Does Behavior Evolve First? Correlated Responses to Selection for Voluntary Wheel-Running Behavior in House Mice.

AbstractHow traits at multiple levels of biological organization evolve in a correlated fashion in response to directional selection is poorly understood, but two popular models are the very general "behavior evolves first" (BEF) hypothesis and the more specific "morphology-performance-behavior-fitness" (MPBF) paradigm. Both acknowledge that selection often acts relatively directly on behavior and that when behavior evolves, other traits will as well but most with some lag. However, this proposition is exceedingly difficult to test in nature. Therefore, we studied correlated responses in the high-runner (HR) mouse selection experiment, in which four replicate lines have been bred for voluntary wheel-running behavior and compared with four nonselected control (C) lines. We analyzed a wide range of traits measured at generations 20-24 (with a focus on new data from generation 22), coinciding with the point at which all HR lines were reaching selection limits (plateaus). Significance levels (226 P values) were compared across trait types by ANOVA, and we used the positive false discovery rate to control for multiple comparisons. This meta-analysis showed that, surprisingly, the measures of performance (including maximal oxygen consumption during forced exercise) showed no evidence of having diverged between the HR and C lines, nor did any of the life history traits (e.g., litter size), whereas body mass had responded (decreased) at least as strongly as wheel running. Overall, results suggest that the HR lines of mice had evolved primarily by changes in motivation rather than performance ability at the time they were reaching selection limits. In addition, neither the BEF model nor the MPBF model of hierarchical evolution provides a particularly good fit to the HR mouse selection experiment.

Association between the Mode of Delivery and Vertical Transmission of Human Papillomavirus.

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36-48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03-12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10-17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Human Papillomavirus Transmission and Persistence in Pregnant Women and Neonates.

Importance: The prevalence of human papillomavirus (HPV) infection during pregnancy and its risk of transmission to newborns are not well documented. Objective: To ascertain the prevalence of HPV in pregnant women, the risk of HPV detection in the placenta and in children at birth, and the probability that HPV detected at birth may persist in newborns. Design, Setting, and Participants: The Human Papillomavirus Perinatal Transmission and Risk of HPV Persistence Among Children (HERITAGE) study was a prospective cohort study that recruited participants between November 8, 2010, and October 16, 2016. Participant follow-up visits were completed on June 15, 2017. Participants, which included pregnant women of at least 18 years of age and at 14 weeks or earlier of gestation, were recruited from 3 academic hospitals in Montreal, Québec, Canada. Laboratory and statistical analysis were completed on November 15, 2022. Exposures: HPV DNA testing on self-collected vaginal and placental samples. Among children of mothers positive for HPV, conjunctival, oral, pharyngeal, and genital samples were collected for HPV DNA testing. Main Outcomes and Measures: Vaginal HPV DNA testing was done on self-collected vaginal samples obtained among pregnant women recruited during their first trimester of pregnancy and in the third trimester for those who had HPV-positive samples in the first trimester. HPV DNA testing was also done on placental samples (swabs and biopsies) collected after birth in all participants. HPV DNA testing among children included conjunctival, oral, pharyngeal, and genital samples collected in children of HPV-positive mothers at birth, 3 months, and 6 months of age. Results: A total of 1050 pregnant women (mean [SD] age, 31.3 [4.7] years) were included in this study. Prevalence of HPV in pregnant women at recruitment was 40.3% (95% CI, 37.3%-43.3%). Among the 422 HPV-positive women, 280 (66.4%) harbored at least 1 high-risk genotype, and 190 (45.0%) were coinfected with multiple genotypes. HPV was detected in 10.7% of placentas (92 of 860; 95% CI, 8.8%-12.9%) overall, but only 3.9% of biopsies (14 of 361) on the fetal side under the amniotic membrane were positive. Neonatal HPV detection (at birth and/or at 3 months) was 7.2% (95% CI, 5.0%-10.3%) overall, with the most frequent site of infection being the conjunctiva (3.2%; 95% CI, 1.8%-5.6%), followed by the mouth (2.9%; 95% CI, 1.6%-5.2%), the genital area (2.7%; 95% CI, 1.4%-4.9%), and the pharynx (0.8%; 95% CI, 0.2%-2.5%). Importantly, all HPV detected in children at birth cleared before the age of 6 months. Conclusions and relevance: In this cohort study, vaginal HPV was frequently detected in pregnant women. Perinatal transmission was infrequent, and in this cohort, no infection detected at birth persisted at 6 months. Although HPV was detected in placentas, it remains difficult to differentiate contamination vs true infection.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

