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World multiple sclerosis Day

Monday, May 28 is World MS Day.

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. It causes the progressive destruction of the myelin sheath surrounding the nerve cells, which is essential for their protection and for the transmission of nerve impulses, leading to motor, sensory, and cognitive disruption.

The ability to effectively repair myelin is a key factor in controlling the progression of the disease.

 

Inserm teams are mobilized to further research into MS.

At present, magnetic resonance imaging (MRI) is widely used to diagnose and follow up patients with the disease. However, no imaging tools exist to predict the onset of relapse.

Researchers from the “SpPrIng” team, led by Fabian Docagne at Inserm Unit 1237 in Caen, France, have developed an MRI technique in which the progression of the disease can be followed in space and time in a murine model of MS. To do this, they used MRI-detectable iron beads that bind to the adhesion molecules.

The ability to effectively repair myelin is a key factor in countering the progression of MS. Understanding why and how some patients are able to better manage the disease than others is essential.

To gain a better understanding of the phenomenon, Inserm researchers transplanted lymphocytes from healthy donors or MS patients into the demyelinated lesions in the spinal cord of mice. The study of lymphocytes from patients with strong capacities for remyelination is a promising route to the development of new myelin regeneration strategies.

Nosocomial infections can also be caused by the Bacillus cereus bacterium

Bacillus cereus – Inserm/Leclerc, Henri, 1990 – Source : Inserm images

 

While Bacillus cereus is well known as a source of food infections, researchers from INRA and ANSES, working with doctors at nine French hospitals[1] including those in the Paris Public Hospital System (AP-HP), have demonstrated for the first time that this bacterium is also responsible for inter- and intra-hospital nosocomial contamination. This study, conducted in 39 patients between 2008 and 2012, also found strains of B. cereus in the hospital environment capable of causing infections that can sometimes be fatal. These results, published in PLOS ONE, suggest that more attention should be paid to these hospital infections, in order to improve patient care.

Bacillus cereus is found everywhere: in soil, in food, on almost all surfaces, on human skin, etc. In spore form, the bacterium is resistant to cooking and pasteurisation. B. cereus is the second most frequent agent responsible for foodborne infections in France and the third in Europe; characteristic symptoms are diarrhoea and vomiting. In rare but more severe cases, B. cereus may also be responsible for non-dietary clinical infections, particularly among vulnerable individuals (such as newborns and the elderly). However, the actual incidence of such clinical infections by B. cereus is unknown and there is little information available on the characteristics of the bacterial strains involved.

Over a five-year period, using clinical and epidemiological data collected from nine participating hospitals in France – including two in the Paris Public Hospital System (AP-HP) – and with the support of laboratories supervised by INSERM, researchers from INRA and ANSES conducted a study on B. cereus in the hospital to obtain an in-depth characterisation (phenotypic and genotypic) of the bacterial strains. This study was conducted in 39 mainly immunocompromised patients who had been infected by B. cereus, eight of whom died.

This work revealed nosocomial contamination by B. cereus and enabled an in-depth analysis of the genetic profile of the strains of B. cereus identified in the hospital. The same B. cereus strain was found in several patients between whom no link could be established, as well as in the hospital environment.

Eight groups of patients carrying the same strain were thus identified, with one strain infecting up to four patients. Moreover, the same B. cereus strain was identified two years apart in separate patients of the same hospital. The pathogen is therefore a source of infection for hospitalised patients, probably due to the ability of B. cereus to sporulate and/or to form biofilms.

Molecular characterisation of the strains also showed that a strain with the same genetic profile could be identified in several patients within the same hospital, as well as in different hospitals.

These results highlight the need for vigilance with regard to B. cereus in the hospital – especially in immunocompromised individuals – and for great thoroughness in cleaning and disinfection procedures. The work also offers insights on the development of diagnostic tests based on virulence factors that are able to determine whether or not the B. cereus strains present a danger to human health.

The in vitro effectiveness of the first-line antibiotic therapies recommended for treating B. cereus infections was also demonstrated. Thus, in order to improve patient care, early diagnosis of a serious B. cereus infection could enable antibiotic treatments to be adjusted, without waiting for the results of additional analyses.

[1] Micalis Institute and MaIAGE – Applied Mathematics and Computer Science, from Genomes to the Environment (INRA, AgroParisTech), ANSES, Institute for Digestive Health Research (University of Toulouse III – Paul Sabatier, INSERM, INRA, ENVT), Toulouse University Hospital (CHU), Centre for Immunology and Infectious Diseases (INSERM, UPMC), Pitié-Salpêtrière Hospital, AP-HP, Antoine-Béclère Hospital, AP-HP, Nice CHU, Strasbourg CHU, Chambéry CHU, Grenoble CHU.

Ebola: Inserm Committed to Fighting this Epidemic

According to a recent report published by WHO on 05/23/2018, the death toll of the Ebola epidemic in the northwest Democratic Republic of the Congo on May 20 is 27 – out of 58 confirmed or suspected cases. The public health risk can be considered high due to its potential to spread into urban areas and neighboring countries.

The latest on Inserm’s commitment to fighting this epidemic.

Inserm and its partners at Aviesan have created REACTing, a multidisciplinary consortium bringing together research groups and laboratories of excellence in order to prepare and coordinate research to combat the health crises linked to emerging infectious diseases.

Concerning research, a significant breakthrough has been made with the identification of the so-called Ebola Zaire strain as responsible for the epidemic currently raging in the Democratic Republic of the Congo.

In order to be better prepared for and help contain future Ebola epidemics, it is also essential to continue research into the vaccination strategy for preventing this fever.

In April 2017, Inserm and the US National Institutes of Health and the London School of Hygiene & Tropical Medicine, in collaboration with the health authorities of Guinea and Liberia, have launched a new large-scale clinical trial of Ebola candidate vaccines, under the aegis of the international consortium PREVAC (Partnership for Research on Ebola VACcination). One year later, more than 2,000 adults and children in Guinea and Liberia have been enrolled into this international clinical trial.

Five years after a stroke treated well, what are the chances of recurrence?

The team of Professor Amarenco, head of the neurology department at the Hospital Bichat Claude Bernard, AP-HP, professor at the University Paris Diderot – Inserm studied the risk of recurrence of stroke for patients who received a care in the 24 hours following the occurrence of a transient ischemic attack. The researchers demonstrate that 1 to 5 years the risk remains constant. These results suggest that prevention of these events should not only focus in the first months after stroke, but should be extended at least 5 years. 

They are published in the New England Journal of Medicine on May 16

Today, about a cardiovascular accident in four is preceded by a transient ischemic attack. It can for example manifest as paralysis of a limb, loss of speech and / or vision, or impaired balance. After a TIA or minor stroke (not giving immediate disability), the long-term risk of developing another stroke, myocardial infarction or vascular death is not known.

After reporting in a first study published in 2016 in the New England Journal of Medicine , the risk of occurrence of a cardiovascular event in a year, the team has focused on measuring the 5-year risk . This work was performed as part of the international project TIAregistry.org .

The study was conducted among 3847 patients from 21 countries (in Europe, Asia, Japan, Latin America) between 2009 and 2011, victims of a TIA or minor stroke within 24 hours to 80% of them and others in 7 days. The goal was especially to assess the patients’ health status, supported in a specialized structure, and the risk of stroke five years after the onset of TIA or minor stroke. Of the 61 initial centers that allowed the first publication of data in 1 year, 42 participated in the monitoring of patients until the 5th year.

Among the 3847 patients followed 5 years, 469 had a cerebral infarction, myocardial infarction or vascular problem are dead, a 5-year risk of 12.9%.

Half of these events occurred during the first year of monitoring, half occurred between the second and fifth years, which shows that prevention of these events should not only focus during the first months of the stroke, but should be extended at least 5 years.

The occurrence of these events remains constant over time, that is to say that the risk does not tend to diminish.

At 5 years, the risk of recurrent stroke was 9.5%, slightly less than half occurred between the second and fifth year.

In the analysis, the predictors of a higher risk between the second and fifth year were the presence of atherosclerotic cause of AVC disease that clogs the arteries of the heart and brain by a deposit-cholesterol or cause embolic cardiac (heart arrhythmia is the most common of these causes), or a high risk score (score combining the presence of hypertension, diabetes, an age over 60 years, a period of the initial episode than 10 minutes, or the presence of paralysis or language impairment in symptoms of TIAs).

After a TIA or minor stroke leaving no disability, the risk of a repeat disabling stroke or myocardial infarction, fatal or not, was 6.4% in the first year and 6.4% between the second and the fifth year. This result was obtained when all the patients in this study were treated optimally, that is to say following the treatment recommendations after stroke.

The authors advocate developing more effective prevention strategies to decrease the risk of stroke. Among them, include new drugs as those acting on cholesterol, or triglycerides, or even simple hygiene measures such as regular exercise (eg 20 to 30 minutes of exercise bike every morning before shower) and weight loss. As only 25% of strokes are preceded by TIAs, other detection strategies of patients at risk must be found. The medicine should also connected to help identify.

The nature of the Ebola virus responsible for the 9th epidemic currently raging in the DRC characterized

 

©Adobestock Microscopic view of the ebola virus

The National Institute for Biomedical Research (INRB) of Kinshasa and Inserm have characterized the nature of the Ebola virus responsible for the 9th epidemic currently raging in the Democratic Republic of Congo (DRC). The strain identified is the so-called Ebola Zaire strain.

According to a latest report published by the WHO (19/5/2018), a total of 46 cases (of which 21 confirmed), due to the current epidemic have been reported in the Democratic Republic of Congo (DRC). The risk for public health can be considered as high because of the possible extension in urban areas and neighboring countries.

Since the outbreak in West Africa in 2014, we have learned that the responsiveness of national and international health authorities is fundamental to accelerate the management and deployment of vaccines and possible treatments such as antivirals, or neutralizing antibodies. The deployment of these strategies, currently under discussion between the DRC authorities and the WHO, depends on the characterization of the virus responsible for the epidemic. Five Ebola strains are known today.

The collaboration established between INRB and INSERM (UMR INSERM / IRD / University of Montpellier), the technology transfer and the exchange of researchers between the two institutes allowed the genetic characterization of the circulating virus in the DRC, responsible of the current epidemic. The strain identified is the so-called Ebola Zaire strain. 

The approach used by the researchers used standard on-site techniques and new generation techniques that did not require the isolation of the live virus. The partnership between the two institutes as part of Inserm’s Reacting platform and its program to monitor the reservoir of the Ebola virus in Africa, supported by the french ministry for education and research with the help of the IRD and of the University of Montpellier, allowed a rapid deployment of these technologies. Reacting, a platform coordinated by Inserm, with its partners in the alliance Aviesan (alliance for life sciences and health), is a multidisciplinary consortium bringing together teams and laboratories of excellence, to prepare and coordinate research to deal with sanitary crises.

“This collaboration has allowed us to respond quickly to a health emergency, to ensure that the nature of the Ebola virus responsible for the epidemic is identified by DRC researchers and to alert the health authorities to rapidly deploy treatment on sites, “says Professor JJ Muyembe, Director General of INRB.

“I congratulate the INRB for this breakthrough under difficult conditions in its mission of monitoring and diagnosis and the excellence of our collaboration,” said Professor Eric Delaporte.

“In this context of health crisis, our experience in Guinea during the Ebola outbreak in 2014, the structuring of the Reacting platform conducted under the responsibility of Prof. Yazdanpanah, and the North / South collaborations put in place allowed us to better prepare and respond quickly. I would like to congratulate Professor Delaporte and Professor Muyembe for this breakthrough. This opens the way to the care of the sick people”, says Pr Yves Lévy, CEO of Inserm. 

European Obesity Day

Crédits: Adobe Stock

Friday, May 18 is European Obesity Day. A day to raise the awareness of healthcare players, caregivers and patients of this issue which affects more than 650 million people worldwide.

According to WHO, 13% of adults worldwide were obese in 2014, a figure which had doubled since 1980.

Obesity is often diagnosed using the body mass index (BMI), a calculation that estimates body fat. BMI is a person’s weight (in kg) divided by the square of their height (in meters). Apart from the psychological and social discomfort generated by this chronic condition, it also leads to health problems, primarily type 2 diabetes, hypertension, osteoarthritis, sleep apnea syndrome, and cardiovascular disease.

 

Teams from Inserm are mobilized to advance research in this field.

Nutri-score: a new nutritional aid for the consumer

A team of researchers (Inserm/ Inra/ Cnam/ Université Paris 13) led by Serge Hercberg, has revealed via a study published in the journal Nutrients  that this 5 color (5-C) nutrition label is the most effective nutritional information system for enabling consumers to recognize and compare the nutritional quality of foods, including those from “at risk” populations (older subjects, those with a low educational level, low income, poor nutritional knowledge, and overweight or obese individuals).

Following this study and as part of the 2016 Health Act, the French government recommended the deployment of Nutri-Score in order to improve product nutrition information and thereby help consumers to buy foods of better nutritional quality.

Read our press release: “The 5-colour nutritional labelling system is the most effective for consumers”

 

Online coaching for abdominal obesity

A study coordinated by Dr. Boris Hansel and Prof. Ronan Roussel, shows that online nutritional coaching – an automated nutritional support program – improves dietary habits and glucose control in patients with type 2 diabetes and abdominal obesity.

The results show a significant increase in the dietary score in the online coaching group (+5.25 points) in comparison with the control group (-1.83) on average.

Read our press release: “Efficacy of online nutritional coaching in patients with type 2 diabetes and abdominal obesity”

And because good health also depends on good diet and exercise, consult our nutrition and health report (only available in French) on the Inserm website.

