Designer Viruses Stimulate the Immune System to Fight Cancer

Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy

Swiss scientists have created artificial viruses that can be used to target cancer. These designer viruses alert the immune system and cause it to send killer cells to help fight the tumor. The results provide a basis for innovative cancer treatments.

2017 Study Abstract

Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTLeff) responses. Conversely, the induction of protective tumour-specific CTLeff and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTLeff responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTLeff influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy.

Sources
  • Designer Viruses Stimulate the Immune System to Fight Cancer, University of Basel, 26 May 2017.
  • Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy, Nature Communications, doi:10.1038/ncomms15327, 26 May 2017.
  • Image : Stable transgene expression and attenuation of artLCMV in vivo, nature, Figure 2, 26 May 2017.

Many children with bi-polar and ADHD symptoms can be helped without the use of dangerous off-label drugs

Let’s try to find ways to relieve illness without the use of drugs

Video by dr rapp, published on 22 February 2008.

Many children with bi-polar and ADHD symptoms can be helped without the use of dangerous off-label drugs.

There are fast, easy and inexpensive answers available.

Each individual is different and the treatment is rarely identical.

Dr. Doris Rapp has dedicated her life to identifying and providing simple solutions to these and other behavior problems.

Our challenge for physicians is to find fast, easy, safe, effective and inexpensive ways to heal.

Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring

DES is one of the major disasters in medicine and it is mandatory to tackle and promote programs of DES-related cancer prevention

2017 Study Highlights

  • Diethylstilbestrol (DES) is a synthetic, non-steroidal estrogen of the stilbestrol group acting as an endocrine disruptor.
  • Adverse pregnancy outcomes, infertility, cancer, and early menopause have been identified in women exposed to DES, their offspring, and subsequent generations.

Abstract

Diethylstilbestrol (DES) was an orally active estrogen prescribed to the pregnant women to prevent miscarriages.

DES is known as a ‘biological time bomb’ and long-term effects of DES have been recorded in the mothers exposed to DES and their offspring (DES-daughters and DES-sons). Adverse pregnancy outcomes, infertility, cancer, and early menopause have been discovered in women exposed to DES, and some events occur in their offspring and subsequent generations. An increased risk of breast cancer is not limited to the DES-exposed daughters.

There is an urgent need to find ways to stop the inheritance cycle of DES and prevent adverse effects of DES in the future generations. The present article reviews the health implications of DES exposure and screening exams currently recommended to DES daughters and their offspring.

  • Reproductive toxicology (Elmsford, N.Y.)., Volume 71, August 2017, Pages 71–77, 2017 Apr 28. Image credit jason wilson.
DES DiEthylStilbestrol Resources

Zéro Phyto 100% Bio – Bande-annonce

Le documentaire des cantines bio et des villes sans pesticides !

Vidéo via Guillaume Bodin diffusée le 27 mars 2017.

Guillaume Bodin, réalisateur du film “Zéro phyto 100% bio” est en train de finaliser le film, l’affiche est prête et de nombreuses avants-premières sont prévues.

En savoir plus

SYNOPSIS

Après Insecticide mon amour, le réalisateur Guillaume Bodin présente Zéro phyto 100 % bio, son nouveau documentaire. Une enquête passionnante sur plusieurs communes françaises qui n’ont pas attendu l’entrée en vigueur le 1er janvier 2017 de la loi Labbé interdisant l’utilisation de pesticides dans les espaces publics pour changer leurs pratiques. Ce film met aussi en avant les pionniers de la restauration collective biologique et leurs partenaires : associations, entreprises, agriculteurs, ingénieurs, artisans qui ensemble contribuent à l’amélioration de la qualité des repas dans les collectivités. Les associations Générations Futures, Bio Consom’acteurs et Agir Pour l’Environnement sont à l’initiative de ce projet.

UNE PETITE RÉVOLUTION EST EN MARCHE DANS LA GESTION DES ESPACES VERTS.

À Versailles, Miramas, Grande-Synthe, Langouët et Laurenan, la présence de pesticides chimiques de synthèse dans les espaces publics est déjà de l’histoire ancienne. À budget constant, voire inférieur, ces villes et villages arrivent à maîtriser les herbes folles autrement et fleurir ou cultiver des surfaces auparavant inutilisées. Cette dynamique écologique renforce les liens sociaux, permet de préserver la santé des techniciens comme des citoyens et engendre d’autres projets, notamment culturels.

