Le philosophe et le peintre

Ce témoignage de l’artiste Pierre Magré, proche de Michel Henry, veut rappeler qu’au gré du puissant intertexte pictural qu’est l’œuvre de Kandinsky, il y a bien une volonté, chez M. Henry, de penser le « Principe même de la Création »

Chronic O-GlcNAcylation and Diabetic Cardiomyopathy: The Bitterness of Glucose

Type 2 diabetes (T2D) is a major risk factor for heart failure. Diabetic cardiomyopathy (DC) is characterized by diastolic dysfunction and left ventricular hypertrophy. Epidemiological data suggest that hyperglycaemia contributes to the development of DC. Several cellular pathways have been implicated in the deleterious effects of high glucose concentrations in the heart: oxidative stress, accumulation of advanced glycation end products (AGE), and chronic hexosamine biosynthetic pathway (HBP) activation. In the present review, we focus on the effect of chronic activation of the HBP on diabetic heart function. The HBP supplies N-acetylglucosamine moiety (O-GlcNAc) that is O-linked by O-GlcNAc transferase (OGT) to proteins on serine or threonine residues. This post-translational protein modification modulates the activity of the targeted proteins. In the heart, acute activation of the HBP in response to ischaemia-reperfusion injury appears to be protective. Conversely, chronic activation of the HBP in the diabetic heart affects Ca2+ handling, contractile properties, and mitochondrial function and promotes stress signaling, such as left ventricular hypertrophy and endoplasmic reticulum stress. Many studies have shown that O-GlcNAc impairs the function of key protein targets involved in these pathways, such as phospholamban, calmodulin kinase II, troponin I, and FOXO1. The data show that excessive O-GlcNAcylation is a major trigger of the glucotoxic events that affect heart function under chronic hyperglycaemia. Supporting this finding, pharmacological or genetic inhibition of the HBP in the diabetic heart improves heart function. In addition, the SGLT2 inhibitor dapagliflozin, a glucose lowering agent, has recently been shown to lower cardiac HBP in a lipodystophic T2D mice model and to concomitantly improve the diastolic dysfunction of these mice. Therefore, targeting cardiac-excessive O-GlcNAcylation or specific target proteins represents a potential therapeutic option to treat glucotoxicity in the diabetic heart

Acetabular rim extension using a personalized titanium implant for treatment of hip dysplasia in dogs: short-term results

Hip dysplasia (HD) is a common orthopedic problem in young dogs. To decrease the laxity of the hip joint related to HD, the surgical treatments are recommended to increase femoral head coverage. ACEtabular rim eXtension (ACE-X) using a personalized 3-dimensional printed titanium shelf implant is a new surgical treatment to increase femoral head coverage and decrease laxity of the dysplastic hip joint, however, the efficacy is less know. Client-owned dogs older than 6 months with clinical signs of coxofemoral joint subluxation and radiographic evidence of HD with no or mild osteoarthritis (OA) were included. The Norberg angle (NA), linear percentage of femoral head overlap (LFO), and percentage of femoral head coverage (PC) were investigated radiographically and with computed tomography (CT) before and after surgery. OA was graded (scores 0–3) according to the maximum osteophyte size measured on CT. In addition, joint laxity (Ortolani) test results, gait analysis, and the Helsinki chronic pain index (HCPI) questionnaire were obtained at preoperative, immediately postoperative and at 1.5- and 3-month evaluations. Acetabular rim extension was performed in 61 hips of 34 dogs; NA, LFO, and PC were significantly higher immediately postoperatively and at the 1.5- and 3-month follow-up examinations compared with preoperative values (p < 0.05). Osteophyte size gradually increased over time (p < 0.05). The OA score significantly increased between preoperatively and directly postoperatively, and between preoperatively and at 3-month follow-up (p < 0.05). The laxity test normalized in 59 out of 61 hips after surgery, and the HCPI questionnaire showed that the pain score decreased significantly at 1.5 and 3 months, postoperatively. The force plate showed no significant improvement during the 3 months follow-up. Although pain reduction by the implant was unclear in short-term results, a personalized shelf implant significantly increased femoral head coverage and eliminated subluxation of the dysplastic hip joint. Further studies are required to study the long-term efficacy of gait, chronic pain, and progression of osteoarthritis

