Dpr-mediated H2O2 resistance contributes to streptococcus survival in a cystic fibrosis airway model system.

The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for persons with CF (pwCF). Streptococcus spp. are highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shown Streptococcus spp. to be associated with better clinical outcomes for pwCF, while others show that high abundance of Streptococcus spp. is correlated with exacerbations. Our lab previously reported a polymicrobial culture system consisting of four CF-relevant pathogens that can be used to study microbial behavior in a more clinically relevant setting. Here, we use this model system to identify genetic pathways that are important for Streptococcus sanguinis survival in the context of the polymicrobial community. We identified genes related to reactive oxygen species as differentially expressed in S. sanguinis monoculture versus growth of this microbe in the mixed community. Genetic studies identified Dpr as important for S. sanguinis survival in the community. We show that Dpr, a DNA-binding ferritin-like protein, and PerR, a peroxide-responsive transcriptional regulator of Dpr, are important for protecting S. sanguinis from phenazine-mediated toxicity in co-culture with Pseudomonas aeruginosa and when exposed to hydrogen peroxide, both of which mimic the CF lung environment. Characterizing such interactions in a clinically relevant model system contributes to our understanding of microbial behavior in the context of polymicrobial biofilm infections. IMPORTANCE: Streptococcus spp. are recognized as a highly prevalent pathogen in cystic fibrosis (CF) airway infections. However, the role of this microbe in clinical outcomes for persons with CF is poorly understood. Here, we leverage a polymicrobial community system previously developed by our group to model CF airway infections as a tool to investigate a Pseudomonas-Streptococcus interaction involving reactive oxygen species (ROS). We show that protection against ROS is required for Streptococcus sanguinis survival in a clinically relevant polymicrobial system. Using this model system to study interspecies interactions contributes to our broader understanding of the complex role of Streptococcus spp. in the CF lung.

Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

BACKGROUND: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. METHODS AND FINDINGS: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. CONCLUSIONS: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Analysis of the obstetrician's posture and movements during a simulated forceps delivery.

BACKGROUND: The objective of this study was to identify and qualify, by means of a three-dimensional kinematic analysis, the postures and movements of obstetricians during a simulated forceps birth, and then to study the association of the obstetricians' experience with the technique adopted. METHOD: Fifty-seven volunteer obstetricians, 20 from the Limoges and 37 from the Poitiers University hospitals, were included in this multi-centric study. They were classified into 3 groups: beginners, intermediates, and experts, beginners having performed fewer than 10 forceps deliveries in real conditions, intermediates between 10 and 100, and experts more than 100. The posture and movements of the obstetricians were recorded between December 2020 and March 2021 using an optoelectronic motion capture system during simulated forceps births. Joint angles qualifying these postures and movements were analysed between the three phases of the foetal traction. These phases were defined by the passage of a virtual point associated with the forceps blade through two anatomical planes: the mid-pelvis and the pelvic outlet. Then, a consolidated ascending hierarchical classification (AHC) was applied to these data in order to objectify the existence of groups of similar behaviours. RESULTS: The AHC distinguished four different postures adopted when crossing the first plane and three different traction techniques. 48% of the beginners adopted one of the two raised posture, 22% being raised without trunk flexion and 26% raised with trunk flexion. Conversely, 58% of the experts positioned themselves in a "chevalier servant" posture (going down on one knee) and 25% in a "squatting" posture before initiating traction. The results also show that the joint movement amplitude tends to reduce with the level of expertise. CONCLUSION: Forceps delivery was performed in different ways, with the experienced obstetricians favouring postures that enabled observation at the level of the maternal perineum and techniques reducing movement amplitude. The first perspective of this work is to relate these different techniques to the traction force generated. The results of these studies have the potential to contribute to the training of obstetricians in forceps delivery, and to improve the safety of women and newborns.

Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.

BACKGROUND: Nitrites and nitrates occur naturally in water and soil and are commonly ingested from drinking water and dietary sources. They are also used as food additives, mainly in processed meats, to increase shelf life and to avoid bacterial growth. Experimental studies suggested both benefits and harmful effects of nitrites and nitrates exposure on type 2 diabetes (T2D) onset, but epidemiological and clinical data are lacking. We aimed to study these associations in a large population-based prospective cohort study, distinguishing foods and water-originated nitrites/nitrates from those from food additives. METHODS AND FINDINGS: Overall, 104,168 adults from the French NutriNet-Santé cohort study (2009 to 2021, 79.1% female, mean age [SD] = 42.7 [14.5]) were included. Associations between self-reported exposure to nitrites and nitrates (evaluated using repeated 24-h dietary records, linked to a comprehensive food composition database and accounting for commercial names/brands details of industrial products) and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). During a median follow-up duration of 7.3 years (interquartile range: [3.2; 10.1] years), 969 incident T2D cases were ascertained. Total nitrites and foods and water-originated nitrites were both positively associated with a higher T2D risk (HRtertile 3 vs.1 = 1.27 (95% CI 1.04 to 1.54), Ptrend = 0.009 and 1.26 (95% CI 1.03 to 1.54), Ptrend = 0.02, respectively). Participants with higher exposure to additives-originated nitrites (i.e., above the sex-specific median) and specifically those having higher exposure to sodium nitrite (e250) had a higher T2D risk compared with those who were not exposed to additives-originated nitrites (HR higher consumers vs. non-consumers = 1.53 (95% CI 1.24 to 1.88), Ptrend < 0.001 and 1.54 (95% CI 1.26 to 1.90), Ptrend < 0.001, respectively). There was no evidence for an association between total, foods and water-originated, or additives-originated nitrates and T2D risk (all Ptrend = 0.7). No causal link can be established from this observational study. Main limitations include possible exposure measurement errors and the lack of validation versus specific nitrites/nitrates biomarkers; potential selection bias linked to the healthier behaviors of the cohort's participants compared to the general population; potential residual confounding linked to the observational design, as well as a self-reported, yet cross-checked, case ascertainment. CONCLUSIONS: The findings of this large prospective cohort did not support any potential benefits for dietary nitrites and nitrates. They suggested that a higher exposure to both foods and water-originated and additives-originated nitrites was associated with higher T2D risk in the NutriNet-Santé cohort. This study provides a new piece of evidence in the context of current debates about updating regulations to limit the use of nitrites as food additives. The results need to be replicated in other populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).

In vivo assessment of the elastic properties of the external anal sphincter in term pregnant women using shear wave elastography.

INTRODUCTION AND HYPOTHESIS: The objective was to assess the intraobserver intersession and interobserver intrasession reliability of shear wave elastography applied to the external anal sphincter in term pregnant women. METHODS: This prospective study involved nulliparous pregnant women at 37 weeks or more with two visits (V1: one observer; V2 two observers) planned within a 12-h to 7-day interval. Measurements were performed using an Aixplorer V12® device with an SL 18-5 linear probe using a transperineal approach, allowing a measurement of the shear modulus (SM) in kPa. Measures were performed at rest, Valsalva maneuver, and maximal contraction. Reliability was assessed using the intraclass correlation coefficient (ICC). The study was approved by an ethics committee (ID RCB: 2020-A00764-65). RESULTS: A total of 37 women were included. Intraobserver reliability was excellent at rest (ICC = 0.91 [0.84-0.95) and good during the Valsalva maneuver (ICC = 0.83 [0.72-0.90]) and contraction (ICC = 0.85 [0.75-0.91]). Interobserver reliability was good at rest (ICC = 0.79 [0.66-0.87]) and during Valsalva (ICC = 0.84 [0.73-0.90]), but moderate during contraction (ICC = 0.70 [0.53-0.82]). CONCLUSIONS: Shear wave elastography is a reliable tool for assessing the elastic properties of the external anal sphincter in term pregnant women.

Impact of fetal manipulation on maternal and neonatal severe morbidity during shoulder dystocia management.