Towards Understanding the Origin of the Most Common Form of Female Infertility

Researchers from Inserm and Université de Lille have discovered that the most common female infertility disorder – polycystic ovary syndrome (PCOS) – may be caused by overexcitation of brain neurons. The culprit? A hormone produced by the ovaries, called “anti-Müllerian hormone” (AMH), which is produced in excess in women with PCOS. Research conducted by the team in mice show the importance of in utero exposure to abnormally high levels of AMH in the occurrence of the disease. These findings, published in Nature Medicine, pave the way for new concepts linked to the embryonic origin of the disease as well as new avenues for the development of a treatment.

One in ten women of childbearing age suffers from polycystic ovary syndrome (PCOS), in which the ovaries produce androgens (male hormones) in excess, disrupting the growth mechanisms of the ovarian follicles. A greater number of these follicles will stagnate – hence the (erroneous) term “polycystic ovaries” – leading to ovulation dysfunction responsible for infertility.

While we currently know how to diagnose the disease, its cause remains unknown. Current therapeutic options aim to reduce symptoms and prevent complications but no preventive or curative treatment exists.

A team coordinated by Paolo Giacobini, Inserm Research Director (Jean-Pierre Aubert Research Center – Neurosciences and cancer, Inserm U1172/Université de Lille/Lille University Hospital), is challenging the hypothesis according to which PCOS only alters the ovaries, by showing that it also modifies the activities of brain neurons in the hypothalamus, which are responsible for controlling reproduction. Implicated is a hormone produced by the ovaries and involved in their functioning: anti-Müllerian hormone (AMH). Patients with PCOS present blood levels of this hormone which are two to three times higher, and directly linked to the severity of the disease.

The team based its research on two observations made in pregnant women with PCOS. The first is its already-known correlation with hyperandrogenism (excessive production of androgens). The second, a new observation, is its correlation with a heightened production of AMH during pregnancy. The researchers have shown that mice treated with AMH during gestation give birth to females that develop the symptoms characteristic of PCOS in adulthood. The production of abnormally high levels of AMH during the prenatal period could therefore be responsible for gestational hyperandrogenism and the abnormal hormonal impregnation of the fetus.

The team also observed that, in mice mimicking PCOS, in utero exposure to abnormally high levels of AMH was responsible for increased activity of the GnRH protein-secreting hypothalamic neurons in adulthood.  This intense GnRH production stimulates the heightened production of another hormone, luteinizing hormone (LH), which itself stimulates the production of androgens.  Paolo Giacobini and his coworkers, including Brooke Tata and Nour El Houda Mimouni, joint first authors of the article, demonstrate here that prenatal exposure to AMH triggers a genuine chain reaction in offspring:  the hypothalamic neurons start secreting more GnRH, which increases LH production by the pituitary gland, in the end triggering this characteristic increase of androgens in the ovaries, which is responsible for the disrupted ovulation observed in PCOS.

Armed with these findings, the researchers applied to mice mimicking PCOS a specific treatment that “normalizes” the increased action of GnRH on LH production, thereby restoring their fertility. These findings observed in the mouse model offer unheard of therapeutic perspectives which remain to be confirmed at human level.

May ’68, Lived and Recounted by the French Scientific Community

Crédits: Inserm/ Schuch Productions

The month of May 1968 saw French society reach boiling point. No exception to this rule was the scientific community, which rose up and reinvented its world. Its members occupied the universities, went on strike in the hospitals and condemned the old ways of the research labs. We invite you to discover “Mai 68, la science s’affiche” (“May ’68, when science took a stand”, only available in French), a series of short films looking back on the events that revolutionized the academic and hospital world. A series created with the support of Inserm, in co-production with CNRS Images and Schuch Productions, in association with Universcience, and with the participation of the French National Center for Cinema and Motion Pictures (CNC).

For some students and young researchers, the month of May ’68 marked the beginning of their political dissent. The protagonists of this series, all scientists, tell us about that month through their own experiences. In the faculties of medicine, students occupied the auditoriums, challenging the elitism and conservatism of their learning.

Each episode in the series looks at an emblematic aspect of May ‘68, commentated and contextualized by academics and researchers from Inserm and CNRS who were there at the time.

“In medicine, too – no more autocrats!”  With May ‘68, it was the entire paternalist model of knowledge and social organization that came toppling down – in the research labs, hospital departments and universities.  In every direction, students and young researchers attacked the hierarchical relationships and authority that they no longer wished to accept.

