The neuronal correlates of mirror illusion in children with spastic hemiparesis: a study with functional magnetic resonance imaging.

To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (p<0.001 at voxel level, family-wise error corrected at cluster level) in the dorsolateral prefrontal cortex and anterior cingulate cortex of the affected and unaffected hemispheres, respectively. No significant effects of the mirror illusion were observed in unimanual experiments and in healthy participants. Mirror illusion in children/adolescents with hemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach

Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance

In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the Km(MCN), less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants tet(X2)T280A and tet(X2)N371I. The structure of the most efficient variant, TetX2T280A, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection

Electronic submission and the movement towards a paperless law office in a modern university

The Government’s target of 50% of all under 30 year olds studying at higher education institutions by 2010, coupled with the National Committee Inquiry into Higher Education’ (1997) concluding that further expansion of higher education could not be afforded under the existing funding arrangements, may have serious ramifications for higher education in the UK. Alongside this increase in numbers, students are increasingly seen as educational consumers with increased choice in a demand-led market which universities must recognise. To compete in this academic environment these institutions are having to be ever more consumer aware in the services they offer and are having to increase choice to attract customers from rival enterprises. Information technology is playing an increasing role in the learning experience as noted by institutional commentators such as the Higher Education Funding Council for England, the Joint Information Systems Committee, the Electronic Books ON-screen Interface group and Lord Dearing’s Report. Technology’s use is further evidenced through institutions’ employment of the internet, e-mail and web-based learning to harness the power of this medium. This paper focuses on the concept of commercialism in the university sector and how a movement to a paperless office may be one way in which a university could gain an early competitive advantage over its rivals. The paper takes a student perspective to demonstrate whether students would wish to move towards electronic methods of submission of assessed work and considers the current problems that are encountered in physical submission of documents. This is the first paper in an on-going research project investigating the benefits and viability of a paperless law office, and the results demonstrate both that the students desire more flexibility in submission of university work and that their acceptance may be the easy first step on the road to the paperless law school

Toward the Understanding of the Metabolism of Levodopa I. DFT Investigation of the Equilibrium Geometries, Acid-Base Properties and Levodopa-Water Complexes

Levodopa (LD) is used to increase dopamine level for treating Parkinson’s disease. The major metabolism of LD to produce dopamine is decarboxylation. In order to understand the metabolism of LD; the electronic structure of levodopa was investigated at the Density Functional DFT/B3LYP level of theory using the 6-311+G** basis set, in the gas phase and in solution. LD is not planar, with the amino acid side chain acting as a free rotator around several single bonds. The potential energy surface is broad and flat. Full geometry optimization enabled locating and identifying the global minimum on this Potential energy surface (PES). All possible protonation/deprotonation forms of LD were examined and analyzed. Protonation/deprotonation is local in nature, i.e., is not transmitted through the molecular framework. The isogyric protonation/deprotonation reactions seem to involve two subsequent steps: First, deprotonation, then rearrangement to form H-bonded structures, which is the origin of the extra stability of the deprotonated forms. Natural bond orbital (NBO) analysis of LD and its deprotonated forms reveals detailed information of bonding characteristics and interactions across the molecular framework. The effect of deprotonation on the donor-acceptor interaction across the molecular framework and within the two subsystems has also been examined. Attempts to mimic the complex formation of LD with water have been performed

Changing use of surgical antibiotic prophylaxis in Thika Hospital, Kenya: a quality improvement intervention with an interrupted time series design.