PURPOSE: There are few data on maternal and neonatal morbidities associated with shoulder dystocia (SD), depending on the use of fetal manipulation (FM). A prior 5-year study was conducted in our center in 2012 for this purpose. Our objective was to compare severe maternal and neonatal morbidities according to FM execution in a larger cohort. METHODS: We conducted a retrospective study between 2007 and 2020. SD was considered when additional maneuvers were required to complete a delivery. Severe maternal morbidity was defined as the occurrence of obstetric anal sphincter injury (OASI). Severe neonatal morbidity was defined as Apgar < 7 at 5 min and/or cord arterial pH < 7.1 and/or or a permanent brachial plexus palsy. We studied these data in the FM group compared to the non- FM group. RESULTS: FM was associated with increased OASI rates (21.1% vs. 3.8%, OR = 6.72 [2.7-15.8]). We found no significant difference in severe neonatal morbidity. Maternal age > 35 and FM appear to be associated with the occurrence of OASI, with ORa = 13.3 [1.5-121.8] and ORa = 5.3 [2.2-12.8], respectively. FM was the only factor associated with the occurrence of severe neonatal morbidity (ORa = 2.3 [1.1-4.8]. The rate of episiotomy was significantly decreased (20% versus 5% p < 0.05) and there was an increase in the rate of SD managed with FM in our center. CONCLUSION: FM is the only factor associated with an increased risk of OASI. In case of failure of non-FM maneuvers, the rapid implementation of FM maneuvers resulted in no difference regarding severe neonatal morbidity.

In vivo measurement of the elastic properties of pelvic floor muscles in pregnancy using shear wave elastography.

OBJECTIVE: We aimed to investigate changes in the elastic properties of levator ani muscle (LAM) and external anal sphincter (EAS) during pregnancy using shear wave elastography (SWE). Our secondary objective was to examine the association between the elastic properties of pelvic floor muscles (PFM) and perineal tears at childbirth. METHODS: This was a prospective monocentric study, including nulliparous women. Three visits were planned (14-18, 24-28, and 34-38 weeks) with a SWE assessment of the LAM and EAS at rest and during Valsalva maneuver. Then, we collected data about the delivery's characteristics. Assessments were performed using an Aixplorer V12® device (SL 18-5 linear probe) using a transperineal approach, reporting the shear modulus in kPa. We looked for changes in PFM's elastic properties during pregnancy using one-way ANOVA for repeated measures. We compared the mean shear modulus in late pregnancy for each muscle and condition between women with an intact perineum at delivery and those with a perineal tear using Student's t test. RESULTS: Forty-seven women were considered. Forty-five women had vaginal delivery of which 38 (84.4%) had perineal tears. We did not report any significant changes in the elastic properties of PFM during pregnancy. Women with an intact perineum at delivery had a stiffer EAS at Valsalva maneuver in late pregnancy (27.0 kPa vs. 18.2 kPa; p < 0.005). CONCLUSIONS: There were no significant changes in the elastic properties of the PFM in pregnancy. Stiffer EAS in late pregnancy appears to be associated with a lower incidence of perineal tears.

Cephalic marks and well-being in newborns after operative vaginal delivery.

OBJECTIVES: To compare the incidence of cephalic marks in newborns exposed to operative vaginal delivery and those who are not. We examined the factors associated with alterations in neonatal well-being and with cephalic mark occurrence. METHODS: Prospective study involving singleton term newborns delivered in a cephalic presentation. Newborns in the operative group were matched with newborns born on the same day without instruments required. A cephalic mark was defined as any mark or edema on the newborn's skin between 12 and 72 hours of life. Neonatal well-being was assessed by analgesic consumption, neonatal discomfort (EDIN score of 1 or more), and prolonged hospitalization (4 days or more). We compared the operative and spontaneous groups and determined the relative risk (RR) for cephalic marks. We investigated the factors associated with alterations in neonatal well-being and factors associated with cephalic mark occurrence in the case of operative delivery using multivariate logistic regression analysis. RESULTS: A total of 135 newborns were included in each group. The incidence of cephalic marks was higher in the operative group (RR = 13.3 [6.0-29.5]). In case of operative delivery, cephalic marks were associated with neonatal discomfort (adjusted odds ratios [aOR] = 8.2 [2.2-30.6]) and analgesic consumption (aOR = 3.0 [1.2-7.1]). The number of cephalic marks was higher in cases with sequential use of vacuum and forceps (aOR = 3.5 [1.1-11.7]) and forceps only deliveries (aOR = 3.0 [1.1-8.1]) relative to vacuum only deliveries. CONCLUSIONS: Operative delivery increases the risk of neonatal cephalic marks, which can negatively affect neonatal well-being.