“A woman’s place…” The wind of freedom brought by the movements of May ’68 was also the starting point in the fight for women’s rights. A means of attacking the gender hierarchy that prevailed even in the scientific circles and world of research.  The account of Inserm researcher Ségolène Aymé, at the time a medical student against her family’s wishes, portrays the difficulty being a woman of science back then.  This period saw the birth of the French women’s liberation movement, the MLF.

“The children we want.” While May ‘68 certainly brought about profound changes in French society, abortion was still illegal. Many doctors, such as Ségolène Aymé and Pierre Jouannet, considered it necessary to defy the law and aid women wishing to terminate their pregnancies. It took another five years to launch the Movement for the freedom of abortion and contraception (MLAC), and another eight for the adoption of Simone Veil’s law legalizing abortion.

Air Pollution in France: a Cost to Fetal Health and Society

Inserm researchers from the Epidemiology of Allergic and Respiratory Diseases (EPAR) team have analyzed data on the risks of children being born with low birth weight linked to air pollution. Their study reveals that there is a high price to pay for exposure to air pollution during pregnancy and its resulting impact on children post birth. A cost to society which is estimated at 1.2 billion euros. The results of this study were published in the May 2018 issue of Archives de Pédiatrie.

We know that pollution has consequences for health, with pregnant women being especially vulnerable. Exposure to pollution during pregnancy can lead to intrauterine growth restriction. In 2012, 2.3% of children born in France had a low birth weight (less than 2.5 kg), despite being at full-term. Half of these cases were caused by the mother’s exposure to fine particulate matter during pregnancy. This low birth weight then has various developmental consequences, with major intellectual deficiencies occurring in some children.

The EPAR Inserm/Sorbonne Université team decided to study the costs associated with managing low birth weight caused by particulate pollution from human activities. The researchers began by calculating the cost of its management in the maternity unit at birth and came to an estimate of 25 million euros.

The study then went on to emphasize that one in four of these children will suffer delayed motor or intellectual development and considers the cost of treating these children throughout their lifespan to be 1.2 billion euros.

“As things currently stand”, considers Isabella Annesi-Maesano, Inserm Researcher and Research Director leading the study, “the estimated costs are covered by the public authorities which fund the healthcare structures. The remaining costs (childcare, parental absenteeism, special education, etc.) are borne by the families.”

In the short term, the study suggests implementing public health measures to protect pregnant women with, for example, the recommendation that they limit their exposure during periods of peak pollution.

“It is necessary to implement genuine air quality improvement policies for future generations,” concludes Annesi-Maesano.

A new gelling molecule for growing neurons in 3D

A multidisciplinary team of researchers from CNRS, INSERM and Université Toulouse III – Paul Sabatier has developed a hydrogel that can grow, develop and differentiate neural stem cells. This biomaterial could provide new paths for the development of in vitro cellular models of brain tissue or of in vivo tissue reconstruction. This work is published in ACS Applied Materials & Interfaces on May 14, 2018.

Although we know how to culture cells on a two-dimensional surface, that is not representative of the actual cell environment in a live organism. In brain tissue, cells are organized and interact in three dimensions in a soft structure. The researchers’ main goal was to imitate this tissue as closely as possible. They developed a hydrogel that meets suitable criteria for permeability, rigidity and biocompatibility; on that, they cultured human neural stem cells[1].

N-heptyl-galactonamide is a new molecule synthesized by these scientists, which is part of a family of gelling agents that usually produces unstable gels. It is biocompatible, has a very simple structure, and can be made quickly, so has many advantages. By working on the parameters for forming the gel, the researchers at the Laboratoire Interactions Moléculaires et Réactivité Chimique et Photochimique (CNRS/Université Toulouse III-Paul Sabatier), Toulouse Neuro Imaging Center (INSERM/Université Toulouse III-Paul Sabatier) and the CNRS Laboratoire d’Analyse et d’Architecture des Systèmes obtained a stable hydrogel with very low density and very low rigidity. Because of that, neural stem cells can penetrate and develop in three dimensions in the hydrogel. It also has a network composed of different types of fibers, some straight and rigid, others curved and flexible. This diversity allows neurons to develop a network of short- and long-distance connections like those in brain tissue.

This new biomaterial could therefore lead to the development of three-dimensional brain tissue models that function in a manner approaching in vivo conditions. In the long run, it could be used to evaluate the effect of a medicine or to enable cells to be transplanted with their matrix to repair brain damage.

[1] Neural stem cells came from patient biopsies (CHU Toulouse – Pôle Neurosciences). These cells are capable of differentiating into neurons and glial cells, the main types of cells in brain tissue.
A new gelling molecule for growing neurons in 3D

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