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

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

Peace, farm and food: The effect of peace on investment and food consumption decisions

This paper studies how peace driven by the demobilization of a non-state armed group affect household's investment decisions and their welfare in the short run. Starting in 2012, the government of Colombia engaged in a peace process that ended with the demobilization of the country's biggest non-state armed group, FARC. This process had multiple cease fire arrangements in 2013 and 2014 that reduced the exposure to violence in those places that were previously under the control of an armed group. Using the presence of armed groups as a measure of exposure to the war through a difference in difference approach, I find that the FARC's demobilization process led to a more than threefold increase in farm investment in areas previously affected by the group, as farmers moved production from annual to perennial crops. I find no evidence that investment came at the expense of short-term consumption. Finally, I find evidence of substantial positive spillovers in investment to neighboring areas that were not directly affected by the FARC. The results suggest that decreased investment may be an important mechanism through which armed conflict affects economic development

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

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

Paracoccidioides species complex : ecology, phylogeny, sexual reproduction, and virulence

Paracoccidioidomycosis (PCM) is a deep systemic mycosis caused by human fungal pathogens of the Paracoccidioides genus. The disease is geographically restricted to subtropical areas of Latin America (from south of Mexico to north of Argentina) with a high prevalence in Brazil, Colombia, Venezuela, and Argentina [1]. The annual incidence rate in Brazil is 10–30 infections per million inhabitants, and the mean mortality rate is 1.4 per million inhabitants per year, making this disease the highest cause of mortality among systemic mycoses [2]. PCM is endemic in rural populations and mainly affects individuals engaged in agricultural activities, who inhale aerosols containing fungal material during manipulation of the soil. Molecular evolutionary studies place the genus Paracoccidioides in the thermodimorphic fungal pathogen clade related to the family Ajellomycetaceae (Ascomycetes), which includes the Blastomyces, Histoplasma, and Emmonsia genera, and with which it shares a common ancestor, Lacazia loboi. PCM can be caused by two species Paracoccidioides brasiliensis and P. lutzii [3]. P. brasiliensis has been considered a single species since its discovery, although several studies including molecular and morphological data support the split of P. brasiliensis into two species [3,4]. P. lutzii is composed of a single monophyletic and recombining population so far found in central, southwest, and north Brazil and Ecuador [3–5]. On the other hand, P. brasiliensis contains a complex of at least four different cryptic species (S1, PS2, PS3 and PS4; Figure 1A [6]). P. brasiliensis S1 represents a monophyletic and recombining population widely distributed in South America and has been associated with the majority of cases of PCM detected up until the present time. Strains belonging to P. brasiliensis S1 have previously been recovered from armadillos, soil, and penguin feces [6]. P. brasiliensis PS2 is a paraphyletic and recombining population identified so far only in Brazil and Venezuela [6]. P. brasiliensis PS3 is comprised of a monophyletic and clonal population that has been recovered in humans and armadillos in endemic regions of Colombia [6]. P. brasiliensis PS4 was recently identified and is composed of a monophyletic population of clinical isolates from Venezuela [5,7]. Besides the typical bicorn cocked hat– and barrel-shaped conidia produced by both species, P. lutzii frequently produces elongated rod-shaped conidia, a characteristic feature that may be used for species identification [3]. Because of the difficulties of conidia production in the laboratory and slight morphological differences among species, molecular identification of Paracoccidioides species has become the most common tool of choice. Several molecular markers have already been applied in population studies of the Pararacoccidioides genus, and for multilocus sequencing typing, gp43, arf, b-tub, and hsp70 loci are the best choices for species delineation [4,6]

Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

Background Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. Methods We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (\u3c32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records. Results A total of 571 preschool children were identified using polymerase chain reaction-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty–eight (n = 58) preschool-age children with HMPV infection were included in this study after excluding those with significant comorbidities. Our data demonstrated that 32.7% of children admitted with HMPV had a history of severe prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Conclusion Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations

Improving air quality in metropolitan Mexico City : an economic valuation

Mexico City has for years experienced high levels of ozone and particulate air pollution. In 1995-99 the entire population of the Mexico City metropolitan area was exposed to annual average concentrations of fine particulate pollution (particulates with a diameter of less than 10micrometers, or PM10) exceeding 50 micrograms per cubic meter, the annual average standard in both Mexico and the United States. Two million people were exposed to annual average PM10 levels of more than 75 micrograms per cubic meter. The daily maximum one-hour ozone standard was exceeded at least 300 days a year. The Mexico Air Quality Management Team documents population-weighted exposures to ozone and PM10 between 1995 and 1999, project exposures in 2010, and computes the value of four scenarios for 2010: A 10 percent reduction in PM10 and ozone. A 20 percent reduction in PM10 and ozone. Achievement of ambient air quality standards across the metropolitan area. A 68 percent reduction in ozone and a 47 percent reduction in PM10 across the metropolitan area. The authors calculate the health benefits of reducing ozone and PM10 for each scenario using dose-response functions from the peer-reviewed literature. They value cases of morbidity and premature mortality avoided using three approaches: Cost of illness and forgone earnings only (low estimate). Cost of illness, forgone earnings, and willingness to pay for avoided morbidity (central case estimate). Cost of illness, forgone earnings, willingness to pay for avoided morbidity, and willingness to pay for avoided mortality (high estimate). The results suggest that the benefits of a 10 percent reduction in ozone and PM10 in 2010 are about $760 million (in 1999 U.S. dollars) annually in the central case. The benefits of a 20 percent reduction in ozone and PM10 are about$1.49 billion annually. In each case the benefits of reducing ozone amount to about 15 percent of the total benefits. By estimating the magnitude of the benefits from air pollution control, the authors provide motivation for examining specific policies that could achieve the air pollution reductions that they value. They also provide unit values for the benefits from reductions in ambient air pollution (for example, per microgram of PM10) that could be used as inputs into a full cost-benefit analysisof air pollution control strategies.Montreal Protocol,Public Health Promotion,Global Environment Facility,Air Quality&Clean Air,Health Monitoring&Evaluation,Montreal Protocol,Air Quality&Clean Air,Health Monitoring&Evaluation,Global Environment Facility,Transport and Environment