Transcriptome and Proteome Analyses Reveal Stage-Specific DNA Damage Response in Embryos of Endangered Sturgeon

DNA damage during early life stages may have a negative effect on embryo development, inducing malformations that have long-lasting effects during adult life. Therefore, in the current study, we analyzed the effect of DNA damage induced by genotoxicants (camptothecin (CPT) and olaparib) at different stages of embryo development. We analyzed the survival, DNA fragmentation, transcriptome, and proteome of the endangered sturgeon Acipenser ruthenus. Sturgeons are non-model fish species that can provide new insights into the DNA damage response and embryo development. The transcriptomic and proteomic patterns changed significantly after exposure to genotoxicants in a stage-dependent manner. The results of this study indicate a correlation between phenotype formation and changes in transcriptomic and proteomic profiles. CPT and olaparib downregulated oxidative phosphorylation and metabolic pathways, and upregulated pathways involved in nucleotide excision repair, base excision repair, and homologous recombination. We observed the upregulated expression of zona pellucida sperm-binding proteins in all treatment groups, as well as the upregulation of several glycolytic enzymes. The analysis of gene expression revealed several markers of DNA damage response and adaptive stress-response, which could be applied in toxicological studies on fish embryo. This study is the first complex analysis of the DNA damage response in endangered sturgeons.

Lifelong Disadvantage and Late Adulthood Frailty

Frailty is a complex state of objective and subjective vulnerability. It tends to increase with age, but the process is influenced by previous life course, especially previous disadvantages. The aim of this paper is to examine how the disadvantages suffered in adulthood (25 to 59 years) in four domains (unemployment, financial hardship, stress, and bad health) affect frailty in late adulthood (60 to 79 years). Using linear regression models on data from the Survey of Health, Ageing, and Retirement in Europe (2004–2017), we estimate frailty levels for several age groups (60–64, 65–69, 70–74, 75–79) accounting for both the persistence of these disadvantages over time and their coexistence, i.e., the number of years when they were simultaneously experienced. Results show that while frailty increases with age, as expected, there is also evidence of an accumulation of risks: the longer the periods of adult life affected by unemployment, stress, financial hardship or, most importantly, bad health, the frailer individuals are in their late years. Furthermore, periods of coexisting disadvantages in adulthood translate into additional frailty in late life. Our findings highlight the importance of fighting disadvantages early in life: long-term improvements in terms of reduced frailty (a concept interrelated with health) may be substantial.

Do partnership dissolutions and living alone affect systemic chronic inflammation? A cohort study of Danish adults

BackgroundPartnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups or years lived alone across 26 years of adult life are associated with levels of inflammation, and if vulnerability with regards to gender or educational level can be identified.Methods4835 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48–62 years were included. Data on accumulated numbers of partnership breakups and years living alone were retrieved from a national standardised annual register. Inflammatory markers interleukin 6 (IL-6) and high sensitivity C-reactive protein (hsCRP) were measured in blood samples. Multivariate linear regression analyses were adjusted for age, educational level, early major life events, body mass index, chronic diseases, medicinal intake affecting inflammation, acute inflammation and personality scores.ResultsFor men, an association was found between an increasing number of partnership breakups or number of years living alone and higher levels of inflammatory markers. No such association was found for women, and no evidence of partnership breakups and educational level having a joint effect was found for either gender.ConclusionThe findings suggest a strong association between years lived alone or accumulated number of partnership breakups and low-grade inflammation for middle-aged men, but not for women. Among those of either sex with a lower level of education, no specific vulnerability to accumulated years lived alone or number of breakups was identified.

Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes

Obstetric and newborn outcomes of assisted reproductive technology (ART) pregnancies are associated with significative prevalence of maternal and neonatal adverse health conditions, such as cardiovascular and metabolic diseases. These data are interpreted as anomalies in placentation involving a dysregulation of several molecular factors and pathways. It is not clear which extent of the observed placental alterations are the result of ART and which originate from infertility itself. These two aspects probably act synergically for the final obstetric risk. Data show that mechanisms of inappropriate trophoblast invasion and consequent altered vascular remodeling sustain several clinical conditions, leading to obstetric and perinatal risks often found in ART pregnancies, such as preeclampsia, fetal growth restriction and placenta previa or accreta. The roles of factors such as VEGF, GATA3, PIGF, sFLT-1, sEndoglin, EGFL7, melatonin and of ART conditions, such as short or long embryo cultures, trophectoderm biopsy, embryo cryopreservation, and supraphysiologic endometrium preparation, are discussed. Inflammatory local conditions and epigenetic influence on embryos of ART procedures are important research topics since they may have important consequences on obstetric risk. Prevention and treatment of these conditions represent new frontiers for clinicians and biologists involved in ART, and synergic actions with researchers at molecular levels are advocated.

