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- Sepanlou, Sadaf G., et al.
(författare)
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The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
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Ingår i: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
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Tidskriftsartikel (refereegranskat)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
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- Andappan, Murugaiah M. S., et al.
(författare)
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From the First Selective Non-Peptide AT(2) Receptor Agonist to Structurally Related Antagonists
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:5, s. 2265-2278
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Tidskriftsartikel (refereegranskat)abstract
- A para substitution pattern of the phenyl ring is a characteristic feature of the first reported selective AT(2) receptor agonist M024/C21 (1) and all the nonpeptidic AT(2) receptor agonists described so far. Two series of compounds structurally related to 1 but with a meta substitution pattern have now been synthesized and biologically evaluated for their affinity to the AT(1) and AT(2) receptors. A high AT(2)/AT(1) receptor selectivity was obtained with all 41 compounds synthesized, and the majority exhibited K-i ranging from 2 to 100 nM. Five compounds were evaluated for their functional activity at the AT(2) receptor, applying a neurite outgrowth assay in NG108-15 cells.. Notably, four of the five compounds, with representatives from both series, acted as potent AT(2) receptor antagonists. These compounds were found to be considerably more effective than PD 123,319, the standard AT(2) receptor antagonist used in most laboratories. No AT(2) receptor antagonists were previously reported among the derivatives with a para substitution pattern. Hence, by a minor modification of the agonist 1 it could be transformed into the antagonist, compound 38. These compounds should serve as valuable tools in the assessment of the role of the AT(2) receptor in more complex physiological models.
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- Bader, Milad, et al.
(författare)
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Modeling and inversion in acoustic-elastic coupled media using energy-stable summation-by-parts operators
- 2023
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Ingår i: Geophysics. - : SOC EXPLORATION GEOPHYSICISTS - SEG. - 0016-8033 .- 1942-2156. ; 88:3
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Tidskriftsartikel (refereegranskat)abstract
- Seismic data acquired at the seafloor are valuable in charac-terizing the subsurface and monitoring producing hydrocarbon fields. To fully use such data, a stable, accurate, and efficient numerical scheme is needed that accounts for acoustic and elas-tic wave propagation, their interaction at the seafloor interface, and for sources and receivers placed on either side of that inter-face. Existing methods either make incorrect assumptions or have high implementation and computational costs. We have developed a high-order finite-difference summation-by-parts framework for the acoustic-elastic wave equations in second -or-der form (in terms of displacements in the solid and an extension of velocity potential in the fluid). Our modified discretization of the elastic operator overcomes the dispersion errors known to plague displacement-based schemes in the high VP/VS limit. We weakly impose boundary and interface conditions using simulta-neous approximation terms, leading to an energy-stable numeri-cal scheme that rigorously handles point injection and extraction. The fully discrete system is self-adjoint after a time reversal and a sign flip and is furthermore a high-order accurate discretization of the continuous problem. The self-adjointness ensures that for-ward and adjoint wavefields are computed with similar accuracy and simplifies gradient computation for inversion purposes. We find that our numerical scheme achieves accuracy comparable to a more computationally expensive spectral-element method and demonstrate its application to full-waveform inversion using the Marmousi2 model.
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- Bitar, Milad S., et al.
(författare)
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Inflammation and apoptosis in aortic tissues of aged type II diabetes : Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism
- 2010
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Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 86:23-24, s. 844-853
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA).
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- Flores, Wilfredo C., et al.
(författare)
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Energy System Observatory of Honduras
- 2021
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Ingår i: 2021 IEEE Electrical Power and Energy Conference (EPEC). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 536-540
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Konferensbidrag (refereegranskat)abstract
- Data management is strategically necessary to make decisions, planning and monitoring within the energy sector. Recently, the Engineering Faculty of the Universidad Tecnológica Centroamericana (UNITEC), Honduras launched a tool called the Energy Observatory of Honduras. This tool fills the gap that exists in the access to energy data within the country. This tool provides data from the demand and generation of electricity in a free and easy way. Also, the information relating to the consumption of fossil fuels and firewood as well as the access to real-time data and energy indexes are shown.
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