Influence of Pore Size in Protein G'-Grafted Mesoporous Silica Nanoparticles as a Serum Pretreatment System for In Vitro Allergy Diagnosis.

Particles with the capacity to bind to immunoglobulin G (IgG) can be used for the purification of IgG or to process clinical samples for diagnostic purposes. For in vitro allergy diagnosis, the high IgG levels in serum can interfere with the detection of allergen-specific IgE, the main diagnostic biomarker. Although commercially available, current materials present a low IgG capture capacity at large IgG concentrations or require complex protocols, preventing their use in the clinic. In this work, mesoporous silica nanoparticles are prepared with different pore sizes, to which IgG-binding protein G' is grafted. It is found that for one particular optimal pore size, the IgG capture capacity of the material is greatly enhanced. The capacity of this material to efficiently capture human IgG in a selective way (compared to IgE) is demonstrated in both solutions of known IgG concentrations as well as in complex samples, like serum, from healthy controls and allergic patients using a simple and fast incubation protocol. Interestingly, IgG removal using the best-performing material enhances in vitro IgE detection in sera from patients allergic to amoxicillin. These results highlight the great translation potential of this strategy to the clinic in the context of in vitro allergy diagnosis.

Sequential class switch recombination to IgE and allergen-induced accumulation of IgE+ plasmablasts occur in the nasal mucosa of local allergic rhinitis patients.

BACKGROUND: The involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients. METHODS: Nine LAR, 5 allergic rhinitis (AR), and 5 non-atopic healthy control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera. RESULTS: NAC-DP induced an increase in IgE+ CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR, and 0% of HC subjects. NAC-DP increased the proportion of peripheral CD19+ CD20+ CD38+ plasmablasts in AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+ CD20+ CD38+ plasmablasts from LAR, AR, and HC individuals was 7%, 5%, and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+ CD20+ CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP-sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 33%, 100%, and 0% of LAR, AR, and HC subjects, respectively. CONCLUSION: These results suggest that allergen exposure induces the sequential εCSR of IgG+ CD19+ CD20+ CD38+ plasmablasts in the nasal mucosa of LAR patients.

Lack of Major Involvement of Common CYP2C Gene Polymorphisms in the Risk of Developing Cross-Hypersensitivity to NSAIDs.

Cross-hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a relatively common, non-allergic, adverse drug event triggered by two or more chemically unrelated NSAIDs. Current evidence point to COX-1 inhibition as one of the main factors in its etiopathogenesis. Evidence also suggests that the risk is dose-dependent. Therefore it could be speculated that individuals with impaired NSAID biodisposition might be at increased risk of developing cross-hypersensitivity to NSAIDs. We analyzed common functional gene variants for CYP2C8, CYP2C9, and CYP2C19 in a large cohort composed of 499 patients with cross-hypersensitivity to NSAIDs and 624 healthy individuals who tolerated NSAIDs. Patients were analyzed as a whole group and subdivided in three groups according to the main enzymes involved in the metabolism of the culprit drugs as follows: CYP2C9, aceclofenac, indomethacin, naproxen, piroxicam, meloxicam, lornoxicam, and celecoxib; CYP2C8 plus CYP2C9, ibuprofen and diclofenac; CYP2C19 plus CYP2C9, metamizole. Genotype calls ranged from 94 to 99%. No statistically significant differences between patients and controls were identified in this study, either for allele frequencies, diplotypes, or inferred phenotypes. After patient stratification according to the enzymes involved in the metabolism of the culprit drugs, or according to the clinical presentation of the hypersensitivity reaction, we identified weak significant associations of a lower frequency (as compared to that of control subjects) of CYP2C8*3/*3 genotypes in patients receiving NSAIDs that are predominantly CYP2C9 substrates, and in patients with NSAIDs-exacerbated cutaneous disease. However, these associations lost significance after False Discovery Rate correction for multiple comparisons. Taking together these findings and the statistical power of this cohort, we conclude that there is no evidence of a major implication of the major functional CYP2C polymorphisms analyzed in this study and the risk of developing cross-hypersensitivity to NSAIDs. This argues against the hypothesis of a dose-dependent COX-1 inhibition as the main underlying mechanism for this adverse drug event and suggests that pre-emptive genotyping aiming at drug selection should have a low practical utility for cross-hypersensitivity to NSAIDs.

Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug-Induced Acute Urticaria/Angioedema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity reactions, probably due to their high consumption worldwide. The most frequent type of NSAID hypersensitivity is NSAID cross-hypersensitivity, in which patients react to NSAIDs from different chemical groups in the absence of a specific immunological response. The underlying mechanism of NSAID cross-hypersensitivity has been linked to cyclooxygenase (COX)-1 inhibition causing an imbalance in the arachidonic acid pathway. Despite NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype, most studies have focused on NSAID-exacerbated respiratory disease. As NSAID cross-hypersensitivity reactions are idiosyncratic, only appearing in some subjects, it is believed that individual susceptibility is under the influence of genetic factors. Although associations with polymorphisms in genes from the AA pathway have been described, no previous study has evaluated the potential role of cytosolic phospholipase A2 (cPLA2) variants. This enzyme catalyzes the initial hydrolysis of membrane phospholipids to release AA, which can be subsequently metabolized into eicosanoids. Here, we analyzed for the first time the overall genetic variation in the cPLA2 gene (PLA2G4A) in NIUA patients. For this purpose, a set of tagging single nucleotide polymorphisms (tagSNPs) in PLA2G4A were selected using data from Europeans subjects in the 1,000 Genomes Project, and genotyped with the iPlex Sequenom MassArray technology. Two independent populations, each comprising NIUA patients and NSAID-tolerant controls, were recruited in Spain, for the purposes of discovery and replication, comprising a total of 1,128 individuals. Fifty-eight tagSNPs were successfully genotyped in the discovery cohort, of which four were significantly associated with NIUA after Bonferroni correction (rs2049963, rs2064471, rs12088010, and rs12746200). These polymorphisms were then genotyped in the replication cohort: rs2049963 was associated with increased risk for NIUA after Bonferroni correction under the dominant and additive models, whereas rs12088010 and rs12746200 were protective under these two inheritance models. Our results suggest a role for PLA2G4A polymorphisms in NIUA. However, further studies are required to replicate our findings, elucidate the mechanistic role, and evaluate the participation of PLA2G4A variants in other phenotypes induced by NSAID cross-hypersensitivity.

Effectiveness of e-Health cardiac rehabilitation program on quality of life associated with symptoms of anxiety and depression in moderate-risk patients.

Exploring new models of medical care requires evaluating the impact of new care strategies not only on physiological parameters but also on the quality of life of the patient. On the other hand the presence of anxiety together with depression requires further consideration when planning appropriate management strategies. The aim of this study was to examine the effectiveness of a home-based cardiac rehabilitation program incorporating an e-Health technology on health-related quality of life associated with symptoms of anxiety and depression in moderate-risk patients. A multicenter, randomized controlled clinical trial was designed to compare a traditional hospital based cardiac rehabilitation program (n = 38, 35 male) with a mixed home surveillance program where patients exercised at home with a remote electrocardiographic monitoring device (n = 33, 31 male). The Short Form-36 (SF-36) Health Survey and the Goldberg questionnaire were used to evaluate quality of life and the presence of symptoms of anxiety and depression respectively. The results of this study show that the type of cardiac rehabilitation program did not influence the improvement in quality of life (p = 0.854), but the presence of symptoms of anxiety and depression did (p = 0.001). Although both programs achieved a decrease in anxiety and depression symptoms and improved functional capacity (p ≤ 0.001), a significant interaction effect was found between the group with or without anxiety and depression symptoms and the type of program in the bodily pain dimension (p = 0.021). Trial registration: Retrospectively registered NCT02796404 (10/06/2016) in clinialtrials.gov.

Deep sequencing of prostaglandin-endoperoxide synthase (PTGE) genes reveals genetic susceptibility for cross-reactive hypersensitivity to NSAID.

BACKGROUND AND PURPOSE: Cross-reactive hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is a relatively common adverse drug event caused by two or more chemically unrelated drugs and that is attributed to inhibition of the COX activity, particularly COX-1. Several studies investigated variations in the genes coding for COX enzymes as potential risk factors. However, these studies only interrogated a few single nucleotide variations (SNVs), leaving untested most of the gene sequence. EXPERIMENTAL APPROACH: In this study, we analysed the whole sequence of the prostaglandin-endoperoxide synthase genes, PTGS1 and PTGS2, including all exons, exon-intron boundaries and both the 5' and 3' flanking regions in patients with cross-reactive hypersensitivity to NSAIDs and healthy controls. After sequencing analysis in 100 case-control pairs, we replicated the findings in 540 case-control pairs. Also, we analysed copy number variations for both PTGS genes. KEY RESULTS: The most salient finding was the presence of two PTGS1 single nucleotide variations, which are significantly more frequent in patients than in control subjects. Patients carrying these single nucleotide variations displayed a significantly and markedly lower COX-1 activity as compared to non-carriers for both heterozygous and homozygous patients. CONCLUSION AND IMPLICATIONS: Although the risk single nucleotide variations are present in a small proportion of patients, the strong association observed and the functional effect of these single nucleotide variations raise the hypothesis of genetic susceptibility to develop cross-reactive NSAID hypersensitivity in individuals with an impairment in COX-1 enzyme activity.

Componentes biosociales y enfermedades prevalentes de la infancia en menores de 5 años del Bañado Sur de Asunción / Biosocial components and prevalent childhood diseases in children under 5 years from the Bañado Sur of Asunción

Introducción: Las enfermedades prevalentes de la infancia en condiciones adversas como la pobreza pueden ser graves o mortales. La Atención Integrada a las Enfermedades Prevalentes de la Infancia (AIEPI) aborda los determinantes sociales de la salud. Objetivo: Conocer las enfermedades prevalentes y las condiciones ambientales de menores de 5 años del Bañado Sur aplicando AIEPI. Metodología: Estudio observacional, descriptivo, transversal, muestreo no probabilístico por cuotas en 4 barrios del Bañado Sur, mediante visitas semanales a 23 hogares (2016-2017). Se interpretó y clasificó la condición de salud según AIEPI (rojo grave, amarillo moderada, verde buena). La participación fue voluntaria, considerándose recomendaciones éticas para investigaciones en contextos vulnerables. La muestra seleccionada no es representativa de toda la población de niños bañadenses. Resultados: 42 menores de 5 años (26 niñas, 16 niños). 71% clasificó rojo y amarillo en simultáneo (por antecedentes y/o hallazgos). De 4 (<2 meses), 1 clasificó rojo y amarillo (diarrea con sangre); 1, amarillo (bajo peso, problemas de alimentación, infecciones, anemia); 2, verde. De 38 niños/as (>2 meses

Introduction: Prevalent childhood diseases in adverse conditions such as poverty can be serious or fatal. Integrated Management of Childhood Illness (IMCI) addresses the social determinants of health. Objective: Know the prevalent diseases and environmental conditions of children under 5 years old from Bañado Sur applying IMCI. Methodology: Observational, descriptive, cross-sectional study, non-probabilistic sampling by quotas in 4 neighborhoods of the Bañado Sur, through weekly visits to 23 households (2016-2017). The health condition was interpreted and classified according to IMCI (severe red, moderate yellow, good green). Participation was voluntary, considering ethical recommendations for research in vulnerable contexts. The selected sample is not representative of the entire population of children from the Bañado. Results: 42 children under 5 years (26 girls, 16 boys). 71% classified red and yellow simultaneously (by background and/or findings). From 4 (<2 months), one classified red and yellow (bloody diarrhea); other, yellow (low weight, nutrition problems, infections, anemia); two, green. Of 38 children (> 2 months <5 years) 55% classified red and yellow; 29% yellow; 16%, green. Of the red, 54% registered severe respiratory conditions; 21%, malnutrition and anemia; 10%, diarrhea with severe dehydration. Developmental surveillance: 1 classified red (hearing loss, language delay); 5, yellow per alert (absence of age skills); 36, yellow for normal development with risk factors such as low schooling of mothers, violence, polluted environment, overcrowding, and poverty. None of them classified green in all its dimensions. Protective factors: stable caregiver, breastfeeding in the first years. Conclusion: The prevalent childhood diseases in children of the Bañado Sur acquire a serious and repetitive character; its socio-environmental conditions are negative. Comprehensive and cross-sector public policies are urgently needed, such as Primary Health Care. IMCI is particularly recommended in its community component. Key Words: Integrated Care for Prevalent Diseases of Children, poverty, social determinants of health

Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most highly consumed drugs worldwide and the main triggers of drug hypersensitivity reactions. The most frequent reaction, named cross-reactive NSAID-hypersensitivity, is due to the pharmacological activity of these drugs by blocking the cyclooxygenase-1 enzyme. Such inhibition leads to cysteinyl-leukotriene synthesis, mainly LTE4, which are responsible for the reaction. Although the complete molecular picture of the underlying mechanisms remains elusive, the participation of platelet-adherent leukocytes (CD61+) and integrins have been described for NSAID-exacerbated respiratory disease (NERD). However, there is a lack of information concerning NSAID-induced urticaria/angioedema (NIUA), by far the most frequent clinical phenotype. Here we have evaluated the potential role of CD61+ leukocytes and integrins (CD18, CD11a, CD11b, and CD11c) in patients with NIUA, and included the other two phenotypes with cutaneous involvement, NSAID-exacerbated cutaneous disease (NECD) and blended reactions (simultaneous skin and airways involvement). A group NSAID-tolerant individuals was also included. During the acute phase of the reaction, the three clinical phenotypes showed increased frequencies of CD61+ neutrophils, eosinophils, and monocytes compared to controls, which correlated with urinary LTE4 levels. However, no correlation was found between these variables at basal state. Furthermore, increased expressions of CD18 and CD11a were found in the three CD61+ leukocytes subsets in NIUA, NECD and blended reactions during the acute phase when compared with CD61-leukocyte subpopulations. During the acute phase, CD61+ neutrophils, eosinophils and monocytes showed increased CD18 and CD11a expression when compared with CD61+ leukocytes at basal state. No differences were found when comparing controls and CD61+ leukocytes at basal state. Our results support the participation of platelet-adherent leukocytes and integrins in cutaneous cross-hypersensitivity to NSAIDs and provide a link between these cells and arachidonic acid metabolism. Our findings also suggest that these reactions do not involve a systemic imbalance in the frequency of CD61+ cells/integrin expression or levels of LTE4, which represents a substantial difference to NERD. Although further studies are needed, our results shed light on the molecular basis of cutaneous cross-reactive NSAID-hypersensitivity, providing potential targets for therapy through the inhibition of platelet-leukocyte interactions.

An Update on the Immunological, Metabolic and Genetic Mechanisms in Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) represent a major burden on the healthcare system since their diagnostic and management are complex. As they can be influenced by individual genetic background, it is conceivable that the identification of variants in genes potentially involved could be used in genetic testing for the prevention of adverse effects during drug administration. Most genetic studies on severe DHRs have documented HLA alleles as risk factors and some mechanistic models support these associations, which try to shed light on the interaction between drugs and the immune system during lymphocyte presentation. In this sense, drugs are small molecules that behave as haptens, and currently three hypotheses try to explain how they interact with the immune system to induce DHRs: the hapten hypothesis, the direct pharmacological interaction of drugs with immune receptors hypothesis (p-i concept), and the altered self-peptide repertoire hypothesis. The interaction will depend on the nature of the drug and its reactivity, the metabolites generated and the specific HLA alleles. However, there is still a need of a better understanding of the different aspects related to the immunological mechanism, the drug determinants that are finally presented as well as the genetic factors for increasing the risk of suffering DHRs. Most available information on the predictive capacity of genetic testing refers to abacavir hypersensitivity and anticonvulsants-induced severe cutaneous reactions. Better understanding of the underlying mechanisms of DHRs will help us to identify the drugs likely to induce DHRs and to manage patients at risk.

Eicosanoid mediator profiles in different phenotypes of nonsteroidal anti-inflammatory drug-induced urticaria.

BACKGROUND: The role of arachidonic acid metabolites in NSAID-induced hypersensitivity has been studied in depth for NSAID-exacerbated respiratory disease (NERD) and NSAID-exacerbated cutaneous disease (NECD). However, no information is available for NSAID-induced urticarial/angioedema (NIUA), despite it being the most frequent clinical entity induced by NSAID hypersensitivity. We evaluated changes in leukotriene and prostaglandin metabolites for NIUA patients, using patients with NECD and single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) for comparison. METHODS: Urine samples were taken from patients with confirmed NSAID-induced urticaria and healthy controls, at baseline and at various time intervals after ASA administration. Eicosanoid measurement was performed using high-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. RESULTS: No differences were found between groups at baseline. Following ASA administration, LTE4 and 9α,11ß-PGF2 levels were increased in both NIUA and NECD patients compared to baseline, rising initially, before decreasing toward initial levels. In addition, the levels of these metabolites were higher in NIUA and NECD when compared with the SNIUAA and control groups after ASA administration. No changes were found with respect to baseline values for SNIUAA and control groups. CONCLUSIONS: We present for the first time data regarding the role of COX-1 inhibition in NIUA. Patients with this entity show a similar pattern eicosanoid levels following ASA challenge to those with NECD. Further studies will help ascertain the cell populations involved and the underlying molecular mechanisms.

Polymorphisms in CEP68 gene associated with risk of immediate selective reactions to non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions. Such reactions can be pharmacologically or immunologically mediated, but in both cases individual susceptibility can be influenced by genetic factors. Polymorphisms in centrosomal protein of 68 kDa (CEP68) have been associated with pharmacologically mediated NSAIDs reactions. Here, we evaluated this gene in immunologically mediated single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) by analyzing 52 single nucleotide polymorphisms in CEP68 in 176 patients and 363 NSAIDs-tolerant controls. Two intronic variants (rs2241160 and rs2241161) were significantly associated with an increased risk of SNIUAA, suggesting CEP68 to be a key player in both types of NSAIDs hypersensitivity. However, we found no overlap with genetic variants previously associated with pharmacologically mediated hypersensitivity, pointing to a complex role for this gene and its potential use in the development of biomarkers of clinical utility to diagnose patients at risk of these reactions and to differentiate entities.

Infecciones respiratorias virales en pacientes hospitalizados en una unidad de cuidados intensivos neonatales / Viral respiratory infections in hospitalized patients in a neonatal intensive care unit

Introducción: Las infecciones respiratorias virales constituyen una problemática nacional y las unidades de cuidados intensivos neonatales, no están exentas de estas. Objetivo: Describir la frecuencia y características clínicas de las infecciones respiratorias virales en neonatos internados en un servicio de Neonatología durante el periodo de enero 2017 a octubre 2018. Materiales y Métodos: Estudio observacional, descriptivo, retrospectivo. Fueron analizadas historias clínicas de pacientes hospitalizados en la unidad de cuidados intensivos neonatales, que tuvieron diagnóstico de infecciones respiratorias de origen viral, el método de diagnóstico fue inmunofluorescencia directa, inmunocromatografía y PCR en tiempo real. Se excluyeron pacientes que procedan de otro servicio y hayan iniciado los síntomas antes del ingreso a nuestro centro. Variables: edad gestacional, edad posnatal, peso de nacimiento, síntomas, tipo de virus, prescripción de antibióticos. Los datos fueron analizados con Excel, utilizando estadísticas descriptivas. Resultados: De los 761 pacientes, 65 pacientes presentaron diagnóstico de infección respiratoria viral: frecuencia del 8,5%. EL promedio de edad fue de 17±10 días El método de diagnóstico más frecuente fue inmunofluorescencia 92%, Los síntomas más comunes fueron las secreciones respiratorias (74%) y desaturaciones (64%); Los virus más frecuentes fueron: Sincitial Respiratorio 26%, Influenza B 25%, Influenza A en un 18%. El 66% requirió tratamiento de soporte respiratorio. Un paciente falleció por causas no relacionadas a la infección respiratoria viral. Conclusiones: La frecuencia de infecciones virales fue del 8,5%. Los virus más frecuentes fueron VSR e influenza B. Más de la mitad necesitaron soporte respiratorio. Ningún paciente falleció.

