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. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

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

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

RESEARCH PRACTICE OF THE METHODS OF MARKETING COMMUNICATIONS AT ATTRACT ENTRANTS IN UNIVERSITY

The authors revealed the relevance of the methods and tools of marketing communication in the Minin university to meet current requirements and potential consumers of high school. The basic types of marketing communications used by the university. Particular attention is paid to the implementation of the methods of marketing communications both electronic (website) and the contact (meetings, open days, school vacations) species. The author reveals the sufficient and necessary components of the site's content through the eyes of high school students of the future; their interest in the ongoing Minin university activities. The article presents the results of the study from February to June of 2015 to identify effective methods of marketing communication that contribute to attracting students to the university. Presented in the article data it is advisable to take into account when planning the marketing activities of the university segment - school graduates and parents

Nanocrystalline Iron Oxides, Composites and Related Materials as a Platform for Electrochemical, Magnetic, and Chemical Biosensors

This review represents a comprehensive attempt to summarize and discuss various sensing applications of iron oxide nanoparticles (NPs), which have attracted a great deal of attention over recent years because of their easy preparation, biocompatibility, nontoxicity, and broad range of biomedical applications. We review the application potential of nanomagnetite based amperometic sensors possessing an intrinsic enzyme mimetic activity similar to that found in natural peroxidases. In addition, we discuss the properties and applications of enzymatic sensors exploiting glucose oxidase, tyrosinase, and other enzymes for sensing a variety of important biomedical species. Among iron oxide-based nanocomposites, we highlight the use of Fe3O4@Au hybrids for designing new electrochemical aptasensors with unique versatility for binding diverse targets, including proteins and peptides. Similarly, sensing applications of composites of iron oxide NPs with graphene derivatives and carbon nanotubes are reviewed. A large part of the review focuses on the development of DNA sensors and iron oxide based immunosensors for the detection of biological and chemical pathogens, contaminants, and other important analytes. Attention is also given to nonelectrochemical sensing, including various types of magnetic, fluorescence, and surface plasmon resonance sensors

Comparison of some physiological markers prior to and post vitrification in Hypericum perforatum L.

The aim of this work is to present the differences between survival rate of Hypericum perforatum L. shoot tips cryoprotected with PVS2 or PVS3 and to compare some physiological patterns prior to and post vitrification procedure. H. perforatum shoot tips pretreated either with 0.076ìM abscisic acid (ABA) for 10 days or 0.3M sucrose for 16 hours were cryoprotected with two different cryoprotective solutions, PVS2 (10% v/v glycerol, 20% w/v sucrose, 10% v/v DMSO) or PVS3 (50% w/v sucrose, 50% v/v glycerol). Survival rate was determined 7 weeks after thawing. As Table 1 shows we have observed 1.47 to 8.6 times higher survival rates (except for the genotypes 40/7/3 and 42/7/3) using PVS3 after ABA pretreatment, whereas in case of sucrose pretreatment survival rate of most genotypes exposed to the same cryoprotection procedure decreased (except for 29/7/5 and 34/7/1, respectively). Recovered plants were subjected to assessment of some physiological markers. Conductivity, H2O2 and MDA content were determined in recovered samples and their control plants (up to 100 mg FW). Our preliminary results indicate that at least one of the parameters studied exceeded level of control values (prior to cryopreservation) after recovery of cryopreserved samples (Figure 2) with an exception of one sample. Possible effect of these findings will be presented and discussed.vokMyynti MTT, Tietopalvelut 31600 Jokioine

An international, multicenter, observational survey to evaluate diabetes control in subjects using insulin for the treatment of type 1 and type 2 diabetes mellitus in the Czech Republic and Slovak Republic: study protocol for a cross-sectional survey

Jan Brož,1 Denisa Janickova Zdarska,1 Jana Urbanova,2 Marek Brabec,3 Bohumila Krivska,4 Viera Donicova,5 Radka Stepanova,6 Emil Martinka,7 Milan Kvapil1 1Department of Internal Medicine, Second Faculty of Medicine, 2Center for Research on Diabetes, Metabolism and Nutrition, Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, 3Institute of Computer Science of the ASCR, vvi, 4Sanofi, Prague, Czech Republic; 5Private Department of Diabetology, Internal Medicine and Metabolism, Kosice, Slovak Republic; 6ADDS sro, Brno, Czech Republic; 7National Institute of Endocrinology and Diabetology, Lubochna, Slovak Republic Background: Despite the improvements in insulin therapy, a large number of patients fail to achieve their target glycated hemoglobin (HbA1c) levels. Control of diabetes is often unsatisfactory because the patient does not know about the principles of successful insulin therapy (ie, blood glucose self-monitoring, the principles of insulin administration, titration, current dose adjustments, dietary recommendations, and physical activity preventive measures) or because these principles are applied incorrectly or insufficiently. Furthermore, the fear of hypoglycemia may lead to maintaining higher than recommended blood glucose levels. Methods/design: This is a noninterventional, international study focusing on a questionnaire survey of diabetes patients (patient-reported outcome) treated with insulin for at least 1 year. It is designed so that the data obtained reflect real access of patients to insulin treatment. The primary objective is to show the results of glycemic control of diabetes (HbA1c) achieved in diabetes patients treated with at least one dose of insulin. The secondary objective is to monitor the factors potentially affecting these results, which include the frequency and other characteristics of hypoglycemia, the frequency of blood glucose self-monitoring, and the effects produced when the results are employed in adjusting the therapy. Furthermore, the study investigates factors related to the principles of insulin administration, dietary regime, and exercise habits. The study will enroll a total of 1,500 patients with type 1 and type 2 diabetes in 150 centers: two-thirds in the Czech Republic and one-third in the Slovak Republic. Discussion: The study is primarily aimed at determining the percentage of insulin-treated diabetes patients reaching the recommended targets for glycemic control (HbA1c). Furthermore, it attempts to identify and describe in detail the factors of failure in achieving the therapeutic goals. An analysis of the data thus obtained may result in recommendations on how to reduce and eliminate all the identified negative factors in the future. Keywords: insulin therapy, glycemic control, HbA1c, hypoglycemia, education, diabetes regimen adherenc

Electrocatalytic effect towards NADH induced by HiPco single-walled carbon nanotubes covalently functionalized by ferrocene derivatives

International audienceThe present work reports the covalent functionalization of single-walled carbonnanotubes (SWCNTs) by ferrocene derivatives with polyethyleneglycol linkers. A very cleaninitial sample was chosen to avoid any residual catalyst and carbon impurities. FunctionalizedSWCNTs (f-CNTs) are deposited on the surface of a glassy carbon electrode (GCE) and thismodified electrode is used for oxidizing the cofactor NADH (dihydronicotinamide adeninedinucleotide) in the presence of diaphorase. A clear electrocatalytic effect is evidenced, whichcan only be attributed to the f-CNTs

Cytotoxic Activities of Several Geranyl-Substituted Flavanones

Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed