Large-scale genomic analyses of ancient human populations have become feasible partly due to refined sampling methods. The inner part of petrous bones and the cementum layer in teeth roots are ...currently recognized as the best substrates for such research. We present a comparative analysis of DNA preservation in these two substrates obtained from the same human skulls, across a range of different ages and preservation environments. Both substrates display significantly higher endogenous DNA content (average of 16.4% and 40.0% for teeth and petrous bones, respectively) than parietal skull bone (average of 2.2%). Despite sample-to-sample variation, petrous bone overall performs better than tooth cementum (p = 0.001). This difference, however, is driven largely by a cluster of viking skeletons from one particular locality, showing relatively poor molecular tooth preservation (<10% endogenous DNA). In the remaining skeletons there is no systematic difference between the two substrates. A crude preservation (good/bad) applied to each sample prior to DNA-extraction predicted the above/below 10% endogenous DNA threshold in 80% of the cases. Interestingly, we observe signficantly higher levels of cytosine to thymine deamination damage and lower proportions of mitochondrial/nuclear DNA in petrous bone compared to tooth cementum. Lastly, we show that petrous bones from ancient cremated individuals contain no measurable levels of authentic human DNA. Based on these findings we discuss the pros and cons of sampling the different elements.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Non-alcoholic steatohepatitis (NASH) is a medical disease of unmet therapeutic need.•Numerous drugs are in various stages of clinical development for NASH.•Improvement of liver fibrosis is the most ...important treatment outcome variable.•Mouse models of NASH have varying clinical translatability.•Anti-NASH drug efficacy can be assessed in relevant mouse models of NASH.
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in the Western world. NAFLD is a complex spectrum of liver diseases ranging from benign hepatic steatosis to its more aggressive necroinflammatory manifestation, nonalcoholic steatohepatitis (NASH). NASH pathogenesis is multifactorial and risk factors are almost identical to those of the metabolic syndrome. This has prompted substantial efforts to identify novel drug therapies for correcting underlying metabolic deficits, and to prevent or alleviate hepatic fibrosis in NASH. Available mouse models of NASH address different aspects of the disease, have varying clinical translatability, and, therefore, also show different utility in drug discovery.
Danish registers contain information on many important health and social issues. Because
all Danish citizens have a unique personal identification number, linkage at the
individual level between ...these nationwide registers and other data sources is possible and
feasible. In this paper we briefly introduce selected Danish registers and the data
structure and requirements for getting access to data at Statistics Denmark, which is the
main provider of register data. We introduce the Danish Data Archive and briefly present
the Act on Processing of Personal Data, which is the legal foundation for analyses of
register-based data in Denmark.
BackgroundSocial inequality trends in life expectancy are not informative as to changes in social disparity in the age-at-death distribution. The purpose of the study was to investigate social ...differentials in trends and patterns of adult mortality in Denmark.MethodsRegister data on income and mortality from 1986 to 2014 were used to investigate trends in life expectancy, life disparity and the threshold age that separates ‘premature’ and ‘late’ deaths. Mortality compression was quantified and compared between income quartiles.ResultsSince 1986, male life expectancy increased by 4.2 years for the lowest income quartile and by 8.4 years for the highest income quartile. The clear compression of mortality apparent in the highest income quartile did not occur for the lowest income quartile. Premature and late deaths accounted both by 2.1 years of the increase in life expectancy in the lowest income quartile and by 6.0 and 2.4 years, respectively, in the highest income quartile. Life expectancy increased by 5.2 years among women in the lowest income quartile, 2.4 years due to premature deaths and 2.8 years due to late deaths. The gain in life expectancy among women in the highest income quartile of 5.6 years was distributed by 5.0 and 0.6 years due to premature and late deaths, respectively.ConclusionThe study demonstrates that the increasing social gap in mortality appears differently in the change of the age-at-death distribution. Thus, no compression of mortality was seen in the lowest income quartile. The results do not provide support for a uniformly extension of pension age for all.
Abstract
Background
The purpose of the study was to quantify the association between body weight and health by estimating the expected lifetime with and without diabetes (diabetes-free life ...expectancy) at age 30 and 65. In addition, the diabetes-free life expectancy was stratified by educational level.
Methods
Life tables by sex, level of education and obese/not obese were constructed using nationwide register data and self-reported data on body weight and height and diabetes from the Danish National Health Survey in 2021. Diabetes-free life expectancies were estimated by Sullivan’s method.
Results
The difference in life expectancy between not obese 30-year-old men with a long and a short education was 5.7 years. For not obese women, the difference was 4.1 years. For obese men and women, the difference in life expectancy at age 30 was 7.0 and 5.2 years. Women could expect more years without and fewer years with diabetes than men regardless of body weight and educational level. Diabetes-free life expectancy differed by 6.9 years between not obese 30-year-old men with a short and a long education and by 7.7 years for obese men with a short and a long education. For women, the differences were 5.9 and 6.6 years.
Conclusion
The results demonstrate an association of obesity and educational level with life expectancy and diabetes-free life expectancy. There is a need for preventive efforts to reduce educational inequality in life expectancy and diabetes-free life expectancy. Structural intervention will particularly benefit overweight people with short education.
