Liver cysts are common, with most cases being asymptomatic. In symptomatic cases, the disease is amenable to treatment. However, huge or multiple liver cysts with vascular narrowing and associated systemic symptoms are extremely rare. Furthermore, the performance of a reliable and effective surgery in such cases remains a major problem. Here, we report a case of multiple giant liver cysts with impaired blood flow surgically treated in a hybrid operating room.A 73-year-old male presented to a previous doctor with leg edema and dyspnea on exertion; computed tomography revealed that the cause complaint was right lung and heart compression and inferior vena cava (IVC) stenosis due to huge liver cysts in the caudal lobe. The patient was referred to our hospital because of disease recurrence despite percutaneous aspiration of the cyst. Multiple liver cysts were observed in addition to the drained cysts, two of which were located on both sides of the IVC and caused IVC stenosis. We performed open surgery for the liver cysts and used the hybrid operating room for intraoperative IVC angiography and measuring the hepatic vein and portal vein (PV) pressure. We performed unroofing of the hepatic cyst and cauterization of the cyst wall on the hepatic side. Angiography was performed before and after unroofing of the liver cysts, and IVC stenosis release was confirmed. IVC pressure measured at the peripheral side of the stenosis and PV pressures were continuously measured during surgery and were confirmed to have decreased during the opening of the liver cysts. The patient had a good postoperative course and was discharged on the 10th postoperative day. No recurrence was observed 6 months postoperatively.Cyst unroofing surgery using angiography in a hybrid operating room is a useful treatment for deep hepatic lesions in that vascular stenosis improvement can be intraoperatively confirmed. Moreover, in cases wherein the cyst compresses the vasculature, intraoperative monitoring of IVC and PV pressures can be used to prove that the liver cyst is hemodynamically involved. Liver cysts are a common disease in which patients are often asymptomatic. However, multiple or enlarged cysts can cause symptoms, such as abdominal pain and multiple organ compression; nevertheless, these are amenable to treatment. Liver cysts causing systemic symptoms due to hemodynamic disturbances of the inferior vena cava (IVC) or portal vein (PV) are very rare, with only a few reports to date. Liver cyst treatment includes medical therapy, such as percutaneous drainage and sclerotherapy with alcohol or minocycline injection into the cyst; however, recurrence cannot be avoided in these therapies . SurgicaA 73-year-old male visited a previous doctor with a chief complaint of progressive leg edema and dyspnea on exertion 1 year prior. The patient had a history of spasmodic angina pectoris, midbrain infarction, and chronic renal failure. Computed tomography (CT) showed multiple hepatic cysts compressing the right lung, right side of the heart, and IVC. He underwent percutaneous aspiration for the largest cyst in segment eight of the liver; however, the leg edema did not improve, and the cyst flared up within a month. He was referred to our hospital for further investigation and treatment.Blood tests at the time of our visit revealed no significant findings other than mildly decreased renal function Table . CT showBased on the above test results, we concluded that the IVC stenosis due to the liver cysts was the cause of the leg edema and dyspnea on exertion and hence decided to treat the liver cysts with fenestration. To confirm the hemodynamic status of the IVC, intraoperative angiography with CT during hepatic arteriography, CT during arterial portography, and angiography were performed in the hybrid operating room to allow IVC and PV angiography before and after liver cyst fenestration. Moreover, portal vein pressure (PVP) and central vein pressure (CVP) were continuously monitored intraoperatively as indices of hemodynamics in relation to the release of IVC stenosis. Furthermore, if the above methods did not improve the IVC stenosis, we were prepared for the dissection of the hepatic caudate lobe from the IVC and the placement of a metallic stent in the vessel.The surgery was performed in a supine position under general anesthesia. To monitor PV pressure, a 15-Fr intravascular catheter  was inserted and fixed peripherally in the jejunum vein. CVP was defined as the pressure measured at the peripheral side of the IVC stenosis and measured by inserting a sensor through the right femoral vein. After mobilization of the left lobe of the liver, we fenestrated the largest lesion in segment eight of the liver. The CVP did not change before and after the fenestration of this lesion. After mobilization of the right lobe, the lesions on both sides of the IVC were identified under ultrasonographic guidance, and the cysts were fenestrated on the left and right sides of the IVC. Before and after fenestration, the CVP decreased from 5 to 1 mmHg, and the PVP decreased from 22 to 17 mmHg. The intraoperative changes in CVP and PVP are summarized in Table To the best of our knowledge, this is the first report on the intraoperative confirmation of the surgical efficacy and successful completion of an operation for a complex condition under the combined use of multiple monitors and investigations in a hybrid operating room. The use of hybrid operating rooms in abdominal surgery is not yet commonly implemented, although there have been reports of such cases, including Furukawa et al.'s surgery for median arcuate ligament syndrome  and SogaLiver cysts are a common liver lesion with an incidence of 0.17–4.75% . MultiplThe diagnosis of liver cysts is mainly based on imaging studies, such as ultrasonography, CT, and magnetic resonance imaging. Depending on the location of the lesion, interventional radiology or endoscopic retrograde cholangiopancreatography may be used to evaluate vascular and bile duct drainage and stenosis. The lesions located in the hilar or dorsal region up to the fourth/eighth segments are difficult to approach from the body surface; therefore, puncture drainage, effective therapy, and laparoscopic surgery cannot be performed.Symptomatic liver cysts are amenable to treatment. The basic treatment involves drainage of the cyst contents and cauterization of the cyst wall. This can be performed by percutaneous cystocentesis, laparotomy fenestration, or laparoscopy. For multiple liver cysts or large lesions, hepatectomy, including the cysts, may be performed. If the lesions involve the entire liver, liver transplantation could be a last resort , 14, 15.Liver surface cysts are commonly treated with surgical fenestration and cauterization , 17. If The other treatment for vascular stenosis is endovascular stenting. It is an option for older adult patients who cannot undergo surgery and has the advantage of being less invasive. However, in this case, the stent was not used because the stenosis was not only in the IVC, but also in the RHV, and it was technically difficult to place the stent at the same time. In the preoperative evaluation, we suspected the possibility of post-hepatic PH due to impaired RHV and IVC outflow, and it was necessary to avoid blocking RHV outflow with a stent in the IVC.In this case, the most important preoperative concern was to accurately identify the cyst responsible for the disease state and ensure that the disease would improve by fenestrating the cyst. To achieve this purpose, it is essential to evaluate the effect of treatment using multiple intraoperative monitors.The choice of laparotomy made it possible to intraoperatively monitor the PVP and CVP. In general, liver cysts rarely cause PH . In our In addition, we were able to use a hybrid operating room with intraoperative IVR to confirm the target lesion. Although it is possible to locate cysts intraoperatively using echocardiography, it is sometimes challenging to visualize cysts around the IVC or on the dorsal side of the liver. Furthermore, if there is an image of IVC stenosis due to a cyst, the hybrid operating room has the advantage of intraoperative confirmation, especially after opening the cyst, such that the IVC stenosis can be released in situ. The disadvantage is that the operation time becomes inevitably longer owing to the need to move the operating table and secure a clean field for intraoperative CT. However, since we have been successful in performing the surgery while confirming reliable results, we consider this extension of the surgery time to be acceptable.The recurrence rate after surgical treatment of liver cysts is reportedly 0–20% . To prevIn the present case, we performed preoperative planning and hybrid surgical fenestration for symptomatic liver cysts with good results. The use of a hybrid operating room for surgical fenestration is useful for deep liver cystic lesions that cause vascular drainage or stenosis. In addition, in cases wherein the cyst is compressing the vasculature, intraoperative monitoring of the IVC and PV pressures can be used to prove that the liver cyst is hemodynamically involved.


