Parasitized mates increase infection risk for partners

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A transcriptomic investigation of handicap models in sexual selection

We are grateful to D. Calder and T. Helps for access to study sites, and G. Murray-Dickson and M. Oliver for help with fieldwork and comments on manuscript drafts. This work was funded by NERC grant NE/D000602/1 (SBP), a NERC advanced fellowship (FM) and a BBSRC studentship (MAW)Peer reviewedPostprin

A comparison of Clinical Risk Index for babies (CRIB-II), Score for Neonatal Acute Physiology (SNAP-II) and SNAPPE-II in predicting parenteral nutrition necessity in low birth weight preterm neonates.

Advances in perinatal care have made it possible to improve survival of low birth weight neonates. Clinical risk index for babies (CRIB-II), score for neonatal acute physiology (SNAP-II), and SNAP-perinatal extension-II (SNAPPE-II) have been used as mortality predictors for preterm infants. Feeding intolerance is very frequent in preterm neonates, and the development of an early effective biomarker for its prediction could be useful for carrying out a proper feeding strategy. Our aim was to compare the ability of CRIB-II, SNAP-II and SNAPPE-II in predict the feeding intolerance and parenteral nutrition necessity in preterm neonates. Methods: A retrospective cohort study on preterm neonates’ born at Jaen Hospital Complex with low birth weight and ≤ 36 weeks of gestation was done. Epidemiological, clinical and clinical scores CRIB II, SNAP-II and SNAPPE-II were recorded. Results: 255 low birth weight preterm neonates, 131 males (51.4%), aged ≤32 weeks of gestation (71%), were enrolled at our hospital. Parenteral nutrition needed were significantly higher in preterm neonates weighed 2500-1500 g (73.3%) and ≤ 1000g (87%). CRIB-II, SNAP-II and SNAPPE-II mean values were higher in neonates group subjected to parenteral nutrition compared with oral nutrition (p<0.05). CRIB-II and SNAPPE-II scores significantly correlated with parenteral nutrition days (p<0.05). Overall mortality rate was 11%. The 78.6% of all deceased infants needed parenteral nutrition. Conclusion: Clinical Risk Index for babies (CRIB-II) better than SNAPPE-II correlated with the feeding intolerance and thus the parenteral nutrition days in preterm neonates with low birth weight.Subvencionado: Ayuda del Plan Propio de Investigación de la UMA. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Anti-Trypanosoma cruzi Activity of Metabolism Modifier Compounds

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC50 = 0.27 μmol L−1) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages

Assessment of Multilocus Sequence Analysis (MLSA) for Identification of Candidatus Liberibacter Solanacearum from Different Host Plants in Spain

