Technical Update No. 433: eHealth Solutions for Urinary Incontinence Among Women.

OBJECTIVE: The purpose of this technical update is to establish the state of the science regarding emerging and novel electronic health (eHealth) and mobile health (mHealth) solutions for urinary incontinence among women. TARGET POPULATION: Women over 18 years with urinary incontinence. OPTIONS: Websites and mobile health applications are useful in the conservative care of urinary incontinence. Relevant care providers should be familiar with such tools, particularly those that use motivational principles for behaviour change, which can be used as adjunct tools for urinary incontinence care. Telemedicine is an effect mode to provide services for the conservative care of urinary incontinence. OUTCOMES: Use of eHealth and mHealth solutions has potentially significant health outcomes for patients, providers, and global health systems. Broader use of telemedicine, in and of itself, could improve care access and reduce costs incurred by patients and the health care system. BENEFITS, HARMS, AND COSTS: Evidence for the efficacy of eHealth and mHealth technologies and applications for urinary incontinence ranges from weak to strong. However, the research landscape for many of these novel solutions is developing rapidly. Furthermore, these options have minimal or no harm and confer an established cost benefit and care access benefit. EVIDENCE: The Cochrane Library, Medline, EMBASE, CENTRAL databases (from January 2014 to April 2019) were searched to find articles related to conservative care of urinary incontinence in women (over 18 years) and studies on eHealth and mHealth interventions for urinary incontinence. Articles were appraised, and the collective evidence was graded. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Relevant primary care providers and medical specialists, including physicians, nurses, midwives, and pelvic health physiotherapists. SUMMARY STATEMENTS: RECOMMENDATIONS.

Technical update nº 433: eHealth solutions for urinary incontinence among women

The purpose of this technical update is to establish the state of the science regarding emerging and novel electronic health (eHealth) and mobile health (mHealth) solutions for urinary incontinence among women. Target population Women over 18 years with urinary incontinence. Websites and mobile health applications are useful in the conservative care of urinary incontinence. Relevant care providers should be familiar with such tools, particularly those that use motivational principles for behaviour change, which can be used as adjunct tools for urinary incontinence care. Telemedicine is an effect mode to provide services for the conservative care of urinary incontinence. Use of eHealth and mHealth solutions has potentially significant health outcomes for patients, providers, and global health systems. Broader use of telemedicine, in and of itself, could improve care access and reduce costs incurred by patients and the health care system. Evidence for the efficacy of eHealth and mHealth technologies and applications for urinary incontinence ranges from weak to strong. However, the research landscape for many of these novel solutions is developing rapidly. Furthermore, these options have minimal or no harm and confer an established cost benefit and care access benefit. The Cochrane Library, Medline, EMBASE, CENTRAL databases (from January 2014 to April 2019) were searched to find articles related to conservative care of urinary incontinence in women (over 18 years) and studies on eHealth and mHealth interventions for urinary incontinence. Articles were appraised, and the collective evidence was graded. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). Relevant primary care providers and medical specialists, including physicians, nurses, midwives, and pelvic health physiotherapists.

No. 397 - Conservative Care of Urinary Incontinence in Women.

OBJECTIVE: To outline the evidence for conservative care, including both assessment and management options, for urinary incontinence in women. INTENDED USERS: Relevant primary care providers and medical specialists including but not limited to physicians, nurses, midwives, and pelvic health physiotherapists. TARGET POPULATION: Women (>18 years of age) with urinary incontinence. OPTIONS: Assessment options include gathering of a detailed history, physical examination, laboratory analysis, urodynamic evaluation, and cystoscopy. Conservative management options include lifestyle management, pelvic floor muscle training, behavioural management, and mechanical devices. OUTCOMES: To provide an evaluation-based summary of current available evidence concerning efficacy of conservative care (assessment and management) strategies for urinary incontinence in women. EVIDENCE: The Cochrane Library and Medline (2013-2018) were searched to find articles related to conservative care of urinary incontinence in women (>18 years). Articles were appraised, and the collective evidence was graded. VALIDATION METHODS: The evidence obtained was reviewed and evaluated by the Society of Obstetricians and Gynaecologists of Canada (SOGC) Urogynecology Committee under the leadership of the principal authors. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, AND COSTS: Evidence for the efficacy of conservative care (assessment and management) options for women with urinary incontinence is strong. Furthermore, these options carry minimal or no harm and confer an established cost benefit. GUIDELINE UPDATE: This SOGC Clinical Practice Guideline will be automatically reviewed 5 years after publication. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 397 - Prise en charge conservatrice de l'incontinence urinaire chez les femmes.

