce an anisotropic interfacial exchange coupling.
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Using a reactive molecular beam with high kinetic energy (Ekin), it is possible to speed gas-surface reactions involving high activation barriers (Eact), which would require elevated pressures (P0) if a random gas with a Maxwell-Boltzmann distribution is used. By simply computing the number of molecules that overcome the activation barrier in a random gas at P0 and in a molecular beam at Ekin = Eact, we establish an Ekin-P0 equivalence curve, through which we postulate that molecular beams are ideal tools to investigate gas-surface reactions that involve high activation energies. In particular, we foresee the use of molecular beams to simulate gas surface reactions within the industrial-range (>10 bar) using surface-sensitive ultra-high vacuum (UHV) techniques, such as X-ray photoemission spectroscopy (XPS). To test this idea, we revisit the oxidation of the Cu(111) surface combining O2 molecular beams and XPS experiments. By tuning the kinetic energy of the O2 beam in the range of 0.24-1 eV, we achieve the same sequence of surface oxides obtained in ambient pressure photoemission (AP-XPS) experiments, in which the Cu(111) surface was exposed to a random O2 gas up to 1 mbar. We observe the same surface oxidation kinetics as in the random gas, but with a much lower dose, close to the expected value derived from the equivalence curve.
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Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell-derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee.
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Anticuerpos Monoclonales Humanizados , Asma , Calidad de Vida , Humanos , Citocinas/metabolismo , Linfopoyetina del Estroma Tímico , Inflamación , Biomarcadores , Inmunoglobulina ERESUMEN
BACKGROUND AND OBJECTIVE: Peach allergy is a prevalent cause of food allergy. Despite the repertoire of allergens available for molecular diagnosis, there are still patients with undetectable IgE levels to peach allergens but presenting symptoms after its ingestion. The objective of this study was to investigate the allergenic profile in a patient population with symptoms produced by peach. METHODS: An exploratory retrospective study was performed with patients presenting symptoms after the ingestion of peach. Forty-two patients were included in the study. The allergenic profile of individual patients was investigated by immunoblot. A serum pool was prepared with the sera that recognized a 70 kDa band. This pool was used to detect this protein in peach peel and pulp and to identify the 70 kDa protein in 2D immunoblot. Spots recognized in the 2D immunoblot were sequenced by LC-MS/MS. Inhibition studies were performed between peach peel and almond. RESULTS: Twenty-two patients (52.4%) recognized the 70 kDa protein in immunoblot. This protein was recognized in peel and pulp. Two different spots were observed in 2D-PAGE, both were identified as (R)-mandelonitrile lyases (RML) with high amino acid similarity with Pru du 10. Peach RML were partially inhibited with an almond extract. No association was found between any reported symptom and sensitization to RML. RML-sensitized patients were older and reported pollen associated respiratory symptoms more frequently than negative patients. CONCLUSION: A new peach allergen, a RML, homologous of Pru du 10, recognized by 52% of the population has been identified.
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BACKGROUND: The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. METHODOLOGY: This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. RESULTS: Out of a cohort of 1,012,257 patients (≤18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. CONCLUSIONS: Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.
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Pólipos Nasales , Rinitis , Índice de Severidad de la Enfermedad , Sinusitis , Humanos , Sinusitis/epidemiología , Pólipos Nasales/epidemiología , Pólipos Nasales/complicaciones , España/epidemiología , Enfermedad Crónica , Rinitis/epidemiología , Prevalencia , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , RinosinusitisRESUMEN
We have developed a numerical method for calculating the second-harmonic generation (SHG) generated by an anisotropic material whose optical properties present an arbitrary modulation in one dimension. The method is based on the Berreman 4 × 4 matrix formalism, which is generalized to include nonlinear optical phenomena. It can be used under oblique incidences of the input beam, and is valid even when the SHG frequency is close to photonic bands, where the usual slowly-varying-amplitude approximation breaks down. As an example of application, we have studied the SHG performance of ferroelectric and helielectric fluids. The obtained results indicate that the present procedure may contribute to improving the structural design and enlarging the variety of nonlinear optical materials for application in optical devices.
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Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response.
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Antiasmáticos , Asma , Humanos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/inducido químicamente , Corticoesteroides/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.
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Asma , Eosinofilia , Humanos , Óxido Nítrico , Multimorbilidad , Asma/diagnóstico , Asma/epidemiología , EosinófilosRESUMEN
BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.
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Asma , Productos Biológicos , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Omalizumab/uso terapéutico , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Olfato , Productos Biológicos/uso terapéutico , Anosmia/complicaciones , Anosmia/tratamiento farmacológico , Calidad de Vida , Estudios Retrospectivos , Asma/complicaciones , Asma/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Enfermedad Crónica , Rinitis/complicaciones , Rinitis/tratamiento farmacológicoRESUMEN
Summary: Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.
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Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O-Rh-O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation.
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BACKGROUND: Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals. In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed. METHODS: The animals (n = 151) were distributed into three groups: (1) a group topically treated with corticosteroids 48 h after intradermal tuberculin tests (n = 53); (2) a group pre-sensitised with bovine and avian purified protein derivatives (PPDs) 3 days before the intradermal tuberculin test used for TB diagnosis (n = 48); and (3) a control group (n = 50). All the animals were tested using single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, an interferon-gamma release assay (IGRA) and a P22 ELISA. RESULTS: The number of SIT test reactors was significantly lower in the group treated with corticosteroids when compared to the pre-sensitised (p < 0.001) and control (p = 0.036) groups. In contrast, pre-sensitisation with bovine and avian PPDs did not cause a significant reduction in the number of SIT and CIT test reactors compared with the control group. In fact, a higher number of reactors was observed after the prior tuberculin injection in the pre-sensitised group (p > 0.05). No significant effect was observed on IGRA and P22 ELISA due to corticosteroids administration. Nevertheless, a previous PPD injection affected the IGRA performance in some groups. CONCLUSIONS: The application of topical corticosteroid 24 h before reading the SIT and CIT tests can reduce the increase in skin fold thickness and subsequently significantly decrease the number of positive reactors. Corticosteroids used can be detected in hair samples. A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs.
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Enfermedades de los Bovinos , Enfermedades de las Cabras , Tuberculosis , Administración Tópica , Corticoesteroides/uso terapéutico , Animales , Bovinos , Enfermedades de las Cabras/diagnóstico , Enfermedades de las Cabras/tratamiento farmacológico , Enfermedades de las Cabras/epidemiología , Cabras , Sensibilidad y Especificidad , Tuberculina , Prueba de Tuberculina/veterinaria , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/veterinariaRESUMEN
PURPOSE: To investigate the association of omentin-1 and inflammatory factors in serum and visceral adipose tissue (VAT) of women with gestational diabetes mellitus (GDM) compared to normal pregnant (NP) subjects. Furthermore, to examine their correlation with maternal clinical characteristics. METHODS: We compared 116 GDM women to 115 NP women, at the time of cesarean section. Circulating omentin-1 and pro-inflammatory (IL-1ß, IL-6, TNF-α), and anti-inflammatory cytokines (IL-1RA, IL-10) were examined. Moreover, their mRNA expression in VAT, along with inflammatory factors involved in the NF-κB pathway (TLR2, TLR4, NF-κB, IKκB), were examined. RESULTS: Circulating omentin-1 (p = 0.022) was lower and circulating IL-1-ß, IL-1RA, as well as IL-10 (p = 0.005, p = 0.007, and p = 0.015, respectively), were higher in GDM compared to NP women. Omentin-1 correlated negatively with pre-pregnancy and gestational BMI, and HOMA-IR in all women, but was not associated with cytokines. TLR2, TLR4, IL-1ß, IL-1RA, IL-6, IL-10 mRNA expression in VAT was lower in GDM compared with controls (p < 0.05 all). In multivariate analysis, BMI at delivery was significantly correlated to omentin-1 concentrations in all and NP subjects. In addition, omentin-1 expression was correlated to inflammatory gene expression in all, GDM and NP, women (p < 0.05 all). CONCLUSION: Serum levels and VAT gene expression of omentin-1 are not independently linked to GDM; notwithstanding, GDM women have a VAT-altered inflammatory status. In addition, no systemic association between omentin-1 and inflammatory factors was found, whereas associations between their expression in all women were observed, indicating that expression of these adipokines is linked between them regardless of GDM.