Privilégier les espèces vivaces et endémiques, aider les professionnels et les citoyens à adopter de nouveaux réflexes, inciter les entreprises à innover pour mieux répondre aux nouvelles pratiques paysagères sont autant d’actions qui participent à une gestion écologique globale des villes, tout en respectant la santé des habitants.

DU 100% LOCAL ET BIOLOGIQUE DANS LA RESTAURATION COLLECTIVE, C’EST POSSIBLE !

Le projet de loi imposant 20 % de produits issus de l’agriculture biologique dans la restauration collective n’a pas été adopté au Sénat, mais cela n’a pas empêché certaines communes de prendre les devants.

À Mouans-Sartoux, la régie agricole municipale répond à l’essentiel des besoins alimentaires de la commune. Le reste est fourni par des fermes biologiques locales.

À Langouët comme à Paris, dans les 2e et 5e arrondissements, les élus ont adopté des mesures drastiques pour améliorer la qualité des repas et collaborent étroitement avec des agriculteurs bio et des associations de leur région.

Comme le dit le maire de Barjac, « nourrir, c’est aimer », alors pourquoi « lésiner » quand il s’agit de nourrir nos enfants ? Les populations des hôpitaux, des prisons, des écoles ou des maisons de retraite n’ont-elles pas droit à une alimentation saine et de qualité ?

Conscients de leurs responsabilités en termes de santé publique et d’environnement, ces acteurs de terrain ne livrent pas de solutions toutes prêtes, mais décrivent plutôt les étapes qu’ils ont franchies pour mener à bien leurs projets. Leur expérience montre que toutes les communes, quelles que soient leur taille et leur couleur politique, peuvent changer leurs pratiques.

UN DOCUMENTAIRE D’UTILITÉ PUBLIQUE À DIFFUSER LE PLUS LARGEMENT POSSIBLE.

À PROPOS
  • Après dix ans passés à travailler dans les vignes, Guillaume Bodin a décidé de réaliser des documentaires pour parler de sujets qui lui tiennent à cœur. La Clef des Terroirs, sorti en mars 2011, dresse le portrait de vignerons qui prennent soin de leurs terres grâce à des techniques écologiques, dont la biodynamie. Dans son deuxième documentaire, Insecticide Mon Amour (sorti en 2015), il mène une recherche approfondie sur le traitement obligatoire contre la flavescence dorée dans le vignoble bourguignon et ses effets sur l’environnement et la santé. Ces deux films ont été remarqués et primés dans plusieurs festivals. Disponibles en DVD, ils sont toujours diffusés en salle en France et à l’étranger. Zéro phyto 100 % bio a fait l’objet d’un financement participatif sur Zeste par la Nef ayant rassemblé plus de 1600 donateurs.
  • En partenariat avec Biocoop, Botanic, NaturéO, Fondation Léa Nature, Bjorg, Danival, Ametis Scop, Rebelle-Santé, Un Plus Bio…
  • Musique Mar-iOn Vincent-Royol, Emily Loizeau, Saint Michel
  • Animation Ludovic Caillot
  • Voix off & Mixage Son SilRêve Studio
  • Illustration de l’affiche Isa Blangonnet
  • Graphisme de l’affiche et des flyers Bon Pied Bon Oeil

Relationship of Air Pollution to Sleep Disruption

The Multi-Ethnic Study of Atherosclerosis (MESA) Sleep and MESA-Air Studies

High levels of air pollution over time may get in the way of a good night’s sleep, according to new research presented at the ATS 2017 International Conference. Image credit Craig Sunter.

2017 Study Abstract

Introduction
Exposure to air pollution is associated with cardiovascular mortality and pulmonary morbidity, including asthma, COPD, lower respiratory infections, and possibly sleep apnea. Although air pollution also may influence sleep quality through alterations in inflammatory or autonomic nervous system pathways, the relationship between air pollution and sleep has not been well studied. We evaluated the relationship between participant-level estimates of long-term ambient-derived traffic-related air pollution exposure with objective sleep fragmentation.