OBJECTIF: Exposer les données probantes relatives à la prise en charge conservatrice, y compris les options d'évaluation et de traitement, de l'incontinence urinaire chez les femmes. UTILISATEURS CONCERNéS: Les fournisseurs de soins de première ligne et les professionnels de la santé spécialisés, y compris, mais sans s'y limiter, les médecins, les infirmières, les sages-femmes et les physiothérapeutes en santé périnéale. POPULATION CIBLE: Les femmes (> 18 ans) atteintes d'incontinence urinaire. OPTIONS: Les options d'évaluation comprennent l'anamnèse détaillée, l'examen physique, les analyses de laboratoire, le bilan urodynamique et la cystoscopie. Les options de traitement conservateur comprennent l'adaptation du mode de vie, la rééducation périnéale, la thérapie comportementale et les dispositifs mécaniques. RéSULTATS: Fournir un résumé reposant sur l'évaluation des données probantes actuellement disponibles sur l'efficacité des stratégies de prise en charge conservatrice (évaluation et traitement) de l'incontinence urinaire chez les femmes. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Cochrane Library et Medline (2013-2018) pour recenser des articles relatifs à la prise en charge conservatrice de l'incontinence urinaire chez les femmes (> 18 ans). Les articles ont été évalués et les données probantes globales ont été cotées. MéTHODES DE VALIDATION: Les données probantes obtenues ont été revues et évaluées par le comité d'urogynécologie de la Société des obstétriciens et gynécologues du Canada (SOGC) sous la direction des auteures principales. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). AVANTAGES, PRéJUDICE ET COûTS: Les données probantes sur l'efficacité des options de prise en charge conservatrice (évaluation et traitement) de l'incontinence urinaire chez les femmes sont fortes. De plus, ces options comportent peu d'effets nuisibles, voire aucun, et ont un rapport coûts-avantages bien établi. MISE à JOUR DE LA DIRECTIVE CLINIQUE: La présente directive clinique de la SOGC sera automatiquement passée en revue cinq ans après sa publication. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

No. 397: conservative care of urinary incontinence in women

To outline the evidence for conservative care, including both assessment and management options, for urinary incontinence in women.Relevant primary care providers and medical specialists including but not limited to physicians, nurses, midwives, and pelvic health physiotherapists. Women (>18 years of age) with urinary incontinence.Assessment options include gathering of a detailed history, physical examination, laboratory analysis, urodynamic evaluation, and cystoscopy. Conservative management options include lifestyle management, pelvic floor muscle training, behavioural management, and mechanical devices. To provide an evaluation-based summary of current available evidence concerning efficacy of conservative care (assessment and management) strategies for urinary incontinence in women.T he evidence obtained was reviewed and evaluated by the Society of Obstetricians and Gynaecologists of Canada (SOGC) Urogynecology Committee under the leadership of the principal authors. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework.

Middle-way flexible docking: Pose prediction using mixed-resolution Monte Carlo in estrogen receptor α.

There is a vast gulf between the two primary strategies for simulating protein-ligand interactions. Docking methods significantly limit or eliminate protein flexibility to gain great speed at the price of uncontrolled inaccuracy, whereas fully flexible atomistic molecular dynamics simulations are expensive and often suffer from limited sampling. We have developed a flexible docking approach geared especially for highly flexible or poorly resolved targets based on mixed-resolution Monte Carlo (MRMC), which is intended to offer a balance among speed, protein flexibility, and sampling power. The binding region of the protein is treated with a standard atomistic force field, while the remainder of the protein is modeled at the residue level with a Go model that permits protein flexibility while saving computational cost. Implicit solvation is used. Here we assess three facets of the MRMC approach with implications for other docking studies: (i) the role of receptor flexibility in cross-docking pose prediction; (ii) the use of non-equilibrium candidate Monte Carlo (NCMC) and (iii) the use of pose-clustering in scoring. We examine 61 co-crystallized ligands of estrogen receptor α, an important cancer target known for its flexibility. We also compare the performance of the MRMC approach with Autodock smina. Adding protein flexibility, not surprisingly, leads to significantly lower total energies and stronger interactions between protein and ligand, but notably we document the important role of backbone flexibility in the improvement. The improved backbone flexibility also leads to improved performance relative to smina. Somewhat unexpectedly, our implementation of NCMC leads to only modestly improved sampling of ligand poses. Overall, the addition of protein flexibility improves the performance of docking, as measured by energy-ranked poses, but we do not find significant improvements based on cluster information or the use of NCMC. We discuss possible improvements for the model including alternative coarse-grained force fields, improvements to the treatment of solvation, and adding additional types of NCMC moves.

Robotic-assisted vesicovaginal fistula repair using an extravesical approach without interposition grafting.

BACKGROUND: Post-hysterectomy vesicovaginal fistula (VVF) is rare. In addition to conventional abdominal and vaginal approaches, robotic-assisted VVF repairs have recently been described. We present a case of an extravesical, robotic-assisted VVF repair, without placement of an interposition graft performed in a Canadian teaching center. CASE: A 51-year-old woman presented with urinary incontinence 5 days after laparoscopic hysterectomy. Computed tomography cystogram, cystoscopy, and methylene blue dye test, confirmed a VVF above the bladder trigone. The patient underwent a robotic-assisted VVF repair 3 months after presentation, without complication. An abdominal, extravesical approach was used. Operative time was 116 min and repeat CT cystogram showed no evidence of persistent. CONCLUSION: We have demonstrated that a VVF repair, using a robotic-assisted, extravesical approach without interposition graft placement, can be safe, less invasive and have a successful outcome at 1 year of follow-up.

C. elegans HAM-1 functions in the nucleus to regulate asymmetric neuroblast division.

All 302 neurons in the C. elegans hermaphrodite arise through asymmetric division of neuroblasts. During embryogenesis, the C. elegans ham-1 gene is required for several asymmetric neuroblast divisions in lineages that generate both neural and apoptotic cells. By antibody staining, endogenous HAM-1 is found exclusively at the cell cortex in many cells during embryogenesis and is asymmetrically localized in dividing cells. Here we show that in transgenic embryos expressing a functional GFP::HAM-1 fusion protein, GFP expression is also detected in the nucleus, in addition to the cell cortex. Consistent with the nuclear localization is the presence of a putative DNA binding winged-helix domain within the N-terminus of HAM-1. Through a deletion analysis we determined that the C-terminus of the protein is required for nuclear localization and we identified two nuclear localization sequences (NLSs). A subcellular fractionation experiment from wild type embryos, followed by Western blotting, revealed that endogenous HAM-1 is primarily found in the nucleus. Our analysis also showed that the N-terminus is necessary for cortical localization. While ham-1 function is essential for asymmetric division in the lineage that generates the PLM mechanosensory neuron, we showed that cortical localization may not required. Thus, our results suggest that there is a nuclear function for HAM-1 in regulating asymmetric neuroblast division and that the requirement for cortical localization may be lineage dependent.

Dissecting the function of a protruding loop in AcrB trimerization.

The resistance-nodulation-cell division family multidrug transporter Acriflavine resistance protein B (AcrB) from Eschericha coli is an obligate homotrimer. Approximately, 45% of the inter-subunit interface is contributed by a protruding loop (also referred to as the thumb) and its corresponding binding tunnel in the neighboring subunit. In an earlier study, we have demonstrated that a single Pro to Gly mutation in the loop drastically destabilized AcrB trimer and reduced its substrate efflux activity. To further dissect the role of the loop during AcrB trimerization, we performed Ala scanning of the loop and examined the effect of each mutation on protein activity. We found that not all conserved residues are important for AcrB function and likewise not all critical residues are conserved. In addition, we replaced the loop of AcrB with the loop of MexB, which is a highly conserved homolog of AcrB. The resultant chimeric protein remained partly active. Structural characterization of the chimeric protein indicated that it was well folded and existed as a mixture of monomer and trimer. Our results indicate that the loop to tunnel interaction, while critical to trimerization and efflux function, is in general rather flexible and tolerant to mutations. In addition, all mutations in the loop that resulted in reduced function clustered closely, suggesting that this may be the site of inter-subunit recognition during trimerization and/or a locking zone to stabilize the inter-subunit interaction during trimerization.