[EN] Liberibacteris a bacterial group causing different diseases and disorders in plants. Among liberibacters,CandidatusLiberibacter solanaceraum (CLso) produces disorders in several species mainly within Apiaceae and Solanaceae families. CLso isolates are usually grouped in defined haplotypes according to single nucleotide polymorphisms in genes associated with ribosomal elements. In order to characterize more precisely isolates of CLso identified in potato in Spain, a Multilocus Sequence Analysis (MLSA) was applied. This methodology was validated by a complete analysis of ten housekeeping genes that showed an absence of positive selection and a nearly neutral mechanism for their evolution. Most of the analysis performed with single housekeeping genes, as well as MLSA, grouped together isolates of CLso detected in potato crops in Spain within the haplotype E, undistinguishable from those infecting carrots, parsnips or celery. Moreover, the information from these housekeeping genes was used to estimate the evolutionary divergence among the different CLso by using the concatenated sequences of the genes assayed. Data obtained on the divergence among CLso haplotypes support the hypothesis of evolutionary events connected with different hosts, in different geographic areas, and possibly associated with different vectors. Our results demonstrate the absence in Spain of CLso isolates molecularly classified as haplotypes A and B, traditionally considered causal agents of zebra chip in potato, as well as the uncertain possibility of the present haplotype to produce major disease outbreaks in potato that may depend on many factors that should be further evaluated in future worksThis research was funded by Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA), grant numbers AT2016-007 and RTA2014-00008-C04-03-E, co-financed by FEDER.Ruiz-Padilla, A.; Redondo, C.; Asensio, A.; Garita-Cambronero, J.; Martinez, C.; Perez-Padilla, V.; Marquinez, R.... (2020). Assessment of Multilocus Sequence Analysis (MLSA) for Identification of Candidatus Liberibacter Solanacearum from Different Host Plants in Spain. Microorganisms. 8(9):1-19. https://doi.org/10.3390/microorganisms8091446S11989Haapalainen, M. (2014). Biology and epidemics ofCandidatusLiberibacter species, psyllid-transmitted plant-pathogenic bacteria. Annals of Applied Biology, 165(2), 172-198. doi:10.1111/aab.12149Raddadi, N., Gonella, E., Camerota, C., Pizzinat, A., Tedeschi, R., Crotti, E., … Alma, A. (2010). ‘Candidatus Liberibacter europaeus’ sp. nov. that is associated with and transmitted by the psyllid Cacopsylla pyri apparently behaves as an endophyte rather than a pathogen. Environmental Microbiology, 13(2), 414-426. doi:10.1111/j.1462-2920.2010.02347.xWang, N., Pierson, E. A., Setubal, J. C., Xu, J., Levy, J. G., Zhang, Y., … Martins, J. (2017). The Candidatus Liberibacter–Host Interface: Insights into Pathogenesis Mechanisms and Disease Control. Annual Review of Phytopathology, 55(1), 451-482. doi:10.1146/annurev-phyto-080516-035513Morris, J., Shiller, J., Mann, R., Smith, G., Yen, A., & Rodoni, B. (2017). Novel ‘Candidatus Liberibacter’ species identified in the Australian eggplant psyllid, Acizzia solanicola. Microbial Biotechnology, 10(4), 833-844. doi:10.1111/1751-7915.12707Alfaro-Fernández, A., Hernández-Llopis, D., & Font, M. I. (2017). Haplotypes of ‘Candidatus Liberibacter solanacearum’ identified in Umbeliferous crops in Spain. European Journal of Plant Pathology, 149(1), 127-131. doi:10.1007/s10658-017-1172-2Haapalainen, M., Wang, J., Latvala, S., Lehtonen, M. T., Pirhonen, M., & Nissinen, A. I. (2018). Genetic Variation of ‘Candidatus Liberibacter solanacearum’ Haplotype C and Identification of a Novel Haplotype from Trioza urticae and Stinging Nettle. Phytopathology®, 108(8), 925-934. doi:10.1094/phyto-12-17-0410-rHaapalainen, M., Latvala, S., Wickström, A., Wang, J., Pirhonen, M., & Nissinen, A. I. (2019). A novel haplotype of ‘Candidatus Liberibacter solanacearum’ found in Apiaceae and Polygonaceae family plants. European Journal of Plant Pathology, 156(2), 413-423. doi:10.1007/s10658-019-01890-0Mauck, K. E., Sun, P., Meduri, V. R., & Hansen, A. K. (2019). New Ca. Liberibacter psyllaurous haplotype resurrected from a 49-year-old specimen of Solanum umbelliferum: a native host of the psyllid vector. Scientific Reports, 9(1). doi:10.1038/s41598-019-45975-6Teixeira, D. C., Eveillard, S., Sirand-Pugnet, P., Wulff, A., Saillard, C., Ayres, A. J., & Bove, J. M. (2008). The tufB-secE-nusG-rplKAJL-rpoB gene cluster of the liberibacters: sequence comparisons, phylogeny and speciation. INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, 58(6), 1414-1421. doi:10.1099/ijs.0.65641-0Glaeser, S. P., & Kämpfer, P. (2015). Multilocus sequence analysis (MLSA) in prokaryotic taxonomy. Systematic and Applied Microbiology, 38(4), 237-245. doi:10.1016/j.syapm.2015.03.007Gevers, D., Cohan, F. M., Lawrence, J. G., Spratt, B. G., Coenye, T., Feil, E. J., … Swings, J. (2005). Re-evaluating prokaryotic species. Nature Reviews Microbiology, 3(9), 733-739. doi:10.1038/nrmicro1236Swisher Grimm, K. D., & Garczynski, S. F. (2019). Identification of a New Haplotype of ‘CandidatusLiberibacter solanacearum’ inSolanum tuberosum. Plant Disease, 103(3), 468-474. doi:10.1094/pdis-06-18-0937-reLin, H., Lou, B., Glynn, J. M., Doddapaneni, H., Civerolo, E. L., Chen, C., … Vahling, C. M. (2011). The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease. PLoS ONE, 6(4), e19135. doi:10.1371/journal.pone.0019135Thompson, S. M., Johnson, C. P., Lu, A. Y., Frampton, R. A., Sullivan, K. L., Fiers, M. W. E. J., … Smith, G. R. (2015). Genomes of ‘Candidatus Liberibacter solanacearum’ Haplotype A from New Zealand and the United States Suggest Significant Genome Plasticity in the Species. Phytopathology®, 105(7), 863-871. doi:10.1094/phyto-12-14-0363-fiLin, H., Pietersen, G., Han, C., Read, D. A., Lou, B., Gupta, G., & Civerolo, E. L. (2015). Complete Genome Sequence of « Candidatus Liberibacter africanus,» a Bacterium Associated with Citrus Huanglongbing. Genome Announcements, 3(4). doi:10.1128/genomea.00733-15Wulff, N. A., Zhang, S., Setubal, J. C., Almeida, N. F., Martins, E. C., Harakava, R., … Gabriel, D. W. (2014). The Complete Genome Sequence of ‘Candidatus Liberibacter americanus’, Associated with Citrus Huanglongbing. Molecular Plant-Microbe Interactions®, 27(2), 163-176. doi:10.1094/mpmi-09-13-0292-rDuan, Y., Zhou, L., Hall, D. G., Li, W., Doddapaneni, H., Lin, H., … Gottwald, T. (2009). Complete Genome Sequence of Citrus Huanglongbing Bacterium, ‘CandidatusLiberibacter asiaticus’ Obtained Through Metagenomics. Molecular Plant-Microbe Interactions®, 22(8), 1011-1020. doi:10.1094/mpmi-22-8-1011Katoh, H., Miyata, S., Inoue, H., & Iwanami, T. (2014). Unique Features of a Japanese ‘Candidatus Liberibacter asiaticus’ Strain Revealed by Whole Genome Sequencing. PLoS ONE, 9(9), e106109. doi:10.1371/journal.pone.0106109Leonard, M. T., Fagen, J. R., Davis-Richardson, A. G., Davis, M. J., & Triplett, E. W. (2012). Complete genome sequence of Liberibacter crescens BT-1. Standards in Genomic Sciences, 7(2), 271-283. doi:10.4056/sigs.3326772Teresani, G. R., Bertolini, E., Alfaro-Fernández, A., Martínez, C., Tanaka, F. A. O., Kitajima, E. W., … Font, M. I. (2014). Association of ‘Candidatus Liberibacter solanacearum’ with a Vegetative Disorder of Celery in Spain and Development of a Real-Time PCR Method for Its Detection. Phytopathology®, 104(8), 804-811. doi:10.1094/phyto-07-13-0182-rLi, W., Hartung, J. S., & Levy, L. (2006). Quantitative real-time PCR for detection and identification of Candidatus Liberibacter species associated with citrus huanglongbing. Journal of Microbiological Methods, 66(1), 104-115. doi:10.1016/j.mimet.2005.10.018Munyaneza, J. E., Sengoda, V. G., Crosslin, J. M., De la Rosa-Lozano, G., & Sanchez, A. (2009). First Report of ‘Candidatus Liberibacter psyllaurous’ in Potato Tubers with Zebra Chip Disease in Mexico. Plant Disease, 93(5), 552-552. doi:10.1094/pdis-93-5-0552aPhillips, J. L., & Gnanakaran, S. (2014). A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps. Proteins: Structure, Function, and Bioinformatics, 83(1), 46-65. doi:10.1002/prot.24632Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Molecular Biology and Evolution, 35(6), 1547-1549. doi:10.1093/molbev/msy096Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. (1993). Molecular Biology and Evolution. doi:10.1093/oxfordjournals.molbev.a040023Rozas, J., Ferrer-Mata, A., Sánchez-DelBarrio, J. C., Guirao-Rico, S., Librado, P., Ramos-Onsins, S. E., & Sánchez-Gracia, A. (2017). DnaSP 6: DNA Sequence Polymorphism Analysis of Large Data Sets. Molecular Biology and Evolution, 34(12), 3299-3302. doi:10.1093/molbev/msx248Liao, J., Wiedmann, M., & Kovac, J. (2017). Genetic Stability and Evolution of the sigB Allele, Used for Listeria Sensu Stricto Subtyping and Phylogenetic Inference. Applied and Environmental Microbiology, 83(12). doi:10.1128/aem.00306-17Tamura, K., Battistuzzi, F. U., Billing-Ross, P., Murillo, O., Filipski, A., & Kumar, S. (2012). Estimating divergence times in large molecular phylogenies. Proceedings of the National Academy of Sciences, 109(47), 19333-19338. doi:10.1073/pnas.1213199109Tamura, K., Tao, Q., & Kumar, S. (2018). Theoretical Foundation of the RelTime Method for Estimating Divergence Times from Variable Evolutionary Rates. Molecular Biology and Evolution, 35(7), 1770-1782. doi:10.1093/molbev/msy044López-Hermoso, C., de la Haba, R. R., Sánchez-Porro, C., Papke, R. T., & Ventosa, A. (2017). Assessment of MultiLocus Sequence Analysis As a Valuable Tool for the Classification of the Genus Salinivibrio. Frontiers in Microbiology, 8. doi:10.3389/fmicb.2017.01107Hajri, A., Loiseau, M., Cousseau-Suhard, P., Renaudin, I., & Gentit, P. (2017). Genetic Characterization of ‘Candidatus Liberibacter solanacearum’ Haplotypes Associated with Apiaceous Crops in France. Plant Disease, 101(8), 1383-1390. doi:10.1094/pdis-11-16-1686-reFang, Y., Wang, Y., Liu, Z., Dai, H., Cai, H., Li, Z., … Wang, D. (2019). Multilocus Sequence Analysis, a Rapid and Accurate Tool for Taxonomic Classification, Evolutionary Relationship Determination, and Population Biology Studies of the Genus Shewanella. Applied and Environmental Microbiology, 85(11). doi:10.1128/aem.03126-18Konstantinidis, K. T., Ramette, A., & Tiedje, J. M. (2006). Toward a More Robust Assessment of IntraspeciesDiversity, Using Fewer GeneticMarkers. Applied and Environmental Microbiology, 72(11), 7286-7293. doi:10.1128/aem.01398-06Ajene, I. J., Khamis, F., Ballo, S., Pietersen, G., van Asch, B., Seid, N., … Mohamed, S. (2020). Detection of Asian Citrus Psyllid (Hemiptera: Psyllidae) in Ethiopia: A New Haplotype and its Implication to the Proliferation of Huanglongbing. Journal of Economic Entomology, 113(4), 1640-1647. doi:10.1093/jee/toaa113Thapa, S. P., De Francesco, A., Trinh, J., Gurung, F. B., Pang, Z., Vidalakis, G., … Coaker, G. (2020). Genome‐wide analyses of Liberibacter species provides insights into evolution, phylogenetic relationships, and virulence factors. Molecular Plant Pathology, 21(5), 716-731. doi:10.1111/mpp.12925Antolinez, C. A., Fereres, A., & Moreno, A. (2017). Risk assessment of ‘Candidatus Liberibacter solanacearum’ transmission by the psyllids Bactericera trigonica and B. tremblayi from Apiaceae crops to potato. Scientific Reports, 7(1). doi:10.1038/srep45534Antolínez, Moreno, Ontiveros, Pla, Plaza, Sanjuan, … Fereres. (2019). Seasonal Abundance of Psyllid Species on Carrots and Potato Crops in Spain. Insects, 10(9), 287. doi:10.3390/insects10090287Wang, J., Haapalainen, M., Schott, T., Thompson, S. M., Smith, G. R., Nissinen, A. I., & Pirhonen, M. (2017). Genomic sequence of «Candidatus Liberibacter solanacearum» haplotype C and its comparison with haplotype A and B genomes. PLOS ONE, 12(2), e0171531. doi:10.1371/journal.pone.0171531Katsir, L., Zhepu, R., Santos Garcia, D., Piasezky, A., Jiang, J., Sela, N., … Bahar, O. (2018). Genome Analysis of Haplotype D of Candidatus Liberibacter Solanacearum. Frontiers in Microbiology, 9. doi:10.3389/fmicb.2018.02933Quintana-González de Chaves, M., Teresani, G. R., Hernández-Suárez, E., Bertolini, E., Moreno, A., Fereres, A., … Siverio, F. (2020). ‘Candidatus Liberibacter Solanacearum’ Is Unlikely to Be Transmitted Spontaneously from Infected Carrot Plants to Citrus Plants by Trioza Erytreae. Insects, 11(8), 514. doi:10.3390/insects1108051

