A gene variant near ATM is significantly associated with metformin treatment response In type 2 diabetes: A replication and meta-analysis of five cohorts

_Aims/hypothesis:_ In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. _Methods:_ Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n=929) and the Rotterdam Study (n=182) from the Netherlands, and the CARDS Trial (n=254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. _Results:_ In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p=0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p=0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p=0.016 and OR 1.25, 95% CI 1.33, 1.38, p=7.8×10-6, respectively). _ Conclusions/inte

Synthesis, spectral analysis and pharmacological study of N'- substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazides

ABSTRACT A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively

Striking multiple synergies in novel three-phase fluoropolymer nanocomposites by combining titanium dioxide and graphene oxide as hybrid fillers

In this study, novel three-phase polymer nanocomposites comprising of polyvinylidene fluoride (PVDF), titanium dioxide (TiO2) nanoparticles and graphene oxide (GO) were prepared using colloidal blending. The PVDF/TiO2/GO nanocomposites were characterized by FTIR, XRD, TGA, optical microscopy, SEM, AFM and contact angle analysis. The dielectric properties of these three-phase polymer nanocomposites were investigated using broadband dielectric spectroscopy in the frequency range 50 Hz–20 MHz and temperature in the range 40–150 °C. The FTIR and XRD results infer good interaction between the constituents of nanocomposites. The microscopic studies infer homogeneous dispersion and distribution of TiO2 nanoparticles and GO within the PVDF matrix. A notable improvement in the thermal stability of PVDF was observed by the addition of TiO2 and GO as hybrid fillers. The dielectric performance of PVDF/TiO2/GO nanocomposite films was significantly improved as compared to PVDF/TiO2 (90/10) nanocomposite film. The dielectric constant increases from 18.57 (50 Hz, 150 °C) for PVDF/TiO2 (90/10) nanocomposite film to 165.16 (50 Hz, 150 °C) for PVDF/TiO2/GO nanocomposite film containing 7 wt% TiO2 and 3 wt% GO loading. In addition, the dielectric loss also increases from 1.71 (50 Hz, 150 °C) for PVDF/TiO2 (90/10) nanocomposite film to 3.68 (50 Hz, 150 °C) for PVDF/TiO2/GO nanocomposite film containing 7 wt% TiO2 and 3 wt% GO loading. These intriguing properties of PVDF/TiO2/GO nanocomposites could shed some light on the incorporation of different types of hybrid fillers in a suitable polymer matrix for the development of novel three-phase nanocomposites as intelligent materials for embedded passive applications.One of the authors, Kalim Deshmukh would like to acknowledge the financial support from the management of B. S. Abdur Rahman University, Chennai, 600048, TN, India in terms of Junior Research Fellowship (JRF) to carry out this research work.Scopu

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Not AvailableCarbon content in soils changes depending on the land use system, type of management practice and time. There is an increasing concern about the soil quality vis-à-vis organic carbon content in soils due to global warming and enhancedCO2 concentration in the atmosphere. This has led to estimate carbon stock in soils at global and regional levels. The objective of the present study was to evaluate RothC model to estimate total organic carbon (TOC) changes under four long term fertilizer experimental sites representing subhumid moist (Sarol and Nabibagh), sub-humid dry (Panjri) and semi-arid (Teligi) climate in India. The plant carbon input rate was calibrated using organic carbon and other soil parameters using RothC. The results showed that RothC could simulate changes in TOC in two contrasting eco-sites for surface soil layers. The root mean square error (RMSE) considered as modelling error ranged from 11.50 to 15.01, 4.70 to 11.60, 2.14 to 6.52 and 1.45 to 13.74 in the surface layers of Sarol, Nabibagh, Panjri, and Teligi sites, respectively. The simulation biases expressed by M (relative error) by Student‘t’ value for all the treatments at these sites were non-significant with two exceptions. Observed trends in TOC consist of an increase for all the four treatments in the sub-humid site of Sarol and Nabibagh; while manures alone or in combination increase TOC appreciably in Teligi and Panjri. TOC remained, however, almost similar over years for the control (no fertilizer or manure) and NPK treatments in all the four sites. Analysis of RothC output data showed that this model could be used as a tool to arrive at different threshold values of rainfall to influence decomposition rate modifier and thus to find out rate of organic carbon sequestration in various bioclimatic systems.Not Availabl

Newly developed biodegradable polymer nanocomposites of cellulose acetate and Al2O3 nanoparticles with enhanced dielectric performance for embedded passive applications

In this study, biopolymer nanocomposites of cellulose acetate (CA) and Al2O3 nanoparticles (Al2O3 NPs) were successfully obtained using solution blending method. The effect of Al2O3 NPs loading on the microstructure, morphology, thermal and dielectric prop erties of CA/Al2O3 nanocomposites was investigated using FTIR, XRD, TGA, optical microscopy, SEM, AFM and impedance spectroscopy technique. The FTIR results infer good interaction between CA and Al2O3 NPs. The XRD and microscopic studies demonstrated that Al2O3 nanoparticles were homogeneously dispersed in the CA matrix. The TGA results indicate that the onset degradation temperature of CA/Al2O3 nanocomposites is shifted towards higher temperature in the presence of Al2O3 NPs. The contact angle measurements infer reduction in the wettability of CA matrix with increasing Al2O3 NPs loading. On the other hand, the dielectric properties of CA were improved due to an incorporation of Al2O3 NPs. The dielectric constant increases from 8.63 (50 Hz, 30 C) for neat CA matrix to 27.57 (50 Hz, 30 C) for CA/Al2O3 nanocomposites with 25 wt% Al2O3 loading. Similarly, the dielectric loss also increases from 0.26 (50 Hz, 30 C) for neat CA matrix to 0.64 (50 Hz, 30 C) for CA/Al2O3 nanocomposites with 25 wt% Al2O3 NPs loading. How ever, very low values of tan d (below 1) were observed for all the samples. These results suggest that CA/Al2O3 nanocomposites with improved dielectric properties seem to be a promising candidate for designing electronic devi ces such as embedded passivesOne of the authors, Kalim Deshmukh would like to acknowledge the financial support from the management of B. S. Abdur Rahman University, Chennai - 600048, TN, India in terms of Junior Research Fellowship (JRF) to carry out this research work.Scopu

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Not AvailableCarbon content in soils changes depending on the land use system, type of management practice and time. There is an increasing concern about the soil quality vis-à-vis organic carbon content in soils due to global warming and enhanced CO2 concentration in the atmosphere. This has led to estimate carbon stock in soils at global and regional levels. The objective of the present study was to evaluate RothC model to estimate total organic carbon (TOC) changes under four long term fertilizer experimental sites representing subhumid moist (Sarol and Nabibagh), sub-humid dry (Panjri) and semi-arid (Teligi) climate in India. The plant carbon input rate was calibrated using organic carbon and other soil parameters using RothC. The results showed that RothC could simulate changes in TOC in two contrasting eco-sites for surface soil layers. The root mean square error (RMSE) considered as modelling error ranged from 11.50 to 15.01, 4.70 to 11.60, 2.14 to 6.52 and 1.45 to 13.74 in the surface layers of Sarol, Nabibagh, Panjri, and Teligi sites, respectively. The simulation biases expressed by M (relative error) by Student‘t’ value for all the treatments at these sites were non-significant with two exceptions. Observed trends in TOC consist of an increase for all the four treatments in the sub-humid site of Sarol and Nabibagh; while manures alone or in combination increase TOC appreciably in Teligi and Panjri. TOC remained, however, almost similar over years for the control (no fertilizer or manure) and NPK treatments in all the four sites. Analysis of RothC output data showed that this model could be used as a tool to arrive at different threshold values of rainfall to influence decomposition rate modifier and thus to find out rate of organic carbon sequestration in various bioclimatic systems.Not Availabl

Eco-Friendly Synthesis of Graphene Oxide Reinforced Hydroxypropyl Methylcellulose/Polyvinyl Alcohol Blend Nanocomposites Filled with Zinc Oxide Nanoparticles for High-k Capacitor Applications

Polymer/inorganic nanocomposites comprising of hydroxypropyl methylcellulose and polyvinyl alcohol as a polymer matrix and unique combination of graphene oxide and zinc oxide nanoparticles as fillers have been prepared using colloidal processing technique and characterized using various analytical methods. The dielectric properties of the nanocomposites are investigated using impedance analyzer. The nanocomposites show improvement in the dielectric properties compared to hydroxypropyl methylcellulose/polyvinyl alcohol (50/50) blends, which results from the homogeneous dispersion of fillers into the polymer matrix. The results indicate that these nanocomposites have a potential to meet the technological demands of high-k dielectrics and/or embedded capacitors.Scopu

Dark Adaptation in Patients with Primary Open-Angle Glaucoma, Pseudoexfoliation Glaucoma and Childhood Glaucoma

Purpose To investigate the state of dark adaptation and macular blood flow in different forms of glaucoma. Methods Eighteen eyes of 18 patients with primary open-angle glaucoma, 14 eyes of 14 patients with pseudoexfoliation glaucoma, and 10 eyes of 10 patients with childhood glaucoma (CG) were examined by means of dark adaptometry, scanning-laser retinal flowmetry, and retinal tomography. Results All glaucomatous eyes had comparable optic disc excavation (one-way ANOVA, p = 0.138). Eyes with CG had significantly lower best-corrected visual acuity than the other groups (Tukey, all p <0.0001). Macular perfusion was comparable in all three groups (one – way ANOVA, p = 0.08). The delay in rod-cone break time in the CG group was significantly higher than in the other groups (Tukey, all p <0.0001). The scotopic sensitivity threshold in the CG group was significantly greater than in the other groups (Tukey, all p <0.01). Conclusion This underlying dysfunction of dark adaptation may contribute, at least to some extent, to the decreased visual perception observed in patients with CG. © Georg Thieme Verlag KG Stuttgart · New York