This paper aims to analyse the relationship between perceived health and earnings across Europe. Empirical analysis is based on the last published round from the European Working Conditions Survey  and offers updated evidence on the effect of earnings on perceived health in 35 countries. The main findings show a positive and significant relationship between earnings and health, which is consistent with the existing literature. Moreover, health seems to be U-shaped relative to earnings. On the other hand, age is negatively related to health, which is consistent with previous research. This paper shows the health differences between countries, where cultural, geographic, and economic differences imply health inequalities across countries. From a practical perspective, understanding the dynamics of perceived health and earnings’ processes can contribute to health policy. Health status is closely related to employment conditions. Job characteristics or the nature of work may put health at risk , but they may also have a positive impact on health . StudiesHealth status depends, not only on healthy habits, but also on income. The demand for health and healthcare, published by Grossman ,6, showeThe current paper aims to go one step further. It focuses on the effect of earnings on health for a population of active workers, considering microeconomic and macroeconomic factors by exploring the interaction between individual factors, occupation characteristics and work environment factors in 35 European countries.Data from the sixth round of the European Working Conditions Survey (EWCS), gathered from September to December 2015, have been used. This questionnaire collected demographic data and a broad range of factors regarding current working conditions. The specificity of this dataset is that it includes a population of active workers only. Retired or unemployed individuals were not considered. Working conditions evaluated in the survey include physical and psychosocial risk factors, employee participation, learning factors, gender issues, work environment, and health risks perceived at work. This EWCS 2015 data is complemented with Eurostat macroeconomic indicators . These aAmong the 35 countries included, 28 are EU state members, and the remaining are Norway, Switzerland, Albania, the former Yugoslav Republic of Macedonia, Montenegro, Serbia and Turkey. In total, our sample comprises N = 43,850 individuals. Each country interviewed a different number of individuals, which ranged from 1000 to 3364 see  below.The level of Health assessed (H), refers to the respondent’s own assessment of his or her health. The European Statistics of Income and Living Conditions (EU-SILC) asks a similar question. The question in the EWCS 2015 used in this study is ‘How is your health in general? Would you say it is …?’. Five categories of response were included, from 1—Very good to 5—Very bad. This variable is inverted for our analysis so that the greater its value the better the individual’s health assessment.The independent variables in The set of individual factors is composed of the following socio-demographic variables: gender, level of education, age, number of hours educating children/grandchildren, type of occupation, reporting having suffered discrimination due to ethnicity, marital status. Existing literature uses these variables for explaining health .Nine different levels of education are considered. To homogenise data from different European countries, the International Standard Classification of Education (ISCED) is used to classify workers. Employees are divided into nine groups according to the highest level of education or training that they report to have successfully completed.Additionally, the International Standard Classification of Occupations (ISCO) is applied to categorise occupations. The ISCO is divided into ten groups, but our sample presents only nine groups , because armed forces are omitted.Variables such as the size of the business or the increase in the number of hours an employee has to work since the job started are included in this category. The size of the company is used as a control variable, with four categories: self-employment/one employee, small firms (from 2 to 9 workers), companies characterized by medium size (10 to 249 employees) and the largest enterprises (250 employees or over). The group of smallest firms (those with one employee) is considered as the baseline. The increase in the number of hours at work is measured on a Likert scale from one to five, with one reflecting that hours had increased significantly since the individual started the job, and five reflecting that these had significantly decreased.The groups of variables that were included to represent the work environment are non-tangible statements related to climate at the workplace. Each statement is measured in a Likert scale (1—strongly disagree to 5—strongly agree). These are questions such as if employees feel appreciated when they do a good job, the degree to which employers trust employees, if conflicts are solved in a fair way, if the work is fairly distributed and if relations with other workers are good.Questions related to health and safety at the workplace are also included in this category. This is used as a risk at work measure because it provides information regarding the positive or negative impact of the workplace on health  are used to measure these situations.The GDP per capita and unemployment rate, at a national level and from Eurostat statistics, are included as macroeconomic indicators. To facilitate comparisons between countries, GDP is measured at purchasing power parity (PPP). A dichotomous variable to distinguish when the GDP/unemployment of a country are above the median versus when its GDP/unemployment is below the median has also been created. Because the country GDP per capita, the unemployment rate of a country and the country are linearly dependent, including more than one of these variables would result in a mis-specified model due to perfect multicollinearity. Therefore, separate models are estimated.Monthly earnings are introduced in the model as a dependent variable. Monthly earnings squared are also included to test for a non-linear association between earnings and health.i represents each worker, h is the possible level of self-assessed health  and k is the number of independent variables or inputs included in the model. The explanatory variables (x) are individual factors (I), job characteristics (JC), work environment (WE), macroeconomic factors (M) and earnings (E), similarly to Wang et al. [The following equation is specified:g et al. . Robust Equations were estimated stepwise to facilitate the analysis of the association between earnings and health, controlling for other variables that may affect this association. A ‘conventional’ health equation was estimated first, which included individual socio-demographic information and job characteristics, work environment and macroeconomic factors only. Then, the macroeconomic variables (GDP and unemployment rate), country dummies and interactions were included in the regression model, separately. Summary statistics are presented in The most common occupations among the surveyed workers are service and sales workers (21.7%) and professionals (17.7%), followed by craft (11.8%) and technicians (11.2%), elementary occupations (10.4%), clerical support workers (8.6%), plant and machine operators (6.8%), managers (6.3%) and skilled agricultural (4.8%). Most employees that participated in the survey worked in medium and large firms (36.1% in businesses with 10 to 249 workers and 26.8% in the group of largest companies). Because the average level of hours increased at work since the job started is 2.85 (SD = 0.68), it can be concluded that most workers did not dramatically change the number of hours they work. Regarding the work environment, all variables present average scores higher than 3.75, which means that these ascribed behaviours occur habitually in the companies of the surveyed workers. The variable that measures if the individual thinks there is cooperation between colleagues at work is the best valued.The mean GDP per capita (PPP) observed is EUR 30,000, and the mean rate of unemployment is 11.9%. The average monthly earnings considered in the sample is EUR 1346.01 (SD = 2278.87).Regression results from estimating probit models are presented in As shown in the three models, men have a greater probability of having very good health, while women are more likely to have a fair level of health assessed compared to the opposed gender. Age appears to be negatively associated with health, increasing the likelihood of bad or very bad health, and decreasing the likelihood of very good health. The number of hours caring for children is also associated with a greater probability of good health. The greater the level of education, the greater the association (and more significant) with the probability of health assessed being very good compared to the lowest educated group, early childhood education. The probability of bad health is also significantly associated with education, with the lowest educated group being more likely than any other group to report bad health. Regarding the type of occupation, compared to elementary workers, managers have a lesser probability of very good health being assessed. Technicians, clerical, or craft workers, though, are significantly more likely than elementary workers to report very bad health. Technician and clerical workers are, however, significantly less likely than the baseline group to report a good level of health.Compared to self-employed individuals, workers at small firms are more likely to report higher health. The probability of a good self-assessed health is also greater for workers in bigger companies of 250 employees or over, but the estimate indicates the difference with self-employed is not as high as it is for employees of small companies. Regarding the interaction between occupation and age, results show how older workers, except for skilled agricultural and craft workers, have a greater probability, compared to elementary workers, of reporting a good or very good level of health.Interestingly, the change in the number of working hours since the job started is not negatively associated with good or bad health reported, per-se. However, there are other work environment factors that are significantly associated with the health assessed. For example, the sense of cooperation between workers at the workplace has the greatest (and most significant) association with the probability of reporting good or very good health. However, both associations are opposite, increasing the likelihood of good health and decreasing the likelihood of very good health. All other work environment factors are also associated with a greater (lower) probability of good or very good (bad or very bad) health, except for the sense of being recognised for doing a good job, which does not show a significant association. Finally, if the employee perceives that his or her health or safety is at risk at work, or that health is affected negatively because of work, the health assessed decreases, as opposed to the increase observed when an employee perceives that health is affected positively because of work.Results of Models 1 (GDP per capita model), 2 (Unemployment model) and 3 (Countries’ differences model) show that, after controlling for individual characteristics and work environment factors, both GDP per capita and unemployment rate associate, with opposite signs (as expected), with the probability of a certain type of self-assessed health. In addition, there are significant differences found when looking at differences in macroeconomic factors. Having a GDP above the median European GDP per capita increases the likelihood of a very bad level of self-assessed health. However, while