The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg−1) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg−1 d−1) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis

Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy

<b>Background and Objectives</b> : Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 &#60; 300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. <b> Methods</b> : We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. <b> Results</b> : From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. <b> Conclusion</b> : The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5&#8710;32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene

Multilayer Substrate Integrated Waveguide Six-Port Circuit

In this paper a new design of a six-port circuit based on multilayer substrate integrated waveguides (SIW) is presented. This design is based on the use of a multilayer structure aimed at reducing the dimension of the circuit while conserving the performances of the component. The designed SIW six-port is composed of two basic elements, a SIW power divider and directional coupler. These two elements are designed, optimized and matched to produce a better performance at the required operating frequency of 11 GHz. The results of simulations show that the new multilayer SIW six-port circuit has good performances including a good return loss and isolation under –20 dB and the transmission magnitude better than –10 dB. This multilayer SIW six-port has the advantage of a small size 160x34.8 mm; its width is about 50% smaller than the planar SIW six-port circuit, which helps to get a higher density of integration in telecommunication systems and allows much smaller devices to be conceived. A microstrip to SIW transition is used in order to facilitate the integration of this component into other planar circuits. The structures are designed, simulated and optimized using the Ansoft HFSS simulation software