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We wish to discuss the importance of MRI in association with the clinical pelvic examination for the study of vaginal prolapse, especially for the posterior compartment (rectocele, elytrocele). The increased sensitivity of static and dynamic MRI allowed a clinicoradiology relation more exactly for the study of prolapse. We describe a clinical observation where the RMI used before and after surgery is more reliable than the only clinic examination. [Copyright &y& Elsevier]

Alzheimer's disease and Type 2 diabetes are pathological processes associated to ageing. Moreover, there are evidences supporting a mechanistic link between Alzheimer's disease and insulin resistance (one of the first hallmarks of Type 2 diabetes). Regarding Alzheimer's disease, amyloid β-peptide aggregation into β-sheets is the main hallmark of Alzheimer's disease. At monomeric state, amyloid β-peptide is not toxic but its function in brain, if any, is unknown. Here we show, by in silico study, that monomeric amyloid β-peptide 1-40 shares the tertiary structure with insulin and is thereby able to bind and activate insulin receptor. We validated this prediction experimentally by treating human neuroblastoma cells with increasing concentrations of monomeric amyloid β-peptide 1-40. Our results confirm that monomeric amyloid β-peptide 1-40 activates insulin receptor autophosphorylation, triggering downstream enzyme phosphorylations and the glucose Transporter 4 translocation to the membrane. On the other hand, neuronal insulin resistance is known to be associated to Alzheimer's disease since early stages. We thus modelled the docking of oligomeric amyloid β-peptide 1-40 to insulin receptor. We found that oligomeric amyloid β-peptide 1-40 blocks insulin receptor, impairing its activation. It was confirmed in vitro by observing the lack of insulin receptor autophosphorylation, and also the impairment of insulin-induced intracellular enzyme activations and the glucose Transporter 4 translocation to the membrane. By biological system analysis, we have carried out a mathematical model recapitulating the process that turns amyloid β-peptide binding to insulin receptor from the physiological to the pathophysiological regime. Our results suggest that monomeric amyloid β-peptide 1-40 contributes to mimic insulin effects in the brain, which could be good when neurons have an extra requirement of energy beside the well-known protective effects on insulin intracellular signalling, while its accumulation and subsequent oligomerization blocks the insulin receptor producing insulin resistance and compromising neuronal metabolism and protective pathways., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Mitochondria play key roles in ATP supply, calcium homeostasis, redox balance control and apoptosis, which in neurons are fundamental for neurotransmission and to allow synaptic plasticity. Their functional integrity is maintained by mitostasis, a process that involves mitochondrial transport, anchoring, fusion and fission processes regulated by different signaling pathways but mainly by the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α also favors Ca 2+ homeostasis, reduces oxidative stress, modulates inflammatory processes and mobilizes mitochondria to where they are needed. To achieve their functions, mitochondria are tightly connected to the endoplasmic reticulum (ER) through specialized structures of the ER termed mitochondria-associated membranes (MAMs), which facilitate the communication between these two organelles mainly to aim Ca 2+ buffering. Alterations in mitochondrial activity enhance reactive oxygen species (ROS) production, disturbing the physiological metabolism and causing cell damage. Furthermore, cytosolic Ca 2+ overload results in an increase in mitochondrial Ca 2+ , resulting in mitochondrial dysfunction and the induction of mitochondrial permeability transition pore (mPTP) opening, leading to mitochondrial swelling and cell death through apoptosis as demonstrated in several neuropathologies. In summary, mitochondrial homeostasis is critical to maintain neuronal function; in fact, their regulation aims to improve neuronal viability and to protect against aging and neurodegenerative diseases.

