The ‘Constances’ cohort, a research network unique in France

Already, more than 65,000 volunteers have been included from the 200,000 expected and 41 research projects have begun.

Two years after its launch, the ‘Constances’ cohort is gathering health related data on more than 65,000 volunteers aged from 18 to 69 years who are affiliated to the general social security system and have been selected at random. Each volunteer gets a health check at a (National) Health Insurance Health Centre (CES) and fills in annual questionnaires. They accept that data relating to them, such as health care consumption, hospitalisation or their socio-professional status may be monitored by researchers from the Constances cohort. Eighteen CESs are involved in 17 French departments. Constances is jointly run by Inserm, the University of Versailles-Saint-Quentin-en-Yvelines, the (National) Health Insurance Scheme and the Pension Insurance Scheme, with the support of the General Directorate of Health.

The Constances cohort will enable the gathering of data which can be used for research purposes and public health policy. Additionally, the very large number of people monitored will enable the study, on an unprecedented scale, of the long-term impact of different factors (pollution, eating habits, medicinal treatments, place of residence…) on the health of France’s living population. 

“The true originality of Constances is to have been conceived from the outset as an epidemiology laboratory open to all research teams in a spirit of sharing. Substantial work has been carried out in order to respect the confidentiality of data, in accordance with the laws on data protection and freedom of information” points out Marie Zins, scientific leader of this cohort.


Distribution of volunteers of the Constances cohort as at 25 March 2015 (© Inserm/M. Nachtigal)

The Constances cohort International Scientific Council has just approved 41 research projects, supported by around thirty teams.

Two projects are particularly advanced:

–            COSMOS (Cohort of mobile phone users and health in France), International Centre for Cancer Research (CIRC, Lyon): as part of a European Study (Denmark, Finland, Sweden, Netherlands and Great Britain), COSMOS evaluates the long-term effects of mobile phones on health. Manager: Joachim Schüz (head of section on environment and radiation) – rf.crai@somsoc

–            ConstancesRespi: monitoring, determinants, history and the impact of chronic respiratory illnesses and the accelerated decline of lung function. A consortium of seven projects, comprised of seven teams led by Nicolas Roche (Professor at Paris Descartes University) – rf.phpa.hcc@ehcor.salocin

Constances in brief

This French national cohort of adults is strongly supported by CNAMTS (French National Health Insurance Fund for Employees) and has the benefit of funding from the ‘Investing in the Future Programme’.

The size and function of the cohort are equivalent to other large cohorts being developed in Europe, particularly in Germany. In the long term, such European collaborations lead to research on a grand scale and unprecedented international comparisons.

The aim is to include 200,000 volunteers.

The next selection of research projects by the Scientific Council will take place in July 2015.

Are you a volunteer? Do you wish to participate? Details and conditions can be obtained by writing to rf.secnatsnoc@tcatnoc and on the website

What if the severity of our seasonal influenza were related to our genetic background?

While most of us recover from influenza after a week, it can be a very severe disease, and even fatal in rare cases, with no reason for physicians to have expected such an outcome. By analysing the genome of a little girl who contracted a severe form of influenza at the age of two and a half years, researchers at the Laboratory of Human Genetics of Infectious Diseases (a joint French-American international laboratory), which brings together researchers from Inserm, Paris Descartes University, and physicians from the Paris public hospitals (AP-HP; Necker Hospital for Sick Children), working at the Imagine Institute, and from The Rockefeller University in New York, have discovered that she has a genetic mutation, unknown until now, that causes a subtle dysfunction in her immune system. More generally, these results show that genetic mutations could be the root cause of some severe forms of influenza in children, and indicate in any event that immune mechanisms missing in this little girl are needed for protection against this virus in humans. These results are published in the journal Science Express.
Woman coughing and blowing her nose in autumn


Seasonal influenza is an acute viral infection caused by the influenza virus. It is characterised by high fever, headaches, sore muscles, etc. Apart from vaccination, there is no treatment for it other than symptomatic (pain) treatment. In most cases, patients recover after a week, but in more vulnerable people influenza can cause acute respiratory distress, which is potentially fatal.

The main known risk factors for severe forms of influenza are some acquired comorbidities, such as chronic lung disease. However, the cause of most fatal cases remains unexplained, especially in children.

The absence of cases of severe influenza in patients with known acquired immunodeficiencies, which usually increase susceptibility to infections, is also surprising.

Given these different observations, the researchers at Jean-Laurent Cassanova’s and Laurent Abel’s laboratory, in Paris and New York, therefore formulated a hypothesis whereby severe influenza in healthy children might be the result of genetic errors.

To test this hypothesis, they sequenced the entire genome of a 7-year-old child who had contracted a severe form of influenza (influenza A virus strain H1N1), requiring her admission to a paediatric intensive care unit in January 2011, at the age of two and a half years. At the time, she showed no other known pathology that might have suggested greater vulnerability to the virus than that of other children.

This analysis, combined with analysis of her parents’ genomes, made it possible to show that the little girl had inherited a mutated allele of the gene encoding interferon regulatory factor (IRF7) from both of her parents. The latter is a transcription factor known to amplify the production of interferons in response to viral infection in mice and humans.

In contrast to her parents, in whom the mutation of a single allele of the gene is of no consequence, in the little girl, mutation of both alleles of the gene encoding IRF7 has led to its inactivation. The result: failure to produce interferons, disrupting her system of defence against influenza virus infection in a cascading manner.

By carrying out a comprehensive series of experiments on blood cells, particularly dendritic cells, and by generating lung cells from stem cells taken from the young girl, the researchers provided proof that the mutations observed in this little girl explain the development of severe influenza. Furthermore, this discovery demonstrates that interferon amplification dependent on IRF7 expression is needed for protection against influenza virus in humans. They now need to search for mutations in this or other genes in other children recruited following an episode of unexplained severe influenza.

Based on these initial observations, the researchers at Inserm believe that therapeutic strategies based on recombinant interferons, available in the pharmacopoeia, could help to combat severe forms of influenza in children.

This multidisciplinary study required multiple collaborations in Europe and the United States.

A pharmacological compound for restoring neuromuscular transmission

Researchers from Inserm, CNRS and Paris Descartes University have just demonstrated the beneficial effect of lithium chloride on a group of genetic disorders responsible for muscle dysfunction known as congenital myasthenias. These results, obtained using a new mouse model of the disease, are published in The Journal of Neuroscience, and constitute an important step in the search for treatments for these rare diseases.

Congenital myasthenic syndromes (CMS) usually begin in the neonatal period, but sometimes begin later in childhood, during adolescence, or even in adulthood. They manifest as muscular weakness in the arms and legs, with involvement of the eyes, and facial and bulbar muscles (sucking, swallowing and vocal function [dysphonia]). They are characterised by dysfunction of neuromuscular transmission. This rare disease affects 1-2 individuals in 500,000 (source: Orphanet).


© Fotolia. Neuron Synapses enable the transmission of neuromuscular messages.

Researchers from the “Centre for Neurophysics, Physiology and Pathology” (French National Centre for Scientific Research [CNRS] / Paris Descartes University) in Paris study the physiopathological mechanisms of these diseases of neuromuscular transmission.

Using a transgenic mouse model of the disease, they have just shown the beneficial effect of a pharmacological compound known as lithium chloride (LiCl). Lithium chloride was already known as a treatment for some diseases of the central nervous system, such as depression and bipolar disorder.

“Treating these mice with lithium chloride reduces muscle weakness and fatigability,” explains Laure Strochlic, Inserm researcher.

Specifically, the researchers injected the product once a day into the peritoneum of the mice. The compound substantially restores the altered structures of the synapses, the structures that allow the transmission of information between nerve cells. It acts by inhibiting an enzyme known as “GSK3” in the muscle, making it possible to restore the motor deficit caused by the disease.

The researchers are now working to see if these results can be reproduced in other models of congenital myasthenia, and are adjusting the dose and duration of treatment. They are planning a clinical trial to test the efficacy of LiCl and other inhibitors of the GSK3 enzyme in 2-3 years’ time.

These results are protected by a patent filed by Inserm Transfert.

Friday 27 March 2015: Sleep Day

According to the French National Institute of Sleep and Alertness (InSV), 1 French person in 5 suffers from insomnia, and up to 9% of these insomniacs are badly affected (poor quality sleep, difficulty falling asleep, multiple awakenings or waking too early).

On average, we spend one-third of our lives asleep.

Indeed, sleep is indispensable to the learning, memorisation, adaptation and growth functions, and is also very important to our state of well-being. Without it, we could not recover our physical and mental abilities.

On the 15th Sleep Day, to be held on Friday 27 March 2015 on the theme of “Sleep and Nutrition,” many public institutions and associations, including InSV, will be working to receive, inform and sensitise the general public.

Throughout the year, researchers at Inserm Unit 1028, the “Lyon Neuroscience Research Center,” and at Inserm Unit 846 are particularly  involved in the research concerning sleep. 

The chronobiology department of Inserm Unit 1028 take interest in light effects on sleep and biological clock. A recent study from the theam, led by Claude Gonfrier shows that the light spectrum can be optimized to enable the circadian system to synchronise and to maintain an appropriate sleep duration in extreme artificial lightning conditions. (See the press release “Dimly lit working environments : correcting your body clock is possible!“)

It has recently been shown that voluntary sleep restriction in humans favors the onset of diseases such as obesity and diabetes , while the mechanisms involved remain unknown, because of the lack of adequate animal model.

The team led by Jian-Sheng Lin has found that the chronic invalidation of the negative feedback of the histamine neurons, an important awakening system of the brain , helps to keep the mice  awake when they are required to perform cognitive tasks. However, there is a price to pay for this sleep resistance  and better performance since in the absence of task, these mice are sleepy. Moreover, they also present a marked obesity. Thus, this model enable the researchers to study how sleep restriction leads to obesity.

Targeting a host receptor instead of the virus: a new experimental approach against hepatitis C virus.

An international collaboration led by Professor Thomas Baumert (Inserm/University of Strasbourg Joint Research Unit 1110, “Institute for Viral and Liver Disease”) has shown that a monoclonal antibody directed specifically against claudin-1, a liver protein essential for infection by the hepatitis C virus (HCV), enables the prevention and treatment of chronic infection by this virus in an animal model. It turns out that this antibody, which was known to inhibit HCV entry and thereby prevent the initiation of infection, can also eliminate infected cells. This discovery, published in a letter in the Nature Biotechnology issue of 23 March 2015, opens the way to developing an approach to hepatitis C that is not only preventive, but therapeutic as well.

Infection with hepatitis C virus (HCV) leads to cirrhosis of the liver and liver cancer, the second leading cause of cancer death in the world. These complications are major indications for liver transplantation, but HCV reinfection of the transplant is a challenge. To date there is no vaccine, and the new treatments developed recently can be accessed by only a minority of patients worldwide because of their high cost. The development of new preventive and therapeutic strategies therefore continues.

The team directed by Prof. Thomas Baumert (Inserm/University of Strasbourg Joint Research Unit 1110, “Institute for Viral and Liver Disease”), in collaboration with international teams, decided to target a liver protein essential for viral infection instead of targeting the virus. They chose claudin-1, a molecule that is important in the initial steps of HCV infection, and involved in cell-cell contacts.

Using mouse models with humanised liver, the researchers show that a monoclonal antibody directed against claudin-1 can prevent HCV infection by blocking the entry of the virus into liver cells. Surprisingly, the researchers also observed that this antibody enables the treatment of chronic HCV infection by inhibiting the activation of intracellular signalling pathways needed by the virus for survival. As a result, the infected cells disappear and are gradually replaced by uninfected cells.

The advantage of this strategy is that it does not need to be combined with an antiviral agent.

 Moreover, by using different viral strains, the researchers show that it is difficult for the virus to escape from this antibody and develop resistance.

“Claudin-1” is a protein that is usually localised in the tight junctions that are the points of contact between adjacent cells. It is interesting to note that tight junction proteins constitute receptors for other pathogens, such as dengue virus and Shigella species. This innovative approach, employing injection of a monoclonal antibody directed against a protein on the host cell, makes it possible to foresee the development of a vaccine strategy and new therapeutic approaches against HCV, and also against other pathogens that use similar infection mechanisms.

This study received support from the European Union (ERC, INTERREG-IV-Upper Rhine [ERDF], FP7), ANRS (French National Agency for Research on AIDS and Viral Hepatitis), the HepSYS and netRNA Laboratories of Excellence of the French National Research Agency (ANR), ARC Foundation for Cancer Research, IHU Strasbourg MIX-Surg, Wilhelm Sander Foundation, Alsace Region, French National Cancer Institute (INCa), French National Institute of Health and Medical Research (Inserm), French National Scientific Research Centre (CNRS), University of Strasbourg, Ghent University (GOA 01G01712), Flanders Research Foundation (FWO) and Cardiex (Nantes).

Predicting the end of fertility for women after paediatric cancer

Researchers from the Paris Public Hospitals (AP-HP), Inserm, the Gustave Roussy and Curie Institutes, and Oscar Lambret Cancer Centre, coordinated by Dr Cécile Thomas-Teinturier of the Paediatric Endocrinology Service at Bicêtre Hospital, have studied the impact of certain therapeutic agents on the fertility of women who have been cured of a paediatric cancer. This research, carried out with support from the French National Cancer League, is published in the journal Human Reproduction on 23 March 2015.

Now that survival is increasing, the impact of therapeutic agents on the future fertility of girls cured of cancer in childhood can affect their quality of life. In all women, the length of reproductive life is related to the number of follicles present in their ovaries, a reserve that cannot be renewed, and that declines over time. Menopause occurs when this number declines below a certain threshold, 5-10 years after the end of fertility.

In this study, the researchers proposed the hypothesis that women who have undergone chemotherapy with a class of drugs known as alkylating agents—cyclophosphamide, ifosfamide, procarbazine—to treat a childhood cancer can have reduced follicular reserve, even though their apparent ovarian function may still be intact (regular cycles).

They evaluated the ovarian reserve in 105 women cured of cancer during childhood, who had received alkylating agents during their childhood, but no radiation therapy in the pelvic area. Investigations included measurement of hormone levels, particularly anti-Müllerian hormone (a reliable marker of ovarian reserve), ultrasound measurement of ovarian size, and follicle count. Results were compared to those for 20 women of the same age who had not received chemotherapy.

The team observed that the 105 women cured of paediatric cancer had smaller ovaries than the untreated women, and a significantly lower level of anti-Müllerian hormone. This reduction was more marked in patients who had received procarbazine for Hodgkin’s lymphoma, or chemotherapy with high doses of alkylating agents prior to a bone marrow transplant. Neither the cyclophosphamide nor ifosfamide dose seemed to be associated with reduced ovarian reserve.

“These results seem to confirm our hypothesis,” explains Dr Thomas-Teinturier. “From a theoretical point of view, the end of fertility is likely to occur earlier in these women who have been cured of a paediatric cancer. This fact, when combined with increasing age at first pregnancy, is likely to increase problems with reproduction.”

However, although assessment of ovarian reserve seems to be a good predictor of the pregnancy rate in infertile women undergoing medically assisted reproduction techniques, there are few data regarding its real use when advising young women cured of paediatric cancer about the potential effects on their fertility, and their risk of early menopause.

“It therefore seems necessary to monitor these markers in this patient cohort in order to define the thresholds that may make it possible to predict the window of fertility and onset of menopause in the following years,” continues Dr Thomas-Teinturier. “The ultimate objective of our study is to be able, in future, to advise these young women individually on their potential for reproduction in the following five years, based on the results of their review at a given moment.

Solar eclipse on 20 March: dangers for the retina

On Friday 20 March 2015, a partial eclipse of the sun will be visible in France between 9:00 and 12:00 am, depending on the place of observation. Why is looking directly at the sun dangerous and a cause of irreversible damage to the retina? Inserm researchers who are specialists at the Vision Institute (Inserm/CNRS/UPMC) can answer your questions.

The French Ministry of National Education, Higher Education and Research (MENESR) recalls the eye hazards involved in directly observing of the sun. There are two types:

–    corneal, keratitis-type lesions, essentially associated with ultraviolet rays, painful but reversible in a few days;

–    retinal burn-type lesions associated with the thermal effect of solar radiation and a photochemical effect on the particularly delicate cells of the retina. These lesions can cause permanent damage to the sight.

The French Directorate General of Health recommends that people who want to safely observe the partial eclipse of the sun on 20 March 2015 take proper protective measures for directly observing the sun.

Manaslu 2015: A scientific expedition at over 5,000 m altitude

For 5 weeks, 5 international research teams will conduct a scientific expedition in Nepal, in the heart of the Himalayas, close to the summit of Mount Manaslu (8,156 m). The French component of the expedition, coordinated by a researcher from Inserm (Unit 1042, “Hypoxia and Cardiovascular and Respiratory Pathophysiologies,” Inserm/Université Joseph Fourier), will conduct an original project on the impact of altitude on the brain and heart, and on sleep disturbances induced by altitude. The French researchers will also study the benefit of a mask specially designed to improve oxygenation in combating the symptoms of acute mountain sickness. To do this, 50 volunteers will accompany them on this 5,000 m high trek.

