Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

IntroductionType II diabetes mellitus (T2DM) is a metabolic disorder that poses a serious health concern worldwide due to its rising prevalence. Hypertension (HT) is a frequent comorbidity of T2DM, with the co-occurrence of both conditions increasing the risk of diabetes-associated complications. Inflammation and oxidative stress (OS) have been identified as leading factors in the development and progression of both T2DM and HT. However, OS and inflammation processes associated with these two comorbidities are not fully understood. This study aimed to explore changes in the levels of plasma and urinary inflammatory and OS biomarkers, along with mitochondrial OS biomarkers connected to mitochondrial dysfunction (MitD). These markers may provide a more comprehensive perspective associated with disease progression from no diabetes, and prediabetes, to T2DM coexisting with HT in a cohort of patients attending a diabetes health clinic in Australia.MethodsThree-hundred and eighty-four participants were divided into four groups according to disease status: 210 healthy controls, 55 prediabetic patients, 32 T2DM, and 87 patients with T2DM and HT (T2DM+HT). Kruskal-Wallis and χ2 tests were conducted between the four groups to detect significant differences for numerical and categorical variables, respectively.Results and discussionFor the transition from prediabetes to T2DM, interleukin-10 (IL-10), C-reactive protein (CRP), 8-hydroxy-2’-deoxyguanosine (8-OHdG), humanin (HN), and p66Shc were the most discriminatory biomarkers, generally displaying elevated levels of inflammation and OS in T2DM, in addition to disrupted mitochondrial function as revealed by p66Shc and HN. Disease progression from T2DM to T2DM+HT indicated lower levels of inflammation and OS as revealed through IL-10, interleukin-6 (IL-6), interleukin-1β (IL-1β), 8-OHdG and oxidized glutathione (GSSG) levels, most likely due to antihypertensive medication use in the T2DM +HT patient group. The results also indicated better mitochondrial function in this group as shown through higher HN and lower p66Shc levels, which can also be attributed to medication use. However, monocyte chemoattractant protein-1 (MCP-1) levels appeared to be independent of medication, providing an effective biomarker even in the presence of medication use. The results of this study suggest that a more comprehensive review of inflammation and OS biomarkers is more effective in discriminating between the stages of T2DM progression in the presence or absence of HT. Our results further indicate the usefulness of medication use, especially with respect to the known involvement of inflammation and OS in disease progression, highlighting specific biomarkers during disease progression and therefore allowing a more targeted individualized treatment plan

A derivational model of discontinuous parsing

The notion of latent-variable probabilistic context-free derivation of syntactic structures is enhanced to allow heads and unrestricted discontinuities. The chosen formalization covers both constituent parsing and dependency parsing. The derivational model is accompanied by an equivalent probabilistic automaton model. By the new framework, one obtains a probability distribution over the space of all discontinuous parses. This lends itself to intrinsic evaluation in terms of perplexity, as shown in experiments.Postprin

Genetics of diabetic kidney disease: A follow-up study in the Arab population of the United Arab Emirates

Background: Two genome-wide association studies in European and Japanese populations reported on new loci for diabetic kidney disease (DKD), including FTO. In this study, we have replicated these investigations on a cohort of 410 Type 2 diabetes mellitus (T2DM) patients of Arab origin from the United Arab Emirates (UAE). Methods and Results: The cohort included 145 diabetic patients diagnosed with DKD and 265 diabetics free of the disease. In general, we were able to confirm the association between the FTO locus and DKD, as reported in the Japanese population. Specifically, there were significant associations with two single nucleotide polymorphisms (SNPs), namely rs1421086 (p =.013, OR = 1.52 depending on allele G, 95% CI: 1.09–2.11) and rs17817449 (p =.0088, OR = 1.55 depending on allele C, 95% CI: 1.12–2.14) of the FTO locus. Both SNPs were in linkage disequilibrium with rs56094641, also as reported in the Japanese population. While the alleles of both SNPs, which increase the risk of DKD, were associated with higher Body Mass Index (BMI), their associations with DKD were independent of the BMI effects. Conclusions: This study confirms that FTO is a multiethnic locus for DKD which is independent from any influence of BMI and/or obesity

Clinical and genetic associations of renal function and diabetic kidney disease in the United Arab Emirates: A cross-sectional study

OBJECTIVES: Within the Emirati population, risk factors and genetic predisposition to diabetic kidney disease (DKD) have not yet been investigated. The aim of this research was to determine potential clinical, laboratory and reported genetic loci as risk factors for DKD. RESEARCH DESIGN AND METHODS: Four hundred and ninety unrelated Emirati nationals with type 2 diabetes mellitus (T2DM) were recruited with and without DKD, and clinical and laboratory data were obtained. Following adjustments for possible confounders, a logistic regression model was developed to test the associations of 63 single nucleotide polymorphisms (SNPs) in 43 genetic loci with DKD (145 patients with DKD and 265 without DKD). Linear regression models, adjusted for age and gender, were then used to study the genetic associations of five renal function traits, including 83 SNPs with albumin-to-creatinine ratio, 92 SNPs with vitamin D (25-OH cholecalciferol), 288 SNPs with estimated glomerular filtration rate (eGFR), 363 SNPs with serum creatinine and 73 SNPs with blood urea. RESULTS: Patients with DKD, as compared with those without the disease, were mostly men (52%vs38% for controls), older (67vs59 years) and had significant rates of hypertension and dyslipidaemia. Furthermore, patients with DKD had T2DM for a longer duration of time (16vs10 years), which in an additive manner was the single factor that significantly contributed to the development of DKD (p=0.02, OR=3.12, 95% CI 1.21 to 8.02). Among the replicated associations of the genetic loci with different renal function traits, the most notable included CONCLUSIONS: Associations were found between several genetic loci and risk markers for DKD, which may influence kidney function traits and DKD in a population of Arab ancestry

Stochastic Modelling: From Pattern Classification to Speech Recognition and Language Translation

This paper gives an overview of the stochastic modelling approach to machine translation. Starting with the Bayes decision rule as in pattern classification and speech recognition, we show how the resulting system architecture can be structured into three parts: the language model probability, the string translation model probability and the search procedure that gener-ates the word sequence in the target language. We discuss the properties of the system components and report results on the translation of spoken dialogues in the VERBMOBIL project. The experience obtained in the VERB-MOBIL project, in particular a large-scale end-to-end evaluation, showed that the stochastic modelling approach resulted in significantly lower error rates than three competing translation approaches: the sentence error rate was 29 % in comparison with 52 % to 62% for the other translation approaches.

Detection of an optical transient following the 13 March 2000 short/hard gamma-ray burst

We imaged the error box of a gamma-ray burst of the short (0.5 s), hard type (GRB 000313), with the BOOTES-1 experiment in southern Spain, starting 4 min after the gamma-ray event, in the I-band. A bright optical transient (OT 000313) with I = 9.4 +/- 0.1 was found in the BOOTES-1 image, close to the error box (3-sigma) provided by BATSE. Late time VRIK'-band deep observations failed to reveal an underlying host galaxy. If the OT 000313 is related to the short, hard GRB 000313, this would be the first optical counterpart ever found for this kind of events (all counterparts to date have been found for bursts of the long, soft type). The fact that only prompt optical emission has been detected (but no afterglow emission at all, as supported by theoretical models) might explain why no optical counterparts have ever been found for short, hard GRBs.This fact suggests that most short bursts might occur in a low-density medium and favours the models that relate them to binary mergers in very low-density enviroments.Comment: Revised version. Accepted for publication in Astronomy and Astrophysics Letters, 5 pages, 3 figure