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Month: February 2023

Pre- and Postnatal Chlordecone Exposure Could Affect the Cognitive Development and Behavior of Children

Posted on by Graziella Cara

Chlordécone

Chlordecone is an organochlorine insecticide that was used in the French West Indies from 1973 to 1993 to control the banana root borer. © Adobe Stock

Despite the fact that chlordecone has not been used as an insecticide in the French West Indies for 30 years now, its persistence in the environment continues to contaminate the populations. While its neurotoxic properties are well established, its impact on neurodevelopment remains to be clarified. An international research team involving Inserm researchers at the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health) studied the impact of pre- and postnatal chlordecone exposure on the cognitive and behavioral abilities at 7 years of age of 576 children from the TIMOUN mother-child cohort in Guadeloupe[1]. Their research shows that this exposure is associated with poorer scores on tests evaluating cognitive abilities and behavioral disorders, with the impact differing according to the child’s sex. These results, published in Environmental Health, call for consideration to be given to the potential impact of these effects at population level, in order to optimize prevention policies.

Chlordecone is an organochlorine insecticide that was used in the French West Indies from 1973 to 1993 to control the banana root borer. Its persistence in the environment is responsible for contaminating the population through the consumption of contaminated foodstuffs. Chlordecone is now considered to be neurotoxic, toxic to reproduction and development, carcinogenic, and an endocrine disruptor. Experimental studies in animals have also shown that exposure of females to chlordecone during gestation leads to neurobehavioral and learning disorders in the offspring, the nature and intensity of which varies according to sex.

The neurotoxicity of chlordecone can be explained by its ability to interact with numerous neurotransmitters[2] and by its hormonal properties, particularly its action on estrogens. Yet estrogens play a crucial role, which differs according to chromosomal sex, in the development of the brain.

In the face of these observations, and in order to better estimate the potential impact of pre- and postnatal exposure to chlordecone on child neurodevelopment, Inserm researchers from the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health), as part of an international research team, examined the intellectual abilities and behaviors of 576 children from the TIMOUN mother-child cohort in Guadeloupe.

In order to assess the children’s levels of pre- and postnatal exposure to chlordecone, the concentration of the pesticide was measured in umbilical cord blood at birth and in the blood of the children at 7 years of age. Their intellectual abilities were assessed according to 4 criteria: verbal comprehension, information processing speed, working memory[3], and perceptive reasoning[4].

The mothers also completed a questionnaire to measure the presence of behavioral difficulties in their child which can be categorized as either “internalizing” – in the form of emotional symptoms and interpersonal problems with peers, or “externalizing” – in the form of social behavior problems (anger, defiance, etc.), hyperactivity, and/or inattention.

Prenatal exposure to chlordecone was found to be associated, for each doubling of the level of exposure, with a 3% increase in the score estimating “internalizing” behavioral difficulties at 7 years of age, with a stronger association among girls (+7%) than among boys (0%).

Postnatal chlordecone exposure was found to be associated with poorer scores estimating general intellectual abilities (0.64 IQ point decrease for each doubling of the level of exposure). This manifests, particularly in boys, as a decrease in perceptive reasoning, working memory and verbal comprehension. In addition, postnatal exposure was associated with a greater number of “externalizing” behavioral difficulties in both boys and girls.

These findings indicate that exposure to chlordecone during periods of in utero development or during childhood is associated with a reduction in intellectual abilities and an increase in behavioral difficulties, with effects sometimes differing in nature and intensity according to sex.

“This is consistent with the estrogenic properties of this pesticide and its effects that vary according to sex and period of brain development,” explains Luc Multigner, Inserm research director who participated in this research.

According to the research team, it is therefore justified to pursue public policies aimed at reducing exposure to chlordecone, particularly among the most vulnerable populations, such as children and pregnant women. The team also calls for monitoring of the prevalence and management of children presenting with psychomotor retardation, sensory, neuromotor or intellectual disorders and/or interpersonal difficulties.

“Although the neurological and neurobehavioral effects observed in this study are relatively moderate and subtle at the individual level, they may, given the widespread exposure of the French West Indian population to chlordecone, have a non-negligible impact at the population level,” concludes Multigner.

