Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

Most cases of Apert syndrome are caused by mutations in the FGFR2 gene, either Ser252Trp or Pro253Arg. In these patients, over the last decades, spring-assisted posterior vault expansion (SA-PVE) has been the technique of choice for cranial vault expansion in the Craniofacial Unit of Great Ormond Street Hospital for Children (GOSH), London. The aim of this study was to investigate if there is a difference in preoperative intracranial volume (ICV) in patients with Apert syndrome with Ser252Trp or Pro253Arg mutation and whether these mutations affect the change in ICV achieved by SA-PVE. The GOSH craniofacial SA-PVE database was used to select patients with complete genetic testing and preoperative and postoperative computed tomography scans. ICV was calculated using FSL (FMRIB Analysis Group, Oxford) and adjusted based on Apert-specific growth curves. Sixteen patients were included with 8 having Ser252Trp mutation and 8 having Pro253Arg mutation. The mean preoperative adjusted computed tomography volume for patients in the Ser252Trp group was 1137.7 cm3 and in the Pro253Arg group was 1115.8 cm3 (P=1.00). There was a significant increase in ICV following SA-PVE in all patients (P<0.001) with no difference in mean change in ICV between the groups (P=0.51). Four (50%) patients with Ser252Trp mutation and 3 (37.5%) with Pro253Arg mutations required a second operation after primary SA-PVE. The results demonstrate that regardless of the mutation present, SA-PVE was successful in increasing ICV in patients with Apert syndrome and that a repeat volume expanding procedure was required by a similar number of patients in the 2 groups

Experimental investigation on compression ignition engine powered with pentanol and thevetia peruviana methyl ester under reactivity controlled compression ignition mode of operation

In the current study, an effort is carried out to study the influence of pentanol as low reactive fuel (LRF) along with diesel and Thevetia peruviana methyl ester (TPME) as high reactive fuels (HRF) in reactivity controlled compression ignition (RCCI) engine. The experiments are conducted on dual fuel engine at 50% load for RCCI mode of operation by varying pentanol percentage in injected fuels. The results revealed that RCCI mode of operation at 10% of pentanol in injected fuels exhibited higher brake thermal efficiency (BTE) of 22.15% for diesel and pentanol fuel combination, which is about 9.1% and 27.3% higher than other B20 and pentanol, B100 and pentanol fuel combinations respectively. As the percentage of pentanol increased in injected fuels, hydrocarbon (HC) and carbon monoxide (CO) emissions are increased while nitrogen oxide (NOx) and smoke emissions are decreased. Among various fuel combinations tested diesel and pentanol fuel combination gives lower HC, CO and smoke emissions and higher NOx emissions. At 10% pentanol in injected fuels, the highest heat release rate (HRR) and in-cylinder pressure are found for diesel and pentanol fuel combinations compared with other fuels

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Display of hidden properties of flexible aerogel based on bacterial cellulose/polyaniline nanocomposites with helping of multiscale modeling

Tuning the synthesis conditions of polyaniline (PANI) such as aniline monomer’s protonation states and adding surfactants into polymerization mixture or even the existence of bacterial cellulose (BC) had a substantial influence on the final properties. To explore the relationship between components presented in the polymerization mixture, simulation tools (molecular dynamics (MD)/Monte Carlo (MC)/Density functional theory (DFT)) can be used. Herein, nanocomposite aerogels of BC/PANI were fabricated in the presence of anionic surfactants; sodium dodecyl benzene sulfonate (SDBS) or sodium dodecyl sulfonate (SDS) at two different concentrations (0.05 M and 1 M) of HCl solution. Two types of aniline monomers were considered in the polymerization mixture based on HCl solution’s concentrations including neutral and protonated aniline in 0.05 and 1 M, respectively. Various morphologies from nanobelts (with a width of 100–500 nm) and polyhedrons (with a thickness of 100–700 nm) in 0.05 M of acid solution in the presence of SDBS or SDS, respectively, were detected. Based on DFT computations it was found that electrostatic interactions and the formation of hydrogen bonds play a vital role in the interfacial interaction mechanism between both surfactants (SDBS and SDS) and different protonation forms of aniline monomers. Nevertheless, in the case of SDBS and aniline monomers (in both 0.05 and 1 M of HCl solutions), an excess interaction mechanism, namely π-π stacking, was observed, which enhanced the interaction between them and confirmed by experimental results. Therefore, the highest conductivity of 0.8 S/cm was obtained for the BC/PANI prepared with SDBS in 1 M of HCl solution. Besides, the smallest energy gap of 2.74 eV was predicted from DFT calculations for this sample that further confirmed its high electrical properties and smaller band gap at 3 nm, which was also confirmed by MD and MC

POSTER: Fuzzy Rough Set as feature selection for QSAR modeling of 2,4,5-trisubstituted imidazoles, nontoxic modulators of P-glycoprotein mediated multidrug resistance

info:eu-repo/semantics/nonPublishe

Facile template preparation of novel electroactive scaffold composed of polypyrrole-coated poly(glycerol-sebacate-urethane) for tissue engineering applications

Poly(glycerol-sebacate-urethane) (PGS-U) is an attractive candidate as a super-elastic and biocompatible scaffold for inserting nanoparticles and polymers with a straightforward synthesis. Herein, a series of PGS-U scaffolds with various crosslink densities was prepared for subsequent polypyrrole (PPy) polymerization. The in-situ polymerization of PPy was employed to deposit the PPy particles throughout the scaffolds, and the continuous electrically conductive pathways were built within the scaffolds. Moreover, due to their favorable mechanical and anti-bacterial properties, zinc oxide (ZnO) nanoparticles were embedded within the scaffold. The composition of the scaffolds was confirmed by different characterization techniques, including FTIR, FE-SEM, and EDX. Static and cyclic compression tests were conducted to evaluate the mechanical performance of scaffolds under dry and hydrated conditions. All scaffolds presented high structural stability and full shape recovery after releasing the load. They were thermally stable up to at least 200 °C. The addition of PPy boosted the electrical conductivity, and the inclusion of ZnO particles improved the surface hydrophilicity and anti-bacterial behavior of the scaffolds. Altogether, this study suggests the further developments of these nanocomposites as satisfactory electrically conductive scaffolds for tissue engineering applications

Development of physical, mechanical, antibacterial and cell growth properties of poly(glycerol sebacate urethane) (PGSU) with helping of curcumin and hydroxyapatite nanoparticles

Biocompatible and antimicrobial elastomers with controlled hydrophilicity and degradation rate, as well as appropriate stiffness and elasticity, are interesting for biomedical applications, such as regenerative medicine and tissue engineering. Nevertheless, most of the tissue-engineered scaffolds do not possess a combination of the aforementioned properties. In this study, we prepare a library of poly(glycerol sebacate urethane)s (PGSU) containing different concentrations of hydroxyapatite nanoparticles (nHA) and curcumin. Poly(glycerol sebacate) prepolymers were crosslinked by hexamethylene diisocyanate, and the resulting elastomers were investigated by FTIR spectroscopy. The bioelastomers had an elastic modulus and ultimate tensile strength within a range of 1.9-4.1 MPa and 1.6-2 MPa, respectively. PGSU showed a water contact angle of 85.0 ± 2.2°. The hydrophilicity significantly improved by adding nHA, and the water contact angle was reduced to 71.8± 1.1°. It was found from the hydrolytic degradation study that while nHA accelerated the degradation rate, the hybrid nHA/curcumin compound noticeably reduced it and then increased the physiological stability of the PGSU matrix. Furthermore, the scaffolds loaded with curcumin exhibited significant antimicrobial activity against both Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) bacteria. The in vitro biocompatibility tests showed significant cell attachment, proliferation, and viability of mouse fibroblast L929 cells. Our findings indicated that the addition of curcumin and nHA into PGSU could impart new features to the PGSU matrix and introduce the PGSU-based elastomers as a promising candidate for a range of tissue engineering applications, specifically hard tissues. This journal i