Anxiety is a potential effect modifier of the association between red and processed meat consumption and cancer risk: findings from the NutriNet-Santé cohort.

PURPOSE: Red and processed meats are recognized by the International Agency for Research on Cancer as probably carcinogenic and carcinogenic to humans, respectively. Heme iron has been proposed as a central factor responsible for this effect. Furthermore, anxiety affects the intestinal barrier function by increasing intestinal permeability. The objective of this work was to assess how anxiety modifies the association between red and processed meat consumption and cancer risk in the NutriNet-Santé prospective cohort (2009-2019). METHODS: Using multi-adjusted Cox models in a sample of 101,269 subjects, we studied the associations between the consumption of red and processed meat, the amount of heme iron coming from these meats and overall, colorectal, prostate, and breast cancer risks, overall and separately among participants with and without anxiety. RESULTS: An increase in red and processed meat consumption was associated with an increased risk of developing colorectal cancer in the total population (HR for an increase of 50 g/day = 1.18 (1.01-1.37), p = 0.03). After stratification on anxiety, the HR 50 g/day was 1.42 (1.03-1.94, p = 0.03) in anxious participants and 1.12 (0.94-1.33, p = 0.20) in other participants. Similar trends were observed for overall cancer risk. Analyses conducted with heme iron also provided similar results. CONCLUSIONS: Our results strengthen the existing body of evidence supporting that red and processed meat consumption and heme iron intake are associated with an increased risk of overall and more specifically colorectal cancer, and suggest that anxiety modifies these associations, with an increased risk in anxious participants.

A core outcome set development for a French national prospective study about the effect of mediolateral episiotomy on obstetric anal sphincter injury during operative vaginal delivery (INSTRUMODA).

BACKGROUND: We aimed at developing a core outcome and variables of interest set to investigate the effects of mediolateral episiotomy on Obstetric Anal Sphincter Injury (OASI) during and after operative delivery in nulliparous women in a large-scale one-year observational French study including 15,000 women (INSTRUMODA). METHODS: A list of outcomes and variables of interest was suggested to obstetricians participating in the INSTRUMODA study using online questionnaires divided into 7 categories: the woman's history and course of pregnancy, course of labor, modalities of operative delivery, episiotomy characteristics, immediate maternal morbidity, one-year maternal morbidity, immediate neonatal morbidity. We used a three-round DELPHI method to reach a consensus. In the first round, outcomes and variables considered as essential by 70% or more of obstetricians were included in the corpus whereas they were excluded when 70% rated them as "not important". In the second round, non-consensual outcomes and variables were reassessed and excluded or definitively included if considered as "not important" or essential by 50% or more of the obstetricians. During the first round, obstetricians were invited to suggest new outcomes and/or variables that were then assessed in the second and third round. We used the same method to develop a core outcome and variables of interest set in a population of women in the community recruited via an association of patients. At the end of the procedure the core outcome and variables of interest sets were merged to provide the final core outcome set for the INSTRUMODA study. RESULTS: Fifty-three obstetricians and 16 women filled out questionnaires. After the 3 rounds of Delphi procedure in each population, 74 outcomes and variables were consensually reported by obstetricians and 92 by women in the community. By mixing these two consensual corpora we reported a final consensual list of 114 variables of interest and outcomes for both obstetricians and women. CONCLUSION: We established a core outcome and variables of interest set among obstetricians and women in the community to investigate the association between mediolateral episiotomy and OASI during operative delivery. TRIAL REGISTRATION: The INSTRUMODA study was registered on https://clinicaltrials.gov on June 25, 2020 ( NCT04446780 ).

Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms.

The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms.IMPORTANCEPseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

Does the McRoberts' manoeuvre need to start with thigh abduction? An innovative biomechanical study.

