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Zika virus found inside spermatozoa

Zika spermaozoides (c) Suberbielle

Spermatozoa infected by Zika virus (green; arrowhead) 

© Elsa Suberbielle, CPTP / Inserm

Recent work has shown that Zika virus persists in semen for up to 6 months after infection[1]. In a correspondence published in The Lancet Infectious Diseases, the researchers, in addition to confirming its long persistence in semen (in this case for more than 130 days, i.e., over 4 months), reveal the presence of the virus even within spermatozoa. This work results from collaboration between researchers from Inserm, CNRS, and academic practitioners from University Toulouse III – Paul Sabatier and Toulouse University Hospital.

 

In this letter, the scientists report the case of a 32-year-old man returning from French Guyana with symptoms suggestive of Zika virus infection, namely, moderate fever, rash, and muscle and joint pain. Zika virus was detected in the patient’s plasma and urine 2 days after the onset of these symptoms. Samples of semen (11 samples), blood (10) and urine (5) were taken and analysed over a total period of 141 days.

Upon analysis, Zika virus was found to be present in all samples up to the 37th day. Beyond that point, the virus was found only in the semen, where it persisted for over 130 days, while the patient was in good health. This result was confirmed in two other patients, in whom the virus persisted for 69 and 115 days in the semen. For the moment, the factors responsible for this variation in persistence amongst individuals are unknown. From the time of diagnosis, however, these patients were advised to use protection during sexual relations.

 

The research team subsequently analysed the semen from the patient and examined the spermatozoa it contains using various microscopy techniques.

“We detected the presence of Zika virus inside approximately 3.5% of this patient’s spermatozoa,explains Guillaume Martin-Blondel, Inserm researcher at the Toulouse Purpan Pathophysiology Centre (Inserm/CNRS/University of Toulouse III – Paul Sabatier) and physician at the Infectious and Tropical Diseases Department of Toulouse University Hospital.

The researchers explain that for other sexually-transmitted viruses, such as HIV, the virus remains “stuck” at the surface of spermatozoa. For purposes of in vitro fertilization, it is therefore possible to “wash” the spermatozoa from HIV-infected patients, whereas this seems to be excluded for patients positive for Zika virus. However, the “active” nature of the Zika virus present in spermatozoa remains to be determined, as well as the ability of these spermatozoa to transmit infection (since the virus is also present outside the spermatozoa, in the seminal fluid).

 

In conclusion, analysis of this case has important implications for the prevention of sexual transmission of this virus, by means that remain unknown at present. These observations also raise many questions on the need to include screening for Zika virus in the testing of sperm donations in fertility centres.

[1] http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22556

Towards an improved diagnosis of certain cancers

Asthme à l'étude

(c) Inserm/Latron, Patrice

Paris Descartes University, AP-HP, CNRS and Inserm have unveiled a royalty-free method that enables wide-scale use of circulating DNA in patients with lung and pancreatic cancer. This study is published in the journal Clinical Chemistry.

 

Detection of genetic alterations in tumour tissues helps to guide patient management for certain cancers, such as lung cancer. At present, these genetic studies are performed on tumour samples taken during biopsies and surgical procedures. Since tumour cells release very small quantities of their DNA into the plasma (circulating tumour DNA) a blood sample may be sufficient for the study of genetic alterations, allowing a “liquid biopsy” to be performed. The objective is not to replace the biopsy indispensable for diagnosing the cancer, but to identify the mutations and guide the prescription of cancer treatment by analysing the circulating tumour DNA. Finally, this analysis makes it possible to monitor the progression of the disease with time, and in some cases to avoid the need for further biopsies.

Before now, the molecular biology techniques needed to perform liquid biopsies were expensive, because their implementation was complex. Indeed, they require great sensitivity because they have to detect very small quantities of DNA, and great specificity to identify them as being of tumour origin. These techniques are developing at a rapid rate, and a team from Paris Descartes University UMR_S1147 has recently developed ultrasensitive techniques, based on droplet digital PCR, which study the most common genetic alterations and analyse epigenetic modifications.

