Nous avons décidé de faire une étude à partir des réunions de concertations pluridisciplinaires (RCP) endométriose afin d’étudier leur impact sur l’amélioration diagnostique et thérapeutique des ...patientes aux HUS et de chercher des pistes d’amélioration de cette RCP.
Il s’agit d’une étude rétrospective des 682 patientes présentées en RCP endométriose depuis sa création en mars 2017 jusqu’à décembre 2020.
La décision de la RCP a été différente de celle initialement proposée par le référent de la patiente pour 406 patientes (60 %). Il a été décidé d’une chirurgie pour 417 patientes (61 %) et d’une prise en charge en procréation médicalement assistée chez 261 patientes (38 %). Une relecture de l’IRM par un radiologue référent a été réalisée pour 348 dossiers (51 %) avec une modification des résultats pour 255 patientes (73 %). Il s’agissait d’une sous-estimation initiale des lésions pour 198 dossiers.
Notre étude a montré l’importance de la présence de RCP dans l’endométriose puisque la proposition thérapeutique a été modifiée dans 60 % des cas. De plus, nous avons appuyé l’importance de radiologues spécialisés dans ce domaine, puisqu’ils apportent une modification dans les deux tiers des IRM relues. Ces résultats montrent l’importance de discussions collégiales qui peuvent modifier les décisions des équipes médicales. Cela souligne l’importance de la mise en place de réseaux d’endométriose.
We decided to conduct a study based on these multidisciplinary team (MDT) in order to investigate their impact at the University Hospitals of Strasbourg and look for ways to improve this MDT.
This is a retrospective study of the 682 patients presented to endometriosis MDT from its inception in March 2017 to December 2020.
The MDT decision was different from that initially proposed by the patient's referent for 406 patients (60%). Surgery was chosen for 417 patients (61%) and assisted reproduction for 261 patients (38%). A review of the MRI by a referring radiologist was carried out for 348 cases (51%), with a modification of the results for 255 patients (73%). Initial underestimation of lesions was noted in 198 cases.
Our study has shown the importance of MDT in endometriosis since the therapeutic proposal was modified in 60% of cases. In addition, we supported the importance of radiologists specializing in this field since they made a modification in two-thirds of the MRIs reread. These results show the importance of collegial discussions, which can modify the decisions of medical teams. This underlines the importance of setting up endometriosis networks.
We decided to conduct a study based on these multidisciplinary team (MDT) in order to investigate their impact at the University Hospitals of Strasbourg and look for ways to improve this MDT.
This is ...a retrospective study of the 682 patients presented to endometriosis MDT from its inception in March 2017 to December 2020.
The MDT decision was different from that initially proposed by the patient's referent for 406 patients (60%). Surgery was chosen for 417 patients (61%) and assisted reproduction for 261 patients (38%). A review of the MRI by a referring radiologist was carried out for 348 cases (51%), with a modification of the results for 255 patients (73%). Initial underestimation of lesions was noted in 198 cases.
Our study has shown the importance of MDT in endometriosis since the therapeutic proposal was modified in 60% of cases. In addition, we supported the importance of radiologists specializing in this field since they made a modification in two-thirds of the MRIs reread. These results show the importance of collegial discussions, which can modify the decisions of medical teams. This underlines the importance of setting up endometriosis networks.
Heart disease remains a major complication of diabetes, and the identification of new therapeutic targets is essential. This study investigates the role of the protein kinase MK2, a p38 ...mitogen-activated protein kinase downstream target, in the development of diabetes-induced cardiomyopathy. Diabetes was induced in control (MK2(+/+)) and MK2-null (MK2(-/-)) mice using repeated injections of a low dose of streptozotocin (STZ). This protocol generated in MK2(+/+) mice a model of diabetes characterized by a 50% decrease in plasma insulin, hyperglycemia, and insulin resistance (IR), as well as major contractile dysfunction, which was associated with alterations in proteins involved in calcium handling. While MK2(-/-)-STZ mice remained hyperglycemic, they showed improved IR and none of the cardiac functional or molecular alterations. Further analyses highlighted marked lipid perturbations in MK2(+/+)-STZ mice, which encompass increased 1) circulating levels of free fatty acid, ketone bodies, and long-chain acylcarnitines and 2) cardiac triglyceride accumulation and ex vivo palmitate β-oxidation. MK2(-/-)-STZ mice were also protected against all these diabetes-induced lipid alterations. Our results demonstrate the benefits of MK2 deletion on diabetes-induced cardiac molecular and lipid metabolic changes, as well as contractile dysfunction. As a result, MK2 represents a new potential therapeutic target to prevent diabetes-induced cardiac dysfunction.
Recent developments in neutron scattering instrumentation and sample handling have enabled studies of more complex biological samples and measurements at shorter exposure times. The experiments are ...typically conducted in D2O‐based buffers to emphasize or diminish scattering from a particular component or to minimize background noise in the experiment. To extract most information from such experiments it is thus desirable to determine accurate estimates of how and when closely bound hydrogen atoms from the biomolecule exchange with the deuterium in the solvent. This article introduces and documents software, PSX, for exploring the effect of hydrogen–deuterium exchange for proteins solubilized in D2O as well as the underlying bioinformatical models. The software aims to be generally applicable for any atomistic structure of a protein and its surrounding environment, and thus captures effects of both heterogenous exchange rates throughout the protein structure and varying the experimental conditions such as pH and temperature. The paper concludes with examples of applications and estimates of the effect in typical scenarios emerging in small‐angle neutron scattering on biological macromolecules in solution. The analysis presented here suggests that the common assumption of 90% exchange is in many cases an overestimate with the rapid sample handling systems currently available, which leads to fitting and calibration issues when analysing the data. Source code for the presented software is available from an online repository in which it is published under version 3 of the GNU publishing licence.
Using established models, the effect of exposing protonated protein samples to D2O is calculated, and the impact on small‐angle neutron scattering experiments is assessed. Software to evaluate the effect of this from a given structure is introduced, and examples of applications are given.
Pelvic organ prolapse (POP) is a common condition that affects 50% of women who have given birth in their lifetime. With stop of vaginal mesh sale in 2019, the sacrospinous fixation technique ...according to Richter with native tissue has seen its incidence tripled in 15 years. Classically, sacrospinous fixation according to Richter is performed unilaterally, however its unilateral or bilateral character is controversial. Objective of this work is to evaluate the efficacy and safety of bilateral sacrospinous fixation according to Richter by the posterior approach with native tissue (SSB).
We performed a retrospective single-center study. From March 12, 2010 to March 23, 2020, all first-time operated patients who underwent SSB in CHU Strasbourg gynecological surgery unit for symptomatic POP management were included. The main endpoint of our work is the anatomical and functional success rate at 12 and 24 months. The secondary judgment criteria of our work were based on the postoperative evaluation of patient's quality of life according to the PFDI-20 score as well as the rate of postoperative complications.
77 patients were included in our work. The anatomical success rate at 12 months is 94 and 81% at 24 months regardless of the compartment affected. The functional success rate is 94% at 12 months and 82% at 24 months. Quality of life evaluation through the PFDI-20 scale revealed a clear improvement in the symptomatology related to POP: 127/300 +/- 27.3. preoperatively and 59.8 ± 14.7 postoperatively.
Bilateral sacrospinous fixation according to Richter by posterior approach with native tissue is a safe and effective surgical technique allowing a clear improvement in patients quality of life.
Neurotensin, a neuropeptide growth factor, and its two specific neurotensin receptors, NTSR1 and NTSR2, were shown to be expressed by human B cell lines. Another NTSR, sortilin, which is common to ...neurotensin and neurotrophins, was also detected as we have previously described. Neurotensin was functional in B cell lines; it induced their proliferation and inhibited apoptosis induced by serum deprivation or Fas activation. Quantitative study of gene expression in two malignant B cell diseases showed that NTSR2 was overexpressed, NTSR1 decreased, and neurotensin was unexpressed in B cell leukemia patient's cells, as compared with healthy B cells. However, these expressions did not significantly change in large diffuse B cell lymphoma lymph nodes compared with benign ones. This study points out that neurotensin and its two specific receptors are expressed in human B lymphocytes. Such expressions were not described, and their relationship in B cell diseases, especially in chronic B cell leukemia, needs to be considered further in regard to these findings.
