Erytrocyte membrane anionic charge in type 2 diabetic patients with retinopathy

BACKGROUND: The Steno hypothesis states that changes in basement membrane anionic charge leads to diabetic microvascular complications. In diabetic nephropathy, loss of basement membrane glycosaminoglycans and the association between glomerular basement membrane heparan sulphate and proteinuria has been documented. A correlation between erythrocyte surface and the glomerular capillary wall charges has also been observed. The aim of this study is to evaluate the relationship between retinopathy and erythrocyte anionic charge and urinary glycosaminoglycan excretion in type 2 diabetic patients. METHODS: 49 subjects (58 ± 7 yrs, M/F 27/22) with type 2 diabetes with proliferative retinopathy (n = 13), nonproliferative retinopathy (n = 13) and without retinopathy (n = 23) were included in the study. 38 healthy subjects were selected as control group (57 ± 5 yrs, M/F 19/19). Erythrocyte anionic charge (EAC) was determined by the binding of the cationic dye, alcian blue. Urinary glycosaminoglycan and microalbumin excretion were measured. RESULTS: EAC was significantly decreased in diabetic patients with retinopathy (255 ± 30 ng alcian blue/10(6 )RBC, 312 ± 30 ng alcian blue/10(6 )RBC for diabetic and control groups respectively, p < 0.001). We did not observe an association between urinary GAG and microalbumin excretion and diabetic retinopathy. EAC is found to be negatively corralated with microalbuminuria in all groups. CONCLUSIONS: We conclude that type 2 diabetic patients with low erythrocyte anionic charge are associated with diabetic retinopathy. Reduction of negative charge of basement membranes may indicate general changes in microvasculature rather than retinopathy. More prospective and large studies needs to clarify the role of glycosaminoglycans on progression of retinopathy in type 2 diabetic patients

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects.</p> <p>Methods</p> <p>20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined.</p> <p>Results</p> <p>Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects.</p> <p>Conclusion</p> <p>The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism.</p

QT dispersion in patients with systemic lupus erythematosus: the impact of disease activity

<p>Abstract</p> <p>Background</p> <p>Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.</p> <p>Methods and Results</p> <p>One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).</p> <p>QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; <it>P </it>< 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, <it>P </it>= 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, <it>P </it>= 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (<it>P </it>< 0.004).</p> <p>Conclusions</p> <p>QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.</p> <p>Trial registration</p> <p>Clinicaltrial.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031797">NCT01031797</a></p

Prevalence of metabolic syndrome-related disorders in a large adult population in Turkey

BACKGROUND: There are few existing large population studies on the epidemiology of metabolic syndrome-related disorders of Turkey. The purpose of this study was to assess the prevalence of metabolic syndrome-related disorders in the Turkish adult population, to address sex, age, educational and geographical differences, and to examine blood pressure, body mass index, fasting blood glucose and serum lipids in Turkey. METHODS: This study was executed under the population study "The Healthy Nutrition for Healthy Heart Study" conducted between December 2000 and December 2002 by the Health Ministry of Turkey. Overall, 15,468 Caucasian inhabitants aged over 30 were recruited in 14 centers in the seven main different regions of Turkey. The data were analyzed with the Students' t, ANOVA or Chi-Square tests. RESULTS: Overall, more than one-third (35.08 %) of the participants was obese. The hypertensive people ratio in the population was 13.66 %, while these ratios for DM and metabolic syndrome were 4.16 % and 17.91 %, respectively. The prevalence of hypertension, metabolic syndrome and obesity were higher in females than males, whereas diabetes mellitus was higher in males than females. The prevalence of metabolic syndrome and related disorders were found to be significantly different across educational attainments for both men and women. The prevalence of hypertension increased with age, while it was remarkable that in the age group of 60–69 years, prevalence of diabetes mellitus and metabolic syndrome reached a peak value and than decreased. For obesity, the peak prevalence occurred in the 50–59 year old group. The prevalence of metabolic syndrome and related disorders were found to be significantly different according to geographical region. CONCLUSION: In conclusion, high prevalence of obesity and metabolic syndrome, particularly among women, is one of the major public health problems in Turkey. Interestingly, obesity prevalence is relatively high, but the prevalence of hypertension and hypercholesterolemia is relatively low in Turkish people. Future studies may focus on elucidating the reasons behind this controversy. Our findings may be helpful in formulating public health policy and prevention strategies on future health in Turkey

Kinetic, Isotherm and Thermodynamic Analysis on Adsorption of Cr(VI) Ions from Aqueous Solutions by Synthesis and Characterization of Magnetic-Poly(divinylbenzene-vinylimidazole) Microbeads

The magnetic-poly(divinylbenzene-1-vinylimidazole) [m-poly(DVB-VIM)] microbeads (average diameter 53–212 μm) were synthesized and characterized; their use as adsorbent in removal of Cr(VI) ions from aqueous solutions was investigated. The m-poly(DVB-VIM) microbeads were prepared by copolymerizing of divinylbenzene (DVB) with 1-vinylimidazole (VIM). The m-poly(DVB-VIM) microbeads were characterized by N2 adsorption/desorption isotherms, ESR, elemental analysis, scanning electron microscope (SEM) and swelling studies. At fixed solid/solution ratio the various factors affecting adsorption of Cr(VI) ions from aqueous solutions such as pH, initial concentration, contact time and temperature were analyzed. Langmuir, Freundlich and Dubinin–Radushkvich isotherms were used as the model adsorption equilibrium data. Langmuir isotherm model was the most adequate. The pseudo-first-order, pseudo-second-order, Ritch-second-order and intraparticle diffusion models were used to describe the adsorption kinetics. The apparent activation energy was found to be 5.024 kJ mol−1, which is characteristic of a chemically controlled reaction. The experimental data fitted to pseudo-second-order kinetic. The study of temperature effect was quantified by calculating various thermodynamic parameters such as Gibbs free energy, enthalpy and entropy changes. The thermodynamic parameters obtained indicated the endothermic nature of adsorption of Cr(VI) ions. Morever, after the use in adsorption, the m-poly(DVB-VIM) microbeads with paramagnetic property were separeted via the applied magnetic force. The magnetic beads could be desorbed up to about 97% by treating with 1.0 M NaOH. These features make the m-poly(DVB-VIM) microbeads a potential candidate for support of Cr(VI) ions removal under magnetic field

A Semianalytical PDF of Downlink SINR for Femtocell Networks

This paper presents a derivation of the probability density function (PDF) of the signal-to-interference and noise ratio (SINR) for the downlink of a cell in multicellular networks. The mathematical model considers uncoordinated locations and transmission powers of base stations (BSs) which reflect accurately the deployment of randomly located femtocells in an indoor environment. The derivation is semianalytical, in that the PDF is obtained by analysis and can be easily calculated by employing standard numerical methods. Thus, it obviates the need for time-consuming simulation efforts. The derivation of the PDF takes into account practical propagation models including shadow fading. The effect of background noise is also considered. Numerical experiments are performed assuming various environments and deployment scenarios to examine the performance of femtocell networks. The results are compared with Monte Carlo simulations for verification purposes and show good agreement

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

In quest of a systematic framework for unifying and defining nanoscience

This article proposes a systematic framework for unifying and defining nanoscience based on historic first principles and step logic that led to a “central paradigm” (i.e., unifying framework) for traditional elemental/small-molecule chemistry. As such, a Nanomaterials classification roadmap is proposed, which divides all nanomatter into Category I: discrete, well-defined and Category II: statistical, undefined nanoparticles. We consider only Category I, well-defined nanoparticles which are >90% monodisperse as a function of Critical Nanoscale Design Parameters (CNDPs) defined according to: (a) size, (b) shape, (c) surface chemistry, (d) flexibility, and (e) elemental composition. Classified as either hard (H) (i.e., inorganic-based) or soft (S) (i.e., organic-based) categories, these nanoparticles were found to manifest pervasive atom mimicry features that included: (1) a dominance of zero-dimensional (0D) core–shell nanoarchitectures, (2) the ability to self-assemble or chemically bond as discrete, quantized nanounits, and (3) exhibited well-defined nanoscale valencies and stoichiometries reminiscent of atom-based elements. These discrete nanoparticle categories are referred to as hard or soft particle nanoelements. Many examples describing chemical bonding/assembly of these nanoelements have been reported in the literature. We refer to these hard:hard (H-n:H-n), soft:soft (S-n:S-n), or hard:soft (H-n:S-n) nanoelement combinations as nanocompounds. Due to their quantized features, many nanoelement and nanocompound categories are reported to exhibit well-defined nanoperiodic property patterns. These periodic property patterns are dependent on their quantized nanofeatures (CNDPs) and dramatically influence intrinsic physicochemical properties (i.e., melting points, reactivity/self-assembly, sterics, and nanoencapsulation), as well as important functional/performance properties (i.e., magnetic, photonic, electronic, and toxicologic properties). We propose this perspective as a modest first step toward more clearly defining synthetic nanochemistry as well as providing a systematic framework for unifying nanoscience. With further progress, one should anticipate the evolution of future nanoperiodic table(s) suitable for predicting important risk/benefit boundaries in the field of nanoscience