Latent Autoimmune Diabetes in Adults in the United Arab Emirates: Clinical Features and Factors Related to Insulin-Requirement

Aims

To describe and to characterize clinical features of latent autoimmune diabetes in adults (LADA) compared to type 1 and type 2 diabetes in the UAE.

Methods

In this cross-sectional study a dataset including 18,101 subjects with adult-onset (>30 years) diabetes was accessed. 17,072 subjects fulfilled the inclusion/exclusion criteria. Data about anthropometrics, demographics, autoantibodies to Glutamic Acid Decarboxylase (GADA) and to Islet Antigen 2 (anti-IA2), HbA1c, cholesterol and blood pressure were extracted. LADA was diagnosed according to GADA and/or anti-IA2 positivity and time to insulin therapy.

Results

437 (2.6%) patients were identified as LADA and 34 (0.2%) as classical type 1 diabetes in adults. Mean age at diagnosis, BMI, waist circumference, systolic blood pressure and HbA1c significantly differed between, LADA, type 2 and type 1 diabetes, LADA showing halfway features between type 2 and type 1 diabetes. A decreasing trend for age at diagnosis and waist circumference was found among LADA subjects when subdivided by positivity for anti-IA2, GADA or for both antibodies (p=0.013 and p=0.011 for trend, respectively). There was a gradual downward trend in autoantibody titre in LADA subjects requiring insulin within the first year from diagnosis to subjects not requiring insulin after 10 years of follow-up (p<0.001).

Conclusions

This is the first study describing the clinical features of LADA in the UAE, which appear to be different from both type 1 and type 2 diabetes. Furthermore, we showed that the clinical phenotype of LADA is dependent on different patterns of antibody positivity, influencing the time to insulin requirement.     

Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of “autism”. The second aim was to compare cognitive profiles obtained on the third edition versus 4^th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger’s Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.     

Effect of adding nano‐titanium dioxide on the microstructure,mechanical properties and in vitro bioactivity of a freeze cast merwinite scaffold

In the present research, merwinite (M) scaffolds with and without nano‐titanium dioxide (titania) were synthesized by water‐based freeze casting method. Two different amounts (7.5 and 10 wt%) of n‐TiO₂ were added to M scaffolds. They were sintered at temperature of 1573.15°K and at cooling rate of 4°K/min. The changes in physical and mechanical properties were investigated. The results showed that although M and M containing 7.5 wt% n‐TiO₂ (MT7.5) scaffolds had approximately the same microstructures in terms of pore size and wall thickness, these factors were different for sample MT10. In overall, the porosity, volume and linear shrinkage were decreased by adding different weight ratios of n‐TiO₂ into the M structure. According to the obtained mechanical results, the optimum mechanical performance was related to the sample MT7.5 (E = 51 MPa and σ = 2 MPa) with respect to the other samples, i.e.: M (E = 47 MPa and σ = 1.8 MPa) and MT10 (E = 32 MPa and σ = 1.4 MPa). The acellular in vitro bioactivity experiment confirmed apatite formation on the surfaces of all samples for various periods of soaking time. Based on cell study, the sample which possessed favorable mechanical behavior (MT7.5) supported attachment and proliferation of osteoblastic cells. These results revealed that the MT7.5 scaffold with improved mechanical and biological properties could have a potential to be used in bone substitute. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:550–556, 2015     

Effects of Initial Values and Convergence Criterion in the Two-Parameter Logistic Model When Estimating the Latent Distribution in BILOG-MG 3

Parameters of the two-parameter logistic model are generally estimated via the expectation-maximization algorithm, which improves initial values for all parameters iteratively until convergence is reached. Effects of initial values are rarely discussed in item response theory (IRT), but initial values were recently found to affect item parameters when estimating the latent distribution with full non-parametric maximum likelihood. However, this method is rarely used in practice. Hence, the present study investigated effects of initial values on item parameter bias and on recovery of item characteristic curves in BILOG-MG 3, a widely used IRT software package. Results showed notable effects of initial values on item parameters. For tighter convergence criteria, effects of initial values decreased, but item parameter bias increased, and the recovery of the latent distribution worsened. For practical application, it is advised to use the BILOG default convergence criterion with appropriate initial values when estimating the latent distribution from data.     

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

Background

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

Hypothesis

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

Methods and Results

We examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.

Conclusion

Taken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression.     

Inhibition of oxidative stress-induced amyloid β formation in NT2 neurons by culture filtrate of a strain of Streptomyces antibioticus

Actinomycetes isolated from Iran soil habitats were tested for the capacity to produce compounds which can protect neurons from cell death generated by oxidative stress in NT2 neurons. Confirmation of our initial hit was accomplished via the determination of amyloid β level using the enzyme-linked immunosorbent assay test. The most interesting amyloid β formation inhibitor discovered in our study was a secondary metabolite which was produced by strain HM45. This bioactive strain was identified as a strain of Streptomyces antibioticus DSM 40234 using polyphasic approach. The strain HM45 was deposited in Deutsche Sammlung von Mikroorganismen und Zellkulturen as S. antibioticus DSM 41955 and University of Tehran Microorganisms Sollection as S. antibioticus UTMC 00105. This work is the first report on efficiency of an actinomycete metabolite in prohibition of neurons death caused by amyloid β formation.     

Prolyl oligopeptidase of Trypanosoma brucei hydrolyzes native collagen,peptide hormones and is active in the plasma of infected mice

Proteases play important roles in many biological processes of parasites, including their host interactions. In sleeping sickness, Trypanosoma brucei proteases released into the host bloodstream could hydrolyze host factors, such as hormones, contributing to the development of the disease's symptoms. In this study, we present the identification of the T. brucei prolyl oligopeptidase gene (poptb) and the characterization of its corresponding enzyme, POP Tb. Secondary structure predictions of POP Tb show a structural composition highly similar to other POPs. Recombinant POP Tb produced in E. coli was active and highly sensitive to inhibitors of Trypanosoma cruzi POP Tc80. These inhibitors, which prevent T. cruzi entry into non-phagocytic cells, arrested growth of the T. brucei bloodstream form in a dose-dependent manner. POP Tb hydrolyzes peptide hormones containing Pro or Ala at the P1 position at a slightly alkaline pH, and also cleaves type I collagen in vitro and native collagen present in rat mesentery. Furthermore, POP Tb is released into the bloodstream of T. brucei infected mice where it remains active. These data suggest that POP Tb might contribute to the pathogenesis of sleeping sickness.     

Preparation,Optimization, and Characterization of SERS Sensor Substrates Based on Two-Dimensional Structures of Gold Colloid

Generally, the immobilization of two-dimensional nanoparticles in immersion procedures is time-consuming (over 24 h). In this paper, we report a very effective and simple method to fabricate two-dimensional gold nanoparticle patterns over large areas with high regularity for surface-enhanced Raman scattering (SERS). We achieved a highly sensitive SERS colloid surface by optimizing temperature and immersion time. The surfaces were characterized by X-ray photoelectron spectroscopy, UV–Vis, atomic force microscopy, and scanning electron microscopy. The SERS activity of surfaces was compared by using two techniques: “dip” and “dip and dry” in an aqueous solution of 10⁻⁶ M crystal violet. The influence of the morphology of the surface was investigated with both the dip and dip and dry techniques.     

Bcl-2 expression modulates cell adhesion and migration promoting branching of ureteric bud cells

Bcl-2 is the founding member of a family of proteins that influence apoptosis. During kidney development bcl-2 not only acts as a survival factor, but may also impact cell adhesive mechanisms and by extension branching morphogenesis. The interrelationship between cell adhesion, migration and apoptosis, important during development, is poorly understood. Here we examined the impact lack of bcl-2, an inhibitor of apoptosis, has on ureteric bud (UB) cell adhesion, migration, and branching morphogenesis. Bcl-2 -/- UB cells demonstrated increased cell migration, increased cell invasion and decreased adhesion to vitronectin and fibronectin compared with wild-type cells. Bcl-2 +/+ UB cells readily branched in collagen gel and Matrigel while bcl-2 -/- UB cells did not undergo significant branching in either matrix. Re-expression of bcl-2 in bcl-2 -/- UB cells restored their ability to undergo branching morphogenesis in Matrigel. Consistent with our in vitro data, we show that in the absence of bcl-2, embryonic kidneys undergo decreased UB branching. We observed decreased numbers of UB branch points, UB branch tips and a decreased distance to the first UB branch point in the absence of bcl-2. The alterations in bcl-2 -/- UB cell adhesion and migration was also associated with a significant alteration in expression of a number of extracellular matrix proteins. Bcl-2 -/- UB cells exhibited increased fibronectin expression and decreased thrombospondin-1 and osteopontin expression. Taken together, these data suggest that bcl-2 is required for the proper regulation of cell adhesive and migratory mechanisms, perhaps through modulation of the cellular microenvironment.