Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture

Summary Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. Introduction The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. Methods Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. Results Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (−60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, −39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (−39%, −21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. Conclusions This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture

La faute médicale caractérisée en droit français est-elle liée à des qualifications d'intensité et de gravité ?

Medical misconduct in criminal law could be qualified as characterized by judge. It would be determined by the fact that the medical practitioner exposes a patient to health danger with full consciousness. This medical misconduct could be done during positive act or guilty abstention. But the legislator didn’t clarify the term “characterized” of fault in the bill. Precise definitions were established by dispute at law. In the medical field, an analysis was performed when indirect causality was involved by supreme judge. The majority of court rulings were based on criminal negligence which couldn’t be ignored by the medical doctor that endangers health patient. Intensity and gravity in criminal negligence were systematically demonstrated. That could be considered as the term “characterized” in the medical fault

A mutual reference shape based on information theory

International audienceIn this paper, we propose to consider the estimation of a refer-ence shape from a set of different segmentation results using both active contours and information theory. The reference shape is defined as the minimum of a criterion that benefits from both the mutual information and the joint entropy of the input segmentations and called a mutual shape. This energy criterion is here justified using similarities between informa-tion theory quantities and area measures, and presented in a continuous variational framework. This framework brings out some interesting evaluation measures such as the speci-ficity and sensitivity. In order to solve this shape optimization problem, shape derivatives are computed for each term of the criterion and interpreted as an evolution equation of an active contour. Some synthetical examples allow us to cast the light on the difference between our mutual shape and an average shape. Our framework has been considered for the estimation of a mutual shape for the evaluation of cardiac segmentation methods in MRI

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

'Magic coins' and 'magic squares': the discovery of astrological sigils in the Oldenburg Letters

Enclosed in a 1673 letter to Henry Oldenburg were two drawings of a series of astrological sigils, coins and amulets from the collection of Strasbourg mathematician Julius Reichelt (1637–1719). As portrayals of particular medieval and early modern sigils are relatively rare, this paper will analyse the role of these medals in medieval and early modern medicine, the logic behind their perceived efficacy, and their significance in early modern astrological and cabalistic practice. I shall also demonstrate their change in status in the late seventeenth century from potent magical healing amulets tied to the mysteries of the heavens to objects kept in a cabinet for curiosos. The evolving perception of the purpose of sigils mirrored changing early modern beliefs in the occult influences of the heavens upon the body and the natural world, as well as the growing interests among virtuosi in collecting, numismatics and antiquities

Effects of 6 Months of Exercise-Based Cardiac Rehabilitation on Autonomic Function and Neuro-Cardiovascular Stress Reactivity in Coronary Artery Disease Patients

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P\u3c0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P\u3c0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P\u3c0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P\u3c0.01). Heart rate variability (all P\u3e0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P\u3e0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P\u3c0.05); yet, responses were reduced following CR (all P\u3c0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training

The influence of sea ice cover and Atlantic water advection on annual particle export north of Svalbard

The Arctic Ocean north of Svalbard has recently experienced large sea ice losses and the increasing prominence of Atlantic water (AW) advection. To investigate the impact of these ongoing changes on annual particle export, two moorings with sequential sediment traps were deployed in ice‐free and seasonally ice‐covered waters on the shelf north (NSv) and east (ESv) of Svalbard, collecting sinking particles nearly continuously from October 2017 to October 2018. Vertical export of particulate organic carbon (POC), total particulate matter (TPM), planktonic protists, chlorophyll a, and zooplankton fecal pellets were measured, and swimmers were quantified and identified. Combined with sensor data from the moorings, these time‐series measurements provided a first assessment of the factors influencing particle export in this region of the Arctic Ocean. Higher annual TPM and POC fluxes at the ice‐free NSv site were primarily driven by the advection of AW, higher grazing by large copepods, and a wind‐induced mixing event during winter. Higher diatom fluxes were observed during spring in the presence of sea ice at the ESv site. Along with sea ice cover, regional differences in AW advection and the seasonal presence of grazers played a prominent role in the biological carbon pump along the continental shelf off Svalbard

Predicted and actual 2-year structural and pain progression in the IMI-APPROACH knee osteoarthritis cohort

ClinicalTrials.gov, https://clinicaltrials.gov, NCT03883568[Abstract] Objectives: The IMI-APPROACH knee osteoarthritis study used machine learning (ML) to predict structural and/or pain progression, expressed by a structural (S) and pain (P) predicted-progression score, to select patients from existing cohorts. This study evaluates the actual 2-year progression within the IMI-APPROACH, in relation to the predicted-progression scores. Methods: Actual structural progression was measured using minimum joint space width (minJSW). Actual pain (progression) was evaluated using the Knee injury and Osteoarthritis Outcomes Score (KOOS) pain questionnaire. Progression was presented as actual change (Δ) after 2 years, and as progression over 2 years based on a per patient fitted regression line using 0, 0.5, 1 and 2-year values. Differences in predicted-progression scores between actual progressors and non-progressors were evaluated. Receiver operating characteristic (ROC) curves were constructed and corresponding area under the curve (AUC) reported. Using Youden's index, optimal cut-offs were chosen to enable evaluation of both predicted-progression scores to identify actual progressors. Results: Actual structural progressors were initially assigned higher S predicted-progression scores compared with structural non-progressors. Likewise, actual pain progressors were assigned higher P predicted-progression scores compared with pain non-progressors. The AUC-ROC for the S predicted-progression score to identify actual structural progressors was poor (0.612 and 0.599 for Δ and regression minJSW, respectively). The AUC-ROC for the P predicted-progression score to identify actual pain progressors were good (0.817 and 0.830 for Δ and regression KOOS pain, respectively). Conclusion: The S and P predicted-progression scores as provided by the ML models developed and used for the selection of IMI-APPROACH patients were to some degree able to distinguish between actual progressors and non-progressors