RETRACTED ARTICLE: Painful os intermetatarseum in athletes: a literature review of this condition is presented

Painful os intermetatarseum is a very rare condition. Gruber et al. first described os intermetatarseum in 1877. This condition is usually asymptomatic. One should consider painful os intermetatarseum as being a possible cause of dorsal foot pain in athletes. Surgical excision of the os intermetatarseum should be considered for those patients failing conservative treatment. Here, a literature review of this condition is presented

High Antipredatory Efficiency of Insular Lizards: A Warning Signal of Excessive Specimen Collection?

We live-captured lizards on islands in the Gulf of California and the Baja California peninsula mainland, and compared their ability to escape predation. Contrary to expectations, endemic lizard species from uninhabited islands fled from humans earlier and more efficiently than those from peninsular mainland areas. In fact, 58.2% (n = 146) of the lizards we tried to capture on the various islands escaped successfully, while this percentage was only 14.4% (n = 160) on the peninsular mainland. Separate evidence (e.g., proportion of regenerated tails, low human population at the collection areas, etc.) challenges several potential explanations for the higher antipredatory efficiency of insular lizards (e.g., more predation pressure on islands, habituation to humans on the peninsula, etc.). Instead, we suggest that the ability of insular lizards to avoid predators may be related to harvesting by humans, perhaps due to the value of endemic species as rare taxonomic entities. If this hypothesis is correct, predation-related behavioral changes in rare species could provide early warning signals of their over-exploitation, thus encouraging the adoption of conservation measures

Holographic studies of quasi-topological gravity

Quasi-topological gravity is a new gravitational theory including curvature-cubed interactions and for which exact black hole solutions were constructed. In a holographic framework, classical quasi-topological gravity can be thought to be dual to the large $N_c$ limit of some non-supersymmetric but conformal gauge theory. We establish various elements of the AdS/CFT dictionary for this duality. This allows us to infer physical constraints on the couplings in the gravitational theory. Further we use holography to investigate hydrodynamic aspects of the dual gauge theory. In particular, we find that the minimum value of the shear-viscosity-to-entropy-density ratio for this model is $\eta/s \simeq 0.4140/(4\pi)$.Comment: 45 pages, 6 figures. v2: References adde

Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

A quantum-mechanical (QM) method rooted on density functional theory (DFT) linked to the Stochastic Liouville equation (SLE) in the Fokker Planck (FP) form has been employed for the first time to sample the methane-thiosulfonate spin label (MTSL) conformational space attached to the Aurora-A kinase activation loop and to calculate the EPR spectrum. The features of the calculated energy surface allowed us to describe the system in a limited number of rotamers stabilized by interactions of the MTSL side chain and neighbouring residues. The relevant magnetic parameters and the electron paramagnetic resonance (EPR) spectrum were subsequently calculated from the trajectories of the spin probe in the protein environment. The comparison between theoretical and experimental continuous wave (CW) EPR spectra revealed some small differences in the EPR line shape which arises from the combinations of g- and A-values obtained from the conformations selected. The theoretical approach adopted in this work can be used to recognise the contribution of MTSL rotamers to the EPR spectrum in order to help extract structural/dynamics properties of protein from the experimental data

VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VXts) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VXts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VXts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.United States. Defense Threat Reduction Agenc

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Problem formulation by medical students: an observation study

