Effect of hip flexion angle on hamstring optimum length after a single set of concentric contractions.

The eccentric contraction mode was proposed to be the primary stimulus for optimum angle (angle at which peak torque occurs) shift. However, the training range of motion (or muscle excursion range) could be a stimulus as important. The aim of this study was to assess the influence of the training range of motion stimulus on the hamstring optimum length. It was hypothesised that performing a single set of concentric contractions beyond optimal length (seated at 80° of hip flexion) would lead to an immediate shift of the optimum angle to longer muscle length while performing it below (supine at 0° of hip flexion) would not provide any shift. Eleven male participants were assessed on an isokinetic dynamometer. In both positions, the test consisted of 30 consecutive knee flexions at 4.19 rad · s⁻¹. The optimum angle was significantly shifted by ∼15° in the direction of longer muscle length after the contractions at 80° of hip flexion, while a non-significant shift of 3° was found at 0°. The hamstring fatigability was not influenced by the hip position. It was concluded that the training range of motion seems to be a relevant stimulus for shifting the optimum angle to longer muscle length. Moreover, fatigue appears as a mechanism partly responsible for the observed shift.

The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d') were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single-trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long-term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time.

A microarray-based system for the simultaneous analysis of single nucleotide polymorphisms in human genes involved in the metabolism of anti-malarial drugs

Background: In order to provide a cost-effective tool to analyse pharmacogenetic markers in malaria treatment, DNA microarray technology was compared with sequencing of polymerase chain reaction (PCR) fragments to detect single nucleotide polymorphisms (SNPs) in a larger number of samples. Methods: The microarray was developed to affordably generate SNP data of genes encoding the human cytochrome P450 enzyme family (CYP) and N-acetyltransferase-2 (NAT2) involved in antimalarial drug metabolisms and with known polymorphisms, i.e. CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and NAT2. Results: For some SNPs, i.e. CYP2A6*2, CYP2B6*5, CYP2C8*3, CYP2C9*3/*5, CYP2C19*3, CYP2D6*4 and NAT2*6/*7/*14, agreement between both techniques ranged from substantial to almost perfect (kappa index between 0.61 and 1.00), whilst for other SNPs a large variability from slight to substantial agreement (kappa index between 0.39 and 1.00) was found, e. g. CYP2D6*17 (2850C>T), CYP3A4*1B and CYP3A5*3. Conclusion: The major limit of the microarray technology for this purpose was lack of robustness and with a large number of missing data or with incorrect specificity.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Résumé Etude de la valeur pronostique de la biopsie du ganglion sentinelle dans une étude prospective monocentrique de 327 patients atteints de mélanome malin But II s'agit de confirmer la validité de la biopsie du ganglion sentinelle, d'en définir la morbidité, d'investiguer les facteurs prédictifs pour le statut du ganglion sentinelle ainsi que de déterminer les facteurs pronostiques pour la survie sans récidive et la survie spécifique liée à la maladie. Matériel et méthode D'octobre 1997 à décembre 2004, 327 patients consécutifs présentant un mélanome cutané primaire des membres, du tronc et de la tête, sans adénopathie clinique ni métastase à distance ont été inclus. La biopsie du ganglion sentinelle a été réalisée selon la triple technique (lymphoscintigraphie, colorant bleu vital et sonde de détection gamma). Les paramètres et la survie ont été évalués par différentes analyses de régression logistique multiple selon Cox et la survie évaluée selon Kaplan Meier. Résultats Vingt-trois pour cent des patients présentaient au moins un ganglion sentinelle métastatique, ce qui était associé de façon significative à l'épaisseur selon Breslow (p<0.001). Le taux de succès de la biopsie du ganglion sentinelle était de 99.1% et sa morbidité de 7.6%. Avec une durée médiane de suivi de 33 mois, la survie sans récidive à 5 ans était de 43% pour les patients avec un ganglion sentinelle positif et de 83.5% pour ceux avec un ganglion sentinelle négatif. La survie spécifique liée à la maladie à 5 ans était de 49% pour les patients avec un ganglion sentinelle positif et de 87.4% pour ceux avec un ganglion sentinelle négatif. Le taux de faux négatif de la biopsie du ganglion sentinelle était de 8.6%. L'analyse multivariée a démontré que la survie sans récidive était significativement péjorée par :l'épaisseur selon Breslow (RR=5.6, p<0.001), un ganglion sentinelle positif (RR=5.0, p<0.001), et le sexe masculin (RR=2.9, p=0.001). La survie spécifique liée à la maladie était significativement diminuée par : un ganglion sentinelle métastatique (RR=8.4, p<O.OOI), le sexe masculin (RR=6.1, p<0.001), l'épaisseur selon Breslow (RR=3.2, p=0.013), et la présence d'une ulcération (RR=2.6, p=0.015). Conclusion La biopsie du ganglion sentinelle est une procédure fiable avec une haute sensibilité (91.4%) et une faible morbidité (7.6%). L'épaisseur selon Breslow était le seul facteur prédictif significatif pour le statut du ganglion sentinelle. La survie sans récidive était péjorée selon un ordre décroissant par :l'épaisseur selon Breslow, un ganglion sentinelle métastatique, et le sexe masculin. De façon similaire la survie spécifique liée à la maladie était péjorée par : un ganglion sentinelle métastatique, le sexe masculin, l'épaisseur selon Breslow, et une ulcération. Ces données renforcent le statut du ganglion sentinelle en tant que puissant moyen pour évaluer le stade tumoral ainsi que le pronostic.

Cryo-negative staining: advantages and applications for three-dimensional electron microscopy of biological macromolecules

Les échantillons biologiques ne s?arrangent pas toujours en objets ordonnés (cristaux 2D ou hélices) nécessaires pour la microscopie électronique ni en cristaux 3D parfaitement ordonnés pour la cristallographie rayons X alors que de nombreux spécimens sont tout simplement trop << gros D pour la spectroscopie NMR. C?est pour ces raisons que l?analyse de particules isolées par la cryo-microscopie électronique est devenue une technique de plus en plus importante pour déterminer la structure de macromolécules. Néanmoins, le faible rapport signal-sur-bruit ainsi que la forte sensibilité des échantillons biologiques natifs face au faisceau électronique restent deux parmi les facteurs limitant la résolution. La cryo-coloration négative est une technique récemment développée permettant l?observation des échantillons biologiques avec le microscope électronique. Ils sont observés à l?état vitrifié et à basse température, en présence d?un colorant (molybdate d?ammonium). Les avantages de la cryo-coloration négative sont étudiés dans ce travail. Les résultats obtenus révèlent que les problèmes majeurs peuvent êtres évités par l?utilisation de cette nouvelle technique. Les échantillons sont représentés fidèlement avec un SNR 10 fois plus important que dans le cas des échantillons dans l?eau. De plus, la comparaison de données obtenues après de multiples expositions montre que les dégâts liés au faisceau électronique sont réduits considérablement. D?autre part, les résultats exposés mettent en évidence que la technique est idéale pour l?analyse à haute résolution de macromolécules biologiques. La solution vitrifiée de molybdate d?ammonium entourant l?échantillon n?empêche pas l?accès à la structure interne de la protéine. Finalement, plusieurs exemples d?application démontrent les avantages de cette technique nouvellement développée.<br/><br/>Many biological specimens do not arrange themselves in ordered assemblies (tubular or flat 2D crystals) suitable for electron crystallography, nor in perfectly ordered 3D crystals for X-ray diffraction; many other are simply too large to be approached by NMR spectroscopy. Therefore, single-particles analysis has become a progressively more important technique for structural determination of large isolated macromolecules by cryo-electron microscopy. Nevertheless, the low signal-to-noise ratio and the high electron-beam sensitivity of biological samples remain two main resolution-limiting factors, when the specimens are observed in their native state. Cryo-negative staining is a recently developed technique that allows the study of biological samples with the electron microscope. The samples are observed at low temperature, in the vitrified state, but in presence of a stain (ammonium molybdate). In the present work, the advantages of this novel technique are investigated: it is shown that cryo-negative staining can generally overcome most of the problems encountered with cryo-electron microscopy of vitrified native suspension of biological particles. The specimens are faithfully represented with a 10-times higher SNR than in the case of unstained samples. Beam-damage is found to be considerably reduced by comparison of multiple-exposure series of both stained and unstained samples. The present report also demonstrates that cryo-negative staining is capable of high- resolution analysis of biological macromolecules. The vitrified stain solution surrounding the sample does not forbid the access to the interna1 features (ie. the secondary structure) of a protein. This finding is of direct interest for the structural biologist trying to combine electron microscopy and X-ray data. developed electron microscopy technique. Finally, several application examples demonstrate the advantages of this newly

Single-trial multisensory memories affect later auditory and visual object discrimination.

