110 research outputs found

    Emotional factors relating to weight gain during the COVID-19 pandemic at post-bariatric women from São Paulo: a cross-sectional study

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    Objective: Evaluate the impact of the covid-19 pandemic on weight regain in post bariatric women and correlate it with symptoms of anxiety, depression, binge eating and fear of covid-19.  Methods: It was collected anthropometric and mental health information with application of psychometric scales at the patients mentioned above, between May/2021 and January/2022. Frequencies (descriptive statistics), test t for independent samples and Spearman were used to obtain correlation between weight gain and the psychometric scales. Results: The sample comprised 25 women. The average age was 53.0 years and average body mass index was 35.2kg/m2 before the pandemic. We observed an average increase at the body mass index of 1.4 points during the pandemic. However, 40% maintained or lost weight during the same period. The weight gain group had higher scores for depression, anxiety and binge eating symptoms. Fear of covid-19 scores did not differ between the groups. Conclusion: Anxiety, depression and binge eating symptoms have influenced weight regain in a small sample of post-bariatric women during the covid-19 pandemic

    Reactive Oxygen Species Production and Mitochondrial Dysfunction Contribute to Quercetin Induced Death in Leishmania amazonensis

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    BACKGROUND: Leishmaniasis, a parasitic disease caused by protozoa of the genus Leishmania, affects more than 12 million people worldwide. Quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. One such activity is exhibited against the bloodstream parasite Trypanosoma brucei and amastigotes of Leishmania donovani. However, the mechanism of protozoan action of quercetin has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we report here the mechanism for the antileishmanial activity of quercetin against Leishmania amazonensis promastigotes. Quercetin inhibited L. amazonensis promastigote growth in a dose- and time- dependent manner beginning at 48 hours of treatment and with maximum growth inhibition observed at 96 hours. The IC(50) for quercetin at 48 hours was 31.4 µM. Quercetin increased ROS generation in a dose-dependent manner after 48 hours of treatment. The antioxidant GSH and NAC each significantly reduced quercetin-induced cell death. In addition, quercetin caused mitochondrial dysfunction due to collapse of mitochondrial membrane potential. CONCLUSIONS/SIGNIFICANCE: The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as Leishmania have been described. The unique mitochondrial features of Leishmania make this organelle an ideal drug target while minimizing toxicity. Quercetin has been described as a pro-oxidant, generating ROS which are responsible for cell death in some cancer cells. Mitochondrial membrane potential loss can be brought about by ROS added directly in vitro or induced by chemical agents. Taken together, our results demonstrate that quercetin eventually exerts its antileishmanial effect on L. amazonensis promastigotes due to the generation of ROS and disrupted parasite mitochondrial function

    Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

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    The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

    Fruit load modulates flowering-related gene expression in buds of alternate-bearing 'Moncada' mandarin

