Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe

Effects of mustard sprouts and allylisothiocyanate on benzo(a)pyrene-induced DNA damage in human-derived cells: A model study with the single cell gel electrophoresis/Hep G2 assay

International audienceThe aim of this study was to investigate the chemoprotective effects of mustard sprouts on benzo(a)pyrene [B(a)P]-induced DNA damage in the single cell gel electrophoresis (SCGE)/Hep G2 assay. This model combines the advantages of the SCGE assay with that of human-derived cells that possess inducible phase I and phase II enzymes. Treatment of the cells with small amounts of mustard juice (0.1-1.25 mul/ml) and B(a)P reduced the genotoxic effect of the carcinogen in a dose-dependent manner. Contrary to the results with the juice, unexpected synergistic effects were observed with allyl isothiocyanate (AITC, 0.3 muM), a breakdown product of sinigrin, which is contained in black mustard and many other cruciferous vegetables. Although these concentrations of AITC did not cause DNA damage per se, pronounced dose-dependent DNA damage was seen with higher concentrations of AITC (greater than or equal to 25 muM). In parallel with the comet assays, also enzyme measurements were carried out which showed that exposure of the cells to mustard juice (2.0 mul/ml) causes a moderate induction of ethoxyresorufin-O-deethylase, and more pronounced (approximately 2-fold) increase of the activity of glutathione-S-transferase. In conclusion, our findings indicate that i) mustard juice is highly protective against B(a)P-induced DNA damage in human derived cells and ii) that induction of detoxifying enzymes may account for its chemoprotective properties. iii) Furthermore, our findings show that the effects of crude juice can not be explained by its allyl isothiocyanate contents

Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and benzo(a)pyrene (B(a)P) in bacterial and human hepatoma (HepG2) cells

International audienceThe aim of the present study was to investigate the antimutagenic effects of chrysin (CR), a flavonoid compound contained in many fruits, vegetables and honey. Earlier investigations with bacterial indicators showed that CR is one of the most potent antimutagens among the flavonoids. In the present study, we tested the compound in the Salmonella strains TA98 and TA100 in combination with benzo(a)pyrene (B(a)P) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and found pronounced protective activity over a concentration range between 10 and 100 μg/ml. The compound itself was devoid of mutagenic activity at all concentrations tested. In the micronucleus (MN) assay with human-derived HepG2 cells, a different pattern of activity was seen. CR itself caused significant induction of MN at dose levels ≥15 μg/ml; in combination experiments with B(a)P and PhIP, U-shaped dose-response curves were obtained and protection was found only in a narrow dose range (5 – 10 μg/ml). Our findings indicate that the molecular mechanisms that account for the antimutagenic effects of CR in bacterial cells are different from those responsible for the effects in HepG2 cells. Earlier reports indicate that the antimutagenic effects of CR towards B(a)P and heterocyclic amines in bacterial indicators is due to inhibition of the activity of CYP1A. In contrast to this, we found a significant induction of CYP1A1 activity in HepG2 cells by CR. It can also be excluded that induction of GST, which is involved in the detoxification of polycyclic aromatic hydrocarbons accounts for the protective effects of CR against B(a)P since this enzyme was not significantly induced in the HepG2 cells. In the case of PhIP, induction of UDGPT and/or inhibition of sulfotransferase seen in human derived HepG2 cells after exposure to CR might play a role in the antimutagenic effects. In conclusion, our findings show that data from antimutagenicity studies with bacterial indicators cannot be extrapolated to HepG2 cells, and that CR causes genotoxic effects at higher dose levels in the latter cells. The implications of these observations for human chemoprevention strategies are discussed

RNA-sequencing studies identify genes differentially regulated during inflammation-driven lung tumorigenesis and targeted by chemopreventive agents

YK:n piirissä on 2013 vuodesta alkaen keskusteltu autonomisista aseista tai tavanomaisemmin tappajaroboteista. Vuodesta 2014 alkaen keskustelu on käyty YK:n eräitä tavanomaisia aseita koskevan yleissopimuksen epävirallisissa istunnoissa, mutta vuodesta 2017 eteenpäin sen virallisissa GGE-muotoisissa kokouksissa. Tutkielmassa analysoidaan Yhdysvaltojen käyttämää retoriikkaa puheenvuoroissaan näissä kokouksissa vuosina 2017-2019. Aineisto on rajattu niihin kokouksiin, joissa aiheena on ollut autonomiset asejärjestelmät (LAWS). Puheista on käytetty Yhdysvaltojen Geneven edustuston sivuilla julkaistuja litteroituja versioita. Puheenvuoroja on analysoitu retorisen analyysin konventioon kuuluvan Chaïm Perelmanin uuden retoriikan avulla. Tämän avulla on puheista pyritty löytämään humanitaariseen oikeuteen ja ihmisoikeuksiin perustuvaa asejärjestelmiä puolustelevaa tai oikeuttavaa argumentaatiota. Aseita on oikeutettu historiallisesti valtioiden puolustuskykyyn ja iskukapasiteettiin vedoten. Hyveellisen sodankäynnin teoria puoltaa aseita oikeuttavan retoriikan analysointia ihmisoikeuksiin perustuvan oikeutuksen näkökulmasta. Autonomisista aseista käyty tutkimuskeskustelu ja YK:ssa kokousosapuolien näkökulmat ovat ristiriitaisia ja edes perustavanlaatuisten termien määrittelystä käydään väittelyä. Tässä kontekstissa Yhdysvaltojen argumentaatio pyrkii luomaan yleisesti hyväksyttävän, oman doktriininsa mukaisen keskustelun. Tutkimus osoittaa argumentoinnin luovan kuvaa autonomisista asejärjestelmistä hyveellisinä sekä humanitaarista oikeutta toteuttavina ja jopa sitä vahvistavana tekijänä. Yhtäältä tämä osoittaa mahdollista muutosta tavassa puhua asekehityksestä. Toisaalta aseiden ’hyveellisyys’ ja ’oikeudellisuus’ ovat humanitaaristen interventioiden ja sodankäynnin oikeutuksen kannalta tässä valossa kriittisen tarkastelun kohteina, sillä puheet eivät välttämättä vastaa tekoja

DNA Adducts in Aldehyde Dehydrogenase-Positive Lung Stem Cells of A/J Mice Treated with the Tobacco Specific Lung Carcinogen 4‑(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Lung cancer is the leading cause of cancer death in the world. Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells. Aldehyde dehydrogenase (ALDH) is a marker of stem cells. To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Using LC–NSI-HRMS/MS–PRM, <i>O</i>⁶-methyl-G, 7-POB-G, and <i>O</i>²-POB-dT were positively identified in ALDH-positive cell DNA. This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis

Yin Yang Gene Expression Ratio Signature for Lung Cancer Prognosis

<div><p>Many studies have established gene expression-based prognostic signatures for lung cancer. All of these signatures were built from training data sets by learning the correlation of gene expression with the patients' survival time. They require all new sample data to be normalized to the training data, ultimately resulting in common problems of low reproducibility and impracticality. To overcome these problems, we propose a new signature model which does not involve data training. We hypothesize that the imbalance of two opposing effects in lung cancer cells, represented by Yin and Yang genes, determines a patient’s prognosis. We selected the Yin and Yang genes by comparing expression data from normal lung and lung cancer tissue samples using both unsupervised clustering and pathways analyses. We calculated the Yin and Yang gene expression mean ratio (YMR) as patient risk scores. Thirty-one Yin and thirty-two Yang genes were identified and selected for the signature development. In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in four independent data sets and it significantly stratified patients into high- and low-risk survival groups (p = 0.02, HR = 2.72; p = 0.01, HR = 2.70; p = 0.007, HR = 2.73; p = 0.005, HR = 2.63). It also showed prediction of the chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk factor was more successful at predicting clinical outcomes than other commonly used clinical factors, with the exception of tumor stage. The YMR can be measured in an individual patient in the clinic independent of gene expression platform. This study provided a novel insight into the biology of lung cancer and shed light on the clinical applicability.</p></div

Mass Spectrometric Analysis of a Cyclic 7,8-Butanoguanine Adduct of N-Nitrosopyrrolidine: Comparison to Other N-Nitrosopyrrolidine Adducts in Rat Hepatic DNA

The well established rat hepatocarcinogen N-nitrosopytrolidine (NPYR, 1) requires metabolic activation to DNA adducts to express its carcinogenic activity. Among the NPYR-DNA adducts that have been identified, the cyclic 7,8-butanoguanine adduct 2-amino-6,7,8,9-tetrahydro-9-hydroxypyrido[2,1-f]purine-4(3H)-one (6) has been quantified using moderately sensitive methods, but its levels have never been compared to those of other DNA adducts of NPYR in rat hepatic DNA. Therefore, in this study, we developed a sensitive new LC-ESI-MS/MS-SRM method for the quantitation of adduct 6 and compared its levels to those of several other NPYR-DNA adducts formed by different mechanisms. The new method was shown to be accurate and precise, with good recoveries and low fmol detection limits. Rats were treated with NPYR by gavage at doses of 46, 92, or 184 mg/kg body weight and sacrificed 16 h later. Hepatic DNA was isolated and analyzed for NPYR-DNA adducts. Adduct 6 was by far the most prevalent, with levels ranging from about 900-3000 mu mol/mol Gua and responsive to dose. Levels of adducts formed from crotonaldehyde, a metabolite of NPYR, were about 0.2-0.9 mu mol/mol dGuo, while those of adducts resulting from reaction with DNA of tetrahydrofuranyl-like intermediates were in the range of 0.01-4 mu mol/mol deoxyribonucleoside. The results of this study demonstrate that, among typical NPYR-DNA adducts, adduct 6 is easily the most abundant in hepatic DNA. Since previous studies have shown that it can be detected in the urine of NPYR-treated rats, the results suggest that it is a potential candidate as a biomarker for assessing human exposure to and metabolic activation of NPYR.National Cancer Institute (NCI/NIH)[CA-85702]FAPESPCNPq (Brazil)Pro-Reitoria de Pos-Graduaqao da Universidade de Sao Paulo (USP), Brazi