Multisensory memory traces established via single-trial exposures can impact subsequent visual object recognition. This impact appears to depend on the meaningfulness of the initial multisensory pairing, implying that multisensory exposures establish distinct object representations that are accessible during later unisensory processing. Multisensory contexts may be particularly effective in influencing auditory discrimination, given the purportedly inferior recognition memory in this sensory modality. The possibility of this generalization and the equivalence of effects when memory discrimination was being performed in the visual vs. auditory modality were at the focus of this study. First, we demonstrate that visual object discrimination is affected by the context of prior multisensory encounters, replicating and extending previous findings by controlling for the probability of multisensory contexts during initial as well as repeated object presentations. Second, we provide the first evidence that single-trial multisensory memories impact subsequent auditory object discrimination. Auditory object discrimination was enhanced when initial presentations entailed semantically congruent multisensory pairs and was impaired after semantically incongruent multisensory encounters, compared to sounds that had been encountered only in a unisensory manner. Third, the impact of single-trial multisensory memories upon unisensory object discrimination was greater when the task was performed in the auditory vs. visual modality. Fourth, there was no evidence for correlation between effects of past multisensory experiences on visual and auditory processing, suggestive of largely independent object processing mechanisms between modalities. We discuss these findings in terms of the conceptual short term memory (CSTM) model and predictive coding. Our results suggest differential recruitment and modulation of conceptual memory networks according to the sensory task at hand.

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

Single acquisition electrical property mapping based on relative coil sensitivities: A proof-of-concept demonstration.

PURPOSE: All methods presented to date to map both conductivity and permittivity rely on multiple acquisitions to compute quantitatively the magnitude of radiofrequency transmit fields, B1+. In this work, we propose a method to compute both conductivity and permittivity based solely on relative receive coil sensitivities ( B1-) that can be obtained in one single measurement without the need to neither explicitly perform transmit/receive phase separation nor make assumptions regarding those phases. THEORY AND METHODS: To demonstrate the validity and the noise sensitivity of our method we used electromagnetic finite differences simulations of a 16-channel transceiver array. To experimentally validate our methodology at 7 Tesla, multi compartment phantom data was acquired using a standard 32-channel receive coil system and two-dimensional (2D) and 3D gradient echo acquisition. The reconstructed electric properties were correlated to those measured using dielectric probes. RESULTS: The method was demonstrated both in simulations and in phantom data with correlations to both the modeled and bench measurements being close to identity. The noise properties were modeled and understood. CONCLUSION: The proposed methodology allows to quantitatively determine the electrical properties of a sample using any MR contrast, with the only constraint being the need to have 4 or more receive coils and high SNR. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Single breath-hold 3D measurement of left atrial volume using compressed sensing cardiovascular magnetic resonance and a non-model-based reconstruction approach.