Methods
We analyzed data from a subpopulation of the Multi-Ethnic Study of Atherosclerosis (MESA) who participated in both MESA Sleep and AIR studies. Exposure to traffic related air pollutants (oxides of nitrogen) were estimated at participants’ homes using spatio-temporal models based on cohort-specific monitoring averaged for one and five years prior to sleep assessment. Objective sleep fragmentation was evaluated with wrist actigraphy recorded over seven 24 hour periods. We used multivariate logistic regression models to evaluate for an association of traffic related air pollution with low sleep efficiency (<88%) and increased wake after sleep onset (WASO; > 60 mins). We adjusted for socio-demographics, sleep apnea (AHI>15), short sleep duration (< 6 hrs) and residential socio-economic status (SES).

Results
MESA participants (n=1863) were an average age 68 (+/- 9) years, 46% male, 36% white, 24% Hispanic, 29% black and 12% Asian. A quarter of the sample had < 88% sleep efficiency and 11% had WASO > 60 mins. The highest quartile NO2 exposure level (> 23.7 ppb) over 5 years compared to the lowest (< 10 ppb) was associated with a 57% greater odds of low sleep efficiency in fully adjusted models with a significant test for trend (table 1). The highest quartile compared to the lowest quartile NO2/x average 1 and 5-years exposure levels were also associated with 71-91% greater odds of > 60min WASO.

Conclusions
Higher levels of traffic-related air pollution are associated with greater odds of objectively measured sleep disruption after adjusting for individual and residential socio-demographics. Further research is needed to identify the mechanisms and whether associations are attributable to oxides of nitrogen, traffic noise, other pollutants or environmental exposures that co-vary with traffic.

Identification of EDCs : people and the environment must be protected without delay

Further delay on flawed EDC criteria maintains unnecessary risks on human health and the environment

Brussels, 18 May 2017 – The criteria to identify hormone disrupting chemicals (or EDCs), for which a decision was expected today, continue to cause disagreements among EU member states.

The EDC-Free coalition urges the European Commission and member states to amend the proposal to ensure that people and the environment are protected and warns that further delays and failure to agree on criteria unnecessarily keep human health at risk.

The coalition has repeatedly criticised that the current proposal requires an unrealistically high burden of proof, which makes the identification of substances as EDCs very difficult and is likely to result in long delays. Another significant loophole is the proposed exemption from identification for certain pesticides and biocides that are designed to be endocrine disrupting, which would strongly undermine protective measures. The EDC-Free coalition also cautions the Commission and member states against industry’s proposals to introduce a derogation based on risk assessment in the pesticides regulation, which would result in continuous exposure of people and the environment to mixtures of toxic pesticides.

After years of setbacks and delays, in June 2016 the European Commission proposed a set of criteria, which have gone through several versions and been the subject of lengthy criticism and controversy. This followed a ruling of the EU Court of Justice, which found that the European Commission breached EU laws by delaying the adoption of measures on EDC criteria.

“The science is clear about the harmful and irreversible effects of endocrine disrupting chemicals. The time for action is now and Europe has the opportunity to lead by example. Protective EDC criteria are needed to reduce people’s exposure to toxic substances and reduce unnecessary burdens on public budgets,”

says Genon K. Jensen, EDC-Free Europe spokesperson.

Scientific professionals and public interest groups such as non-profit health insurers alike have consistently called for the swift adoption of high quality, scientifically sound criteria to accelerate actions to reduce peoples’ exposure to EDCs. Meanwhile over 359,000 citizens have signed a petition calling on member states to take action to ban EDCs.

The failure to minimise exposure to EDCs will maintain a high burden on public health budgets from the diseases arising from exposure to EDCs in the European Union (which is estimated at 163 billion Euro per year). As it stands, it is also a perfect counter-example of the better regulation approach that the Commission has made its motto of.

The EDC-Free coalition calls on the European Commission and member states to amend the proposal so that EDC exposure can be swiftly reduced and environment and health will be protected.

Natacha Cingotti, EDC-Free Europe, a coalition of more than 70 environmental, health, women’s and consumer groups across Europe who share a concern about endocrine disrupting chemicals (EDCs) and their impact on our health and wildlife. EDC-Free Europe is a coalition of more than 70 environmental, health, women’s and consumer groups across Europe who share a concern about endocrine disrupting chemicals (EDCs) and their impact on our health and wildlife.

Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds

Lessons from diethylstilbestrol : psychosis associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity in the DES-exposed.

2017 Study Abstract

BACKGROUND
In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis.

METHODS
From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip® in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We also compared exposed individuals with (n = 7) and without psychosis (n = 30).

RESULTS
There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9). Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 (ZFP57).

CONCLUSIONS
In utero exposure to DES was not associated with methylation changes at specific CpG or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.

  • Image credit Morgaine. Read and download the full study (free access) on the NCBI, PubMed, PMC5390994, 2017 Apr 13.
DES DiEthylStilbestrol Resources

U.S. health care quality and access index far from the top in global study

Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990–2015: a novel analysis from the Global Burden of Disease Study 2015

2017 Study Summary

Background
National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.

Methods
We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure–the Healthcare Quality and Access (HAQ) Index–on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time.

Findings
Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0–42·8) in 1990 to 53·7 (52·2–55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015.

Interpretation
This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world.

Sources and Press Releases
  • Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990–2015: a novel analysis from the Global Burden of Disease Study 2015, the lancet, dx.doi.org/10.1016/S0140-6736(17)30818-8, May 18, 2017.
  • Image : Map of HAQ Index values, by decile, in 1990 (A) and 2015 (B) – credit lancet.
  • ‘An embarrassment’: U.S. health care far from the top in global study, washingtonpost, May 18 2017.

About The Personal Care Products Safety Act

Bill would help protect consumers from chemicals that disrupt hormones

Endocrine Society applauds new push to regulate chemicals in personal care products

Washington, DCThe Endocrine Society praised the reintroduction of a Senate bill to ensure consumers are protected from hazards associated with exposure to chemicals in personal care products such as cosmetics and lotions.

The Personal Care Products Safety Act, co-sponsored by U.S. Sens. Dianne Feinstein and Susan Collins, would set a rigorous safety standard for personal care products and provide the public with more information about the chemicals in the products they are purchasing. This is an area of concern for the Society and its 18,000 members, including researchers studying how endocrine-disrupting chemicals (EDCs) disrupt the body’s hormones.

An EDC is a chemical or mixture of chemicals that can cause adverse health effects by interfering with hormones in the body. There are more than 85,000 manufactured chemicals, of which thousands may be EDCs. EDCs are found in everyday products and throughout the environment.
The evidence is more definitive than ever before that EDCs disrupt hormones in a manner that harms human health. EDC-related health outcomes include male reproductive disorders, premature death, obesity and diabetes, neurological impacts, breast cancer, endometriosis, female reproductive disorders, immune disorders, liver cancer, osteoporosis, Parkinson’s disease, prostate cancer and thyroid disorders.

The Personal Care Products Safety Act calls for some chemicals found in shampoo, deodorant, cosmetics and other personal care products to be reviewed for safety for the first time. The Society applauded the bill’s inclusion of propyl paraben, a potential EDC linked to reproductive disorders, as one of the first five chemicals slated for review.
By providing the necessary authority and fees for the FDA to properly regulate personal care products, the Society believes that this legislation will effectively and efficiently ensure a safer marketplace for personal care products and reduce harms from exposure to EDCs and other toxic chemicals.

Sources and Press Releases

  • Endocrine Society applauds new push to regulate chemicals in personal care products, TheEndoSociety, May 15, 2017.
  • Senators Seek Enhanced Safety Looks at Cosmetic Ingredients, promomarketing, May 15, 2017.
  • Personal Care Products Safety Act Would Improve Cosmetics Safety, ewg.
Endocrine Disruptors

Victimes Suisses du DES : Appel à Témoin

Votre mère a-t-elle pris du Clinestrol, Cyren B, Cyren S, Estril, Estrobene, Oestrostilben ou Syntostrol ?

En 2012, l’émission 36°9, de la chaîne RTS, avait publié un excellent reportage Distilbène: un héritage empoisonné, traitant des conséquences multi-générationnelles du DES – annonçé ici.

Aujourd’hui en 2017, RTS santé recherche des victimes Suisses du DES distilbène – également commercialisé en Suisse de 1953 à 1977 sous les noms de Clinestrol, Cyren B, Cyren S, Estril, Estrobene, Oestrostilben, Syntostrol – une mère à qui on l’aurait prescrit pendant sa grossesse ou des enfants qui en subissent les conséquences.

Veuillez contacter Réseau DES France via leur site sécurisé.

Les journalistes suisses se déplaceront fin mai près de Perpignan, pour interviewer les victimes de la Dépakine et Marine Martin, présidente de l’APESAC.

Les Filles DES de la région Occitanie, prêtes à témoigner de leur parcours, peuvent contacter Réseau DES France, d’ici ce mardi 23, par courriel.

Le Distilbène DES, en savoir plus