Comparison of skin and shoe marker placement on metatarsophalangeal joint kinematics and kinetics during running.

This study investigated the effects of marker placement (skin- vs shoe-mounted) on metatarsophalangeal joint (MTP) kinematics and kinetics during running. Fifteen trained men ran on a 15-m track at 10 and 13 km/h with three (low, standard and high stiffness) shoe longitudinal bending stiffnesses (LBS). Reflective markers were fixed on the shoe upper, and on the skin using holes cut in the shoe. Three-dimensional marker positions and ground reaction forces were recorded at 200 and 2000 Hz, respectively. Kinematic and kinetic parameters were analyzed using one-dimensional metrics (statistical parametric mapping). MTP joint was less dorsiflexed at midstance ([57% to 100%] of braking phase and [0% to 48%] of pushing phase), and the MTP joint plantarflexion moment was higher ([22% to 55%] of pushing phase) with the shoe markerset in comparison with the skin markerset. The effect of LBS on MTP angle was found to be significant for a larger percentage of each stride using the shoe markerset compared to the skin markerset. However, the effect of LBS on plantarflexion moment was significant with the shoe markerset only. The effect of running speed on MTP angle was significant for a larger percentage of each stride with the skin markerset. This study demonstrates that the placement of markers influences the measurement of MTP kinematics and kinetics and that these effects are mediated by other variables such as LBS or running speed. It is concluded that the shoe markerset does not fully reflect the movement of the MTP joint.

A skills framework integrating professionally relevant medicinal chemistry proficiencies to strengthen the contemporary practice of pharmacy.

OBJECTIVE: Our aim was to define a repository of competences in Medicinal Chemistry, to be developed during Pharmacy studies and expected in professional practices, while highlighting the fundamental character of the subject and its interdisciplinary links within the Pharmaceutical Sciences. METHODS: A first version, based on both our professional and educational experience, consolidated by a review of educational articles and good practice guidelines, was obtained by following a competency-based approach. It was then completed by Medicinal Chemistry teachers in various French Pharmacy Faculties to obtain a comprehensive data set. The final version was reviewed in the light of relevant comments from 15 experts from related disciplines. RESULTS: A comprehensive competency framework with extensive practical applications was developed. CONCLUSIONS: This pilot study provides a teaching repository for medicinal chemistry for use by teachers of medicinal sciences. It highlights the fundamental role of the discipline within Pharmacy studies and provides links with professional practices. This repository will be useful to various teaching teams in a context of integrated disciplines and could be replicated in related disciplines.

Degradation of energy cost with fatigue induced by trail running: effect of distance.

PURPOSE: The effect of trail running competitions on cost of running (Cr) remains unclear and no study has directly examined the effect of distances in similar conditions on Cr. Accordingly, the aims of this study were to (i) assess the effect of trail running races of 40-170 km on Cr and (ii) to assess whether the incline at which Cr is measured influences changes in Cr. METHODS: Twenty trail runners completed races of < 100 km (SHORT) and 26 trail runners completed races of > 100 km (LONG) on similar courses and environmental conditions. Oxygen uptake, respiratory exchange ratio, ventilation, and blood lactate were measured before and after the events on a treadmill with 0% (FLAT) and 15% incline (UH) and Cr was calculated. RESULTS: Cr increased significantly after SHORT but not LONG races. There was no clear relationship between changes in Cr and changes in ventilation or blood lactate. There was a significant correlation (r = 0.75, p < 0.01) between changes in FLAT and UH Cr, and the change in Cr was not affected by the incline at which Cr was measured. CONCLUSION: The distance of the trail running race, but not the slope at which it is measured, influence the changes in Cr with fatigue. The mechanism by which Cr increases only in SHORT is not related to increased cost of breathing.

Artificial intelligence solution to classify pulmonary nodules on CT.

PURPOSE: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques. MATERIALS AND METHOD: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC). RESULTS: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%). CONCLUSION: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

Expeditious synthesis and cytotoxic activity of new cyanoindolo[3,2-c]quinolines and benzimidazo[1,2-c]quinazolines.

Novel 6-cyanoindolo[3,2-c]quinoline and 6-cyanobenzimidazo[1,2-c]quinazoline derivatives have been synthesised by treatment of the appropriate aromatic amines with 4.5-dichloro-1,2,3-dithiazolium chloride 1 (Appel salt). The cytotoxicity and the effect of these compounds on cellular growth were measured.

Synthesis and antiproliferative evaluation of 7-aminosubstituted pyrroloiminoquinone derivatives.

Coupling of five amines on the 7-methoxy-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline core was achieved and afforded, in particular, an opened analogue of the natural alkaloid wakayin. Evaluation of cytotoxic activity of compounds 2, 10-13 on L1210 cells afforded IC50 in the range 0.25 5.3 microM.

Biophysical and biological properties of newly synthesized dioxinocoumarin derivatives. II. Dark and photoinduced effects on T7 phage, yeast and HeLa cells.

The dioxinocoumarin derivatives 5H-[2]benzopyrano-[3,4-g][1,4]benzodioxin-5-one (I), 5H-[2]benzopyrano-[3,4-g][2,3]-dihydro-[1,4]benzodioxin-5-on e II, 6H-[2]benzopyrano[3,4-f]-1,4-benzodioxin-6-one (III) and 6H-[2]benzopyrano[3,4-f]-2,3-dihydro-1,4-benzodioxin-6-one (IV) were synthesized. Their biological effect was studied in the presence and absence of UVA radiation, and compared with that of 8-methoxypsoralen (8-MOP) and angelicin derivatives on T7 phage, diploid yeast (Saccharomyces cerevisiae) and HeLa cells. The photobiological activities of compounds I and III were stronger than that of 8-MOP in phage inactivation and DNA synthesis inhibition in HeLa cells, whereas compounds II and IV, with a saturated dioxin ring, showed very poor activity. The photosensitizing activity of dioxinocoumarins on phage inactivation decreased by a factor of two to three in the absence of oxygen. Treatments with compound I and UVA in the presence of oxygen modified the helical structure and stability of phage DNA and proteins. Compounds I and II were more active than IV for photoinduced cell killing in yeast, although always less active than 8-MOP. At comparable photocytotoxic levels, compounds I and III were as strong inducers of cytoplasmic "petite" mutants in yeast as angelicin, suggesting a possible monofunctional mode of action with cellular DNA.

Biophysical and biological properties of newly synthesized dioxinocoumarin derivatives. Part I: Dark effects on T7 phage and HeLa cells.

Several dioxinocoumarin derivatives have been synthesized for photochemotherapeutical purposes. The physicochemical properties of 3,4-benzo-6,7-dioxinocoumarin and its biological activity in the dark were studied with regard to future photobiological applications. It was found that molecular aggregates are formed in aqueous solution at a concentration higher than 10(-5) mol l-1. In the dark, 3,4-benzo-6,7-dioxinocoumarin inactivates T7 phage and inhibits the growth of HeLa cells in a concentration-dependent manner. The dark inactivation of T7 phage was quantitatively characterized. It was found to be higher than that of 8-methoxypsoralen (8-MOP) and approximately equal to 4,6,4'-trimethylangelicin (TMA). From the inactivation kinetics and the lack of a quenching effect of polynucleotides on the fluorescence emission of the drug, it appears that, apart from the induction of DNA damage, other events are implicated in T7 phage dark inactivation. These results are important for the interpretation of the photobiological effects of this type of compound.