Gaze anticipation during human locomotion

During locomotion, a top-down organization has been previously demonstrated with the head as a stabilized platform and gaze anticipating the horizontal direction of the trajectory. However, the quantitative assessment of the anticipatory sequence from gaze to trajectory and body segments has not been documented. The present paper provides a detailed investigation into the spatial and temporal anticipatory relationships among the direction of gaze and body segments during locomotion. Participants had to walk along several mentally simulated complex trajectories, without any visual cues indicating the trajectory to follow. The trajectory shapes were presented to the participants on a sheet of paper. Our study includes an analysis of the relationships between horizontal gaze anticipatory behavior direction and the upcoming changes in the trajectory. Our findings confirm the following: 1) The hierarchical ordered organization of gaze and body segment orientations during complex trajectories and free locomotion. Gaze direction anticipates the head orientation, and head orientation anticipates reorientation of the other body segments. 2) The influence of the curvature of the trajectory and constraints of the tasks on the temporal and spatial relationships between gaze and the body segments: Increased curvature resulted in increased time and spatial anticipation. 3) A different sequence of gaze movements at inflection points where gaze plans a much later segment of the trajectory.     

Age determination of adult individuals by three-dimensional modelling of canines

Accurate age determination is fundamental in both forensic medicine and anthropology. Many methods that relate dental characteristics to adult age have been proposed, but there is still no simple and reliable method that does not damage the study material. The aim of this work was to propose a relevant and practical technique for determining age in adults that could be used in both living and deceased individuals. The sample was composed of 210 CT scans from individuals aged from 15 to 85 years old, with four healthy canines present in the mouth. The 840 canines were modelled using Mimics® 10.01 software. The pulp volume/total volume ratio ×100 was determined for each tooth. Seven mathematical models, corresponding to all possible real situations, were determined by the weighted least squares method and ranked in order of relative performance. The adequacy of the seven models to the data was very high with the regressions proposed (0.915?<?R ² _adjusted?<?0.964). Ranked in order of performance, the maxillary model was the most powerful of the seven models for age determination, followed by the 4 canines model, the 13 model and the 23 model.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).     

Detection of acute pulmonary embolism: feasibility of diagnostic accuracy of MRI using a stepwise protocol

Multidetector computed tomography (MDCT) has become the imaging method of choice in patients suspected of having pulmonary embolism (PE) but has the inherent limitation of radiation dose and the side effects of contrast agents. The purpose of the study was to assess the feasibility of a stepwise MRI protocol in the clinical setting of acute PE. The stepwise approach should make it possible to diagnose acute PE in critically ill patients using fast MR sequences and included the option to add comprehensive sequences when patients were stable. Forty-five patients with acute PE (26 men, 19 women; 41?±?16 years) were included in this prospective study. The diagnosis was initially confirmed by MDCT as gold standard. MRI at 1.5 T was subsequently performed without any delay in medical treatment. The MRI protocol proceeded stepwise from robust to detailed imaging techniques (i.e., from TrueFISP and single shot HASTE sequence to MR perfusion and 3D-MR angiography) if the patient was able to tolerate additional imaging time. Diagnostic accuracy was evaluated on the central (lobar) and peripheral (segmental) levels. The complete MR protocol was applied in 40 of the 45 patients (88 %). In the remaining five patients with severe dyspnea the diagnosis of acute PE was established by using fast TrueFISP sequences that were insensitive to respiratory movement. All five patients suffered from a major central PE. Highest sensitivity was achieved by MR perfusion (lobar, 98 %; segmental, 95 %). Real-time TrueFISP and MR angiography showed the highest specificity (lobar, 90–100 %; segmental, 95–97 %). The combination of all MR sequences matched closely the results of MDCT (lobar: sensitivity 98 %, specificity 100 %; segmental: sensitivity 95 %, specificity 97 %). MRI using a stepwise protocol is a promising approach for diagnosing acute PE. The protocol can be tailored for dyspneic patients with central PE using real-time MRI sequences. The diagnostic accuracy for peripheral PE can be improved by using combined MR techniques, achieving comparable results to MDCT.     

Neuroglobin Gene Therapy Prevents Optic Atrophy and Preserves Durably Visual Function in Harlequin Mice

Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates the adverse effects of hypoxic and ischemic insults. We previously demonstrated the functional link between NGB and mitochondria since it is required for respiratory chain function. Thus, here, we evaluated the relevance of this effect in the Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss and optic atrophy due to a respiratory chain complex I (CI) defect. A twofold decrease of NGB amounts was observed in Hq retinas. We constructed a recombinant adeno-associated virus which combines to the mouse NGB open reading frame, its 5′ and 3′UTR, for guarantying mRNA stability and translation capacity. The vector was administrated intravitreally to Hq mice and NGB expression was stable for up to 7 months without negative effect on retinal architecture or function. On the contrary, RGCs and their axons were substantially preserved from degeneration; consequently, CI activity in optic nerves was protected conferring improvements in vision. Hence, we established that NGB prevents respiratory chain impairment, therefore, protecting visual function otherwise compromised by mitochondrial energetic failure.     

Frequent expression of PD‐L1 on circulating breast cancer cells

Immune checkpoint regulators such as PD‐L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non‐responders are urgently needed. In the present paper, we provide evidence that PD‐L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor‐positive, HER2‐negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch® system and found PD‐L1(+) CTCs in 11 patients (68.8%). The fraction of PD‐L1(+) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD‐L1 on CTCs. The established CTC/PD‐L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade.