Scientific Rationale for the Use of Alpha-Adrenergic Agonists and Glucocorticoids in the Therapy of Pediatric Stridor

Purpose. The most common pharmacological therapies used in the treatment of stridor in children are glucocorticosteroids (GC) and alpha-adrenergic (αAR) agonists. Despite the long-standing reported efficacy of these medications, there is a paucity of data relating to their actual mechanisms of action in the upper airway. Summary. There is compelling scientific evidence supporting the use of αAR-agonists and GCs in pediatric stridor. αAR signaling and GCs regulate the vasomotor tone in the upper airway mucosa. The latter translates into better airflow dynamics, as delineated by human and nonhuman upper airway physiological models. In turn, clinical trials have demonstrated that GCs and the nonselective αAR agonist, epinephrine, improve respiratory distress scores and reduce the need for further medical care in children with stridor. Future research is needed to investigate the role of selective αAR agonists and the potential synergism of GCs and αAR-signaling in the treatment of upper airway obstruction and stridor

Novel Mutation of Interferon-γ Receptor 1 Gene Presenting as Early Life Mycobacterial Bronchial Disease

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a) Interferon-γ receptor deficiency can present resembling common disorders of the lung; (b) mycobacterial infections should be suspected when parenchymal lung disease, hilar lymphadenopathy, and endobronchial disease are present; and (c) high index of suspicion for immunodeficiency should be maintained in patients with disseminated nontubercular mycobacterial infection

An Architecture to Support the Design and Evaluation of Software Platforms for Partially Virtual Communities

Several researchers have identified the design of collaborative systems as a particularly challenging task, because it has to consider services that are not easily identifiable by software designers. The systems that support the activities of partially virtual communities (PVC) are not an exception. Typically, designers of PVC supporting systems are able to identify services that have a visual representation on the user interface, but they usually overlook those that run in the system back-end. In an attempt to help designers to consider these two types of services, this article proposes a software architecture that can be used for both, designing new PVC supporting systems and evaluating existing ones. The architecture was used in three case studies as a design guideline during the development of PVC supporting platforms, and also as an instrument to evaluate three commercial systems. Although the obtained results are still preliminary, they indicate that the architecture is able to accomplish both roles

An Architecture to Support the Design and Evaluation of Software Platforms for Partially Virtual Communities

Several researchers have identified the design of collaborative systems as a particularly challenging task, because it has to consider services that are not easily identifiable by software designers. The systems that support the activities of partially virtual communities (PVC) are not an exception. Typically, designers of PVC supporting systems are able to identify services that have a visual representation on the user interface, but they usually overlook those that run in the system back-end. In an attempt to help designers to consider these two types of services, this article proposes a software architecture that can be used for both, designing new PVC supporting systems and evaluating existing ones. The architecture was used in three case studies as a design guideline during the development of PVC supporting platforms, and also as an instrument to evaluate three commercial systems. Although the obtained results are still preliminary, they indicate that the architecture is able to accomplish both roles

Characterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life.

Human respiratory conditions are largely influenced by the individual\u27s sex resulting in overall higher risk for males. Sex-based respiratory differences are present at birth suggesting a strong genetic component. Our objective was to characterize early life sex-based genomic signatures determined by variable X-chromosome methylation in the airways. We compared male versus female genome-wide DNA methylation in nasal airway samples from newborns and infants aged 1-6 months (N = 12). We analyzed methylation signals across CpG sites mapped to each X-linked gene using an unsupervised classifier (principal components) followed by an internal evaluation and an exhaustive cross-validation. Results were validated in an independent population of children (N = 72) following the same algorithm. X-linked genes with significant sex-based differential methylation in the nasal airway of infants represented only about 50% of the unique protein coding transcripts. X-linked genes without significant sex-based differential methylation included genes with evidence of escaping X-inactivation and female-biased airway expression. These genes showed similar methylation patterns in males and females suggesting unbalanced X-chromosome dosage. In conclusion, we identified that the human airways have already sex-based DNA methylation signatures at birth. These early airway epigenomic marks may determine sex-based respiratory phenotypes and overall predisposition to develop respiratory disorders later in life

Oximetry signal processing identifies REM sleep-related vulnerability trait in asthmatic children

Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n=134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level p ≤ 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children

Building capacity on ecosystem-based adaptation strategy to cope with extreme events and sea-level rise on the Uruguayan coast

Purpose - This study aims to show a case study of ecosystem-based adaptation (EbA) measures to increase coastal system’s resilience to extreme weather events and sea-level rise (SLR) implemented at Kiyú (Uruguayan coast of the Rio de la Plata river estuary). Design/methodology/approach - A participatory process involving the community and institutional stakeholders was carried out to select and prioritise adaptation measures to reduce the erosion of sandy beaches, dunes and bluffs due to extreme wind storm surge and rainfall, SLR and mismanagement practices. The recovery of coastal ecosystems was implemented through soft measures (green infrastructure) such as revegetation with native species, dune regeneration, sustainable drainage systems and the reduction of use pressures. Findings - Main achievements of this case study include capacity building of municipal staff and stakeholders, knowledge exchanges with national-level decision makers and scientists and the incorporation of EbA approaches by subnational-level coastal governments. To consolidate EbA, the local government introduced innovations in the coastal management institutional structure. Originality/value - The outcomes of the article include, besides the increase in the resilience of social-ecological systems, the strengthening of socio-institutional behaviour, structure and sustainability. This experience provides insights for developing a strategy for both Integrated Coastal Management and climate adaptation at the national scale

Characterization of cytomegalovirus lung infection in non-HIV infected children

Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes

Co2TiO4/reduced graphene oxide nanohybrids for electrochemical sensing applications

For the first time, the synthesis, characterization, and analytical application for hydrogen peroxide quantification of the hybrid materials of Co2TiO4 (CTO) and reduced graphene oxide (RGO) is reported, using in situ (CTO/RGO) and ex situ (CTO+RGO) preparations. This synthesis for obtaining nanostructured CTO is based on a one-step hydrothermal synthesis, with new precursors and low temperatures. The morphology, structure, and composition of the synthesized materials were examined using scanning electron microscopy, X-ray diffraction (XRD), neutron powder diffraction (NPD), and X-ray photoelectron spectroscopy (XPS). Rietveld refinements using neutron diffraction data were conducted to determine the cation distributions in CTO. Hybrid materials were also characterized by Brunauer-Emmett-Teller adsorption isotherms, Scanning Electron microscopy, and scanning electrochemical microscopy. From an analytical point of view, we evaluated the electrochemical reduction of hydrogen peroxide on glassy carbon electrodes modified with hybrid materials. The analytical detection of hydrogen peroxide using CTO/RGO showed 11 and 5 times greater sensitivity in the detection of hydrogen peroxide compared with that of pristine CTO and RGO, respectively, and a two-fold increase compared with that of the RGO+CTO modified electrode. These results demonstrate that there is a synergistic effect between CTO and RGO that is more significant when the hybrid is synthetized through in situ methodology.Fil: Venegas, Constanza J.. Universidad de Chile; Chile. Universidad de Santiago de Chile; ChileFil: Gutierrez, Fabiana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Eguílaz Rubio, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Marco, José F.. Consejo Superior de Investigaciones Científicas; EspañaFil: Reeves-McLaren, Nik. University Of Sheffield; Reino UnidoFil: Rivas, Gustavo Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Ruiz-León, Domingo. Universidad de Santiago de Chile; ChileFil: Bollo, Soledad. Universidad de Chile; Chil