A novel and generally applicable method for determining structures of membrane proteins in solution via small‐angle neutron scattering (SANS) is presented. Common detergents for solubilizing membrane ...proteins were synthesized in isotope‐substituted versions for utilizing the intrinsic neutron scattering length difference between hydrogen and deuterium. Individual hydrogen/deuterium levels of the detergent head and tail groups were achieved such that the formed micelles became effectively invisible in heavy water (D2O) when investigated by neutrons. This way, only the signal from the membrane protein remained in the SANS data. We demonstrate that the method is not only generally applicable on five very different membrane proteins but also reveals subtle structural details about the sarco/endoplasmatic reticulum Ca2+ ATPase (SERCA). In all, the synthesis of isotope‐substituted detergents makes solution structure determination of membrane proteins by SANS and subsequent data analysis available to nonspecialists.
A generally applicable method for determining structures of membrane proteins in solution via small‐angle neutron scattering (SANS) is presented. Common detergents for solubilizing membrane proteins were synthesized in isotope‐substituted versions such that they became effectively invisible in heavy water (D2O) when investigated by neutrons. We demonstrate that this method is generally applicable and makes solution structure determination of membrane proteins by SANS and subsequent data analysis available to nonspecialists.
Deep infiltrating pelvic endometriosis and its surgical management is associated with a risk of major postoperative complications. Magnetic Resonance Imaging (MRI) is recommended preoperatively in ...order to obtain the most precise mapping of the extent of endometriotic lesions. The aim of this work was to assess the feasibility and clinical interest of 3D modeling by surface rendering as a preoperative planning tool in a patient with deep infiltrating pelvic endometriosis. We report on a 42 years old patient with history of endometriosis and persistent pain underwent pre operative imaging with MRI that was consistent with deep infiltrating endometriosis. A 3D model of the deep infiltrating endometriosis was generated from the MRI and retrospectively compared to the intra-operative findings. The nodule's location and relationship to the uterus and the rectum was clearly defined by the 3D model and correlated with surgical findings. Virtual reality based on 3D models could be an interesting tool to assist in the preoperative planning of complex surgeries.
Three dimers of the amphipathic α-helical peptide 18A have been synthesized with different interhelical linkers inserted between the two copies of 18A. The dimeric peptides were denoted 'beltides' ...where Beltide-1 refers to the 18A-dimer without a linker, Beltide-2 is the 18A-dimer with proline (Pro) as a linker and Beltide-3 is the 18A-dimer linked by two glycines (Gly-Gly). The self-assembly of the beltides with the phospholipid DMPC was studied with and without the incorporated membrane protein bacteriorhodopsin (bR) through a combination of coarse-grained MD simulations, size-exclusion chromatography (SEC), circular dichroism (CD) spectroscopy, small-angle scattering (SAS), static light scattering (SLS) and UV-Vis spectroscopy. For all three beltides, MD and combined small-angle X-ray and -neutron scattering were consistent with a disc structure composed by a phospholipid bilayer surrounded by a belt of peptides and with a total disc diameter of approximately 10 nm. CD confirmed that all three beltides were α-helical in the free form and with DMPC. However, as shown by SEC the different interhelical linkers clearly led to different properties of the beltides. Beltide-3, with the Gly-Gly linker, was very adaptable such that peptide nanodiscs could be formed for a broad range of different peptide to lipid stoichiometries and therefore also possible disc-sizes. On the other hand, both Beltide-2 with the Pro linker and Beltide-1 without a linker were less adaptable and would only form discs of certain peptide to lipid stoichiometries. SLS revealed that the structural stability of the formed peptide nanodiscs was also highly affected by the linkers and it was found that Beltide-1 gave more stable discs than the other two beltides. With respect to membrane protein stabilization, each of the three beltides in combination with DMPC stabilizes the seven-helix transmembrane protein bacteriorhodopsin significantly better than the detergent octyl glucoside, but no significant difference was observed between the three beltides. We conclude that adaptability, size, and structural stability can be tuned by changing the interhelical linker while maintaining the properties of the discs with respect to membrane protein stabilization.
Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of ...systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data.
Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles.
Serum NGF levels were higher in SSc patients (288.26 ± 170.34 pg/mL) than in control subjects (170.34 ± 50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9 ± 158.1 vs 1372.9 ± 190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2 ± 2296 vs 2959.3 ± 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls).
Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc.
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