Influence of hyperhomocysteinemia on the cellular redox state - Impact on homocysteine-induced endothelial dysfunction

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteines deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteineinduced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide

Difference in balance measures between patients with chronic ankle instability and patients after an acute ankle inversion trauma

Neuromuscular control of the ankle is disturbed in patients with chronic ankle instability due to an initial ankle inversion trauma. Static balance is assumed to be a measure for this disturbance. Functional (ankle) scores are another way to evaluate ankle impairment. The hypothesis was that there is a difference in static balance measures between small groups of healthy subjects, patients after an acute ankle inversion trauma and patients with chronic ankle instability and that static balance measures correlate well with functional scores. Static balance in healthy subjects (N = 15), patients after a primary ankle inversion injury (N = 14) and patients with chronic ankle instability (N = 23) was tested with a single leg test on a force plate (Postural Sway test) and on a compliant floor (Simple Balance test). Functional impairment was evaluated with the Karlsson, AOFAS and SF-36 (ankle) scores. There was a statistically significant and clinically relevant difference in functional (ankle) scores, but not a statistically significant difference in balance measures between the groups. Balance measures did not correlate to the functional scores. It was concluded that, despite a clinically relevant difference in functional outcome measures between the groups, static balance measures do not appear to be useful for clinical application in the individual patient

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Detecting suicidality among adolescent outpatients: evaluation of trained clinicians' suicidality assessment against a structured diagnostic assessment made by trained raters

<p>Abstract</p> <p>Background</p> <p>Accurate assessment of suicidality is of major importance. We aimed to evaluate trained clinicians' ability to assess suicidality against a structured assessment made by trained raters.</p> <p>Method</p> <p>Treating clinicians classified 218 adolescent psychiatric outpatients suffering from a depressive mood disorder into three classes: 1-no suicidal ideation, 2-suicidal ideation, no suicidal acts, 3-suicidal or self-harming acts. This classification was compared with a classification with identical content derived from the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) made by trained raters. The convergence was assessed by kappa- and weighted kappa tests.</p> <p>Results</p> <p>The clinicians' classification to class 1 (no suicidal ideation) was 85%, class 2 (suicidal ideation) 50%, and class 3 (suicidal acts) 10% concurrent with the K-SADS evaluation (γ²= 37.1, df 4, p = 0.000). Weighted kappa for the agreement of the measures was 0.335 (CI = 0.198–0.471, p < 0.0001). The clinicians under-detected suicidal and self-harm acts, but over-detected suicidal ideation.</p> <p>Conclusion</p> <p>There was only a modest agreement between the trained clinicians' suicidality evaluation and the K-SADS evaluation, especially concerning suicidal or self-harming acts. We suggest a wider use of structured scales in clinical and research settings to improve reliable detection of adolescents with suicidality.</p

Measurement of vertebral rotation in adolescent idiopathic scoliosis with low-dose CT in prone position - method description and reliability analysis

<p>Abstract</p> <p>Background</p> <p>To our knowledge there is no report in the literature on measurements of vertebral rotation with low-dose computed tomography (CT) in prone position.</p> <p>Aims</p> <p>To describe and test the reliability of this new method, compare it with other methods in use and evaluate the influence of body position on the degree of vertebral rotation measured by different radiological methods.</p> <p>Study design</p> <p>Retrospective study.</p> <p>Methods</p> <p>25 consecutive patients with adolescent idiopathic scoliosis scheduled for surgery (17 girls, 8 boys) aged 15 ± 2 years (mean ± SD) were included in the analysis of this study. The degree of the vertebral rotation was in all patients measured according to the method of Perdriolle on standing plain radiographs and on supine CT scanogram, and according to the method of Aaro and Dahlborn on axial CT images in prone position and on magnetic resonance imaging (MRI) in supine position. The measurements were done by one neuroradiologist at two different occasions. Bland and Altman statistical approach was used in the reliability assessment.</p> <p>Results</p> <p>The reliability of measuring vertebral rotation by axial CT images in prone position was almost perfect with an intraclass correlation coefficient of 0.95, a random error of the intraobserver differences of 2.3°, a repeatability coefficient of 3.2° and a coefficient of variation of 18.4%. Corresponding values for measurements on CT scanogram were 0.83, 5.1°, 7.2°, and 32.8%, respectively, indicating lower reliability of the latter modality and method. The degree of vertebral rotation measured on standing plain radiographs, prone CT scanogram, axial images on CT in prone position and on MRI in supine position were 25.7 ± 9.8°, 21.9 ± 8.3°, 17.4 ± 7.1°, and 16.1 ± 6.5°, respectively. The vertebral rotation measured on axial CT images in prone position was in average 7.5% larger than that measured on axial MRI in supine position.</p> <p>Conclusions</p> <p>This study has shown that measurements of vertebral rotation in prone position were more reliable on axial CT images than on CT scanogram. The measurement of vertebral rotation on CT (corrected to the pelvic tilt) in prone position imposes lower impact of the recumbent position on the vertebral rotation than did MRI in supine position. However, the magnitude of differences is of doubtful clinical significance.</p

Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape

BACKGROUND: Antigen-specific CTL responses are thought to play a central role in containment of HIV-1 infection, but no consistent correlation has been found between the magnitude and/or breadth of response and viral load changes during disease progression. METHODS AND FINDINGS: We undertook a detailed investigation of longitudinal CTL responses and HIV-1 evolution beginning with primary infection in 11 untreated HLA-A2 positive individuals. A subset of patients developed broad responses, which selected for consensus B epitope variants in Gag, Pol, and Nef, suggesting CTL-induced adaptation of HIV-1 at the population level. The patients who developed viral escape mutations and broad autologous CTL responses over time had a significantly higher increase in viral load during the first year of infection compared to those who did not develop viral escape mutations. CONCLUSIONS: A continuous dynamic development of CTL responses was associated with viral escape from temporarily effective immune responses. Our results suggest that broad CTL responses often represent footprints left by viral CTL escape rather than effective immune control, and help explain earlier findings that fail to show an association between breadth of CTL responses and viral load. Our results also demonstrate that CTL pressures help to maintain certain elements of consensus viral sequence, which likely represent viral escape from common HLA-restricted CTL responses. The ability of HIV to evolve to escape CTL responses restricted by a common HLA type highlights the challenges posed to development of an effective CTL-based vaccine

Business model innovation and transition to a sustainable food system: A case study in the Lisbon metropolitan area

The food systems’ transition towards a sustainable involves structural changes, namely the emphasis on local production, short supply chains, and the preference for organic products. The shift in the agri-food system is taking place through the creation of entirely new businesses and individual farms moving towards organic production. In both cases, the enterprises use a combination of well-established agricultural knowledge and techniques, new scientific knowledge on productive methods and new technological platforms for commercialization. These mixed sources permit the creation of innovative business models (BMs). They exemplify how traditional industries can absorb/generate innovation at technological and organizational levels, and become part of the new knowledge-based era. The study has three objectives: to analyse the emerging agri-food businesses in the Lisbon Metropolitan Area (LMA); to characterize innovative sustainable BMs within the transition dynamics; to reflect on the challenges that the characteristics of the food system pose for the emergence of these BMs. The study is part of an interdisciplinary project on Spatial Planning for Change (SPLACH). The analysis addresses the food system transition in a specific territory, namely the LMA. The paper presents results of the research conducted, focusing on the case of an organic food initiative, Quinta do Oeste.info:eu-repo/semantics/acceptedVersio

Techniques of EMG signal analysis: detection, processing, classification and applications

Electromyography (EMG) signals can be used for clinical/biomedical applications, Evolvable Hardware Chip (EHW) development, and modern human computer interaction. EMG signals acquired from muscles require advanced methods for detection, decomposition, processing, and classification. The purpose of this paper is to illustrate the various methodologies and algorithms for EMG signal analysis to provide efficient and effective ways of understanding the signal and its nature. We further point up some of the hardware implementations using EMG focusing on applications related to prosthetic hand control, grasp recognition, and human computer interaction. A comparison study is also given to show performance of various EMG signal analysis methods. This paper provides researchers a good understanding of EMG signal and its analysis procedures. This knowledge will help them develop more powerful, flexible, and efficient applications