Internet users will be able to follow this expedition in real time on the social networks using the hashtag #scienceausommet

Echocardiographie réalisée au sommet du Mont Blanc lors d'une précédente expédition © Samuel Verges

Echocardiography at the summit of Mont Blanc during a previous expedition © Samuel Vergès

The development of recreational activities, and the increasing number of periods spent at medium and high altitude by people who are often inexperienced raises the issue of altitude intolerance. These problems of adaptation are the result of physiopathological mechanisms associated with the progressive reduction in oxygen availability as one rises to higher altitudes.

These illnesses, which are disabling to the point of interrupting one’s period at high altitude, and can be serious or even fatal, are acute mountain sickness (a combination of symptoms such as headache, fatigue, nausea, etc.), high altitude pulmonary oedema, (usually associated with a cough, and breathlessness due to a potentially serious fluid accumulation in the lungs), and high altitude cerebral oedema (fluid leakage in the brain, a particularly serious phenomenon, with marked effects on behaviour). Acute forms occur in people who are poorly acclimatised to altitude, with a rapid onset following exposure (6 h to 4 days). The more devastating forms occur even after acclimatisation, at altitudes above 5,000 metres. Generally speaking, one out of every two people is affected by acute mountain sickness above 4,000 metres, and three out of four people are affected above 5,000 metres.

These conditions may, to a certain extent, be avoided by following simple rules for prevention. However, it also appears that some people are more likely than others to develop these symptoms at high altitudes. Factors predicting altitude tolerance, the mechanisms underlying problems of adaptation, the management of these problems, and the optimum strategies for acclimatisation are still particularly poorly known.

These are the themes that will be studied by the French research team, under the coordination of Samuel Vergès, an Inserm Research Fellow at Unit 1042, “Hypoxia and Cardiovascular and Respiratory Pathophysiologies.” The team is made up of 6 experienced scientists and physicians, all of whom have experience of high mountains and scientific expeditions of this type.

A first research project on the heart and brain

With three main strands, this project is aimed at using innovative and portable techniques (that can be used at high altitude) to define in detail the effects of spending a period at high altitude on the brain and heart, and to assess the effect of a positive expiratory pressure ventilation mask on these cerebral and cardiac responses.

  • Lack of oxygen and the brain

In vitro and in vivo studies show that lack of oxygen impairs neuronal function and may reduce human cognitive performance. A series of studies in the laboratory and at high altitude (VALLOT Observatory, Mont Blanc massif) has revealed significant brain disturbances induced by hypoxia, both in the initial hours of exposure and after several days. The anatomy of the brain, cerebral perfusion and oxygenation, and motor neuron function are particularly affected by hypoxia, a finding that has led to reconsideration of the mechanisms for adapting to altitude, with inclusion of the brain component as a factor that probably plays a major role.

  • Altitude and heart function

High altitude exposure is associated with major cardiac changes. Previous studies have shown that acute hypoxia leads to changes in the relaxation properties of the myocardium. A reduction in the contractile properties of the cardiomycytes might be responsible for this phenomenon, although objective proof has not yet been obtained. Many studies have also shown that exposure to high altitude generates changes in the right ventricle, which may play an important role in the relaxation of the left ventricle, although the mechanical phenomena involved are incompletely known.

In recent times, a new technology based on following the acoustic signatures produced during echocardiography (Speckle Tracking Imaging) has made it possible to measure myocardial speeds and deformations in a comprehensive manner, allowing investigation of the myocardium’s contractility and ability to relax, thus opening up new perspectives in the understanding of the effects of altitude hypoxia on the heart.

  • Development of a mask that minimises the harmful effects of high altitude

Applying positive expiratory pressure (PEP) at mouth level in individuals under high altitude conditions allows an artificial increase in the intra-pulmonary pressure, and has been suggested by some research teams as a possible method for preventing or minimising the harmful effects of high altitude. Researchers at the Hypoxia-Physiopathology Laboratory (HP2) in Grenoble recently demonstrated the utility of this method for increasing oxygenation of the blood and muscles.[1]

Their results suggest that a portable mask type device inducing an increase in expiratory pressure might constitute an original and effective non-pharmacological method for improving altitude acclimatisation and alleviating the symptoms associated with acute mountain sickness. A large-scale field study at a high mountain location is needed to determine whether PEP is likely to become widely used method. The commercialisation of a PEP mask system may be envisaged, given its advantage of being portable, compact, non-medicinal and usable by most people.