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Citocinas/sangre , Diabetes Gestacional , Inflamación/sangre , Grasa Intraabdominal/metabolismo , Lectinas/sangre , Adulto , Índice de Masa Corporal , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/inmunología , Femenino , Proteínas Ligadas a GPI/sangre , Perfilación de la Expresión Génica/métodos , Humanos , FN-kappa B , Embarazo , ARN Mensajero/análisis , Factores de Riesgo , Transducción de SeñalRESUMEN
BACKGROUND: NCBI Taxonomy is the main taxonomic source for several bioinformatics tools and databases since all organisms with sequence accessions deposited on INSDC are organized in its hierarchical structure. Despite the extensive use and application of this data source, an alternative representation of data as a table would facilitate the use of information for processing bioinformatics data. To do so, since some taxonomic-ranks are missing in some lineages, an algorithm might propose provisional names for all taxonomic-ranks. RESULTS: To address this issue, we developed an algorithm that takes the tree structure from NCBI Taxonomy and generates a hierarchically complete taxonomic table, maintaining its compatibility with the original tree. The procedures performed by the algorithm consist of attempting to assign a taxonomic-rank to an existing clade or "no rank" node when possible, using its name as part of the created taxonomic-rank name (e.g. Ord_Ornithischia) or interpolating parent nodes when needed (e.g. Cla_of_Ornithischia), both examples given for the dinosaur Brachylophosaurus lineage. The new hierarchical structure was named Taxallnomy because it contains names for all taxonomic-ranks, and it contains 41 hierarchical levels corresponding to the 41 taxonomic-ranks currently found in the NCBI Taxonomy database. From Taxallnomy, users can obtain the complete taxonomic lineage with 41 nodes of all taxa available in the NCBI Taxonomy database, without any hazard to the original tree information. In this work, we demonstrate its applicability by embedding taxonomic information of a specified rank into a phylogenetic tree and by producing metagenomics profiles. CONCLUSION: Taxallnomy applies to any bioinformatics analyses that depend on the information from NCBI Taxonomy. Taxallnomy is updated periodically but with a distributed PERL script users can generate it locally using NCBI Taxonomy as input. All Taxallnomy resources are available at http://bioinfo.icb.ufmg.br/taxallnomy .
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Bases de Datos Genéticas , Metagenómica , Biología Computacional , Almacenamiento y Recuperación de la Información , FilogeniaRESUMEN
AIM: To analyse the safety and efficacy parameters of endovascular treatment of anterior communicating artery (ACoA) aneurysms, according to their morphological considerations and three-dimensional orientation in a multicentric registry. MATERIALS AND METHODS: A retrospective analysis was undertaken of a prospective database of consecutive patients that underwent endovascular embolisation for ACoA aneurysm in four high-volume neuroradiology interventional departments. The study has been registered in ClinicalTrial.gov. Data were collected regarding the clinico-demographic variables of the patients, anatomical variations of the circle of Willis, morphological considerations and spatial orientation of ACoA aneurysms were recorded. Safety and efficacy variables were also recorded. Associations between anatomical variations of the circle of Willis, morphological considerations, and spatial orientation of the ACoA aneurysms and safety and efficacy variables were assessed. RESULTS: Data from 122 consecutive patients were collected in the MACAARET study (mean age (±SD) was 55 (±14) and 50.8% (62/122) were male). One hundred and five patients (86.1%) presented with subarachnoid haemorrhage (SAH). ACoA aneurysms with a neck size of >4 mm had less chance of having successful endovascular treatment than those of ≤4 mm (19.8% versus 46.7%; p=0.002) and were also more likely to recanalise during follow-up (61.5% versus 19.5%; p=0.003). Moreover, ACoA aneurysms with an aspect ratio of >1.7 had more chance of having immediate therapeutic success than those with a ratio of ≤1.7 (70.7% versus 44.8%; p=0.012). There were no other associations between the anatomical variables of the ACoA aneurysms and the safety-efficacy variables. CONCLUSION: ACoA aneurysms are suitable for both endovascular and microsurgical approaches, but more data are required to determine which is the best approach regarding the morphological and spatial orientation of the aneurysm and the anatomical variations of the circle of Willis.
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Arteria Cerebral Anterior/diagnóstico por imagen , Arteria Cerebral Anterior/cirugía , Procedimientos Endovasculares/métodos , Aneurisma Intracraneal/cirugía , Sistema de Registros , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: The definition of severe uncontrolled asthma and the best phenotype-driven management are not fully established. Objective: We aimed to reach a consensus on the definition of severe uncontrolled asthma and give recommendations on optimal management with phenotype-targeted biological therapies. METHODS: A modified Delphi technique was used. A scientific committee provided statements addressing the definition of severe uncontrolled asthma and controversial issues about its treatment with biologics. The questionnaire was evaluated in 2 rounds by expert allergists. With the results, the scientific committee developed recommendations and a practical algorithm. RESULTS: A panel of 27 allergists reached agreement on 27 out of the 29 items provided (93.1%). A consensus definition of severe uncontrolled asthma was agreed. Prior to initiation of therapy, it is mandatory to establish the asthma phenotype and assess the presence of clinically important allergic sensitizations. Anti-IgE, anti-IL-5, anti-IL-5 receptor, and anti-IL-13/IL-4 receptor inhibitors are suitable options for patients with allergic asthma and a blood eosinophil level >300/µL (>150/µL in patients receiving oral corticosteroids). IL-5 and anti-IL-5 receptor inhibitors are recommended for patients with an eosinophilic phenotype and can also be used for patients with severe eosinophilic allergic asthma with no or a suboptimal response to omalizumab. Dupilumab is recommended for patients with moderate-severe asthma and a TH2-high phenotype. Only physicians with experience in the treatment of severe uncontrolled asthma should initiate biological treatment. CONCLUSION: We provide consensus clinical recommendations that may be useful in the management of patients with severe uncontrolled asthma.
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Asma/diagnóstico , Terapia Biológica/métodos , Eosinófilos/inmunología , Células Th2/inmunología , Asma/terapia , Consenso , Progresión de la Enfermedad , Directrices para la Planificación en Salud , Humanos , Inmunización , Inmunoglobulina E/metabolismo , Fenotipo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.
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COVID-19 , Salud Laboral , Seguridad del Paciente , Hipersensibilidad Respiratoria/fisiopatología , Sistema Respiratorio/fisiopatología , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/transmisión , Personal de Salud , Humanos , Tamizaje Masivo , Pruebas de Función Respiratoria , VentilaciónRESUMEN
Summary: Background. We assessed differences in allergic sensitization and clinical characteristics in a foreign-born population. Methods. Prospective, observational, descriptive study of patients aged > 12 years who were seen at the Department of Allergy, La Paz Hospital (Madrid, Spain), between January 2017 and December 2018. Patients were classified by geographical origin and ethnicity. Results. We included 150 patients (110 female) with a mean age of 38.38 years. Mean time to onset of respiratory symptoms after immigration was 8.47 years. Significant differences were observed between ethnic groups (p = 0.007). The most frequent sensitization was to grass pollen (75.2%), which was more common in South American patients (p = 0.005). We found that 59% of patients were sensitized to Cupressus and Olea pollen (higher in Asian patients, p = 0.032 and p = 0.049). Conclusions. Allergic sensitization in the foreign-born population was similar to that of the autochthonous population although differences between the groups were identified.
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Alérgenos , Hipersensibilidad , Adulto , Pueblo Asiatico , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/epidemiología , Polen/inmunología , Estudios ProspectivosRESUMEN
Two-dimensional melting is one of the most fascinating and poorly understood phase transitions in nature. Theoretical investigations often point to a two-step melting scenario involving unbinding of topological defects at two distinct temperatures. Here, we report on a novel melting transition of a charge-ordered K-Sn alloy monolayer on a silicon substrate. Melting starts with short-range positional fluctuations in the K sublattice while maintaining long-range order, followed by longer-range K diffusion over small domains, and ultimately resulting in a molten sublattice. Concomitantly, the charge order of the Sn host lattice collapses in a multistep process with both displacive and order-disorder transition characteristics. Our combined experimental and theoretical analysis provides a rare insight into the atomistic processes of a multistep melting transition of a two-dimensional materials system.
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The immune response of teleosts (bonefish) is altered by diazinon (DZN), an organophosphate pesticide. It has been suggested that such alteration is due to the extraneuronal cholinergic system in fish leukocytes that renders these cells a target of pesticides. Diazoxon (DZO), the oxon metabolite of DZN, has been attributed immunotoxic effects. Still, to date there are no reports on the effects of DZO upon parameters involved in the signaling cascade of immune response cells. Therefore, this work evaluated the effect of DZO on key parameters of cell signaling (intracellular Ca2+ flux, ERK 1/2 phosphorylation), cell proliferation, and antiproliferative processes (apoptosis, senescence, mitochondrial membrane potential) in spleen mononuclear cells of Nile tilapia fish. The results obtained show that DZO does not affect cell proliferation but causes a lack of response to stimulation with PMA and ionomycin to release intracellular calcium. In addition, it inhibits ERK 1/2 phosphorylation and causes loss of mitochondrial membrane potential, apoptosis, and senescence. These results suggest that the lack of cell response to release intracytoplasmic Ca2+ inhibits ERK which disrupts the mitochondrial membrane potential, leading to cell apoptosis and senescence. These findings prove that DZO significantly affects key parameters involved in the survival of immune response cells.