Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome.

Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS). Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject's dominant leg was measured for straight leg raise (SLR) range of motion (ROM) before and after interventions. Data were analyzed with a 3 × 2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested.

Implementation of zonal control algorithms in adaptive optical systems with sparse control matrices

Miralls deformables més i més grans, amb cada cop més actuadors estan sent utilitzats actualment en aplicacions d'òptica adaptativa. El control dels miralls amb centenars d'actuadors és un tema de gran interès, ja que les tècniques de control clàssiques basades en la seudoinversa de la matriu de control del sistema es tornen massa lentes quan es tracta de matrius de dimensions tan grans. En aquesta tesi doctoral es proposa un mètode per l'acceleració i la paral.lelitzacó dels algoritmes de control d'aquests miralls, a través de l'aplicació d'una tècnica de control basada en la reducció a zero del components més petits de la matriu de control (sparsification), seguida de l'optimització de l'ordenació dels accionadors de comandament atenent d'acord a la forma de la matriu, i finalment de la seva posterior divisió en petits blocs tridiagonals. Aquests blocs són molt més petits i més fàcils de fer servir en els càlculs, el que permet velocitats de càlcul molt superiors per l'eliminació dels components nuls en la matriu de control. A més, aquest enfocament permet la paral.lelització del càlcul, donant una com0onent de velocitat addicional al sistema. Fins i tot sense paral. lelització, s'ha obtingut un augment de gairebé un 40% de la velocitat de convergència dels miralls amb només 37 actuadors, mitjançant la tècnica proposada. Per validar això, s'ha implementat un muntatge experimental nou complet , que inclou un modulador de fase programable per a la generació de turbulència mitjançant pantalles de fase, i s'ha desenvolupat un model complert del bucle de control per investigar el rendiment de l'algorisme proposat. Els resultats, tant en la simulació com experimentalment, mostren l'equivalència total en els valors de desviació després de la compensació dels diferents tipus d'aberracions per als diferents algoritmes utilitzats, encara que el mètode proposat aquí permet una càrrega computacional molt menor. El procediment s'espera que sigui molt exitós quan s'aplica a miralls molt grans.

Modelling short-term ultraviolet exposure as an alternative to individual dosimetry

Background: Excessive exposure to solar Ultra-Violet (UV) light is the main cause of most skin cancers in humans. Factors such as the increase of solar irradiation at ground level (anthropic pollution), the rise in standard of living (vacation in sunny areas), and (mostly) the development of outdoor activities have contributed to increase exposure. Thus, unsurprisingly, incidence of skin cancers has increased over the last decades more than that of any other cancer. Melanoma is the most lethal cutaneous cancer, while cutaneous carcinomas are the most common cancer type worldwide. UV exposure depends on environmental as well as individual factors related to activity. The influence of individual factors on exposure among building workers was investigated in a previous study. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure. A high variance of short-term exposure was observed between different body locations, indicating the occurrence of intense, subacute exposures. It was also found that effective short-term exposure ranged between 0 and 200% of ambient irradiation, suggesting that ambient irradiation is a poor predictor of effective exposure. Various dosimetric techniques enable to assess individual effective exposure, but dosimetric measurements remain tedious and tend to be situation-specific. As a matter of facts, individual factors (exposure time, body posture and orientation in the sun) often limit the extrapolation of exposure results to similar activities conducted in other conditions. Objective: The research presented in this paper aims at developing and validating a predictive tool of effective individual exposure to solar UV. Methods: Existing computer graphic techniques (3D rendering) were adapted to reflect solar exposure conditions and calculate short-term anatomical doses. A numerical model, represented as a 3D triangular mesh, is used to represent the exposed body. The amount of solar energy received by each "triangle is calculated, taking into account irradiation intensity, incidence angle and possible shadowing from other body parts. The model take into account the three components of the solar irradiation (direct, diffuse and albedo) as well as the orientation and posture of the body. Field measurements were carried out using a forensic mannequin at the Payerne MeteoSwiss station. Short-term dosimetric measurements were performed in 7 anatomical locations for 5 body postures. Field results were compared to the model prediction obtained from the numerical model. Results: The best match between prediction and measurements was obtained for upper body parts such as shoulders (Ratio Modelled/Measured; Mean = 1.21, SD = 0.34) and neck (Mean = 0.81, SD = 0.32). Small curved body parts such as forehead (Mean = 6.48, SD = 9.61) exhibited a lower matching. The prediction is less accurate for complex postures such as kneeling (Mean = 4.13, SD = 8.38) compared to standing up (Mean = 0.85, SD = 0.48). The values obtained from the dosimeters and the ones computed from the model are globally consistent. Conclusion: Although further development and validation are required, these results suggest that effective exposure could be predicted for a given activity (work or leisure) in various ambient irradiation conditions. Using a generic modelling approach is of high interest in terms of implementation costs as well as predictive and retrospective capabilities.

Validity of four short physical activity questionnaires in middle-aged persons.

PURPOSE: Self-administered questionnaires continue to be the most widely used type of physical activity assessment in epidemiological studies. However, test-retest reliability and validity of physical activity questionnaires have to be determined. In this study, three short physical activity questionnaires already used in Switzerland and the International Physical Activity Questionnaire (IPAQ) were validated. METHODS: Test-retest reliability was assessed by repeated administration of all questionnaires within 3 wk in 178 volunteers (77 women, 46.1+/-14.8 yr; 101 men 46.8+/-13.2 yr). Validity of categorical and continuous data was studied in a subsample of 35 persons in relation to 7-d accelerometer readings, percent body fat, and cardiorespiratory fitness. RESULTS: Reliability was fair to good with a Spearman correlation coefficient range of 0.43-0.68 for measures of continuous data and moderate to fair with Kappa values between 0.32 and 0.46 for dichotomous measures active/inactive. Total physical activity reported in the IPAQ and the Office in Motion Questionnaire (OIMQ) correlated with accelerometry readings (r=0.39 and 0.44, respectively). In contrast, correlations of self-reported physical data with percent body fat and cardiorespiratory fitness were low (r=-0.26-0.29). Participants categorized as active by the Swiss HEPA Survey 1999 instrument (HEPA99) accumulated significantly more days of the recommended physical activities than their inactive counterparts (4.4 and 2.7 d.wk, respectively, P<0.05). However, compared with accelerometer data, vigorous physical activities were overreported in investigated questionnaires. CONCLUSION: Collecting valid data on physical activity remains a challenging issue for questionnaire surveys. The IPAQ and the three other questionnaires are characterized to inform decisions about their appropriate use.

Fusion telomérique de deux chromosomes X par leurs bras courts chez une patiente présentant un syndrome de Turner atypique. [Telomeric fusion of the short arms of both X chromosomes in a patient presenting an atypical Turner syndrome.]

A case of atypical Turner's syndrome with unusual karyotype is reported. The chromosome complements of the patient, studied with different banding techniques, is 45,XO/46,X,dic(X)(Xqter leads to p22::p22 leads to qter). In the literature 8 similar cases have been reported. Short stature and amenorrhea are the most constant findings. The mechanisms by which the observed chromosomal "rearrangement" can be produced are briefly discussed.

Effects of short-term high-fructose diets in humans: modulation by environmental factors

It is currently suspected that sugar overconsumption, and more specifically fructose, may promote the development of obesity and of several cardio-metabolic disorders. However, environmental factors, such as fish oil and dietary proteins, may prevent some deleterious effects of fructose. The aim of this thesis was to identify potential environmental factors that may modulate the metabolic effects of fructose. The first study was designed to evaluate the impact of endurance exercise in healthy young men fed a high-fructose, isocaloric diet. Fructose-induced effects on lipid profile were totally prevented by endurance exercise and may be explained by an enhanced clearance of TRL-TG and the inhibition of de novo lipogenesis. As energy intake was adjusted to energy requirement, we can conclude that exercise acts on fructose metabolism independently of energy imbalance. The second study aimed at determining whether coffee and more specifically chlorogenic acid consumption may prevent fructose-induced intrahepatic lipids accumulation, hypertriglyceridemia and hepatic insulin resistance, through a stimulation of lipid oxidation. Coffee did not prevent the fructose-induced increase in IHCL or plasma TG. Interestingly, the three coffees tested prevented the decrease in hepatic insulin sensitivity, independently of their content in caffeine or chlorogenic acid. Finally, in the third study, we evaluated the effect of essential amino acid supplementation on the increase of hepatic lipids induced by a high-fructose diet. This intervention slightly decreased IHCL concentration. The exact mechanisms remain unidentified but may involve an increased secretion of VLDL-TG. In conclusion, the environmental factors evaluated allow to prevent some of the deleterious effects of fructose and suggest that recommendations on fructose consumption should also take into account environmental factors.

Assessment of liver tumor response by high-field (3T) MRI after radiofrequency ablation: Short- and mid-term evolution of diffusion parameters within the ablation zone.

