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The Imminent Return of Astronaut Thomas Pesquet

© Inserm/Delapierre Patrick

After 6 months of life in space as part of the Proxima mission, French ESA astronaut Thomas Pesquet will land on Friday, June 2, 2017, in the middle of the afternoon (4:08 p.m. Paris time), aboard the Soyuz capsule which is expected to touch down in the Kazakhstani steppes.

On the station, he carried out scientific experiments developed by the research team from Inserm Unit 1093 “Cognition, action and sensorimotor plasticity” (Inserm/Université de Bourgogne).

The perception of spatial markers among astronauts in zero gravity, space adaptation syndrome through study of the inner ear and cognitive function, biological risks and individual susceptibility to radiation in space, together with the determination of energy needs during spaceflight are some of the themes explored by Inserm researchers.

Once the French astronaut returns to earth, Inserm researchers will be able to study accelerated aging and potential bone changes related to spaceflight.

For news on this subject:

Read the press release “Minimum effort for maximum effect“, published on December 2, 2016.

Read the press release “Décollage de l’astronaute Thomas Pesquet pour l’ISS (Astronaut Thomas Pesquet takes off for the ISS)“, published on November 15, 2016 (only available in French)

Fecal incontinence : a novel therapy for a distressing condition

Plan B for no toilet paper

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Inserm researchers in Rouen (Unit 1234 “PANTHER: Physiopathology, autoimmunity, neuromuscular diseases and regenerative therapies”, Inserm/Université de Rouen Normandie) have tested with success a cell therapy aiming to restore the ability of the sphincters to contract in patients with fecal incontinence. As part of a clinical study conducted in partnership with Rouen University Hospital, 60% of the patients who received this innovative therapy observed a reduction in their incontinence.

This research was published in Annals of surgery.

 Fecal incontinence affects 1 million people in France, 350,000 of whom to a severe extent, and its personal, social, and economic impacts are profound. Particularly affected are young women after childbirth (with 10-15% experiencing incontinence in the subsequent weeks and 4-5% who continue to suffer from a severe and chronic form of the condition). Sphincter damage or dysfunction, which are among the causes of fecal incontinence, are characterized by the fact that the sphincters, the rings of muscle surrounding the anal area, lose their ability to contract correctly.

Researchers at Inserm Unit 1234 “Physiopathology, autoimmunity, neuromuscular diseases and regenerative therapies” associated with the Université de Rouen Normandie joined forces with the Biotherapy Laboratory and Digestive Surgery Department of the University Hospital of Rouen to design a clinical study evaluating therapy with adult stem cells (myoblasts) that are capable of differentiating into effective muscle cells.

 To begin with, a model of the disease was developed at the Inserm research unit. Rats treated with myoblasts showed recovery of their sphincter function. This was associated with the in vivo production of new functional muscle fibers. The researchers then studied the genetic stability of the myoblasts and demonstrated that it was compatible with use in humans. The conditions were therefore ideal for the clinical study to go ahead.

During the study, thigh muscle fragments were taken from the patients,  following which the myoblasts were cultivated in order to obtain sufficient numbers of them. With the help of ultrasound, these myoblasts were then injected into the deficient sphincter so that they could differentiate into functional muscle fibers. A total of 24 patients were enrolled in the study, with half receiving the innovative stem-cell therapy and half receiving a placebo form. The severity of their condition was assessed using the Cleveland Clinic Incontinence (CCI) Score questionnaire at 6 months and 12 months after administration.

One year after the injection, the treatment had worked in 7 of the 12 stem cell patients (58%) whereas only 1 of the 12 (8%) placebo patients had noted an improvement. At the same time, the median CCI score had significantly decreased from 15 to 6.5 points in the treated group, whereas in the placebo group the median score after one year had decreased from 15 to 14.

In light of these positive results, the placebo group patients were also given the possibility to receive the therapy, with their cryopreserved muscle cells. Their response rate was just as satisfactory as that of the first group.

As such, the authors propose an innovative therapeutic solution for refractory fecal incontinence by demonstrating its efficacy and safety. Given the constraints of the reference treatment (sacral neurostimulation), which involves the implantation of exogenous material, it is hoped that in time a place for this cell therapy might be found.

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Months post-injection. ©Olivier Boyer

An alternative route for cholesterol

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©F Alpy/IGBMC

Cholesterol plays a central role in many living processes. In a new study, a team led by Catherine-Laure Tomasetto, Inserm research director at the Institute of Genetics and Molecular and Cellular Biology (Inserm/CNRS/Université de Strasbourg) reveals the role played by the STARD3 protein in the distribution of cholesterol within cells. A little like molecular velcro, this protein has the capacity to form membrane contacts between two cell organelles, enabling it to transport cholesterol from one organelle to another.

This research has been published in the EMBO Journal

Cholesterol is a component of biological membranes and essential for human cell functioning. A cell has two ways of obtaining cholesterol: by capturing it in the blood and internalizing it using endosomes, or by producing it in the endoplasmic reticulum, a network covering the inside of the cell that synthesizes most lipids. Once captured or synthesized, cholesterol is redistributed throughout the cell’s membranes via mechanisms that have not all been elucidated.

Since cholesterol is not water-soluble, its movements within the cell are very limited. To ensure its transport, the cells have specialized transporters. Catherine-Laure Tomasetto’s team is interested in one of them, protein STARD3, the role of which had remained quite a mystery until now. In this new study, the researchers unraveled some of that mystery. STARD3 is anchored to the endosomes, cell organelles that ensure communication between the outside and the inside of cells. Within the cell, STARD3 attaches to VAP, a protein that is itself fixed to the endoplasmic reticulum. This association creates close appositions between the endosome and the endoplasmic reticulum that are known as membrane contact sites. At these sites, the membranes of the two organelles are very close (less than 30 nm), thus facilitating communication and exchange. In this study, the researchers demonstrated that these membrane contact sites between the endosomes and the endoplasmic reticulum form a type of bridge, enabling STARD3 to transfer cholesterol from the membrane of the endoplasmic reticulum to that of the endosome, thereby rerouting some of the cholesterol that was intended for the plasma membrane.

These results therefore identify a new pathway that regulates cholesterol flow within cells. Understanding how cells balance the two available cholesterol sources will probably help us better understand the mechanisms of certain neurodegenerative or cardiovascular disorders presenting alterations in cholesterol distribution.

This study was funded by the French National Cancer Institute (INCA), the French foundation for medical research (FRM), the French League against cancer, the Ara Parseghian Medical Research Foundation, and the Vaincre les Maladies Lysosomales (overcoming lysosomal diseases) association.

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The formation of a membrane contact site for the transport of cholesterol

Image credit: F Alpy/IGBMC

Healing a mother’s skin lesions using her fetal cells?

Schwangere Frau liegend betrachtet Ultraschallbilder

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Since the end of the 20th century, it has been proven that women who have been pregnant (including those who have miscarried or aborted) store the fetal cells of their children in their bone marrow for at least 50 years. The team of Professor Selim Aractingi – Paris Descartes Faculty of Medicine, Cochin Hospital (Paris hospital group) Dermatology Department, “Saint Antoine Research Center” Inserm joint research unit, and Université Pierre et Marie Curie – have recently proven that it is possible, in mice, to mobilize these fetal cells to accelerate the healing of chronic skin wounds. These results were published in Nature Communications on May 18, 2017.

Fetal cells transferred to mothers have the particularity of being potentially beneficial in the event of a health problem. For example, research teams have observed that thyroid or liver problems in pregnant women caused this cell type to participate in the regeneration of these organs. This is known as microchimerism because the mother mobilizes cells which, although not her own, are contained in her body in very small quantities (non-self cells) to accelerate the repair process of a damaged organ.

However, the signals sent by the mother to the fetal cells nested in the bone marrow, enabling them to mobilize and aid maternal healing, had remained unelucidated until now. Professor Selim Aractingi and his team recently made a discovery in this respect: “we have identified a molecular signaling pathway called Ccl2/Ccr2”, he explains. The next objective was then to try to potentiate this effect by artificially activating this signaling pathway.

This research has shown that injecting small quantities of this molecular pathway into the chronic wounds of a mouse that had long since given birth, results in healing at the same rate as that of a normal wound. This is made possible by mobilizing a specific population of fetal progenitor cells by Ccl2/Ccr2.

