The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Quantification of the presence of enzymes in gelatin zymography using the Gini index.

Gel zymography quantifies the activity of certain enzymes in tumor processes. These enzymes are widely used in medical diagnosis. In order to analyze them, experts classify the zymography spots into various classes according to their tonalities. This classification is done by visual analysis, which is what makes it a subjective process. This work proposes a methodology to carry out this classifications with a process that involves an unsupervised learning algorithm in the images, denoted as the GI algorithm. With the experiments shown in this paper, this methodology could constitute a tool that bioinformatics scientists can trust to perform the desired classification since it is a quantitative indicator to order the enzymatic activity of the spots in a zymography.

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior.

Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

BACKGROUND: Chronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications. METHODS: A cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessments, as well chronic kidney disease diagnosis according to the KDIGO guideline. Urinary MMP-9 was quantified by ELISA and adjusted using urinary creatinine (UCr). RESULTS: A total of 111 patients were included. Most participants were women (66%). Mean age was 61 ± 10 years and median T2DM duration was estimated at 11 years. Through multivariate analysis, MMP-9/UCr was found to be associated with albumin concentration and albumin to creatinine ratio. DISCUSSION: Validation of non-invasive biomarkers of chronic kidney disease among T2DM patients is necessary. Here, we demonstrate MMP-9/UCr as a potential biomarker of albumin concentration and albumin to creatinine ratio in Mexican patients with T2DM.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Molecularly imprinted polypyrrole based electrochemical sensor for selective determination of 4-ethylphenol.

This work describes the development of an electrochemical sensor based on a molecularly imprinted polymer (MIP) for sensitive and selective determination of 4-ethylphenol in wine. The sensor has been built by means of the electrosynthesis of the MIP on a glassy carbon electrode surface using cyclic voltammetry. The electropolymerization has been performed in the presence of 4-ethylphenol and pyrrole as template molecule and functional monomer, respectively. The influence of the molar ratios of template molecules to functional pyrrole monomers and the time needed to remove the template have been optimized taking into account the differential pulse voltammetric response of 4-ethylphenol. Under the optimal experimental conditions the developed MIP/GCE sensor shows good capability of detection (0.2 µM, α = ß = 0.05) and reproducibility (3.0%) in the concentration range from 0.2 to 34.8 µM. The influence of possible interfering species in the analytical response has been studied and the sensor has successfully been applied to the determination of 4-ethylphenol in different wine samples.

The Constrained NMSSM with right-handed neutrinos.

In this article, we demonstrate that the inclusion of right-handed neutrino superfields in the Next-to-Minimal Supersymmetric Standard Model (NMSSM) makes it possible to impose universality conditions on the soft supersymmetry-breaking parameters at the Grand Unification scale, alleviating many of the problems of the so-called Constrained NMSSM. We have studied the renormalization group equations of this model, showing that right-handed neutrinos greatly contribute to driving the singlet Higgs mass-squared parameter negative, which makes it considerably easier to satisfy the conditions for radiative electroweak symmetry breaking. The new fields also lead to larger values of the Standard Model Higgs mass, thus making it easier to reproduce the measured value. As a consequence, all bounds from colliders and low-energy observables can be fulfilled in wide areas of the parameter space. However, the relic density in these regions is generally too high requiring some form of late entropy production to dilute the density of the lightest supersymmetric particle.

Confronting dark matter with the diphoton excess from a parent resonance decay.

A diphoton excess with an invariant mass of about 750 GeV has been recently reported by both ATLAS and CMS experiments at LHC. While the simplest interpretation requires the resonant production of a 750 GeV (pseudo)scalar, here we consider an alternative setup, with an additional heavy parent particle which decays into a pair of 750 GeV resonances. This configuration improves the agreement between the 8 and 13 TeV data. Moreover, we include a dark matter candidate in the form of a Majorana fermion which interacts through the 750 GeV portal. The invisible decays of the light resonance help to suppress additional decay channels into Standard Model particles in association with the diphoton signal. We realise our hierarchical framework in the context of an effective theory, and we analyse the diphoton signal as well as the consistency with other LHC searches. We finally address the interplay of the LHC results with the dark matter phenomenology, namely the compatibility with the relic density abundance and the indirect detection bounds.