Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Estudos sobre a S-palmitoilação de proteínas em Trypanosoma cruzi

Submitted by Repositório Arca ([email protected]) on 2019-03-07T12:08:29Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Manoel Barata ([email protected]) on 2019-04-29T19:02:48Z (GMT) No. of bitstreams: 2 Tese_Cassiano_Martin.pdf: 4713961 bytes, checksum: 6a9ac28ce2c5cf3e15e20950fad351cf (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-04-29T19:02:48Z (GMT). No. of bitstreams: 2 Tese_Cassiano_Martin.pdf: 4713961 bytes, checksum: 6a9ac28ce2c5cf3e15e20950fad351cf (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.S-palmitoilação é uma modificação proteica pós-traducional que consiste na adição de ácido palmítico a resíduos de cisteína através de ligação tioéster, regulando assim a localização subcelular e função das proteínas palmitoiladas, principalmente a inserção em membranas por conferir hidrofobicidade. Objetivo desta tese foi realizar um estudo global da S-palmitoilação em Trypanosoma cruzi. Análise in silico identificou 15 proteínas contendo o motivo DHHC ou DHYC em um domínio rico em císteína, além de regiões transmembrana, indicando que estas proteínas podem ser DHHC palmitoil transferases (PATs) de T. cruzi. Os genes codificantes para estas proteínas (TcPATs 1-15) foram identificados e amplificados por PCR, exceto para TcPAT1 (TcHIP, já caracterizada) e TcPAT6 (negativa no PCR). Formas epimastigotas foram transfectadas para expressar PATs fusionadas à etiqueta FLAG e a localização subcelular foi examinada por microscopia de fluorescência, sendo a maioria localizada na região anterior do parasita, próximo ao cinetoplasto, compatível com complexo de Golgi, bolsa flagelar e/ou vacúolo pulsátil. A mesma estratégia identificou duas palmitoil tioesterases (PPTs) em T. cruzi, ambas com localização dispersa por todo o corpo do parasita. Também foi desenvolvida uma metodologia de isolamento de amastigotas intracelulares por cavitação, os quais foram utilizados em ensaios de endocitose, tratamento com um inibidor de S-palmitoilação (2-BP) e palmitoil proteômica. Incubação de diferentes formas de T. cruzi com 2-BP interferiu em diversos eventos biológicos (morfologia, endocitose, diferenciação e infecção in vitro), indicando que S-palmitoilação é uma modificação bioquímica importante para o parasita. Ensaios por Acyl Biotinyl Exchange (ABE) em epimastigotas permitiram obter dados sobre a palmitoil proteômica de T. cruzi (abordagem PalmPISC), sendo identificadas 3097 proteínas, das quais 466 (15%) de alta confidencia (p<0,01). Destas, 35% (152) tinham função desconhecida e 13% (59) eram de metabolismo. Estes dados podem auxiliar na compreensão da função da S-palmitoilação em T. cruzi, uma vez que diversas proteínas de interesse podem estar palmitoiladas e envolvidas em importantes vias metabólicas, tais como endocitose, sinalização celular e movimento flagelar.S-palmitoylation is an important post-translational protein modification consisting in addition of palmitic acid to cysteine residues, thus allowing the subcellular localization and function of palmitoylated proteins to be regulated, principally by inserting these proteins in membrane by hydrophobicity assembly. Aim of this thesis was to perform a global study of Spalmitoylation in Trypanosoma cruzi, the etiologic agent of Chagas disease. In silico analysis allowed to identify 15 proteins containing the DHHC or DHYC motifs in a cysteine-rich domain, in addition to transmembrane regions, thus indicating that these proteins may be PATs of T. cruzi. Genes encoding these proteins (TcPATs 1 to 15) were identified and amplified by PCR, except for TcPAT1 (TcHIP, already characterized) and TcPAT6 (negative on PCRs). T. cruzi epimastigotes were transfected to super-express the PATs fused to FLAG tags and the subcellular location of PATs was determined by fluorescence microscopy, most of them showing localization in the anterior region of the parasite, close to the kinetoplast, compatible with Golgi complex, flagellar pocket or contractile vacuole. The same strategy was used identify two palmitoyl thioesterases (PPTs) in T. cruzi, both with subcellular location dispersed throughout the body of the parasite. A methodology was developed to isolate intracellular amastigotes by cavitation and these parasites were used in endocytosis assays, treatment with 2-bromopalmitate (2-BP, an S-palmitoylation inhibitor) and palmitoyl proteomics. Incubation of different T. cruzi developmental forms with 2-BP affected several biological events (morphology, endocytosis, differentiation and infection in vitro), indicating that palmitoylation is an important modification for the parasite. Acyl Biotinyl Exchange (ABE) assays in epimastigotes allowed to obtain data on the palmitoyl proteomic (PalmPISC approach) of T. cruzi, with 3097 proteins identified, 466 of them (15%) of high confidentiality (p <0.01). From these, 35% (152) had unknown function, and 13% (59) were part of metabolic pathways. The data could help future studies aiming to characterizae the Spalmitoylation function in T. cruzi, since several target proteins could be palmitoylated and involved in important metabolic pathways, such as endocytosis, cell signaling and flagellar movement