 

[1] The TIMOUN mother-child cohort was designed to evaluate the health impact of chlordecone exposures on pregnancy and childhood development. Led by the Research Institute for Environmental and Occupational Health (Inserm/Université de Rennes/EHESP School of Public Health) and the Gynecology-Obstetrics Department of University Hospital Guadeloupe, this cohort consists of 1,068 women included during their pregnancy between 2004 and 2007. Following their birth, the children were monitored at 3, 7 and 18 months of age and then at 7 years of age.

[2] Neurotransmitters are chemical substances that ensure the transmission of information between nerve cells.

[3] Working memory is a form of short-term memory that uses the information obtained in the present moment in the performance of a specific task.

[4] Perceptive reasoning measures the cognitive ability to integrate and manipulate visual and spatial information in order to solve complex visual problems.

Cannabis: Insomnia Twice as Common Among Students Who Use It Every Day

Posted on by Graziella Cara

The likelihood of suffering from insomnia was found to be 45% higher in cannabis users compared to non-users. © Unsplash

In France, over half of students suffer from sleep complaints. These are particularly concerning as they can affect the success of their studies, and their physical and mental health. A real public health issue, the evaluation of these health risks is one of the research subjects of a team of scientists from Inserm, Université de Bordeaux and Bordeaux University Hospital. In a new study published in Psychiatry Research, they focused on cannabis use by students – with the knowledge that its consumption among 18-25-year-olds in France is particularly high – and tried to measure its effects on sleep. What they found was that cannabis use increased the risk of sleep disturbances, with the frequency of insomnia doubling among those who smoke it daily. This study was conducted based on the analysis of the data of 14,787 student volunteers, who are members of the i-Share cohort.

Poor sleep quality has been shown to affect 55% of students and insomnia 19%. These sleep alterations are all the more concerning because of their detrimental effects on mental health, physical health, and cognitive capacities – with a subsequent negative impact on the students’ academic success.

Some studies have already investigated the causes of these disturbances, particularly in relation to cannabis use, the level of which is particularly high among young people in France: 13.9% of 18-25-year-olds report using it monthly and 4% daily[1].

In this new article, researchers from Inserm, Université de Bordeaux and Bordeaux University Hospital at the Bordeaux Population Health research center have for the first time conducted an in-depth analysis of the association between cannabis use and sleep disturbances in a sample of 14,787 university students. These participants all come from the i-Share cohort that studies the general health of students, which is led by the last author of this study, Christophe Tzourio.

The students answered an online self-questionnaire on the frequency of their cannabis use over the past year (daily, weekly, monthly or rarely/never), as well as the quality of their sleep in the last three months[2], with a question specifically about insomnia. Other questions concerned their sociodemographic characteristics, lifestyle (e.g. alcohol or tobacco consumption) and mental health, in order to refine the analysis and avoid any bias or confounding factors.

The results of this study confirm the existence of an association between cannabis use and sleep disturbances, particularly insomnia, among students. The likelihood of suffering from insomnia was found to be 45% higher in cannabis users compared to non-users, reaching a 2-fold higher likelihood compared to never/rarely users.

 “The originality of this study lies in the fact that we had access to a particularly large sample of students who provided accurate data on their cannabis use and sleep quality. The richness of the data collected through the questionnaires provides new evidence of the association between insomnia and cannabis use,” explains Julien Coelho, first author of the study.

 

“Although causality cannot be confirmed with certainty, these findings suggest the importance of stepping up public health messages for the purposes of prevention among students, as well as raise the awareness of health professionals on the dangers of high levels of cannabis use on the health of young people,” concludes Tzourio.

 

[1] Source: Santé publique France Health Barometers, with data utilization by the French Monitoring Centre for Drugs and Drug Addiction (OFDT)

[2] The questions focused on four items: insomnia, sleepiness, poor sleep quality, and sleep deprivation. 

New data of efficacy of a Meningococcal B Vaccine and a Preventive Antibiotic in Reducing the Risk of Sexually Transmitted Bacterial Infections and proven efficacy of the MVA-BN Vaccine Against Mpox

Posted on by Graziella Cara

This study, sponsored and funded by ANRS | Emerging Infectious Diseases in partnership with Roche[1], was conducted by a research team from the Paris Public Hospitals Group AP-HP, Université Paris Cité, Inserm, and Sorbonne Université in collaboration with the associations AIDES and Coalition PLUS. It demonstrates the efficacy of both a meningococcal B vaccine in reducing the risk of gonorrhea infection and the use of the antibiotic doxycycline as a preventive treatment against sexually transmitted infections, when taken within 72h after sex. Following the first mpox cases in France, the study scope was expanded, adding the possibility to observe the efficacy of the Modified Vaccinia Ankara (MVA-BN) vaccine against the mpox virus responsible for the epidemic that emerged in 2022.

In recent years, France has seen an increase in sexually transmitted infections (STIs), including bacterial infections such as syphilis, chlamydia and gonorrhea, which particularly affect men who have sex with men (MSM). It was this population which has been mainly affected by the mpox epidemic, which emerged in France in May 2022.

The ANRS DOXYVAC trial was designed to evaluate interventions aimed at preventing these infections. It has been ongoing since January 2021 in MSM using PrEP to prevent HIV infection and highly exposed to the risk of STIs and having presented at least one STI during the year prior to their participation in it[2].

 

The ANRS DOXYVAC trial aims to measure the efficacy of an antibiotic and a vaccine in preventing bacterial STIs in MSM.

Enrollment was stopped early and the two interventions were proposed to all participants following the promising results with doxycycline in the U.S. study DOXYPEP and at the recommendation of the data and safety monitoring board following an interim analysis requested by them.

The study is evaluating the efficacy of post-exposure prophylaxis (PEP)[3] for bacterial STIs that combines the antibiotic doxycycline and vaccination with Bexsero® against meningococcus B[4]. Between January 2021 and July 2022, 502 MSM volunteers living in the Paris region were randomly assigned to into four groups: the first receiving doxycycline PEP to be taken within 72h after condomless sex; the second receiving vaccination with Bexsero®; the third a combination of these two interventions; and the fourth none of the two interventions.

The volunteers had a median age of 39 years, a median of 10 sexual partners in the last 3 months and received a median follow-up of 9 months. They were monitored and tested every 3 months for symptoms of gonorrhea, chlamydia and syphilis infections.

The researchers compared the incidence of a first episode of chlamydia or syphilis infection between the group that received doxycycline and the group that did not and found it to be 5.6 and 35.4 per 100 person-years[5], respectively (84% reduction in the risk of chlamydia or syphilis infection). As for the incidence of a first episode of gonorrhea infection in these same groups, this was found to be 20.5 and 41.3 per 100 person-years (51% reduction). After 3 months, the incidence of a first episode of gonorrhea infection in the Bexsero®-vaccinated group and the unvaccinated group was 9.8 and 19.7 per 100 person-years (51% reduction). No severe adverse effects relating to these two procedures were observed.

“The use of doxycycline for post-exposure prophylaxis has shown itself to be effective in reducing the incidence of both chlamydia and syphilis infection. This antibiotic has also had a significant impact, just like the meningococcal B vaccine, on the incidence of gonorrhea infections. This is the first time that a vaccine has shown an effect on a sexually transmitted bacterial infection,” concludes Prof. Jean-Michel Molina (Université Paris Cité and Department of Infectious Diseases at Hôpital Saint-Louis and Lariboisière, AP-HP, and Université Paris Cité), the study’s coordinating investigator.

Follow-up of the participants will continue until the end of 2023 to ensure that these prevention strategies, which have now been offered to all the participants, are effective in the medium term.

This study, which forms part of a global prevention effort, combines several risk reduction measures (repeated screening for HIV and STIs, vaccination against hepatitis A and B, distribution of condoms and gels). The participants also have the possibility to benefit from community support, therapeutic education, or both.

 

Beyond bacterial STIs, DOXYVAC has made it possible to analyze the impact of the MVA-BN vaccine on the incidence of the mpox virus rapidly after the appearance of the first cases.

In France, the first cases of infection with the mpox virus appeared in May 2022. For the first time, the risk of human-to-human transmission of this virus through sexual contact has been observed. It has therefore been recommended since July 11, 2022 that the vaccine be used as a protective measure for multi-partner MSM.

In view of this observation, the research teams considered it necessary to include in DOXYVAC a component dedicated to studying the vaccine impact on the incidence of mpox virus in MSM taking PrEP, given that these volunteers are at risk of developing mpox. Among the 502 participants in DOXYVAC, the researchers analyzed, in this specific component, the information regarding 472 people whose data were available before and after May 8, 2022. These participants had reported having a median of 10 partners in the previous 3 months, and 20% had received a smallpox vaccine in childhood.