[Therapeutic Education Programs for the Patient (ETP) undergoing an allogeneic hematopoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Programme d'éducation thérapeutique du patient (ETP) faisant l'objet d'une allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Patients undergoing an allogeneic hematopoietic cell transplant (allo-HCT) need to understand and adhere to the transplant process as well as post-transplant follow-up requirements. A working group has met during the eleventh edition of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) Practice Harmonization Workshops. The analysis of a survey that was sent to several transplant centers belonging to the SFGM-TC has been used as a milestone to this article. While, post-transplant medical follow-up was comparable from one center to another, nursing care was found to lack harmonization between centers, although, all patients would receive therapeutic education at one time or another regarding potential transplant-related complications. A few centers in France has established a therapeutic education program that was approved by French health authorities. The aim of this work was to set up guidelines to help centers establishing such a program in well-harmonized way.

Transcranial direct current stimulation for provoked vestibulodynia: What roles do psychosexual factors play in treatment response?

There is growing evidence that provoked vestibulodynia (PVD), a frequent and debilitating condition, is characterized by central sensitization. This study aimed to examine predictive factors of transcranial direct current stimulation (tDCS) efficacy in this chronic pain population. Exploratory analysis derived from a randomized controlled trial was performed to assess predictors of pain reduction among 39 women with PVD who received 10 daily sessions of either active or sham tDCS. Clinical characteristics (e.g. pain intensity, duration and pain sensitivity) and psychosexual factors (e.g. pain catastrophizing, pain-related fear, anxiety, depressive symptoms and vaginal penetration cognitions) were assessed at baseline and used to predict tDCS response at 3-month follow-up. Analysis revealed that higher depressive symptoms and lower negative self-image cognitions were significant predictors of pain reduction at follow-up and accounted for 62.3% of the variance in the active tDCS group. Higher genital incompatibility cognitions were related to poorer response, regardless of treatment group. These findings suggest that women with PVD presenting higher depressive symptoms and lower levels of negative self-image cognitions could derive greater benefits from tDCS. These results suggest that tDCS could be effective in a subgroup of women with PVD - a possibility worth exploring with future prospective larger studies.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth.

Importance: Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. Objective: To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. Design, Setting, and Participants: The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Exposures: Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. Main Outcomes and Measures: The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. Results: The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. Conclusions and Relevance: The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

Pathophysiology of Vaginal Erosions in Women Using Pessary: A Pilot Study Examining Vaginal Microbiota.

OBJECTIVE: Many women with pelvic organ prolapse opt for a pessary, and some of these women develop erosions of the vaginal mucosa. Ongoing erosions might lead to the discontinuation of this otherwise effective, non-invasive, and inexpensive treatment. The objectives of this study were to investigate the differences in vaginal pH and variations of the vaginal microbiota among pessary and non-pessary users. METHODS: For this descriptive observational study, 30 women, followed in our urogynecology clinic, were recruited to form 3 equal groups: 2 groups of women using a pessary (with and without erosions) and 1 control group of women not using a pessary. Vaginal pH was measured distally and next to the erosion. Vaginal swabs were used to investigate the vaginal microbiota by sequencing the V4 region of the 16S ribosomal RNA gene and analyzing the data with Qiime2. Descriptive statistics were reported using the median values. Vaginal pH comparisons between groups were made using a Kruskal-Wallis test with Dunn's correction for multiple comparisons. RESULTS: The pH of the vagina was more alkaline in women with erosions compared with women in the other 2 groups (P < 0.01). Also, the pH of the distal vagina was not different from the pH next to the erosion (P = 0.25). Patients with erosions displayed significant differences in their vaginal microbiota, which contained a much greater bacterial diversity with an increase in gram-negative bacteria (e.g., Bacteroidetes, Actinobacteria) and a decrease in lactobacilli. CONCLUSION: In our study, women with vaginal erosions had significantly higher vaginal pH and more complex vaginal microbiota than women in the control groups. Treatments focusing on lowering the vaginal pH and/or re-establishing the vaginal microbiota should be considered.