Treatment of Trypanosoma cruzi with 2-bromopalmitate alters morphology, endocytosis, differentiation and infectivity

Abstract Background The palmitate analogue 2-bromopalmitate (2-BP) is a non-selective membrane tethered cysteine alkylator of many membrane-associated enzymes that in the last years emerged as a general inhibitor of protein S-palmitoylation. Palmitoylation is a post-translational protein modification that adds palmitic acid to a cysteine residue through a thioester linkage, promoting membrane localization, protein stability, regulation of enzymatic activity, and the epigenetic regulation of gene expression. Little is known on such important process in the pathogenic protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. Results The effect of 2-BP was analyzed on different developmental forms of Trypanosoma cruzi. The IC50/48 h value for culture epimastigotes was estimated as 130 μM. The IC50/24 h value for metacyclic trypomastigotes was 216 nM, while for intracellular amastigotes it was 242 μM and for cell derived trypomasigotes was 262 μM (IC50/24 h). Our data showed that 2-BP altered T. cruzi: 1) morphology, as assessed by bright field, scanning and transmission electron microscopy; 2) mitochondrial membrane potential, as shown by flow cytometry after incubation with rhodamine-123; 3) endocytosis, as seen after incubation with transferrin or albumin and analysis by flow cytometry/fluorescence microscopy; 4) in vitro metacyclogenesis; and 5) infectivity, as shown by host cell infection assays. On the other hand, lipid stress by incubation with palmitate did not alter epimastigote growth, metacyclic trypomastigotes viability or trypomastigote infectivity. Conclusion Our results indicate that 2-BP inhibits key cellular processes of T. cruzi that may be regulated by palmitoylation of vital proteins and suggest a metacyclic trypomastigote unique target dependency during the parasite development

mAb CZP-315.D9: An Antirecombinant Cruzipain Monoclonal Antibody That Specifically Labels the Reservosomes of Trypanosoma cruzi Epimastigotes

Submitted by Luciane Willcox ([email protected]) on 2016-10-05T16:32:32Z No. of bitstreams: 1 mAb CZP-315.D9.pdf: 4001115 bytes, checksum: 9de77b3139e5b19d363ff68bc009c53b (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-10-05T17:52:52Z (GMT) No. of bitstreams: 1 mAb CZP-315.D9.pdf: 4001115 bytes, checksum: 9de77b3139e5b19d363ff68bc009c53b (MD5)Made available in DSpace on 2016-10-05T17:52:52Z (GMT). No. of bitstreams: 1 mAb CZP-315.D9.pdf: 4001115 bytes, checksum: 9de77b3139e5b19d363ff68bc009c53b (MD5) Previous issue date: 2014-01-23Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.Reservosomes are large round vesicles located at the posterior end of epimastigote forms of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. They are the specific end organelles of the endocytosis pathway of T. cruzi, and they play key roles in nutrient uptake and cell differentiation. These lysosome-like organelles accumulate ingested macromolecules and contain large amounts of a major cysteine proteinase (cruzipain or GP57/51 protein). Aim of this study was to produce a monoclonal antibody (mAb) against a recombinant T. cruzi cruzipain (TcCruzipain) that specifically labels the reservosomes. BALB/c mice were immunized with purified recombinant TcCruzipain to obtain the mAb. After fusion of isolated splenocytes with myeloma cells and screening, a mAb was obtained by limiting dilution and characterized by capture ELISA. We report here the production of a kappapositive monoclonal IgG antibody (mAb CZP-315.D9) that recognizes recombinant TcCruzipain. This mAb binds preferentially to a protein with a molecular weight of about 50 kDa on western blots and specifically labels reservosomes by immunofluorescence and transmission electron microscopy. The monoclonal CZP-315.D9 constitutes a potentially powerful marker for use in studies on the function of reservosomes of T. cruzi