“Our concept involves natural fetal stem cell therapy”, continues Professor Aractingi. In that respect, it differs from more traditional cell therapy techniques in which cultured cells are injected into diseased tissue. The one restriction of this technique is that it can only benefit mice that have given birth. The same methods have been tested in mice that had never gestated and they were not shown to be effective.

The prospects offered by this study are very interesting because we can hope to ultimately reproduce this type of therapy in women. “Some testing is still required, but we are hopeful that this will lead to beneficial treatments for women who have been pregnant relatively soon” concludes Professor Aractingi.

From context to cortex: Discovering social neurons

Crowd

© Fotolia

The existence of new “social” neurons has just been demonstrated by scientists from the Institut de neurosciences des systèmes (Aix-Marseille University / INSERM), the Laboratoire de psychologie sociale et cognitive (Université Clermont Auvergne / CNRS), and the Institut de neurosciences de la Timone (Aix-Marseille University / CNRS). Their research on monkeys has shown that when these animals are made to perform a task, the presence or absence of a conspecific—that is, another monkey—determines which neurons are activated. Published in Social Cognitive and Affective Neuroscience, these findings broaden our knowledge of the social brain and help us better grasp the phenomenon of social facilitation.[1]

Understanding how the brain functions within a social context is a major challenge facing neuroscientists.  Through their unique multidisciplinary collaboration, a primate neurophysiologist and an experimental social psychologist have now discovered two new classes of neurons in the prefrontal cortex: social and asocial neurons.

Most areas of the brain are associated with specific tasks. Some are specialized in the processing of information related to life in society: they make up the so-called social brain. In connection with thesis research conducted by Marie Demolliens,[2] CNRS researchers Driss Boussaoud and Pascal Huguet assigned monkeys the task of matching a picture shown on a touch screen with one of four different items displayed at the corners of the same screen. Executing such a task requires use of the prefrontal cortex but not the “social” areas of the brain. The researchers made daily recordings of neuronal electrical activity in this region of the brain while monkeys performed the task in the presence or in the absence of a conspecific.

Though the monitored neurons of the prefrontal cortex are primarily involved in execution of the visuomotor task, the study showed most of them also reacted strongly to either the presence or absence of another monkey. During the experiment, some of these neurons were only strongly activated in the presence of a conspecific. They have thus been dubbed social neurons. On the other hand, the activity levels of other, asocial neurons only spiked in the absence of a fellow monkey. Even more surprisingly, the greater the intensity of social neuron activity in the presence of a conspecific, the better the subject performed the task. Social neurons are hence at the root of social facilitation. Likewise, the greater the activity of asocial neurons in the absence of conspecifics, the better the subject performed the task—though not as well as in the presence of another, when social neurons are stimulated. The researchers also demonstrated that in the other, rare permutations—activation of social neurons in the absence of conspecifics, or of asocial neurons in their presence—the monkeys did not perform as well.

This work reveals the important connection between social context and neuronal activity, and the consequences on behavior: which neurons the brain uses depends on whether a conspecific is present, even if the task is the same. Thus, rather than being limited to the areas of the brain principally associated with social activity, social neurons might actually be dispersed throughout the brain and play a role in various tasks—whether or not the latter are social in nature.  These findings cast new light on the nature of the social brain as well as certain behavioral disorders characteristic of autism and schizophrenia.

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Figure 1: Differential activation of social and asocial neurons depending on whether the monkey performing the touch screen task is in the presence or absence of a conspecific.

© M. Demolliens

 [1]. Social facilitation refers to enhanced performance of an activity due to the presence of a conspecific. It is observed among all species whose members live in groups (i.e., social species).

[2]. Under the joint supervision of Driss Boussaoud and Pascal Huguet.

Men/Women: not all equal in the face of allergic asthma

Hand with marker writing the word Asthma

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Researchers led by Jean-Charles Guéry of the Centre for Pathophysiology Toulouse Purpan (Inserm/Université Toulouse III – Paul Sabatier/ CNRS) are providing new insights into the possible link between male hormones and differences in gender in susceptibility to allergic asthma. This study demonstrates that hormones such as testosterone act on the immune system. The results are published in the scientific review The Journal of Experimental Medicine on 8 May 2017.

 Asthma is a complex disorder defined by bronchial hyperresponsiveness and chronic inflammation of the respiratory tract. It is common and affects more than 4 million people in France. The first signs occur mostly during childhood. Epidemiological studies show that there are disparities between men and women. There is a greater prevalence in boys compared with girls below the age of 10 years, while this tendency is reversed at puberty. In the global adult population, allergic asthma is twice as common in women and they develop more severe forms of the disease.

