 It's left. Thank you. Yes, in my talk, I will speak about obesity, the main nutritional problem in adolescence, then the relationship between nutrient intake and obesity and the main nutritional risk factors for obesity in adolescence. We have listened in the talk before that the global syndemic of obesity under nutrition and climate change is a problem. In particular, the pandemic of obesity under nutrition and climate change represent three of the greatest treats to human health and survival. These pandemics constitute a global syndemic consisting with their clustering in time and space, interactions at biological, psychological, and social levels, and common large-scale societal drivers and determinants. Therefore, it's a real problem. If you look at the BMI, who is an index of overweight and obesity in the population, you can see that there is a strong relationship between the level of BMI and mortality. This mortality is associated with cardiovascular disease and coronary heart disease. But more interestingly, Mendelian randomization studies were able to demonstrate that there is a causal relationship between overweight and obesity and the coronary heart disease mortality. So increasing your body mass index, you increase your risk to die from a coronary heart disease. But what about children and adolescents? We listened before that the global prevalence of obesity is dramatically increasing. And that in 10 years, we will have more than 250 million of overweight, obese children and adolescents. Therefore, it's a big problem. But why obesity has to be prevented and treated? But there are four reasons at least. One, the prevalence. The second one is the persistence of obesity from adolescence to adulthood. And in 40% to 80% of cases, a child who is obese will become an obese adult. Then you have the resistance to treatment. It's very difficult to treat obesity, especially severe obesity. And there is a high risk of relapse. The way I can claim the syndrome is very common in people who are obese. So they can lose weight, but they can regain weight very easily. And then there is another important question. It's morbidity. Morbidity and mortality. In fact, if you look at the association between BMI and morbidity in adolescent with obesity, you can see that you may have cardiovascular disorder associated with overweight and obesity, especially hypertension. But also we are very interested in metabolic disturbances. First of all, impaired glucose tolerance, type 2 diabetes, fat delivery disease and dyslipidemia were very common in adolescent with obesity, especially severe obesity. But interestingly, if you look at this slide, you can see that the number of cardiovascular risk factor increase with the BMI of adolescents. In other words, obese adolescents, 35% of them have at least two cardiovascular risk factors. But increasing the number of cardiovascular risk factors, I can see here, is associated with anatomical damages of the vascular system. So the aorta and coronary artery disease are affected by this condition. You had the fatty stress and the fibrosplex that can be found in the artery of people who are young adults who are affected by obesity. So we have anatomical damage associated with exposition to overweight in young ages. In fact, if you now you have to, the question is why a so high number of children and adolescents became obese and why there is this trend to increase morbidity in these people? So you can see there is a relationship between overweight and insulin resistance and between insulin resistance and the metabolic disturbances associated with overweight. But interestingly, there are two other factors. One was accelerating the process. One is the ectopic fat accumulation, especially in the liver and the skeletal muscle. So you increase your body weight, your fat mass increase. So you tend to increase your fat accumulation in tissue and you are not usually able to increase the accumulation of fat, especially the liver. And then you may have also another factor which is low-grade inflammation. Low-grade inflammation is being clearly demonstrated also in repubertal children. And this accumulation of fat in the abdominal area is associated with inflammatory areas where there are cells who are promoting or producing interleukin-6, for instance. Interleukin-6 is able to stimulate ectopic fat accumulation but also it enables to stimulate insulin resistance. So all these process are increasing the speed of development of insulin resistance and the development of these complications. But the morbidity is associated also to mortality. In this longitudinal studies, authors were able to demonstrate that people who are obese in adolescence, this part of the plot, have a higher chance to die for cardiovascular disease in respect to people who are normal weight in adolescence, this line. Therefore, if you are exposed to overweight and obesity in adolescence, independently from confounders, you are at higher risk to die for cardiovascular disease. These evidences were able to accelerate the interest or stimulate the interest of to call to action and that the World Health Organization, the European Association for the Study of Obesity, the Endocrine Society, and also the European Commission were involved. And there is a trend to take care of this problem. There is more susceptibility or sensitivity to this problem in the policymaker but also in the scientists. But if you have to proposal to plan a prevention and treatment strategy to face obesity effectively, you have to know what are the factors who are involved in the development of this disorder. And so we know that this is a multifactorial disease. So you have genetic component, environmental component, psychological endocrine, neurological component, and then you have drug induced, some form of drug induced obesity. But we have to consider that obesity is a disease with a high genetic predisposition. From 40 to 70% of BMI is inherited from the parents, the four genes are very important for this disorder. But genes, then the subject is exposed to environmental and the environmental exposition of the subject is able to modulate the expression of the genes. So epigenetic mechanisms are able to modify the phenotype of the subject. And then you may have a different behavior because food intake is associated to a behavior and this behavior is also affected by several factors in particular, the narrow endocrine system. But why I'm speaking about the narrow endocrine system? Because in the narrow endocrine system, there is the regulatory system. It is the regulatory system who are able to stimulate the subject to eat or the subject to perform physical activity. And this effect is very important because the afferent information or the afferent action of the regulatory system is affected by integration of the information coming from the cortex to four senses. And but also from the periphery, the glucose, amino acids, filtrate acid are affecting this kind of integration. But it's very important to focus the attention to the gut. In fact, recently the gut was demonstrated that some hormones producing the pancreas and the gut are able to affect this kind of regulation, in particular insulin, who is the most important one, but also we have grayling, PIP, GIP, GLP-1, P-way-way and oxyntomodulin, cholecystokinin. So there are several hormones who are affecting this kind of nuclei. These are two important nuclei who are integrating this information and then they are stimulating to response of the individual, modifying the behavior of the individual. These discoveries were able to stimulate the drug companies to perform some research. This is a recent study in which the companies are developing new drugs, hormones in particular, who are able to take care of this problem, especially this one is semaglutide. This is the last one's drug that was produced and this study published on December in the New England Journal of Medicine were demonstrating that administration of semaglutide, one injection per day subcutaneous, was able to promote weight loss, abstainable weight loss, 15% of weight loss in children and adolescents, also in adults of course. But if you stop the injection of these hormones, of course you have a relapse of the disease. So this is not the definitive reply to the question. But if you look at nutrition, there is an association about the epidemiological data and nutritional data, demonstrated that there is another association between food and beverage intake and the risk of overweight and obesity in adolescent, in particular high intake of sugars within beverages and high intake of fast food are associated with this kind of risk, is a well-known information. But in the past, it was clearly demonstrated that energy dense food, so energy dense diet, so high-fat diet and low-fiber diet was directly associated with fatness in children and adolescents. But why fat intake is promoting fat accumulation, but there is a strong relationship between dietary fat intake and fat mass. But this is reasonable because fatty food is more palatable. This food has a high energy density and at least less satiating if you consider a per gram in comparison to protein and carbohydrates. Then fat intake is associated to reduce thermogenesis induced by food. If you get some food, you increase your thermogenesis physiologically. But if in your meal, you have a higher concentration of fat, the thermogenesis induced by food intake is significantly lower. If you eat another meal who has the same energy, the same protein, but a lower proportion of fat and carbohydrates or a different ratio between fat and carbohydrates. So this is an energy-saving mechanism. But if you look at food intake and you look at fat, you can see here that saturated fat intake independently for several confounders is associated with an unfurlable lipid profile. So if you get more fat in your diet, you increase your risk to have an unfurlable lipid profile. But interestingly, these data have been developed and obtained in fasting conditions. But if you look at the patient after food intake, you can see that the relationship between circulating lipids and cardiovascular risk and cardiovascular events is much stronger. Therefore, if you have to measure triglyceride, not in fasting condition, but after food intake to have an idea of what is the cardiovascular risk. In fact, if you measure five hours after food intake, the oxidative LDL cholesterol, you can see that these molecules are much higher in comparison to... If you eat a meal with high fat content, in comparison with a meal with the same energy, the same protein, but a low fat intake. Therefore, fat intake is not able just to stimulate fat accumulation, but it's also a statement to increase the cardiovascular risk of the subject. But if you have a high fat, low carb diet, like Professor Giulio presented before, it was well, Sir Harold Hinsworth was able to demonstrate in the past that high-fat, low carb diet is associated with the poorer glucose tolerance insulin resistance. And this is confirmed recently in our study in which in type one diabetes subject, they try to compare two different meals, one low-fat diet and high-fat diet. If you eat an high-fat diet, your request of insulin is much higher. So you have to give more insulin to have a metabolic control. Therefore, eating a high-fat, low-carb diet, you need more insulin. And so your insulin resistance increase, so your metabolic involvement is much higher. Then if, as we already seen, there are some evidence that carbohydrate intake has to be maintained. In fact, in this study, in the also conducted two independent study conducted in Harvard in Mates and Females, we're able to demonstrate that carbohydrate intake is important, roughly 50% of carbohydrate has been associated with the lowest rate of mortality. And there is another independent study very well performed in which authors demonstrated that if you have the highest visceral adipose tissue accumulation, this one, was associated with less than 0.2 servings per day of world grain and less than one serving per day of refined grain. Therefore, eating low carb is associated with the highest intradominal fat accumulation, so the worst. If you have the lowest visceral fat accumulation has been found in subjects who are getting two refined serving per day and at least three serving per day of world grain. This is roughly what is the recommendation for a normal population. Therefore, eating carbohydrate is not per se associated with the worst condition. Oh, we say, we listened before the advantage to use a Mediterranean diet. And in children was demonstrated that Mediterranean diet was inversely associated with obesity and with wise ways to conference but also increase academic performances, we hope. But if you look at Mediterranean diet, Mediterranean diet is the vegetarian diet, pretty. There are some, you know, if you look, this is all the overlap between the two diet. This is a vegetarian diet, this is a Mediterranean one. You can see that most of the components of the diet are the same. You have protein from the soya from vegetarian diet, meat and fish for the Mediterranean one, but low meat, more fish, but, you know, they are pretty similar. So the Mediterranean diet has a high intake of vegetables and fruit and cereals. So is vegetarian diet a solution? Yeah, probably it could be. And this study, authors were trying to compare different diets in people who were overweight or obese. So vegan, vegetarian, Pisco vegetarian, semi-vegetarian and omnivore, and they were able to demonstrate that vegan and vegetarian people were the people who were losing more weight in comparison to the others. Therefore, the veg diet is better than the other for this purpose at least. But why it's useful to have low-fat, high-fiber diet? Because these components in the diet, these nutrients are affecting the gastrointestinal microbiota and there is an association between the gastrointestinal microbiota and obesity. In fact, in this study, we try to measure the effect of high-fat meal on systemic inflammation, glucose, homeostasis, and all these children are the lesson and we were able to find that taking high-fat meal, you have an increasing endotoxemia. Endotoxemia is the worst condition for promoting metabolic disturbance associated with obesity. But getting fiber with your diet, the fermentation of this fiber in the glut is able to produce short-chain fatty acids. This short-chain fatty acid may act as regulatory molecules for the lipid and glucose metabolism in testing on homeostasis and meal response and also they are able to regulate gen expression. What about sugar? Sugar is a pure white and deadly jotkin said several decades ago. And this is through, in fact, the World Health Organization where it was pushing on the reduction of sugar intake in the population not to more than 10% of total energy but preferably less than 5% of total energy. Unfortunately, this is not what happens, especially in North America, but also in Europe because added sugar are very, very high. The recommendation is 60 spoon of sugar per day. But look at here, we have really a lot of people who are getting more than 50% of children