Suchergebnisse

BACKGROUND: The aim of the study is 2-fold. Firstly, it attempts to investigate the potential impact of major political and economic changes on inequalities in all-cause mortality among men and women with different levels of education in three Eastern European countries. Secondly, to identify changes in contribution of smoking and drinking to educational differences in all-cause mortality. Study covers the period from 1982 to 2013. METHODS: Data were collected in 2013-14 as a part of the PrivMort retrospective cohort study. Participants in Russia, Belarus and Hungary provided information on their educational attainment, health-related behaviors and vital statistics of their close relatives (N = 179 691). Odds ratios for mortality and relative indices of inequality (RII) were estimated for individuals aged 20-65 years, stratifying by three levels of educational attainment: higher, secondary and less than secondary education. RESULTS: Those in lower educational groups were significantly more likely to die, through most time periods and sub-groups. The RII increased over time in all countries and both genders, except for Hungarian men. Alcohol consumption and smoking have increasingly contributed to educational inequalities in mortality during this period. CONCLUSION: Educational inequalities in mortality in these Eastern European countries have increased during recent decades. Smoking and alcohol consumption, two major health-related behaviors, made a significant contribution to these increases in inequality.

Cells naturally produce mitochondrial reactive oxygen species (mROS), but the in vivo pathophysiological significance has long remained controversial. Within the brain, astrocyte-derived mROS physiologically regulate behaviour and are produced at one order of magnitude faster than in neurons. However, whether neuronal mROS abundance differentially impacts on behaviour is unknown. To address this, we engineered genetically modified mice to down modulate mROS levels in neurons in vivo. Whilst no alterations in motor coordination were observed by down modulating mROS in neurons under healthy conditions, it prevented the motor discoordination caused by the pro-oxidant neurotoxin, 3-nitropropionic acid (3-NP). In contrast, abrogation of mROS in astrocytes showed no beneficial effect against the 3-NP insult. These data indicate that the impact of modifying mROS production on mouse behaviour critically depends on the specific cell-type where they are generated. ; J.P.B. is funded by the Agencia Estatal de Investigación (SAF2016-78114-R, PID2019-105699RB-I00/AEI/10.13039/501100011033 and RED2018-102576-T), Plan Nacional sobre Drogas (2020I028), ISCIII (CB16/10/00282), Junta de Castilla y Le ́on (Escalera de Excelencia CLU-2017-03), Ayudas Equipos Investigación Biomedicina 2017 Fundaci ́on BBVA and Fundaci ́on Ram ́on Areces. A.A. is funded by the ISCIII (PI18/00265, RD16/0019/0018), AEI (SAF2017-90794-REDT) and European Union's Horizon 2020 Research and Innovation Program (Grant Agreement 686009). J.P.B. and A.A. are funded by the grant CSI151P20 from the Junta de Castilla y Leon.

BACKGROUND: We summarise the work of the Childhood Cancer Research Group, particularly in relation to the UK National Registry of Childhood Tumours (NRCT). METHODS: The Group was responsible for setting up and maintaining the NRCT. This registry was based on notifications from regional cancer registries, specialist children's tumour registries, paediatric oncologists and clinical trials organisers. For a large sample of cases, data on controls matched by date and place of birth were also collected. RESULTS: Significant achievements of the Group include: studies of aetiology and of genetic epidemiology; proposals for, and participation in, international comparative studies of these diseases and on a classification system specifically for childhood cancer; the initial development of, and major contributions to, follow-up studies of the health of long-term survivors; the enhancement of cancer registration records by the addition of clinical data and of birth records. The Group made substantial contributions to the UK government's Committee on Medical Aspects of Radiation in the Environment. CONCLUSION: An important part of the ethos of the Group was to work in collaboration with many other organisations and individuals, both nationally and internationally: many of the Group's achievements described here were the result of such collaborations.

Neurons depend on oxidative phosphorylation for survival, whereas astrocytes do not. Mitochondrial respiratory chain (MRC) complexes can be organized in higher structures called supercomplexes, which dictate MRC electron flux and energy efficiency. Whether the specific metabolic shapes of neurons and astrocytes are determined by the specific organization of MRC complexes is unknown. Here, we found that, in astrocytes, most complex I is free, resulting in poor mitochondrial respiration but high reactive oxygen species (ROS) production. In contrast, neurons show complex I to be mostly embedded into supercomplexes, thus resulting in high mitochondrial respiration and low ROS production. Thus, MRC organization dictates different bioenergetics preferences of neurons and astrocytes impacting on ROS production, possibly playing a role in neurodegenerative diseases. ; J.P.B. is funded by the Ministry of Economy and Competitiveness (SAF2013-41177-R), Instituto de Salud Carlos III (RD12/0043/0021), European Union (EU) SP3-People-MC-ITN Programme (608381), EU BATCure Grant 666918, and NIH/National Institute on Drug Abuse Grant 1R21DA037678-01. A.A. is funded by Instituto de Salud Carlos III (PI12/00685 and RD12/0014/0007). ; Peer Reviewed

AbstractPregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.

BACKGROUND: Population-level data suggest that economic disruptions in the early 1990s increased working-age male mortality in post-Soviet countries. This study uses individual-level data, using an indirect estimation method, to test the hypothesis that fast privatisation increased mortality in Russia. METHODS: In this retrospective cohort study, we surveyed surviving relatives of individuals who lived through the post-communist transition to retrieve demographic and socioeconomic characteristics of their parents, siblings, and male partners. The survey was done within the framework of the European Research Council (ERC) project PrivMort (The Impact of Privatization on the Mortality Crisis in Eastern Europe). We surveyed relatives in 20 mono-industrial towns in the European part of Russia (ie, the landmass to the west of the Urals). We compared ten fast-privatised and ten slow-privatised towns selected using propensity score matching. In the selected towns, population surveys were done in which respondents provided information about vital status, sociodemographic and socioeconomic characteristics and health-related behaviours of their parents, two eldest siblings (if eligible), and first husbands or long-term partners. We calculated indirect age-standardised mortality rates in fast and slow privatised towns and then, in multivariate analyses, calculated Poisson proportional incidence rate ratios to estimate the effect of rapid privatisation on all-cause mortality risk. FINDINGS: Between November, 2014, and March, 2015, 21 494 households were identified in 20 towns. Overall, 13 932 valid interviews were done (with information collected for 38 339 relatives [21 634 men and 16 705 women]). Fast privatisation was strongly associated with higher working-age male mortality rates both between 1992 and 1998 (age-standardised mortality ratio in men aged 20-69 years in fast vs slow privatised towns: 1·13, SMR 0·83, 95% CI 0·77-0·88 vs 0·73, 0·69-0·77, respectively) and from 1999 to 2006 (1·15, 0·91, 0·86-0·97 vs 0·79, 0·75-0·84). After adjusting for age, marital status, material deprivation history, smoking, drinking and socioeconomic status, working-age men in fast-privatised towns experienced 13% higher mortality than in slow-privatised towns (95% CI 1-26). INTERPRETATION: The rapid pace of privatisation was a significant factor in the marked increase in working-age male mortality in post-Soviet Russia. By providing compelling evidence in support of the health benefits of a slower pace of privatisation, this study can assist policy makers in making informed decisions about the speed and scope of government interventions. FUNDING: The European Research Council.