The researchers compared the pre-epidemic (i.e. until May 8, 2022) characteristics of the 77 volunteers having contracted mpox to the “control” volunteers who had not had the virus. They found that the cases of mpox affected younger people (37 vs. 40 years) who had had more sexual partners in the previous 3 months (7 vs. 5), and among whom fewer had been vaccinated against smallpox in childhood (4% vs. 23%). In people who did not have mpox infection, the proportion having had more than 10 partners over a 3-month period had decreased between the pre-epidemic and epidemic periods (up to and after May 8, 2022).

The incidence of mpox virus infection was 67.4 per 1 000 person-months between May 9 and July 10. It fell to 24.4 per 1 000 person-months between July 11 (date from which it was possible to get vaccinated) and September 20. The research team found that simply being vaccinated against the mpox virus in 2022 was associated with a reduced risk of developing the disease with an efficacy of 99%; the impact of behavioral change was limited in this highly vaccinated population (87%).

“This vaccine provides a high level of protection against the mpox virus,” explains Prof. Jade Ghosn (Université Paris Cité, Department of Infectious and Tropical Diseases of Bichat-Claude-Bernard Hospital AP-HP), DOXYVAC co-investigator and the researcher behind the implementation of the study’s “mpox” component.

AIDES, which has developed numerous risk reduction tools during the mpox crisis and participated in providing community support in these studies, welcomes these results.

For Camille Spire, president of the association, “the emergence of new effective tools to add to the existing prevention arsenal is to be welcomed, especially since during the mpox crisis we have noted a high level of vaccine uptake by the people exposed to the virus. We will work to ensure that the effective accessibility of these tools is supported by public policies in terms of the fight against STIs”.

Vincent Leclercq, managing director of Coalition PLUS adds: “in order to achieve their full potential, these prevention tools must reach all the populations at which they are targeted. However, access to vaccines and medicines is too often restricted to the richest countries. We have seen it with the mpox epidemic: only the countries of the North have been able to set up vaccination campaigns”.

 

[1] Roche Molecular System and Roche Diagnostics France provided – free of charge – the kits, consumables and reagents needed to detect Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium.

[2] These men are participants in the HIV infection prevention cohort ANRS PREVENIR.

[3] Post-exposure prophylaxis (PEP) is the use of preventive treatment in people who have recently been exposed to a risk of disease transmission to prevent them from developing it.

[4] Meningococcus B (Neisseria meningitidis) is a bacterium that can cause meningitis. It is close to gonococcus (Neisseria gonorrhoeae).

[5] X per 100 person-years: this means that out of 100 patients followed up for one year, there is a probability of observing X events (in this case an STI).

A blood factor involved in depression

Posted on by Graziella Cara

A small group of neural stem cells isolated from mice and cultured in vitro observed under a confocal microscope. (LaminB1 in green, Sox2 in red) © Perception and Memory Unit – Institut Pasteur

The process of aging is often related to the onset of cognitive decline, depression and memory loss. Scientists from the Institut Pasteur, CNRS and Inserm have discovered that administration of the GDF11 protein, which is known to regenerate murine neural stem cells, improves cognitive abilities and reduces the depressive state in aged mice. They also demonstrated the mechanism of action of this protein in different mouse models. The scientists then investigated these results further in relation to depression, and showed that in humans, the levels of GDF11 are inversely related to depressive episodes. The results of this study were published in the journal Nature Aging on February 2, 2023.

The process of aging is often related to the onset of neurological symptoms such as cognitive decline, memory loss or mood disorders such as depression. Previous studies have shown that the growth factor GDF11, a protein found in blood, has a beneficial effect on olfactory perception and on the generation of new cells in the brains of aged mice. The mechanism of action of GDF11 in the brain remained unknown.

Researchers from the Institut Pasteur, CNRS and Inserm have discovered that long-term administration of the GDF11 protein to aged mice improves their memory and significantly reduces behavioral disturbances related to depression, allowing them to return to a behavior similar to that seen in younger mice.

The scientists conducted further studies in different aged mouse models or mouse models with depression-like behavioral disorders and in vitro neuronal cultures, which enabled them to identify the molecular mechanism of action of GDF11. They discovered that administration of GDF11 activates the natural process of intracellular cleaning, called “autophagy”, in the brain and the elimination of senescent cells. The GDF11 protein thus indirectly increases cell turnover in the hippocampus and restores neuronal activity.

To better understand the link between depressive disorders and the GDF11 protein in humans, scientists from the Institut Pasteur, CNRS and Inserm, in collaboration with scientists from McMaster University, quantified the protein in the blood serum of an international cohort of young patients with major depressive disorder. They observed that GDF11 levels are significantly lower in these patients. Moreover, by measuring the levels of this protein at different stages, the scientists observed a fluctuation in the level depending on the depressive state.

“This work provides clinical evidence linking low blood levels of GDF11 to mood disorders in patients with depression,” said Lida Katsimpardi, a researcher in the Institut Pasteur’s Perception and Memory Unit, affiliated with Inserm at the Institut Necker-Enfants Malades, and co-last author of the study. “In the future, this molecule could be used as a biomarker to diagnose depressive episodes. It could also serve as a therapeutic molecule for the treatment of cognitive and affective disorders,” she concludes.

Obesity and Overweight: Almost One in Two French People Affected. Current Situation, Prevention and Therapeutic Solutions

Posted on by Graziella Cara

balance

© Photo i yunmai / Unsplash

Obesity is a global public health problem whose incidence continues to increase. According to the World Health Organization (WHO), the number of cases worldwide has almost tripled since 1975.

Obesity is associated with many comorbidities and has a high rate of mortality. This complex chronic disease is therefore estimated to increase the risk of cardiovascular disease (the leading cause of death worldwide), diabetes, musculoskeletal disorders, many forms of cancer (endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, colon, etc.). More recently, data have shown that people with obesity are more susceptible to severe forms of COVID-19. Its impact on population health and its economic and social costs are therefore considerable.

This major public health issue is also one that affects France. In order to evaluate the impact of preventive measures such as the country’s National Nutrition and Health Program (PNNS), it was important to take thorough stock of the current epidemiological situation. The latest study on the subject, on the initiative of the French League Against Obesity and coordinated by researchers from Inserm and Montpellier University Hospital, was published in February in the Journal of Clinical Medicine. Based on the figures collected by the Odoxa polling institute, this study reveals the extent of the problem in highlighting that 47.3% of French adults are obese or overweight. It also provides specific information on the most affected populations by age group, region and socioprofessional activity, making it possible to refine prevention policies.

And beyond these prevention measures that are crucial to fighting obesity, how can we support individuals who are overweight or obese? While lifestyle interventions, particularly diet and physical activity, are essential, appropriate management is based on multidisciplinary and personalized approaches that also incorporate solutions in the form of medication, surgery, or both. Much progress has been made in recent years in the field of medication, as described in a literature review published in The Lancet, to which contributed Karine Clément, professor of nutrition and director of the Inserm unit Nutrition and Obesities: Systemic Approaches (Nutriomics).

Overweight and Obesity: Definition Elements

Obesity is defined by excessive body fat and modification of the adipose tissue, which cause health problems and can reduce life expectancy. Its causes are complex. It is the result of several factors – dietary, genetic, epigenetic and environmental – that come together and influence the development and progression of this chronic disease.

Adults are considered to be overweight when their body mass index (BMI) is equal to or greater than 25 and obese when their BMI is equal to or greater than 30. For children, age must be taken into account when defining overweight and obesity.

Read our special feature on obesity (only available in French).

The Latest Figures for France

Obépi-Roche is the name given to a series of surveys which had been coordinated by Inserm every three years between 1997 and 2012 in order to produce estimates of overweight and obesity prevalence in France. A new edition of this survey was launched by the French League Against Obesity in 2020, based on questionnaires collected by the Odoxa polling institute on a sample of 9 598 people living in mainland France, aged 18 years or older, and built using the quota-sampling method[1]. Coordinated by Annick Fontbonne, researcher at Inserm and David Nocca, doctor at Montpellier University Hospital, the analysis of the results reveals a worrying situation.

It showed that the prevalence of excess weight (which includes both overweight and obesity) was 47.3%, with 17% of subjects being obese. At first glance, these figures do not appear to be very different from the last estimates of the Obépi-Roche study of 2012. However, if we bear in mind the trends since 1997 and consider overweight and obesity separately, the observation is less favorable.

Since 1997, the prevalence of overweight has always fluctuated at around 30%, whereas that of obesity has continued to rise rapidly, from 8.5% in 1997 to 15% in 2012, and then to 17% in 2020. This increase is even more marked in the youngest age groups and for morbid obesity, whose prevalence had multiplied by around seven over the period.

