Hemorrhagic stroke outcomes of KApSR patients with co-morbid diabetes and Alzheimer’s disease

Background: Vascular risk factors, such as diabetes mellitus (DM), are associated with poorer outcomes following many neurodegenerative diseases, including hemorrhagic stroke and Alzheimer’s disease (AD). Combined AD and DM co-morbidities are associated with an increased risk of hemorrhagic stroke and increased Medicare costs. Therefore, we hypothesized that patients with DM in combination with AD, termed DM/AD, would have increased hemorrhagic stroke severity. Methods: Kentucky Appalachian Stroke Registry (KApSR) is a database of demographic and clinical data from patients that live in Appalachia, a distinct region with increased health disparities and stroke severity. Inpatients with a primary indication of hemorrhagic stroke were selected from KApSR for retrospective analysis and were separated into four groups: DM only, AD only, neither, or both. Results: Hemorrhagic stroke patients (2,071 total) presented with either intracerebral hemorrhage (ICH), n=1,448, or subarachnoid hemorrhage (SAH), n=623. When examining all four groups, subjects with AD were significantly older (AD+, 80.9±6.6 yrs) (DM+/AD+, 77.4±10.0 yrs) than non AD subjects (DM-/AD-, 61.3±16.5 yrs) and (DM+, 66.0±12.5 yrs). A higher percentage of females were among the AD+ group and a higher percentage of males among the DM+/AD+ group. Interestingly, after adjusting for multiple comparison, DM+/AD+ subjects were ten times as likely to suffer a moderate to severe stroke based on a National Institute of Health Stroke (NIHSS) upon admission [odds ratio (95% CI)] compared to DM-/AD- [0.1 (0.02–0.55)], DM+ [0.11 (0.02–0.59)], and AD+ [0.09(0.01–0.63)]. The odds of DM+/AD+ subjects having an unfavorable discharge destination (death, hospice, long-term care) was significant (P Conclusions: In our retrospective analysis utilizing KApSR, regardless of adjusting for age, sex, and comorbidities, DM+/AD+ patients were significantly more likely to have had a moderate or severe stroke leading to an unfavorable outcome following hemorrhagic stroke

Towards a conceptual framework demonstrating the effectiveness of audiovisual patient descriptions (patient video cases): a review of the current literature

Background: Technological advances have enabled the widespread use of video cases via web-streaming and online download as an educational medium. The use of real subjects to demonstrate acute pathology should aid the education of health care professionals. However, the methodology by which this effect may be tested is not clear. Methods: We undertook a literature review of major databases, found relevant articles relevant to using patient video cases as educational interventions, extracted the methodologies used and assessed these methods for internal and construct validity. Results: A review of 2532 abstracts revealed 23 studies meeting the inclusion criteria and a final review of 18 of relevance. Medical students were the most commonly studied group (10 articles) with a spread of learner satisfaction, knowledge and behaviour tested. Only two of the studies fulfilled defined criteria on achieving internal and construct validity. The heterogeneity of articles meant it was not possible to perform any meta-analysis. Conclusions: Previous studies have not well classified which facet of training or educational outcome the study is aiming to explore and had poor internal and construct validity. Future research should aim to validate a particular outcome measure, preferably by reproducing previous work rather than adopting new methods. In particular cognitive processing enhancement, demonstrated in a number of the medical student studies, should be tested at a postgraduate level

Human rights culture: solidarity, diversity and the right to be different

The concept of a human rights culture has been crucial to the incorporation of the European Convention of Human Rights into UK law. In this paper media and activist representations of human rights for lesbian, gay, bisexual and transgender human rights are considered as indicative of an emerging human rights culture, especially around the Civil Partnerships Act 2004. A typology of representations of rights is developed and discussed. It is concluded that insofar as there is an emerging human rights culture, it is one that is concerned above all with creating and maintaining civic relationships rather than with the assertion of individual liberty, and as inviting political compromise rather than a principled stance on universal human rights

Label-free electrochemical monitoring of DNA ligase activity

This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase

Is there a role for expectation maximization imputation in addressing missing data in research using WOMAC questionnaire? Comparison to the standard mean approach and a tutorial

<p>Abstract</p> <p>Background</p> <p>Standard mean imputation for missing values in the Western Ontario and Mc Master (WOMAC) Osteoarthritis Index limits the use of collected data and may lead to bias. Probability model-based imputation methods overcome such limitations but were never before applied to the WOMAC. In this study, we compare imputation results for the Expectation Maximization method (EM) and the mean imputation method for WOMAC in a cohort of total hip replacement patients.</p> <p>Methods</p> <p>WOMAC data on a consecutive cohort of 2062 patients scheduled for surgery were analyzed. Rates of missing values in each of the WOMAC items from this large cohort were used to create missing patterns in the subset of patients with complete data. EM and the WOMAC's method of imputation are then applied to fill the missing values. Summary score statistics for both methods are then described through box-plot and contrasted with the complete case (CC) analysis and the true score (TS). This process is repeated using a smaller sample size of 200 randomly drawn patients with higher missing rate (5 times the rates of missing values observed in the 2062 patients capped at 45%).</p> <p>Results</p> <p>Rate of missing values per item ranged from 2.9% to 14.5% and 1339 patients had complete data. Probability model-based EM imputed a score for all subjects while WOMAC's imputation method did not. Mean subscale scores were very similar for both imputation methods and were similar to the true score; however, the EM method results were more consistent with the TS after simulation. This difference became more pronounced as the number of items in a subscale increased and the sample size decreased.</p> <p>Conclusions</p> <p>The EM method provides a better alternative to the WOMAC imputation method. The EM method is more accurate and imputes data to create a complete data set. These features are very valuable for patient-reported outcomes research in which resources are limited and the WOMAC score is used in a multivariate analysis.</p

Dissecting protein-induced DNA looping dynamics in real time

Many proteins that interact with DNA perform or enhance their specific functions by binding simultaneously to multiple target sites, thereby inducing a loop in the DNA. The dynamics and energies involved in this loop formation influence the reaction mechanism. Tethered particle motion has proven a powerful technique to study in real time protein-induced DNA looping dynamics while minimally perturbing the DNA–protein interactions. In addition, it permits many single-molecule experiments to be performed in parallel. Using as a model system the tetrameric Type II restriction enzyme SfiI, that binds two copies of its recognition site, we show here that we can determine the DNA–protein association and dissociation steps as well as the actual process of protein-induced loop capture and release on a single DNA molecule. The result of these experiments is a quantitative reaction scheme for DNA looping by SfiI that is rigorously compared to detailed biochemical studies of SfiI looping dynamics. We also present novel methods for data analysis and compare and discuss these with existing methods. The general applicability of the introduced techniques will further enhance tethered particle motion as a tool to follow DNA–protein dynamics in real time

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

R2P from Below: Does the British Public View Humanitarian Interventions as Ethical and Effective?

One of the major barriers to the implementation of the Responsibility to Protect principle is the lack of a political will. Public attitudes towards intervention will have a crucial impact on elite willingness to prevent mass atrocities, yet we have little understanding of the factors that influence those attitudes. This article provides the first examination of UK public perceptions about the moral justifiability and effectiveness of humanitarian interventions. The article shows that decisions about justifiability and effectiveness are very different. Attitudes towards justification were more easily explained suggesting that judgements about effectiveness are more contextual and less easily accounted for by individuals’ background characteristics and attitudes. Experiences with both Iraq and Afghanistan have contaminated public perceptions of both the ethics and effectiveness of humanitarian interventions. Although the public is broadly supportive about the justifiability of humanitarian interventions they are extremely sceptical about the likelihood that those interventions will be successful