Thoracic empyema with scarlatiniform rash and acral desquamation: a case report

A 5 year old girl with thoracic empyema developed a scarlatiniform rash and acral desquamation. Cultures from blood, throat, and pleural fluid all grew Streptococcus pyogenes, a common etiologic agent of pediatric thoracic empyema. The presence of a scarlatiniform rash and acral desquamation in children with a thoracic empyema may help identify the causative organism

Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11–18 years

myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11–18 years. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for 2 non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland–Altman plots (using between and within-individual information) and weighted κ to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data, and ICC ranged from 0·46 for Na to 0·88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was −230 kJ (−55 kcal) (95 % CI −490, 30 kJ (−117, 7 kcal); P=0·4) with limits of agreement ranging between 39 % (3336 kJ (−797 kcal)) lower and 34 % (2874 kJ (687 kcal)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ w =0·64). The agreement between day 1 and day 2 was as good for myfood24 as for the interviewer-administered MPR, reflecting the reliability of myfood24. myfood24 Has the potential to collect dietary data of comparable quality with that of an interviewer-administered MPR

Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice

Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers

Characterization of voltage-gated ionic currents in a peripheral sensory neuron in larval Drosophila.

BACKGROUND: The development, morphology and genetics of sensory neurons have been extensively studied in Drosophila. Sensory neurons in the body wall of larval Drosophila in particular have been the subject of numerous anatomical studies, however, little is known about the intrinsic electrical properties of larval sensory cells. FINDINGS: We performed whole cell patch recordings from an identified peripheral sensory cell, the dorsal bipolar sensory neuron (dbd) and measured voltage-gated ionic currents in 1st instar larvae. Voltage clamp analysis revealed that dbds have a TEA sensitive, non-inactivating IK type potassium current as well as a 4-AP sensitive, inactivating IA type potassium current. dbds also show a voltage-gated calcium current (ICa) and a voltage-gated sodium current (INa). CONCLUSIONS: This work provides a first characterization of voltage-activated ionic currents in an identified body-wall sensory neuron in larval Drosophila. Overall, we establish baseline physiology data for future studies aimed at understanding the ionic and genetic basis of sensory neuron function in fruit flies and other model organisms.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The Dynamical Mechanism of Auto-Inhibition of AMP-Activated Protein Kinase

We use a novel normal mode analysis of an elastic network model drawn from configurations generated during microsecond all-atom molecular dynamics simulations to analyze the mechanism of auto-inhibition of AMP-activated protein kinase (AMPK). A recent X-ray and mutagenesis experiment (Chen, et al Nature 2009, 459, 1146) of the AMPK homolog S. Pombe sucrose non-fermenting 1 (SNF1) has proposed a new conformational switch model involving the movement of the kinase domain (KD) between an inactive unphosphorylated open state and an active or semi-active phosphorylated closed state, mediated by the autoinhibitory domain (AID), and a similar mutagenesis study showed that rat AMPK has the same auto-inhibition mechanism. However, there is no direct dynamical evidence to support this model and it is not clear whether other functionally important local structural components are equally inhibited. By using the same SNF1 KD-AID fragment as that used in experiment, we show that AID inhibits the catalytic function by restraining the KD into an unproductive open conformation, thereby limiting local structural rearrangements, while mutations that disrupt the interactions between the KD and AID allow for both the local structural rearrangement and global interlobe conformational transition. Our calculations further show that the AID also greatly impacts the structuring and mobility of the activation loop

Multipurpose made colorimetric materials for amines, pH change and metal ion detection

Sensors are routinely developed for specific applications, but multipurpose sensors are challenging, due to stability and poor functional design. We report organic materials that operate in solution and gas phase. They show a strong response behaviour to at least three types of environmental changes: pH, amine and metal ion binding/detection. We have confirmed and validated our findings using various analytical and computational methods. We found that the changes in polarity of the solvent and pH not only red shift the tail of the absorption spectra, but also extend the peak optical absorption of these structures by up to 100 nm, with consequential effects on the optical gap and colour changes of the materials. Acid–base response has been studied by spectrophotometric titrations with trifluoroacetic acid (TFA) and triethyl amine (TEA). The experiments show excellent reversibility with greater sensitivity to base than acid for all compounds. Analysis into metal sensing using Zn(II) and Cu(II) ions as analytes show that the materials can successfully bind the cations forming stable complexes. Moreover, a strong suppression of signal with copper gives an operative modality to detect the copper ion as low as 2.5 × 10−6 M. The formation of the metal complexes was also confirmed by growing crystals using a slow diffusion method; subsequent single crystal X-ray analysis reveals the ratio of ligand to metal to be 2 to 1. To test sensitivity towards various amine vapours, paper-based sensors have been fabricated. The sensors show a detection capability at 1 ppm of amine concentration. We have employed CIE L*a*b* colour space as the evaluation method, this provides numeric comparison of the samples from different series and allows comparison of small colour differences, which are generally undetectable by the human-eye. It shows that the CIE L*a*b* method can assess both sensitivity to a particular class of analytes and a specificity response to individual amines in this subclass offering an inexpensive and versatile methodology

Validation of the Oxford WebQ online 24-hour dietary questionnaire using biomarkers

Oxford WebQ is an online dietary questionnaire covering 24 hours, appropriate for repeated administration in large-scale prospective studies including UK Biobank and the Million Women Study. We compared performance of the Oxford WebQ and a traditional interviewer-administered multi-pass 24-hour recall against biomarkers for protein, potassium and total sugar intake, and total energy expenditure estimated by accelerometry. 160 participants were recruited between 2014 and 2016 in London, UK, and measured at 3 non-consecutive time-points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, sugars and total energy intake estimated by the mean of 2 Oxford WebQs were 0.37, 0.42, 0.45, and 0.31 respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean of 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorised or ranked, was 0.47, 0.39, 0.40, and 0.38 respectively, also improving with repeated administration. These were similar to the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average is taken over repeated administration, reducing measurement error bias in assessment of diet-disease associations

Epistasis in a Model of Molecular Signal Transduction

Biological functions typically involve complex interacting molecular networks, with numerous feedback and regulation loops. How the properties of the system are affected when one, or several of its parts are modified is a question of fundamental interest, with numerous implications for the way we study and understand biological processes and treat diseases. This question can be rephrased in terms of relating genotypes to phenotypes: to what extent does the effect of a genetic variation at one locus depend on genetic variation at all other loci? Systematic quantitative measurements of epistasis – the deviation from additivity in the effect of alleles at different loci – on a given quantitative trait remain a major challenge. Here, we take a complementary approach of studying theoretically the effect of varying multiple parameters in a validated model of molecular signal transduction. To connect with the genotype/phenotype mapping we interpret parameters of the model as different loci with discrete choices of these parameters as alleles, which allows us to systematically examine the dependence of the signaling output – a quantitative trait – on the set of possible allelic combinations. We show quite generally that quantitative traits behave approximately additively (weak epistasis) when alleles correspond to small changes of parameters; epistasis appears as a result of large differences between alleles. When epistasis is relatively strong, it is concentrated in a sparse subset of loci and in low order (e.g. pair-wise) interactions. We find that focusing on interaction between loci that exhibit strong additive effects is an efficient way of identifying most of the epistasis. Our model study defines a theoretical framework for interpretation of experimental data and provides statistical predictions for the structure of genetic interaction expected for moderately complex biological circuits