Quality of life and challenges experienced by the surviving adults with transfusion dependent thalassaemia in Malaysia: a cross sectional study

Background Improvement in medical management has enabled transfusion dependent thalassaemia (TDT) patients to survive beyond childhood, building families, and contributing to the labour force and society. Knowledge about their adult life would provide guidance on how to support their needs. This study aims to explore the general well-being of adults with TDT, their employment status and challenges. Methods This study recruited 450 people with TDT, aged 18 and above, of both genders through all regional Thalassaemia societies in Malaysia and from the two participating hospitals, over five months in year 2016. A self-administered questionnaire including ‘Healthy Days Core Module’, WHOQOL-BREF and employment measurements was used. Multiple linear regression models were fitted with associations adjusted for several potential confounders. Results A total of 196 adults with TDT responded to the survey (43.6% response rate). Almost half (45%) had comorbidities and 9% suffered multiple complications: bone-related (13%), hormonal (12%), cardiac (3%) and infections (2%), resulting in 23% seeking treatment more than twice monthly. Within a month, they suffered from at least three days with poor physical and or mental health and their normal daily activities were disrupted up to three days. 36% were jobless and 38% of those with a job were receiving salaries below RM1000. The mean WHOQOL-BREF score (mean (SD)) was: physical health 62.6 (15.5), psychological health 64.7 (15.7), social relationship 64 (15.9), environmental health 60.8 (16.7). Having days with mental issues, financial status, education level, ethnic and marital status were main factors affecting QOL scores. Open questions showed dissatisfaction with health service provision, conflicting judgement in prioritising between health and job, and poor public empathy. Conclusion The adults with TDT perceived their health as good and had less unhealthy days when compared with people with other chronic diseases. However, some perceived themselves to be facing more life disruption in a rather non-supportive community and that health services do not meet their needs. Future qualitative studies are needed to focus on their perceived needs and to look for more tailored supportive approaches.

Generational differences in income trajectories in the Nordic welfare state

How much it matters for your income development what generation you happen to be born? We answer this question by using registers of the total population, we study generational income inequality during 1970–2018 and, for men and women in Finland. We follow the income trajectories of the cohorts born in 1920–1983 over their adult life course and observed, how certain structural factors explain differences in income trajectories. Our study expands state-of-the-art knowledge, as previous research has often bypassed the question of how much generational income differences explains of populations total income inequalities and what factors may explain the different generational income trajectories. Results show that overall generational income differences explained quarter for women and 6 percent for men total income inequality. Each successive cohort until 1980s had a higher average income trajectory. However, generation born in the 1980s has been falling behind. For both men and women, age structure and education were the most important factors associated with income inequality. On contrary to previous findings on Nordic welfare state, our results also indicate that, generational income trajectories are affected by economic shocks.

Ethical and Bioethical Aspects in the Use of Stem Cells in Chronic Spinal Cord Injuries

One of the fundamental dogmas maintained in neuroscience until the last century held that regeneration of the nervous system cannot occur in stages of adult life. However, it has been shown in several species during the postnatal stage and throughout life, that new neurons continue to be generated in some places in the human body. Objectives: The research was: to evaluate ethical and bioethical aspects in patients who were treated with an autologous stem cell implant in chronic spinal cord injuries. Method. An analysis is made of the ethical aspects that accompany the implantation of autologous stem cells in chronic spinal cord injuries. The results are evaluated at the "Enrique Cabrera" Surgical Clinical Teaching Hospital. Results: Ethical dilemmas are expressed and that have, among their relevant principles, the inviolability of human life. In higher animals, stem cells according to their evolutionary state can be embryonic and somatic or adult. Currently there is an extraordinary controversy about which stem cells to use from embryonic or adult ones, a debate in which both scientific, ethical, religious, social and political aspects have been included. One aspect of the scientific debate is related to the generative capacity of tumors by embryonic cells. From the ethical point of view, it has been argued that the use of human embryonic stem cells implies the destruction of embryos and it has been considered that life begins at the same moment of the union of the sperm with the ovum and that this would be equivalent to the destruction of a human life which would not be justifiable. Others do not agree with these criteria and argue that their use to save lives through research or therapy would be justified. Conclusions The physical disability produced by a chronic spinal cord injury raises an ethical dilemma about the use of stem cells, anticipating that the main controversy about this action has to do fundamentally with the way in which they are obtained.