Association of Irisin Serum Concentration and Muscle Strength in Normal-Weight and Overweight Young Women

Background: Irisin is a muscle-contraction-induced myokine. In previous studies, it has been related to exercise type, fitness and physical activity; however, evidence is not consistent. Thus, the aim of this study was to research the association between health-related fitness and irisin in young women. Methods: The study was designed as a prospective cross-sectional one. Young, healthy, nonsmoking women were enlisted. The sample comprised 40 overweight (OW) and 40 normal-weight (NW) individuals. The average age was 18.63 ± 0.63 and 18.78 ± 0.73 years, respectively. Components of health-related fitness, metabolic parameters, serum irisin and body composition were analyzed. Results: Statistically significant differences were found in physical tests between NW and OW groups for one-leg standing, hand grip strength, vertical jump, modified push-up, fitness index and maximal oxygen uptake (VO2MAX). There were no differences in concentrations of serum irisin between the groups. We found a positive correlation between irisin and hand grip strength (r = 0.374, p = 0.023). In a multivariate analysis adjusted by body fat, a significant association between irisin and hand grip strength was observed in OW group (β = 0.380, p = 0.026); as well, a positive association between irisin and one-leg standing test in NW group (β = 0.311, p = 0.044) was found. Conclusions: According to our findings, hand grip strength could be linked to irisin concentration in overweight young women