BACKGROUND: Left atrial (LA) dilatation is associated with a large variety of cardiac diseases. Current cardiovascular magnetic resonance (CMR) strategies to measure LA volumes are based on multi-breath-hold multi-slice acquisitions, which are time-consuming and susceptible to misregistration. AIM: To develop a time-efficient single breath-hold 3D CMR acquisition and reconstruction method to precisely measure LA volumes and function. METHODS: A highly accelerated compressed-sensing multi-slice cine sequence (CS-cineCMR) was combined with a non-model-based 3D reconstruction method to measure LA volumes with high temporal and spatial resolution during a single breath-hold. This approach was validated in LA phantoms of different shapes and applied in 3 patients. In addition, the influence of slice orientations on accuracy was evaluated in the LA phantoms for the new approach in comparison with a conventional model-based biplane area-length reconstruction. As a reference in patients, a self-navigated high-resolution whole-heart 3D dataset (3D-HR-CMR) was acquired during mid-diastole to yield accurate LA volumes. RESULTS: Phantom studies. LA volumes were accurately measured by CS-cineCMR with a mean difference of -4.73 ± 1.75 ml (-8.67 ± 3.54%, r2 = 0.94). For the new method the calculated volumes were not significantly different when different orientations of the CS-cineCMR slices were applied to cover the LA phantoms. Long-axis "aligned" vs "not aligned" with the phantom long-axis yielded similar differences vs the reference volume (-4.87 ± 1.73 ml vs. -4.45 ± 1.97 ml, p = 0.67) and short-axis "perpendicular" vs. "not-perpendicular" with the LA long-axis (-4.72 ± 1.66 ml vs. -4.75 ± 2.13 ml; p = 0.98). The conventional bi-plane area-length method was susceptible for slice orientations (p = 0.0085 for the interaction of "slice orientation" and "reconstruction technique", 2-way ANOVA for repeated measures). To use the 3D-HR-CMR as the reference for LA volumes in patients, it was validated in the LA phantoms (mean difference: -1.37 ± 1.35 ml, -2.38 ± 2.44%, r2 = 0.97). Patient study: The CS-cineCMR LA volumes of the mid-diastolic frame matched closely with the reference LA volume (measured by 3D-HR-CMR) with a difference of -2.66 ± 6.5 ml (3.0% underestimation; true LA volumes: 63 ml, 62 ml, and 395 ml). Finally, a high intra- and inter-observer agreement for maximal and minimal LA volume measurement is also shown. CONCLUSIONS: The proposed method combines a highly accelerated single-breathhold compressed-sensing multi-slice CMR technique with a non-model-based 3D reconstruction to accurately and reproducibly measure LA volumes and function.

Single stage transforaminal retrojugular tumor resection: The spinal keyhole for dumbbell tumors in the cervical spine.

BACKGROUND: Dumbbell tumors are defined as having an intradural and extradural component with an intermediate component within an expanded neural foramen. Complete resection of these lesions in the subaxial cervical spine is a challenge, and it has been achieved through a combined posterior/anterior or anterolateral approach. This study describes a single stage transforaminal retrojugular (TFR) approach for dumbbell tumors resection in the cervical spine. METHODS: This is a retrospective review of a series of 17 patients treated for cervical benign tumors, 4 of which were "true" cervical dumbbell tumors operated by a simplified retrojugular approach. The TFR approach allows a single stage gross total resection of both the extraspinal and intraspinal/intradural components of the tumor, taking advantage of the expanded neural foramen. All patients were followed clinically and radiologically with magnetic resonance imaging (MRI). RESULTS: Gross total resection was confirmed in all four patients by postoperative MRI. Minimal to no bone resection was performed. No fusion procedure was performed and no delayed instability was seen. At follow up, one patient had a persistent mild hand weakness and Horners syndrome following resection of a hemangioblastoma of the C8 nerve root. The other three patients were neurologically normal. CONCLUSIONS: The TFR approach appears to be a feasible surgical option for single stage resection in selective cases of dumbbell tumors of the cervical spine.

Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level.

In sport events like Olympic Games or World Championships competitive athletes keep pushing the boundaries of human performance. Compared to team sports, high achievements in many athletic disciplines depend solely on the individual's performance. Contrasting previous research looking for expertise-related differences in brain anatomy at the group level, we aim to demonstrate changes in individual top athlete's brain, which would be averaged out in a group analysis. We compared structural magnetic resonance images (MRI) of three professional track-and-field athletes to age-, gender- and education-matched control subjects. To determine brain features specific to these top athletes, we tested for significant deviations in structural grey matter density between each of the three top athletes and a carefully matched control sample. While total brain volumes were comparable between athletes and controls, we show regional grey matter differences in striatum and thalamus. The demonstrated brain anatomy patterns remained stable and were detected after 2 years with Olympic Games in between. We also found differences in the fusiform gyrus in two top long jumpers. We interpret our findings in reward-related areas as correlates of top athletes' persistency to reach top-level skill performance over years.