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    Background and Aims Gene determination of flowering is the result of complex interactions involving both promoters and inhibitors. In this study, the expression of flowering-related genes at the meristem level in alternate-bearing citrus trees is analysed, together with the interplay between buds and leaves in the determination of flowering. Methods First defruiting experiments were performed to manipulate blossoming intensity in `Moncada¿ mandarin, Citrus clementina. Further defoliation was performed to elucidate the role leaves play in the flowering process. In both cases, the activity of flowering-related genes was investigated at the flower induction (November) and differentiation (February) stages. Key Results Study of the expression pattern of flowering-genes in buds from on (fully loaded) and off (without fruits) trees revealed that homologues of FLOWERING LOCUS T (CiFT), TWIN SISTER OF FT (TSF), APETALA1 (CsAP1) and LEAFY (CsLFY) were negatively affected by fruit load. CiFT and TSF activities showed a marked increase in buds from off trees through the study period (ten-fold in November). By contrast, expression of the homologues of the flowering inhibitors of TERMINAL FLOWER 1 (CsTFL), TERMINAL FLOWER 2 (TFL2) and FLOWERING LOCUS C (FLC) was generally lower in off trees. Regarding floral identity genes, the increase in CsAP1 expression in off trees was much greater in buds than in leaves, and significant variations in CsLFY expression (approx. 20 %) were found only in February. Defoliation experiments further revealed that the absence of leaves completely abolished blossoming and severely affected the expression of most of the flowering-related genes, particularly decreasing the activity of floral promoters and of CsAP1 at the induction stage. Conclusions These results suggest that the presence of fruit affects flowering by greatly altering gene-expression not only at the leaf but also at the meristem level. Although leaves are required for flowering to occur, their absence strongly affects the activity of floral promoters and identity genes.This work was supported by a grant from the Instituto Nacional Investigaciones Agrarias, Spain (RTA2009-00147). M. C. Gonzalez was the recipient of a contract by the Fundacion Agroalimed (Conselleria d'Agricultura, Pesca i Alimentacio, Generalitat Valenciana).Muñoz Fambuena, N.; Mesejo Conejos, C.; Gonzalez Más, MC.; Primo-Millo, E.; Agustí Fonfría, M.; Iglesias, DJ. (2012). Fruit load modulates flowering-related gene expression in buds of alternate-bearing 'Moncada' mandarin. Annals of Botany. 110(6):1109-1118. doi:10.1093/aob/mcs190S110911181106Abe, M. (2005). FD, a bZIP Protein Mediating Signals from the Floral Pathway Integrator FT at the Shoot Apex. Science, 309(5737), 1052-1056. doi:10.1126/science.1115983Bustin, S. (2002). Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. Journal of Molecular Endocrinology, 23-39. doi:10.1677/jme.0.0290023Corbesier, L., & Coupland, G. (2006). The quest for florigen: a review of recent progress. Journal of Experimental Botany, 57(13), 3395-3403. doi:10.1093/jxb/erl095Dornelas, M. C., Camargo, R. L. B., Figueiredo, L. H. M., & Takita, M. A. (2007). A genetic framework for flowering-time pathways in Citrus spp. Genetics and Molecular Biology, 30(3 suppl), 769-779. doi:10.1590/s1415-47572007000500006Endo, T., Shimada, T., Fujii, H., Kobayashi, Y., Araki, T., & Omura, M. (2005). Ectopic Expression of an FT Homolog from Citrus Confers an Early Flowering Phenotype on Trifoliate Orange (Poncirus trifoliata L. Raf.). Transgenic Research, 14(5), 703-712. doi:10.1007/s11248-005-6632-3Esumi, T., Hagihara, C., Kitamura, Y., Yamane, H., & Tao, R. (2009). Identification of anFTortholog in Japanese apricot (Prunus mumeSieb. et Zucc.). The Journal of Horticultural Science and Biotechnology, 84(2), 149-154. doi:10.1080/14620316.2009.11512496Esumi, T., Kitamura, Y., Hagihara, C., Yamane, H., & Tao, R. (2010). Identification of a TFL1 ortholog in Japanese apricot (Prunus mume Sieb. et Zucc.). Scientia Horticulturae, 125(4), 608-616. doi:10.1016/j.scienta.2010.05.016Giakountis, A., & Coupland, G. (2008). Phloem transport of flowering signals. Current Opinion in Plant Biology, 11(6), 687-694. doi:10.1016/j.pbi.2008.10.003Hashimoto, J. G., Beadles-Bohling, A. S., & Wiren, K. M. (2004). Comparison of RiboGreen®and 18S rRNA quantitation for normalizing real-time RT-PCR expression analysis. BioTechniques, 36(1), 54-60. doi:10.2144/04361bm06Jaeger, K. E., Graf, A., & Wigge, P. A. (2006). The control of flowering in time and space. Journal of Experimental Botany, 57(13), 3415-3418. doi:10.1093/jxb/erl159Jang, S., Torti, S., & Coupland, G. (2009). Genetic and spatial interactions betweenFT,TSFandSVPduring the early stages of floral induction in Arabidopsis. The Plant Journal, 60(4), 614-625. doi:10.1111/j.1365-313x.2009.03986.xJaya, E. S. K. D., Clemens, J., Song, J., Zhang, H., & Jameson, P. E. (2009). Quantitative expression analysis of meristem identity genes in Eucalyptus occidentalis: AP1 is an expression marker for flowering. Tree Physiology, 30(2), 304-312. doi:10.1093/treephys/tpp117Koshita, Y., Takahara, T., Ogata, T., & Goto, A. (1999). Involvement of endogenous plant hormones (IAA, ABA, GAs) in leaves and flower bud formation of satsuma mandarin (Citrus unshiu Marc.). Scientia Horticulturae, 79(3-4), 185-194. doi:10.1016/s0304-4238(98)00209-xKotoda, N., Hayashi, H., Suzuki, M., Igarashi, M., Hatsuyama, Y., Kidou, S., … Abe, K. (2010). Molecular Characterization of FLOWERING LOCUS T-Like Genes of Apple (Malus × domestica Borkh.). Plant and Cell Physiology, 51(4), 561-575. doi:10.1093/pcp/pcq021Li, D., Liu, C., Shen, L., Wu, Y., Chen, H., Robertson, M., … Yu, H. (2008). A Repressor Complex Governs the Integration of Flowering Signals in Arabidopsis. Developmental Cell, 15(1), 110-120. doi:10.1016/j.devcel.2008.05.002Lord, E. M., & Eckard, K. J. (1985). Shoot Development in Citrus sinensis L. (Washington Navel Orange). I. Floral and Inflorescence Ontogeny. Botanical Gazette, 146(3), 320-326. doi:10.1086/337531Mathieu, J., Warthmann, N., Küttner, F., & Schmid, M. (2007). Export of FT Protein from Phloem Companion Cells Is Sufficient for Floral Induction in Arabidopsis. Current Biology, 17(12), 1055-1060. doi:10.1016/j.cub.2007.05.009Matsuda, N., Ikeda, K., Kurosaka, M., Takashina, T., Isuzugawa, K., Endo, T., & Omura, M. (2009). Early Flowering Phenotype in Transgenic Pears (Pyrus communis L.) Expressing the CiFT Gene. Journal of the Japanese Society for Horticultural Science, 78(4), 410-416. doi:10.2503/jjshs1.78.410Michaels, S. D., Himelblau, E., Kim, S. Y., Schomburg, F. M., & Amasino, R. M. (2004). Integration of Flowering Signals in Winter-Annual Arabidopsis. Plant Physiology, 137(1), 149-156. doi:10.1104/pp.104.052811Moss, G. I. (1971). Effect of fruit on flowering in relation to biennial bearing in sweet orange(Citrus sinensis). Journal of Horticultural Science, 46(2), 177-184. doi:10.1080/00221589.1971.11514396Muñoz-Fambuena, N., Mesejo, C., Carmen González-Mas, M., Primo-Millo, E., Agustí, M., & Iglesias, D. J. (2011). Fruit regulates seasonal expression of flowering genes in alternate-bearing ‘Moncada’ mandarin. Annals of Botany, 108(3), 511-519. doi:10.1093/aob/mcr164Muñoz-Fambuena, N., Mesejo, C., González-Mas, M. C., Iglesias, D. J., Primo-Millo, E., & Agustí, M. (2012). Gibberellic Acid Reduces Flowering Intensity in Sweet Orange [Citrus sinensis (L.) Osbeck] by Repressing CiFT Gene Expression. Journal of Plant Growth Regulation, 31(4), 529-536. doi:10.1007/s00344-012-9263-yNishikawa, F., Endo, T., Shimada, T., Fujii, H., Shimizu, T., Omura, M., & Ikoma, Y. (2007). Increased CiFT abundance in the stem correlates with floral induction by low temperature in Satsuma mandarin (Citrus unshiu Marc.). Journal of Experimental Botany, 58(14), 3915-3927. doi:10.1093/jxb/erm246Nishikawa, F., Endo, T., Shimada, T., Fujii, H., Shimizu, T., Kobayashi, Y., … Omura, M. (2010). Transcriptional changes in CiFT-introduced transgenic trifoliate orange (Poncirus trifoliata L. Raf.). Tree Physiology, 30(3), 431-439. doi:10.1093/treephys/tpp122Notaguchi, M., Abe, M., Kimura, T., Daimon, Y., Kobayashi, T., Yamaguchi, A., … Araki, T. (2008). Long-Distance, Graft-Transmissible Action of Arabidopsis FLOWERING LOCUS T Protein to Promote Flowering. Plant and Cell Physiology, 49(11), 1645-1658. doi:10.1093/pcp/pcn154Peña, L., Martín-Trillo, M., Juárez, J., Pina, J. A., Navarro, L., & Martínez-Zapater, J. M. (2001). Constitutive expression of Arabidopsis LEAFY or APETALA1 genes in citrus reduces their generation time. Nature Biotechnology, 19(3), 263-267. doi:10.1038/85719Pillitteri, L. J., Lovatt, C. J., & Walling, L. L. (2004). Isolation and Characterization of a TERMINAL FLOWER Homolog and Its Correlation with Juvenility in Citrus. Plant Physiology, 135(3), 1540-1551. doi:10.1104/pp.103.036178Pillitteri, L. J., Lovatt, C. J., & Walling, L. L. (2004). Isolation and Characterization