White Matter Microstructural Alteration in Type 2 Diabetes: A Combined UK Biobank Study of Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging

Background: Type 2 diabetes mellitus impacts the brain microstructural environment. Diffusion tensor imaging (DTI) has been widely used to characterize white matter microstructural abnormalities in type 2 diabetes but fails to fully characterise disease effects on complex white matter tracts. Neurite orientation dispersion and density imaging (NODDI) has been proposed as an alternative to DTI with higher specificity to characterize white matter microstructures. Although NODDI has not been widely applied in diabetes, this biophysical model has the potential to investigate microstructural changes in white matter pathology.Aims and objectives: (1) To investigate brain white matter alterations in people with type 2 diabetes using DTI and NODDI; (2) To assess the association between white matter changes in type 2 diabetes with disease duration and diabetes control as reflected by glycated haemoglobin (HbA1c) levels.Methods: We examined white matter microstructure in 48 white matter tracts using data from the UK Biobank in 3,338 participants with type 2 diabetes (36% women, mean age 66 years) and 30,329 participants without type 2 diabetes (53% women, mean age 64 years). The participants had undergone 3.0T multiparametric brain imaging, including T1 weighted imaging and diffusion imaging for DTI and NODDI. Region of interest analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and isotropic water fraction (IsoVF) were conducted to assess white matter abnormalities. A general linear model was applied to evaluate intergroup white matter differences and their association with the metabolic profile.Result: Reduced FA and ICVF and increased MD, AD, RD, ODI, and IsoVF values were observed in participants with type 2 diabetes compared to non-type 2 diabetes participants (P<0.05). Reduced FA and ICVF in most white matter tracts were associated with longer disease duration and higher levels of HbA1c (0< r ≤0.2, P<0.05). Increased MD, AD, RD, ODI and IsoVF also correlated with longer disease duration and higher HbA1c (0< r ≤0.2, P<0.05).Discussion: NODDI detected microstructural changes in brain white matter in participants with type 2 diabetes. The revealed abnormalities are proxies for lower neurite density and loss of fibre orientation coherence, which correlated with longer disease duration and an index of poorly controlled blood sugar. NODDI contributed to DTI in capturing white matter differences in participants with type 2 diabetes, suggesting the feasibility of NODDI in detecting white matter alterations in type 2 diabetes.Conclusion: Type 2 diabetes can cause white matter microstructural abnormalities that have associations with glucose control. The NODDI diffusion model allows the characterisation of white matter neuroaxonal pathology in type 2 diabetes, giving biophysical information for understanding the impact of type 2 diabetes on brain microstructure

Investigation of the Effect of Substrate Orientation on the Structural, Electrical and Optical Properties of n-type GaAs1-xBix Layers Grown by Molecular Beam Epitaxy

Current-Voltage (I-V), Capacitance-Voltage (C-V), Deep Level Transient Spectroscopy (DLTS), Laplace DLTS, Photoluminescence (PL) and Micro-Raman techniques have been employed to investigate the effect of the orientation of the substrates on the structural, electrically and optically active defects in dilute GaAs1−xBix epilayers structures having a Bi composition x = ~5.4%, grown by Molecular Beam Epitaxy (MBE) on (100) and (311)B GaAs planes. X-ray diffraction results revealed that the in-plane strain in the Ga(As,Bi) layer of the samples grown on (100)-oriented substrate (−0.0484) is significantly larger than that of the samples grown on (311)B-oriented substrate. The substrate orientation is found to have a noticeable impact on the Bi incorporation and the electrical properties of dilute GaAsBi Schottky diodes. The I-V characteristics showed that (100) Schottky diodes exhibited a larger ideality factor and higher barrier height compared with (311)B samples. The DLTS measurements showed that the number of electrically active traps were different for the two GaAs substrate orientations. In particular, three and two electron traps are detected in samples grown on (100) and (311)B GaAs substrates, respectively, with activation energies ranging from 0.12 to 0.41 eV. Additionally, one hole trap was observed only in sample grown on (100) substrates with activation energy 0.24 eV. The observed traps with small activation energies are attributed to Bi pair defects. The photoluminescence (PL) and Raman spectra have evidenced different compressive strain which affects considerably the optical properties. Furthermore, the PL spectra were also affected by different contributions of Bi- related traps which are different for different substrate orientation in agreement with DLTS results

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic &lsquo;Umrah&rsquo; ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia