Caffeine intake in Hungary – A population based estimation

Caffeine is a bitter, white crystalline xanthine alkaloid that is synthesized in different parts of more than 60 plant species. In a previous study, caffeine content of 377 food samples obtained from the Hungarian market was measured by a validated HPLC technique. These analytical data were built up into a food composition database called NutriComp. Dietary caffeine intake of the Hungarian population was estimated based on the data of the National Nutritional Status Survey 2009. Daily caffeine intake of Hungarian adult males and females were 147±6.2 mg per capita (95% CI: 135–160), and 138±4.2 mg per capita (95% CI: 129–147), respectively. There was no significant difference between genders. The oldest men and women consumed significantly less caffeine than the people between 35–64 years of age. The main sources of caffeine are coffee and tea with 58–59%, and 35–37% of the total intake in men and women, respectively

Inequalities in education and national income are associated with poorer diet: pooled analysis of individual participant data across 12 European countries

Background: Malnutrition linked to noncommunicable diseases presents major health problems across Europe. The World Health Organisation encourages countries to conduct national dietary surveys to obtain data to inform public health policies designed to prevent noncommunicable diseases. Methods: Data on 27334 participants aged 19-64y were harmonised and pooled across national dietary survey datasets from 12 countries across the WHO European Region. Weighted mean nutrient intakes were age-standardised using the Eurostat 2013 European Standard Population. Associations between country-level Gross Domestic Product (GDP) and key nutrients and nutrient densities were investigated using linear regression. The potential mitigating influence of participant-level educational status was explored. Findings: Higher GDP was positively associated with total sugar intake (5·0% energy for each 10% increase in GDP, 95% CI 0·6, 9·3). Scandinavian countries had the highest vitamin D intakes. Participants with higher educational status had better nutritional intakes, particularly within lower GDP countries. A 10% higher GDP was associated with lower total fat intakes (-0·2% energy, 95% CI -0·3, -0·1) and higher daily total folate intakes (14µg, 95% CI 12, 16) in higher educated individuals. Interpretation: Lower income countries and lower education groups had poorer diet, particularly for micronutrients. We demonstrate for the first time that higher educational status appeared to have a mitigating effect on poorer diet in lower income countries. It illustrates the feasibility and value of harmonising national dietary survey data to inform European policy regarding access to healthy diets, particularly in disadvantaged groups. It specifically highlights the need for strong policies supporting nutritional intakes, prioritising lower education groups and lower income countries

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Substantial variation across geographic regions in the obesity prevalence among 6–8 years old Hungarian children (COSI Hungary 2016)

Abstract Background There have been previous representative nutritional status surveys conducted in Hungary, but this is the first one that examines overweight and obesity prevalence according to the level of urbanization and in different geographic regions among 6–8-year-old children. We also assessed whether these variations were different by sex. Methods This survey was part of the fourth data collection round of World Health Organization (WHO) Childhood Obesity Surveillance Initiative which took place during the academic year 2016/2017. The representative sample was determined by two-stage cluster sampling. A total of 5332 children (48.4% boys; age 7.54 ± 0.64 years) were measured from all seven geographic regions including urban (at least 500 inhabitants per square kilometer; n = 1598), semi-urban (100 to 500 inhabitants per square kilometer; n = 1932) and rural (less than 100 inhabitants per square kilometer; n = 1802) areas. Results Using the WHO reference, prevalence of overweight and obesity within the whole sample were 14.2, and 12.7%, respectively. According to the International Obesity Task Force (IOTF) reference, rates were 12.6 and 8.6%. Northern Hungary and Southern Transdanubia were the regions with the highest obesity prevalence of 11.0 and 12.0%, while Central Hungary was the one with the lowest obesity rate (6.1%). The prevalence of overweight and obesity tended to be higher in rural areas (13.0 and 9.8%) than in urban areas (11.9 and 7.0%). Concerning differences in sex, girls had higher obesity risk in rural areas (OR = 2.0) but boys did not. Odds ratios were 2.0–3.4 in different regions for obesity compared to Central Hungary, but only among boys. Conclusions Overweight and obesity are emerging problems in Hungary. Remarkable differences were observed in the prevalence of obesity by geographic regions. These variations can only be partly explained by geographic characteristics. Trial registration Study protocol was approved by the Scientific and Research Ethics Committee of the Medical Research Council (61158–2/2016/EKU)

Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI)

Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI) has resulted in a surveillance system which provides regular, reliable, timely, and accurate data on children's weight status—through standardized measurement of bodyweight and height—in the WHO European Region. Additional data on dietary intake, physical activity, sedentary behavior, family background, and school environments are collected in several countries. In total, 45 countries in the European Region have participated in COSI. The first five data collection rounds, between 2007 and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI, data are collected according to a common protocol, using standardized instruments and procedures. The systematic collection and analysis of these data enables intercountry comparisons and reveals differences in the prevalence of childhood thinness, overweight, normal weight, and obesity between and within populations. Furthermore, it facilitates investigation of the relationship between overweight, obesity, and potential risk or protective factors and improves the understanding of the development of overweight and obesity in European primary-school children in order to support appropriate and effective policy responses

Breast and other cancer dormancy as a therapeutic endpoint: speculative recombinant T cell receptor ligand (RTL) adjuvant therapy worth considering?

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Most individuals who died of trauma were found to harbour microscopic primary cancers at autopsies. Surgical excision of the primary tumour, unfortunately, seems to disturb tumour dormancy in over half of all metastatic relapses. PRESENTATION OF THE HYPOTHESIS: A recently developed immune model suggested that the evolutionary pressure driving the creation of a T cell receptor repertoire was primarily the homeostatic surveillance of the genome. The model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected T cell receptors and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. The repertoire is maintained by continuous peripheral stimulation via soluble forms of self-peptide-presenting major histocompatibility complex molecules governed by the law of mass action. The model states that foreign peptides inhibit the complementary interactions between the major histocompatibility complexes and T cell receptors. Since the vast majority of clinically detected cancers present self-peptides the model assumes that tumour cells are, paradoxically, under homeostatic T cell control.The novelty of our hypothesis therefore is that resection of the primary tumour mass is perceived as loss of 'normal' tissue cells. Consequently, T cells striving to reconstitute homeostasis stimulate rather than inhibit the growth of dormant tumour cells and avascular micrometastases. Here we suggest that such kick-start growths could be prevented by a recombinant T cell receptor ligand therapy that modifies T cell behaviour through a partial activation mechanism. TESTING THE HYPOTHESIS: The homeostatic T cell regulation of tumours can be tested in a tri-transgenic mice model engineered to express potent oncogenes in a doxycycline-dependent manner. We suggest seeding dissociated, untransformed mammary cells from doxycycline naïve mice into the lungs of two mice groups: one carries mammary tumours, the other does not. Both recipient groups to be fed doxycycline in order to activate the oncogenes of the untransformed mammary cells in the lungs, where solitary nodules are expected to develop 6 weeks after injection. We expect that lung metastasis development will be stimulated following resection of the primary tumour mass compared to the tumour-free mice. A recombinant T cell receptor ligand therapy, starting at least one day before resection and continuing during the entire experimental period, would be able to prevent the stimulating effect of surgery. IMPLICATIONS OF THE HYPOTHESIS: Recombinant T cell receptor ligand therapy of diagnosed cancer would keep all metastatic deposits microscopic for as long as the therapy is continued without limit and could be pursued as one method of cancer control. Improving the outcome of therapy by preventing the development of metastases is perhaps achievable more readily than curing patients with overt metastases

Socioeconomic differences in food habits among 6- to 9-year-old children from 23 countries-WHO European Childhood Obesity Surveillance Initiative (COSI 2015/2017)

Background: Socioeconomic differences in children's food habits are a key public health concern. In order to inform policy makers, cross-country surveillance studies of dietary patterns across socioeconomic groups are required. The purpose of this study was to examine associations between socioeconomic status (SES) and children's food habits. Methods: The study was based on nationally representative data from children aged 6-9 years (n = 129,164) in 23 countries in the World Health Organization (WHO) European Region. Multivariate multilevel analyses were used to explore associations between children's food habits (consumption of fruit, vegetables, and sugar-containing soft drinks) and parental education, perceived family wealth and parental employment status. Results: Overall, the present study suggests that unhealthy food habits are associated with lower SES, particularly as assessed by parental education and family perceived wealth, but not parental employment status. We found cross-national and regional variation in associations between SES and food habits and differences in the extent to which the respective indicators of SES were related to children's diet. Conclusion: Socioeconomic differences in children's food habits exist in the majority of European and Asian countries examined in this study. The results are of relevance when addressing strategies, policy actions, and interventions targeting social inequalities in children's diets.The authors gratefully acknowledge support from a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. Data collection in the countries was made possible through funding from Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health; Bulgaria: Ministry of Health, National Center of Public Health and Analyses, WHO Regional Office for Europe; Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe; Czechia: Ministry of Health of the Czech Republic, grant nr. AZV MZČR 17-31670 A and MZČ–VO EÚ 00023761; Denmark: Danish Ministry of Health; Georgia: WHO; Ireland: Health Service Executive; Italy: Ministry of Health and Italian National Institute of Health; Kazakhstan: Ministry of Health of the Republic of Kazakhstan and WHO Country Office; Kyrgyzstan: World Health Organization; Latvia: Ministry of Health, Centre for Disease Prevention and Control; Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO; Malta: Ministry of Health; Montenegro: WHO and Institute of Public Health of Montenegro; Norway: Ministry of Health and Norwegian Institute of Public Health; Poland: National Health Programme, Ministry of Health; Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS); Romania: Ministry of Health; Russian Federation: WHO; San Marino: Health Ministry, Educational Ministry; Serbia: This study was supported by the World Health Organization (Ref. File 2015-540940); Spain: Spanish Agency for Food Safety and Nutrition (AESAN); Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection; Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health; Turkey: Turkish Ministry of Health and World Bank. The CO-CREATE project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 774210.info:eu-repo/semantics/publishedVersio

Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI)

Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI)has resulted in a surveillance system which provides regular, reliable, timely, andaccurate data on children's weight status—through standardized measurement ofbodyweight and height—in the WHO European Region. Additional data on dietaryintake, physical activity, sedentary behavior, family background, and schoolenvironments are collected in several countries. In total, 45 countries in the EuropeanRegion have participated in COSI. The first five data collection rounds, between 2007and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI,data are collected according to a common protocol, using standardized instrumentsand procedures. The systematic collection and analysis of these data enables inter-country comparisons and reveals differences in the prevalence of childhood thinness,overweight, normal weight, and obesity between and within populations. Furthermore,it facilitates investigation of the relationship between overweight, obesity, and poten-tial risk or protective factors and improves the understanding of the development ofoverweight and obesity in European primary-school children in order to supportappropriate and effective policy responses.The authors gratefully acknowledge support through a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. The ministries of health of Austria, Croatia, Greece, Italy, Malta, Norway, and the Russian Federation provided financial support for the meetings at which the protocol, data collection procedures, and analyses were discussed. Data collection in countries was made possible through funding from the following: Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health. Austria: Federal Ministry of Labor, Social Affairs, Health and Consumer Protection of Austria. Bulgaria: Ministry of Health, National Center of Public Health and Analyses, and WHO Regional Office for Europe. Bosnia and Herzegovina: WHO country office support for training and data management. Croatia: Ministry of Health, Croatian Institute of Public Health, and WHO Regional Office for Europe. Czechia: Ministry of Health of the Czech Republic, grant number 17-31670A and MZCR—RVO EU 00023761. Denmark: Danish Ministry of Health. Estonia: Ministry of Social Affairs, Ministry of Education and Research (IUT 42-2), WHO Country Office, and National Institute for Health Development. Finland: Finnish Institute for Health and Welfare. France: Santé publique France (the French Agency for Public Health). Georgia: WHO. Greece: International Hellenic University and Hellenic Medical Association for Obesity. Hungary: WHO Country Office for Hungary. Ireland: Health Service Executive. Italy: Ministry of Health. Kazakhstan: Ministry of Health of the Republic of Kazakhstan, WHO, and UNICEF. Kyrgyzstan: World Health Organization. Latvia: Ministry of Health and Centre for Disease Prevention and Control. Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO. Malta: Ministry of Health. Montenegro: WHO and Institute of Public Health of Montenegro. North Macedonia: Government of North Macedonia through National Annual Program of Public Health and implemented by the Institute of Public Health and Centers of Public Health; WHO country office provides support for training and data management. Norway: the Norwegian Ministry of Health and Care Services, the Norwegian Directorate of Health, and the Norwegian Institute of Public Health. Poland: National Health Programme, Ministry of Health. Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates, and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS). Romania: Ministry of Health. Russian Federation: WHO. San Marino: Health Ministry, Educational Ministry, and Social Security Institute and Health Authority. Serbia: WHO and the WHO Country Office (2015-540940 and 2018/873491-0). Slovakia: Biennial Collaborative Agreement between WHO Regional Office for Europe and Ministry of Health SR. Slovenia: Ministry of Education, Science and Sport of the Republic of Slovenia within the SLOfit surveillance system. Spain: Spanish Agency for Food Safety and Nutrition. Sweden: Public Health Agency of Sweden. Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection. Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health. Turkey: Turkish Ministry of Health and World Bank.info:eu-repo/semantics/publishedVersio

Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified