The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling.

BACKGROUND: There is evidence of glandular tissue in the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) that has similar morphology and immunohistochemistry to the prostate in men. Surgical injury to this tissue has been suggested as a potential cause of sexual dysfunction following midurethral sling (MUS) procedures. However, the anatomy and embryology of these glands have not been fully resolved. This has led to difficulties in classifying this tissue as a prostate and defining its clinical significance related to MUS procedures. AIM: To describe the histological and immunohistochemical characteristics of the female periurethral glands using markers of prostate tissue and innervation and to examine their anatomical relationships to an implanted MUS. METHODS: Using gross and fine dissection, the AVW-FPT was dissected from 9 cadavers. Prior to dissection, 2 cadavers underwent simulation of the MUS procedure by a urogynecologist. Samples were paraffin embedded and serially sectioned. Immunohistochemistry was performed using markers of prostate tissue and innervation. OUTCOMES: Immunohistochemical localization of markers for prostatic tissue and innervation of the glandular tissue of the AVW-FPT, including the region of MUS implantation. RESULTS: Female periurethral glands were immunoreactive for markers of male prostatic tissue, including prostate-specific antigen, androgen receptor, HOXB13, and NKX3.1. Markers of innervation (protein gene product 9.5, choline acetyl transferase, and vasoactive intestinal polypeptide) also localized to certain regions of the glandular tissue and associated blood supply. Surgical simulation of the MUS procedure demonstrated that some periurethral glands are located in close proximity to an implanted sling. CLINICAL TRANSLATION: The AVW-FPT contains glandular tissue in the surgical field of MUS implantation. Iatrogenic damage to the female periurethral glands and the associated innervation during surgery could explain the negative impacts on sexual dysfunction reported following MUS procedures. STRENGTHS AND LIMITATIONS: This is the first study to characterize the female periurethral glands using markers of prostatic tissue in concert with markers of general and autonomic innervation and characterize their anatomical relationships within the surgical field of MUS implantation. The small sample size is a limitation of this study. CONCLUSION: We provide further evidence that the AVW-FPT contains innervated glands that are phenotypically similar to the male prostate and may share a common embryonic origin. The microscopic and immunohistochemical features of the periurethral glands may be indicative of their functional capacity in sexual responses. The location of these glands in the surgical field of MUS procedures underscores the clinical significance of this tissue.

Pelvic floor muscle training as an adjunct to a midurethral sling: a single-blind randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: This single-blind, randomised controlled trial was aimed at determining whether peri-operative physiotherapist-supervised pelvic floor muscle (PFM) training was superior to standard care (handout) in terms of improvements in stress urinary incontinence (SUI) symptoms, cure rate, and/or post-operative filling or voiding symptoms among women undergoing surgical mid-urethral sling (MUS) insertion for SUI. METHODS: Women with SUI were recruited from surgical wait lists at four participating urogynecology clinics. Participants were assessed at baseline (V1) then randomised (1:1 allocation) to receive supervised PFM training or a handout. Immediately following the 12-week intervention period (V2) and at 12 weeks following surgery (V3) the groups were compared based on the Female Lower Urinary Tract Symptoms (FLUTS) questionnaire total score and urinary incontinence, filling, and voiding subscale scores as well as on a standardised 30-min pad test administered by a blinded assessor. Intention-to-treat analyses were performed. RESULTS: A total of 52 participants were randomised to physiotherapy and 51 to the control group between December 2012 and August 2016. The groups were not different on any outcomes at V1 and all were improved at V3 compared with V1 (p < 0.001). At V3 the physiotherapy group reported significantly fewer UI symptoms (FLUTS UI subscale score) than the control group; yet, there were no group differences in FLUTS overall score or the pad test (p > 0.05). Based on a FLUTS UI subscale score <4, the cure rate at V3 was higher in the intervention group (73%) than in the control group (47%); (2.36 < OR < 3.47, p = 0.012). There were no group differences in cure rate at V3 based on a pad test (p = 0.27). No group differences were found in the filling or voiding symptoms at V3 (p > 0.05). No adverse events were reported. CONCLUSION: Physiotherapist-supervised PFM training improves SUI cure rates associated with surgical MUS insertion when considering symptoms of SUI, but does not improve post-operative continence function as measured by a pad test, nor does it lead to fewer post-operative voiding or filling symptoms.

The Impact of Continuity of Care on Cervical Cancer Screening: How Visit Pattern Affects Guideline Concordance.

Cervical cancer can be prevented and highly curable if detected early. Current guidelines recommend women to receive cervical cancer screening starting at age 21. Our study aims to investigate how improving continuity of care (COC) may influence guideline concordance of cervical cancer screening. Using the eligibility and claims data, we created a person-month panel data set for women who were enrolled in Oregon Medicaid for at least 80% of the period from 2008 to 2015. We then selected our study cohort following the cervical cancer screening guidelines. Our dependent variable is whether a woman received cervical cancer screening concordant with guidelines in a given month, when she did not receive Pap test in the past 36 months and did not receive co-testing of HPV test plus Pap test in the past 60 months. We used both population-averaged logit model and conditional fixed-effect logit model to estimate the association between the guideline concordance and the COC index, after controlling for high risk, pregnancy, age, race, and ethnicity. A total of 466,526 person-month observations were included in our main models. A 0.1 unit increase of the COC score was significantly associated with a decrease in the odds of receiving guideline-concordant cervical cancer screening (population-averaged logit model: OR = 0.988, p < .001; conditional fixed-effect logit model: OR = 0.966, p < .001). Our findings remain robust to a series of sensitivity analyses. A better COC may not be necessarily beneficial to improving cervical cancer prevention. Educations for both physicians and patients should be supplemented to assure quality of preventive care.

Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation.

BACKGROUND: Female sexual dysfunction, including female orgasm disorder, has been reported following mid-urethral sling (MUS) surgery to treat bothersome stress urinary incontinence. Anterior vaginal wall-female periurethral tissue (AVW-FPT) likely contains autonomic and sensory innervation involved in the female sexual response, and injury to these nerves may result from MUS implantation. AIM: To characterize, using fresh cadaveric tissue, autonomic and sensory nerves in AVW- FPT using immunohistochemistry (IHC), and to assess their proximity to an implanted MUS. METHODS: AVW-FPT was excised following careful dissection from four fresh cadavers. Prior to dissection, one cadaver underwent simulation of the MUS procedure by a urogynegologist, using a fascial sling. All samples were paraffin embedded, sectioned, and stained with hematoxylin. Serial sectioning and IHC were performed to identify nerves. IHC markers were used to characterize the sensory and autonomic innervation. OUTCOMES: IHC localization of autonomic and sensory nerve markers consistent with neural tissue within the region of MUS implantation. RESULTS: IHC of AVW-FPT using protein gene product 9.5 (PGP9.5), a general nerve stain, revealed innervation throughout the region targeted by the MUS implantation. More specifically, immunoreactivity for both autonomic (tyrosine hydroxylase, TH) and sensory (Nav1.8 and S100ß) nerves were found in close proximity (<1 mm) to the implanted MUS. In addition, a subset of S100ß positive nerves also showed immunoreactivity for calcitonin gene-related peptide (CGRP). Combining the IHC findings with the surgical simulation of the MUS implantation revealed the potential for damage to both autonomic and sensory nerves as a direct result of the MUS procedure. CLINICAL TRANSLATION: The identified autonomic and sensory nerves of the AVW-FPT may contribute to the female sexual response, and yet are potentially negatively impacted by MUS procedures. Given that surgeries performed on male genital tissue, including the prostate, may cause sexual dysfunction secondary to nerve damage, and that urologists routinely provide informed consent regarding this possibility, urogynaecologists are encouraged to obtain appropriate informed consent from prospective patients undergoing the MUS procedure. STRENGTHS & LIMITATIONS: This is the first study to characterize the sensory and autonomic innervation within the surgical field of MUS implantation and demonstrate its relationship to an implanted MUS. The small sample size is a limitation of this study. CONCLUSION: The present study provides evidence of potential injury to autonomic and sensory innervation of AVW-FPT as a consequence of MUS implantation, which may help explain the underlying mechanisms involved in the reported post-operative female sexual dysfunction in some women. Giovannetti O, Tomalty D, Gaudet D, et al. Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation. J Sex Med 2021;18:1168-1180.

International Urogynecology Consultation Chapter 1 Committee 5: relationship of pelvic organ prolapse to associated pelvic floor dysfunction symptoms: lower urinary tract, bowel, sexual dysfunction and abdominopelvic pain.

INTRODUCTION AND HYPOTHESIS: This article from Chapter 1 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) establishes the prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP. METHODS: An international group of nine urogynecologists/urologists and one medical student performed a search of the literature using pre-specified search terms in Ovid, MEDLINE, Embase and CINAHL from January 2000 to March 2019. Publications were eliminated if not relevant or they did not include clear definitions of POP or the symptoms associated with POP. Definitions of POP needed to include both a physical examination finding using a validated examination technique and the complaint of a bothersome vaginal bulge. Symptoms were categorized into symptom groups for ease of evaluation. The Specialist Unit for Review Evidence (SURE) was used to evaluate for quality of the included articles. The resulting list of articles was used to determine the prevalence of various symptoms in women with POP. Cohort studies were used to evaluate for possible causation of POP as either causing or worsening the symptom category. RESULTS: The original search yielded over 12,000 references, of which 50 were used. More than 50% of women with POP report lower urinary tract symptoms. Cohort studies suggest that women with POP have more obstructive lower urinary tract symptoms than women without POP. Pain described in various ways is frequently reported in women with POP, with low back pain being the most common pain symptom reported in 45% of women with POP. In cohort studies those with POP had more pain complaints than those without POP. Sexual dysfunction is reported by over half of women with POP and obstructed intercourse in 37-100% of women with POP. Approximately 40% of women have complaints of bowel symptoms. There was no difference in the median prevalence of bowel symptoms in those with and without POP in cohort studies. CONCLUSIONS: The prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP are common but inconsistently reported. There are few data on incidence of associated symptoms with POP, and cohort studies evaluating causality are rare or inconsistent. Obstructive voiding, lower abdominal and pelvic pain, and sexual dysfunction are most frequently associated with POP.

A model identifying characteristics predictive of successful pelvic floor muscle training outcomes among women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to prospectively identify aspects of baseline demographic, clinical, and pelvic morphology of women with stress urinary incontinence (SUI) that are predictive of cure with physiotherapist-supervised pelvic floor muscle training (PFMT). METHODS: Women ≥18 years old with SUI were recruited from urogynecology and pelvic health physiotherapy clinics. Participants completed a 3-day bladder diary, the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF), a standardized pad test, manual assessment of pelvic floor muscle (PFM) strength and tone, and transperineal ultrasound (TPUS) assessment of their urogenital structures at rest while in a supine position and standing, and during contraction, straining, and coughing. Participants attended six physiotherapy sessions over 12 weeks and performed a home PFMT program. The assessment was repeated after the intervention; cure was defined as a dry (≤2 g) pad test. RESULTS: Seventy-seven women aged 50 (±10) years completed the protocol; 38 (49%) were deemed cured. Based on univariate testing, four predictors were entered into a binary logistic regression model: ICIQ-UI-SF, PFM tone, bladder neck (BN) height in a quiet standing position, and BN height during a cough in a standing position. The model was significant (p < 0.001), accurately classifying outcome in 74% of participants. The model, validated through bootstrapping, performed moderately, with the area under the receiver operating characteristic curve = 0.80 (95% CI: 0.69-0.90; p = 0.00), and with 70% sensitivity and 75% specificity. CONCLUSIONS: Women with better bladder support in a standing position and less severe symptoms were most likely to be cured with PFMT. CLINICAL TRIAL REGISTRATION: #NCT01602107.

Directive clinique n° 411 : Utilisation des pessaires.

OBJECTIF: Passer en revue l'utilisation, l'entretien et l'ajustement des pessaires. POPULATION CIBLE: Les femmes qui ont besoin d'utiliser un pessaire en raison d'un prolapsus génital et/ou d'une incontinence urinaire d'effort. L'utilisation peut être indiquée chez les femmes enceintes dans certains scénarios cliniques liés à la grossesse, dont l'incarcération utérine et le risque de travail préterme liée à l'incompétence du col. OPTIONS: Les pessaires constituent une option pour les femmes atteintes d'un prolapsus et/ou d'une incontinence urinaire d'effort. De plus, certains types de pessaires peuvent être utilisés chez des patientes atteintes d'incompétence du col ou d'une incarcération utérine. ISSUES: Il est possible de trouver un pessaire efficace chez la plupart des femmes atteintes d'un prolapsus génital ou d'une incontinence urinaire d'effort de façon à obtenir un excellent soulagement des symptômes, un taux de satisfaction élevé et des complications minimes. BéNéFICES, RISQUES ET COûTS: Les femmes atteintes d'un prolapsus génital et/ou d'une incontinence urinaire d'effort peuvent choisir d'utiliser un pessaire pour traiter leurs symptômes au lieu de subir une intervention chirurgicale ou dans l'attente d'une telle intervention. Des complications majeures ont été observées seulement en cas de soins de pessaire négligés. Les complications mineures (telles que les pertes vaginales, les odeurs et les érosions) sont généralement traitables avec succès. DONNéES PROBANTES: Des recherches ont été effectuées dans la base de données Medline afin de récupérer les articles pertinents publiés jusqu'en décembre 2018. Le présent document constitue une mise à jour de la mise à jour technique de la SOGC publiée en 2013, laquelle a été la première directive clinique publiée à l'international relativement à l'utilisation des pessaires. Une ligne directrice australienne sur l'utilisation des pessaires pour le traitement du prolapsus a été publiée plus tard en 2013. MéTHODES DE VALIDATION: Les auteures ont évalué la qualité des données probantes et la solidité des recommandations au moyen des critères du cadre méthodologique du Groupe d'étude canadien sur les soins de santé préventifs (annexe A). PROFESSIONNELS CONCERNéS: Gynécologues, obstétriciens, médecins de famille, physiothérapeutes, résidents et moniteurs cliniques (fellows). DÉCLARATIONS SOMMAIRES: RECOMMANDATION.

Guideline No. 411: Vaginal Pessary Use.

OBJECTIVE: To review the use, care, and fitting of pessaries. TARGET POPULATION: Women requiring the use of vaginal pessaries for pelvic organ prolapse and/or stress urinary incontinence. Use may also be indicated for women with certain pregnancy-related clinical scenarios, including incarcerated uterus. OPTIONS: Pessaries are an option for women presenting with prolapse and/or stress urinary incontinence. In addition, certain types of pessaries can be considered for patients with cervical insufficiency or incarcerated uterus. OUTCOMES: Most women with prolapse or stress urinary incontinence can be successfully fitted with a pessary and experience excellent symptom relief, high satisfaction rates, and minimal complications. BENEFITS, HARMS, AND COSTS: Women with pelvic organ prolapse and/or stress urinary incontinence may choose to use a pessary to manage their symptoms rather than surgery or while waiting for surgery. Major complications have been seen only when pessaries are neglected. Minor complications such as vaginal discharge, odour, and erosions can usually be successfully treated. EVIDENCE: Medline was searched for relevant articles up to December 2018. This is an update of the SOGC technical update published in 2013, which was the first internationally published guidance on pessary use. Subsequently, an Australian guideline on the use of pessaries for the treatment of prolapse was published later in 2013. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the approach of the Canadian Task Force on Preventive Health Care (Appendix A). INTENDED AUDIENCE: Gynaecologists, obstetricians, family physicians, physiotherapists, residents, and fellows. SUMMARY STATEMENTS: RECOMMENDATION.

Attitudes towards chiropractic: a repeated cross-sectional survey of Canadian family physicians.

BACKGROUND: Many primary care patients receive both medical and chiropractic care; however, interprofessional relations between physicians and chiropractors are often suboptimal which may adversely affect care of shared patients. We surveyed Canadian family physicians in 2010 to explore their attitudes towards chiropractic and re-administered the same survey a decade later to explore for changes in attitudes. METHODS: A 50-item survey administered to a random sample of Canadian family physicians in 2010, and again in 2019, that inquired about demographic variables, knowledge and use of chiropractic. Imbedded in our survey was a 20-item chiropractic attitude questionnaire (CAQ); scores could range from 0 to 80 with higher scores indicating more positive attitudes toward chiropractic. We constructed a multivariable regression model to explore factors associated with CAQ scores. RESULTS: Among eligible physicians, 251 of 685 in 2010 (37% response rate) and 162 of 2429 in 2019 (7% response rate) provided a completed survey. Approximately half of respondents (48%) endorsed a positive impression of chiropractic, 27% were uncertain, and 25% held negative views. Most respondents (72%) referred at least some patients for chiropractic care, mainly due to patient request or lack of response to medical care. Most physicians believed that chiropractors provide effective therapy for some musculoskeletal complaints (84%) and disagreed that chiropractic care was beneficial for non-musculoskeletal conditions (77%). The majority agreed that chiropractic care was a useful supplement to conventional care (65%) but most respondents (59%) also indicated that practice diversity among chiropractors presented a barrier to interprofessional collaboration. In our adjusted regression model, attitudes towards chiropractic showed trivial improvement from 2010 to 2019 (0.31 points on the 80-point CAQ; 95%CI 0.001 to 0.62). More negative attitudes were associated with older age (- 1.55 points for each 10-year increment from age 28; 95%CI - 2.67 to - 0.44), belief that adverse events are common with chiropractic care (- 1.41 points; 95% CI - 2.59 to - 0.23) and reported use of the research literature (- 6.04 points; 95% CI - 8.47 to - 3.61) or medical school (- 5.03 points; 95% CI - 7.89 to - 2.18) as sources of knowledge on chiropractic. More positive attitudes were associated with endorsing a relationship with a specific chiropractor (5.24 points; 95% CI 2.85 to 7.64), family and friends (4.06 points; 95% CI 1.53 to 6.60), or personal treatment experience (4.63 points; 95% CI 2.14 to 7.11) as sources of information regarding chiropractic. CONCLUSIONS: Although generally positive, Canadian family physicians' attitudes towards chiropractic are diverse, and most physicians felt that practice diversity among chiropractors was a barrier to interprofessional collaboration.

Perturbing the activity of the superior temporal gyrus during pain encoding prevents the exaggeration of pain memories: A virtual lesion study using single-pulse transcranial magnetic stimulation.

BACKGROUND: Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories. OBJECTIVE: /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias. METHODS: Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. RESULTS: Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ±â€¯9, 43% female; sham TMS = 25 years ±â€¯4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). CONCLUSIONS: Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness.

Urinary incontinence among competitive rope-skipping athletes: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to determine the prevalence, impact and management of stress urinary incontinence (SUI) among rope-skipping (RS) athletes. METHODS: A cross-sectional observational study was employed. Survey #1 (current athletes): RS athletes aged ≥13 years attending a national RS competition (183) were invited to participate. The primary outcome was the prevalence of SUI during RS (yes/no question). Secondary outcomes included SUI interference with RS (Likert scale, 0-10), quality of life (ICIQ-SF), and the prevalence and bothersomeness of SUI for each RS event (un-validated sport-specific questionnaire inspired by the IIQ-7). Survey #2 (retired athletes): retired RS athletes were invited to complete an online questionnaire to identify whether SUI contributed to their retirement from RS. RESULTS: Survey #1: 56% (103 out of 183) of athletes responded. Athletes were predominantly girls of adolescent age, normal weight, menarchal, and nulliparous. Seventy-five percent of the girls (67 out of 89) and 7% of boys (1 out of 14) reported SUI during RS, mostly when competing "double-unders" and "triple-unders." Twenty-one percent (14 out of 67) of affected girls indicated a moderate or greater interference of SUI with RS, although the median impact of SUI on their overall quality of life was slight. Female athletes managed SUI with containment products, fluid limitation, and timed voiding. Survey #2: one of the 77 respondents (74 females, 3 males) indicated that SUI contributed to their retirement from RS. CONCLUSIONS: Similar to other high-impact sports, female RS athletes experience a relatively high rate of SUI while participating in RS, which may lead to decreased quality of life.

Testing for Occult Stress Urinary Incontinence in Patients With Pelvic Organ Prolapse? Results of a Pragmatic Approach.

OBJECTIVE: Pelvic organ prolapse (POP) surgery may unmask occult stress urinary incontinence (OSUI) in otherwise asymptomatic patients. Preoperative urodynamic studies (UDSs) with prolapse reduction may, by potentially unmasking OSUI, assist surgical decision making. This study investigated the long-term objective postoperative rate of SUI, according to the presence of OSUI. METHODS: This retrospective cohort study was conducted with a cross-sectional survey of women with no SUI or rare SUI presenting at Kingston General Hospital in Kingston, Ontario from 2003-2013 for POP. Patients were compared on the basis of preoperative UDS results and whether an anti-incontinence procedure was performed in addition to POP surgery. The study included a chart review of 1-year follow-up subjective results and a survey of long-term objective results (symptoms and quality of life) ascertained by validated questionnaires. RESULTS: The study enrolled 113 women, 51 of whom had undergone anti-incontinence surgery (42 for identified OSUI, 9 prophylactically). In women whose UDS results indicated OSUI, 1-year subjective and long-term objective postoperative SUI results were, respectively, 8.8% and 12.5% among women undergoing POP and anti-incontinence surgery and 18.2% and 42.9% among those undergoing POP surgery alone. In women with negative UDS results, those rates were 0.0% and 50.0% and 12.8% and 27.6%, respectively. There was no significant difference in any outcomes, according to procedure choice in the OSUI-positive group. There were no predictors for postoperative SUI. CONCLUSION: Although a trend was seen for less long-term validated subjective SUI in women having a concomitant SUI procedure along with POP corrective surgery, no significant difference in outcomes was found, on the basis of procedure of choice, and no reliable predictors for postoperative SUI could be identified. UDS testing may be useful to rule in OSUI, but its clinical value in surgical decision making is uncertain.

Retrospective Comparison of PGE2 Vaginal Insert and Foley Catheter for Outpatient Cervical Ripening.

OBJECTIVE: To compare the efficacy of two methods of outpatient cervical ripening (CR): an intracervical Foley catheter and a prostaglandin E2 (PGE)2 slow-release vaginal insert. METHODS: All records of women receiving outpatient CR at a tertiary care hospital from January 2017 to June 2018 were retrospectively reviewed. We compared time from insertion of first CR agent until delivery between groups using a Cox proportional hazards (CPH) model. Exclusion criteria included age <18 years, multiple gestation, or contraindication to either CR method. Secondary outcomes included time from removal of agent and time from admission until delivery, additional CR used, uterine tachysystole, labour and delivery complications, type of delivery, and adverse neonatal outcomes. RESULTS: A total of 153 patients were included (82 Foley; 71 PGE2). Baseline characteristics were comparable except for lower dilation in the PGE2 group (16% vs. 38% <1cm dilated; P < 0.05). In the CPH model, time from insertion to delivery was not different between PGE2 and Foley catheter groups (median 27 vs. 33 h), controlling for parity, gestational age, initial dilation, and use of oxytocin (HR 1.13, 95% confidence interval 0.77-1.68). Patients in the PGE2 group were more likely to experience uterine tachysystole (9% vs. 0%; P < 0.01) and require another method of CR (34% vs. 1%; P < 0.001). There were no differences in neonatal or maternal adverse outcomes between groups. CONCLUSION: Our results suggest that outpatient Foley catheter and PGE2 CR are comparable in time from insertion to delivery; however, PGE2 inserts are associated with higher rates of tachysystole and the need for second CR method. A prospective study is warranted to further investigate these findings.

Chitinolytic functions in actinobacteria: ecology, enzymes, and evolution.

Actinobacteria, a large group of Gram-positive bacteria, secrete a wide range of extracellular enzymes involved in the degradation of organic compounds and biopolymers including the ubiquitous aminopolysaccharides chitin and chitosan. While chitinolytic enzymes are distributed in all kingdoms of life, actinobacteria are recognized as particularly good decomposers of chitinous material and several members of this taxon carry impressive sets of genes dedicated to chitin and chitosan degradation. Degradation of these polymers in actinobacteria is dependent on endo- and exo-acting hydrolases as well as lytic polysaccharide monooxygenases. Actinobacterial chitinases and chitosanases belong to nine major families of glycosyl hydrolases that share no sequence similarity. In this paper, the distribution of chitinolytic actinobacteria within different ecosystems is examined and their chitinolytic machinery is described and compared to those of other chitinolytic organisms.

Unravelling the effect of experimental pain on the corticomotor system using transcranial magnetic stimulation and electroencephalography.

The interaction between pain and the motor system is well-known, with past studies showing that pain can alter corticomotor excitability and have deleterious effects on motor learning. The aim of this study was to better understand the cortical mechanisms underlying the interaction between pain and the motor system. Experimental pain was induced on 19 young and healthy participants using capsaicin cream, applied on the middle volar part of the left forearm. The effect of pain on brain activity and on the corticomotor system was assessed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), respectively. Compared to baseline, resting state brain activity significantly increased after capsaicin application in the central cuneus (theta frequency), left dorsolateral prefrontal cortex (alpha frequency), and left cuneus and right insula (beta frequency). A pain-evoked increase in the right primary motor cortex (M1) activity was also observed (beta frequency), but only among participants who showed a reduction in corticospinal output (as depicted by TMS recruitment curves). These participants further showed greater beta M1-cuneus connectivity than the other participants. These findings indicate that pain-evoked increases in M1 beta power are intimately tied to changes in the corticospinal system, and provide evidence that beta M1-cuneus connectivity is related to the corticomotor alterations induced by pain. The differential pattern of response observed in our participants suggest that the effect of pain on the motor system is variable from on individual to another; an observation that could have important clinical implications for rehabilitation professionals working with pain patients.

Can We Quickly and Thoroughly Assess Pain with the PACSLAC-II? A Convergent Validity Study in Long-Term Care Residents Suffering from Dementia.

A previous study found that the modified version of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC-II) is a valid tool to assess pain in elderly individuals suffering from dementia and who are unable to communicate verbally. The primary objective of this study was to confirm the convergent validity of the PACSLAC-II using direct evaluation of long-term care residents in real-life situations, using two other well-validated pain assessment scales (i.e., PACSLAC and Pain Assessment in Advanced Dementia [PAINAD]). A secondary objective was to document and compare the time required to complete and score each assessment scale. During two potentially painful procedures (i.e., transfer/mobilization), 46 long-term care residents (mean age = 83 ± 10 years) suffering from dementia were observed by three independent evaluators, each using one of the assessment scales (randomly assigned). Correlational analyses and analysis of variance were used to evaluate the association between each scale and to compare scoring time. The PACSLAC (r = 0.61) and the PAINAD (r = 0.65) were both moderately associated with the PACSLAC-II (all p values < .001). The PAINAD's average scoring time (63 ± 19 seconds) was lower than the PACSLAC-II's (96 ± 2 seconds), which was lower than the PACSLAC's (135 ± 53 seconds) (all p values < .001). These results suggest that the PACSLAC-II is a valid tool for assessing pain in individuals with dementia. The time required to complete and score the PACSLAC-II was reasonable, supporting its usefulness in clinical settings.

Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair.

OBJECTIVE: To review the evidence relating to obstetrical anal sphincter injuries (OASIS) with respect to diagnosis, repair techniques and outcomes. To formulate recommendations as to patient counselling regarding route of delivery for subsequent pregnancy after OASIS. OPTIONS: Obstetrical care providers caring for women with OASIS have the option of repairing the anal sphincter using end-to-end or overlapping techniques. They may also be involved in counselling women with prior OASIS regarding the route of delivery for future pregnancies. OUTCOMES: The outcome measured is anal continence following primary OASIS repair and after subsequent childbirth. EVIDENCE: Published literature was retrieved through searches of Medline, EMBASE, and The Cochrane Library in May 2011 using appropriate controlled vocabulary (e.g., anal canal, obstetrics, obstetric labour complication, pregnancy complication, treatment outcome, surgery, quality of life) and key words (obstetrical anal sphincter injur*, anus sphincter, anus injury, delivery, obstetrical care, surgery, suturing method, overlap, end-to-end, feces incontinence). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to September 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: Benefits from implementation of these guidelines include: improved diagnosis of OASIS, optimal functional outcomes following repair, and evidence-based counselling of women for future childbirth.

