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Screens and Child Cognitive Development: Exposure Time is Not the Only Factor to Consider

Enfant déjeunant en regardant l'écran d'un ordinateur portableTo what extent does early or excessive screen exposure affect children’s cognitive development? © AdobeStock

To what extent does early or excessive screen exposure affect children’s cognitive development? This is a question that is currently dividing scientists. A team led by Inserm researcher Jonathan Bernard at the Center for Research in Epidemiology and Statistics (Inserm/INRAE/Université Paris Cité/Université Sorbonne Paris Nord) studied the data of nearly 14,000 children from the French Elfe cohort[1] for each child from the age of 2 to 5.5 years. While this is not the first study to show a negative relationship between exposure time and development, it also highlights that this relationship is not true for all domains of cognition and is much weaker when the family context is properly taken into account. Its findings also confirm[2] a non-negligible negative relationship between exposure to television during family meals and early language development. This research, published in The Journal of Child Psychology and Psychiatry, suggests that while screen time is important, the context of exposure also matters.

In the face of rapid changes in the use of screens and their growing place in everyday life, one question continues to divide scientists: to what extent does too early and/or excessive exposure to screens influence child development? With the majority of studies having focused on language development, less attention has been paid to other cognitive domains. The same applies to the potential influence of the family environment, as well as the child’s daily activities.

The team led by Inserm researcher Jonathan Bernard at the Center for Research in Epidemiology and Statistics (Inserm/INRAE/Université Paris Cité/Université Sorbonne Paris Nord) sought to evaluate the associations between screen use and cognitive development in early childhood, taking into account factors related to social, perinatal, family, and lifestyle conditions. To do this, it looked at data from nearly 14,000 children from the French cohort Elfe, collected for each child from the age of 2 to 5.5 years, between 2013 and 2017.

The parents reported their children’s daily screen time at ages 2, 3.5 and 5.5 years. They were also asked to report whether they had the television on during family meals in their children’s second year. Many factors related to the children’s lifestyle and daily activities also had to be specified. Finally, various cognitive domains were evaluated: language development at age 2, non-verbal reasoning at age 3.5 and overall cognitive development at ages 3.5 and 5.5.

The research team observed that at ages 3.5 and 5.5, screen exposure was associated with lower overall cognitive development scores, particularly in the areas of fine motor, language and autonomy. However, when lifestyle factors likely to influence cognitive development were taken into account in the statistical models, the negative relationship decreased and became of small magnitude.

The results of the study also show that, regardless of exposure time, having the television on during family meals at age 2 (which concerned 41% of children) was associated with lower language development scores at the same age. These children also had poorer overall cognitive development at age 3.5.

“This could be explained by the fact that television, by capturing the attention of family members, interferes with the quality and quantity of interactions between parents and child. Yet such interaction is crucial at this age for the acquisition of language,” explains Shuai Yang, PhD student and first author of the study. He continues: In addition, television adds background noise to family discussions that makes it difficult for the child to decipher sounds and limits verbal understanding and expression. “

These findings suggest that screen time is not the only factor to consider: the context in which screen use takes place could also be an important factor. It is also suggested that not all areas of cognition would be affected in a similar way.

“The first years of life are decisive, not just for cognitive development but also for the establishment of lifestyle habits, adds Bernard. When a child uses a screen excessively, they do so at the expense of other social activities or interactions that are essential for their development. “

The robustness of this study is due to the large number of participants, but also the consideration of factors related to the social profile of the families and the activities of the children.

“While our findings suggest that the harmful effects of screen use in early childhood have a low impact on cognitive development at the individual level and can be compensated for in the years that follow, they do however justify remaining vigilant at population level. When it comes to public health, these little things all add up,” explains Bernard. He added that more long-term studies are needed to evaluate the cumulative impact of these effects from early childhood to adolescence.

The research by his team is continuing through the follow-up of the children in the Elfe cohort in order to answer these questions.

 

[1]Elfe is France’s first national, longitudinal study dedicated to the follow-up of children from birth to adulthood. More than 18,000 children born in metropolitan France in 2011 were enrolled in it (i.e. one in every 50 children born in 2011). Since the first contact with the families during the maternity stay, the participating parents are regularly interviewed in order to better understand how the environment, family setting and living conditions influence the development, health and socialization of the children. The ELFE study mobilizes around 150 researchers from a variety of scientific disciplines.

[2]See our press release from June 8, 2021: Television During Meals Linked to Poorer Language Development in Young Children

Association Between the Consumption of Food Additive Emulsifiers and the Risk of Cardiovascular Disease

cœurThe scientists used the data reported by 95,442 French adults participating in the NutriNet-Santé study. © Mathilde Touvier/Inserm

Emulsifiers are among the additives most widely used by the food industry, helping to improve the texture of food and extend its shelf life. Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional epidemiology research team (EREN-CRESS), studied the impacts on cardiovascular health of the consumption of emulsifiers. They analyzed the health data of 95,442 adults participating in the French NutriNet-Santé cohort study in terms of their overall consumption of this type of food additive. The results suggest an association between the dietary intake of emulsifiers and an increased risk of cardiovascular disease. They have been published in the British Medical Journal.

In Europe and North America, 30 to 60% of dietary energy intake in adults is provided by ultra-processed foods. Recent epidemiological studies have linked high intakes of ultra-processed foods with higher risks of obesity, mortality and chronic diseases (cardiovascular disease, type 2 diabetes, cancer, etc.). Emulsifiers are among the most commonly used additives in industrial foods. They are often added to processed and packaged foods such as certain industrial cakes, cookies and desserts, as well as ice creams, candy bars, breads, margarines and ready meals, in order to improve their appearance, taste and texture and lengthen shelf life. These include celluloses, mono- and diglycerides of fatty acids, modified starches, lecithins, carrageenans, phosphates, gums and pectins.

As with all food additives, the safety of emulsifiers is regularly evaluated on the basis of the scientific evidence available at a given time. However, some recent studies suggest that emulsifiers can disrupt the gut microbiota and increase the risk of inflammation, leading to potentially increased susceptibility to cardiovascular problems.

In order to explore this question in greater depth, French researchers undertook to evaluate the links between exposure to emulsifiers and the risk of cardiovascular disease, including coronary heart- and cerebrovascular disease, i.e. conditions that affect blood circulation and blood vessels in the heart and brain.

Their conclusions are based on the analysis of data from 95,442 French adults (average age 43 years; 79% women) with no history of cardiovascular disease who voluntarily participated in the NutriNet-Santé cohort study (see box below) between 2009 and 2021.

During the first two years of follow-up, the participants completed at least three (and up to 21) days of online dietary records. Each food or drink consumed was then matched against databases to identify the presence and level of food additives, including emulsifiers. Laboratory assays were also performed in order to provide quantitative data.

The participants were asked to declare any major cardiovascular events, such as heart attack or stroke, which were validated by an expert committee following examination of their medical records. Deaths related to cardiovascular disease were also recorded using the French national registry of deaths.

Several well-known risk factors for heart disease, including age, sex, weight (BMI), educational level, family history, smoking and levels of physical activity, as well as overall quality of the diet (e.g. consumption of sugar, salt, energy and alcohol) were taken into account.

After an average follow-up of seven years, the scientists found that the higher intakes of total celluloses (food additive codes E460[1] to E468) were associated with higher risks of cardiovascular disease. In particular, this combination was specifically observed for intakes of E460 (microcrystalline cellulose, powdered cellulose) and E466 (carboxymethylcellulose).

On the other hand, higher intakes of mono- and diglycerides of fatty acids (E471 and E472) were associated with higher risks for all the diseases studied. Among these emulsifiers, lactic ester of mono- and diglycerides of fatty acids (E472b) was associated with a higher risk of cardiovascular and cerebrovascular disease, and citric acid ester of mono- and diglycerides of fatty acids (E472c) was associated with a higher risk of cardiovascular- and coronary heart disease.

High intake of trisodium phosphate (E339) was also associated with an increased risk of coronary heart disease.

No association was detected in this study between the other emulsifiers and the development of cardiovascular diseases.

Given its observational nature, the study cannot therefore establish causality on its own, and the scientists acknowledge it to have certain limitations. For example, the high proportion of women, the higher educational background and overall more health-conscious behaviors among the NutriNet-Santé study participants compared with the general French population, which may limit the generalizability of the results.

That being said, the study sample was large and the authors were able to consider a wide range of potentially confounding factors, while using detailed and unique data on food additives, down to the brand of the products consumed. In addition, the results remained unchanged after multiple sensitivity analyses, thereby strengthening their robustness.

“While these findings need to be replicated in other studies worldwide, they bring new key knowledge to the debate on re-evaluating the regulations around the use of additives in the food industry, in order to better protect consumers,” explains Mathilde Touvier, Research Director at Inserm, and Bernard Srour, Junior Professor at INRAE, principal authors of the study.

NutriNet-Santé is a public health study coordinated by the Nutritional epidemiology research team (EREN-CRESS, Inserm/INRAE/Cnam/Université Sorbonne Paris Nord/Université Paris Cité) which, thanks to the commitment and loyalty of over 170,000 participants (known as Nutrinautes), advances research into the links between nutrition (diet, physical activity, nutritional status) and health. Launched in 2009, the study has already given rise to over 270 international scientific publications. In France, a drive to recruit new participants is still ongoing in order to continue to further research into the relationship between nutrition and health.

By devoting a few minutes per month to answering questionnaires on diet, physical activity and health through the secure online platform etude-nutrinet-sante.fr, participants in France contribute to furthering knowledge of the links between diet and health.

[1] Food additives are identified in the list of ingredients by a European code consisting of the letter “E”, followed by a number making it possible to easily identify the category. For example, E100 for colorants, E200 for preservatives, E400 for emulsifiers and texture agents.

Air Pollution Accelerates Eye Ageing

© Freepik© Freepik

Numerous studies are now reporting the harmful effects of air pollution on the central nervous system (neurodegenerative diseases in adults, neurodevelopmental disorders in children). Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve whose principal characteristic is thinning of the retinal nerve fiber layer. In a study of a cohort of 683 elderly Bordeaux residents followed up over 10 years, researchers from Inserm and Université de Bordeaux at the Bordeaux Population Health research center showed accelerated thinning of the retinal nerve fiber layer in the participants more exposed to air pollution, especially those who had a greater exposure to PM2.5 (fine particulate matter of a diameter of 2.5 microns or less). This study therefore suggests a possible increased glaucoma risk for the inhabitants of areas with fine particulate pollution, even at levels below the current European Union regulatory thresholds (25 micrograms/cubic meter). The results have been published in Environmental Research.

Air pollution is a global public health issue. The harmful effects of air pollutants on respiratory and cardiovascular functions have been widely documented in the scientific literature. It is also increasingly evident that chronic exposure to air pollution has adverse effects on the central nervous system, with an increased risk of neurodegenerative diseases in adults and neurodevelopmental disorders in children.

The retinal nerve fiber layer (RNFL) is part of the central nervous system, and its thinning represents the main characteristic of glaucoma[1], an eye disease associated with the progressive destruction of the optic nerve, most often caused by excessive pressure inside the eye. This disease is the second leading cause of blindness in the developed countries.

Researchers from Inserm and Université de Bordeaux studied the effect of exposure to higher concentrations of air pollutants (fine particulate matter[2] and nitrogen dioxide) on the ocular neurodegenerative processes. To do that, they followed up for a 10-year period a population of 683 people aged 75 years or over who were resident in Bordeaux at the time of their inclusion in the Aliénor[3] cohort. This is the first prospective study on this subject.

As part of this study, the volunteers underwent eye exams every two years between 2009 and 2020 in order to measure changes in RNFL thickness.

In addition, their exposure to air pollution over the previous 10 years was determined using their home address, with the help of annual exposure maps for each pollutant. These detailed maps, with a resolution of 100 meters, were produced using air quality control station measurements and meteorological and geographical characteristics (proximity of a road, population density, distance from the sea, altitude, etc.)[4].

According to the results of this study, people having been exposed to higher concentrations of fine particulate matter had more rapid thinning of the retinal nerve layer over time.

These results are represented in the figure above which shows that the participants exposed to a 25 µg/m3 concentration of PM2.5 had a faster reduction in the thickness of this layer compared to those exposed to a 20 µg/m3 concentration.

These findings suggest that exposure to a high concentration of pollutants over time could increase the risk of glaucoma.

As regards PM2.5, the 10-year average exposure estimates were below the annual regulatory threshold of the European Union (established at a maximum of 25 μg/m3) for all participants, but above the limit values recommended by the WHO in 2005 (10 μg/m3) and further reduced in 2021 (5 μg/m3).

“The results of this study confirm the previous observations on the effects of air pollution on neurodegenerative processes – at ocular level in our case. They constitute an additional argument in favor of lowering the European regulatory thresholds[1], as recommended by the WHO, as well as lowering the effective exposure of the French population, which continues to exceed current regulatory thresholds in some places,” explains Laure Gayraud, PhD student in epidemiology and first author of the study.

“More generally, our study documents the effects of air pollutants on neurological aging. Taking the example of ocular aging, it suggests that exposure to high concentrations of pollutants over time could lead to an acceleration of neurological ageing, as was observed in studies on brain aging,” explains Cécile Delcourt, Inserm research director and last author of this research.

The aim is now for the scientists to expand the field of study to national level, using data from other French cohorts in order to learn more about the effects of pollutants on eye aging.

 

Diagram of the eye and retina

© Adobe stock

 

[1]To learn more, consult our in-depth article on glaucoma (only available in French).

[2]PM2.5 corresponds to fine particulate matter of a diameter of 2.5 microns or less.

[3]Alienor is an epidemiological study in the general elderly population that explores the relationships between age-related eye diseases and other major determinants of these diseases (genetic, nutritional, environmental, or vascular factors).

[4]These maps were previously produced by the team of Kees de Hoogh and Danielle Vienneau from the Swiss Tropical and Public Health Institute (co-authors of the publication).

[5]The Members of the European Parliament’s Environment Committee recently voted in favor of lowering the thresholds for several pollutants by 2030, including fine particulate matter.

A global overview of antibiotic resistance determinants

Proportion of third-generation cephalosporin resistance in Klebsiella pneumoniae, for blood infections, 2019 (data from ATLAS, Pfizer) © Institut Pasteur, Eve Rahbé

To understand the main determinants behind worldwide antibiotic resistance dynamics, scientists from the Institut Pasteur, Inserm, Université de Versailles Saint-Quentin-en-Yvelines and Université Paris-Saclay developed a statistical model based on a large-scale spatial-temporal analysis. Using the ATLAS antimicrobial resistance surveillance database, the model revealed significant differences in trends and associated factors depending on bacterial species and resistance to certain antibiotics. For example, countries with high quality health systems were associated with low levels of antibiotic resistance among all the gram-negative bacteria1 investigated, while high temperatures were associated with high levels of antibiotic resistance in Enterobacteriaceae. Surprisingly, national antibiotic consumption levels were not correlated with resistance for the majority of the bacteria tested. The results suggest that antibiotic resistance control measures need to be adapted to the local context and to targeted bacteria-antibiotic combinations. The results of the study were published in the journal The Lancet Planetary Health on July 10, 2023.

Antibiotic resistance (ABR) is currently one of the most urgent threats to global health. It is a natural phenomenon, but improper use of antibiotics is contributing to it by selecting resistance and complicating bacterial infection-control strategies.

Worldwide surveillance of antibiotic resistance, especially under the aegis of WHO has been set up, and several databases have been created to record ABR worldwide, with the long-term aim of improving understanding of the causes to help tackle the phenomenon.

Antibiotic resistance varies considerably depending on the bacterial species, but a recent study2 estimated that in 2019, 1.27 million deaths worldwide were attributable globally to ABR and ABR was associated with 4.95 million deaths.

To identify the main factors associated with worldwide antibiotic resistance dynamics, a multidisciplinary research team at the Institut Pasteur developed a statistical model and analyzed antibiotic resistance data from the ATLAS database, which contains data collected since 2004 in more than 60 countries on every continent. The scientists analyzed the data by testing a large number of determinants to reveal the main factors of antibiotic resistance and understand how they relate to the dynamics observed worldwide.

Research teams study how antibiotic resistance emerges in a bacterium in a Petri dish or in an individual, but we are currently lacking a population-level, global overview that can be used to investigate links between resistance and specific factors like national health system quality for different species of pathogenic bacteria. To understand the dynamics of antibiotic resistance, it needs to be studied at every level. That is what this study sets out to do,” explains Eve Rahbé, a PhD research student in the Institut Pasteur’s Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and first author of the study.

The first stage of the study was to select relevant factors that could influence antibiotic resistance dynamics.

“Although some biological factors are known, it was also important for us to investigate hypotheses associated with socioeconomic and climate factors,” continues the scientist.

A total of eleven independent factors were selected, including health system quality (based on the GHS index3), antibiotic consumption and national wealth (GDP per capita), as well as data on travel and climate variables. Statistical models were then developed to study potential associations between the ATLAS data and the selected factors.

The analysis of global data for the period 2006-2019 initially revealed an increase in resistance to carbapenems for several species, although global trends were stable for other resistances. The study also demonstrated that the dynamics and factors associated with antibiotic resistance depend on bacteria-antibiotic combinations. Surprisingly, however, national antibiotic consumption was not significantly associated with resistance for the majority of bacteria tested (except for quinolone consumption for fluoroquinolone-resistant Escherichia coli and Pseudomonas aeruginosa and carbapenem consumption for carbapenem-resistant Acinetobacter baumannii).

Conversely, high health system quality was associated with low levels of antibiotic resistance in all the gram-negative bacteria1 tested. High temperatures were associated with high levels of antibiotic resistance, but only for Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae).

This study reveals the wide range of factors leading to antibiotic resistance among different pathogenic bacteria at global level, and the need to adapt resistance control approaches to the local context (country, transmission context) and the specific bacteria-antibiotic combination,” concludes Philippe Glaser, Head of the Institut Pasteur’s Ecology and Evolution of Antibiotic Resistance Unit and co-last author of the study.

“Our statistical model can be applied to other databases, such as the WHO database. Improving understanding of resistance determinants, which differ from one country to the next and probably even vary among regions in the same country, is crucial and will be useful in adapting public health measures,” concludes Lulla Opatowski, a Professor at Université de Versailles Saint-Quentin-en-Yvelines, scientist in the Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and co-last author of the study.

This research was funded by the research organizations cited above, the LabEx IBEID and an independent research Pfizer Global Medical Grant. 

See the fact sheet about antibiotic resistance at pasteur.fr

1 Gram-negative bacteria are bacteria with two membranes that are more resistant to antibiotics because of the low permeability of their outer membrane.

2 Lancet, https ://doi.org/10.1016/S0140-6736(21)02724-0

3 GHS: Global Health Security Index

The Record Heat of Summer 2022 Caused Over 61,000 Deaths in Europe, With Nearly 5,000 in France

Europe is the continent experiencing the greatest warming, up to 1°C above the global average. © Adobe Stock

The summer of 2022 was the hottest ever recorded in Europe, characterized by an intense series of heatwaves that beat records of temperature, drought, and forest fires. Although Eurostat had already reported unusually high excess mortality for these dates, the fraction of mortality that could be attributed to the heat had not until now been quantified. And this is precisely what a study by scientists from Inserm and the Barcelona Institute for Global Health (ISGlobal) set out to do. Their analysis estimates that between May 30 and September 4, 2022 there had been 61,672 heat-related deaths in Europe. These findings suggest that our current strategies for adapting to heatwaves may still be insufficient. The full study has been published in Nature Medicine.

In 2003, Europe experienced one of the most intense heatwaves in its history, causing over 70,000 deaths. Since then, adaptation strategies have been developed in an attempt to respond quickly to intense heat and protect the most vulnerable populations. Given the continuous increase in heatwave episodes in recent years and the estimations that they could double in number by 2050, it is crucial to better characterize the mortality associated with them and evaluate the efficacy of the strategies put in place.

With the summer of 2022 being the hottest ever recorded in Europe, scientists from Inserm at the France Cohorts JSU[1] and the Barcelona Institute for Global Health looked at the number of heat-related deaths for this period.

The research team obtained temperature and mortality data for the 2015-2022 period in 823 regions of 35 European countries, representing a total population of over 543 million people. These data were used to estimate epidemiological models to predict heat-related mortality for each region and week of the summer period.

The records first revealed that the temperatures were above average throughout all the weeks of the summer period. The largest heat-related abnormality was recorded between July 11 and August 14, during which, according to the researchers, 38,881 deaths were caused by the heat. In this period, there was a particularly intense pan-European heatwave between July 18 and 24, for which a total of 11,637 deaths were attributed to the excess heat. All in all, the analysis reveals that between May 30 and September 4, 2022 there would have been 61,672 heat-related deaths in Europe.

France is the country that recorded the greatest increase in temperature compared with the seasonal averages, with +2.43ºC above the average values for 1991-2020, followed by Switzerland (+2.30ºC), Italy (+2.28°C), Hungary (+2.13ºC) and Spain (+2.11ºC).

 

Analyses by Country, Age and Sex

Based on the epidemiological models they built, incorporating data on temperature and number of deaths[2], the scientists were also able to propose a country-specific analysis. They showed in absolute terms that the country with the largest number of heat-related deaths throughout the summer of 2022 was Italy, with a total of 18,010 deaths, followed by Spain (11,324), and Germany (8,173). France comes in 4th place with 4,807 heat-related deaths[3].

Beyond the estimated number of heat-related deaths, the study also included an analysis based on age and sex. At European level, the results highlight a very marked increase in mortality in the upper age groups, with the vast majority of deaths concentrated in the age range of 80 and over.

For the sex-based analysis, the data show that heat-related premature mortality was 63% higher in women than in men. This increased vulnerability of women to heat is observed in the general population and above all among the over-80s, where the mortality rate is 27% higher than that of men. In contrast, the male mortality rate is 41% higher among those under 65 and 13% higher between the ages of 65 and 79.

For the research team, these findings should encourage us to take action to implement more robust preventive and protective measures. Indeed, the fact that many countries already had active prevention plans, unlike in 2003, suggests that the adaptation strategies available to us today may still be insufficient.

“The acceleration of warming observed over the past ten years underlines the urgency of in-depth re-evaluation and reinforcement of prevention plans, paying particular attention to the differences between European countries and regions, as well as between age and sex, which currently mark the differences in vulnerability to heat,” explains Hicham Achebak, Inserm researcher and last author of the study.

Europe is the continent with the highest level of warming, up to 1°C more than the world average. In this context, the team’s estimates also suggest that in the absence of an effective adaptive response, the continent will face an average of over 68,000 excess deaths each summer by 2030 and over 94,000 by 2040.

 

[1] The France Cohorts Joint Service Unit (JSU) brings together several academic supervisory bodies, including Inserm, Ined, Université Paris-Saclay, Université Paris Cité, and Sorbonne Université. Its long-term objective is to offer a range of services for epidemiological cohorts.

[2] The mortality data were obtained via Eurostat and the temperature data via ERA5-land reanalysis.

[3] This study focuses on heat-related mortality during the summer of 2022 using weekly data and estimated nearly 5,000 deaths in France. On the other hand, Santé Publique France has recently used daily data for the same period and estimated nearly 7,000 deaths. This difference is due to the fact that the weekly data generally underestimate the impact of heat on mortality.

A Major Advance in the Genetics and Risk Factors of a Form of Infarction That Mainly Affects Women

SCAD is a form of infarction that mainly affects women. © Fotalia

 

Spontaneous coronary artery dissection, more commonly known under the acronym SCAD, is a cause of infarction of which 9 out of 10 of its victims are women in their forties in apparent good health. Still poorly understood, it is often underdiagnosed, which complicates treatment despite the fact that it could represent up to one third of infarction cases in women under 60 years of age. In order to understand its genetic causes and biological mechanisms, a new international study led by Inserm Research Director Nabila Bouatia-Naji at the Paris-Cardiovascular Research Center – PARCC (Inserm/Université Paris Cité) was set up. Its findings show the genetic causes that define the risk of SCAD to be very numerous and distributed across the entire patient genome. The study has identified 16 genomic regions associated with a higher risk of SCAD, paving the way for a better understanding of the biological mechanisms that underlie this disease. The study was published on May 29, 2023 in Nature Genetics.

Unlike the majority of cardiovascular diseases, such as myocardial infarction, which mainly affect older and/or overweight men, spontaneous coronary artery dissection (SCAD) is a form of infarction that affects women in 9 out of 10 cases. Although these women are often in their forties, the disease can occur earlier – in the year after giving birth, or later – during the transition to menopause. Despite being increasingly recognized as a major form of infarction within this population, SCAD remains quite poorly documented due to a lack of data and a lack of knowledge of its specific risk factors – particularly genetic.

Over the past 20 years, considerable progress has been made in detailing the mechanisms of development of coronary diseases such as atherosclerosis and the very rare and syndromic forms of cardiovascular diseases. Such knowledge is essential in order to better understand these diseases and devise improved and personalized strategies for their prevention and treatment.

Nevertheless, research has lagged far behind in the understanding of diseases such as SCAD that affect women at key stages of their lives. It is therefore essential to now focus on this understudied cardiovascular disease and its own specific genetic risk.

The team of Inserm geneticist Nabila Bouatia-Najia conducted a large-scale study on the subject, coordinating a meta-analysis of 8 genome-wide association studies (GWAS)[1].  By comparing the genetic data of over 1900 patients with around 9300 healthy individuals, the scientists identified 16 genomic regions (or loci) of genetic predisposition to SCAD.

 

Towards a Better Understanding of the Biological Mechanisms

This study began by showing that the genetic variations most commonly found in patients having survived SCAD play a role in the composition of the “cement” that surrounds the coronary artery cells.

However, one of the genes identified is F3 and it encodes the tissue coagulation factor. Normally, the tissue factor initiates coagulation at cell level in order to resorb any hematomas. The results of the study suggest that a lack of F3 expression is often found in patients, constituting a potential cause of poor artery repair, which can lead to tearing. Poor hematoma resorption would therefore be a hitherto unknown genetic cause.

One of the other objectives of this study was to position SCAD in relation to other cardiovascular diseases in order to better understand its epidemiological particularities. Using the data that determine genetic cardiovascular risk factors and clever statistical methods, the scientists revealed a robust link between high blood pressure and risk of SCAD, while confirming that high cholesterol, overweight, and type 2 diabetes had no impact on this risk.

“This finding could therefore be clinically interesting in the longer term, to encourage doctors to closely monitor blood pressure changes in patients at increased genetic risk of SCAD,” explains Bouatia-Naji, Inserm Research Director and last author of the study.

Finally, this study reveals a genetic link between SCAD-related infarction and atherosclerosis-related infarction. Indeed, the researchers have shown that a large number of genomic regions predisposing to SCAD are shared with those of atherosclerosis-related infarction. However, even if these were the same genetic variants, the alleles[2] that are more common in SCAD patients are routinely described as being less common in subjects with atherosclerosis-related infarction.

“This finding is very surprising because they show that, depending on whether you are faced with a young woman with no risk factors, or an older man with risk factors, the genetic causes and biological mechanisms associated with their infarction can be opposed.  Our findings highlight the need to better understand the particularities of cardiovascular diseases in young women in order to improve their follow-up, which is currently identical to that of atherosclerosis-related infarction,” concludes Bouatia-Naji.

Building on these findings, the team is now working to develop new cell and animal models that better account for the genetic factors involved in the disease, particularly in order to better study their impact on the condition of the arteries. Always with a longer-term objective in mind: to shed the spotlight on a cardiovascular disease that is essentially female and all too often neglected, and to improve how it is understood and treated.

 

[1] Genome-wide association study, widely performed for several years now, which consists of analyzing the entire genome of thousands of healthy and sick individuals in order to identify the genomic regions which contain the genes influencing the vulnerability of people to the condition in question

[2] An allele is a version of a genetic variant resulting from a change in the DNA sequence. Any DNA sequence can have several alleles, which often determine the appearance of different hereditary characteristics.

Women and Parkinson’s Disease: Physical Activity Found to Be Beneficial More Than Twenty Years Before Diagnosis

marche sportive retraitée© AdobeStock

Although physical activity is regularly discussed as being one of the avenues for preventing Parkinson’s disease (PD), studies so far had been unable to eliminate certain biases or had not focused on its specific role in women. Researchers from Inserm, Université Paris-Saclay and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) with the Gustave Roussy Institute studied the impact of physical activity on the development of PD in nearly 100,000 women from the French cohort E3N followed up over 29 years. They observed that the more the participants had been active in their lives, the lower was their risk of developing the disease – with such a benefit already present more than 20 years before diagnosis. The researchers have also shown that in women with PD there had been a significant decrease in physical activity in the 10 years prior to diagnosis, probably due to bothersome precursor symptoms. These findings, to be published in Neurology, call for consideration to be given to the rollout of preventive physical activity-based programs in people at risk of PD.

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the destruction of certain neurons in the brain and the accumulation of proteins toxic to them. It is the second most common neurodegenerative disease in France and there is still no cure; therefore it is essential to identify avenues for prevention.

Previous studies had shown a reduced risk of developing PD in people with who engage in high levels of physical activity. However, the limited number of such studies involving women did not make it possible to confirm this association in that population. In addition, these studies generally had a relatively short participant follow-up period with only one evaluation of physical activity, which did not make it possible to eliminate certain biases – particularly that of reverse causation.

Reverse causation is expressed as follows: precursor symptoms of PD (constipation, sleep disorders, smell disorders, subtle motor signs, etc.) may be present several years before the disease is diagnosed. Their effects could lead people to modify their behavior (such as how much physical activity they do) prior to diagnosis, which is liable to distort the statistical analyses that study the relationship between these behaviors and the risk of developing the disease.

A team led by Alexis Elbaz, Inserm researcher at the Epidemiology and Population Health Research Center (Inserm/Université Paris-Saclay/UVSQ), studied the impact of physical activity on the onset of PD in women from the E3N cohort over a follow-up period of 29 years. E3N is a French cohort of nearly 100,000 women who have been followed-up since 1990. With nearly 1,200 women with PD identified in 2018[1], it is currently the world’s largest female prospective cohort for this disease.

The changes in the physical activity[2] of each participant throughout the 29 years of follow-up were estimated based on the information collected via six individual questionnaires completed at different stages of the follow-up. The data obtained compared the practice of physical activity prior to diagnosis in the participants with PD with those of the participants of the same age without PD.

In order to reduce the risk of a reverse causation bias resulting from the potential influence of the precursor symptoms on physical activity in the years prior to diagnosis, the scientists examined the impact of physical activity evaluated more than 5, 10, 15 and 20 years prior to diagnosis on the risk of developing PD.

What they observed was that the more physically active the participants, the less likely they were to develop PD, even when the physical activity had been evaluated more than 20 years before diagnosis. The most active women therefore had a 25% less risk of developing the disease compared with the least active.

Overall, the participants with PD had been less active than the others throughout the follow-up period, including more than 20 years before diagnosis. This gap between women with and without PD increased further in the 10 years before diagnosis, suggesting that the precursor symptoms occurring in this interval could indeed be responsible for a decrease in physical activity in the women who will go on to develop the disease but who have not yet been diagnosed.

 

“These findings support the protective effect in women of physical activity against the risk of developing Parkinson’s disease, even over the very long term, specifies Berta Portugal, PhD student and first author of this research. They support the utility of implementing physical activity programs to prevent Parkinson’s disease in people at risk and call for conducting other studies in order to understand what activity type and level of intensity are the most beneficial,” she adds.

 

“This study demonstrates the importance of studies with a lengthy follow-up within large-scale cohorts to better account for the precursor symptoms and the statistical bias they cause in evaluating the benefit of physical activity on the development of Parkinson’s disease,” concludes Elbaz.

 

[1]The percentage of women with PD in the cohort is similar to that of the general population in Europe over the same period of time.

[2]The concept of “physical activity” goes beyond sport alone. In this study, it is quantified by the distance walked daily, the number of flights of stairs climbed, journeys taken by bicycle, time spent doing light and heavy household activities, time spent doing recreational activities, whether light (gardening, sports of moderate intensity) or vigorous (intensive sports).

Eating Broccoli to Limit Skin Allergies

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The scientists specifically focused on dietary compounds naturally present in cruciferous vegetables, such as broccoli. © Unsplash

The severity of skin allergies can vary depending on many environmental factors, including diet. However, the role of specific nutrients had not been well documented until now. In a new study, researchers from Inserm and Institut Curie at the Immunity and Cancer[1] unit have shown that the absence in the diet of compounds found in certain vegetables, particularly broccoli and cabbage, could worsen skin allergies in animal models. These findings, published in Elife, highlight the importance of a balanced diet alongside therapeutic interventions offered to patients.

Skin allergies are caused by an inappropriate immune response to compounds present in the environment, with the extent of their severity varying according to many factors, including diet. However, the impact of the different compounds present in food is still poorly understood, which complicates the use of nutrition-based strategies to alleviate patient symptoms.

In this research, the scientists focused on dietary compounds that act on a molecule present in the body called the aryl hydrocarbon receptor (AhR). Such nutrients are naturally present in cruciferous vegetables, such as broccoli.

While previous studies had already shown an association between these dietary compounds and the worsening of inflammatory bowel disease and neuroinflammation, their effect on allergic immune reactions had not been documented until now.

 

Worsening Allergies

The research team used a mouse model of skin allergy. Some of the animals were fed a diet containing no AhR-activating compounds in order to evaluate its potential impact on the severity of their allergy.

The researchers showed that the absence of these nutrients is associated with an increase in the skin’s inflammatory state and a worsening of the skin allergy, which did not occur in the mice whose diet contained those compounds.

The scientists wished to go further in order to understand the biological mechanisms of action of these nutrients. When the nutrients were absent, they observed the overproduction of a molecule called TGF-beta in the epidermis of the mice. This overproduction disrupts the normal functioning of a population of immune cells called “Langerhans cells”, which are exclusively present in the skin and act as a modulator of skin immune responses.

The scientists then validated these findings by showing that the AhR-activating compounds also control TGF-beta production in human skin cells.

“Our results suggest that an imbalanced diet could increase allergic skin reactions in humans through mechanisms that we have described precisely. In essence, we could say that our research helps to explain why eating vegetables such as broccoli and cabbage may limit the severity of skin allergies and why it is therefore important to include them in one’s diet,” emphasizes Inserm researcher Elodie Segura, who led this study at Institut Curie.

The findings of this study may also apply to other skin diseases in which inflammatory mechanisms are involved, such as psoriasis. Furthermore, they also open up interesting research avenues for improving the study of the gut-skin axis in the development of allergic diseases.

Based on these data, the research team now wishes to look at the role of AhR-activating dietary compounds in other inflammatory disease settings, such as tumors.

 

[1] Conducted at the Immunity and Cancer unit (Inserm, Institut Curie), this research was carried out with particular thanks to Institut Curie’s experimental pathology platform and new metabolomics and lipidomics platform.

Health Outcomes of the Nuclear Tests in French Polynesia

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Between 1966 and 1974, France performed 41 atmospheric nuclear tests in French Polynesia. © Unsplash

The health outcomes of the nuclear tests performed in French Polynesia in the 1970s have been the subject of epidemiological studies at Inserm for several years. Previous research published by a team from Inserm and Université Paris-Saclay with the Gustave-Roussy Institute had studied the relationship between the frequency of thyroid cancer in French Polynesia and the atmospheric nuclear tests performed by France. It had found a very probable slight increase in the thyroid cancer risk with the radiation dose received following the nuclear tests. In a new publication, the scientists confirm these findings and conduct a risk prediction analysis showing that these nuclear tests could be responsible for 2.3% of the thyroid cancer cases. The particularity of this study, whose results have been published in JAMA Network Open, lies in the access to the original internal reports by the radiation-protection services that relate to 41 atmospheric nuclear tests performed by France between 1966 and 1974 in French Polynesia, declassified by the French military in 2013.

Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia. For several years, research teams have attempted to evaluate the potential consequences of the radioactive fallout on population health. They have particularly focused on diseases that may be radiation-induced, such as cancer, cardiovascular diseases, and cataracts.

In an Inserm Collective Expert Review produced in 2021 (only available in French), researchers mentioned two epidemiological studies published on the subject, one of which concerns the risk of developing thyroid cancer. Due to the amount of radioactive iodine released in nuclear tests and its active absorption by the thyroid, this form of cancer is the most serious health risk for the population living near the nuclear test sites.

This is because when radioactive iodine binds to the thyroid instead of natural iodine, it exposes the gland to the radiation it emits. If high levels of this radioelement are found in the thyroid, this radiation may damage the DNA and lead to the development of cancerous tumors.

In a study published in 2010 in the British Journal of Cancer, researchers from Inserm and Université Paris-Saclay at the Center for Research in Epidemiology and Population Health (CESP) at the Gustave-Roussy Institute compared the radiation exposures of 229 Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 with those of 373 “control” individuals who had not developed thyroid cancer in the same population. This case-control study conducted in the local population had shown a small increase in the risk of thyroid cancer in line with an increase in the dose received by the thyroid before the age of 15.

Although these findings are insufficient in providing a firm conclusion on the links between the fallout of the atmospheric nuclear tests and the occurrence of radiation-induced diseases in French Polynesia, they also did not rule out the existence of health impacts.

Continuing this research, the same team conducted a second epidemiological study, this time on 395 cases of thyroid cancer diagnosed between 1984 and 2016 in Polynesia and 555 controls from the general population. For the first time, they had access to the original radiation-protection service reports relating to the 41 atmospheric nuclear tests performed by France between 1966 and 1974 in French Polynesia, declassified by the French military in 2013.

Thanks to these declassified documents, meteorological data, and interviews with cases and controls (population movements, dietary habits, etc.), the researchers were able to simulate the radioactive cloud of each nuclear test and estimate the dose of radiation received to the thyroid of the study participants. This was on average 4.7 milligray for the cases and 4.6 milligray for the controls.

For all of the cancer cases (395 people), the scientists did not find a significant association between the dose of radiation received by the thyroid and the risk of thyroid cancer. However, the relationship was significant if the analysis only considered the invasive cancers requiring treatment, and excluded the noninvasive microcarcinomas that are common and usually do not need surgery.

Using these cross-referenced data (population movements, dietary habits and rates of thyroid cancer incidence), the researchers also made a risk prediction and showed that, based on current risk models, the nuclear tests performed by France could be responsible for a total of 2.3% of all thyroid cancer cases (confidence interval between 0.6 and 7.7%[1]).

“These findings are consistent with our previous conclusions and confirm that the nuclear tests are most likely responsible for a small increase in the incidence of thyroid cancers in French Polynesia. However, these findings should be considered with caution as the estimated radiation doses received by the thyroid over 50 years ago are bound to be inaccurate,” explains Florent de Vathaire, Inserm researcher at Gustave-Roussy, and first author of the study.

The scientists are continuing their research with the aim of adding to their analysis the evaluation of the genetic susceptibilities of the populations (hereditary factors and genetic combination specific to each individual) that could affect the development of thyroid cancers in the region.

 

[1] The confidence interval defines a minimum and maximum value between which, for a given risk of error, the exact value of the entire population is situated.

AI: A New GPT-Inspired French Algorithm Improves Trauma Surveillance

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Scientists have developed an algorithm to better understand the traumas that represent one third of emergency department visits. © Unsplash

In France, one third of emergency department (ED) visits are the result of trauma. In order to better understand the mechanisms and improve the management of trauma, researchers from Inserm and Université de Bordeaux at the Bordeaux Population Health Research Center, with teams from Bordeaux University Hospital, have developed an algorithm capable of classifying ED visits for trauma through the artificial intelligence (GPT) analysis of clinical reports. This project, called TARPON[1], which has achieved performance accuracy levels of 97%, is described in the Journal of Medical Internet Research Artificial Intelligence. With these findings, the imminent establishment of a national trauma observatory can be envisaged.

Trauma accounts for 9% of mortality in France and often affects populations of young people. More than one third of the 21 million annual emergency department (ED) visits are for trauma. It is therefore a major public health problem that represents a significant health, social and economic burden for which the scientists are working to provide solutions.

The idea for the TARPON project conducted by researchers from Inserm and Université de Bordeaux with Bordeaux University Hospital is based on the observation that the medical staff write a report for each ED visit. These reports represent a wealth of information: symptoms, patient condition, as well as many details on the circumstances in which the trauma occurred.

However, these data remain untapped, with few statistics available on victims of daily life accidents, violence or suicide attempts. For road accidents, an observatory exists, but it is only complete for mortality and the majority of accidents related to cycle, pedestrian or scooter travel are not included. Therefore, the analysis of anonymized information from ED reports would make it possible to constitute the basis for a virtually-exhaustive trauma surveillance system.

These reports are unstructured texts written using a mixture of everyday, medical and technical terms, as well as abbreviations. In order to extract the relevant information without having to read them all, the research teams have developed an automatic language-processing technique based on artificial neural networks. They have adapted the GPT artificial intelligence model and trained it with a sample of over 500,000 reports from adult emergencies at Bordeaux University Hospital[2]. The result is a French-speaking clinical language-processing tool that is compliant with GDPR.

With the support of the Health Data Hub, Bpifrance, the Nouvelle Aquitaine region, the French medicines agency (ANSM) and the Road safety delegation (DSR), the researchers were able to fund the purchase of a powerful server dedicated to artificial intelligence and installed in the hospital itself. This server has been used to implement the algorithm developed by the scientists, in order to automatically classify trauma by type – with surprising precision.

The method developed by the researchers makes it possible to correctly classify 97% of the reports (compared with 86% using the former methods), as described by the researchers in their scientific article. Thanks to this first step, it will be possible to begin studying this data on the Health Data Hub’s technology platform by this summer.

These findings pave the way for the establishment of a national trauma surveillance system, as well as epidemiological analyses concerning, for example, the impact of medication use on the risk of accidents. Research which should therefore provide new insight into major public health issues. In the immediate future, TARPON will be extended to include fifteen EDs across the entire French territory.

 

[1] TARPON: Automatic processing of ED summaries to create a national observatory

[2] This research meets the obligations of the General Data Protection Regulation (GDPR).

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