Currently, this same team, working with physicians and biologists from Georges Pompidou European Hospital (HEGP) and Pitié Salpêtrière Hospital, of the Paris Public Hospitals (AP-HP), propose a method for detecting circulating tumour DNA based on next generation sequencing (NGS). It uses data from any type of NGS sequencer. It does not require the installation of expensive new machines, nor does it generate any additional costs compared with detection of mutations within tissues. It performs optimal processing of NGS data using a statistical method based on comparison of the patient plasma sample with samples from a cohort of control subjects.

Compared with digital PCR, this method obtains a comparable mutation rate, while being applicable to a greater number of genes and a greater number of patients.

This method could ultimately be used widely in the different molecular biology platforms that cover the whole territory, and facilitate the analysis of circulating tumour DNA as part of the care and follow-up of cancer patients. Additional clinical studies are needed in order to validate the ability of this new technique to guide the management of patients.

 

This study involved researchers from the laboratories “Personalized Medicine, Pharmacogenomics, Therapeutic Optimization” (UMR-S1147, Paris Descartes University/Inserm, CNRS SNC 5014), and “Mother and Child Facing Tropical Infections” (MERIT; UMR 216, French Institute for Development Research [IRD] and Paris Descartes University) and physicians from the Georges Pompidou European Hospital and Pitié-Salpêtrière Hospital AP-HP.

A new way to combat viruses

The team “Physiopathology and therapeutics of chronic viral hepatitis and related cancers” of the Mondor Institute of Biomedical Research (Inserm/UPEC), located on the premises of Henri Mondor Hospital AP-HP, in collaboration with the researchers of the Centre for Structural Biochemistry (CNRS/Inserm/Montpellier University), with the support of ANRS, has created a whole new family of molecules that inhibit cyclophilins – proteins indispensable to cell metabolism – and have strong therapeutic potential as broad-spectrum antiviral drugs. This discovery, published in Nature Communications on 22 September 2016, also opens the possibility of using these new inhibitors to protect cells in the context of ischaemia-reperfusion (organ transplants, recovery after ischaemic accidents, or neurodegenerative diseases).

 

Cyclophilins are cellular proteins that play complex and indispensable roles in cell metabolism. They are very often used by viruses to help complete their life cycle. Cyclophilins therefore represent a potential target for broad-spectrum antiviral drugs, i.e. drugs that are effective against many virus families. Cyclophilin inhibitors also have cell protection properties associated with inhibiting the opening of the mitochondrial pore. Unfortunately, the existing inhibitors, all derived from cyclosporin A, present considerable problems that impede their clinical development.

 

The teams led by Professor Jean-Michel Pawlotsky (Mondor Institute of Biomedical Research [IMR], Henri Mondor Hospital AP-HP, Inserm/University Paris-Est Créteil [UPEC]) and Dr Jean-François Guichou (Centre for Structural Biochemistry [CBS], Montpellier University/CNRS/Inserm), have joined forces and used innovative techniques to create and optimise a whole new family of chemicals that directly target cyclophilins. This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). The new inhibitors thus specifically block the action of cyclophilins by inhibiting the multiplication of viruses from different viral families such as hepatitis C virus, HIV, hepatitis B virus and several coronavirus strains.

This work therefore made it possible to create a whole new family of cyclophilin inhibitors with strong therapeutic potential as broad-spectrum antiviral agents, i.e. active against many viral families for which there is currently no treatment. This discovery also provides an opportunity to use new inhibitors to protect cells in the context of ischaemia-reperfusion (organ transplants, recovery after ischaemic disease, or neurodegenerative diseases).

 

This work was carried out as part of a close collaboration between Dr Abdelhakim AHMED-BELKACEM and Prof. Jean-Michel PAWLOTSKY for the team “Physiopathology and therapeutics of chronic viral hepatitis and related cancers” (Mondor Institute of Biomedical Research, Inserm/UPEC). It also involves Dr Lionel COLLIANDRE and Dr Jean-François GUICHOU from the Centre for Structural Biochemistry (CBS; Montpellier University/Inserm/CNRS) and researchers from the Institute of Analytical Sciences (ISA; CNRS/ENS Lyon/Claude Bernard Lyon 1 University).

