12 research outputs found

    Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

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    Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio

    The development and maintenance of the mononuclear phagocyte system of the chick is controlled by signals from the macrophage colony-stimulating factor (CSF1) receptor

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    BACKGROUND: Macrophages have many functions in development and homeostasis as well as innate immunity. Recent studies in mammals suggest that cells arising in the yolk sac give rise to self-renewing macrophage populations that persist in adult tissues. Macrophage proliferation and differentiation is controlled by macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34), both agonists of the CSF1 receptor (CSF1R). In the current manuscript we describe the origin, function and regulation of macrophages, and the role of CSF1R signaling during embryonic development, using the chick as a model. RESULTS: Based upon RNA-sequencing comparison to bone marrow-derived macrophages grown in CSF1, we show that embryonic macrophages contribute around 2% of the total embryo RNA in day 7 chick embryos, and have similar gene expression profiles to bone marrow-derived macrophages. To explore the origins of embryonic and adult macrophages, we injected Hamburger-Hamilton stage 16 to 17 chick embryos with either yolk sac-derived blood cells, or bone marrow cells from EGFP(+) donors. In both cases, the transferred cells gave rise to large numbers of EGFP(+) tissue macrophages in the embryo. In the case of the yolk sac, these cells were not retained in hatched birds. Conversely, bone marrow EGFP(+) cells gave rise to tissue macrophages in all organs of adult birds, and regenerated CSF1-responsive marrow macrophage progenitors. Surprisingly, they did not contribute to any other hematopoietic lineage. To explore the role of CSF1 further, we injected embryonic or hatchling CSF1R-reporter transgenic birds with a novel chicken CSF1-Fc conjugate. In both cases, the treatment produced a large increase in macrophage numbers in all tissues examined. There were no apparent adverse effects of chicken CSF1-Fc on embryonic or post-hatch development, but there was an unexpected increase in bone density in the treated hatchlings. CONCLUSIONS: The data indicate that the yolk sac is not the major source of macrophages in adult birds, and that there is a macrophage-restricted, self-renewing progenitor cell in bone marrow. CSF1R is demonstrated to be limiting for macrophage development during development in ovo and post-hatch. The chicken provides a novel and tractable model to study the development of the mononuclear phagocyte system and CSF1R signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0121-9) contains supplementary material, which is available to authorized users

    Seasonal Variation in Undiagnosed HIV Infection on the General Medicine and Trauma Services of Two Urban Hospitals

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    OBJECTIVE: To examine the seroprevalence of undiagnosed HIV and variation by season among patients admitted to the general internal medicine (GIM) and trauma services of two urban hospitals. DESIGN: A cross-sectional blinded HIV-1 seroprevalence survey. SETTING: A 725-bed academic medical center's hospital and an affiliated 324-bed tertiary care hospital. PARTICIPANTS: Residual serological specimens were obtained for unique patients aged 17 to 65 to study services in summer (June 16 to September 4, 2001) and fall to winter (November 1, 2001 to January 8, 2002). METHODS: Hospital files provided data on demographics, service type, and discharge clinical categories (fall–winter group only). HIV ELISA (enzyme-linked immunosorbent assay) tests with confirmatory Western blot were linked to subjects' de-identified files. We excluded 34 subjects with known HIV. Of the remaining unique admissions in summer (n=604) and fall–winter (n=978), 60% and 55% were tested, respectively. Predictors of undiagnosed HIV infection were examined using multivariate analysis. RESULTS: The summer cohort (n=362) had significantly lower unadjusted seroprevalence of undiagnosed HIV infection (1.4%; 95% confidence interval [CI], 0.4% to 3.2%) than the fall–winter cohort (n=539; 3.7%; 95% CI, 2.3% to 5.7%; P=.04). Overall, undiagnosed HIV was somewhat less likely in women (adjusted odds ratio [AOR], 0.45; 95% CI, 0.19 to 1.07) but more likely in black patients (AOR, 3.46; 95% CI, 0.70 to 17.06). In the fall–winter cohort, undiagnosed HIV was more likely for discharges with the following clinical categories versus those with a cardiac condition: dermatologic/breast (AOR, 14.90; 95% CI, 1.20 to 184.77), renal/urological (AOR, 22.43; 95% CI, 2.12 to 236.75), or infectious (AOR, 31.08; 95% CI, 2.40 to 402.98). CONCLUSIONS: The higher seroprevalence of undiagnosed HIV in the fall–winter admissions to GIM and trauma services supports especially targeting HIV testing in these months
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