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Background PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. Objective We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 ( PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. Methods We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/ FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. Results There was an interaction between asthma status and the PAI-1 polymorphism on FEV1/ FVC ( P=.03). The gain-of-function variants, genotypes ( AA/ AG), were associated with lower FEV1/ FVC in subjects with asthma (β=−1.25, CI: −2.14,−0.35, P=.006), but not in controls. Subjects with asthma and the AA/ AG genotypes had a 5% decrease in FEV1/ FVC ( P<.001). In asthmatics, the risk genotype ( AA/ AG) was associated with a 39% increase in risk of clinically relevant airway obstruction ( OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. Conclusions and Clinical Relevance The decrease in the FEV1/ FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation. [ABSTRACT FROM AUTHOR]

Phaeosphaeriaceae is a family in the order Pleosporales containing numerous plant pathogens, endophytes, lichenised fungi, and environmental saprobes. A novel genus, Tintelnotia is introduced containing two species, one of which caused an eye infection and several nail infections in humans. All species of Tintelnotia produce conidia in soft pycnidia with a wide ostiole. The generic type species is T. opuntiae causing necrotic spots on cactus plants. The isolates of the human opportunist T. destructans showed variable susceptibility pattern to a panel of common antifungal agents. The MICs of amphotericin B, voriconazole, posaconazole and itraconazole were 1 μg/mL, complemented by an in vitro MEC of 16 μg/mL against caspofungin; the MIC of terbinafine was 0.125 μg/mL. The latter compound contributed to the successful therapy in the ocular mycosis refractory to standard antifungal therapy, the benefit of terbinafine should be highlighted as a therapeutic option especially in difficult-to-treat fungal keratitis. [ABSTRACT FROM AUTHOR]

Background Younger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations. Objectives We sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children. Methods We included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship. Results Maternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors ( OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans ( OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma ( OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings ( OR = 0.44, 95% CI: 0.23-0.81). Conclusion and Clinical Relevance In contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability. [ABSTRACT FROM AUTHOR]

Background Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) in asthma have been inconclusive. Objective To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. Methods The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent–child trios of Mexican and Puerto Rican origin. Results In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos ( P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function ( P=0.018) in Puerto Ricans. A gene–gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), ( P=0.003, in the combined sample). Conclusion Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations. Cite this as: M. Via, A. De Giacomo, H. Corvol, C. Eng, M. A. Seibold, C. Gillett, J. Galanter, S. Sen, H. Tcheurekdjian, R. Chapela, J. R. Rodríguez-Santana, W. Rodríguez-Cintrón, S. Thyne, P. C. Avila, S. Choudhry and E. González Burchard on behalf of the Genetics of Asthma in Latino Americans (GALA) Study, Clinical & Experimental Allergy, 2010 (40) 582–589. [ABSTRACT FROM AUTHOR]

Fusarium infections are associated with high mortality after allogeneic stem cell transplantation. We report on successful treatment of a disseminated cutaneous Fusarium proliferatum infection using liposomal amphotericin B and terbinafine. In vitro susceptibility tests of antifungal drugs suggest that terbinafine is a potent additional antifungal drug for disseminated cutaneous fusariosis. [ABSTRACT FROM AUTHOR]