The team “Physiopathology and therapeutics of chronic viral hepatitis and related cancers” at the Mondor Institute of Biomedical Research is developing research on two main themes: the development of broad-spectrum antiviral approaches (building on its experience in the development of new treatments for hepatitis C), and the role of inflammation and the liver microenvironment in the occurrence and progression of primary liver cancers.

Meanwhile, the team “Structures and screening of therapeutic and environmental targets” at the Centre for Structural Biochemistry is developing an integrated approach to spur and rationalise the development of new molecules with potential therapeutic applications, using X-ray crystallography and structural bioinformatics.

Too much fat rapidly unbalances the intestinal flora

Visuel sansonneti microbiote

Localisation of the bacteria the ileum of a mouse fed a standard diet (left) or a high-fat diet (right).

© Institut Pasteur

A disruptive element such as a change in diet, and the whole intestinal flora becomes disrupted, with possible repercussions for health. An international research study conducted by the Molecular Microbial Pathogenesis Unit (Institut Pasteur/Inserm), directed by Philippe Sansonetti, has just demonstrated, in mice, the direct influence of a diet too high in fat on the intestinal flora and its environment. In response to this new diet, the bacterial communities reorganise themselves and the small intestine itself is transformed. And this happens in the first month. These results were published in the journal PNAS on 16 September.

 

The billions of bacteria that populate our intestine – known as the microbiota – play a central role in digestion, but also have a role in some diseases such as type 2 diabetes or obesity. These diseases have often been associated with an imbalance of the intestinal flora, with some bacteria becoming clearly predominant, and a permeable intestine, likely to release inflammatory substances into the bloodstream. But although many studies have been conducted on the state of the microbiota once the disease has become established, few have focused on the development of this intestinal imbalance, e.g. when a high-fat diet is introduced. For this reason, an international research team has addressed the question. “We wanted to see, from an early stage, how the intestinal bacteria behave in the presence of a high-fat diet,” emphasises Thierry Pédron, a research engineer in the Molecular Microbial Pathogenesis Unit (Institut Pasteur/Inserm). “And we soon focused our research on the small intestine, because that was where we saw the most obvious variations!”

 

Some mice in the study were therefore fed an ordinary diet, whereas others were fed a diet containing 70% lipid. Using genomic techniques, the researchers were able to identify the different bacterial species contained in faecal samples, and monitor the changes in composition of the microbiota in time. They also localised and accurately identified the bacteria within the small intestine.

“Only one month after starting this new high-fat diet, we observed changes in the composition of the microbiota,” says Thierry Pédron. “Some bacterial species proliferated, whereas others declined, and the species Candidatus arthromitus actually disappeared completely. Furthermore, and as never seen before, we observed a massive concentration of bacteria between the intestinal villi.”

 

Ordinarily, bacteria cannot come close to or even cross the intestinal wall because the epithelium releases antimicrobial peptides and is lined with a protective mucus. The researchers then focused on these intestinal wall defences: they found that production of antimicrobial peptides fell following massive ingestion of fat, and that the mucus layer became thinner. In other words, not only does the microbiota become reorganised under the influence of lipids, but the intestine itself undergoes transformation. And the modifications do not end there. Additional measurements made it possible to demonstrate an increase in the permeability of the small intestine, and a reduction in PPAR-γ activity. “PPAR-γ is a molecule with many functions. It plays an important role in fatty acid metabolism, as well as in inflammation and embryonic development,” explains Thierry Pédron. “This drop seems closely related to the drop in antimicrobial peptide level.” And although the connections between all these results and their potential involvement in some dietary imbalances have not yet been established, it is reassuring to note that when the mice are put back on a balanced diet, everything returns to normal within a month!

Ile-de-France residents + public transport = Champions of daily exercise

tramway à strasbourg

(c) Fotolia

Ile-de-France Transport Union (STIF), the public transport authority for the Ile-de-France (Greater Paris) region, and Inserm, the French National Institute of Health and Medical Research, have revealed the results of a study* measuring the physical activity associated with the daily journeys of Ile-de-France residents. This study shows that the use of public transport contributes significantly to the physical activity of Ile-de-France residents, an important behaviour for staying healthy.