A second project on the impact of altitude on sleep

Altitude is known to profoundly disrupt sleep and induce sleep apnoea, known as central sleep apnoea. From an altitude of 2,500 m, a moderate reduction and cyclic oscillations are observed in blood oxygenation. The development of these disorders is also accompanied by a reduction in sleep efficiency, an increase in the time it takes to fall asleep, a shortening in the duration of phases of deep sleep, and a substantial increase in intrasleep awakenings. The quantification of these disorders was for a long time limited to the analysis of oscillations in arterial O2 saturation.

However, at the present time, one question has not had a clear answer: is central apnoea a marker of bad or good adaptation of the body to altitude? This question is important because there are large intersubject variations in the intensity of sleep disturbances induced by altitude exposure. It was recently shown in the laboratory directed by Samuel Vergès that individuals showing severe symptoms of high altitude intolerance (in the course of one night in an altitude simulation laboratory) have less sleep apnoea than comparable individuals who tolerate high altitude well. However, this remains to be established in the field at high altitude.

Study of this question should improve understanding of the mechanisms of adaptation to altitude, and influence the advice and assessments offered to people travelling to high altitude.

The study proposed by the French group within the scientific expedition therefore has the following objectives:

  • To assess the effects of the expiratory resistance mask (ventilation with PEP) on arterial and tissue oxygenation, on pulmonary extravascular leakage and on symptoms of acute mountain sickness during a period at high altitude for a large sample of volunteers.
  • To study, on the basis of new technologies (near-infrared spectroscopy Speckle Tracking echocardiography), the changes to the brain and heart induced by lack of oxygen (hypoxia) at high altitude, and to assess their reversibility through wearing the mask.
  • To compare altitude-induced sleep modifications in trekkers that adapt well to altitude compared to those who show symptoms of acute mountain sickness.


The researchers’ study of the effects of lack of oxygen on the healthy body at high altitude should enable a better understanding of the consequences of lack of oxygen on some patients at normal altitudes, for example those with respiratory diseases. The high altitude is thus a real open-air laboratory, constituting an original study model for the adaptive abilities and limitations of the human body.


An initial phase of study at normal altitude

All participants in the trek and Manaslu climb made themselves available, between 16 and 23 February last, for a battery of scientific and medical assessments at sea level in Wales (Bangor University). All measurements that will be done at high altitude were carried out at sea level, thus enabling reference values to be obtained for every subject, for comparison with measurements taken at high altitude.

test doppler plaine

Measurements at normal altitude © Samuel Vergès

The phase of testing at normal altitude was an opportunity to address technical and logistic issues that needed to be resolved so that the tests can be repeated under the best possible conditions at high altitude at reduced atmospheric pressure (which strongly affects equipment), and in the cold (down to -20°C), and when the bodies of both the researchers and volunteer subjects will be severely affected by the altitude.

A science laboratory installed at 5,000 metres

Five groups of 10 people will leave Kathmandu at intervals of 1 day each to spread the measurements. It will take 10 days to reach the destination. The 5 international research teams will set up their laboratory and all the necessary logistics (tents, production of solar and wind energy, etc.) slightly above the Manaslu base camp, at a little over 5,000 metres altitude. Most of the high altitude measurements will be performed on all those participating in the trek, who will arrive day after day. Other measurements will be performed during the trek and during the Manaslu climb (8,156 m). The entire expedition will last 5 weeks, from 21 March to 26 April.

As with assessments carried out at normal altitude, assessments will involve measuring the pulmonary extravascular fluid by pleuropulmonary ultrasound, cerebral perfusion by transcranial Doppler, cerebral oxygenation by near-red spectroscopy, and cardiac function by Speckle Tracking echocardiography, before and during ventilation under positive expiratory pressure. Symptoms will be assessed by questionnaire. Finally, sleep will be assessed during nights spent in tents at the Manaslu base camp, by placement of various sensors that enable identification of the quality of sleep, and the occurrence of sleep apnoea associated with a drop in blood oxygenation, such as is frequently observed at high altitude. These measurements are identical to the tests known as polygraphy that are carried out in sleep laboratories in hospitals to diagnose sleep apnoea syndrome in patients.

Following 4 days of acclimatisation at 5,000 metres, this battery of tests will be repeated in order to observe the adaptations of the human body to this high altitude. All participants will spend 10 days at base camp, and the team will then complete the Manaslu circuit with a 3-day descent to Beshisahar.