Alzheimer's disease (AD) is tightly linked to oxidative stress since amyloid beta-peptide (A β ) aggregates generate free radicals. Moreover, the aggregation of A β is increased by oxidative stress, and the neurotoxicity induced by the oligomers and fibrils is in part mediated by free radicals. Interestingly, it has been reported that oxidative stress can also induce BACE1 transcription and expression. BACE1 is the key enzyme in the cleavage of the amyloid precursor protein to produce A β , and the expression of this enzyme has been previously shown to be enhanced in the brains of Alzheimer's patients. Here, we have found that BACE1 expression is increased in the hippocampi from AD patients at both the early (Braak stage II) and late (Braak stage VI) stages of the disease as studied by immunohistochemistry and western blot. To address the role of A β and oxidative stress in the regulation of BACE1 expression, we have analyzed the effect of subtoxic concentrations of A β oligomers (0.25  μ M) and H 2 O 2 (10 mM) on a human neuroblastoma cell line. Firstly, our results show that A β oligomers and H 2 O 2 induce an increase of BACE1 mRNA as we studied by qPCR. Regarding BACE1 translation, it is dependent on the phosphorylation of the eukaryotic initiation factor 2 α (eIF2 α ), since BACE1 mRNA bears a 5'UTR that avoids its translation under basal conditions. BACE1 5'UTR contains four upstream initiating codons (uAUGs), and its translation is activated when eIF2 α is phosphorylated. Consistently, we have obtained that A β oligomers and H 2 O 2 increase the levels of BACE1 and p-eIF2 α assayed by western blot and confocal microscopy. Our results suggest that A β oligomers increase BACE1 translation by phosphorylating eIF2 α in a process that involves oxidative stress and conforms a pathophysiological loop, where the A β once aggregated favors its own production continuously by the increase in BACE1 expression as observed in AD patients., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Pol Picón-Pagès et al.)

High-level competition sports can have a variety of negative effects on the female urogenital apparatus. Perineal trauma is rare and is usually associated with certain sports (impalement or hydrotubation during water-skiing, indurated perineal nodules in racing cyclists, and horse-riders' perineum). Effort incontinence is seen in all sports involving abrupt repeated increases in intra-abdominal pressure that may exceed perineal floor resistance. Sportswomen should be questioned about possible incontinence and be informed of preventive and therapeutic measures.

Forty-three patients with genital prolapse prospectively underwent blinded pre and postoperative MRI, with dynamic assessment of each compartment. MRI was significantly more accurate than physical examination for the diagnosis of posterior defects (rectocele, enterocele) but not for anterior defects or uterine prolapse (hysterocele, cystocele). Postoperative MRI confirmed the surgical outcome and also identified risk factors for recurrence. MRI was particularly reliable for recurrent prolapse and vault prolapse. The authors consider that dynamic MRI can advantageously replace colpocystodefecography, as it is rapid and well tolerated. Technical improvements should help to understand the role of muscular and fascia lesions.

Objectives: Describe a new surgical technique of sling procedure using a vaginal sling and report complications and mid-term functional results. According to these results, it's necessary to discuss the best indications., Material and Methods: Retrospective study of the first 75 patients operated for urinary stress incontinence., Results: The average age of patients was 56 (30-90). Preoperative complications have been rare with only one bladder injury (1.3%). Postoperative complications have been more frequent and the most of them was caused by 76% of urine retention lasting a mean of 14 days and 44% of urinary infections. 20% of the patients have presented secondary dysuria and/or urinary urgency. 4 patients (5.3%) have presented a vaginal mucocele between 9 and 32 months after the operation. At mean follow-up of 25.1 months, the success rate was 70.6%, with 61.3% of patients who have been cured and 9.3% which was improved. In case of severe sphincter insufficiency, the success rate was 80%. Success rate was 30% when the vaginal sling was the only procedure and 66.1% when it was associated to another vaginal procedure (p = 0.006) as vaginal hysterectomy or sacro-spinous suspension., Conclusion: This original surgical technique for cure of urinary stress incontinence is inexpensive and easy to learn. It can be associated to other operations by vaginal way. The realization of this procedure under regional anaesthesia should enable to warn urine retention which is the mean postoperative complication. The success rate of this series is cheerful because it takes into account any patients no selected and operated on the learning phase of the technique. The best results of this technique are urinary stress incontinence associated with vaginal surgery for genital prolapse. The final assessment of this surgical technique will be require longer follow-up and comparative studies with other procedures on an elevated number of patients.

SYDESCO is a new 3D vision system developed for trunk surface topography. This structured light surface scanner uses the principle of triangulation-based range sensing to infer 3D shape. The complete trunk acquisition is fast (2 seconds). The accuracy of the metric data is ensured by a subpixel image detection and a calibration process, which rectifies image deformations. A preliminary study presents results on 50 children in a gymnastics school. These children, aged between eight to sixteen years, are particularly exposed to spinal deformities. An asymmetry index is calculated from the 3D data to detect the pathologic cases. These results have been compared to an independent medical diagnosis. The system results have been confirmed for 72,1% of the patients.

Objective: Many operative techniques have been proposed for urinary stress incontinence, a common finding in women. The goal of operating solely via a vaginal approach using autologous material has led to the development of a sling technique using a band of vaginal tissue., Methods: We described the operative technique and analyzed outcome in the first 35 patients operated with the new vaginal tissue sling technique., Results: Mean duration of the procedure was 35 minutes. The procedure was performed in two cases and thus could be used for prolapsus cure. We had no peroperative complications. Postoperative complications were mainly urine retention (50%) lasting a mean 4.4 days. Transfixation of the bladder was observed late in one case with resection of an intravesicular suture. At mean follow-up of 16.9 months, the success rate was 80% with 68.5% of the patients free of urine leakage. In case of sphincter insufficiency, the success rate was 85.7% (64.3% of the patients were free of leakage). Three of the four patients who had undergone prior Burch colpopexy were cured., Discussion: Our series demonstrated the feasibility of the new vaginal tissue sling technique. It appears to be an adapted procedure for urinary stress incontinence with sphincter insufficiency and particularly well adapted for low closure pressures and after failure of surgical cure. The final assessment of this technique will require longer follow-up and comparative studies with other methods.

Objective: Our purpose was to evaluate the long term sequelae after vaginal hysterectomy., Study Design: A retrospective case control study to evaluate the long term complications after vaginal hysterectomy compared with control patients who had during the same period undergone cholecystectomy for benign pathology. Excluded were hysterectomies during which adnexectomy or treatment of prolapse, stress incontinence or genital cancer was also effected. We selected 221 patients who had undergone simple vaginal hysterectomy and 232 where cholecystectomy had been performed. The questionnaire listed 149 questions that dealt with matching characteristics and queries relating to symptoms., Results: 117 questionnaires suitable for analysis were received from the patients in the hysterectomy group and 95 from the cholecystectomy group. After the matching process 61 patients who had a simple vaginal hysterectomy and 58 who had undergone cholecystectomy were selected. After simple vaginal hysterectomy there was a significant worsening of all urinary problems, of digestive problems and sexual intercourse. After cholecystectomy there is also an increase in the severity of most symptoms surveyed., Conclusion: Many long-term complications following hysterectomy cannot be attributed to the intervention. Vaginal hysterectomy should not be considered as being responsible for major complications appearing during the first 4 years of follow-up.

Several studies have shown that estrogen replacement therapy protects postmenopausal women against coronary artery disease. This protective effect has been ascribed to the hormone's effect on serum lipids, as well as a direct action on the vascular wall. Concurrent administration of a progestin to protect women from the risk of endometrial hyperplasia may alter the protective effects of estrogen. The aim of this study was to assess the evolution of the endothelial function in postmenopausal women given a sequential combination of oral 2 mg estradiol valerate for 11 days, followed by 2 mg estradiol valerate associated with 1 mg cyproterone acetate for ten days (Climène). Each 21-day sequence was followed by a seven-day treatment-free interval. The women received a three-month treatment course. Thirty-one healthy postmenopausal women participated in the study (median age: 51 years; range: 45-59 years). Flow-mediated dilatation (FMD), a reflection of endothelium-dependent vasomotor function, increased from 8.47% at baseline (range: 4.57-11.02%) to 9.64% (range: 7.07-13.12%) at the end of the first treatment cycle; i.e., a 15% increase over baseline (P < 0.0001). FMD further increased after three treatment cycles to 10.59% (range: 8.09-15.22%); i.e., a 28.6% increase over baseline (P < 0.0001). FMD at the end of the first combined sequence or after the 11 days of estradiol only were similar (delta = 0.25%; range: -2.31-5.81%; not significant). In conclusion, in postmenopausal women, a three-month sequential treatment combining estradiol valerate and estradiol valerate plus cyproterone acetate (Climène) has beneficial effects on endothelial function as demonstrated by the evolution of the FMD. There was no decrease in the effect of estradiol on FMD when cyproterone acetate was added to estradiol.