Extensive sequential polymorphic interconversion in the solid-state: Two hydrates and ten anhydrous phases of hexamidine diisethionate

Crystal polymorphism and solvent inclusion is a dominant research area in the pharmaceutical industry and continues to unveil complex systems. Here, we present the solid-state system of hexamidine diisethionate (HDI), an antiseptic drug compound forming a dimorphic dihydrate as well as ten anhydrous polymorphs. The X-ray and neutron crystal structures of the hydrated crystal forms and related interaction energies show no direct interaction between the cation and water but very strong interactions between cation and anion, and anion and water. This is observed macroscopically as high stability of the hydrate against dehydration by temperature and humidity. The anhydrous polymorphs reveal a rare case of sequential and reversible polymorphic transformations, which are characterized by thermal analysis and variable-temperature powder X-ray diffraction (PXRD). While most transitions are accompanied by significant structural changes, the low-energy transitions can only be detected as slight changes in the reflection positions with temperature. HDI thus represents a model compound to investigate polymorphic transitions with small structural changes

Thyroid function in Danish greenhouse workers

BACKGROUND: From animal studies it is known that currently used pesticides can disturb thyroid function. METHODS: In the present study we investigated the thyroid function in 122 Danish greenhouse workers, to evaluate if greenhouse workers classified as highly exposed to pesticides experiences altered thyroid levels compared to greenhouse workers with lower exposure. Serum samples from the greenhouse workers were sampled both in the spring and the fall to evaluate if differences in pesticide use between seasons resulted in altered thyroid hormone levels. RESULTS: We found a moderate reduction of free thyroxine (FT4) (10–16%) among the persons working in greenhouses with a high spraying load both in samples collected in the spring and the fall, but none of the other measured thyroid hormones differed significantly between exposure groups in the cross-sectional comparisons. However, in longitudinal analysis of the individual thyroid hormone level between the spring and the fall, more pronounced differences where found with on average 32% higher thyroid stimulating hormone (TSH) level in the spring compared to the fall and at the same time a 5–9% lower total triiodthyroxin (TT3), free triiodthyroxine (FT3) and FT4. The difference between seasons was not consistently more pronounced in the group classified as high exposure compared to the low exposure groups. CONCLUSION: The present study indicates that pesticide exposure among Danish greenhouse workers results in only minor disturbances of thyroid hormone levels

A Prior Myocardial Infarction: How Does it Affect Management and Outcomes in Recurrent Acute Coronary Syndromes?

Background Despite improved secondary prevention efforts, acute coronary syndrome (ACS) recurrence among patients with prior history of coronary events remains high. The differences in presentation, management, and subsequent clinical outcomes in patients with and without a prior myocardial infarction (MI) and presenting with another episode of ACS remain unexplored. Methods A total of 3,624 consecutive patients admitted to the University of Michigan with ACS from January 1999 to June 2006 were studied retrospectively. In-hospital management, outcomes, and postdischarge outcomes such as death, stroke, and reinfarction in patients with and without a prior MI were compared. Results Patients with a prior MI were more likely to be older and have a higher incidence of diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease. In-hospital outcomes were not significantly different in the 2 groups, except for a higher incidence of cardiac arrest (4.3% versus 2.5%, p < 0.01) and cardiogenic shock (5.7% versus 3.9%, p = 0.01) among patients without a prior MI. However, at 6 mo postdischarge, the incidences of death (8.0% versus 4.5%, p < 0.0001) and recurrent MI (10.0% versus 5.1%, p < 0.0001) were significantly higher in patients with a prior history of MI compared with those without. Conclusion Patients with prior MI with recurrent ACS remain at a higher risk of major adverse events on follow-up. This may be partly explained by the patients not being on optimal medications at presentation, as well as disease progression. Increased efforts must be directed at prevention of recurrent ACS, as well as further risk stratification of these patients to improve their overall outcomes. Copyright © 2008 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61452/1/20356_ftp.pd

Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

<p>Abstract</p> <p>Background</p> <p>The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate.</p> <p>Results</p> <p>The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (Δ<it>G</it>_ATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of Δ<it>G</it>_ATPasein the beating heart.</p> <p>Conclusion</p> <p>The CK system stabilizes Δ<it>G</it>_ATPaseby both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.</p

Endothelium-derived Vasoactive Factors and Hypertension: Possible Roles in Pathogenesis and as Treatment Targets