Reopening During the Unprecedented: The Association of Biomolecular Resource Facilities Community Coronavirus Disease 2019 Pandemic Response. Part 2: Efforts to Effectively Ramp Up Core Facility Activities.

Shared research resources, also known as core facilities, serve a crucial role in supporting research, training, and other needs for their respective institutions. In response to the coronavirus disease (COVID-19) pandemic, all but the most critical laboratory research was halted in many institutions around the world. The Association of Biomolecular Resource Facilities conducted 2 surveys to understand and document institutional responses to the COVID-19 pandemic from core facility perspectives. The first survey was focused on initial pandemic response and efforts to sustainably ramp down core facility operations. The second survey, which is the subject of this study, focused on understanding the approaches taken to ramp up core facility operations after these ramp-down procedures. The survey results revealed that many cores remained active during the ramp-down, performing essential COVID-19 research, and had a more coordinated institutional response for ramping up research as a whole. The lessons gained from this survey will be indexed to serve as a resource for the core facility community to understand, plan, and mitigate risk and disruptions in the event of future disasters.

Évaluer les besoins des femmes enceintes : une étude-pilote du dispositif Ariane.

INTRODUCTION: The organization of perinatal prevention in France is based on a system of universalism. Maternal and child protection services are thus open to all, at the risk of excluding people who do not know where or how to find them. Targeted preventive corrective measures, based on risk factors, correct some of this inequity but create other negative effects. PURPOSE OF RESEARCH: This article presents an innovative social protocol in public health: the Ariane systematic prenatal contact. It is based on the principle of proportionate universalism. Ariane consists of a text message and a phone call at the beginning of pregnancy. Aimed at all pregnant women, it allows information to be transmitted orally on public systems of prevention and support for parents. It also makes it possible to assess the needs of families, along eight axes. METHOD: This article presents the results of the pilot study of this system, conducted in Moselle. In total, 14 midwiwes ant 11 parturients who were contacted during their pregnancy participated in post-project interviews. RESULTS: The results show a very high level of acceptability of the calls by all parties. According to the midwives, Ariane has made it possible to increase the relevance of the identification, making it possible to move from a prevention logic based on criteria to a prevention logic based on the needs of families. The contact was easy, according to both the women and the clinicians. CONCLUSION: Our results show that the Ariane protocol make possible to establish a relationship of trust between the families and the services. Implications for outreach policies are also presented in this article.

Antibodies to human papillomavirus types 6, 11, 16 and 18: Vertical transmission and clearance in children up to two years of age.

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children. Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life. Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70-0·88), 0·68 (95% CI:0·5-0·80), 0·90 (95% CI:0·83-0·94) and 0·85 (95% CI:0·76-0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures. Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months. Funding: The Canadian Institutes of Health Research (CIHR).

Exploration of the effect of human papillomavirus (HPV) vaccination in a cohort of pregnant women in Montreal, 2010-2016.

HPV vaccination efficacy has been shown in clinical trials but it is important to verify population level vaccine effectiveness (VE). We aimed to explore VE and herd effect using HPV infection data from a cohort study of Canadian pregnant women. We analyzed the baseline data of the HERITAGE study, which includes pregnant women recruited in Montreal between 2010-2012 and 2015-2016. Cervicovaginal samples self-collected in the first trimester were tested for 36 HPV types. Vaccination status was self-reported. VE and 95% confidence intervals (CI) were estimated by comparing the prevalence of HPV between vaccinated and unvaccinated women. Herd effect was explored by comparing HPV prevalence in unvaccinated women between the 2 recruitment periods. Adjusted ORs (95%CI) were estimated using exact logistic regression. The proportion of vaccinated women with at least one dose of 4vHPV was 7.5%. Although most of them were vaccinated after the onset of sexual activity, a high VE was found for HPV-16/18 (86.1% (95%CI: 15.0-99.7)). For HPV-6/11/16/18 and for HPV-31/33/45, VE was 61.9% (-23.5-92.6) and 57.0% (-47.7-92.0%), respectively. We also observed a non-statistically significant reduction in the prevalence of HPV-6/11/16/18 and HPV-31/33/45 among unvaccinated women recruited during the second recruitment period (adjusted OR: 0.8 (0.4-1.8) and 0.8 (0.3-1.7), respectively).

Return to Work Interventions for Cancer Survivors: A Systematic Review and a Methodological Critique.

Cancer patients are more at risk of being unemployed or having difficulties to return to work (RTW) compared to individuals without health concerns, and is thus a major public health issue. The aim of this systematic review is to identify and describe the interventions developed specifically to help cancer patients to RTW after treatment. Two researchers independently screened the articles for inclusion and Critical Appraisal Skills Program (CASP) checklists were used to assess the methodology of the included studies. Ten manuscripts met the inclusion criteria. The type of studies were three quasi-experimental studies, three longitudinal studies, three randomized controlled trials (RCTs) and a qualitative study. RTW interventions were conducted in or outside the hospital (n = 6 and 3 respectively), or both (n = 1). Improvements in RTW were only observed in quasi-experimental studies. No improvement in RTW was noted in RCTs, nor in other measures (e.g., quality of life, fatigue). Lack of statistically significant improvement does not necessarily reflect reality, but may be attributed to non-adapted research methods. This systematic review underscores the need for researches in the RTW field to reach a consensus on RTW criteria and their assessment. Recommendations to this effect are suggested.

[Stem cell transplantation unit: Guidelines from the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC)]. / Unité de greffe : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Allogeneic hematopoietic cell transplantation (HCT) is part of the standard of care for many hematological diseases. Over the last decades, significant advances in patient and donor selection, conditioning regimens as well as supportive care of patients undergoing allogeneic HCT leading to improved overall survival have been made. In view of many new treatment options in cellular and molecular targeted therapies, the place of allogeneic transplantation in therapy concepts must be reviewed. Most aspects of HCT are well standardized by national guidelines or laws as well as by certification labels such as FACT-JACIE. However, the requirements for human resources, construction and layout of a unit treating patients during the transplantation procedure and for different complications are not well defined. Here, we describe the process of planning a transplant unit in order to open a discussion that could lead to more precise guidelines in the field of personnel and infrastructural requirements for hospitals caring for people with severe immunosuppression.

Efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia.

BACKGROUND: Provoked vestibulodynia is a highly prevalent condition characterized by acute recurrent pain located at the vaginal entrance in response to pressure application or attempted vaginal penetration. Despite a wide variety of treatments offered to women with provoked vestibulodynia, a high proportion of women are refractory to conventional treatment. Transcranial direct-current stimulation is a noninvasive brain stimulation technique that has been shown effective for improving various chronic pain conditions. Growing evidence suggests that the central nervous system could play a key role in provoked vestibulodynia. Targeting the central nervous system could therefore be a promising treatment for women with provoked vestibulodynia. OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy of active and sham transcranial direct-current stimulation in reducing pain intensity during intercourse in patients with provoked vestibulodynia. STUDY DESIGN: We conducted a triple-blind, parallel-group, randomized controlled trial. Women aged 17-45 years diagnosed with provoked vestibulodynia by a gynecologist using a validated protocol were randomized to 10 sessions of either active transcranial direct-current stimulation (intensity = 2 mA) or 10 sessions of sham transcranial direct-current stimulation, over a 2-week period. Both active and sham transcranial direct-current stimulation were applied for 20 minutes, with the anode positioned over the primary motor cortex, and the cathode over the contralateral supraorbital area. Outcome measures were collected at baseline, 2 weeks after treatment, and at 3-month follow-up by an evaluator blinded to group assignment. The primary objective was to assess pain intensity during intercourse, using a numerical rating scale. Secondary outcomes focused on sexual function and distress, vestibular sensitivity, psychological distress, treatment satisfaction, and patient impression of change. Statistical analyses were conducted on the intention-to-treat basis, and treatment effects were evaluated using a mixed linear model for repeated measures. RESULTS: A total of 40 patients were randomly assigned to receive either active (n = 20) or sham (n = 20) transcranial direct-current stimulation treatments from November 2014 through February 2016. Baseline characteristics were similar between the active and sham transcranial direct-current stimulation groups. In full compliance with the study protocol, every participant followed all courses of the study treatment, including assessments at 2-week and 3-month follow-up. Pain during sexual intercourse was not significantly different between active and sham treatment groups 2 weeks after treatment (P = .84) and at follow-up (P = .09). Mean baseline and 2-week assessment pain intensity were, respectively, 6.8 (95% confidence interval, 5.9-7.7) and 5.6 (95% confidence interval, 4.7-6.5) for active transcranial direct-current stimulation (P = .03) vs 7.5 (95% confidence interval, 6.6-8.4) and 5.7 (95% confidence interval, 4.8-6.6) for sham transcranial direct-current stimulation (P = .001). Nonsignificant differences between the 2 groups were also found in their sexual function and distress after treatment (P > .20) and at follow-up (P > .10). Overall, at 2-week assessment 68% assigned to active transcranial direct-current stimulation reported being very much, much, or slightly improved compared to 65% assigned to sham transcranial direct-current stimulation (P = .82), and still comparable at follow-up: 42% vs 65%, respectively (P = .15). CONCLUSION: Findings suggest that active transcranial direct-current stimulation is not more effective than sham transcranial direct-current stimulation for reducing pain in women with provoked vestibulodynia. Likewise, no significant effects were found on sexual function, vestibular sensitivity, or psychological distress.

