Epidemiology and population structure of Staphylococcus aureus in various population groups from a rural and semi urban area in Gabon, Central Africa

Little data is available on the epidemiology of Staphylococcus aureus in Africa. In the present study we aim at characterizing the population structure of S. aureus in healthy subjects from a rural and a semi-urban area in Lambaréné, Gabon as well as in hospital staff and inpatients. In total, 500 subjects were screened for S. aureus colonization of the nares, axillae and inguinal region. Overall, 146 (29%) were positive. We found 46 different spa types. The most frequent spa types were t084 (35%) and the agr II was the most prevalent subtype of the accessory gene regulator (56%, n=82). Five isolates (3%) were methicillin resistant S. aureus (MRSA). Carriage rates of S. aureus in Gabon are comparable to developed countries. MRSA is for the first time described and could pose a significant health threat in this region with limited access to microbiological laboratory facilities and to adequate antimicrobial agents.     

The effects of background noise on dichotic listening to consonant-vowel syllables: An fMRI study

The present fMRI study attempts to identify brain areas that may underlie the effect of different background noises on functional brain asymmetry in a dichotic listening task. Previous studies have shown that the prominent right ear advantage in dichotic listening to consonant-vowel syllables is affected by background noise. To explore the underlying neuronal processes, haemodynamic brain responses using fMRI were recorded while participants performed the dichotic listening task in two different noisy backgrounds (conversational “babble” and traffic noise). The behavioural results showed a reduction of the right ear advantage in the background noise conditions, especially in the traffic noise condition. The behavioural results are discussed in terms of alertness-attentional mechanisms. The effects of background noise on brain activation involved significant activations in a speech-processing network. Specifically the changes in activations in the peri-Sylvian region of the superior temporal gyrus and in the temporo-parietal junction part in the left hemisphere, as well as in the superior temporal gyrus/sulcus area in the right hemisphere may mirror the effects of noise on behavioural performance. The effects of noise on brain activation are discussed with regard to pre-activation mechanisms.     

Adaptive Smoothing as Inference Strategy

Although spatial smoothing of fMRI data can serve multiple purposes, increasing the sensitivity of activation detection is probably its greatest benefit. However, this increased detection power comes with a loss of specificity when non-adaptive smoothing (i.e. the standard in most software packages) is used. Simulation studies and analysis of experimental data was performed using the R packages neuRosim and fmri. In these studies, we systematically investigated the effect of spatial smoothing on the power and number of false positives in two particular cases that are often encountered in fMRI research: (1) Single condition activation detection for regions that differ in size, and (2) multiple condition activation detection for neighbouring regions. Our results demonstrate that adaptive smoothing is superior in both cases because less false positives are introduced by the spatial smoothing process compared to standard Gaussian smoothing or FDR inference of unsmoothed data.     

Electrochemical functionalization of gold and silicon surfaces by a maleimide group as a biosensor for immunological application

In the present study we investigated the preparation of biofunctionalized surfaces using the direct electrochemical grafting of maleimidophenyl molecules with subsequent covalent immobilization of specific peptide to detect target antibody, thereby extending the application of the biosensing systems towards immunodiagnostics. Para-maleimidophenyl (p-MP) functional groups were electrochemically grafted on gold and silicon surfaces from solutions of the corresponding diazonium salt. A specially synthesized peptide modified with cysteine (Cys-peptide) was then immobilized on the p-MP grafted substrates by cross-linking between the maleimide groups and the sulfhydryl group of the cysteine residues. Accordingly, the Cys-peptide worked as an antigen that was able to bind specifically the target antibody (anti-GST antibody), while it was non-sensitive to a negative contrast antibody (i.e. anti-Flag β). The immobilization of both specific and non-specific antibodies on the Cys-peptide-modified surfaces was monitored by infrared spectroscopic ellipsometry, a quartz crystal microbalance integrated in flow injection analysis system and potentiometric response. The results obtained clearly demonstrated that the direct modification of a surface with maleimidophenyl provides a very simple and reliable way of preparing biofunctionalized surfaces suitable for the construction of immunological biosensors.     

Biomarkers for Type 2 Diabetes and Impaired Fasting Glucose Using a Nontargeted Metabolomics Approach

Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10⁻⁹) and was moderately heritable (h² = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10⁻⁶) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10⁻³). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication.     

Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation

Following organ engraftment, initial dosing of tacrolimus is based on recipient weight and adjusted by measured C₀ concentrations. The bioavailability and elimination of tacrolimus are affected by the patients CYP3A5 genotype. Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype prior to transplantation are lacking. A nonparametric population model was developed for tacrolimus in renal transplant recipients. Data from 99 patients were used for model development and validation. A three‐compartment model with first‐order absorption and lag time from the dosing compartment described the data well. Clearances and volumes of distribution were allometrically scaled to body size. The final model included fat‐free mass, body mass index, hematocrit, time after transplantation, and CYP3A5 genotype as covariates. The bias and imprecision were 0.35 and 1.38, respectively, in the external data set. Patients with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability. Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3‐4 tacrolimus concentrations were known. After this, a model without CYP3A5 genotype predicted just as well. The present models seem applicable for clinical individual dose predictions but need a prospective evaluation.     

Judging roughness by sight—A 7‐tesla fMRI study on responsivity of the primary somatosensory cortex during observed touch of self and others

Observing another person being touched activates our own somatosensory system. Whether the primary somatosensory cortex (S1) is also activated during the observation of passive touch, and which subregions of S1 are responsible for self‐ and other‐related observed touch is currently unclear. In our study, we first aimed to clarify whether observing passive touch without any action component can robustly increase activity in S1. Secondly, we investigated whether S1 activity only increases when touch of others is observed, or also when touch of one's own body is observed. We were particularly interested in which subregions of S1 are responsible for either process. We used functional magnetic resonance imaging at 7 Tesla to measure S1 activity changes when participants observed videos of their own or another's hand in either egocentric or allocentric perspective being touched by different pieces of sandpaper. Participants were required to judge the roughness of the different sandpaper surfaces. Our results clearly show that S1 activity does increase in response to observing passive touch, and that activity changes are localized in posterior but not in anterior parts of S1. Importantly, activity increases in S1 were particularly related to observing another person being touched. Self‐related observed touch, in contrast, caused no significant activity changes within S1. We therefore assume that posterior but not anterior S1 is part of a system for sharing tactile experiences with others. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.