Response Surface Methodology of the Unsteady Axisymmetric Magnetic Hybrid Nanofluid Flow Subject to a Shrinking Disk

This study examines the unsteady Fe3O4-CoFe2O4/H2O flow over a shrinking disk using both procedures (numerical and statistical). The respective boundary layer model is first transformed into a set of ODEs (ordinary differential equations) using the similarity transformations, and then solved numerically using the bvp4c solver. The duality of solutions is presented within specific use of the parameters such as magnetic field, suction strength and volumetric concentration of hybrid nanoparticles. From the numerical results, the velocity profile increases as the suction and magnetic parameters slightly increase. However, the temperature profile shows a reverse trend as compared to the velocity profile. Meanwhile, the justification of present physical factors (magnetic parameter, suction parameter) whether they are significant or not on the development of responses is tested using the model in Minitab. In addition, the generated response equation is also beneficial in predicting the flow and thermal distributions of this working fluid for other values of the emerging parameters

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

MHD Stagnation Point flow Towards an Exponentially Stretching Sheet with Prescribed wall Temperature and Heat Flux

The effects of thermal radiation on magnetohydrodynamic stagnation point flow and heat transfer towards an exponentially stretching sheet in the presence of prescribed wall temperature and prescribed heat flux are investigated. The governing partial differential equations are transformed into ordinary differential equations and then solved numerically by using Keller-box method. Numerical results for the velocity and temperature fields are shown graphically for various material parameters. The evaluated results are also compared with previously published papers which show excellent agreement. It is found that the thermal boundary layer thickness increases with increasing the values of magnetic parameter. The solutions for the linear stretching sheet are also recovered. The momentum boundary layer thickness increases with increasing the values of magnetic parameter. The temperature decreases when Prandtl number and velocity ratio parameter are increased

The Diagnostic Utility of Natural Killer Cell Subsets in Deep Vein Thrombosis

Alshaymaa M Alhabibi,1 Maisa A Wahab,2 Ahmed Khairy Sakr,2 Samar M Abd El-Hamid,1 Mohamed Yahia Zakaria,3 Azza Ali Althoqapy,4 Hanaa Mohammed Eid El Sayed,5 Sammar Ahmed Kasim,5 Hanan F Ibrahim,4 Ola I Saleh,6 Howida A Ahmed,6 Alaa H Sayed,7 Mahmoud Lotfy8 1Department of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 2Department of Vascular Surgery, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 3Department of Vascular and EndoVascular Surgery, Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt; 4Medical Microbiology and Immunology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 5Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 6Department of Radio-Diagnosis, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 7Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; 8Molecular Biology Department, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, Sadat City, Minufiya, EgyptCorrespondence: Alshaymaa M Alhabibi, Tel +201002894075, Email [email protected]: Natural killer (NK) cells are important components of adaptive and innate immune responses. NK cell subsets have different functions and may play a role in vascular disorders. This study aimed to evaluate the proportions of NK cells and their subsets to determine whether they can be used as markers of venous thrombosis and to identify whether there was a link between NK cell proportion and citrullinated histone (H3) levels.Patients and Methods: This study included 100 participants divided into Group I (n=50, patients with deep venous thrombosis (DVT)) and Group II (n=50, age- and sex-matched healthy controls). Group I was further categorized into Group Ia (n=25, patients with acute DVT) and Group Ib (n=25, patients with chronic DVT). The proportions of NK cells and their subsets were evaluated by flow cytometry using CD3/CD16/CD56. The levels of citrullinated histones (H3) were estimated using enzyme-linked immunosorbent assay (ELISA).Results: Compared to the control group, DVT patients had a significantly lower proportion of (CD56 dim/CD16+) NK cells, a significantly higher proportion of (CD56-/CD16+) NK cells and a high level of citrullinated histone (H3).Conclusion: NK cell subsets and citrullinated histone (H3) could be used as markers for DVT and as targets for therapeutic drugs to inhibit the formation or progression of thrombosis.Keywords: natural killer cell, natural killer cell subsets, citrullinated histone, deep venous thrombosi

ECS does not induce neuronal loss.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3A</a>: Representative images of the DG of sham and ECS-treated rats immunostained with neural marker NeuN. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3B</a>: Representative images from sham and ECS-treated rats stained with anti-NeuN, anti-activated caspase 3, propidium iodide, and Hoechst33342. Arrows show activated caspase 3-positive apoptotic cells. Apoptotic cells stained for activated caspase 3-positive are characterized by compacted and shrunken nucleus as accessed by Hoechst33342 and PI. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3C</a>: Histogram illustrating that there is no difference in the number of activated caspase 3-positive cells in the DG from sham (n = 8) and ECS (n = 7) rats. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3D</a>: Distribution of activated caspase 3-labeled cells in the DG, illustrating that the hilus and inner molecular layer contains the majority of apoptotic cells. The SZG had very few apoptotic cells and the granular cell layer (GCL) did not show cells positive or activated caspase 3. Scale bars: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3A</a>, 100 µm; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g003" target="_blank">Fig. 3B</a>, 10 µm.</p

BrdU⁺ dividing cells and Nile red⁺ pyknotic cells in glioblastomas.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7A</a>: Low magnification images of an RCAS-TVA-J12p16/M9Pten mouse with a glioblastoma (GBM), characterized by high cell density as demonstrated by counter-staining nuclei using PI. BrdU⁺ dividing cells are clearly evident within the tumor. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7B</a>: Higher magnification images of the tumor, demonstrating high proliferative activity; BrdU⁺ dividing cells are distributed throughout the tumor (upper panel). Pyknotic cells are present in the very center of the tumor (lower panel). Pyknotic cells are characterized by PI staining as having smaller and more compact nuclei (lower panel). Scale bars, 10 µm. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7C</a>: Higher magnification images of the tumor showing Nile red⁺ lipid droplets (visualized as small densely stained green structures). Nile red⁺ cells with intracellular lipid droplets (white arrows) and extracellular Nile red⁺ lipid droplets (red arrowheads) are clearly visible. The perimeter of the tumor (upper panel) is characterized by a smaller number of Nile red⁺ lipid droplets as compared to the center of the tumor (lower pane) suggesting that the latter contains more necrotic cells. Hoechst33342 (H), a nuclear counter-staining dye. Scale bars, 10 mµ; please note that in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7B–C</a> representative images of cell density and populations are acquired at 0.5 µm of z stack depth. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7D</a>: Cell density was determined by Hoechst33342 (H) staining. The tumor-enriched area is characterized by significantly higher cell density when compared to that of control mice or tumor-free tissue. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7E</a>: Dividing cells were determined by BrdU immunohistochemisty and non-dividing cells by the nuclear counter-staining with PI. About 22% of cells were BrdU⁺ dividing cells in the tumor-enriched areas; and when correcting for cell density there were 40-fold more BrdU⁺ cells in the tumor when compared to non-tumor tissue. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7F</a>: Pyknotic cells with small and compact nuclei are observed in the very center of the tumor. Approximately 5% of cells in the tumor-enriched area were pyknotic (20-fold more dead cells were observed in the tumor when compared to normal tissue). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094755#pone-0094755-g007" target="_blank">Fig. 7G</a>: When accounting for cell density there were at least10-fold more lipid-containing cells in the tumor when comparing to non-tumor tissue.</p