Structural modeling of protein-RNA complexes using crosslinking of segmentally isotope-labeled RNA and MS/MS.

Ribonucleoproteins (RNPs) are key regulators of cellular function. We established an efficient approach, crosslinking of segmentally isotope-labeled RNA and tandem mass spectrometry (CLIR-MS/MS), to localize protein-RNA interactions simultaneously at amino acid and nucleotide resolution. The approach was tested on polypyrimidine tract binding protein 1 and U1 small nuclear RNP. Our method provides distance restraints to support integrative atomic-scale structural modeling and to gain mechanistic insights into RNP-regulated processes.

[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review]. / Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée.

INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

A Review of the EUSO-Balloon Pathfinder for the JEM-EUSO Program.

EUSO-Balloon is a pathfinder for JEM-EUSO, the mission concept of a spaceborne observatory which is designed to observe Ultra-High Energy Cosmic Ray (UHECR)-induced Extensive Air Showers (EAS) by detecting their UltraViolet (UV) light tracks "from above." On August 25, 2014, EUSO-Balloon was launched from Timmins Stratospheric Balloon Base (Ontario, Canada) by the balloon division of the French Space Agency CNES. After reaching a floating altitude of 38 km, EUSO-Balloon imaged the UV light in the wavelength range ∼290-500 nm for more than 5 hours using the key technologies of JEM-EUSO. The flight allowed a good understanding of the performance of the detector to be developed, giving insights into possible improvements to be applied to future missions. A detailed measurement of the photoelectron counts in different atmospheric and ground conditions was achieved. By means of the simulation of the instrument response and by assuming atmospheric models, the absolute intensity of diffuse light was estimated. The instrument detected hundreds of laser tracks with similar characteristics to EASs shot by a helicopter flying underneath. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. The reconstruction of the direction of the laser tracks was performed. In this work, a review of the main results obtained by EUSO-Balloon is presented as well as implications for future space-based observations of UHECRs.

[Role of ultrasound in the evaluation of patients after laparoscopic sacropexy: preliminary study]. / Intérêt de l'échographie dans le suivi des patientes après promontofixation par coelioscopie: étude préliminaire.

OBJECTIVES: To evaluate results of laparoscopic sacropexy with introital and vaginal ultrasonography, that is to observe dynamic behavior of the mesh, to measure precisely its position and to conclude on the feasibility of this exam. PATIENTS AND METHODS: The surgery was a laparoscopic subtotal hysterectomy and a suspension of the cervix with an anterior vesicovaginal mesh and a posterior rectovaginal mesh. These meshes are joined together and fixed on the sacrum. Ultrasound was performed in fifteen patients to see in the sagital plane the position of the mesh. The distance anterior mesh-bladder neck and the distance posterior mesh-anal sphincter were measured at rest, during straining and during retaining. The spreading out and the dynamic behavior of the mesh were studied. RESULTS: The distance anterior mesh-bladder neck is 12 mm at rest, 15 mm during straining and 13 mm during retaining. The distance posterior mesh-anal sphincter is 30 mm at rest, 26 mm during straining and 31 mm during retaining. The mesh is always seen as spread out, or folded, but never strained. Video recording shows that sacropexy does not block pelvic dynamics. DISCUSSION AND CONCLUSION: Ultrasound imaging appears in this study as a simple and efficient exam to study and measure prosthesis. It could be a good help for clinical examination to explain failure or complication of surgery.

[Is hysterectomy required during vaginal reconstructive pelvic surgery? About histopathological results]. / Faut-il conserver l'utérus lors de la cure de prolapsus ? Réflexions à partir des résultats anatomo-pathologiques.

OBJECTIVES: To evaluate the rate of pre-cancerous and cancerous endometrial lesions in hysterectomy during vaginal reconstructive pelvic surgery. PATIENTS AND METHODS: In this retrospective and continuous study, a vaginal procedure including reconstructive pelvic surgery with vaginal mesh, hysterectomy and adnexectomy was performed in 152 patients between April 2001 and January 2006. An ultrasonography evaluation was done before surgery. A histopathological analysis of uterus, ovaries and tubes was also performed. RESULTS: In the analysis of 136 cases, precancerous and cancerous lesions have been diagnosed while ultrasonography or cervical smear were normal: 2 (1.4%) endocervical dysplasia, 1 (0.7%) cervical epidermoid carcinoma, 10 (7.35%) endometrial complex non-atypical hyperplasia, 7 (5.1%) endometrial atypical hyperplasia and 2 (1.4%) endometrioid endometrial carcinoma. There was not any cancerous lesions in tubes or ovaries. At 10months, mesh exposure was low at 2.9% (four cases). DISCUSSION AND CONCLUSION: The important rate of cancerous and precancerous lesions raise the question of hysterectomy or hysteroscopy and endometrial biopsy in case of uterine preservation during a vaginal reconstructive pelvic surgery.

Nuclear magnetic resonance analysis of protein-DNA interactions.

Recent methodological and instrumental advances in solution-state nuclear magnetic resonance have opened up the way to investigating challenging problems in structural biology such as large macromolecular complexes. This review focuses on the experimental strategies currently employed to solve structures of protein-DNA complexes and to analyse their dynamics. It highlights how these approaches can help in understanding detailed molecular mechanisms of target recognition.