Neonatal exposure to DES induced permanent alterations in DNA methylation status of specific genes in mouse uteri
2008 Study Summary
We have provided evidence that early-life exposure of the mice to the xenoestrogen Diethylstilbestrol (DES) or the phytoestrogen GEN induces life reprogramming of the mouse uterine epigenome. Specific genes with no previously documented associations with the uterus were identified by an unbiased methylation profiling methodology. These genes encode proteins involved in a wide-range of cellular functions. Detailed studies were conducted on one of the reprogrammable genes, Nucleosomal Binding Protein 1 (Nsbp1), which is a nucleosome binding and transcriptional activation element. Our data support the paradigm that manifestation of early-life epigenetic reprogrammed gene expression in the mouse uterus is dependent on adult ovarian steroids and changes over the course of natural aging of the animal. The complex interplay among the type of estrogen, timing of exposure, reproductive status, and aging time line all significantly contribute to the phenotypical outcome of the epigenetic reprogramming in this model system.
Sources and Full Study
Persistent Hypomethylation in the Promoter of Nucleosomal Binding Protein 1 (Nsbp1) Correlates with Overexpression of Nsbp1 in Mouse Uteri Neonatally Exposed to Diethylstilbestrol or Genistein, NCBI, Endocrinology. 2008;149(12):5922-5931. doi:10.1210/en.2008-0682, PMC2613067, Dec 2008.
In celebration of International Women’s Day, take part in YouTube’s global #DearMe initiative to inspire and empower young girls everywhere. We all know that growing up is tough. But if you could go back in time, what wisdom would you share with your teenage self? It all starts with two words. Dear Me.
Autism condition is far more heritable than previously thought
2015 Study Abstract
Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.
To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.
Design, Setting, and Participants
We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview–Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs).
Main Outcomes and Measures
Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis.
On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).
Conclusions and Relevance
The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.
Sources and more information
Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample, JAMA Psychiatry, doi:10.1001/jamapsychiatry.2014.3028, articleid=2173394, March 04, 2015.
Autism ’caused by genetics’, study suggests, independent, 05 March 2015.
Le Formindep appelle la ministre de la santé à appliquer enfin la loi
Le Conseil d’État s’est enfin prononcé sur le dispositif de publication des conventions et des avantages et de déclaration des liens d’intérêts.
Ses deux arrêts du 24 février 2015 (n°369074 et 370432) apportent des éléments de réponse aux différentes critiques qui avaient été soulevées par le Formindep et le CNOM.
La définition des conventions qui doivent être rendues publiques et la nature des informations correspondantes sont validées, avec une interprétation qui en réalité renforce la portée du dispositif.
Il faut en retenir que toutes les conventions se traduisant par un versement de la part d’une entreprise à un professionnel de santé sont donc visées par l’obligation de publication, quand bien même elle se rapporterait à un achat ou une prestation de service la plus banale qui soit (par exemple un rapport d’expertise médicale, le paiement de redevances de propriété intellectuelle etc..).
La notion d’avantages est également éclairée par le Conseil d’Etat, avec cette fois-ci plus de vigueur.
Il faut en retenir que toutes les rémunérations (honoraires, commissions, salaires …) versées aux professionnels de santé qui ne travaillent pas comme salariés à titre principal doivent être déclarées comme avantaqes, ce qui double l’obligation de publication de la convention.
Sources et plus d’information
Requête en annulation des décrets 413 et 414 :Décisions contrastées du Conseil d’État, formindep, vendredi 6 mars 2015.
Le Formindep appelle la ministre de la santé à appliquer enfin la loi, formindep, jeudi 5 mars 2015.
Chemical exposure linked to hundreds of billions of Euros per year in health care costs in the EU only
Exposure to hormone-disrupting chemicals is likely leading to an increased risk of serious health problems costing hundreds of billions (U.S.) per year in Europe alone…
2015 Study Abstract
Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability.
The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU).
A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data.
Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or $209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs.
Conclusions: EDC exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those EDCs with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.
Sources and more information
Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union, Endocrine Society, doi/pdf/10.1210/jc.2014-4324, March 05, 2015.
Male Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union, Endocrine Society, doi/pdf/10.1210/jc.2014-4325, March 05, 2015.
Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union, Endocrine Society, doi/pdf/10.1210/jc.2014-4326, March 05, 2015.
Neurobehavioral Deficits, Diseases and Associated Costs of Exposure to Endocrine Disrupting Chemicals in the European Union, Endocrine Society, doi/pdf/10.1210/jc.2014-4323, March 05, 2015.
Chemical Exposure Linked to Billions in Health Care Costs, nationalgeographic, MARCH 5, 2015.
” MMU presents the video ’10 Hours of Walking in NYC as a Woman’ from the anti-street harassment organisation Hollaback!. Students are warmly welcomed to view the short piece and participate in group discussions in the MMUBS atrium. Everybody has the right to walk down the street in peace, regardless of their gender. Yet, abuse can be a daily encounter for some people. So join us in sharing your perspective and help shine a spotlight on street harassment. ”
Join “Hey Gorgeous!” An exploration of street harassment on and off campus, Venue: G.26 MMU Business School, M15 6BH, 4:00pm Thursday, 5th March 2015 – 5:00pm Thursday, 5th March 2015, mmu, +44 (0)161 247 2000.
We are lucky in England to have excellent cancer services and to be seeing improving outcomes for cancer patients through diagnosing more people earlier and delivering more effective treatments.
This is driven by work across the sector between many partners like the NHS, charities and government. PHE and our National Cancer Intelligence Network are central to supporting this, and improving people’s outcomes by using the vast information collected about cancer patients in England for analysis, publication and research.
However, our data shows us that the needs of cancer patients are changing. Nearly two thirds of cancer diagnoses occur in the over 65s and one third in people aged 75, with over half of all cancer deaths occurring in people aged 75 and over.
By 2020 there will be nearly two million people aged 65 and over with a cancer diagnosis.
Indeed, we examined the impacts of cancer on older people in a report we jointly published in December with NHS England and others like MacMillan, Cancer Research UK, Incisive Health, Quality Health, Department of Health and the Geriatric Oncology Expert Reference Group.
The report covers a wide range of issues and of course, not all older people are the same. Things like ethnicity, socio-economic background, type of cancer or the patient’s general health impact the way they are affected by the disease.
The report does however highlight some important general points on the treatment of cancer in older people.
Late diagnosis is a problem for older people and more needs to be done to encourage older people to recognise the signs and symptoms of cancer and seek appropriate help.
Older people are more likely to be diagnosed following an emergency presentation at hospital, which usually means the cancer is more advanced and therefore harder to treat. Cancer survival decreases with increasing age, in particular for people over 70.
Somewhat controversially, the report also shows that older patients are also less likely to receive active cancer treatment, be it surgery, radiotherapy or cancer drugs.
In some cases, there will be good reasons for this, where frailty affects the effectiveness of treatment or treatment will have unacceptable impacts on quality of life. However, the NHS has stated that age should not be a barrier to treatment and the NCIN will continue to work with its partners to provide high quality information and analysis to ensure patients receive appropriate treatment.
From a wider public health perspective, the evidence shows that there is more that older people could do to help reduce their risk of developing cancer, and also be fit for more aggressive (but more effective) cancer treatments by changing their lifestyle.
It’s never too late for lifestyle change, but the earlier it starts, the better.
The evidence suggests that more than 4 in 10 of all cancer cases in the UK each year could be prevented by lifestyle changes, with the key factors being smoking, alcohol (both less common in older people than the adult population overall), overweight and obesity, and physical inactivity (both more common in older people than the adult population overall).
Information on how to take action and make positive changes to your lifestyle can be found at the Change4Life website.
I have touched upon just some of the main issues outlined in the report. It sets out in detail what the evidence shows are the other major issues affecting older people with cancer, including the facts that older people are more likely to be satisfied with the treatment they receive, but less likely to be involved in cancer research.
Age is just one of the areas of inequality that the NCIN looks at, but the report should form an excellent starting point from which the NCIN and importantly, our partners can help to improve the outcomes for older people with cancer.
Have you found what I have highlighted interesting?
Are there people you know who would benefit from seeing the report?
Please feel free to share this blog and the report itself and expand the network of people who might benefit from our work.