unemployment rates above the mean associate positively with a good level of self-assessed health, they also associate negatively with very good levels of self-assessed health, compared with workers who live in countries with a worse unemployment situation.According to our results, health is associated with monthly earnings following a U-shaped function when the level of health assessed is bad, and U-inverted when the level of self-assessed health is very good.Finally, the countries’ differences model estimates show that, for most countries, there is a significant effect of being from a certain country over the health assessed. Although country dummies are not shown in the table, for ease of visualization of the regression results, these are included. Only for two countries (Denmark and the United Kingdom), there is a not statistically significant association.This article presents empirical evidence of the positive relationship between perceived health and earnings based on a model that includes a dataset from 35 European countries and 43,850 responses from active workers. As mentioned, data for the research were collected in 2015 and published in 2017. This is the most recent dataset available at the moment, allowing us to study the effect of earnings on self-assessed health while controlling with macroeconomic and microeconomic factors.Our approach offers a quantitative analysis of the inequality of perceived health and earnings in Europe. To do so, a model to analyse the influence of earnings on different levels of self-assessed health across Europe has been conducted. This model supports the idea evidencing the positive relation between those variables based on the studied data. Furthermore, estimations of the sensitivity of earnings to age and interactions between occupation and age in the explanation of perceived health provide a more disaggregated analysis of the relationship between earnings and health compared to what is commonly offered in the literature. As an example, our results show that employees of small firms of 2–9 employees are more likely to report a very good health status compared to self-employed individuals (or firms of one worker). A behavioural explanation for this result could be the fact that workers tend to report lower health when they work more hours and are therefore overemployed, or they are working more hours than the hours that would be considered optimal . Indeed,As a final note, health inequality across Europe was also tested, comparing the situation of richer and poorer countries in the European Union. As the existing literature posits, there are significant differences between countries according to their economic situation according to the effect found for unemployment. This article also confirms the large dispersion of health at work across European countries.Regarding the methodology used, existing studies have developed a similar strategy estimating OLS regression models ,20. HoweUnderstanding the dynamics of perceived health and earnings processes is important for theoretical as well as practical reasons. From a theoretical point of view, this research presents updated evidence that complements previous studies, and the results are consistent with the existing literature. From a practical perspective, these findings should contribute to health policy. because a positive and significant relationship is found between earnings and health assessed, this could be considered in the definition of economic aids and healthcare services. This is even more relevant in a context characterised by the diversity of healthcare systems in the European Union, which may also be affecting the inequality in health assessed. However, this cannot be concluded by only looking at the results from the econometric model estimated. More information would be necessary to better understand the reasons for the differences in health assessed in the different health systems. Further research on this is, therefore, highly encouraged.As with every research study, this paper presents some limitations. Health measurement is based on data of perceived health instead of data of the real health situation. Workers surveyed answered a question related to their perceived health status . Their perceptions may differ from their real health situations. The relation between the health status and other variables used in the analysis may create an endogeneity problem. Workers with better health will live for more years and they will be able to earn more money. For that reason, our results cannot be interpreted as causal effects, because of the strong correlation between earnings and health; healthier employees are able to work for longer hours, and age is also related to health. Although the aim of our model is not to demonstrate causality but to explore the association between these two variables, we understand this might be an issue and took this into consideration. Including an indicator of the GDP per capita or unemployment being above the median allows one to partially deal with the endogeneity problem, and indeed we demonstrated that this positive association between GDP and health, or the negative association between unemployment and health, is no longer true when both reach a certain threshold . We encourage further research to focus on refuting this association because our results show that the direction of the association between health and earnings might not be unique.On the other hand, these data present several advantages: the novelty of the data, collected in 2015 and published in 2017, and the possibility of including 35 countries with a high number of answers per country (more than 1500 data per country). Furthermore, as mentioned, the scales reported (from one to five) are similar to those used by other health institutions, such as the European Community Health Indicators Monitoring Joint Action. Additionally, and as was mentioned, the model only includes individual earnings from the workers who responded to the survey. The additional income of their household is not considered because the data did not provide this information. Therefore, global income should be measured because behaviours and habits are determined by the complete household income.The research is also conditioned by the nature of the dataset. As was mentioned, no causal effects can be considered. Consequently, the development of panel data would improve this and other studies in the field. These data will allow the valuation of causal effects between the variables considered in the paper, which will offer new avenues in the field. Along this line, further research might consider real health status instead of perceived health or, moreover, the comparison between these two variables: real and self-reported health. These results could have relevant health policy implications and help to address health inequalities across Europe.


It is now well established that all animals and plants harbor abundant and diverse microorganisms, including bacteria, archaea, viruses, and eukaryotic microorganisms. This conglomerate of the host and its microbes has been termed holobiont ,2 and meNine interesting papers were included in this Special Issue, titled “Role of microorganisms in the evolution of animals and plants”. All of the articles discuss the interaction of microbiota and the host, as well as the importance of the wholeness of the structure termed holobiont. Three papers deal with plant microbiomes, three with animal microbiomes and three with more general aspects. Most of the articles lead to general concepts, such as tradeoffs between positive and negative effects of microbiota, potential application of microbiota in agriculture, how human intervention changed microbial evolution, and the vertical and horizontal transmission of microbiota.Caenorhabditis elegans, the concept of tradeoffs may be general.Three articles deal with the role of microbiota in stress. The article by Slowinski et al.  argues tElytrigia atherica, which is invasive to salt marshes across the North Atlantic Coast from Northern Portugal to Southern Denmark, the authors show how microbiota influence the adaptability of their host plant to salt concentrations in soil. The data suggest that E. atherica is flexible in its association with soil bacteria and that ecotype-specific bacteria are dissimilar. This may help explain salinity and drought tolerance in relation to the local environmental needs of each ecotype.The second paper on stress by Hernández et al.  discusseEuphyllia paradivisa, with and without photosymbionts. Meron et al. [The third article deals with temperature and antibiotic stress on the coral n et al.  demonstrArgiope bruennichi, from geographically distant, but genetically similar, populations in Germany and Estonia. Overall, the microbiome differed significantly between populations and individuals, but not between tissue types. A novel bacterial symbiont, affiliated with Tenericutes, was found to be present and abundant in every tissue type in spiders from geographically distinct populations. Since it was also present in offspring, the authors conclude it is transmitted vertically. The data demands further inquest regarding the role of this novel but abundant symbiont in the ecology and evolution of its host Tenericutes spider.The report by Sheffer et al.  characteDrosophila pseudoobscura can affect host mate choice and that an intact microbiota is a key component of attractiveness in older males. The data indicate that the fly bacteria provides a signal used by females to assess male’s age, and that a damaged microbiome disrupts this signal. Thus, age-based preferences may break down in environments where the microbiome is impaired . For example, the authors report that D. pseudoobscura older males reared on an antibiotic-supplemented diet have decreased attractiveness to females.Choosing the right mate can have a major impact on the fitness of a female’s offspring. Heys et al.  demonstrSariola and Gilbert  discuss Donald Smith and his coworkers at McGill University have contributed two papers to this Special Issue. One is a theoretical article, which discusses the critical role microbes have played in the origin and evolution of plants . StartinThe second paper  discusseThe last article in the issue deals with the transmission of microbiota and their genes between generations . After r


Improving the nutrient density of processed foods is one way to bring the global food supply closer to the WHO Sustainable Development Goals. Nutrient profiling (NP) has emerged as the preferred method of monitoring the progress toward product innovation and reformulation. This paper presents PepsiCo Nutrition Criteria (PNC), a new internal NP model that was designed to guide and monitor improvements in nutrient density and overall nutritional quality of foods and beverages. The new PNC NP model assigns food products into four classes of increasing nutritional value, based on the content of nutrients to limit, along with nutrients and ingredients to encourage. The nutrient standards used for category assignment followed those developed by global dietary authorities. Standards are proposed for calories, sodium, added sugars, saturated, and industrially produced trans fats. Also included are minimum values for food groups to encourage, low-fat dairy, and for country-specific gap nutrients. Internal use of the NP model has spurred product changes that are consistent with WHO goals for industry transparency. An audited review of company products showed that 48% met added sugar, 65% met sodium, and 71% met saturated fat goals. By the end of 2020, in the top 26 regions in which products are sold, 48% of the total sales volume of global beverages had 100 kcal or less from added sugars per 355 ml serving representing 80% of beverage volume and over 90% of food volume sold globally. The PNC NP model is not consumer-facing but is specifically intended for internal use to motivate stepwise and incremental product innovation and reformulation. Transparent and published NP models further WHO goals of engaging industry stakeholders in the (re)formulation of processed foods and beverages consistent with public health goals. The World Health Organization (WHO) has called on the food industry to reduce the amounts of saturated and trans fats, added sugar, and salt in the global food supply. Noting that “the global burden and threat of non-communicable diseases (NCDs) constitutes a major public health challenge” . The WHOQuantitative methods to assess the nutrient density of foods to meet public health goals are part of a growing scientific field that is known as nutrient profiling or NP . NP methWhereas some NP methods such as Smart Spot  or SmartNutrient profiling schemes with stepwise criteria, still a novel concept, can inform product reformulation goals that are technically feasible while meeting consumer standards of cost, taste and convenience. One such progressive scheme, the PepsiCo Nutrition Criteria (PNC), was specifically developed by PepsiCo for product reformulation and is presented here. Consistent with progressive reformulation goals, stepwise imposition of incremental nutrition criteria was the main driving concept and a unique feature of the PNC model. Applying progressively more stringent nutrition criteria to product reformulation allows for better benchmarking of progress toward nutrition goals. While taking the limits of food technology into account, the PNC addresses nutrients to limit as well as nutrients and food ingredients to encourage.A secondary goal was to show how the PNC has been used internally to guide product reformulation and product innovation. Some preliminary evaluations of the PepsiCo global product portfolio are included. One of the primary characteristics of the PNC is that there is the incentivization of small changes rather than requiring all or nothing nutrition goals. The PNC guidelines may thus provide a roadmap for others in the food industry to more rapidly make product changes that may benefit the population at large.Making the PNC more broadly available will permit the tracking and monitoring of companies' progress toward reaching public health nutrition goals. The WHO goals are to limit fat, sugar and salt and to encourage the incorporation in processed foods of nutrients of public health concern, that is vitamins and minerals shown to have shortfalls in the population or segments of the population. Incorporating dietary ingredients of interest  can also make for more nutrient-rich and healthier diets.The present goal of transparency and disclosure is consistent with the Access to Nutrition Initiative (ATNI) goals to encourage companies to improve the nutrient density of their product portfolios . The ATNTo develop an incremental NP system to help guide the formulation of new foods and beverages or the reformulation of existing ones, a cross-functional team was convened that included internal nutrition scientists and food technologists as well as external independent academic nutrition scientist advisors. The principles that underlay the development of the PNC included external authoritative recommendations from leading global and regional authorities, consideration of the overall diet in the context of individual foods and beverages and published scientific research.The criteria used a synthesis of nutrition recommendations from global or regional authorities including the recommendations of WHO, Food and Agricultural Organization, US Institute of Medicine, European Food Safety Authority, United States Department of Agriculture Evidence Analysis Library (EAL), Euro diet and country-specific dietary guidelines from the USA, Canada, China, India, Saudi Arabia, Australia, Malaysia, Mexico, Argentina, Chile, Ecuador, Russia, UK, Turkey, France, and South Africa , 22–42.From this synthesis, the generic nutrients to limit were defined , with both saturated fat and added sugars at or below 10% of total energy, sodium at or below 2,000 mg per day, with no partially hydrogenated vegetable oils (PHVOs) and industrially-produced trans fatty acids (iTFA) as low as technically feasible .Food groups to encourage (FGE) included fruits, vegetables, whole grains, low-fat dairy (dairy product with between 0.5 and 2% milkfat), nuts, seeds, pulses, and legumes. The minimum inclusion in a product was set at od group , 43. Theod group , 44. ForThe PNC were designed to be inclusive of the global portfolio of PepsiCo Inc. foods and beverages and was divided into 20 defined product categories . The catData for sales volume and for the amounts of nutrients to limit and food groups or nutrients to encourage were determined for PepsiCo Inc. products in the top 26 countries or regions and on a global basis. The countries and regions were determined by examining and placing into order by the sales volumes for foods and beverages. Countries with the largest volumes were chosen first. This captured over 80% of total sales volume. Additional regions or countries with the next highest volumes were then added to reach over 97% of total volume sold. The remaining regions or countries contributed such a small percentage of total sales volumes that adding them individually had virtually no effect on the total sales volume and thus they were excluded from this analysis. Data were used both from the years prior to the PNC being introduced and by year since the PNC were introduced. It should be noted that product development meeting PNC criteria was incentivized. All data tracking noted in the results below guided by the PNC criteria were independently audited by The Partnership for a Healthier America , 48.Individual categories of food and beverage products were assigned criteria for calories, saturated fats, iTFA, added sugars and sodium (NTLs). Some categories had additional specific requirements as noted . In addiEnergy had a daily reference value of 2,000 kcal and limits for categories were then based on this value. For example, it is generally accepted in dietary guidelines that an individual snack can contribute up to 10% of daily calories if consumed within a healthy balanced diet and that several planned snacks per day can help improve diet quality –56. ThusFor saturated fat, an upper limit of 10% total dietary energy was used. Therefore, based on a 2,000 kcal diet, 1.1 g per 100 kcal was the saturated fat limit for relevant categories. The limits for trans fats were in line to reduce intake as much as possible and of eliminating PHVOs. Thus, the limit of iTFAs was ≤ 0.1 g/100 g finished product and the resulting limit of PHVOs, was applied to most categories. For products in categories that contain greater amounts of oils, the limit was set so that in the finished product no more than 2% of all oils were iTFAs  trans-faWhile there is global consensus on limiting the intake of sugars in the diet, guidelines vary in the specifics of the exact definition of what sugars to limit and whether to include total sugars, added sugars, free sugars, or only non-intrinsic sugars. However, in general, limiting the intakes of added sugars to no more than 10% of total dietary energy is agreed upon and therefore we chose to use the 10% added sugar guidance as our limit . We usedatterns” . All catatterns” , 5A.The application of the category criteria to the global PepsiCo foods and beverages portfolio have had measurable effects since they were implemented . This ouFor saturated fats, 71% of PepsiCo's global portfolio does not exceed 1.1 g of saturated fat per 100 kcal in the top 26 markets representing 89% of all food sales , 7 47, , 61–63. It is more difficult to assess progress toward meeting positive nutrition criteria, as this covers a wider range of products and sales data do not necessarily track these improvements. However, no food company relies on a single program (such as PNC) to drive portfolio change. Sales growth of oat, nut, seed, or legume based products (specific FGE) are being driven primarily by consumer demand and thus the portfolio has shown a marked expansion of a wide range these products .To meet the recommendations of WHO and ATNI for industry transparency we have described here the NP system that PepsiCo has implemented , 7, 24. Using the PNC, conceptually and practically, could drive industry consistency of new and reformulated products. Implementation of this system has produced measurable significant progress toward improved nutrition goals to date. Progress is not only at an individual product level but also across the portfolio. To ensure significant transformation, the company set challenging public goals for the reduction of nutrients to limit by 2025 across its global food and beverage portfolio . For exaSince the PNC is a science-based system that follows governmental nutrition guidelines and translates these guidelines into meaningful criteria for a wide range of food and beverage products, utilizing it for several purposes is possible. The emphasis on positive nutrition is extremely important and ultimately the goal of all NP systems is to improve the quality of the diet of individuals and as such requires more than just limiting certain nutrients.There are some limitations of the current PNC that will need expansion in the future. For example, the PNC is not currently designed to meet the needs of special populations such as women of childbearing age, adolescents, or older adults. These populations have special nutrition needs and it will be important to address this in future versions of the PNC especially for products that are targeted to these population segments. While recognizing this is important, it is expected that the current system will be beneficial for all subpopulations. In addition, any such system will need to be updated regularly to respond to changes in dietary guidance. The PNC is not intended to be consumer-facing and is not designed to educate consumers on the nutritional quality of products, unlike other NP schemes. Like all NP schemes, the potential intended impact on public health is challenging to demonstrate due to numerous factors inconsistency in product composition across global markets, and independent factors impacting public health. Therefore, the public health impact of the PNC is not an outcome that was feasible to include in this paper.One of the aims of this publication is to make transparent not only the nutrition criteria but also how they are being utilized to promote product reformulation and innovation. As noted previously the effects of implementing the PNC on NTL are being independently evaluated by the PHA, an organization that works with the private sector to help improve health and reduce childhood obesity.In the end, the approach is validated such that the portfolio it has been applied to has improved in its nutritional quality to enable choices to meet changing consumer needs. Yet there is still significant progress to be made in the transformation of the product portfolio, not only to reach stated 2025 company goals but moreover to provide individuals with more nutrient-dense choices to support improved dietary patterns. By having a transparent process that promotes reducing added sugars, saturated fat and salt, while encouraging key food groups and leads to the development of a broader portfolio of product choices we hope to enable a broader focus on positive nutrition.The initial success of the PNC system suggests the possibility of a potential model for the improvement of the processed food supply. For example, small companies that are unable to develop their systems could easily adopt the PNC system as it applies to most food categories sold by the food industry. More broadly as recently noted by Drewnowski et al. the importance of healthy food choices and dietary patterns is a major emphasis of dietary recommendations . These eDrewnowski et al. also highlight the need for profiling systems that go beyond a focus on specific NTL , extending to the total nutrient density of the food or beverage . The PNCWhile the practice of developing and implementing these criteria into the innovation process of a large CPG company is challenging, it is also very worthwhile in terms of the cumulative value on improving the nutritional profile of the product portfolio for consumers globally. Continued efforts across the industry of food and beverage manufacturers to reformulate and innovate new products with improved nutrient profiles will be necessary to help support consumers with choices to improve their diet and health.We have developed a novel NP system that considers nutrients to limit, nutrients to encourage, food groups to encourage and sets category-specific incremental step-wise goals to facilitate rapid changes in food and beverage products. Making public this NP system meets WHO and ATNI stated recommendations for industry transparency.The incremental nature of the current system encourages reformulation and innovation of products within practical manufacturing considerations. The system is a possible industry road map for guiding product development and reformulation to better meet well-agreed-upon population dietary goals with a focus on positive nutrition.https://www.pepsico.com/sustainability-report/downloads.Publicly available datasets were analyzed in this study. This data can be found at: All authors contributed to the design of this research, analysis of the data, writing, reading, and approval of the final manuscript.This study was fully funded by PepsiCo Inc. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. The funders approved the submitted manuscript prior to submission.DG, RB, JW, and MO'S were full-time employees of PepsiCo Inc. at the time this research was performed. AD was the originator of the Nutrient Rich Food Index, an early NP model, has received grants, contracts, and honoraria from entities both public and private with an interest in nutrient profiling and (re) formulation of foods, and served as a consultant to PepsiCo Inc. for this project.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Iftar) and one before dawn (Sohor). During this month, it is also an opportunity to share a meal with family and friends, a period of highly intensified socialization. In parallel with the nutritional changes brought about by this unique pattern of fasting in Ramadan, other metabolic and physiological changes may occur, such as fluctuations in body weight and/or disturbance in the quantity and quality of the sleep-wake circadian rhythm. In the verses of the Qur'an, the exemption from fasting in certain situations such as illness is clearly stated. Despite this religious tolerance, many faithful who are eligible for the exemption observe the fast of Ramadan either for the spiritual aspect it provides by performing it, by religious guilt or to mark a normalization in the Muslim community for fear of the gaze of others. The world is experiencing an increase in the emergence of non-communicable diseases (NCDs); leading cause of the global mortality. Environmental and behavioral risk factors related to lifestyle, such as smoking, excessive alcohol consumption, unhealthy diet, and sedentarity have a causal association with NCDs. Other factors, such as genetic and physiological factors may also be associated . Diabetes is one of the highest prevalent NCDs in the world and it continues increasing year by year. This chronic disease can lead to significant potential complications  to the patient's health. This requires an individual and appropriate care, both dietetic and therapeutic and over the long term will at best make it possible to sensitize the diabetic patient to the adverse effects related to his disease and thus improve its quality of life. Performing the Fast of Ramadan for a diabetic is a common situation. Diabetes is the only chronic disease widely studied in relation to Ramadan fasting. In the literature, many studies have investigated the effects of Ramadan intermittent fasting on diabetic patients. This article aims to provide a general overview and highlight if there are many effect of Ramadan fasting on diabetes, as an example of a NCDs.Although Ramadan lasts only for 1 month each year, it can be accompanied by significant changes in: both energy and nutritional intake; in the diet composition; in the working hours; and the usual way of life. The majority of practitioners consume two meals, one after sunset ( Ramadan is one of the five pillars of Islam. It constitutes the month of fasting, a holy month for Muslims who have the duty to fast from sunrise to sunset. Ramadan lasts between 29 and 30 days depending on the lunar cycle, shifts from year to year and gradually changes from one season to another. This religious rite concerns all healthy Muslims in good health, and only those who are at risk of harm from fasting are exempted from this obligation such as people with non-communicable diseases (NCDs) or other disabling diseases. In the Muslim community, there is an intense desire to participate in fasting, even among those who are eligible for the religious exemption . DespiteThe PubMed and Google Scholar databases were searched. We also used a national online documentation system of the algerian university (SNDL.cerist). The key words used were “Ramadan fasting,” “fasting” and we have associated with each of these word “diabetes,” “NCDs,” “circadian rhythm,” “complications,” “dietary habits,” “physical activity,” “body composition,” “nutritionnal education.” We mainly took the recent and most relevant studies focused on human studies. The Ramadan comes without transition, and practitioners move from one way of life to another overnight. The whole rhythm of everyday life is upset, thus reflecting a reversal of activities characterizing day and night. Normally, people eat during the day, and most socializing activities take place during the day. During Ramadan, the schedule of meals and activities is changed. These changes vary according to the seasons, geographical and socio-economic situations as well specific traditions of each country. In these conditions, the fasting body tries to adapt twice in the space of a month: at the beginning and end of Ramadan . The manp < 0.05). The results of another study carried out on 1,266 diabetic patients showed an average sleep duration between 5 to 8 h in 70.3% of T2DM and 65.5% of T1DM. The same results both for the DMF and DMNF , followed by those treated with oral agents including sulfonylureas as compared to oral agents excluding sulfonylureas   . In para 0.2984) . The pat 0.2984) , 69, 70. 0.2984)  having r 0.2984)  between  0.2984) .Several international recommendations and consensus of experts have resulted in proposals to optimize diabetes management during the month of Ramadan:- The first international recommendations for a good practice of fasting were those of the Hassan II Foundation in Morocco in 1995. This consensus proposed criteria authorizing and prohibiting fasting and reinforced clinical-biological surveillance before, during and after Ramadan, a monitoring of glycemic control, adaptation of treatment, education of diabetics, and their families on the contraindications of fasting, the risk of acute complications and the means of prevention and treatment .- Other recommendations follow those of Morocco, including those of the American Diabetes Association (ADA) published in 2005 . In thes- In 2010 , researc- The third update to the recommendations of the ADA Working Group  was also- In the 2020 update , the res- The International Diabetes Federation (IDF) and the Diabetes and Ramadan (DAR) International Alliance met to provide comprehensive guidance on this topic. This guide  highligh- The update of the IDF-DAR International Alliance Practical Guidelines features new guidance based on a greater and more recent body of evidence . This inIftar) hyperglycemia and also prevent hypoglycaemia during the period of fast. With the use of analoges, these objectives may be met more easily.- In addition, the Asian recommendations of the South Asian Consensus Guideline, where researchers  indicateThe importance of the socio-cultural context of the holy month of Ramadan associated with the culturally-religious identity to which the diabetic patient is or wants to adhere are parameters to be included in the decision to fast. The advice of health professionals and members of religion will only reassure the diabetic in the accuracy of their decision. Each patient must be monitored individually, taking into account in particular the evolution of his disease, his therapeutic treatment, his socio-economic level, his level of education, his age, and his family status.Fasting is a very sensitive period for the glycemic control of DMF and DMNF patients, requiring multidisciplinary preparation and expert advice. This work gave a brief visualization of the effect of Ramadan fasting on a NCDs which is diabetes. The few studies cited reflecting the various points raised  showed heterogeneity of the results found probably due to the number of days of fasting, climatic conditions, cultural variations in eating habits, etc. Some slight advantages were noted. These particularities must be taken into account in the development of any study project on this topic. Effective management of diabetes with regular glycemic control will allow the patient to maintain an appropriate metabolic profile. Education on fasting and diabetes management is useful beyond Ramadan. It is important that recommendations have to be based on the gaps in existing data.MBenc: study design, literature searching, and article draft writing. IS, MBent, and FB: draft revision and literature searching. YB: draft revision. All authors agree to be accountable for the content of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has been characterized by unprecedented rates of spatio-temporal spread. Here, we summarize the main events in the pandemic's timeline and evaluate what has been learnt by the public health community. We also discuss the implications for future public health policy and, specifically, the practice of epidemic control. We critically analyze this ongoing pandemic's timeline and contrast it with the 2002–2003 SARS outbreak. We identify specific areas  wherein the international community learnt valuable lessons from the SARS outbreak. However, we also identify the key areas where international public health policy failed leading to the exponential spread of the pandemic. We outline a clear agenda for improved pandemic control in the future. EPI_ISL_402119 and EPI_ISL_402121)  and later named RaTG13 following the bat species, samples location and year. The institute ignored this sequence when they found it is distantly related to SARS-CoV. In 2018, they decided to sequence as much as possible of the full-length genome from their stock samples which are positive for SARS-related coronavirus. They completed the nearly full-length genome sequence of RaTG13 but didn't publish it. In 2020, after they received the SARS-CoV-2 sequence, the institute compared it with all of their unpublished sequences and found its closest relative RaTG13 (96.2% nucleotide identity), and they then completed the whole genome sequence  was reported from a cluster of patients who were initially linked epidemiologically to the Huanan Seafood Market in Wuhan, China , and the_402121) , and rep_402121) , a findi_402121) . Specifisequence –13.It is clear that both China and the WHO demonstrated dramatically improved responses to COVID-19 with the lessons learned from previous epidemics see . For exaWhile identifying the origin of COVID-19 is essential to prevent the next pandemic , the actDifferent strategies have been implemented to combat the pandemic in different countries. Some countries  initially tried so-called herd immunity by natural infections and some used mitigation or suppression, but in general these approaches had minimal effects on stopping the spread of the disease within and between countries. Generally, most countries across the globe tried to limit the spread of the pathogen through various non-pharmaceutical interventions (NPIs), including the implementation of lockdowns of varying intensity and geographic scope. However, it has been noted that the inadequate  or delayed  implementation of lockdowns could have reduced their efficacy in impeding the spread of infections in many countries . Just asWe have learnt many critical lessons from the ongoing coronavirus pandemic with respect to the requirements for rapid response and large-scale surveillance, as well as the needs for effective and coordinated strategies to control novel pathogens. While there remain many unknowns and uncertainties relating to the control of future pandemics, based on what we learnt from SARS-CoV-2 we make the following recommendations:While pandemics are unpredictable by nature, proper preparation and prior planning can help manage them better. For a long time, coronaviruses have been identified as pathogens with high pandemic potential, and have thus been high on the prioritized preparedness list. Yet the globe was still unprepared to effectively deal with COVID-19. There is no doubt that many of the science-based requirements for pandemic control—rapid identification of the causative agent, genome sequence and determination of the key epidemiological parameters related to transmission—were met, but the global management of the pandemic still failed in many respects. Clearly, science alone cannot control a pandemic. In the long run, active science outreach to the public and policy makers are fundamental to achieving a coordinated implementation of intervention across scales, sectors and population groups . There iBoth China and international communities outside China have learnt the vital need for improved preparedness to rapidly identify and limit the spread of emerging pathogens. Stockpiling of emergency supplies and the logistics of meeting rapidly ramped-up demand was a major bottleneck in the response to COVID-19. From the very beginning medical and public health workers were faced with the shortage of many essential items, including equipment for oxygenation support  and even personal protection equipment . Despite the lesson learnt, there seems to be no practical way to address this issue because there is no easy way to store such supplies in bulk for logistic and economic reasons. Additionally, the next pandemic may be characterized by other symptomatology  rather than respiratory failure. Thus, there is a need to think of creative solutions to address our ability to meet such sudden supply-demand dynamics in the future, and we would like to leave this as an open question to the readers.The WHO has to be given a much stronger role in the coordination of the implementation of the various control-measures. Given the exponential nature of pathogen spread it is imperative that we ensure the rapid mobilization of mitigation and control strategies at international scales before local epidemics can progress to pandemics. The authority of the WHO for global coordination of pandemic responses must be strengthened.There is also an urgent need to address several open questions related to COVID-19, particularly the possible reservoir or intermediate host(s), the role of live-animal markets in introducing or maintaining the virus in the human population. China-WHO Joint Study Group recently spent a month  in Wuhan to investigate the origins of the virus, but with no definitive answers yet. For the whole year of 2020, scientists and public health professionals in China and across the globe have been trying to answer this critical question, but with limited success. For example, it still remains unclear if SARS-CoV-2 differs fundamentally from other coronaviruses  in terms of its epidemiology and entry into the human population . Given tIt is encouraging that shortly after the genome was made publicly available identification of potential vaccine candidates was initiated, with NIH joining up with Moderna Inc. in mid-January . PotentiWhile vaccines are a key component of control, the recent pandemic has also highlighted the fundamental importance of NPIs given their efficacy in reducing viral spread . While tMost importantly, an international scientific conference should be convened, as soon as possible, to discuss not only the biomedical issues related to the pandemic, but also other issues related to pandemic control, such as the effectiveness of the various interventions adopted in different countries  and the The ongoing COVID-19 pandemic caused by SARS-CoV-2 has brought to the fore the devastating societal and economic consequences associated with emerging infectious diseases. Human history has been punctuated by many such global pandemics including the bubonic plague (14th century), the flu (20th century) and HIV/AIDS (20th and 21st century), and it is unlikely that COVID-19 will be the last one. Indeed, the risk of emergence of novel diseases in human populations is increasing at an alarming rate due to numerous factors including the rapid range expansion of disease vectors, destabilization of natural ecosystems, as well as the rapid increase in agriculture and urbanization. By critically comparing the 2002–2003 SARS outbreak and COVID-19 pandemic, we identified that significant strides have been made in terms of rapid pathogen identification and expedited initial outbreak reporting by China, as well as the PHEIC declaration by WHO. However, one of the major failures was the delayed international response to the PHEIC declaration by the WHO, a delay which allowed for the exponential spread of the pandemic. We recommend that these are the critical areas that the international public health community must focus on to better control future pandemics in a highly connected global population. In the end we feel that the most essential lesson we can learn from COVID-19 is that pandemic control hinges on rapid, effective, coordinated and sustained pandemic response at local, national and international levels.NS developed the idea. GD and NS wrote the first draft of the manuscript. GD coordinated input from other authors. All other authors contributed to specific sections, discussed results, and edited the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cardiovascular diseases create an important burden on the public health systems, especially in the elderly, mostly because this group of patients frequently suffer from multiple comorbidities. Accumulating cardiovascular risk factors during their lifetime has a detrimental effect on an older adult‘s health status. The modifiable and non-modifiable cardiovascular risk factors are very diverse, and are frequently in a close relationship with the metabolic comorbidities of the elderly, mainly obesity and Diabetes Mellitus. In this review, we aim to present the most important cardiovascular risk factors which link aging and cardiovascular diseases, starting from the pathophysiological links between these factors and the aging process. Next, we will further review the main interconnections between obesity and Diabetes Mellitus and cardiovascular diseases of the elderly. Lastly, we consider the most important aspects related to prevention through lifestyle changes and physical activity on the occurrence of cardiovascular diseases in the elderly. Cardiovascular disease currently ranks first in terms of global mortality and morbidity . ElderlyRegarding the risk factors for the occurrence of cardiovascular diseases, the most frequent are hypertension , Diabetes Mellitus, dyslipidemia, obesity, smoking and age—these are all factors that are also involved in the development and progression of atherosclerosis ,9.Age is an unchangeable risk factor, also considered an independent risk factor for atherogenesis and for further cardiovascular disease . HoweverIt is assumed that the occurrence of hypertension in older adults could be related to the fact that as physiological aging occurs, a number of changes take place at the vascular level, leading to structural and functional alterations of the vascular walls  . This thAccording to the US Center for Disease Control and the American Association for Prevention and Health, presence of comorbidities in which there is a state of chronic inflammation  and external predisposing factors  in the elderly put them at risk not only of hypertension progression, but also of the occurrence of other cardiovascular conditions ,16. The In the elderly, prevention of cardiovascular disease by physical exercise plays not only a beneficial effect on physical functioning, but also in the amelioration of general quality of life .This review aims to present the main pathophysiological pathways and cardiovascular risk factors linking aging and cardiovascular diseases, to explain the importance of comorbidities and to review physical exercise as a method of prevention needed to diminish the burden of cardiovascular diseases of the elderly on public health systems.Advanced age implies numerous functional cardiac changes, such as systolic and diastolic dysfunctions but also dysfunctions related to the electrical activity of the heart, presenting with different types of arrhythmias . Over tiThe high number of elderly people with cardiovascular pathologies is influenced by the multiple changes that together occur with the aging process. Among the most frequent of these are a high production of oxygen free radicals (OFR), increased oxidative stress, chronic inflammation, apoptotic processes, myocardial degeneration and insulin resistance in diabetic and obese subjects . The levElderly patients with an increased percentage of adipose tissue have considerably more chronic systemic inflammation than elderly subjects with normal body mass indexes (BMIs). The explanation for this might be the ability of the adipose tissue to secrete a number of cytokines , such as resistin, which are capable of initiating and maintaining a state of chronic inflammation and insulin resistance ,25. MoreEnhanced production of proinflammatory factors like cytokines will lead in time to a cardiac remodeling due mainly to the extracellular matrix (ECM) reorganization at the cardiomyocite cellular level. Cardiac remodeling occurs through the cardiac accumulation of collagen fibers, secondary to changes in the expression of the tissue inhibitor of metalloproteinase and matrix metalloproteinase. Metalloproteinases are proteolytic enzymes which, when activated, destroy the ECM; thus an augmented level of metalloproteinase expression will cause a severe degradation of the matrix. The build-up of collagen fibers in the heart engenders hypertrophy of the heart muscle and eventually cardiac fibrosis ,28. A stNormal cardiac metabolism is dependent on an adequate production of mitochondrial ATP; in the elderly, the excessive production of OFR, secondary to increased oxidative stress, impedes the normal function of mitochondria, which will resolute in cardiac dysfunction ,30. A stAnother mechanism by which oxidative stress exerts a negative effect on the normal functionality of the heart muscle cell is by disrupting the ryanodine type 2 receptor, the main receptor involved in the release of calcium from the sarcoplasmic reticulum . Since cMitochondrial damage due to an increased production of OFR is involved in the development of atherosclerosis by accelerated oxidation of plasma lipids. This was demonstrated in 2018 by an experimental study on a group of elderly mice, which were fed a diet rich in unsaturated fats (omega 6) . The autIn addition to the events encountered in the physiological phenomenon of aging that can lead to cardiovascular diseases , there are many pathological conditions that lead to the precipitation of cardiovascular events, their occurrence not being strictly related to the consequences of aging or the frailty which an older adult presents. As previously mentioned, the most common pathological conditions that risk the occurrence of cardiovascular disease are Diabetes Mellitus and obesity .There are many common pathophysiological pathways both for the risk factors for cardiovascular disease and for the actual cardiovascular conditions . These associations have many other triggers or molecular consequences which are both intricate and difficult to properly quantify when designing clinical studies on the elderly ,25,27,36A synthesized scheme of the interactions between the key actors that might explain the association between aging and cardiovascular disease is presented below  reported an impressive increase in the incidence of diabetes: the number of patients diagnosed with this disease is 4 times higher (422 million adults) than in 1980. It is also estimated that the number of cases diagnosed by 2045 will exceed 692 million ,39.Type 2 Diabetes Mellitus (T2DM) is the most common form, with approximately 90% of patients diagnosed with diabetes having type 2, and over 95% of them being over 60 years old. The substrate of this pathology is an increased insulin resistance, the end result being a state of chronic hyperglycemia . In the The vast majority of patients diagnosed with T2DM have obesity, or their percentage of body fat is higher, being predominantly distributed in the abdomen; however, at the same time, obesity is considered an important risk factor in the occurrence of T2DM . Mokdad The presence of hyperglycemia, chronic inflammation and metabolic changes in diabetes puts the body under increased oxidative stress .Chronic hyperglycemia, associated with other metabolic changes encountered in diabetes, predisposes the body to a series of injuries to various organs and systems, producing life-threatening complications for patients . Among tCardiovascular diseases in patients diagnosed with diabetes can materialize either in the form of hypertension, ischemic heart disease, heart failure or diabetic cardiomyopathy (DC) . The latNecropsy studies performed in patients diagnosed with diabetes who died suddenly, showed structural myocardial changes representative of DC, i.e., a decrease in the number of cardiac muscle cells due to the processes of necrosis and apoptosis, changes in parasympathetic/sympathetic innervation, hypertrophy of the remaining cardiomyocytes and changes in microcirculation, but also the presence of excess amount of interstitial tissue ,54,55.From an echocardiographic point of view, the presentation of diabetic cardiomyopathy can be in the form of severe diastolic and systolic dysfunction (taking the form of dilated cardiomyopathy) or isolated diastolic or systolic dysfunction, but it can also emerge as an isolated left ventricular hypertrophy .Other cardiovascular complications in diabetic elderly patients, such as strokes, unstable angina pectoris and acute myocardial infarction—which are complications secondary to diabetic microangiopathy—are more common among patients with long-term diabetes or patients with unbalanced T2DM. Due to the presence of diabetic neuropathy in these elderly patients, another manifestation of cardiovascular disease may be in the form of silent ischemic events .Although the occurrence of T2DM in the elderly has a slightly higher incidence among males, some studies have shown that in the case of elderly women who have been diagnosed with T2DM, the risk of developing cardiovascular disease such as heart failure is higher compared to men, with an increasing mortality due to coronary heart disease . StudiesRegarding the mortality from cardiovascular diseases in diabetic patients, there is an increased level of evidence which states that an increased serum level of inflammatory markers is associated with a significant increase in mortality ,61. ThusRecent work has revealed that the risk of cardiovascular disease in people over 63–65 years, could be attributed, among other things, to the presence of a protein, namely fetuin A. Fetuin A is a glycoprotein belonging to the class of fetuins, synthesized in the liver and in adipocytes performing carrier protein functions . The higAs mentioned before, age plays a role as an individual risk factor for cardiovascular diseases, because, with an advancement in age, the appearance of conditions such as obesity and T2DM becomes more common. As in the case of diabetic patients, patients with obesity can associate a status of chronic inflammation and increased oxidative stress .The cardiovascular risks to an elderly patient with an increased BMI are largely influenced by blood glucose levels, plasma cholesterol levels and the presence or absence of hypertension . HoweverIn light of these data, BMI should be considered an individual risk factor in the occurrence of cardiovascular disease in elderly patients and beyond . To suppOther studies have shown that the association between the advanced age of patients and the presence of excessive abdominal obesity predisposes patients to a much greater risk of developing atherosclerotic cardiovascular disease, through mechanisms incompletely elucidated so far. The same team reported that an equivalent or superunit ratio between the waist of elderly patients and their height increases the risk of cardiovascular disease by approximately 5% ,73.Regarding the gender difference, a slightly higher incidence of cardiovascular disease was observed among older women. This difference has been attributed to the presence of menopause among females, due to hormonal changes, especially due to decreased levels of estrogen hormones, which will increase the risk of metabolic syndrome and increase the number of complications among older, obese women at menopause ,75.Among the most daunting cardiovascular diseases, with potential life-threatening complications in the elderly, is the stroke. Stroke is one of the main causes of hospitalization, disability and death among elderly patients; cerebrovascular pathologies represent at the same time a risk factor in the development of vascular dementia ,77.When it comes to the prevention of strokes among older adults, several issues need to be addressed : firstlyBlood pressure values are especially important in elderly patients at risk of developing a stroke, because it is known that high blood pressure is the most important risk factor in the occurrence of a stroke . AlthougAlthough it is not yet known what the optimal blood pressure values would be to prevent strokes in patients over the age of 70, at present there is consistent evidence that a decrease in blood pressure in elderly hypertensive patients also reduces the risk of a stroke .In terms of lifestyle, one of the most harmful behaviors is smoking. Smoking is a very important risk factor when it comes to strokes. It is estimated that a smoker has an approximately 3–5 times higher risk of developing a stroke compared to a non-smoking elderly adult . The WorIn the case of elderly patients who have smoked, who suffered a stroke, and then gave up smoking, a decrease in the risk of a new cerebrovascular event was observed in approximately 15% of cases .It is well known that a balanced diet is extremely important for all age groups. The American Heart Association (AHA) supports and recommends the adoption of a Mediterranean diet, high in fruits and vegetables, grains, fiber and white meat (fish), to reduce the risk of stroke . PhysicaCoronary heart disease includes several conditions, such as acute myocardial infarction, coronary artery failure and unstable angina pectoris. These conditions are among the leading causes of mortality and morbidity among elderly patients. However, age predisposes to coronary heart disease regardless of the presence or absence of other risk factors. Nonetheless, in the presence of additional risk factors, such as family history of coronary heart disease, menopause, dyslipidemia, sedentary lifestyle, tobacco use, the presence of obesity or T2DM, an incidence of coronary heart disease of up to 25% higher was observed .Regarding the prevention of coronary artery disease, it is known that in the case of hypertensive patients, especially in the elderly, effective antihypertensive medication diminishes the risk of coronary heart disease or a stroke .Smoking or tobacco use in any form is strongly associated with the appearance of many pathologies, such as malignancies and cardiovascular diseases, especially coronary heart disease and acute myocardial infarction. A study performed on a group of patients who were over 65 years of age, had coronary artery disease and smoked showed that the mortality of these patients was 23–30% higher compared to the control group consisting of elderly patients with coronary heart disease but who did not smoke . In the Regarding dietary measures, the debate is still ongoing about the benefits of certain dietary interventions in the prevention of coronary heart disease. The most studied measure, the Mediterranean diet, proved a useful protector against ischemic heart disease occurrence. However, randomized studies have established that replacing saturated fats with vegetable oils rich in linoleic acid lowered serum cholesterol levels, but without a concurrent reduction regarding the risk of death from ischemic coronary heart disease .Physical activity reduces the risk of coronary heart disease in older adults. A study conducted in the Netherlands on patients aged 65–70 years concluded that even housework or cycling reduces the risk of coronary events and death from coronary heart disease .Regarding lipid-lowering agents, a body of evidence suggested that statins administered for primary prevention in patients aged 65 to 74 years (with hypertension and moderate dyslipidemia) do not confer any benefits, and in patients over 75 years, the benefits are insignificant . HoweverPeripheral arterial disease is characterized by gradual and chronic narrowing of the arterial lumen, which results in inadequate and inefficient irrigation of tissues. Clinical manifestations are characterized by acute or chronic ischemia, translated as pain in the territory served by the artery, with reduced lumen, functional impotence and, finally, the occurrence of tissue necrosis .The frequency of peripheral arterial diseases increases with age, so that at the age of 80–90 years, the incidence of this pathology peaks, being about 15–20% higher than in other age groups. Due to the most often silent and prolonged development of peripheral vascular disease, patients go to the doctor in the final stages of the disease, the only solution for them usually being amputation. Among the risk factors in its occurrence in addition to age are tobacco use, dyslipidemia, neglected hypertension and diabetes .As is the case for the aforementioned pathologies, a good control of hypertension, diabetes, smoking cessation and a diet rich in fiber of plant origin are the keys to success in terms of peripheral arterial disease .In patients who have developed this condition, lifestyle changes, smoking cessation, exercise  and treatment with statins can lead to a slowdown in the pathophysiological process and a slight improvement in the quality of life of these patients . AdditioIn elderly people with peripheral artery disease, which is often associated with hypertension and ischemic heart disease, a key factor which ameliorates the quality of life is good treatment adherence. Non-adherence to treatment in the elderly can lead to further aggravation of their physical or mental symptoms, together with a further burden on health systems and caregivers .Cardiovascular disease prevention in the general population, and especially in older adults, starts from lifestyle modification . BecauseTo prevent cardiovascular disease not just in elderly patients, but in all age groups, it is recommended to avoid a sedentary lifestyle and to exercise within the limits of individual tolerance . There iIt is common knowledge that physical exercise has a positive impact on improving health and quality of life. In the elderly, regular exercise can exert an important contribution in reducing falls, maintaining good physical function and maintaining a good quality of life .There are multiple studies that aimed to establish the mechanisms by which physical activity has a positive impact on health status of the elderly, the benefits being already reviewed since the early 2000s . BesidesThe cardiovascular benefits gained by the elderly due to regular physical exercise are also linked with an increased general quality of life, because it is proven at present that wellbeing and cognitive functioning are also improved in the elderly who exercise regularly .The effects of physical exercise on cardiovascular risk factors and the quality of life of the elderly are highlighted in the following figure .The key principles of the recommended physical activity in older adults are the following: the preferred exercises are aerobic ones, which need to be supplemented by balance, strengthening and flexibility exercises . Both th® elastic bands), lifting weights (even carrying shopping bags) or yoga and Pilates exercises [Many studies emphasize that there should not exist an ideal exercise to be prescribed in a certain profile of the older adult, because it was shown that even modest levels of physical activity offer benefits in terms of cardiovascular risk, compared to being completely inactive . To datexercises ,115. Oldxercises .Unfortunately, during the COVID-19 pandemic, older adults have suffered a further reduction of physical exercise, due to social distancing. At present, there is low to moderate evidence that mobile or internet-delivered  interventions may be efficient in promoting and increasing the levels of physical activity in the elderly .Regardless of the exercise performed, whether it is running or walking, many studies have reported that during the active contraction of striated muscles, there is an increase in the translocation of type 4 glucose transporter (GLUT4) from the cytoplasm of striated muscle cells, the result being the promotion of blood glucose absorption, thus improving insulin resistance; this mechanism is known to play a major role in the development of T2DM ,119. AftAs previously mentioned, high blood pressure predisposes a person to cardiovascular disease, as well as complications such as acute myocardial infarction, heart failure or stroke . FollowiStudies which determined the beneficial effect of physical activity on blood pressure proved that physical activity maintained over a long period of time leads to a decrease in systolic blood pressure by about 5 mmHg, and a reduction in diastolic blood pressure by about 3.5 mmHg. It is well known that a reduction in systolic blood pressure values by 2–3 mmHg decreases the risk of death secondary to a stroke by about 5%, and secondary to an acute coronary episode by 3–4%. However, the decrease in blood pressure is a transient one, which is why performing physical exercises, such as walking, must be performed daily ,124. Nonetheless, when performing exercises of much higher intensity, and without these being adjusted to age and muscle mass, opposite effects occur, namely increased vasoconstrictor activity, an increase in oxidative stress and an increase in blood pressure. Because of these observations, light physical activity is recommended at present for the elderly, such as walking for 30 min daily .In conclusion, cardiovascular diseases remain a major cause of disability or mortality among elderly patients, age being a major risk factor in their occurrence. This role is accentuated by the increased probability that, in the case of this category of patients, and in addition to old age and frailty, there is an impressive number of other factors, such as obesity, smoking, sedentary lifestyle or pathologies such as diabetes mellitus and hypertension.However, as mentioned above, in the case of accumulating risk factors, their detection and treatment is crucial in the subsequent evolution of these patients. By treating them, changing their lifestyle and exercising regularly, the occurrence of cardiovascular diseases can be delayed or their progression might be slowed down.Physical activity plays an important role in maintaining a good physical functioning and improving the quality of life of the elderly. Better-designed studies are needed to evaluate the particularities of each specific clinical setting, in order to help doctors to prescribe a tailored schedule of physical activity for a certain type of patient.


The aim of this document is to share the action plan from the young Italian Association of Radiotherapy and Clinical Oncology (yAIRO). We believe it is important to enhance a constructive dialog between societies. The hope is to offer to young radiation oncologists a wealth of opportunities to refine their skills and gain access to the latest developments, according to a shared European vision. The Young Italian Association of Radiotherapy and Clinical Oncology (yAIRO) represents the young radiotherapy community in Italy. It consists of Italian radiation oncologists and residents younger than 40 years. yAIRO’s primary aim is to develop and foster high-level educational, scientific and professional measures in the field of radiation oncology for young members. Considerable agreement has been reached in the yAIRO committee to support needs, priorities and expectations of residents and junior radiation oncologists at the early stages of their careers.Among the others, the yAIRO steering committee has the responsibility to ensure that the scientific and educational proposals of the next generation of clinicians and scientists are carefully evaluated by the designated governance organs.In line with the purpose of ESTRO Young, yAIRO provides a networking platform for young professionals; is responsible for the annual congress young session; collaborates with homologous national and international societies and plans educational activities and meetings.With the intent to fully align yAIRO to the ESTRO 2030 vision , our ambThe start point is the ESTRO core set of the four “good” elements : (i) gooThe yAIRO committee includes six members: the coordinator, the past-coordinator and four councilors. The yAIRO committee has defined new inputs to refresh the content of yAIRO program with the aim to guarantee high-value radiation therapy landscape throughout the young Italian community. A first proposal was written after a literature revision until December 2020.A virtual meeting was organized to discuss the initial document. At the end of the virtual meeting, feedback from all members was incorporated to create the final program.The topics considered of highest importance were grouped in four focus groups, corresponding to the four “good” ESTRO elements . Once yAn = 134 in 2020) and young in-training professionals receive first year free AIRO membership in order to introduce them in our national society and scientific community.Although the number of new residents in radiation oncology is considerable every year in Italy  how to structure and write a scientific paper for radiation oncology subspecialty, (ii) how to organize and fill in a clinical database, design a research project, apply for ethical approval and document results, (iii) assessment and management of work-related stress risk, (iv) share national and international experiences.This format will give a valid opportunity to brainstorm freely and potentially build a network with in-training, young radiation oncologists and researchers throughout Italy.In addition, each workshop’s group will be invited to submit a contribution that includes key points arising from the workshop, as well as current situation, perceived problems, research directions, next steps, potential recommendations. The format might be any combination of overview, editorials or systematic review.The yAIRO online educational library will be further improved, expanded and promoted.A dedicated yAIRO video program will be set up, aiming to provide educational online contents that show and discuss the availability and the cost-benefits of the radiotherapy technologies active across the different Italian departments, presenting the state of the art of our discipline in the country.The hope is to open a new window to this direction with a useful and efficient hub of the students/young members’ needs and expectation across Italy, reducing technological distances and efficaciously transferring knowledge and facilitating career development.Young members are invited to take an active part in the yAIRO initiatives: Their contribution can be addressed to the yAIRO Journal Club, that promotes the writing of reviews and comments on relevant, practice changing, scientific articles, or collaborating to the re-organization and update of the yAIRO website.Furthermore, in order to improve the communication of news to the members, the participation of yAIRO on the main social media platforms is encouraged.Advances in radiation oncology, both technological and clinical, have been extremely rapid in the last years and these changes have had a profound impact on the field. The development of scientific resources, including policy statements and documentation such as AIRO guidelines, core curricula, educational publications, conference proceedings and patients advocacy documents, requires a higher level of expertise. yAIRO will make every effort to reinforce analysis of scientific evidence and decision-making process in useful forms and actionable formats.Clinical evidence is not static; therefore, an evolutionary process should be provided.A documentation checklist, easily accessible on the website, should be useful to provide a quick-reference material with the latest news on consensus conferences, recommendations and key information. Strategic involvement of young members in specific committees, task groups and special meetings organized by the AIRO society will be promoted.At present, the concept of good partnership is strictly linked to multidisciplinary management. The increasingly complex multimodal treatments necessitate a close and a well-coordinated collaboration among specialists and to collaborate with other educational groups to increase multidisciplinary perspectives is therefore paramount. yAIRO is conscious of the importance of solid collaboration across disciplines and sectors. The purpose is to establish closer collaboration with other young national and international societies in the oncology field.Steps will be made to promote this strategy.yAIRO will facilitate its members to create collaborations, design clinical studies and support collaborative research in order to promote exchange of ideas, development of new inter- and intra-disciplinary networks and disseminate guidelines.The magnitude of this task makes it unrealistic for yAIRO to tackle it alone and appropriate countermeasures to implement innovation, creativity, organization and open approach to data sharing should be taken at a national level to make it possible. An interdisciplinary vision, involving medical, statistical and social sciences, engineering and economics should be facilitated at best.Finally, yAIRO could play a crucial role in bridging AIRO with the other medical societies to forge a strong partnership and improve the performance of the future AIRO members at national and international level.We believe that this document will assist all yAIRO members to collectively support the future priorities that will influence the direction of yAIRO’s activities at a national and international level in the forthcoming years.