Morphologic Changes of the Intervertebral Disk During Growth

Study Design. Cross-sectional. Objective. The aim of this study was to describe morphologic changes of the annulus fibrosus (AF) and nucleus pulposus (NP) in children during growth using magnetic resonance imaging. Summary of Background Data. Little is known of intervertebral disk (IVD) maturation as opposed to degeneration, such as changes in relative AF/NP proportions and orientation during growth. Studies suggest that IVD plays a role in the etiology of pediatric spinal deformities. Therefore, understanding the morphologic development of the AF and NP during growth is key. Materials and Methods. An existing database of children aged 0 to 18 that had magnetic resonance imaging for indications unrelated to the spine were analyzed. The AF/NP were segmented semiautomatically from T1 to L5. The parameters: mean IVD height, cross-sectional area, slenderness (height/width ratio), volume (ratio), and relative position of the centroid of the NP within the IVD in three directions (x, y, z) were extracted, and compared between age, sex, and spinal level. Results. IVD height increased modestly and predominantly in the low-thoracic and lumbar spine during the first 5 to 10 years of life. Cross-sectional area and thus volume increased steadily at all levels throughout growth. IVD slenderness decreased sharply in the first years of life and remains relatively stable throughout the remainder of growth. IVDs were smaller and more slender in females, especially in the mid-thoracic spine at early adolescence. In the upper-thoracic and mid-thoracic spine the NP comprises 10% to 12% of total IVD volume during growth, this percentage increases in the low-thoracic and lumbar spine towards 20% to 25%. In the anterior-posterior direction, the position of the nucleus increasingly shifts with age, possibly in line with the developing sagittal profile of the spine. Conclusion. This study describes the development of thoracic and lumbar IVDs during growth and may be used as a reference for future studies on the role of IVD in the etiology of disk-related disorders

Prediction of the Proximal Humerus Morphology Based on a Statistical Shape Model with Two Parameters: Comparison to Contralateral Registration Method

(1) Background: Complex proximal humerus fractures often result in complications following surgical treatment. A better understanding of the full 3D displacement would provide insight into the fracture morphology. Repositioning of fracture elements is often conducted by using the contralateral side as a reconstruction template. However, this requires healthy contralateral anatomy. The purpose of this study was to create a Statistical Shape Model (SSM) and compare its effectiveness to the contralateral registration method for the prediction of the humeral proximal segment; (2) Methods: An SSM was created from 137 healthy humeri. A prediction for the proximal segment of the left humeri from eight healthy patients was made by combining the SSM with parameters. The predicted proximal segment was compared to the left proximal segment of the patients. Their left humerus was also compared to the contralateral (right) humerus; (3) Results: Eight modes explained 95% of the variation. Most deviations of the SSM prediction and the contralateral registration method were below the clinically relevant 2 mm distance threshold.; (4) Conclusions: An SSM combined with parameters is a suitable method to predict the proximal humeral segment when the contralateral CT scan is unavailable or the contralateral humerus is unhealthy, provided that the fracture pattern allows measurements of these parameters

Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia

International audienceFamilial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species

Cochlear implant positioning: development and validation of an automatic method using computed tomography image analysis

UNLABELLED: The aim of this study was to preoperatively asses the feasibility of drilling a bony recess for the fixation of a cochlear implant in the temporal bone. Even though complications are rare with cochlear implantations, drilling at the site of implantation have resulted in hematoma or cerebrospinal fluid leakage. Mainly in cases with a reduced temporal bone thickness, the risk for complications has increased, such as in paediatric patients. METHODS: An in-house designed semi-automatic algorithm was developed to analyse a 3D model of the skull. The feasibility of drilling the recess was determined by a gradient descent method to search for the thickest part of the temporal bone. Feasibility was determined by the residual bone thickness which was calculated after a simulated drilling of the recess at the thickest position. An initial validation of the algorithm was performed by measuring the accuracy of the algorithm on five 3D models with known thickest locations for the recess. The accuracy was determined by a part comparison between the known position and algorithm provided position. RESULTS: In four of the five validation models a standard deviation for accuracy below the predetermined cut-off value of 4.2 mm was achieved between the actual thickest position and the position determined by the algorithm. Furthermore, the residual thickness calculated by the algorithm showed a high agreement (max. 0.02 mm difference) with the actual thickness. CONCLUSION: With the developed algorithm, a semi-automatic method was created to analyse the temporal bone thickness within a specified region of interest on the skull. Thereby, providing indications for surgical feasibility, potential risks for anatomical structures and impact on procedure time of cochlear implantation. This method could be a valuable research tool to objectively assess feasibility of drilling a recess in patients with thin temporal bones preoperatively

A star is born again: Methods for larval rearing of an emerging model organism, the False clownfish Amphiprion ocellaris

As interest increases in ecological, evolutionary, and developmental biology (Eco-Evo-Devo), wild species are increasingly used as experimental models. However, we are still lacking a suitable model for marine fish species, as well as coral reef fishes that can be reared at laboratory scales. Extensive knowledge of the life cycle of anemonefishes, and the peculiarities of their biology, make them relevant marine fish models for developmental biology, ecology, and evolutionary sciences. Here, we present standard methods to maintain breeding pairs of the anemonefish Amphiprion ocellaris in captivity, obtain regular good quality spawning, and protocols to ensure larval survival throughout rearing. We provide a detailed description of the anemonefish husbandry system and life prey culturing protocols. Finally, a “low-volume” rearing protocol useful for the pharmacological treatment of larvae is presented. Such methods are important as strict requirements for large volumes in rearing tanks often inhibit continuous treatments with expensive or rare compounds