151 research outputs found

    A Fatal Case of Pseudomonas aeruginosa Community-Acquired Pneumonia in an Immunocompetent Patient: Clinical and Molecular Characterization and Literature Review

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    Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa (PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with SARS-CoV-2, who was admitted for dyspnea, fever, cough, hemoptysis, acute respiratory failure and a right upper lobe opacification. Six hours after admission, despite effective antibiotic therapy, he experienced multi-organ failure and died. Autopsy confirmed necrotizing pneumonia with alveolar hemorrhage. Blood and bronchoalveolar lavage cultures were positive for PA serotype O:9 belonging to ST1184. The strain shares the same virulence factor profile with reference genome PA01. With the aim to better investigate the clinical and molecular characteristics of PA-CAP, we considered the literature of the last 13 years concerning this topic. The prevalence of hospitalized PA-CAP is about 4% and has a mortality rate of 33–66%. Smoking, alcohol abuse and contaminated fluid exposure were the recognized risk factors; most cases presented the same symptoms described above and needed intensive care. Co-infection of PA-influenza A is described, which is possibly caused by influenza-inducing respiratory epithelial cell dysfunction: the same pathophysiological mechanism could be assumed with SARS-CoV-2 infection. Considering the high rate of fatal outcomes, additional studies are needed to identify sources of infections and new risk factors, along with genetic and immunological features. Current CAP guidelines should be revised in light of these results

    Demographic and sociocultural risk factors for adulthood weight gain in Hispanic/Latinos: results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

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    Background United States (US) Hispanic/Latinos experience a disproportionate burden of obesity, which may in part be related to demographic or sociocultural factors, including acculturation to an US diet or inactive lifestyle. Therefore, we sought to describe the association between adulthood weight histories and demographic and sociocultural factors in a large diverse community-based cohort of US Hispanic/Latinos. Methods We estimated the effect of several factors on weight gain across adulthood, using multivariable linear mixed models to leverage 38,759 self-reported current body weights and weight histories recalled for 21, 45 and 65 years of age, from 15,203 adults at least 21 years of age at the baseline visit of the Hispanic Community Health Study/Study of Latinos (2008–2011). Results The average rate of weight gain was nearly 10 kg per decade in early adulthood, but slowed to < 5 kg a decade among individuals 60+ years of age. Birth cohort, gender, nativity or age at immigration, Hispanic/Latino background, and study site each significantly modified the form of the predicted adulthood weight trajectory. Among immigrants, weight gain during the 5 years post-migration was on average 0.88 kg (95% CI: 0.04, 1.72) greater than the weight gain during the 5 years prior. The rate of weight gain appeared to slow after 15 years post-migration. Conclusions Using self-reported and weight history data in a diverse sample of US Hispanic/Latinos, we revealed that both demographic and sociocultural factors were associated with the patterning of adulthood weight gain in this sample. Given the steep rate of weight gain in this population and the fact that many Hispanic/Latinos living in the US immigrated as adults, efforts to promote weight maintenance across the life course, including after immigration, should be a top priority for promoting Hispanic/Latino health and addressing US health disparities more broadly

    Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

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    BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

    Distinct Loci in the CHRNA5 / CHRNA3 / CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking

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    Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype

    Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

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    Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.Main funding: This work was funded by the Wellcome Trust, The Wellcome Sanger Institute (WT098051), the U.K. Medical Research Council (G0901213-92157, G0801566, and MR/K013491/1), and the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS core funding
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