INTRODUCTION: In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. METHODS: We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. RESULTS: From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. CONCLUSION: Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution

The Repeatability of Adaptive Radiation During Long-Term Experimental Evolution of Escherichia coli in a Multiple Nutrient Environment

Adaptive radiations occur when a species diversifies into different ecological specialists due to competition for resources and trade-offs associated with the specialization. The evolutionary outcome of an instance of adaptive radiation cannot generally be predicted because chance (stochastic events) and necessity (deterministic events) contribute to the evolution of diversity. With increasing contributions of chance, the degree of parallelism among different instances of adaptive radiations and the predictability of an outcome will decrease. To assess the relative contributions of chance and necessity during adaptive radiation, we performed a selection experiment by evolving twelve independent microcosms of Escherichia coli for 1000 generations in an environment that contained two distinct resources. Specialization to either of these resources involves strong trade-offs in the ability to use the other resource. After selection, we measured three phenotypic traits: 1) fitness, 2) mean colony size, and 3) colony size diversity. We used fitness relative to the ancestor as a measure of adaptation to the selective environment; changes in colony size as a measure of the evolution of new resource specialists because colony size has been shown to correlate with resource specialization; and colony size diversity as a measure of the evolved ecological diversity. Resource competition led to the rapid evolution of phenotypic diversity within microcosms. Measurements of fitness, colony size, and colony size diversity within and among microcosms showed that the repeatability of adaptive radiation was high, despite the evolution of genetic variation within microcosms. Consistent with the observation of parallel evolution, we show that the relative contributions of chance are far smaller and less important than effects due to adaptation for the traits investigated. The two-resource environment imposed similar selection pressures in independent populations and promoted parallel phenotypic adaptive radiations in all independently evolved microcosms

Gingival crevicular fluid MMP-8-concentrations in patients after acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the presence of matrix metalloproteinase-8 in the gingival crevicular fluid (GCF) of patients after acute myocardial infarction (AMI).</p> <p>Methods</p> <p>A total of 48 GCF samples from 20 AMI patients, hospitalized at the Department of Cardiology and Angiology of the Johannes Gutenberg University Mainz, were investigated. Besides the myocardial infarction all patients suffered from chronic periodontal disease. Fifty-one GCF samples from 20 healthy age matched individuals with similar periodontal conditions served as controls. The dental examination included the assessment of oral hygiene, gingival inflammation, probing pocket depth, clinical attachment level and X-ray examination. The study was only carried out after the positive consent of the regional ethic commission. A quantitative assessment of aMMP-8 levels in the gingival crevicular fluid was performed with the help of the DentoAnalyzer (Dentognostics GmbH, Jena, Germany), utilising an immunological procedure.</p> <p>Results</p> <p>The aMMP-8 concentrations found in the gingival crevicular fluid of the AMI patients significantly differed (p = 0.001; mean value 30.33 ± 41.99 ng/ml aMMP-8) from the control group (mean value 10.0 ± 10.7 ng/ml aMMP-8). These findings suggest that periodontal inflammation in AMI patients might be associated with higher MMP-8-values compared to the healthy controls.</p> <p>Conclusions</p> <p>The acute myocardial infarction seems to influence the degree of periodontal inflammation, thus the measurement of the gingival crevicular fluid MMP8 levels seems to be a helpful biochemical test to obtain information about the severity of the periodontal disease.</p

The effects on chronic periodontitis of a subgingivally-placed redox agent in a slow release device

Adjunctive chemical agents can reduce the need for meticulous plaque control. The aim of this investigation was to evaluate the periodontal treatment potential of subgingival application of the redox agent methylene blue in a slow release device. This randomized, single-blind, split-mouth study included 18 patients aged 35- 57 years, with chronic adult periodontitis, pocketing of at least 5mm and radiographic evidence of regular bone loss. All experimental sites received subgingival debridement at day 0. Test sites received 32% w/w methylene blue in the slow release device at days 0 and 28. Clinical examination and microbiological sampling were performed at days 0, 7, 28, 56 and 84. Clinical improvements were seen in both groups, but test sites showed consistently greater improvements, some of which were statistically significant (as determined by between-group comparisons utilising SNDs). Significant between-group differences in relation to baseline levels were seen in bleeding index at days 7 and 56, in probable pocket depth at day 56 and for the Perioscan BANA test at day 7. This pilot study thus showed that adjunctive methylene blue in a slow-release device can produce greater clinical and microbiological improvements than subgingival debridement alone.peer-reviewe