Background: The pension age in Denmark is adjusted in line with projected increasing life expectancy without taking health differentials between occupational groups into account. The purpose was to ...study occupational disparities in partial life expectancy and health expectancy between the ages of 50 and 75. Methods: Register data on occupation and mortality were combined with data from the Danish part of Survey of Health, Ageing and Retirement in Europe in 2010–2014 (N=3179). Expected lifetime without and with activity limitations and without and with long-term illness was estimated by Sullivan’s method and comparisons made between four occupational groups. Results: We found clear differences between occupational groups. Expected lifetime without activity limitations between the ages of 50 and 75 was about 4.5 years longer for men and women in high skilled white-collar occupations than for men and women in low skilled blue-collar occupations. Men in high skilled blue-collar and low skilled white-collar occupations could expect 2.3 and 3.8 years shorter lifetimes without activity limitations, respectively, than men in high skilled white-collar occupations. For women in low skilled white-collar occupations, lifetime without activity limitations was 2.6 years shorter than for women in high skilled white-collar occupations. Due to few observations, no results were obtained for women in the high skilled blue-collar group. The social gradient was also significant when health was measured by years without long-term illness. Conclusions: The results support implementation of a flexible pension scheme to take into account the health differentials between occupational groups.
Trends in health inequalities in 27 European countries Mackenbach, Johan P.; Valverde, José Rubio; Artnik, Barbara ...
Proceedings of the National Academy of Sciences - PNAS,
06/2018, Letnik:
115, Številka:
25
Journal Article
Recenzirano
Odprti dostop
Unfavorable health trends among the lowly educated have recently been reported from the United States. We analyzed health trends by education in European countries, paying particular attention to the ...possibility of recent trend interruptions, including interruptions related to the impact of the 2008 financial crisis. We collected and harmonized data on mortality from ca. 1980 to ca. 2014 for 17 countries covering 9.8 million deaths and data on self-reported morbidity from ca. 2002 to ca. 2014 for 27 countries covering 350,000 survey respondents. We used interrupted time-series analyses to study changes over time and country-fixed effects analyses to study the impact of crisis-related economic conditions on health outcomes. Recent trends were more favorable than in previous decades, particularly in Eastern Europe, where mortality started to decline among lowly educated men and where the decline in less-than-good self-assessed health accelerated, resulting in some narrowing of health inequalities. In Western Europe, mortality has continued to decline among the lowly and highly educated, and although the decline of less-than-good self-assessed health slowed in countries severely hit by the financial crisis, this affected lowly and highly educated equally. Crisis-related economic conditions were not associated with widening health inequalities. Our results show that the unfavorable trends observed in the United States are not found in Europe. There has also been no discernible short-term impact of the crisis on health inequalities at the population level. Both findings suggest that European countries have been successful in avoiding an aggravation of health inequalities.
Syn‐rift successions contain both prolific organic‐rich and coarse‐grained rocks, but these rocks are usually studied independently. Thus, the interplay among organic matter deposition, tectonics and ...sediment supply is not commonly assessed. In this study, we use well logs, Total Organic Carbon (TOC) content, biostratigraphy and seismic data from the SW Barents Sea to unravel the variability of organic‐rich successions and its interaction with potential reservoir rocks in areas affected by active normal faulting versus tectonically stable areas. Four Transgressive‐Regressive (T‐R) sequences were defined for the Middle to Upper Jurassic Fuglen Formation and for the organic‐rich Upper Jurassic to lowermost Cretaceous Hekkingen Formation. Three TOC trends, controlled by palaeobathymetric variations, and organic matter dilution, were identified within the two main organic‐rich sequences (sequences 2 and 3): (a) wells with the highest TOC values (>10 wt %) at the base of the succession; (b) wells with the highest TOC values at the top of the succession and (c) wells with high TOC values at the base and top of the succession. Our interpretation indicates that fault activity controlled the TOC trends in two different ways: Firstly, by creating a sharp topographic contrast‐triggering hyperpycnal flows, and shallowing the footwalls, where higher oxygen content and less developed stratified waters lowered organic matter preservation. Secondly, by significantly increasing the input of clastic material, which inherently led to dilution of organic matter and resulted in lower TOC values (<6 wt %). We interpret that sand deposition was controlled by the size and geomorphology of the sediment source areas. The western part of the study area (i.e. the Loppa High) was characterized by uplifted footwall islands and localized sands along their flanks, whereas the southern part (i.e. the Finnmark Platform) constituted a larger sediment source area for the Volgian age. This work has implications for a better understanding of the distribution of reservoir and source rocks in active rift basins.
Palaeobathymetric variations and organic matter dilution controlling TOC trends. (a) Tectonically stable areas or areas affected by minor faulting. (b) Area affected by active normal faults.
Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 ...increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity. siRNA experiments further suggest that induction of ApoA-I mRNA is mediated by BET family member BRD4. These data indicate that RVX-208 increases ApoA-I production through an epigenetic mechanism and suggests that BET inhibition may be a promising new approach to the treatment of atherosclerosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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