 In the case of allergic asthma, certain cells of the immune system have abnormal secretions of Th2 cytokine proteins. These proteins are part of the inflammatory reaction of the lungs during an asthma attack. Recently, a new group of immune cells was identified in the lungs, type 2 innate lymphoid cells (ILC2). Due to their ability to produce mediators of allergic asthma very soon after sensitisation of the lungs to an allergen, these cells carry out a central function in the initiation and orchestration of immune responses leading to the development of the disease.

 A team of French researchers[1], led by Jean-Charles Guéry, of the Pathophysiology Centre of Toulouse-Purpan, in collaboration with Australian researchers from the Walter and Elisa Hall Institute in Melbourne, are interested in the possible link between the immune system and sex hormones, which could in part contribute to the differences between men and women. First of all, they have highlighted the fact that, as in humans, male mice develop allergic asthma to dust mites which is much less severe than in females. This same response bias was observed when the researchers induced inflammation of the lungs. This difference disappeared where males were neutered, while “neutering” of females had no effect, which suggests a key role for male hormones (androgens). Essentially, the ILC2s possess the androgen receptor but the question remains as to whether this receptor functioned in response to the testosterone.

In the in vitro experiments, the researchers showed that testosterone inhibited the development of the ILC2s, while an anti-androgen, a molecule which reduces the activity of male hormones, had the reverse effect.  In non-neutered male mice without the androgen receptor in their type 2 innate lymphoid cells, the researchers observed a greater proliferation in the lungs associated with greater inflammation, than in the previous experiments. This last observation confirms the key role of the androgen receptor in respiratory disorders dependant on ILC2s.

According to Jean-Charles Guéry, this work highlights a new mechanism at the root of the differences linked to gender in allergic asthma : “The androgen receptor could represent a new  therapeutic target, for the purposes of inhibiting the action of type 2 innate lymphoid cells in asthmatic patients. In the medium term, that could become a treatment for allergic asthma in humans. 

[1] This team involves researchers from the Centre for Pathophysiology Toulouse Purpan (Inserm/Université Toulouse III – Paul Sabatier/CNRS), the Institute of Genetics and Molecular and Cellular Biology (Inserm/Université de Strasbourg/CNRS) and the Institute of Pharmacology and Structural Biology (CNRS/Université Toulouse III – Paul Sabatier).

Vitamin D, a New Avenue in the Prevention of Alzheimer’s Disease?

Do you like the salad?

Known to be a possible cause of several chronic diseases, vitamin D deficiency is also suspected to lead to a high risk of developing Alzheimer’s disease, especially where the diet is also poor in ‘good fats’ and antioxidant carotenoids. This is what two studies led by Catherine Féart and Cécilia Samieri, researchers at Inserm unit 1219 Bordeaux Population Health (BPH) (Inserm/ Bordeaux University), have shown. The research was published recently in Alzheimer’s & Dementia.

Whereas the number of people with Alzheimer’s disease continues to rise with the increase in life expectancy, the search for a cure will remain a major challenge for decades to come. The Three-City(3C) study is a cohort about almost 10,000 people aged 65 and over, in good health, or at least not suffering from Alzheimer’s disease, in year 2000. Much information was collected, including blood parameters which were stored in a biobank. After their inclusion in the cohort, the 3C cohort participants were seen by psychologists at regular intervals (follow-up is ongoing with 17 years’ hindsight to date). During these visits, they underwent a battery of neuropsychological tests which enabled the cohort neurologists to diagnose and list all new cases of dementia, especially Alzheimer’s. Catherine Féart and Cécilia Samieri, two Inserm researchers in Bordeaux, used the biobank samples to analyze the blood status of the participants on their inclusion in the cohort, in particular nutrient concentrations: fatty acids, carotenoids, and vitamins E, D and A. Several of these nutrients may predict the risk of dementia, however, no studies had looked at their combined role.

Féart and her co-investigators, which included Samieri, first began by looking at vitamin D1. A drop in blood vitamin D levels has previously been linked to several chronic diseases, including the onset of osteoporosis. However, the risk of developing a neurological disease had not been clearly established. Recent work carried out at the BPH thus revealed that out of 916 participants without dementia, 177 developed a dementia, including 124 cases of Alzheimer’s, in the 12 years’ follow-up. The participants with vitamin D deficiency (25%) or insufficiency (60%) had a twofold risk of developing dementia and an almost threefold risk of developing Alzheimer’s disease, compared to those with sufficient vitamin D status.

In a second study2, Samieri and Camille Amadieu (first author of the publication) attempted to establish nutrient biomarker profiles (combining vitamin D with other markers) related to the risk of onset of dementia in the long term. To do this, the researchers studied blood concentrations of 22 lipid-soluble nutrients (vitamin D, 12 fatty acids, 2 forms of vitamin E, 6 kinds of carotenoids and vitamin A) among 666 3C cohort participants without dementia. These lipid-soluble nutrients play an important role in brain function, and are provided by our diet (fish, nuts, vegetable oils, fruits and vegetables with high carotene content, etc.). A specific profile emerged. Elderly people with the lowest combined blood vitamin D, carotenoid and polyunsaturated fatty acid (‘good fat’) concentrations had a fourfold risk of developing dementia including Alzheimer’s disease, compared to those with the highest blood concentrations on these nutrients.

Thanks to the 3C cohort, vitamin D deficiency was established to be highly common among the elderly. According to the researchers, “this kind of deficiency appears to be linked to a high risk of developing Alzheimer’s disease, especially when there is also a negative ‘good fat’ profile and antioxidant carotenoid intake is poor. The additional risk from this multiple nutrient deficiency appears to be significantly higher than the genetic risk.” Therefore, maintaining adequate vitamin D blood status in the elderly could help delay or prevent dementia, especially Alzheimer’s.

Is the Link Between Early Cannabis Use and Academic Performance Becoming Clearer?

Pen and pot on paper

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The hypothesis that cannabis consumption has a direct effect on concentration, motivation, and the academic success of young people in the long-term is supported by neuroscience research data which demonstrates specific lesions in teenage users. Maria Melchior, Inserm Research Director (Pierre Louis Institute of Epidemiology and Public Health, Inserm-Université Pierre et Marie Curie, Paris), and her French and North American colleagues wished to study the possible existence of a causal relationship between early cannabis consumption (before age 17) and the level of education completed later on. Their study, which involved more than 1,000 people, is being published today in the International Journal of Epidemiology.

Studies currently available show that cannabis use during adolescence predict the level of education completed later on. However, numerous factors making some young people more likely to use cannabis earlier on than others, such as family traits or even psychological or educational difficulties, were not taken into account.

 The researchers analyses are based on data from the TEMPO cohort, which collected information from 1,103 people aged 25 to 35 in 2009. The parents of these young adults are part of the GAZEL cohort, a longitudinal study which began in 1989. It was used to record the characteristics of their initial social background and childhood education. Early cannabis use was defined by consumption before the age of 17. The level of education completed was defined by whether they obtained a high school diploma or not.

In order to compare early (<17 years) and non-early (>=17 users) users of cannabis to non-users, ‘propension’ scores were calculated from the sociodemographic characteristics of the participants and their parents, and integrated in the analyses.

The researchers were able to reach several conclusions:

— By taking the age and sex of the participants into account, early consumers are more likely not to obtain a high school diploma (OR=1.77, 95%CI 1.22-2.55), compared to non-users.

— By taking individual and family traits likely to predict early cannabis use into account, the association is slightly lower but remains statistically significant (OR=1.64, 95%CI 1.13-2.40).

— Young people who began using cannabis after 17 have a diploma level comparable to non-users.

— Early cannabis use and level of education appears to be more strongly related in young girls than in young boys.

According to Melchior and her co-authors, “Early cannabis use can therefore lead to educational difficulties, resulting in a level of education lower than that achieved by young non-users in the long term, regardless of their social background, psychological or educational difficulties.”

“The mechanisms by which early cannabis use affects future education may be linked to effects such as a lack of motivation, and memorization and concentration difficulties,” explain the researchers. “In a context where, in France, one middle school student in ten (one in five in 9th grade) and almost one high school student in two has already tried cannabis, a major public health objective is to try to get people to wait until they are older to use it for the first time,” they also say.

