Suchergebnisse

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5-71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05-1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome. Pulmonary tuberculosis (PTB) kills almost 2 million individuals every year and is thus a leading cause of death among adults worldwide. Mycobacterium tuberculosis (Mtb) infects more than 10 million people each year 1-3. Mtb potently induces cytokines and chemokines from polymorphonuclear cells and monocytes, thus resulting in intense local inflammation in the lungs 4. Alveolar macrophages are anti-inflammatory in nature, but their function can be impaired by pollutants, including mineral dusts, thereby diminishing the body's ability to clear infections 5-8. This is probably why mineworkers are more susceptible to develop PTB. Telomere length (TL) reflects the history of oxidative stress and chronic inflammation, and is a marker for age-related disease susceptibility 9-12. In normal physiology, mitochondria are important in the cell as they generate most of the adenosine triphosphate (ATP) through the oxidative phosphorylation mechanism (OXPHOS), which is a critical energy supply for cellular processes and partially encoded with mitochondrial DNA (mtDNA). The OXPHOS mechanism uses dietary intake to produce ATP, but it also produces ROS which can destroy mitochon-drial DNA, impairs respiratory chain function and cause nuclear DNA damage 12-14. Further, Mitochondrial DNA (mtDNA) damage can result in genomic instability, cellular senescence and altered intercellular communication. Hallmarks of aging genomic instability and deregulated nutrient sensing can contribute to reduced mitochondrial OPEN ; Funding P.D.M.C.K was fellow of the Fonds Marc Vervenne of the KU Leuven (Belgium) and he is supported by the US National Institutes of Health (NIH)-Fogarty Postdoctoral Fellowship: Grant no. 1D43TW010937-01A1. D.S.M is a FWO postdoc, with funding number: FWO Grant 12X9620N. Fieldwork has been supported by the KU Leuven Alumni Association and the University of Antwerp-USOS via the CEGEMI of the Catholic University of Bukavu. The costs of measuring Telomere length and mtDNA were covered by a grant of the European Research Council (ENVIRONAGE). The funders had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to all the study data and had final responsibility for the decision to submit for publication. Acknowledgements We thank Profs J. Balmes (UCSF), N. Lorent, E. André (KU Leuven), and C. Tonne (ISGlobal) for their critical appraisal of the manuscript. We are grateful to the study participants and their relatives, the TB clinics, and the DRC's National/Provincial TB and HIV programs for their collaboration.

Abstract
Fine particulate matter (PM2.5) has been shown to cause oxidative stress, which has negative health consequences. The oxidative potential (OP) of PM2.5, a promising health exposure metric, was assessed in five Colombian cities using the synthetic respiratory tract lining fluid assay that tracks the depletions of glutathione and ascorbate. For this, a set of 91 integrated 2-week ambient PM2.5 samples were collected using Ultrasonic Personal Aerosol Samplers (UPAS) at background (5), traffic (37), industrial (12) and residential (37) sites. Across all site types, mean PM2.5 mass concentration was 20.20 ± 9.36 µg m− 3. The oxidative potential (OPAA for ascorbate and OPGSH for glutathione) varied widely across cities with an average of 2.67 ± 1.27 for AA and 2.93 ± 1.22 % depletion m− 3 for GSH. OP metrics among cities were not correlated with PM2.5 mass concentrations. Overall, industrial sites showed higher PM2.5 mass concentrations and OPAA. In contrast, OPGSH was not found to differ among industrial, traffic, or residential sites, but was lower for background sites. Our findings provide substantial evidence of variations in PM2.5 OP between cities and within the cities. Further research is needed to assess the association between OP and adverse health effects, as well as to attribute the sources that cause such variations.

The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.

The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise.

Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome.