How the sialylation level of serum N-acetyl-beta-D-glucosaminidase A form in Type 1 diabetes mellitus influences their activity?

It was verified that the serum N-acetyl-beta-D-glucosaminidase (NAG) activity is elevated in diabetes, but there are no reports about changes in the sialic acid (SA) content in the carbohydrate parts of the NAG A form and its influence on the total changes in NAG activity in type 1 diabetes mellitus patients with and without secondary complications. The NAG A form was isolated from the serum of 81 insulin-dependent diabetes mellitus (IDDM) patients with and without secondary complications (retinopathy, polyneuropathy and nephropathy) and 25 healthy persons, and purified and characterised. The content of alpha-2,6-bound SA, the isoenzyme patterns of the purified A form, and the total NAG and A form activities were determined. In all diabetic groups, the sialylation levels of the A form were 2-3.5 times lower compared to control, while their acidities (fractions with pI 4.25-5.1) increased, particularly with progression of secondary complications. Total serum NAG activities and percentages of A form were significantly higher (P lt 0.001) in all diabetic groups and negatively correlated with the alpha-2,6-bound SA content of the A form. In addition, they decreased as secondary diabetic complications became more complex. The observed changes could be the consequence of structural changes in the A form due to significant increases in its acidity, i.e., negative charge, which originated from groups other than SA

Mortality After Pediatric Arterial Ischemic Stroke

OBJECTIVES: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). METHODS: Neonates (0-28 days) and children (29 days- < 19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality. RESULTS: Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were strokerelated, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI] : 1.23-12.29; P = .021), posterior plus anterior circulation stroke (OR: 5.36; 95% CI: 1.70-16.85; P = .004), and stroke presentation without seizures (OR: 3.95; 95% CI: 1.26-12.37; P = .019) were associated with in-hospital mortality for neonates. Hispanic ethnicity (OR: 3.12; 95% CI: 1.56-6.24; P = .001), congenital heart disease (OR: 3.14; 95% CI: 1.75-5.61; P < .001), and posterior plus anterior circulation stroke (OR: 2.71; 95% CI: 1.40-5.25; P = .003) were associated with in-hospital mortality for children. CONCLUSIONS: In-hospital mortality occurred in 2.6% of pediatric AIS cases. Most deaths were attributable to stroke. Risk factors for in-hospital mortality included congenital heart disease and posterior plus anterior circulation stroke. Presentation without seizures and Hispanic ethnicity were also associated with mortality for neonates and children, respectively. Awareness and study of risk factors for mortality represent opportunities to increase survival

Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism

Abstract: Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R2 = 0.096%, P < 2 × 10−16), self-harm ideation (max R2 = 0.108%, P < 2 × 10−16), and self-harm (max R2 = 0.13%, P < 2 × 10−16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 ± 0.05, P = 8.13 × 10−11), self-harm ideation (rg = 0.49 ± 0.05, P = 4.17 × 10−21) and self-harm (rg = 0.48 ± 0.05, P = 4.58 × 10−21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = −0.023 ± 0.005, P = 6.74 × 10−5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10−3 ± 2.76 × 10−3, P = 2.42 × 10−3) and self-harm ideation (β = 7.47 × 10−3 ± 2.76 × 10−3, P = 6.71 × 10−3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09–0.32) for depression to 0.008 (95% CI: 0.004–0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Design and Management of Interfirm Networks

International audienceOffers an interdisciplinary understanding of the economics and management of interfirm networks Presents new research perspectives on the relationship between networks and innovation Highlights a network-centric view of the new digital economyInterfirm networks include franchising, retail and service chains, cooperatives, financial networks, joint ventures, strategic alliances, licensing, public-private partnerships and new network forms in the digital economy. This book gathers the latest research studies that approach these networks – and the creation of innovation under the conditions of a complex, dynamic, knowledge-intensive and digital economy – from an interdisciplinary perspective. The studies, all of which were written by respected experts, explore how firms can improve their competitiveness by securing access to innovation, knowledge, complementary resources and capabilities otherwise not available to them. In addition, they highlight how, driven by an unpredictable environment, firms embedded in inter-organizational networks are increasingly transforming from co-operators to collaborators and valuable co-creators of innovation

Serum N-acetyl-beta-D-glucosaminidase profiles in type 1 diabetes secondary complications: Causes of changes and significance of determination

The connection between changes in the activity of serum N-acetyl-beta-D-glucosaminidase (NAG, E.C.3.2.1.30) and iso-enzymes and degree of secondary complications was analyzed in four groups of type 1 diabetic patients (n=69): without complications (n=22); with retinopathy (n=16); with retinopathy and polyneuropathy (n= 13), and with retinopathy, neuropathy, and nephropathy (n=18). In all groups statistically significant higher (P lt 0.001) percent fraction of A form (83.84 +/- 6.09, 84.37 +/- 5.74, 81.76 +/- 6.02, 76.37 +/- 7.38%, resp.) and lower (P lt 0.001, P lt 0.01) fraction of B form (15.87 +/- 5.65, 15.66 +/- 5.74, 18.33 +/- 5.98, 23.63 +/- 7.38, resp.) in total NAG compared with the control (A = 69.38 +/- 4.79%, B = 30.61 +/- 4.78%) were found. The differences in A as well as B forms between diabetic groups were not statistically significant. Significant strong positive correlations between total NAG and glycemia (0.494-0.623), total NAG and A form (0.934-0.966), and A form and glycemia (0.512-0.638) were found in all groups. No correlation was found between the fractions of B and A forms, except in the fourth group. The A form of diabetic patients in the fourth group was more acidic compared with the control and other diabetic groups. It was concluded that the changes in serum NAG and isoenzymic profiles in diabetes are the consequence of its increased exocytose, especially of the A form, in hyperglycemia and posttranslational modifications of iso-enzymes. The total activity of serum NAG and iso-enzymic profiles cannot be used for monitoring the development and distinction of type 1 diabetes secondary complications

A way to determine radiation-induced loss in fiber-optic digital communication link

The gamma radiation (Co-60) effect to the PCS fiber-optic in real digital communication link was investigated. The radiation-induced loss were determined by new method, using discrete data obtained by the sampling oscilloscope and processed on the computer, The experimental results confirm the validity of the processing method proposed. (c) 2005 Published by Elsevier Inc

Spontaneous resolution of a rhegmatogenous retinal detachment

A retinal detachment is the term used to describe detachment of the neurosensory retina from the underlying membrane, the retinal pigment epithelium (RPE). Rhegmatogenous detachments are caused by a break in the retina through which fluid passes from the vitreous cavity into the subretinal space. The incidence of rhegmatogenous retinal detachment in the general population in Europe is 1 in 10 000 persons per year. Danger is the greatest in the age range from 55 to 70 years. Without treatment, blindness in the affected eye may occur. Individual risks depend on the presence or absence of specific factors including myopia, positive family anamnesis, retina rupture, trauma, ablation in the other eye, ablation in a vitreous body, retina high-risk peripheral degenerations and vitreoretinal degenerations. Majority of the untreated rhegmatogenous retina ablations progress to the subtotal or total retinal detachment and blindness. This paper describes a very rare case of the spontaneous complete reattachment of the sensory retina to the retinal pigment epithelium in a patient with the total rhegmatogenous retinal ablation in the right eye. The female patient, who was 52 years old, was examined by an Ophthalmologist after she had experienced a sudden loss of vision, 2 months before appointment. After a detailed ophthalmological examination, a total rhegmatogenous retinal ablation of the right eye was diagnosed. The best corrected visual acuity, evaluated on a Snellen chart, was 2/60. The patient was referred to a tertiarylevel Institution since a surgical intervention of the ablation was needed. Due to technical inabilities in the above-mentioned Institution, the operation was not performed, and despite the recommendation to perform the intervention in another tertiary-level Institution, the patient did not have ophthalmological examinations during the following three months. During the next visit, the Ophthalmologist determined that there was a spontaneous retinal fixation on the retinal pigment epithelium and a partial restoration of the visual function of the affected eye which was evaluated at 0.5