Novel purine chemotypes with activity against Plasmodium 2 falciparum and Trypanosoma cruzi

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.SAF2016-76080-R (Spanish Ministry of Economy (AEI/FEDER, UE))PID2019-110810RB-I00 (Spanish Ministry of Science and Innovation)Generalitat of Catalonia Universities and Research Department, Spain (AGAUR; 2017SGR00924)Carlos III Health Institute (ISCIII)RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD12/0018/0010)Generalitat of Catalonia Department of Health (PERIS 2016–2010 SLT008/18/00132)Spanish Ministry of Education, Culture, and Sports (FPU grant ref. 14/00818)Spanish Ministry of Science, Innovation, and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S)CERCA Progra

The OTELO survey: A case study of [O III] lambda 4959,5007 emitters at z=0.83

Context. The OSIRIS Tunable Filter Emission Line Object (OTELO) survey is a very deep, blind exploration of a selected region of the Extended Groth Strip and is designed for finding emission-line sources (ELSs). The survey design, observations, data reduction, astrometry, and photometry, as well as the correlation with ancillary data used to obtain a final catalogue, including photo-z estimates and a preliminary selection of ELS, were described in a previous contribution. Aims. Here, we aim to determine the main properties and luminosity function (LF) of the [O III] ELS sample of OTELO as a scientific demonstration of its capabilities, advantages, and complementarity with respect to other surveys. Methods. The selection and analysis procedures of ELS candidates obtained using tunable filter pseudo-spectra are described. We performed simulations in the parameter space of the survey to obtain emission-line detection probabilities. Relevant characteristics of [O III] emitters and the LF ([O III]), including the main selection biases and uncertainties, are presented. Results. From 541 preliminary emission-line source candidates selected around z = 0.8, a total of 184 sources were confirmed as [O III] emitters. Consistent with simulations, the minimum detectable line flux and equivalent width in this ELS sample are ∼5 × 10−19 erg s−1 cm2 and ∼6 Å, respectively. We are able to constrain the faint-end slope (α = −1.03 ± 0.08) of the observed LF ([O III]) at a mean redshift of z = 0.83. This LF reaches values that are approximately ten times lower than those from other surveys. The vast majority (84%) of the morphologically classified [O III] ELSs are disc-like sources, and 87% of this sample is comprised of galaxies with stellar masses of M⋆ <  1010 M⊙

Physiological Stress Mediates the Honesty of Social Signals

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Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life