Introduction: Viral respiratory infections are a national problem and neonatal intensive care units are not exempt from these infections. Objective: To describe the frequency and clinical characteristics of viral respiratory infections in newborns admitted to a Neonatology unit during january 2017 to october 2018 timeframe. Materials and Methods: This was an observational, descriptive and retrospective study. We reviewed the clinical records of patients admitted to the neonatal intensive care unit who were also diagnosed with a viral respiratory infection. To determine the etiology, we used direct immunofluorescence, immunochromatography and real-time PCR. Patients who were transferred from another service and whose symptoms began prior to transfer to our unit were excluded. Variables: gestational age, postnatal age, birth weight, symptoms, type of virus, antibiotic prescription. Data were analyzed with Excel, using descriptive statistics. Results: Of the 761 patients, 65 patients were diagnosed with a viral respiratory infection, a frequency of 8.5%. The average age was 17 ± 10 days. The most frequent diagnostic method was immunofluorescence (92%). The most common symptoms were respiratory secretions (74%) and desaturations (64%); The most frequent viruses were: Respiratory Syncytial (26%), Influenza B (25%) and Influenza A (18%). 66% required respiratory support treatment. One patient died from causes unrelated to the viral respiratory infection. Conclusions: The frequency of viral infections was 8.5%. The most frequent viruses were RSV and influenza B. More than half needed respiratory support. No patient died.

Effectiveness and safety of a home-based cardiac rehabilitation programme of mixed surveillance in patients with ischemic heart disease at moderate cardiovascular risk: A randomised, controlled clinical trial.

BACKGROUND: Previous studies have documented the feasibility of home-based cardiac rehabilitation programmes in low-risk patients with ischemic heart disease, but a similar solution needs to be found for patients at moderate cardiovascular risk. The objective of this study was to analyse the effectiveness and safety of a home-based cardiac rehabilitation programme of mixed surveillance in patients with ischemic cardiopathology at moderate cardiovascular risk. METHODS: A randomised, controlled clinical trial was designed wherein 28 patients with stable coronary artery disease at moderate cardiovascular risk, who met the selection criteria for this study, participated. Of these, 14 were assigned to the group undergoing traditional cardiac rehabilitation in hospital (control group) and 14 were assigned to the home-based mixed surveillance programme (experimental group). The patients in the experimental group went to the cardiac rehabilitation unit once a week and exercised at home, which was monitored with a remote electrocardiographic monitoring device (NUUBO®). The in-home exercises comprised of walking at 70% of heart rate reserve during the first month, and 80% during the second month, for 1 h per day at a frequency of 5 to 7 days per week. A two-way repeated measures analysis of variance (ANOVA) was performed to evaluate the effects of time (before and after intervention) and time-group interaction regarding exercise capacity, risk profile, cardiovascular complications, and quality of life. RESULTS: No significant differences were observed between the traditional cardiac rehabilitation group and the home-based with mixed surveillance group for exercise time and METS achieved during the exertion test, and the recovery rate in the first minute (which increased in both groups after the intervention). The only difference between the two groups was for quality of life scores (10.93 [IC95%: 17.251, 3.334, p = 0.007] vs -4.314 [IC95%: -11.414, 2.787; p = 0.206]). No serious heart-related complications were recorded during the cardiac rehabilitation programme. CONCLUSIONS: The home-based cardiac rehabilitation programme with mixed surveillance appears to be as effective and safe as the traditional model in patients with ischemic heart disease who are at moderate cardiovascular risk. However, the cardiac rehabilitation programmes carried out in hospital seems to have better results in improving the quality of life. TRIAL REGISTRATION: Retrospectively registered NCT02796404 (May 23, 2016).

Exploración de una herramienta para evaluar si se aplican cuidados del neurodesarrollo en unidades neonatales

Introducción: El Protocolo de Atención Neonatal Integral (ANI) es una normativa nacional para los cuidados del neurodesarrollo y la atención centrada en la familia. Objetivo: Explorar un instrumento de evaluación del cumplimiento del protocolo en unidades neonatales de 3 hospitales maternoinfantiles de Paraguay. Material y Método: Estudio prospectivo, descriptivo, transversal. Se diseñó el "Instrumento de evaluación del desempeño en la aplicación del Protocolo ANI" con estándares de calidad de atención y criterios objetivos de verificación de cumplimiento. La información se obtuvo por observación directa; entrevistas al personal de salud, madres y familiares de bebés internados; revisión de registros clínicos, en dos guardias distintas en cada hospital. Resultados: Instrumento diseñado con meta de 80% de cumplimiento. Porcentaje de cumplimiento de cada estándar por hospital identificados como 1°, 2°, 3°: Acceso irrestricto de madres, padres o tutores y participación en los cuidados: 50%, 75%, 25%. Información, educación y comunicación: 30%, 59%, 53%. Contacto piel a piel: 0%, 0%, 0%. Manejo integral del dolor: 12,5%, 25%, 12,5%. Medidas ambientales para disminuir estrés y procurar confort: 33%, 33%, 25%. Atención individualizada según sueño: 50%, 50%, 0%. Prevención de Retinopatía del Prematuro: 55%, 44%, 66%. Lactancia y nutrición precoz: 66%, 50%, 33%. Registros clínicos completos, métodos diagnósticos auxiliares: 0%, 50%, 50%. Albergue: 38%, 71%, 57%. Capacitación de 80% del personal asistencial: 75%, 25%, 25%. Total de cumplimiento: 1° 37%, 2° 44%, 3° 31,5%. Conclusiones: El instrumento aplicado fue pertinente y aceptado. Ningún Hospital cumple con la meta del 80%. Recomendación: Monitorear sistemáticamente la implementación de normativas.

Introduction: The Comprehensive Neonatal Care Protocol (CNCP) is a national standard for neurodevelopmental and family-centered care. Objective: To explore an instrument to evaluate compliance with the protocol in the neonatal units of 3 maternal-infant hospitals in Paraguay. Materials and Methods: This was a prospective, descriptive and cross-sectional study. The "Performance Evaluation Instrument in the Application of the CNCP Protocol" was designed with standards of quality of care and objective criteria to verify compliance. The information was obtained by direct observation, interviews with health personnel, mothers and relatives of hospitalized infants and review of clinical records during two different shifts at each hospital. Results: The instrument was designed with an 80% compliance goal. The percentages of compliance of each standard per hospital were identified as 1st, 2nd and 3rd: Unrestricted access of mothers, parents or guardians and participation in care: 50%, 75%, 25%. Information, education and communication: 30%, 59%, 53%. Skin-to-skin contact: 0%, 0%, 0%. Comprehensive pain management: 12.5%, 25%, 12.5%. Environmental measures to reduce stress and seek comfort: 33%, 33%, 25%. Individualized care according to sleep: 50%, 50%, 0%. Prevention of Retinopathy of Prematurity: 55%, 44%, 66%. Breastfeeding and early nutrition: 66%, 50%, 33%. Complete clinical records, ancillary diagnostic methods: 0%, 50%, 50%. Hostel: 38%, 71%, 57%. Training of 80% of care staff: 75%, 25%, 25%. Total compliance: 1st: 37%, 2nd: 44%, 3rd: 31.5%. Conclusions: The instrument applied was pertinent and accepted. No Hospital meets the 80% goal. Recommendation: Systematically monitor the implementation of regulations.

Pharmacogenomics of Prostaglandin and Leukotriene Receptors.

Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

Characteristics of the dimensions and sub-dimensions of young basketball players´ personalities

The aim of the present work is to assess the personality traits of young basketball players aged 16-18 years (n=186)through the description of the dimensions and sub-dimension from the Big Five Questionnaire (BFQ) regarding personality.This was a non-experimental study in which a descriptive transversal design was used. The results that were obtained indicate theplayers in the selected sample are characterized as people who are: a) moderately dynamic, extraverted and dominant; b)moderately altruistic, understanding and tolerant; c) moderately responsible, orderly, and diligent; d) moderately balanced, calm,patient, and able to manage their emotions moderately well; and e) rather uncreative, unimaginative, and not well informed(AU)

Participation of minibasketball players during small-sided competitions

This study presents the differences of competition between mini-basketball with the traditional rules (5-a-side) andminibasket with rule modifications (3-a-side) such as: reduced number of players on court, compulsory participation in 2 of thematch’s 4 periods, reduced court size, placing the free throw line at 3m from the basket, and including a three-point line. Thesample that was selected included 47 mini-basketball players, and the study was carried out using a quasi-experimental designwithout a control group. The aim was to determine the effect of rule modifications on the participation of the player with theball. It was demonstrated that the degree of individual participation is greater in mini-basketball with modified rules(AU)

Invertir en la familia. Las voces del TID: develando injusticias desde otro tiempo cultural. Estudio sobre factores preventivos y de vulnerabilidad al trabajo infantil doméstico en familias rurales y urbanas de Paraguay / To invest in the family. The voices of the TID: revealing injustices from another cultural time. Study on preventive factors and of vulnerability to the domestic infantile work in rural and urban families of Paraguay

La investigación recoge y sistematiza información sobre el trabajo infantil doméstico en una zona urbana y una rural de Paraguay. Estudia los factores preventivos y la vulnerabilidad al trabajo infantil doméstico en familias rurales y urbanas.

Alteraciones asociadas con la cataratas congénitas en niños menores de 7 años atendidos en el Centro Nacional de Oftalmología durante el período comprendido entre enero del 2001 - junio del 2003 / Alterations associated with the congenital cataracts in children 7-year-old minors attended in the National Ophthalmology Center during the period understood between January of the 2001 - June of the 2003

Presenta estudio de como identificar los factores asociados a las cataratas congénitas en los niños menores de 7 años atendidos en consulta externa del Centro Nacional de oftalmología en el periodo comprendido entre Enero del año 2001 a Junio del 2003. Este estudio es de tipo descriptivo y de corte transversal, en el cual se hizo revisión de expedientes clínicos de los niños sometidos al estudio. Los resultados más importantes fueron: El 39.2 porciento correspondió a las cataratas congénitas, la edad de la primera consulta que más predominó fue de 4ù7 años con un 39.4 porciento, seguido del grupo de 1ù3 años con un 37.4 porciento. El 55.6 porciento fueron cataratas bilaterales y el 44.4 fueron unilaterales. Entre las alteraciones asociadas mas frecuentes se encontró el estrabismo y el nistagmo con 34.6 porciento para cada uno, 35 pacientes presentaron antecedentes prenatales, de los cuales el 60 porciento eran exantema e infección viral. De los pacientes detectados entre 1ù6 meses, el 40.9 porciento llegó a la primera consulta entre 1 y 3 años de edad y los detectados en el grupo de 7ù11 meses de edad, en el 50 porciento acudieron entre 1y3 años de edad y el otro 50 porciento entre los 4y7 años de edad. Los niños que llegaron a consulta antes de los 2 meses de edad, al 42.8 porciento se les realizó la cirugía antes del año de edad, al 28.6 porciento se les realizó entre 1y3 años de edad y al otro 28.6 porciento no se le ha realizado. Y los que llegaron entre los 2y 6 meses de edad al 40 porciento se les realizó después del año de edad. El tipo de catarata más frecuente fue la subcapsular posterior y en el 60.7 porciento la cirugía fue realizada entre los 4 y 7 años de edad. Se concluyó que: El 39.4 porciento de los niños llegaron a su primera consulta entre los 4y7 años y el 37.4´porciento entre 1y3 años, el 78 porciento de los niños tenían otras alteraciones asociadas las más frecuentes estrabismo y nistagmo, el 35.5 porciento tenían antecedentes prenatales el más frecuente exantema e infección viral, y el 29.3 porciento de estos presentaban antecedentes familiares de catarata. Se recomienda Implementar programas y métodos que permitan la captación de pacientes con catarata congénita a su debido tiempo a nivel de atención primaria, aprovechar la primer consulta de la madre después del parto para darle a conocer la manera de detectar problemas visuales en sus niños