PURPOSE: To compare the apparent diffusion coefficient (ADC) values of malignant liver lesions on diffusion-weighted MRI (DWI) before and after successful radiofrequency ablation (RF ablation). MATERIALS AND METHODS: Thirty-two patients with 43 malignant liver lesions (23/20: metastases/hepatocellular carcinomas (HCC)) underwent liver MRI (3.0T) before (<1month) and after RF ablation (at 1, 3 and 6months) using T2-, gadolinium-enhanced T1- and DWI-weighted MR sequences. Jointly, two radiologists prospectively measured ADCs for each lesion by means of two different regions of interest (ROIs), first including the whole lesion and secondly the area with the visibly most restricted diffusion (MRDA) on ADC map. Changes of ADCs were evaluated with ANOVA and Dunnett tests. RESULTS: Thirty-one patients were successfully treated, while one patient was excluded due to focal recurrence. In metastases (n=22), the ADC in the whole lesion and in MRDA showed an up-and-down evolution. In HCC (n=20), the evolution of ADC was more complex, but with significantly higher values (p=0.013) at 1 and 6months after RF ablation. CONCLUSION: The ADC values of malignant liver lesions successfully treated by RF ablation show a predictable evolution and may help radiologists to monitor tumor response after treatment.

Versión reducida del cuestionario CaMir (CaMir-R) para la evaluación del apego [Short version of CaMir questionnaire (CaMir-R) to assess attachment].

The CaMir is a questionnaire aimed at measuring attachment cognitions. It is based on subjects' evaluations of past and present attachment experiences and family functioning. It is a widely used tool both in research and in clinical settings. The aim of this study was to develop a short version of CaMir in Spanish (CaMir-R) and to obtain evidence about its validity and reliability in a sample of 676 adolescents (364 female and 312 male) belonging to different groups (clinical, maltreated, and community samples) with an age range between 13 and 19 years (M = 15.62, SD = 1.49). We examined its internal structure, convergent, and decision validity, the relationship between its dimensions and psychopathological symptoms, as well as its internal consistency and temporal stability. The CaMir-R included 7 factors whose internal consistency indexes ranged between 0.60 and 0.85. With the exception of the «Parental Permissiveness» dimension, which did not show good reliability, the results suggest that the CaMir-R provides a valid and reliable assessment of attachment representations and of the conception of family functioning.

Fast docking using the CHARMM force field with EADock DSS.

The prediction of binding modes (BMs) occurring between a small molecule and a target protein of biological interest has become of great importance for drug development. The overwhelming diversity of needs leaves room for docking approaches addressing specific problems. Nowadays, the universe of docking software ranges from fast and user friendly programs to algorithmically flexible and accurate approaches. EADock2 is an example of the latter. Its multiobjective scoring function was designed around the CHARMM22 force field and the FACTS solvation model. However, the major drawback of such a software design lies in its computational cost. EADock dihedral space sampling (DSS) is built on the most efficient features of EADock2, namely its hybrid sampling engine and multiobjective scoring function. Its performance is equivalent to that of EADock2 for drug-like ligands, while the CPU time required has been reduced by several orders of magnitude. This huge improvement was achieved through a combination of several innovative features including an automatic bias of the sampling toward putative binding sites, and a very efficient tree-based DSS algorithm. When the top-scoring prediction is considered, 57% of BMs of a test set of 251 complexes were reproduced within 2 Å RMSD to the crystal structure. Up to 70% were reproduced when considering the five top scoring predictions. The success rate is lower in cross-docking assays but remains comparable with that of the latest version of AutoDock that accounts for the protein flexibility. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011.

Suppression of short interfering RNA-mediated gene silencing by the structural proteins of hepatitis C virus.

Viruses have evolved strategies to overcome the antiviral effects of the host at different levels. Besides specific defence mechanisms, the host responds to viral infection via the interferon pathway and also by RNA interference (RNAi). However, several viruses have been identified that suppress RNAi. We addressed the question of whether hepatitis C virus (HCV) suppresses RNAi, using cell lines constitutively expressing green fluorescent protein (GFP) and inducibly expressing HCV proteins. It was found that short interfering RNA-mediated GFP gene silencing was inhibited when the entire HCV polyprotein was expressed. Further studies showed that HCV structural proteins, and in particular envelope protein 2 (E2), were responsible for this inhibition. Co-precipitation assays demonstrated that E2 bound to Argonaute-2 (Ago-2), a member of the RNA-induced silencing complex, RISC. Thus, HCV E2 that interacts with Ago-2 is able to suppress RNAi.

Probabilistic base calling of Solexa sequencing data.

BACKGROUND: Solexa/Illumina short-read ultra-high throughput DNA sequencing technology produces millions of short tags (up to 36 bases) by parallel sequencing-by-synthesis of DNA colonies. The processing and statistical analysis of such high-throughput data poses new challenges; currently a fair proportion of the tags are routinely discarded due to an inability to match them to a reference sequence, thereby reducing the effective throughput of the technology. RESULTS: We propose a novel base calling algorithm using model-based clustering and probability theory to identify ambiguous bases and code them with IUPAC symbols. We also select optimal sub-tags using a score based on information content to remove uncertain bases towards the ends of the reads. CONCLUSION: We show that the method improves genome coverage and number of usable tags as compared with Solexa's data processing pipeline by an average of 15%. An R package is provided which allows fast and accurate base calling of Solexa's fluorescence intensity files and the production of informative diagnostic plots.

Change in defense mechanisms and coping over the course of short-term dynamic psychotherapy for adjustment disorder.

Short-term dynamic psychotherapy (STDP) has rarely been investigated with regard to its underlying mechanisms of change, even if psychoanalytic theory informs us about several potential putative mechanisms of change in patients. Change in overall defensive functioning is one. In this study, we explored the role of overall defensive functioning, by comparing it on the process level with the neighbouring concept of overall coping functioning. A total of N=32 patients, mainly presenting adjustment disorder, were included in the study. The patients underwent STDP up to 40 sessions; three sessions per psychotherapy were transcribed and analyzed by using two observer-rating scales: Defense Mechanism Rating Scales (Perry, 1990) and Coping Action Patterns (Perry, Drapeau, Dunkley, & Blake, 2005). Hierarchical linear modeling was applied to model the change over the course of therapy and relate it to outcome. Results suggest that STDP has an effect on the target variable of overall defensive functioning, which was absent for overall coping functioning. Links with outcome confirm the importance of the effect. These results are discussed from methodological and clinical viewpoints.

Perineuronal nets protect fast-spiking interneurons against oxidative stress.

A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.

Lymphodepletion by short-term chemotherapy does not alter the highly stable and persistent EBV specific CD8 T cell repertoire

Protective T cell responses againstpersistent viruses like Epstein-Barrvirus in healthy individuals are characterizedby a remarkable stability ofthe T cell receptor (TCR) clonotypicrepertoire, with highly preservedclonotype selection and persistenceover time. Here, we extended recentwork to the study of EBV-specificCD8 T cell responses in melanomapatients treated by short-term chemotherapyfor transient lymphodepletion,followed by adoptive cell transfer(ACT) and immune reconstitutionfor cancer therapy. After this treatment,we observed increased proportionsof virus-specific T cells in 3/5patients, accompanied by a more differentiatedphenotype (EMRA/CD28neg), compared to specific cells ofhealthy individuals. Yet, similarly tohealthy donors, clonotype selectionand composition of virus-specific Tcells varied along the pathway of celldifferentiation, with some clonotypesthat were selected with late differentiation,while others were not. Aftertreatment, we did not observe noveldominant clonotypes, likely related toabsence of EBV reactivation measuredas viral load levels by quantitativePCR in PBMCs and antibody levelsin plasma samples. Furthermore,public TCR BV signatures were frequentlyfound within T cell clonotypesthat dominated the repertoiresof patients, in line with those observedin healthy individuals. Ourfindings indicate that even in situationswhere the immune system isstrongly challenged such as followinglymphodepletion and homeostatic repopulation,cytotoxic T cells specificfor EBV remain strikingly stable interms of clonotype selection and com-position along T cell differentiation.We are currently characterizing theclonotype selection and gene expressionprofiles of single EBV-specificCD8 T lymphocytes sorted ex-vivo inone patient who underwent two cyclesof lymphodepletion with escaladingdoses of chemotherapy overone-year interval. Observations madefrom this setting will provide additionalinsight into the degree of stabilityof virus specific T cells, and changesin the expression levels of genesimportant for cytolytic function andlong-term survival of T cells. Thiswork is supported by the Swiss NationalCenter of Competence in Research(NCCR) Molecular Oncology,and the Swiss National Science Foundation.

Handling macromolecule signals in the quantification of the neurochemical profile.

In vivo localized proton magnetic resonance spectroscopy (1H MRS) became a powerful and unique technique to non-invasively investigate brain metabolism of rodents and humans. The main goal of 1H MRS is the reliable quantification of concentrations of metabolites (neurochemical profile) in a well-defined region of the brain. The availability of very high magnetic field strengths combined with the possibility of acquiring spectra at very short echo time have dramatically increased the number of constituents of the neurochemical profile. The quantification of spectra measured at short echo times is complicated by the presence of macromolecule signals of particular importance at high magnetic fields. An error in the macromolecule estimation can lead to substantial errors in the obtained neurochemical profile. The purpose of the present review is to overview methods of high field 1H MRS with a focus on the metabolite quantification, in particular in handling signals of macromolecules. Three main approaches of handling signals of macromolecules are described, namely mathematical estimation of macromolecules, measurement of macromolecules in vivo, and direct acquisition of the in vivo spectrum without the contribution of macromolecules.