Does our childhood shape our political choices?

portrait of beautiful girl reading a newspaper at home/in the news/modern children

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Do our childhood experiences shape our political attitudes? A team of Inserm researchers from Unit 960 “Cognitive Neuroscience Laboratory” (Inserm/ENS) have discovered the answer to this question, the results of which have recently been published in the journal Evolution and Human Behavior. Childhood poverty is associated with stronger adherence to authoritarian political attitudes in adulthood, not only in the French population, but also in a sample of 46 European countries.

Understanding the origins behind the success of authoritarianism is an important key to preserving current democracies. Since the early 2000s, most Western countries have seen a historic rise in authoritarian parties. At the same time, authoritarian attitudes are becoming the norm in many political parties. Analysis of these political phenomena is usually based on contextual factors, such as the economic crisis or terrorist threat, which tend to favor authoritarian attitudes. However, recent studies in biology and psychology have shown that a person’s childhood environment can also shape their behavior in adulthood. Inserm researchers, in collaboration with SciencesPo, wished to determine whether these processes came into play in shaping political attitudes. The researchers focused more specifically on the effect of childhood poverty on authoritarian attitudes.

The researchers used tests in which the participants described their first impressions of faces, to ascertain their political preferences. Previous psychology studies have, in fact, shown that political attitudes influenced preferences for certain types of faces, and that simple judgments based on candidates’ faces could predict election outcomes. Inspired by these studies, the researchers from the Cognitive Neuroscience Laboratory determined the preference for fictitious male politicians, represented by computer-modeled faces and calibrated to represent variable degrees of dominance and trustworthiness.

The “trustworthiness” and “dominance” dimensions are orthogonal to each other. All combinations are possible: a face can be very dominant and less trustworthy, very dominant and very trustworthy, less dominant and less trustworthy, or less dominant and very trustworthy.

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The researchers developed two tests: a simplified version for children and another for adults.

Forty-one 7-year-olds were asked to choose their team captain to lead a mountain expedition, from among faces showing varying degrees of dominance and trustworthiness.

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This initial test showed that children exposed to negative socioeconomic conditions preferred more dominant and less trustworthy captains, compared with their classmates living in more comfortable surroundings.

Based on this early effect of poverty, the researchers then examined its impact on shaping subsequent political preferences. In partnership with the IPSOS polling institute, they determined the preferences of a representative sample of the French population (1,000 participants, quota sampling) for male politicians displaying varying degrees of dominance and trustworthiness. In this part of the study, faces displaying varying degrees of dominance and trustworthiness were randomly shown to pairs of participants, with the following question: “Who would you vote for?”

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This study revealed that childhood poverty increased the preference for dominant and less trustworthy male politicians in adulthood, irrespective of the participants’ current socioeconomic status and level of education.

Lastly, the research team focused more specifically on explicitly authoritarian attitudes, by asking the study participants to describe the extent to which they agreed with the following phrase: “I think having a strong man who does not care about parliament or elections as the leader of a country is a good thing“. Analysis of these responses showed that childhood poverty increased adherence to explicitly authoritarian attitudes, not only in the French population sample interviewed, but also in a panel of 46 European countries.

Based on three different tests, these studies highlight the importance of early factors in determining political attitudes, and thus provide a more in-depth understanding of the dynamics of democracies.

May 15 to 19: French skin cancer prevention and screening week

The French Federation of Dermatologists-Venereologists (SNDV) is proposing an information week on the precautions to take in the sun, along with free skin cancer screenings, to take place across the country. This initiative is also an opportunity to raise public awareness of the risk factors that can lead to skin cancer.

According to the French National Cancer Institute (INCa), the number of new skin cancer cases had more than tripled between the years of 1980 and 2012.

There are two main types of skin cancer: Basal and squamous cell carcinomas, which represent 90% of skin cancers, and melanomas, which are rarer but also more dangerous due to their strong potential to spread to other areas of the body.

It is estimated that 65 to 95% of melanomas are caused by exposure to the sun. In 20% of cases, they develop from an existing mole (nevus).

With 11,176 new cases of melanoma in metropolitan France in 2015, improvements in screening have led to a 0.8% reduction in annual melanoma mortality in women (INCa).

Read the latest Inserm news in this category:

“Skin cancer: a team synthesises new drugs with surprising powers”, published May 25, 2016.

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