Objectif : Analyser les données probantes traitant des lésions obstétricales du sphincter anal (LOSA) en ce qui concerne leur diagnostic, les techniques visant leur réparation et les résultats de l'intervention. Formuler des recommandations permettant d'éclairer les conseils offerts aux patientes ayant connu des LOSA en ce qui a trait à la voie d'accouchement à privilégier dans le cadre des grossesses subséquentes. Options : Les fournisseurs de soins obstétricaux qui comptent des patientes ayant connu des LOSA disposent de l'option de réparer le sphincter anal en faisant appel à la méthode de suture « bout à bout ¼ (end-to-end) ou à la méthode « en paletot ¼ (overlapping). Ils pourraient également être appelés à conseiller des femmes ayant déjà connu des LOSA en ce qui a trait à la voie d'accouchement à privilégier pour les grossesses subséquentes. Issues : Le critère d'évaluation était la continence anale à la suite d'une réparation primaire de LOSA et à la suite d'un accouchement subséquent. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans Medline, EMBASE et The Cochrane Library en mai 2011 au moyen d'un vocabulaire contrôlé (p. ex. anal canal, obstetrics, obstetric labour complication, pregnancy complication, treatment outcome, surgery, quality of life) et de mots clés (p. ex. obstetrical anal sphincter injur*, anus sphincter, anus injury, delivery, obstetrical care, surgery, suturing method, overlap, end-to-end, feces incontinence) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs. Aucune restriction n'a été imposée en matière de date ou de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en septembre 2014. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Avantages, désavantages et coûts : Parmi les avantages de la mise en œuvre de la présente directive clinique, on trouve : l'amélioration du diagnostic des LOSA, l'obtention d'issues fonctionnelles optimales à la suite de la réparation et l'offre de conseils reposant sur des données probantes aux femmes en ce qui concerne leurs futures grossesses. Déclarations sommaires 1. Les lésions obstétricales du sphincter anal mènent à des comorbidités considérables, dont l'incontinence anale, les fistules rectovaginales et la douleur. (II-2) 2. Les lésions obstétricales du sphincter anal sont plus souvent associées aux accouchements par forceps qu'aux accouchements par ventouse obstétricale. (II-2) 3. Réparation des lésions obstétricales du sphincter anal : a. L'utilisation de polyglactin 2-0 ou de polydioxanone 3-0 donne lieu, après six semaines, à des taux semblables de morbidité liée aux sutures. (I) b. La réparation du sphincter anal interne est recommandée puisque les femmes chez lesquelles la présence d'une anomalie affectant ce sphincter est révélée au cours de l'échographie postpartum sont plus susceptibles de connaître une incontinence anale. (III) c. La réparation du sphincter anal externe devrait englober la gaine fasciale. Le recours à la technique de suture « en paletot ¼ (chevauchement) nécessite souvent une mobilisation et une dissection de plus grande envergure des extrémités du sphincter; l'utilisation de cette technique n'est possible qu'en présence de déchirures sphinctériennes de degré 3b ou plus. (III) d. La présence persistante d'une anomalie du sphincter anal externe longtemps après l'accouchement pourrait accroître le risque de voir apparaître une aggravation des symptômes à la suite des accouchements vaginaux subséquents. (II-2) 4. Les lésions obstétricales du sphincter anal sont associées à une hausse du risque de rétention urinaire postpartum. (II-2) 5. À la suite de la réparation réussie d'une lésion obstétricale du sphincter anal, la plupart des femmes peuvent connaître un accouchement vaginal en toute sûreté dans le cadre d'une grossesse subséquente. (III) 6. Services de counseling offerts aux femmes au sujet de leurs accouchements subséquents : a. Le risque de récurrence d'une lésion obstétricale du sphincter anal dans le cadre d'un accouchement subséquent est de 4-8 %. (II-2) b. On a calculé que, pour prévenir un cas d'incontinence anale chez des femmes ayant déjà subi une lésion obstétricale du sphincter anal, la tenue de 2,3 césariennes planifiées s'avérerait nécessaire, le tout s'accompagnant alors d'une hausse des risques maternels. (II-2) Recommandations 1. Toutes les femmes devraient faire l'objet d'un examen rigoureux visant la détection de déchirures périnéales ou vaginales; celles qui présentent une déchirure dont la profondeur est plus que superficielle devraient, avant la mise en œuvre d'une réparation, faire l'objet d'un examen rectal systématique cherchant à établir la présence de lésions obstétricales du sphincter anal. (II-2B) 2. Le système de classification de l'Organisation mondiale de la santé devrait être utilisé pour classer les lésions obstétricales du sphincter anal. Ce système permet l'établissement d'une distinction entre le degré de déchirure du sphincter externe (3a < 50 % ou 3b ≥ 50 %) et la présence d'anomalies du sphincter interne (3c). La présence d'une lésion en boutonnière (button-hole injury) constitue un incident distinct et devrait être classée en conséquence. (III-B) 3. Chez les femmes qui connaissent un accouchement vaginal spontané, le taux de lésions obstétricales du sphincter anal est amoindri lorsque le fournisseur de soins obstétricaux ralentit la tête fœtale au moment du dégagement. (II-2A) 4. Épisiotomie : a. Dans le cadre d'un accouchement vaginal spontané ou instrumental, le fournisseur de soins obstétricaux devrait, pour assurer la prévention des lésions obstétricales du sphincter anal, respecter une politique prévoyant une utilisation « restreinte ¼ de l'épisiotomie (c.-à-d. seulement lorsque cela s'avère indiqué), plutôt qu'une utilisation « libre ¼ de cette intervention (c.-à-d. de façon systématique). (I-A) b. Lorsque la tenue d'une épisiotomie est jugée indiquée, l'octroi d'une préférence envers la tenue d'une incision médiolatérale (plutôt qu'envers la tenue d'une incision médiane) devrait être envisagé. (II-2B) L'angle d'incision optimal semble être d'au moins 45 degrés (idéalement, aux alentours de 60 degrés). (II-2B) 5. La réparation peut être différée (pendant 8-12h) sans effets nuisibles. La mise en œuvre d'un délai pourrait s'avérer nécessaire jusqu'à ce que les services d'un fournisseur de soins disposant de l'expérience nécessaire pour procéder à la réparation puissent être retenus. (I-A) 6. L'administration prophylactique d'une dose intraveineuse unique d'antibiotiques (céphalosporine de 2e génération, p. ex. céfotétan ou céfoxitine) devrait être mise en œuvre pour assurer la baisse des taux de complications de lésion périnéale à la suite de la réparation des lésions obstétricales du sphincter anal. (I-A) 7. Des laxatifs (p. ex. lactulose) devraient être prescrits à la suite de la réparation primaire d'une lésion obstétricale du sphincter anal puisqu'ils sont associés à des premières selles moins douloureuses et survenant plus rapidement, et à l'obtention plus rapide du congé de l'hôpital. L'utilisation d'agents constipants et d'agents de gonflement n'est pas recommandée. (I-A) 8. Les anti-inflammatoires non stéroïdiens et l'acétaminophène sont les analgésiques de première intention. Les opioïdes ne devraient être utilisés qu'avec précaution. La constipation devrait être évitée au moyen d'un laxatif ou d'un émollient fécal. (1-A) 9. À la suite de la constatation d'une lésion obstétricale du sphincter anal, les fournisseurs de soins devraient divulguer à leurs patientes le degré de la lésion subie et prendre les dispositions nécessaires à la mise en œuvre d'un suivi. Il est nécessaire de procéder à la documentation détaillée de la lésion et de sa réparation. (III-L) 10. Les femmes qui connaissent une incontinence anale après avoir subi une lésion obstétricale du sphincter anal devraient être orientées vers des services de physiothérapie du plancher pelvien. (I-A).

