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

Skeletal Muscle Pump Drives Control of Cardiovascular and Postural Systems

The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions. Data were acquired simultaneously from young participants (25 ± 2 years, n = 18) during a 10-minute sit-to-stand test. In the young population, skeletal muscle pump was found to drive blood pressure control (EMG → SBP) as well as control the postural sway (EMG → COPr) through the significantly higher causal drive in the direction towards SBP and COPr. Furthermore, the effect of aging on muscle pump activation associated with blood pressure regulation was explored. Simultaneous EMG and SBP were acquired from elderly group (69 ± 4 years, n = 14). A significant (p = 0.002) decline in EMG → SBP causality was observed in the elderly group, compared to the young group. The results highlight the potential of causality to detect alteration in blood pressure regulation with age, thus, a potential clinical utility towards detection of fall proneness

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

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 63093 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 11476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11235 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 10428 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.peer-reviewe

Assessment of Mode of Action and Histopathological Changes Induces by Bacillus thurengiensis. in Various Tissues and Organs of Spodoptera littoralis Larvae

The present study was devoted to elucidate the mode of action and histopathological effects of the spore delta-endotoxin complex of B.t. var aizawai on the larvae of the cotton leaf worm Spodoptera littoralis.The results obtained has clearly shown that the consequence of symptoms of infection could be divided in morphologically distinct four stages. Furthermore, the results of this investigation have indicated that the sequence of symptoms starts with cessation of feeding followed by movement sluggishness, vomiting and diarrheae, excessive sluggishness, complete paralysis and finally death of the insect. On the other hand, the histopathological effects of the endotoxin observed in the dissected insect fed on diet containing the toxin were followed periodically. The results have clearly demonstrated marked histopathological alterations in the midgut epithelium, layers and clumping of both exo-and endocuticle of the integument. Furthermore, the uptake of bacterial deltaendotoxin has caused a marked degeneration of the nerve cells of the fourth abdominal nerve ganglion. The nerve cells and fibers were partially destroyed. In addition a notable destruction and vacuolation of the fat body cells became evident and the fat tissues became soft and easily crushed as compared to those of the healthy insect

Synthesis and antimicrobial evaluation of 3-hydrazino-quinoxaline derivatives and their cyclic analoaues

A series of quinoxaline derivatives has been synthesized by reacting 3-hydrazinoquinoxalines 1a,b with many bifunctional reagents. Reaction of 1a,b with chloroacetyl chloride and ethyl chloroacetate afforded 1-chloromethyl[1,2,4]tnazoIo[4,3-a]quinoxalines 2a,b and dihydro[1,2,4]triazino[4,3-a]quinoxalin-2-ones 3a,b respectively. Condensation of 1a,b with ethyl acetoacetate and acetylacetone yielded 2-quinoxalinylhydrazonobutanoates 4a,b and 2-quinoxalinylhydrazono-2-pentanones 5a,b respectively. Cyclization of 5a,b gave 3,5-dimethylpyrazolylquinoxalines 6a,b. Moreover, reaction of compounds 2a,b with N-phenyl piperazine derivatives afforded 4-(4-Arylpiperazin-1-yl)-1-[(4-arylpiperazin-1-yl) methyl)]triazoloquinoxalines 7a−e. The prepared compounds were screened for in vitro antibacterial and antifungal activities. None of the tested compounds showed significant activity towards Pseudomonas aeruginosa. However, remarkable activities were noticed for compounds 5a and 5b against Eschenchia coli. Staphylococcus aureus and Candida albicans. Compounds 6a and 6b lacked any antimicrobial activities against the tested microorganisms

Optimum conditions for surface modification of PET by lipase enzymes produced by Egyptian bacilli in comparison with standard one

165-172<span style="mso-fareast-font-family: AdvOT863180fb;mso-bidi-language:AR-EG" lang="EN-GB">The optimum conditions for surface modification of polyethylene terephthalate (PET) by lipase enzymes produced under economic conditions by two Egyptian bacilli (Bacillus isolate 6C and Bacillus isolate 5W) have been obtained and then compared with reference sample. The optimum conditions are found to be 0.04 mg/mL enzyme concentration, 0.5 h incubation time, room temperature (25 ºC) and pH 8 under shaking conditions. Addition of 0.15% CaCl2<span style="mso-fareast-font-family:AdvOT863180fb; mso-bidi-language:AR-EG" lang="EN-GB"> to the treatment bath enhances both the hydrophilicity (18-26%) and dyeability (22- 194%). The effect of hydrolytic activity of enzymatic process on the weight loss after treatment does not show any significant difference. Printing both untreated and treated PET fabrics with transfer printing shows high leveling properties w.r.t. ∆E values, where it is considered as acceptable values of color differences. PET treated with different sources of lipase enzyme under optimum conditions shows good physical properties and high water regain. SEM of the surface of lipase treated PET samples shows cracks and voids compared to smooth surface of untreated PET fabrics. </span

Enzymatic surface hydrolysis of polyamide fabric by protease enzyme and its production

273-279The present study is aimed at finding out the protease enzyme specific for hydrolysis of polyamide fabric surface and its production in cost effective medium for application in textile industry. Hydrolysis of polyamide fabric by <span style="mso-ansi-language: EN-US" lang="EN-US">protease enzymes produced by Bacillus isolates 2W, 16P and 36P is confirmed by improved hydrophilic properties, enhanced staining with basic dyes, scanning electron microscope and FTIR. SEM images of protease treated fabric show heterogeneous appearance as cracks, pits and rough surfaces. FTIR measurements prove the increase in free amino groups on the surface of protease treated <span style="mso-ansi-language: EN-US" lang="EN-US">polyamide. At the same time, treated fabric shows good physical and mechanical properties. It is also observed that the loss of strength of treated fabric is 6%. Air permeability increases and static charges reduce. Bacillus isolate 16P is chosen for economic production of polyamide surface modifying protease enzyme using 14 agro-industrial by-products as growth media. The highest protease production (175 U/mL) is achieved in media containing 6% linen meal at pH 7, after 72 h incubation period. Addition of KCl to linen meal medium enhances the protease production to about 18%. </span