“So we have to note that contrary to the expectations of public authorities and health professionals alike, obesity in France has continued to grow year on year since the rollout of the PNNS in 2001,” emphasize Annick Fontbonne and David Nocca.

The researchers went further in the analysis by highlighting differences in prevalence according to sex and age, region, and socioprofessional category.

Sex and Age

Older people are more overweight or obese than their younger counterparts, with excess weight affecting 57.3% of people aged 65 years and over compared to 23.2% of 18-24-year-olds. Nevertheless, the trends are more worrying, given that the youngest age groups have had the highest prevalence of obesity over the years. Since 1997, obesity among the 18-24-year-olds has more than quadrupled, and has almost tripled among the 25-34-year-olds, while the increase among those aged 55 and older has been low since 2009.

Differences between the sexes have also been observed. In 2020, while men were more often overweight than women (36.9% vs. 23.9%, respectively), the opposite was the case for obesity (16.7% vs. 17.4%, respectively).

obésitéEvolution of the prevalence of obesity by age groups between the 1997-2012 Obépi-Roche surveys and the 2020 Obépi survey.

 

Regional Disparities

The prevalence of obesity in 2020 exceeds 20% in north and northeastern France, and is the lowest (below 14.5%) in Île-de-France and Pays de la Loire. If we exclude the latter two regions and Brittany, we see a decrease in the prevalence gradient when moving from the northern to the southern regions of France.

obésitéGeographic distribution of the prevalence of obesity in 2020 in the French regions

 

Socioprofessional Categories

The scientific literature reveals that overweight and obesity are generally more common in the disadvantaged social categories. The Obépi 2020 study confirms this observation for the occupational qualification criterion, as the prevalence of excess weight is 51.1% among factory workers or equivalent, 45.3% among clerks, 43% among people in intermediate jobs, and 35% among managers or people in equivalent positions.

The trend is the same when we look at obesity: while the figures are similar for factory workers or equivalent (18%) and clerks (17.8%), they are markedly lower among managers or people in equivalent positions (9.9%). The intermediate jobs have a prevalence of obesity of 14.4%. It should also be noted that the trends have been increasing since 1997 in all occupational categories.

The authors conclude: “The study had been much awaited in order to obtain a rigorous overview of overweight and obesity in France. When compared to previous surveys, it has shown that although the prevalence of excess weight (overweight and obesity) is appearing to plateau, the prevalence of obesity is increasing rapidly and has doubled since 1997. In addition, the slope is more pronounced in younger generations and for the most severe degrees of obesity. Given the slight differences in methodology between the 1997-2012 and 2020 surveys, it would be desirable to repeat this series of surveys in order to confirm and monitor these worrying trends. “

 

Managing Obesity: Innovative Multidisciplinary Approaches

While prevention is the cornerstone in the fight against obesity and its associated comorbidities, it is also necessary to recognize that it is a complex chronic disease, to which therapeutic responses should also be provided.

The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (e.g. prevention and control of type 2 diabetes, hypertension, fatty liver disease, cardiovascular diseases and obstructive sleep apnea), as well as quality of life.

However, maintaining the weight loss is the major challenge of obesity management. Like all complex chronic diseases, obesity depends on factors that vary from one individual to another and managing it requires a long-term, multimodal approach, taking into account each individual’s treatment goals, and the benefits and risks of the different therapies.

Lifestyle interventions (dietary habits, physical activity/inactivity, sleep, psychological difficulties, etc.) form the first pillar of this management, but they are rarely sufficient in achieving and maintaining significant long-term weight loss. Depending on individual situations, management can therefore be combined with other strategies that include anti-obesity medications and bariatric surgery.

 

Medication

Most available “historical” anti-obesity medications work on neurotransmitters (such as serotonin) that act on appetite regulation and reward circuits, in order to reduce hunger, promote the feeling of satiety, and decrease the reward sensation associated with food. Many of these treatments have had to be withdrawn due to side effects, leaving patients and their doctors without pharmacological tools.

However, over the past five years, significant therapeutic advances have led to the development of a new generation of anti-obesity medications. These new treatments, which are similar to the intestinal hormones (incretins) and also used in combination with other molecules (GLP1, GIP, etc.), are highly effective. They are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Known for their initial actions on the pancreas by promoting the secretion of insulin, they also act on satiety mechanisms in the central nervous system. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited in order to make progress in bringing these medications to market.

These advances also concern a new targeted treatment for rare and very severe forms of genetic obesity that begin in childhood. This treatment induces weight loss by acting on the serious eating disorders experienced by these patients and leads to an improvement in their quality of life and that of those around them.

 

And What About Surgery?

Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity and in mortality. Less invasive endoscopic techniques are also possible in some cases. However, the surgical approach, more invasive than medication, has not yet been compared to the new-generation anti-obesity treatments.

“Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments for these complex pathologies,” concludes Clément, co-author of the literature review published in The Lancet.

 

[1]The quota method is a sampling method that consists of ensuring the representativeness of a sample by assigning it a structure similar to that of the general population.

Who are the first ancestors of present-day fish?

Posted on by Graziella Cara

poisson arowana

Arowana fish © Pixabay

What is the origin of the ancestors of present-day fish? What species evolved from them? A 50-year-old scientific controversy revolved around the question of which group, the “bony-tongues” or the “eels”, was the oldest. A study by INRAE, the CNRS, the Pasteur Institute, Inserm and the Muséum National d’Histoire Naturelle, has just put an end to the debate by showing through genomic analysis that these fishes are in fact one and the same group, given the rather peculiar name of “Eloposteoglossocephala”. These results, published in Science, shed new light on the evolutionary history of fish.

Understanding the evolutionary history of species through their relatedness is an essential issue and regularly the subject of scientific controversy. One of them concerns the position, in the tree of life, of the three oldest groups of teleost fishes, which appeared towards the end of the Jurassic period (from 201.3 to 145 million years ago) and which include most of our present-day fishes. These three groups consist of the “bony-tongues”, the “eels” and a group that unites all other species of teleost fishes. Early classifications in the 1970s, based solely on anatomical criteria, had classified the “bony-tongues” as the oldest group. Modern classification approaches, however, based on the use of DNA sequences to reconstruct the evolutionary history of life, placed the “eels” as the oldest group. Ever since, controversy has ensued.

What if both hypotheses were wrong?

To investigate this question, scientists sequenced the genomes of several species in the “eel” group, including the European eel and the giant moray eel. They analysed the DNA sequences to gain insight into the structure and organisation of the genes within the genome. They were thus able to reconstruct, in a very reliable way, the relationships between the different teleost fishes, which led to an end of the controversy without winners or losers: neither hypothesis was valid!

Surprisingly, scientists have discovered that the two groups of “eels” and “bony-tongues” are in fact one and the same in terms of evolutionary history. The researchers have named this group “Eloposteoglossocephala”. These results put an end to more than fifty years of controversy about the evolutionary history of the main branches of the teleost fish tree of life.

They shed new light on the evolutionary history of fishes and the understanding of evolutionary processes.

Who are the first ancestors of present-day fish?

 

Teleost fish trees of life representing the two hypotheses of the controversy and its resolution in the present study

 

Study funded by l’ANR GenoFish

Professor Didier Samuel Appointed Chairman and Chief Executive Officer of Inserm

Posted on by Graziella Cara

Didier Samuel PDG Inserm 1er février 2023

Didier-Samuel ® Christophe-PEUS

Appointed today in the Council of Ministers following the proposal of the Minister of Higher Education and Research and the Minister of Health and Prevention, Professor Didier Samuel becomes Chairman and Chief Executive Officer of Inserm.

Doctor and researcher, Didier Samuel has devoted himself to both fields throughout his career.

Professor of Hepatology at Université Paris-Saclay, Director of the Department of Hepatology and Hepatic Intensive Care at Paul-Brousse Hospital and Medical Director of the liver transplant program at the same hospital, Samuel has treated and monitored over 4,500 liver transplant patients. Dean of the Paris-Saclay Faculty of Medicine since 2017 and elected Chair of the Conference of Deans of Medicine in 2022, he also chaired France’s National Committee for Research Coordination.

Since 2005, Samuel led an Inserm research unit devoted to the physiopathogenesis and treatment of liver diseases. His expertise in the field of liver diseases and liver transplantation is internationally renowned.

“I am pleased and honored to have been appointed to carry out the important mission of chairing Inserm, which plays a central role in medical research in France. Committed to the quality of our scientific research, convinced that it is also the foundation for high-quality medicine, it is my wish to promote innovation, excellence, and fruitful coordination among all who endeavor for our biomedical research, serving the health of all citizens,” declares Professor Didier Samuel, Chairman and Chief Executive Officer of Inserm.

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