The participants in this trek show a classic profile of populations taking part in treks at high altitude, aged from 22 to 65 years, with relatively varied levels of physical fitness and altitude experience. They have volunteered to complete a trek of several weeks around Manaslu and have also volunteered to participate in scientific experiments in this context, including 5 consecutive days at the camp located at the highest point in the Manaslu circuit, where the laboratories will be installed.


The other 4 international scientific projects conducted as part of the MEDEX project

MEDEX ( was created in Great Britain in 1992 to encourage scientific and medical expeditions. Since then, several large-scale scientific expeditions have been organised at 4-5 year intervals: Everest in 1994, Kanchejunga in 1998, Hongu in 2003 and Hidden Valley in 2008. These expeditions have led to major scientific and medical advances associated with altitude, resulting in scientific publications, news stories for the general public, and training activities for professionals and high mountain climbers.

During this expedition, 4 other scientific projects will be conducted at the same time as the 2 conducted by Samuel Vergès’ team.

  • Coping strategies for those working at altitude – Sue Paddon’s team (Advanced Personnel Management, Australia-UK)
  • Influence of physical and mental preparation on the success of an expedition at high altitude – team led by Sam Olivier and Jamie Macdonald (Bangor University)
  • Disruption of heart rate as an indicator of acute mountain sickness? Jamie Macdonald (Bangor University)
  • Impact of treks on the health of Nepalese staff employed to accompany expeditions – Mary Morrell (Imperial College London)

Following the expedition on social media

To bring a scientific expedition to life for Internet users as if they were there, even though the location (the summit of Manaslu) is particularly inaccessible, Inserm is doing all it can to follow the expedition. Enriched content (photos or videos) will be posted daily on @Insermlive and on the Institute’s Facebook page. From the day-to-day (plan, arrival at location, setting up), to details of scientific experiments (design, goals, measurements, etc.)

A hashtag #scienceausommet

A relay on @inserm_en is also planned for the international community

At the Inserm press room, an instant discussion module will be open to take questions for the researchers before they leave and after they return.

[1] These results have been published in PlosOne

An antihypertensive drug improves corticosteroid-based skin treatments

Basic research on blood pressure has led researchers from Inserm (Inserm Unit 1138, “Cordeliers Research Centre”) to obtain unexpected results: drugs used to treat hypertension (high blood pressure) reduce side effects from corticosteroid-based creams used to treat certain skin diseases.

This work is published in the Journal of Investigative Dermatology.

To switch the subtitles of the movie on or off during playback check/uncheck the Subtitles enabled option.

Corticosteroid-based dermatological creams are indicated for the symptomatic treatment of inflammatory skin conditions, such as atopic dermatitis and psoriasis, for example. However, they have frequent side effects, such as a slight burning sensation, and very often end by inducing skin atrophy (thinning of the skin, which becomes fragile), which is inconvenient for the patient, and for which there is presently no treatment.

The researchers from Inserm formulated a hypothesis whereby this harmful effect might be related to the inappropriate activation by these creams of mineralocorticoid receptors located in the epidermis. These receptors, which are present in the kidney, heart, eye, and certain neurons in particular, reacted with aldosterone, a hormone that regulates the blood pressure. Moreover, previous studies also showed them to be highly sensitive to corticosteroids.

Application of corticosteroids to cultured skin causes it to become thinner: in 6 days, the thickness of the epidermis was reduced by one-third. The researchers then induced a pharmacological blockade of the receptors by adding specific antagonists to the corticosteroid treatment. The inability of the corticosteroid to bind to the mineralocorticoid receptors restores proliferation of the epidermal cells, and partially corrects epidermal atrophy.

From the clinical point of view, it turns out that spironolactone, a drug used for a very long time as an antihypertensive drug (and which has marketing authorisation), is an antagonist of the mineralocorticoid receptor. The researchers therefore tested a treatment based on spironolactone for 28 days in 23 healthy volunteers. Creams of different composition were applied to 4 areas of their arms:

– a cream containing a corticosteroid used in dermatology

– a cream containing spironolactone

– a combination of both drugs

– a placebo

The results obtained show that adding spironolactone to the corticosteroid significantly limits skin atrophy.

For Nicolette Farman, “This is a highly original piece of work, at the crossroads between endocrinology and dermatology, and brings together researchers in basic science and clinicians. Now it remains to reformulate this old drug for a new application, and test this product in patients with various skin diseases in order to confirm the reduction in side effects from corticosteroids without loss of efficacy.”

Female hands using skin cream

© fotolia

The new face of our adolescents

A large survey, coordinated by Inserm Unit 1178, “Mental Health and Public Health,” and the University Division of Fondation Vallée, describes the current situation regarding issues and challenges in adolescence. These data, collected by means of self-administered questionnaires, reflect the perceptions of 15,235 young people attending school, aged 13-18 years, regarding their own adolescence. The study addresses subjects as varied as their physical and mental health, consumption patterns, recreational activities and even sexuality. The results reaffirm the complex nature of these future adults, with marked differences between boys and girls, and an age-related gradient. They should help to improve our knowledge of adolescent behaviours, and help identify new indicators of problems that can be used in the introduction of preventive measures.

Key figures:

  • Nearly 50% of adolescents are confident about the future;
  • For 56% of young people surveyed, adolescence is not always an easy time;
  • A very large majority (5% of girls and 57.6% of boys), favour isolation when they are unhappy;

75% of adolescents recognise the need for boundaries.

Adolescence, the transition between childhood and adulthood, is a period of complex psychological and physiological upheaval that may cause certain problems and lead to risky behaviours. The “Portraits of Adolescents” survey, coordinated by Inserm Unit 1178, “Mental Health and Public Health,” and the University Division of Fondation Vallée, makes it possible to analyse the “profiles” of these 15,235 young school-goers from their third year of secondary school to the end of the senior cycle, using data collected via anonymous self-administered questionnaires.

Adolescents are far from stereotypical
The current generation of adolescents is often portrayed as heedless, disenchanted, lazy and more reliant on things than on relationships. This study shows, however, that nearly half of adolescents (48.4%) are confident about the future (especially boys, 58.6%, compared with 38.9% of girls).
A large majority feel good about their relationships with their parents, and believe that their parents see them in a positive light. Furthermore, most of them judge that adults generally worry too much about adolescents (72.8%).

88% of these young people (90.3% of girls versus 85.5% of boys) believe that their intrinsic value does not depend on the number of things they own. They value themselves in relation to the image they convey to others, their academic results, and their creativity.

With respect to boundaries, today’s adolescents are far from stereotypical: although more than half of them think that adults set too many boundaries, even more recognise that they need them (74.9%). However, over three-quarters of them believe that too many boundaries, on the other hand, encourage risk-taking (77%).

Risk taking is, moreover, generally described as an essential part of adolescence. For over a third of these young people (34.1%), to live a good life, “you have to take risks without counting the cost”. These data reflect the well-known ambivalence of adolescents.

New forms of unhappiness

Adolescents are aware that the period they are going through is not an easy one: they often question themselves (49.3%), especially girls (61.7% vs 35.7% of boys). Half of them question themselves about the people in their entourage, girls (57.8%) more than boys (49.6%). This period of profound evolution of identity, conducive to risky behaviours, accentuates the psychopathological vulnerability of these young people.

Attempted suicide seems to be more frequent than before: 7.8% of young people have already attempted suicide once, and 3.7%, more than once. Depression affects 16.8% of girls and 7% of boys. Furthermore, 38.9% of young people have already thought that “life wasn’t worth living.” Alarming figures, especially since a very large majority of adolescents (74.5% of girls and 57.6% of boys) prefer isolation as a “way of coping” when they are not feeling good. This makes it less likely that others will become aware of their unhappiness, since friends represent only the third resource, after listening to music (mostly girls) or playing video games (mostly boys). We can also be concerned about figures for young “subdepressives” or mild depressives: 33.6% of girls and 21.6% of boys, strongly increased compared with the last available data.

Although the goal of this study was to better understand adolescents’ self-perception, this report contains many results, particularly with regard to:

-Their relationship with social networks:

88% of adolescents are on social networks. For 76.9% of them, this choice is justified by the presence of friends on the same network.

-Their use of psychoactive substances:

Generally, girls use mainly tobacco (9.2% of them claim to be “hooked,” compared with 7.8% of boys), while boys use mainly alcohol, with worrying figures for binge drinking in the month prior to the survey (37.6%). 7.1% of young people are regular users of cannabis.

-Their sexuality:

10.7% of boys versus 4.2% of girls state that they had sexual relations before the age of 13 years, which remains a worrying figure.

-Their education:

The vast majority find school tiring, stressful and irritating, or even painful. Only a third of young people find it enjoyable, although they believe it to be essential.

-Their recreational activities:

Sport, music, friends, the Internet and computer games (especially boys) are the most popular pastimes among adolescents.