Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Improvements in the learnability of smartphone haptic interfaces for visually impaired users.

We report the results of a study on the learnability of haptic icons used as alerts or notifications in smartphones. The aim was to explore the feasibility of using haptic icons to create assistive technologies for people with visual impairments. We compared the performance and satisfaction of users with different visual capacities (visually impaired vs. sighted) and using different learning processes (with or without a reinforcement learning stage). The reinforcement learning stage improves the recognition rate in both types of users, although the improvement obtained by the visually impaired users is even better as their recognition rates become very similar to those obtained by the sighted users. Finally, it was observed that the better recognized haptic icons are those assigned to the most employed applications by the user.

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy.

Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease.

Immunologic responses to the major allergen of Olea europaea in local and systemic allergic rhinitis subjects.

OBJECTIVE: To evaluate the in vivo and in vitro responses to nOle e 1 in allergic rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree pollen (OL) confirmed by nasal allergen provocation test (NAPT). METHODS: Twelve subjects with AR, 12 with LAR and 12 subjects as control group (CG) were selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic cationic protein (ECP) and tryptase were measured in nasal lavages before and after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation studies were carried out. RESULTS: All AR (12/12) and 10/12 (83%) of LAR had a +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%); 8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019 and P = 0.001, respectively). CONCLUSION: Both AR and LAR had a similar in vivo response to nOle e 1 with release of inflammatory mediators. Specific basophil activation with OL and nOle e 1 was observed in LAR confirming previous data obtained with dust mites.

Caso 4. Aneurisma sacular postestenosis del istmo aórtico en un adulto / Case 4. Post-stenosis saccular aneurysm of the aortic isthmus in an adult

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Solución del caso 4. Aneurisma sacular postestenosis del istmo aórtico en un adulto / Solution of case 4. Post-stenosis saccular aneurysm of the aortic isthmus in an adult

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Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study.

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP-LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats

There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHRSNP-ΔHRPHE/ΔMAPSNP-ΔMAPPHE))-0.4-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.

An improved strategy for evaluating the extent of chronic arterial baroreceptor denervation in conscious rats.

There is no index or criterion of aortic barodenervation, nor can we differentiate among rats that have suffered chronic sham, aortic or sino-aortic denervation. The objective of this study was to develop a procedure to generate at least one quantitative, reproducible and validated index that precisely evaluates the extent of chronic arterial barodenervation performed in conscious rats. Data from 79 conscious male Wistar rats of about 65-70 days of age with diverse extents of chronic arterial barodenervation and used in previous experiments were reanalyzed. The mean arterial pressure (MAP) and the heart rate (HR) of all rats were measured systematically before (over 1 h) and after three consecutive iv bolus injections of phenylephrine (PHE) and sodium nitroprusside (SNP). Four expressions of the effectiveness of barodenervation (MAP lability, PHE ratio, SNP ratio, and SNP-PHE slope) were assessed with linear fixed models, three-level average variance, average separation among levels, outlier box plot analysis, and overlapping graphic analysis. The analysis indicated that a) neither MAP lability nor SNP-PHE slope was affected by the level of chronic sodium intake; b) even though the Box-Cox transformations of both MAP lability [transformed lability index (TLI)] and SNP-PHE slope [transformed general sensitivity index (TGSI), {((3-(ΔHR(SNP)-ΔHR(PHE)/ΔMAP(SNP)-ΔMAP(PHE)))(-0.4)-1)/-0.04597}] could be two promising indexes, TGSI proved to be the best index; c) TLI and TGSI were not freely interchangeable indexes for this purpose. TGSI ranges that permit differentiation between sham (10.09 to 11.46), aortic (8.40 to 9.94) and sino-aortic (7.68 to 8.24) barodenervated conscious rats were defined.

A needleless closed system device (CLAVE) protects from intravascular catheter tip and hub colonization: a prospective randomized study.

Hub colonization and subsequent intraluminal progression due to frequent opening and manipulation of intravenous systems is the cause of many catheter-related infections (CRI). A prospective, comparative, randomized study was performed to assess a new closed-needleless hub device (CLAVE) compared with conventional open systems (COS). End-points were hub and skin colonization, catheter tip colonization, catheter-related bloodstream infection (CRBSI) and number of accidental needlesticks. All cultures were processed following standard semiquantitative microbiological techniques. The study involved patients who underwent heart surgery over an 11-month period in a post-surgical ICU. During the study period, 352 patients underwent major heart surgery and 1774 catheters were inserted. Overall, 865 catheters in 178 patients were allocated to the CLAVE system and 909 catheters in 174 patients to COS. The groups were similar regarding underlying conditions and risk factors for infection. Comparison of endpoint results in CLAVE and COS groups was as follows: incidence density per 1000 catheter-days of tip colonization: 59.2 versus 83.6 (P=0.003); of hub colonization: 7.56 versus 24.66 (P=0.0017); of skin colonization: 41.5 versus 58.9 (P=0.038); and of CRBSI 3.78 versus 5.89 (P=0.4). There was one accidental needlestick and one catheter-related prosthetic endocarditis in the COS group. Multivariate analysis showed that CLAVE use was an independent protective factor for tip colonization. CLAVE offered significant protection from catheter-tip and hub colonization.