Chitosanases from Family 46 of Glycoside Hydrolases: From Proteins to Phenotypes.

Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC) or chitosan oligosaccharides (CHOS) from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46 are among the best-studied chitosanases, with four crystallography-derived structures available and more than forty enzymes studied at the biochemical level. They were also subjected to numerous site-directed mutagenesis studies, unraveling the molecular mechanisms of hydrolysis. This review is focused on the taxonomic distribution of GH46 proteins, their multi-modular character, the structure-function relationships and their biological functions in the host organisms.

A highly conserved arginine residue of the chitosanase from Streptomyces sp. N174 is involved both in catalysis and substrate binding.

BACKGROUND: Streptomyces sp. N174 chitosanase (CsnN174), a member of glycoside hydrolases family 46, is one of the most extensively studied chitosanases. Previous studies allowed identifying several key residues of this inverting enzyme, such as the two catalytic carboxylic amino acids as well as residues that are involved in substrate binding. In spite of the progress in understanding the catalytic mechanism of this chitosanase, the function of some residues highly conserved throughout GH46 family has not been fully elucidated. This study focuses on one of such residues, the arginine 42. RESULTS: Mutation of Arg42 into any other amino acid resulted in a drastic loss of enzyme activity. Detailed investigations of R42E and R42K chitosanases revealed that the mutant enzymes are not only impaired in their catalytic activity but also in their mode of interaction with the substrate. Mutated enzymes were more sensitive to substrate inhibition and were altered in their pattern of activity against chitosans of various degrees of deacetylation. Our data show that Arg42 plays a dual role in CsnN174 activity. CONCLUSIONS: Arginine 42 is essential to maintain the enzymatic function of chitosanase CsnN174. We suggest that this arginine is influencing the catalytic nucleophile residue and also the substrate binding mode of the enzyme by optimizing the electrostatic interaction between the negatively charged carboxylic residues of the substrate binding cleft and the amino groups of GlcN residues in chitosan.