of LEAFY and APETALA1 Homologues from Citrus sinensis L. Osbeck `Washington’. Journal of the American Society for Horticultural Science, 129(6), 846-856. doi:10.21273/jashs.129.6.0846Rottmann, W. H., Meilan, R., Sheppard, L. A., Brunner, A. M., Skinner, J. S., Ma, C., … Strauss, S. H. (2000). Diverse effects of overexpression of LEAFY and PTLF, a poplar (Populus) homolog of LEAFY/FLORICAULA, in transgenic poplar and Arabidopsis. The Plant Journal, 22(3), 235-245. doi:10.1046/j.1365-313x.2000.00734.xSherman, W. B., & Beckman, T. G. (2003). CLIMATIC ADAPTATION IN FRUIT CROPS. Acta Horticulturae, (622), 411-428. doi:10.17660/actahortic.2003.622.43Southerton, S. G., Strauss, S. H., Olive, M. R., Harcourt, R. L., Decroocq, V., Zhu, X., … Dennis, E. S. (1998). Plant Molecular Biology, 37(6), 897-910. doi:10.1023/a:1006056014079Sreekantan, L., & Thomas, M. R. (2006). VvFT and VvMADS8, the grapevine homologues of the floral integrators FT and SOC1, have unique expression patterns in grapevine and hasten flowering in Arabidopsis. Functional Plant Biology, 33(12), 1129. doi:10.1071/fp06144Takada, S., & Goto, K. (2003). TERMINAL FLOWER2, an Arabidopsis Homolog of HETEROCHROMATIN PROTEIN1, Counteracts the Activation of FLOWERING LOCUS T by CONSTANS in the Vascular Tissues of Leaves to Regulate Flowering Time. The Plant Cell, 15(12), 2856-2865. doi:10.1105/tpc.016345Tan, F.-C., & Swain, S. M. (2007). Functional characterization of AP3, SOC1 and WUS homologues from citrus (Citrus sinensis). Physiologia Plantarum, 131(3), 481-495. doi:10.1111/j.1399-3054.2007.00971.xTränkner, C., Lehmann, S., Hoenicka, H., Hanke, M.-V., Fladung, M., Lenhardt, D., … Flachowsky, H. (2010). Over-expression of an FT-homologous gene of apple induces early flowering in annual and perennial plants. Planta, 232(6), 1309-1324. doi:10.1007/s00425-010-1254-2Vemmos, S. N. (1999). Carbohydrate content of inflorescent buds of defruited and fruiting pistachio (Pistacia vera L) branches in relation to biennial bearing. The Journal of Horticultural Science and Biotechnology, 74(1), 94-100. doi:10.1080/14620316.1999.11511079Wada, M., Cao, Q., Kotoda, N., Soejima, J., & Masuda, T. (2002). Plant Molecular Biology, 49(6), 567-577. doi:10.1023/a:1015544207121Wigge, P. A. (2005). Integration of Spatial and Temporal Information During Floral Induction in Arabidopsis. Science, 309(5737), 1056-1059. doi:10.1126/science.1114358Yahata, D., Matsumoto, K., & Ushijima, K. (2004). Relationship between Flower-bud Differentiation and Carbohydrate Contents in Spring Shoots of Very-early, Early and Late Maturing Cultivars of Satsuma Mandarin. Engei Gakkai zasshi, 73(5), 405-410. doi:10.2503/jjshs.73.405Yamaguchi, A., Kobayashi, Y., Goto, K., Abe, M., & Araki, T. (2005). TWIN SISTER OF FT (TSF) Acts as a Floral Pathway Integrator Redundantly with FT. Plant and Cell Physiology, 46(8), 1175-1189. doi:10.1093/pcp/pci151Yan, J., Yuan, F., Long, G., Qin, L., & Deng, Z. (2011). Selection of reference genes for quantitative real-time RT-PCR analysis in citrus. Molecular Biology Reports, 39(2), 1831-1838. doi:10.1007/s11033-011-0925-9YU, Q., MOORE, P. H., ALBERT, H. H., ROADER, A. H. K., & MING, R. (2005). Cloning and characterization of a FLORICAULA/LEAFY ortholog, PFL, in polygamous papaya. Cell Research, 15(8), 576-584. doi:10.1038/sj.cr.7290327Yu, X., Klejnot, J., & Lin, C. (2006). Florigen: One Found, More to Follow? Journal of Integrative Plant Biology, 48(6), 617-621. doi:10.1111/j.1744-7909.2006.00309.

    The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

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    Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

    Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

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    Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

    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

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    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

    Repositioning of the global epicentre of non-optimal cholesterol

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    High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

    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

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    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 &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;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
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