Consumo de MDMA (extasis) en estudiantes de secundaria / MDMA (ecstasy) consumption in secondary school students

Objetivos: Describir la prevalencia de consumo de MDMA y el perfil toxicológico y psicológico en una muestra de estudiantes de secundaria.Sujetos y Método: Durante el curso académico 1998-99 se evaluó una muestra compuesta por 2.862 jóvenes de ambos sexos [edad media (SD): 15.87 (1.48); 50.6 por ciento hombres], estudiantes de secundaria de Oviedo (Asturias) Evaluación: Cuestionario de la OMS de consumo de alcohol y drogas, cuestionario de personalidad de Eysenck versión adultos (EPQ-A) y, la escala de búsqueda de sensaciones de Zuckerman (EBS).Resultados: Las prevalencias vida, último año y último mes, de consumo de MDMA fueron 3.8 por ciento, 2.7 por ciento y 1.6 por ciento, ocupando la MDMA la 7ª posición entre las drogas ilegales consumidas alguna vez. Los hombres mostraron mayores prevalencias de consumo, vida, último año y último mes, que las mujeres (p< .05). Comparados con los estudiantes que nunca han consumido MDMA (pero que pueden haber consumido otras drogas ilegales), los usuarios de MDMA refieren una historia más extensa de uso de drogas. La MDMA es, tras la heroína, la droga asociada a un mayor índice de policonsumo. Los jóvenes que han usado MDMA alguna vez obtuvieron puntuaciones más elevadas en la subescala de psicoticismo del EPQ-A y refirieron niveles más elevados de búsqueda de sensaciones.Conclusiones: Los consumidores de MDMA son policonsumidores de otras sustancias legales e ilegales. Aquellos que consumen MDMA tienen un perfil psicológico diferente, caracterizado por elevados niveles de búsqueda de sensaciones y psicoticismo. (AU)

[Severe chronic ischemic ventricular dysfunction. Determinants of surgical risk and long-term clinical outcome]. / Disfunción ventricular isquémica crónica severa. Determinantes del riesgo quirúrgico y del resultado clínico a largo plazo.

INTRODUCTION: In patients with chronic ischemic heart disease, a severe ventricular dysfunction is associated with a higher operative risk and to a worse late clinical outcome. However, when there is sufficient viable myocardium, surgical revascularization can improve ventricular performance and above all the functional capacity and survival of these patients. OBJECTIVES: To analyze long-term results of a large series of patients with an ejection fraction < or = 0.30 that underwent isolated coronary artery bypass surgery and to investigate factors, mainly clinical, that determined favorable clinical results: being that the patient was alive and free of incapacitating symptoms. PATIENTS AND METHODS: This series included 100 patients, 93 males and 7 females, with a mean age of 62 +/- 8 years. The predominant clinical manifestation was angina in 37, congestive heart failure in 22 and both in 41. Seventy-nine patients were in functional class III or IV, and 19 had emergency surgery. RESULTS: There were 10 in-hospital deaths, 6 of which occurred in patients who had emergency surgery. Mortality in the elective cases was 4.9%. Only age (p < 0.05), functional class (p < 0.05) and emergency surgery (p < 0.0001) were identified as independent predictors of early mortality. Actuarial survival rates after 5 and 8 years were 65 and 52% respectively. Long-term clinical outcome was considered favorable in 66 patients. We did not find any preoperative clinical variables that were predictors of the clinical outcome. Only preoperative mitral insufficiency correlated with a poor long-term clinical result. CONCLUSIONS: Patients with chronic and severe ventricular dysfunction secondary to coronary artery disease have an acceptable surgical risk when they are operated on electively, before their clinical condition deteriorates. Long-term results are satisfactory in the majority of the patients. In these types of patients clinical manifestations are of limited value in the selection process for surgical revascularization.

The presence and cytotoxicity of CD16+ CD2- subset from PBL and NK cells in long-term IL-2 cultures enhanced by Prothymosin-alpha.

The aim of this study was to characterize the LAK cell subpopulation on which Prothymosin-alpha (ProT alpha) exerts its enhancing effect on cytotoxicity. We investigated the role of ProT alpha on LAK induction from peripheral blood lymphocytes (PBL) and NK-enriched cells, both cultured for 5 weeks with IL-2 and ProT alpha. The different cultures were separated into several subsets throughout the culture time using two color fluorescence activated cell sorting (FACS) and CD56, CD16, CD2 and CD8 monoclonal antibodies. Each cell subset was then tested for cytotoxicity against K562 and Daudi cells. The CD16+ CD2- subset from both, PBL and NK-enriched cells, was the only subset on which ProT alpha had an effect, significantly enhancing this subpopulation. Within the CD16 population, the cells CD16+ CD2+ were the most cytotoxic, although CD16+ CD2- cells were also cytotoxic. ProT alpha only potentiated the cytotoxicity of CD16+ CD2- subset significantly, with 29% and 41% for K562 and Daudi cells, respectively.