between one and three are getting more than 60 teaspoon of sugar per day. But also in other lessons, you can see more than 90% of people are getting more sugar than is recommended. So sugar intake is too high. And then what about sweet sugar and beverages intake and the relationship between this intake and overweight and obesity association is strong. So this is a way for children and adolescents to get sugar usually. But what can we do? In USA, there are two attempts to modify the quality of the diet and population to healthy hunger free kids act and the women infant and children package reduce childhood obesity. These two strategies were based on increasing world grains, fruit and vegetables and increasing fat free milk or 1% milk in the population in children and adolescents. And these were effective. There are some data that are demonstrating that this kind of approach is affecting. So people are changing a little bit their behavior, nutritional behavior. But also the ESO and DFD position statement nutrition, medical nutrition therapy of the management of overweight and obesity in children and adolescents recommend the same. So reduce the energy density through increased vegetable consumption at the weight protein takes a limited fruit juice consumption. And this was accompanied by the suggestion to increase the personalized dietary coaching. It's very important to think that one thing is to consider the population level. The other thing to consider the patient or the family. So the personalized approach is extremely important for the clinician. But what is the efficacy of the treatment in adolescent and fortunately, the effect of multidisciplinary lifestyle intervention at this multidisciplinary lifestyle intervention is the first intervention that all the clinician has to do for children and adolescent with overweight and obesity. Unfortunately, it's very effective in children but it's not effective in adolescent, you can see. Adolescent is a very difficult period of life in which people are not sensitive to health and education and suggestions for health care, for the parents, for the school. So it's a very difficult target for the clinician. Therefore, I think that the pandemic of obesity one of the greatest treats to human health and survival. Nutritional behavior, adolescent affect diet composition leading to high fat, high sugar, low fiber intake and to increase body fat mass. The adoption of healthy eating habits is necessary for preventing and treating obesity in adolescent although to chain nutritional habits is a difficult target really challenging especially in adolescent. Thank you very much for your attention. Thank you very much. I mean, it was very exciting lecture. So we have 10 minutes for discussion. Then I have one question at the end. I have actually two questions for the first speaker and the second, if you allow. So for the... Make one, please. Make it short. Yeah, it will be short. It's just my comments here on the paper. First, Professor Marchesini about the intermittent fasting. So as I understood from your presentation that in a short term, it's okay, but long run, it's bad, right? Is it correct as I understand? Yeah, in some way it is this way and it may be effective in the short term but it's very difficult to be maintained as any modification of the diet. Okay, so it's because it's bad for the health or just because people cannot maintain it? Because people cannot maintain. For me, for example, if I maintain, it's okay or it's bad? Permanently. It doesn't produce any harm. Okay. Well, for the health benefits, it may be the same. What is the Anglo-Saxon countries have a sort of mantra? They say a calorie is a calorie. You have to take calories and you can eat calories with wherever you wish in the course of the day, whenever you wish. And it doesn't matter if you eat in the morning or in the afternoon or in the... What is mandatory is that you have to reduce your calorie intake. And if you go to intermittent fasting, it may be also beneficial for your body because in some part of the week, you have a sort of getting rid of all what you have accumulated during the previous day, but probably it's much better if you can eat regularly all over the day, all over the week, without any this sort of Scottish shower. Okay. So it makes no harm, yeah? Okay, thank you very much. And for you, Professor, also second question. In one of your latest presentation, you had one of the measures is to reduce the consumption of fat milk. Yeah, to reduce, to consume fat-free milk. But what about the assimilation of fat soluble vitamins, which are very important for adolescence? So if you reduce the fat in milk up to 1% or less, then the vitamins, those water-soluble A and other, they are not absorbed properly. And for hormone building, which is very important for adolescence, it will not be properly so good to do. Yeah, right, but this data are coming from US and they are supplemented. So it's supplemented for vitamin and so on. So no problem about that. Okay, thank you. Yes, it's from US, not from Europe. Okay, thank