Endothelial cells regulate vascular tone by releasing various contracting and relaxing factors including nitric oxide (NO), arachidonic acid metabolites (derived from cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases), reactive oxygen species, and vasoactive peptides. Additionally, another pathway associated with the hyperpolarization of the underlying smooth muscle cells plays a predominant role in resistance arteries. Endothelial dysfunction is a multifaceted disorder, which has been associated with hypertension of diverse etiologies, involving not only alterations of the L-arginine NO-synthase–soluble guanylyl cyclase pathway but also reduced endothelium-dependent hyperpolarizations and enhanced production of contracting factors, particularly vasoconstrictor prostanoids. This brief review highlights these different endothelial pathways as potential drug targets for novel treatments in hypertension and the associated endothelial dysfunction and end-organ damage

FORG3D: Force-directed 3D graph editor for visualization of integrated genome scale data

<p>Abstract</p> <p>Background</p> <p>Genomics research produces vast amounts of experimental data that needs to be integrated in order to understand, model, and interpret the underlying biological phenomena. Interpreting these large and complex data sets is challenging and different visualization methods are needed to help produce knowledge from the data.</p> <p>Results</p> <p>To help researchers to visualize and interpret integrated genomics data, we present a novel visualization method and bioinformatics software tool called FORG3D that is based on real-time three-dimensional force-directed graphs. FORG3D can be used to visualize integrated networks of genome scale data such as interactions between genes or gene products, signaling transduction, metabolic pathways, functional interactions and evolutionary relationships. Furthermore, we demonstrate its utility by exploring gene network relationships using integrated data sets from a <it>Caenorhabditis elegans </it>Parkinson's disease model.</p> <p>Conclusion</p> <p>We have created an open source software tool called FORG3D that can be used for visualizing and exploring integrated genome scale data.</p

The UK Space and Planetary Robotics Network

No abstract available

Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers

Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training

Bullying: An ecological approach to intervention in schools

Bullying is a major concern in education worldwide, particularly in countries such as New Zealand that are reported to have high rates of bullying in schools. In this article it is proposed that, in order to effectively prevent or substantially reduce bullying in schools, a systemic approach needs to be adopted, with interventions organized at various levels. An ecological model for bullying prevention is presented that suggests strategies and interventions at the levels of teachers, schools, communities, and society. Examples of interventions that have been found in the literature to have evidence supporting their effectiveness have been outlined at each of these levels. Guidelines are presented for schools adopting such an ecological model for addressing bullying and for bringing about the changes needed to implement it successfully

The effectiveness of a multidisciplinary intervention strategy for the treatment of symptomatic joint hypermobility in childhood:A randomised, single Centre parallel group trial (The Bendy Study)

Introduction: Joint hypermobility is common in childhood and can be associated with musculoskeletal pain and dysfunction. Current management is delivered by a multidisciplinary team, but evidence of effectiveness is limited. This clinical trial aimed to determine whether a structured multidisciplinary, multisite intervention resulted in improved clinical outcomes compared with standard care. Method: A prospective randomised, single centre parallel group trial comparing an 8-week individualised multidisciplinary intervention programme (bespoke physiotherapy and occupational therapy in the clinical, home and school environment) with current standard management (advice, information and therapy referral if deemed necessary). The primary endpoint of the study was between group difference in child reported pain from baseline to 12 months as assessed using the Wong Baker faces pain scale. Secondary endpoints were parent reported pain (100 mm visual analogue scale), parent reported function (child health assessment questionnaire), child reported quality of life (child health utility 9-dimensional assessment), coordination (movement assessment battery for children version 2) and grip strength (handheld dynamometer). Results: 119 children aged 5 to 16 years, with symptomatic hypermobility were randomised to receive an individualised multidisciplinary intervention (I) (n = 59) or standard management (S) (n = 60). Of these, 105 completed follow up at 12 months. No additional significant benefit could be shown from the intervention compared to standard management. However, there was a statistically significant improvement in child and parent reported pain, coordination and grip strength in both groups. The response was independent of the degree of hypermobility. Conclusion: This is the first randomised controlled trial to compare a structured multidisciplinary, multisite intervention with standard care in symptomatic childhood hypermobility. For the majority, the provision of education and positive interventions aimed at promoting healthy exercise and self-management was associated with significant benefit without the need for more complex interventions. Trial registration: The trial was registered prospectively with the national database at the Clinical Research Network (UKCRN Portfolio 9366). The trial was registered retrospectively with ISRCTN (ISRCTN86573140)