<p>Abstract</p> <p>Background</p> <p>Medical problems are often complex and ill-structured. In formulating the problem, one has to discriminate pertinent elements from irrelevant information in order to effectively find a solution. In this observation study, we describe how medical students formulate the problem of a complex case.</p> <p>Methods</p> <p>32 third year medical students were presented with a complex case of endocarditis. They were asked to synthesize the case and give the best formulation of the problem. They were then asked to provide a diagnosis. A subsequent group of 25 students were presented with the problem already formulated and were also asked for the diagnosis. We analyzed the student's problem formulations using the presence or absence of essential elements of the case, the use of higher-order concepts and the use of relations between concepts.</p> <p>Results</p> <p>12/32 students presented with the case made the correct diagnosis. Diagnostic accuracy was significantly associated with the use of higher-order concepts and relations between concepts. Establishing explicit relations was particularly important. Almost all students who missed the diagnosis could not elicit any relations between concepts but only reported factual observations. When presented with an already formulated problem, 19/25 students made the correct diagnosis. (p < 0.05)</p> <p>Conclusion</p> <p>When faced with a complex new case, students may not have the structured knowledge to recognize the nature of the problem. They have to build new schema or problem representation. Our observations suggest that this process involves using higher-order concepts and establishing new relations between concepts. The fact that students could recognize the disease when presented with a formulated problem but had more difficulty when presented with the original complex case indicates that knowledge of the clinical features may be necessary but not sufficient for problem formulation. Our hypothesis is that problem formulation represents a distinct ability.</p

Operational forecasting of daily summer maximum and minimum temperatures in the Valencia Region

Extreme-temperature events have a great impact on human society. Thus, knowledge of summer temperatures can be very useful both for the general public and for organizations whose workers operate in the open. An accurate forecasting of summer maximum and minimum temperatures could help to predict heatwave conditions and permit the implementation of strategies aimed at minimizing the negative effects that high temperatures have on human health. The objective of this work is to evaluate the skill of the regional atmospheric and modelling system (RAMS) model in determining daily summer maximum and minimum temperatures in the Valencia Region. For this, we have used the real-time configuration of this model currently running at the Centro de Estudios Ambientales de Mediterráneo Foundation. This operational system is run twice a day, and both runs have a 3-day forecast range. To carry out the verification of the model in this work, the information generated by the system has been broken into individual simulation days for a specific daily run of the model. Moreover, we have analysed the summer forecast period from 1 June to 31 August for 2007, 2008, 2009 and 2010. The results indicate good agreement between observed and simulated maximum temperatures, with RMSE in general near 2 °C both for coastal and inland stations. For this parameter, the model shows a negative bias around −1.5 °C in the coast, while the opposite trend is observed inland. In addition, RAMS also shows good results in forecasting minimum temperatures for coastal locations, with bias lower than 1 °C and RMSE below 2 °C. However, the model presents some difficulties for this parameter inland, where bias higher than 3 °C and RMSE of about 4 °C have been found. Besides, there is little difference in both temperatures forecasted within the two daily RAMS cycles and that RAMS is very stable in maintaining the forecast performance at least for three forecast days

A unified framework for multi-locus association analysis of both common and rare variants

<p>Abstract</p> <p>Background</p> <p>Common, complex diseases are hypothesized to result from a combination of common and rare genetic variants. We developed a unified framework for the joint association testing of both types of variants. Within the framework, we developed a union-intersection test suitable for genome-wide analysis of single nucleotide polymorphisms (SNPs), candidate gene data, as well as medical sequencing data. The union-intersection test is a composite test of association of genotype frequencies and differential correlation among markers.</p> <p>Results</p> <p>We demonstrated by computer simulation that the false positive error rate was controlled at the expected level. We also demonstrated scenarios in which the multi-locus test was more powerful than traditional single marker analysis. To illustrate use of the union-intersection test with real data, we analyzed a publically available data set of 319,813 autosomal SNPs genotyped for 938 cases of Parkinson disease and 863 neurologically normal controls for which no genome-wide significant results were found by traditional single marker analysis. We also analyzed an independent follow-up sample of 183 cases and 248 controls for replication.</p> <p>Conclusions</p> <p>We identified a single risk haplotype with a directionally consistent effect in both samples in the gene <it>GAK</it>, which is involved in clathrin-mediated membrane trafficking. We also found suggestive evidence that directionally inconsistent marginal effects from single marker analysis appeared to result from risk being driven by different haplotypes in the two samples for the genes <it>SYN3 </it>and <it>NGLY1</it>, which are involved in neurotransmitter release and proteasomal degradation, respectively. These results illustrate the utility of our unified framework for genome-wide association analysis of common, complex diseases.</p