you. Please. Okay, thank you so for the impressive lecture. Mine is very straightforward and simple. I'm looking at, is there any relationship between nutrition and neuroplasticity in humans, no matter the age range? Is that possible? And also, I'm also looking at environmental changes in the environment, how that can also reflect into the health apart from the side of obesity, because the side of obesity has to do with the nutrition, the feeding. So if you can explore that more for me, it'd be very nice. Thank you so much. Thank you for your question. I didn't face the problem of early nutrition, but of course it's very important. I said that the first 1,000 day of life, intrauterine life and extra-uterine life for the first two years is very important for neuroplasticity. In fact, we have a p-genetic effect on the anatomical and functional development on the neurological system, and especially in the hypothalamus. Sorter is the so-called programming, and this programming is able to, you know, modify the reactivity of the system to the environment. So you are, you know, you are, let's see, say it in English, sorry, you are, you are prone to became obese, you know, as a predisposition, predispose yourself to became obese. So if you during pregnancy, for instance, the mother is as affected from obesity or diabetes, or getting more body weight or gestational diabetes, or a deep under nutrition, anorectic mother, for instance, or mother who is exposed during pregnancy, so low food intake, this effect affects the embryo and the fetus. So the programming of the hypothalamus, the functional of the hypothalamus, is effect for a long term. So you are predisposed to became overweight and or obese if after birth you are exposed to a normal nutrition. One of the important factor is also smoking of the mother. There's one additional question. Same question. And we have two points which are really important. One is epigenetics. And if during pregnancy, mother has some sort of nutritional defect, there is some sort of methylation of the genes which predispose the fetuses and the newborn to obesity. And this is very important and it's going to be studied more and more. And it's one of the main issues for the future. The other point I would like to say in response to what you asked for, is that for sure the environment is important. For example, in terms of diabetes, we are not studying what is called urban diabetes, because the urbanization of the population is leading to a massive increase in diabetes in certain areas, which are by the way, the areas which are in some way frail or which are in note well-developed also inside the same town. For example, if there are studies in Rome and also in Italy, in Bologna, we are part of a very large consortium which is studying urban diabetes around the world which is sponsored by Novo Nordisk, by the foundation Novo Nordisk. And they are trying to define which are the best practices to address these very challenging areas inside the city. Consider that by 2050, approximately 75% of the population will live in towns. And towns are definitely areas where it's much more difficult to have physical activity and to have the possibility to buy fresh fruit or because there are also problems with the punishment, with the provision of food and so on and so forth. So it's a real problem that the areas of poverty inside the towns which are difficult to address for health and nutrition. If I may add another thing is important. Sorry, very important is stress also. Stress is a key factor in promoting fat accumulation. So in the city, there is a lot of stress usually. All over the world, I think. There's one last question. Please. Thank you to both the speakers for the interesting talk. There's no microphone. It doesn't work. So I had a small question. You mentioned something about an ideal diet. Ideal diet. So would the definition of this ideal diet be affected by factors like the age, sex or a geographical location of a particular population? That's the first question. And for the second speaker. Well, stop, stop, stop. I mean, answer it. This sort of ideal diet was something we will develop inside that publication. So you can look at the publication in order to have the idea what the authors mean for ideal diet is sort of an ideal diet in terms of nutrition and developing and reduce the burden of diseases. No, let's wait for the second question, then combine. We're running out of time, so please be sure. Second question is a very general one. So as the young population nowadays, we are sort of influenced by these different kinds of diets that are being promoted, especially the keto diet, which is a high fat diet. So I would just like to know what is your take on it like? Is it, would you suggest it for the young population? Because nowadays, everywhere I see the Gen Z's and the millennials, we are all obsessed with these kinds of diets, so. Sid, thank you for your question. I do not support this kind of diet because I think the better thing for young kids or for adolescents is to have a correct diet, in other words, education to a normal approach to food. And in reply to the previous question, I think that the ideal diet is the diet we're respecting the energy and nutrient requests from the body. Therefore, you have to guarantee in your diet one gram per, roughly one gram per kilogram of the ideal body weight and two grams per kilogram, no, sorry, one gram per kilo of fat and I don't remember, three or four gram per kilo of body weight of carbohydrate. Is the ideal requirements of everybody from the age of two to the age of 60, 70, okay? So you have to look at the requirements. You have to guarantee energy, protein, fat, and carbohydrate. And the amount of carbohydrate are directly associated to physical activity. If you increase your physical activity, you can get more carbohydrate. If you reduce your physical activity, you have to reduce your carbohydrate. That is the, in my opinion, of course, in my opinion, it's the best diet you can find. Then you have to look at food and you do guarantee the food who are, you know, the mix of food who are able to guarantee this kind of intake and who are pleasurable because you have to have some reward when you are eating because you have to be a good moment in your life. It's not to be stress time or, you know, and keto diet is not a- It's not a sin. It's not a sin. There's one last question here from the coordinator. I cannot say no to him. I guess it's a question for both. I mean, when it comes to dietary recommendations, consumers are overwhelmed by contrasting messages that change from source to source. They change from time to time, often going exactly into opposite directions. And many of them appear to be non-scientific. So how can we get the right message to the consumers so that they can trust the sources and rely on those to make their choices? The right message should be simple. And what I say to my patient is we have a nutritional, let's say, recommendations which are very well defined and the amount of carbohydrate in your diet, the amount of fat, the amount of protein. And you have to choose your food according to this recommendation. The mix is what you prefer. And the mix is what you can feel that is affordable and sustainable. And this is really a must because we should not convince people to modify their diet in one direction or the other if we are not sure that this modification might be sustained in the long-term. And to be sustained in the long-term, a modification must be easy to be done. It must be affordable, which means that one of the main concern is public health problem. It's a public health problem. We should make a healthy diet easier and we should make healthy diet more affordable than unhealthy diets. The only way to be sustainable in the long-term and be affordable is to make good choices more easy to be done and easier to be done and easier to be sustained in the long-term. This is a matter of cost. It's a matter of affordability. It's a matter of pleasure. It's a matter of what to add to your diet to increase your favorite. I totally agree with him, but from a clinical point of view, you have to take care when you're promoting a diet in subjects. You have to take care of the cultural and traditional of the family first of all. And then you have to train the parents and not the child. So if the parent changing, the child is imprinted from the behavior in the family and is able to take at least in part the behavior, nutrition behavior of the family. Well, let me finish with thanking all the speakers, but let me add one additional point that in my opinion is important. You mentioned culture, which is very important. The background is important. And even more important in my opinion is that we need to understand that one size doesn't fit all. I mean, if you address an issue of obesity in Norway, it's difficult, it's different from if you address the same issue in Sicily. I mean, this is what, and this is what we need to be careful when you are reading the large studies. What is true in US cannot be true in Africa and it's definitely not true in Japan. So we need to be flexible and we need to use a lot of good sense. I mean, what is missing now is the good sense. The good sense is means that we need to be flexible, but we need to be also driven by science, which is very important. And forget about all the advertising we are seeing in the TV every single day. Go to Burger King and go to whatever. I mean, has it been shown that the so-called the sodas are full of sugars that they're like, I mean, they're really dangerous to drink and all our kids are drinking soda because it's fashionable. So I think it's that, but having said so, I keep my question for discussing with the two speakers about the culture background. This is an extra virgin olive oil, which in my opinion is a very important asset we have and others don't have. And I close this session. I thank the two speakers for the excellent presentations and all of you for the very vivid discussion. I'll pass the floor to our... I will stay here. I mean, you are the guy who's now running the show.