<i>Trypanosoma cruzi</i> Intracellular Amastigotes Isolated by Nitrogen Decompression Are Capable of Endocytosis and Cargo Storage in Reservosomes

<div><p>Epimastigote forms of <i>Trypanosoma cruzi</i> (the etiologic agent of Chagas disease) internalize and store extracellular macromolecules in lysosome-related organelles (LROs) called reservosomes, which are positive for the cysteine protease cruzipain. Despite the importance of endocytosis for cell proliferation, macromolecule internalization remains poorly understood in the most clinically relevant proliferative form, the intracellular amastigotes found in mammalian hosts. The main obstacle was the lack of a simple method to isolate viable intracellular amastigotes from host cells. In this work we describe the fast and efficient isolation of viable intracellular amastigotes by nitrogen decompression (cavitation), which allowed the analysis of amastigote endocytosis, with direct visualization of internalized cargo inside the cells. The method routinely yielded 5x10⁷ amastigotes—with typical shape and positive for the amastigote marker Ssp4—from 5x10⁶ infected Vero cells (48h post-infection). We could visualize the endocytosis of fluorescently-labeled transferrin and albumin by isolated intracellular amastigotes using immunofluorescence microscopy; however, only transferrin endocytosis was detected by flow cytometry (and was also analyzed by western blotting), suggesting that amastigotes internalized relatively low levels of albumin. Transferrin binding to the surface of amastigotes (at 4°C) and its uptake (at 37°C) were confirmed by binding dissociation assays using acetic acid. Importantly, both transferrin and albumin co-localized with cruzipain in amastigote LROs. Our data show that isolated <i>T</i>. <i>cruzi</i> intracellular amastigotes actively ingest macromolecules from the environment and store them in cruzipain-positive LROs functionally related to epimastigote reservosomes.</p></div

Flow cytometry analysis of transferrin-AlexaFluor 633 endocytosis by amastigotes and epimastigotes of <i>Trypanosoma cruzi</i>.

<p>(A) Flow cytometry histograms of parasites incubated with transferrin at different temperatures, and then treated with acetic acid, or left untreated. Epimastigotes were used as positive control, and negative control parasites (black) were incubated in medium without labeled transferrin. These data show that isolated intracellular amastigotes internalize transferrin at 37°C. (B) Normalized medians (stained/unstained control) of the fluorescence peaks. Note the low endocytosis levels in axenic amastigotes (N = 3). ***p<0.001. a, acetic acid treatment.</p

Flow cytometry analysis of albumin-AlexaFluor 488 endocytosis in <i>T</i>. <i>cruzi</i> by isolated intracellular amastigotes.

<p>(A) Flow cytometry histograms of cells incubated with labeled albumin at different temperatures. Epimastigotes were used as positive control, and negative control parasites (black) were incubated in medium without labeled albumin. These data show that isolated intracellular amastigotes internalize low amounts of albumin at 37°C. (B) Normalized medians of the fluorescence peaks, relative to the negative control (N = 3). ***p<0.001.</p

Fluorescence microscopy analysis of transferrin-AlexaFluor 633 endocytosis by <i>Trypanosoma cruzi</i> epimastigotes.

<p>Cells were allowed to ingest transferrin and were then labeled with an anti-transferrin antibody (in red) and with the anti-cruzipain mAb CZP-315.D9 (CZP; in green). At 4°C no co-localization was observed (A), while transferrin and cruzipain co-localized at the posterior region of the cell after incubation at 28°C (B), resulting in yellow staining of the reservosomes. The nucleus (arrow) and kinetoplast (arrowhead) are stained with Hoechst 33342 (in blue). DIC, differential interference contrast. Scale bars, 5 μm.</p