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Background Pain is one of the major symptoms complained about by patients in the prehospital setting, especially in trauma. Due to the mountainous topography, there may be a time delay between injury and arrival of professional rescuers, in particular on ski slopes. Administration of a safe opioid by first responders (FR) may improve overall treatment. We therefore assessed the use of nasally administered Nalbuphine as analgesic treatment in trauma patients by FR at various skis resort in Switzerland.Methods This observational study examined a cohort of 267 patients given Nalbuphine by FR in various ski resorts in Switzerland. All FR were instructed how to administer Nalbuphine before treating patients. A treatment algorithm was developed and distributed to assure that Nalbuphine was only administered following a strict protocol. Data regarding pain scores and pain reduction after administration of Nalbuphine were collected on-site. Refills were handed out with each completed questionnaire.Results Nalbuphine decreased the level of pain statistically significant and clinically relevant by a median of 3 units on the NRS for pain. The multivariate regression model showed that pain reduction was more pronounced in patients with higher initial pain level. Nalbuphine was less effective in patients aged 20-60 years compared to the adolescent population. No major side effects were observed.Conclusion Nasal Nalbuphine by FR was a noninvasive pain management strategy that provided safe and effective analgesia in prehospital, acute­ly injured patients. This may be an alternative method especially in circumstances of severe pain and prolonged time between arrival of the FR and arrival of EMS / HEMS personnel on scene.

Si toute l'attention est actuellement focalisée sur la Chine pour déterminer le point de départ de la pandémie de Covid-19, l'Afrique a beaucoup à dire - et à faire - en matière de gestion des maladies infectieuses d'origine animale. Une jeune chercheuse de l'IRD, Eve Miguel, porte un projet ambitieux pour faire collaborer ensemble sciences vétérinaires, sociologie et écologie au Zimbabwe. Dans ce pays possédant l'un des écosystèmes les plus riches du continent africain, les épidémies bovines érodent la santé et l'économie depuis près de vingt ans. Alors la chercheuse veut comprendre comment se transmettent les infections, dans un milieu où se côtoient sans cesse faune sauvage et faune domestique. Un véritable laboratoire de la biodiversité, influencé par la présence humaine...

BACKGROUND: Patellofemoral osteoarthritis (OA) and anterior knee pain sometimes are considered contraindications for unicompartmental knee arthroplasty (UKA). However, several studies have demonstrated excellent patient-reported outcome scores in patients with patellofemoral OA treated with medial mobile-bearing UKA. Because these studies assessed the outcome of mobile-bearing UKA only, we were interested to see whether that finding also applies to fixed-bearing medial UKA. QUESTIONS/PURPOSES: (1) Does patellofemoral OA influence patient-reported outcome scores after medial fixed-bearing UKA? (2) Does untreated medial patellofemoral OA increase the revision rate after medial fixed-bearing UKA? METHODS: Between 2008 and 2015, one surgeon performed 308 medial fixed-bearing UKAs of a single design. Of those, 80 (26%) had patellofemoral OA of at least moderate severity (ICRS III or IV), and 228 (74%) did not. During that period, the surgeon did not use patellofemoral OA as a contraindication to UKA. In all, 13 patients (10%) in the patellofemoral OA group were lost before 2-year minimum followup, and 20 (11%) in the control group (without patellofemoral OA) were lost; all other patients were available, seen in the last 5 years, and included in this retrospective study. Mean (± SD) followup in the patellofemoral OA group was 39 ± 25 months, and it was 41 ± 23 in the control group. There were 100 women and 120 men. Patients had a mean age ± SD of 65 ± 10 years and mean ± SD BMI of 29 ± 4.5 kg/m(2).The intraoperative status of the patellofemoral joint was assessed using the International Cartilage Repair Society (ICRS) classification. The primary study endpoint was the Forgotten Joint Score (FJS-12); we also compared scores on the Lonner PatelloFemoral Score (LPFS), Oxford Knee Score (OKS) and Short-Form 12 (SF-12). With the numbers available, we had 80% power to detect a difference of 12.3 points on the Forgotten Joint Score. A secondary endpoint was femoral or tibial component revision for any reason verified over the phone for each included patient. RESULTS: With the numbers available, there was no difference in FJS-12 score between the UKA with patellofemoral OA group and the group without patellofemoral OA 71 ± 29 versus 77 ± 26, mean difference - 6; 95% CI, -16 to 4.5; p = 0.270). Likewise, with the numbers available, we saw no differences in LPFS, OKS and SF-12. There was no difference in survivorship from all-cause revision at 4 years between the patellofemoral OA group and the group without patellofemoral OA (98%; 95% CI, 85.8–99.7 versus 99.5%; 95% CI, 96.0–99.2%; p = 0.352). CONCLUSIONS: Patients with medial osteoarthritis in this single-center study generally benefitted from medial fixed-bearing UKA with good-to-excellent outcomes scores at short term, whether or not medial patellofemoral wear is present. LEVEL OF EVIDENCE: Level III, therapeutic study.

We present a detailed coarse-grained computer simulation and single molecule fluorescence study of the walking dynamics and mechanism of a DNA bipedal motor striding on a DNA origami. In particular, we study the dependency of the walking efficiency and stepping kinetics on step size. The simulations accurately capture and explain three different experimental observations. These include a description of the maximum possible step size, a decrease in the walking efficiency over short distances and a dependency of the efficiency on the walking direction with respect to the origami track. The former two observations were not expected and are non-trivial. Based on this study, we suggest three design modifications to improve future DNA walkers. Our study demonstrates the ability of the oxDNA model to resolve the dynamics of complex DNA machines, and its usefulness as an engineering tool for the design of DNA machines that operate in the three spatial dimensions.

Clopidogrel hydrogen sulfate, a thienopyridine derivative, is an ADP receptor antagonist that inhibits platelet aggregation. Clopidogrel is an enantiopure carboxylic ester of S-configuration. The R-enantiomer is devoid of antithrombotic activity and can provoke convulsions at high doses in animals. During preclinical safety evaluation, the possible chiral inversion of clopidogrel has, therefore, been investigated in vivo after repeated oral administration of different dose levels of clopidogrel to male and female rats. Due to rapid metabolism in the liver and low plasma levels of unchanged drug, possible chiral inversion was assessed by monitoring the plasma concentrations of the carboxylic acid metabolites, i.e., the (S)- and (R)-acid, by means of a stereoselective assay. The production of 4 to 8% of (R)-acid was observed. This could be the result of chiral inversion of either clopidogrel or its main metabolite, the (S)-acid. Thus, the possibility of nonenzymatic and enzymatic inversion of clopidogrel and its carboxylic acid metabolite was studied in vitro by chiral HPLC and (1)H NMR. Nonenzymatic chiral inversion of clopidogrel at 37 degrees C in 0.1 M phosphate buffers could be observed but was found to be slow, with estimated half-lives of 7 to 12 days, depending on the pH. The (S)-acid was configurationally fully stable up to 45 days in phosphate buffers. Neither clopidogrel nor its carboxylic acid metabolites were subject to enzymatic chiral inversion in isolated rat hepatocyte suspensions. We conclude that the nonenzymatic inversion of clopidogrel accounts for the 4 to 8% of chiral inversion seen in vivo in the rat.