 

In Ile-de-France, taking public transport generates 27 minutes of physical activity for users!

The study reveals that although cycling represents the greatest source of moderate or vigorous activity involved in daily journeys, only 2% of the Ile-de-France population are bike users. In second place, public transport generates the most physical activity for users: the 29% of Ile-de-France residents who use public transport daily actually get an average of 27 minutes’ physical activity per day using this mode of transport, i.e. an expenditure of 180 kcal.

We tend to forget that travellers using bus, métro (underground), tramway, RER (suburban rail), or a combination of these modes during a single journey, generally make part of the trip on foot. Public transport offers travellers many opportunities to walk, either between the departure or arrival points and stations, or when making connections.

On average, journeys involving public transport generate even more daily physical activity for users than journeys made entirely on foot, since people who travel on foot get an average of 16 minutes of physical activity per day during these walks.

 

Parisians are the most active in their daily journeys

The average duration of physical activity performed by Ile-de-France residents during their daily commute depends on where they live. Because they have the longest journeys, and are the most likely to use modes of transport other than cars, Parisians are the most active, getting 29 minutes of physical activity per day while commuting. Indeed, 30% of their journeys are done on public transport, and over half on foot. Ile-de-France residents from the inner and outer suburbs respectively get 22 minutes and 18 minutes of physical activity during their daily commutes.

 

Encouraging use of public transport to combat inactivity

“Our study shows that Ile-de-France commuters who choose public transport get an average of nearly 30 minutes of exercise per day on weekdays, i.e. the average duration recommended by WHO and the national health authorities in order to stay healthy and fit. Apart from the strictly active modes of transport such as walking and cycling, promotion of public transport use seems to constitute a particularly effective lever for increasing the level of physical activity in the population,” adds Basile Chaix, scientific manager of the study and Inserm Research Director, and Ruben Brondeel, a PhD student working on the project.

Combating inactivity is currently a real challenge for society and for public health. WHO also considers inactivity to be the 4th leading risk factor for mortality worldwide. Insufficient physical activity is a cause of overweight and obesity, but is also the main cause of many cancers and cardiovascular diseases, which represent over 55% of the 550,000 annual deaths in France. Walking in all its forms is the simplest form of exercise, and is accessible to all.

 

STIF is working to improve the integration of transport systems in Ile-de-France

The study conducted with Inserm demonstrates that the use of public transport has advantages in combating inactivity among Ile-de-France residents. The encouragement of public transport use, and hence of daily physical activity, among Ile-de-France residents is undergoing further integration. To accomplish this, no type of mobility will be neglected in increasing and facilitating the links between the different types of public transport, the future Grand Paris Express network and the car, bike and motorised two-wheel vehicles. To enhance the provision of services that facilitate and promote active modes of transport and public transport, STIF is committed to:
• developing and encouraging cycling, with the development of parking spaces for Véligo bikes near stations, offering a secure collective storage facility accessible by Navigo card, and a self-service covered shelter,
• increasing park and ride options to facilitate access for travellers to the rail network by creating new car-parks close to stations,
• and establishing more balanced road-sharing, especially for buses, in order to provide a safer and more efficient service.

 

KEY FIGURES from the study:

• 41 million journeys per day in Ile-de-France, i.e. an average of 3.87 journeys per person per day

Duration of physical activity as a function of the transport modes used by Ile-de-France residents
• 22 minutes  mean duration of daily physical activity by Ile-de-France residents during journeys, for all types of transport combined
• 8 minutes  mean duration of daily physical activity by users of individual motorised modes of transport during journeys by these modes (car, motorised two-wheel vehicles, taxi, etc.), i.e. 58 kcal
• 16 minutes  mean duration of daily physical activity by Ile-de-France residents who travel entirely on foot during these journeys, i.e. 103 kcal
• 27 minutes  mean duration of daily physical activity by users of public transport during journeys by this mode, i.e. 180 kcal
• 48 minutes  mean duration of daily physical activity by bike users during journeys by this mode

Duration of physical activity of Ile-de-France residents as a function of place of residence
• Residents living in Paris do 29 min. of physical activity during their daily journeys
• Residents living in the inner suburbs do 22 min. of physical activity during their daily journeys
• Residents living in the outer suburbs do 18 min. of physical activity during their daily journeys

 

*Methodology of the study:
The study is based on the intersecting results of the Record GPS Study conducted by Inserm in 2012-2013, which is based on an objective and precise measurement of physical activity performed during movement using accelerometry, and the 2010 General Transport Survey (EGT) conducted by STIF and DRIEA (Regional and Interdepartmental Directorate of Equipment and Development) under Omnil (Ile-de France Observatory for Mobility). Results relate to Ile-de-France residents aged 35-83 years.

About STIF (Ile-de France Transport Union)
STIF designs, organises and funds public transport for all Ile-de-France residents. At the heart of the Ile-de-France transport network, STIF brings together all the stakeholders (travellers, elected representatives, builders, carriers, infrastructure managers etc.), and invests and innovates to improve the service provided to travellers. It selects and manages projects for the development of the networks and modernisation of all forms of transport that it entrusts to carriers.
Chaired by Valérie Pécresse, President of Ile-de-France Regional Council, STIF is made up of the Ile-de-France Region and eight other Ile-de-France departments, and is thus responsible for the overall vision of Ile-de-France’s transport systems (train, RER, métro, tramway, T Zen [high-quality bus service] and bus). www.stif.info and www.stif.org

About Inserm (French National Health and Medical Research Institute)
Created in 1964, Inserm is a public scientific and technical research institution, under the joint supervision of the French Ministry of Education, Higher Education and Research and the French Ministry of Social Affairs, Health and Women’s Rights. Inserm is the only French public body dedicated to biological and medical research and human health, and occupies a position along the entire pathway from the laboratory to the patient’s bedside. Its researchers study all diseases from the most common to the most rare.
Inserm supports nearly 300 laboratories distributed throughout the French territory. Together the teams comprise nearly 15,000 researchers, engineers, technicians, managers, clinician-researchers, post-doctoral fellows, etc.

 

The Nemesis team, led by Basile Chaix, Inserm Research Director, focuses on the relationships between environment, mobility and health, primarily studying the effects of living quarters on health, and secondly the impact of transport habits on health. The Nemesis team is part of the Pierre Louis Institute of Epidemiology and Public Health (IPLESP), which reports to both Inserm (French National Institute of Health and Medical Research, www.inserm.fr) and Pierre and Marie Curie University (UPMC, www.upmc.fr).

 

Other partners in the study: the Directorate-General for Infrastructure, Transport and the Sea (DGITM) of the Ministry of Ecology, the Centre for Studies and Expertise on Risks, Environment, Mobility, and Urban and Country Planning (CEREMA), RATP (Autonomous Operator of Parisian Transports), Ile-de-France Regional Council, and the Regional and Interdepartmental Directorate of Equipment and Development (DRIEA).

A tailored sports training programme for people with paraplegia

handisport

(c) Gaëlle Deley

 

Now that the 2016 Summer Olympic Games are over, Rio de Janeiro will be hosting the Paralympic Games from 7 to 18 September. The participating athletes will be attempting to win Olympic medals, thus testing their bodies to the limit.

What are the risks for the top athletes? What lines of prevention can be developed? What techniques could optimise their physical abilities ?

 

Gaëlle Deley, who is involved year-round in research on the interactions between exercise, sport and health, has, with her colleagues at Inserm Unit 1093 and in collaboration with the Cardiovascular Research Center (CVRC) of Harvard University in Boston, established a training programme called “Stimule ton Handicap”, to enable people with paraplegia to exercise using all their muscles. Every week, participants perform an exercise using a rowing machine connected to an electrical stimulation system, in an individually tailored session. Electrodes taped to the participants’ thighs transmit a low-intensity current. Their muscles contract and propel the seat backwards. Arm movements and stimulation of the hamstrings then make it possible to return the seat to the front.

After 6 months of training, the muscle strength of people with paraplegia increased by over 170%, their muscle mass by over 102% and their aerobic capacity by over 77%, and a real impact on their quality of life was observed.

Following these encouraging results, the researchers adapted the programme to people with quadriplegia (cared for in Boston), hemiplegia or cerebral palsy.

If added to their training, this method would enable top level athletes, such as the Paralympic athletes, to develop their physical performances.

 

To obtain further information about this programme, you can contact Gaëlle Deley.

Space and Health In the presence of the President of France, CNES and Inserm sign a framework agreement at the Elysée Palace

JMH-4-4

 ©Jean Marie Heidinger/Inserm

CNES and Inserm, respectively the institution in charge of proposing and implementing French space policy and the leading biomedical research organisation in Europe, have decided to expand their cooperation in the area of space and health. For the first time, they have signed a framework agreement that will cover the advances in basic research made possible by studying the human being in space, as well as the applications of findings from space research in matters of health.

 

Space is an extraordinary laboratory for medicine and medical research on Earth. The loss of muscle mass and bone density, and the accelerated ageing of the arteries or disruption of the internal body clock observed in astronauts affected by zero gravity have led to improved knowledge of the human body. There has been a human presence in space almost continuously for over 40 years, and the main concern of the space agencies has always been to ensure astronauts’ health by taking appropriate measures. But in recent years, there have been instruments that allow comprehensive medical monitoring of astronauts, opening the opportunity for basic studies in physiology and medicine, conducted by Inserm and CNES. Moreover, these instruments may also find applications in medical research and public health.

 

This agreement, signed in the presence of the President of France by Yves Lévy, Chairman and Chief Executive Officer of Inserm and Jean-Yves Le Gall, President of CNES, provides for collaboration in the area of health in order to gain a better understanding of:

  • the impact of space conditions on physiology and its consequences for health (particularly the sensory, cognitive, biomechanical and immunological effects)

Its aim is to develop methods, tools and services based on, among other things, space technologies in the area of health, particularly:

  • the development of connected devices, particularly those designed for astronaut flight,
  • the development of medical instruments

It will also give rise to a large number of experiments during the period spent by Thomas Pesquet on board the international space station. Access to simulation experiments conducted on earth will also be possible, as well as the opportunity to conduct research projects during parabolic flights or in recoverable capsules.

 

“Thomas Pesquet’s space mission will make it possible to write a new chapter in French excellence in the area of manned flight. With this framework agreement signed with Inserm, medical research will benefit from all the advances enabled by studying the human being in space, and major advantages both for applications and for routine health matters,” stated Jean-Yves Le Gall, President of CNES.

“This agreement is a first between our two institutions, each of which embodies French excellence in Europe and worldwide in its own domain. This is an important step, which allows us to combine exploration of extreme environments and the use of the most advanced technologies for research on human health,” emphasised Yves Lévy, Chairman and Chief Executive Officer of Inserm.

Saturday 10 September 2016: World Suicide Prevention Day

desperate

(c) Fotolia

Suicide causes more than 800,000 deaths every year according to estimates by the World Health Organisation, i.e. one death every 40 seconds. It affects all age categories, and spares no region of the world.

To find out more about suicide mortality data for France, you may contact Grégoire Rey, director of CépiDc-Inserm (Epidemiological Center on Medical Causes of Death).

 

For those aged 15-29 years, suicide is the second leading cause of mortality. Moreover, a large survey, coordinated by Inserm Unit 1178, “Mental Health and Public Health,” and the University Division of Fondation Vallée, conducted in 2013 among 15,235 young students aged 13-18 years, shows that suicide attempts appear to be more common than before: 7.8% of young people have already attempted suicide once, and 3.7%, more than once. Alarming figures, which highlight the need for action to prevent suicidal behaviours.

See the press release “The new face of our adolescents.

 

World Suicide Prevention Day, which will be held on Saturday 10 September 2016, at the initiative of the International Association for Suicide Prevention and WHO, is aimed at emphasising the scale of this public health problem, and at making the public aware of the existing preventive measures.

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