Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2 ) and cerebral metabolic rate of oxygen (CMRO2 ). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2 ), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well-correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty-stenting.
We have developed a multiwell-based protein aggregation assay to study the kinetics of insulin adsorption and aggregation on hydrophobic surfaces and to investigate the molecular mechanisms involved. Protein-surface interaction progresses in two phases: (1) a lag phase during which proteins adsorb and prefibrillar aggregates form on the material surface and (2) a growth phase during which amyloid fibers form and then are progressively released into solution. We studied the effect of three bacterial chaperones, DnaK, DnaJ, and ClpB, on insulin aggregation kinetics. In the presence of ATP, the simultaneous presence of DnaK, DnaJ, and ClpB allows good protection of insulin against aggregation. In the absence of ATP, DnaK alone is able to prevent insulin aggregation. Furthermore, DnaK binds to insulin adsorbed on hydrophobic surfaces. This process is slowed in the presence of ATP and can be enhanced by the cochaperone DnaJ. The peptide LVEALYL, derived from the insulin B chain, is known to promote fast aggregation in a concentration- and pH-dependent manner in solution. We show that it also shortens the lag phase for insulin aggregation on hydrophobic surfaces. As this peptide is also a known DnaK substrate, our data indicate that the peptide and the chaperone might compete for a common site during the process of insulin aggregation on hydrophobic surfaces.
Introduction. Pneumocystis jirovecii pneumonia (PCP) is a severe disease affecting immunocompromised patients. Diagnosis is difficult due to the low sensitivity of direct examination and inability to grow the pathogen in culture. Quantitative PCR in bronchoalveolar lavage fluid (BAL) has high sensitivity, but limited specificity for distinguishing PCP from colonization. Aim. To assess the performance of an in-house quantitative PCR to discriminate between PCP and colonization. Methodology. This was a single-centre retrospective study including all patients with a positive PCR result for P. jirovecii in BAL between 2009 and 2017. Irrespective of PCR results, PCP was defined as the presence of host factors and clinical/radiological criteria consistent with PCP and (i) the presence of asci at direct examination of respiratory sample or (ii) anti-PCP treatment initiated with clinical response and absence of alternative diagnosis. Colonization was considered for cases who did not receive anti-PCP therapy with a favourable outcome or an alternative diagnosis. Cases who did not meet the above mentioned criteria were classified as ‘undetermined’. Results. Seventy-one patients with positive P. jirovecii PCR were included (90 % non-HIV patients). Cases were classified as follows: 37 PCP, 22 colonization and 12 undetermined. Quantitative PCR values in BAL were significantly higher in patients with PCP versus colonization or undetermined ( P <0.0001). The cut-off of 5×10 3 copies/ml was able to discriminate PCP cases from colonization with 97 % sensitivity, 82 % specificity, 90 % positive predictive value and 95 % negative predictive value. Conclusions. Our quantitative PCR for P. jirovecii in BAL was reliable to distinguish PCP cases from colonization in this predominantly non-HIV population.
Digit-tracking, a simple, calibration-free technique, has proven to be a good alternative to eye tracking in vision science. Participants view stimuli superimposed by Gaussian blur on a touchscreen interface and slide a finger across the display to locally sharpen an area the size of the foveal region just at the finger's position. Finger movements are recorded as an indicator of eye movements and attentional focus. Because of its simplicity and portability, this system has many potential applications in basic and applied research. Here we used digit-tracking to investigate visual search and replicated several known effects observed using different types of search arrays. Exploration patterns measured with digit-tracking during visual search of natural scenes were comparable to those previously reported for eye-tracking and constrained by similar saliency. Therefore, our results provide further evidence for the validity and relevance of digit-tracking for basic and applied research on vision and attention.
Abstract-Functional Magnetic Resonance Imaging (fMRI) is a neuroimagingtechnique that allows the non-invasive study of brain function. It is based on the hemodynamic variations induced by changes in cerebral synaptic activity following sensory or cognitive stimulation. The measured signal depends on the variation of blood oxygenation level (BOLD signal) which is related to brain activity: a decrease in deoxyhemoglobin concentration induces an increase in BOLD signal. The BOLD signal is delayed with respect to changes in synaptic activity, which can be modeled as a convolution with the Hemodynamic Response Function (HRF) whose exact form is unknown and fluctuates with various parameters such as age, brain region or physiological conditions.In this paper we present PyHRF, a software to analyze fMRI data using a Joint Detection-Estimation (JDE) approach. It jointly detects cortical activation and estimates the HRF. In contrast to existing tools, PyHRF estimates the HRF instead of considering it as a given constant in the entire brain. Here, we present an overview of the package and showcase its performance with a real case in order to demonstrate that PyHRF is a suitable tool for clinical applications.
Learning to read is a journey full of challenge for first-graders that can be hindered by perceptual and attentional mechanisms. To alleviate some of these barriers, we tested a reading protocol inspired by the Digit-tracking method where the reading text was blurred to reduce visual clutter and attentional interference and increase multi-modal attentional focalisation through finger pointing. As the index finger moved through the blurred text, the letters just above the finger position were unblurred and visible in foveal vision. We hypothesized that this approach might facilitate orthographic decoding and promote efficient ocular-digital scanning. Fifty-four first-grade children were divided into two groups in a crossover design: half of the children did digit-tracking exercises first, followed by plain paper exercises; the reverse order was used for the other half. Results showed that improvement in letters, syllables and meaningless text-reading after digit-tracking training was higher than after paper training. Using recorded finger trajectories as a proxy for eye movements, we found that text scanning patterns (saccade length, landing position, regressive saccades) predicted children’s reading text difficulty and orthographic decoding skills. We conclude that a training that employed digit-tracking on a tablet device improves first graders’ reading performance in the short term more than the same training performed on paper and may provide a sensitive metric of reading competences, that should be confirmed by future replication studies.
One source of difficulty in reading acquisition for first‐graders is that they are hindered by acrowding effect whereby the identification of a target letter or syllable is interfered with bysurrounding letters. We tested a reading protocol inspired by the Digit‐tracking method wherethe reading text was blurred to reduce visual clutter and attentional interference. As the indexfinger moved through the blurred text, the letters just above the finger position were unblurredand visible in foveal vision. We hypothesized that this approach might facilitate orthographicdecoding and promote efficient ocular‐digital scanning. Fifty‐four first‐grade children weredivided into two groups in a crossover design: half of the children did digit‐tracking exercises first,followed by plain paper exercises; the reverse order was used for the other half. Results showedthat progress in letters and syllables reading after digit‐tracking training was higher than afterpaper training. Using recorded finger trajectories as a proxy for eye movements, we found thattext scanning patterns (saccade length, landing position, regressive saccades) predicted children’sreading text difficulty and orthographic decoding skills. We conclude that digit‐tracking improvesfirst graders' reading and provides a sensitive metric of reading competences.
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