Pelvic floor morphometry and function in women with and without puborectalis avulsion in the early postpartum period.

BACKGROUND: Pelvic floor muscles are subject to considerable stretching during vaginal birth. In 13-36% of women, stretching results in avulsion injury whereby the puborectalis muscle disconnects from its insertion points on the pubis bone. Until now, few studies have investigated the effect of this lesion on pelvic floor muscles in the early postpartum period. OBJECTIVE: The primary aim of this study was to compare pelvic floor muscle morphometry and function in primiparous women with and without puborectalis avulsion in the early postpartum period. Our secondary objective was to compare the 2 groups for pelvic floor disorders and impact on quality of life. STUDY DESIGN: In all, 52 primiparous women diagnosed with (n = 22) or without (n = 30) puborectalis avulsion injury were assessed at 3 months postpartum. Pelvic floor muscle morphometry was evaluated with 3-/4-dimensional transperineal ultrasound at rest, maximal contraction, and Valsalva maneuver. Different parameters were measured in the midsagittal and axial planes: bladder neck position, levator plate angle, anorectal angle, and levator hiatus dimensions. The dynamometric speculum was used to assess pelvic floor muscle function including: passive properties (passive forces and stiffness) during dynamic stretches, maximal strength, speed of contraction, and endurance. Pelvic floor disorder-related symptoms (eg, urinary incontinence, vaginal and bowel symptoms) and impact on quality of life were evaluated with the International Consultation on Incontinence Questionnaire and the Pelvic Floor Impact Questionnaire-Short Form. Pelvic Organ Prolapse Quantification was also assessed. RESULTS: In comparison to women without avulsion, women with avulsion presented an enlarged hiatus area at rest, maximal contraction, and Valsalva maneuver (P ≤ .013) and all other ultrasound parameters were found to be significantly altered during maximal contraction (P ≤ .014). They showed lower passive forces at maximal and 20-mm vaginal apertures as well as lower stiffness at 20-mm aperture (P ≤ .048). Significantly lower strength, speed of contraction, and endurance were also found in women with avulsion (P ≤ .005). They also presented more urinary incontinence symptoms (P = .040) whereas vaginal and bowel symptoms were found to be similar in the 2 groups. Pelvic Organ Prolapse Quantification revealed greater anterior compartment descent in women with avulsion (P ≤ .010). The impact of pelvic floor disorders on quality of life was found to be significantly higher in women with avulsion (P = .038). CONCLUSION: This study confirms that pelvic floor muscle morphometry and function are impaired in primiparous women with puborectalis avulsion in the early postpartum period. Moreover, it highlights specific muscle parameters that are altered such as passive properties, strength, speed of contraction, and endurance.

3D Cohort Study: The Integrated Research Network in Perinatology of Quebec and Eastern Ontario.

BACKGROUND: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. METHODS: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. RESULTS: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. CONCLUSIONS: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes.

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment.

It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti- or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti- and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions.

Efficacy of transcranial direct-current stimulation (tDCS) in women with provoked vestibulodynia: study protocol for a randomized controlled trial.

BACKGROUND: Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. METHODS/DESIGN: This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient's global impression of change. DISCUSSION: To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02543593 . Registered on September 4, 2015.