BACKGROUND: Guidelines and description about the achievement of the McRoberts manoeuvre are discordant, particularly concerning the need for abduction before the beginning of the manoeuvre. We sought to compare the biomechanical efficiency of the McRoberts' manoeuvre, with and without thigh abduction. METHODS: In a postural comparative study, twenty-three gravidas > 32 weeks of gestational age and not in labour were assessed during three repetitions of two McRoberts' manoeuvre that differed in terms of starting position. For the (i) McRoberts, the legs were initially placed in stirrups; for the (m) McRoberts, the legs were resting on the bed, with thighs in wide abduction. For each manoeuvre, flexion of the plane of the external conjugate of the pelvis on the spine (ANGce), hip flexion and abduction, were assessed using an optoelectronic motion capture system. Lumbar curve were assessed with Epionics Spine® system. Temporal parameters including movement duration or acceleration of the external conjugate were also computed. All values ​​obtained for the two types of manoeuvres were compared using a Wilcoxon matched-pairs signed-ranks test. The significance level was defined as p < 0.05. RESULTS: The starting position of McRoberts' otherwise had no effect on the maximum ANGce (p = 0.199), the minimal lordosis of the lumbar curve (p = 0.474), or the maximal hip flexion (p = 0.057). The other parameters were not statistically different according to the starting position (p > 0.005). CONCLUSION: Regardless of the starting position, the McRoberts' manoeuvre allows ascension of the pubic symphysis and reduction of the lumbar lordosis. This results imply that the McRoberts' manoeuvre could be performed with the legs initially placed in the stirrups.

Balloon catheter vs oxytocin alone for induction of labor in women with a previous cesarean section: A randomized controlled trial.

INTRODUCTION: The aim of this study was to compare the efficacy and maternal-neonatal morbidity between balloon catheter and oxytocin for induction of labor in women with a previous cesarean section and an unfavorable cervix. MATERIAL AND METHODS: This open-label randomized controlled trial took place in seven French hospitals. Inclusion criteria were medical indication for labor induction in pregnant women, ≥37 weeks, with lower segment cesarean section, Bishop score ≤4, no pre-labor rupture of membranes, singleton fetus in cephalic presentation. Women were allocated randomly to induction with a 50-mL balloon catheter for 12 hours or a low-dose oxytocin infusion. Primary outcome was the rate of vaginal birth. Secondary outcomes were maternal and neonatal complications. RESULTS: The study enrolled 204 women from 26 December 2010 to 31 December 2013: 101 were allocated to receive balloon catheter and 103 to oxytocin. Vaginal birth rate was 50% (n = 51) in the balloon catheter group vs 37% (n = 38) in the oxytocin group (P = 0.050). Maternal and neonatal morbidity did not differ between balloon catheter and oxytocin groups: two uterine dehiscences vs one, one vs four maternal infections, five vs two hemorrhages and 11 vs five neonatal transfers, respectively. Heterogeneity of treatment effect for vaginal delivery was observed across initial Bishop scores. Balloon catheter was more effective for low values of bishop score. CONCLUSIONS: Balloon catheter tended to be associated with a higher probability of vaginal delivery as compared with low-dose intravenous oxytocin when used for induction of labor in women with a previous cesarean section and low Bishop score at induction.

In vivo assessment of the elastic properties of women's pelvic floor during pregnancy using shear wave elastography: design and protocol of the ELASTOPELV study.

BACKGROUND: Animal studies have reported an increase in pelvic floor muscle stiffness during pregnancy, which might be a protective process against perineal trauma at delivery. Our main objective is to describe the changes in the elastic properties of the pelvic floor muscles (levator ani, external anal sphincter) during human pregnancy using shear wave elastography (SWE) technology. Secondary objectives are as follows: i) to look for specific changes of the pelvic floor muscles compared to peripheral muscles; ii) to determine whether an association between the elastic properties of the levator ani and perineal clinical and B-mode ultrasound measures exists; and iii) to provide explorative data about an association between pelvic floor muscle characteristics and the risk of perineal tears. METHODS: Our prospective monocentric study will involve three visits (14-18, 24-28, and 34-38 weeks of pregnancy) and include nulliparous women older than 18 years, with a normal pregnancy and a body mass index (BMI) lower than 35 kg.m- 2. Each visit will consist of a clinical pelvic floor assessment (using the Pelvic Organ Prolapse Quantification system), an ultrasound perineal measure of the anteroposterior hiatal diameter and SWE assessment of the levator ani and the external anal sphincter muscles (at rest, during the Valsalva maneuver and during pelvic floor contraction), and SWE assessment of both the biceps brachii and the gastrocnemius medialis (at rest, extension and contraction). We will collect data about the mode of delivery and the occurrence of perineal tears. We will investigate changes in continuous variables collected using the Friedman test. We will look for an association between the elastic properties of the levator ani muscle and clinical / ultrasound measures using a Spearman test at each trimester. We will investigate the association between the elastic properties of the pelvic floor muscles and perineal tear occurrence using a multivariate analysis with logistic regression. DISCUSSION: This study will provide original in vivo human data about the biomechanical changes of pregnant women's pelvic floor. The results may lead to an individualized risk assessment of perineal trauma at childbirth. TRIAL REGISTRATION: This study was registered on https://clinicaltrials.gov on July 26, 2018 (NCT03602196).

Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort NutriNet-Santé.

PURPOSE: Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes. METHODS: This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations. RESULTS: SFA intake was associated with increased overall [n = 1722 cases, HRQ5vsQ1 = 1.44 (1.10-1.87), p-trend = 0.008] and breast [n = 545 cases, HRQ5vsQ1 = 1.98 (1.24-3.17), p-trend = 0.01] cancer risks. n-6 PUFA [HRQ5vsQ1 = 0.56 (0.32-0.97), p-trend = 0.01] and MUFA (HRQ5vsQ1 = 0.41 [0.18-0.0.95), p-trend = 0.009] intakes were associated with a decreased risk of digestive cancers (n = 190 cases). Associations between n-6 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes and digestive cancer risk were modulated by dietary fibre, vitamin C and fruit and vegetable intakes. CONCLUSION: These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.

In vivo assessment of the levator ani muscles using shear wave elastography: a feasibility study in women.

INTRODUCTION AND HYPOTHESIS: We hypothesized that shear wave elastography (SWE) technology might be useful for assessing the elastic properties of the pelvic floor in women. Our primary objective was to evaluate the feasibility of assessing the levator ani muscles using SWE in women. Our secondary aim was to investigate the changes in their elastic properties from rest to Valsalva maneuver. METHODS: During this prospective feasibility study in nonpregnant female volunteers, we collected data on participant age, body mass index (BMI), parity, and time since the delivery. The levator ani muscles of each participant were assessed using SWE technology at rest and during a Valsalva maneuver by measuring the shear modulus (in kilopascals). We then assessed the changes in the shear modulus at rest and during the Valsalva maneuver using a Wilcoxon test. RESULTS: Twelve parous women participated in this study. The mean time since the last delivery was 14 months, the mean age was 31 years, and mean BMI was 28 kg.m-2. All the assessments performed at rest were successfully completed, but we encountered two failures during the Valsalva maneuver. The mean shear modulus increased by a factor of more than 2 from rest to the Valsalva maneuver for both the right (16.0 vs 35.4 kPa) and left side (17.1 vs 37.6 kPa). CONCLUSIONS: An assessment of the elastic properties of the levator ani muscles is feasible for nonpregnant women. The reproducibility of the technique and its application in pregnant women and women with pelvic floor disorders must be investigated.

Is there an impact of feet position on squatting birth position? An innovative biomechanical pilot study.

BACKGROUND: The squatting birth position is widely used for "natural" birth or in countries where childbirth occurs in non-medical facilities. Squatting birth positions, like others, are roughly defined so a biomechanical assessment is required with the availability of noninvasive technology in pregnant women. In practice, we can observe spontaneously two kinds of squatting birth position: on tiptoes and with feet flat. OBJECTIVE: To compare the impact of foot posture on biomechanical parameters considered essential in obstetrical biomechanics during a squatting birth position: on tiptoes versus with feet flat on the floor. STUDY DESIGN: Thirteen pregnant women beyond 32 weeks of gestational age who were not in labor were assessed during squatting birth position firstly spontaneously and secondly with the foot posture that was not taken spontaneously (on the tiptoes vs with feet flat). For each position, ANGle of flexion on the spine of the plane of the pelvis external conjugate (ANGec), hip flexion and abduction, and lumbar curve were assessed using an optoelectronic motion capture system and a biomechanical model adapted from the conventional gait model as well as a measuring system of the lumbar curve. RESULTS: Spontaneously, 11 out of 13 women squatted on tiptoe at the first test. On tiptoes the hip flexion was lower than with feet flat (p < 0.02), whereas hip abduction was not significantly different (p = 0.28). A lower ANGec angle (p = 0.003) was noticed for the tiptoe position than feet flat. The lumbar curve (lordosis) was more marked for the squatting position on tiptoes than for the position with feet flat (p < 0.001). On tiptoes no woman had a pelvic inlet plane perpendicular to the spine and none had a flat back or kyphosis. No woman on tiptoes fulfilled the two conditions necessary for the position that we consider optimal. CONCLUSION: In squatting birth position, foot posture has a biomechanical impact on lumbar curve and pelvic orientation. When comparing squatting positions (on tiptoes vs feet flat), feet flat on the ground is closer to optimal birth conditions than on tiptoes.

Tissue biomechanical behavior should be considered in the risk assessment of perineal trauma at childbirth.

Perineal trauma at childbirth is associated with strong negative impacts on a woman's health but remains unpredictable. Pregnancy induces several changes in biomechanical behavior in humans as in animals, namely, an increase in ligamentous laxity and an increase in vaginal distensibility. Pelvic floor muscles in rats are reported to exhibit specific behaviors during pregnancy. Increases in both stiffness and the number of sarcomeres in series are observed and might process that protect against perineal trauma at childbirth. Some data in humans have shown that the risk of perineal trauma is highly linked to the intrinsic characteristics of the tissue, suggesting the potential benefit of incorporating intrinsic biomechanical characteristics in the risk prediction for perineal trauma. Shear wave elastography might be a useful noninvasive tool to investigate the elastic properties of these tissues in pregnant women in vivo, with the goal of implementing these properties as a predictive strategy.

Does the implementation of a restrictive episiotomy policy for operative deliveries increase the risk of obstetric anal sphincter injury?

PURPOSE: Our main objective was to investigate whether the implementation of a restrictive episiotomy policy in operative deliveries changes the incidence of obstetric anal sphincter injury (OASI). METHODS: This is an observational study over an 11-year period in Poitiers University Maternity, France. We included women with vaginal operative deliveries after 34 gestational weeks for singleton births in cephalic presentation. We collected data on the mother and operative delivery characteristics: indication, instrument, epidural analgesia, labor length, episiotomy, OASI, and birthweight. We investigated the changes in the mediolateral episiotomy (MLE) and OASI rates and the association between MLE and OASI. The primary outcome was the evolution of the OASI and MLE rates. The secondary outcome was the occurrence of OASI during operative delivery with or without MLE. RESULTS: In total, 2357 operative deliveries were assessed, including 847 vacuum-, 1350 forceps- and 160 spatula-assisted deliveries. Of these, 950 were performed with MLE and 1407 without; 37 OASIs (3.9%) occurred in the MLE group, and 137 (9.7%) in the no-MLE group. Between 2005 and 2015, MLE use decreased from 78.5 to 16.2% and OASI occurrence increased from 3.1 to 12.7%. The increase in OASI occurrence was significant for forceps deliveries, but not for vacuum or spatula deliveries. Operative delivery with MLE was associated with a three times lower OASI occurrence than that without MLE (adjusted OR = 0.29, 95% CI [0.20-0.43]). CONCLUSIONS: Implementation of a restrictive MLE policy for operative delivery seems to be associated with an increase in OASI incidence with forceps, but not with vacuum.

Red and processed meat intake and cancer risk: Results from the prospective NutriNet-Santé cohort study.

The International Agency for Research on Cancer (WHO-IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet-Santé cohort (2009-2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow-up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HRQ5vs.Q1 =1.31 (1.10-1.55), ptrend = 0.01) and breast cancer (HRQ5vs.Q1 = 1.83 (1.33-2.51), ptrend = 0.002]. The latter association was observed in both premenopausal [HRQ5vs.Q1 =2.04 (1.03-4.06)] and postmenopausal women [HRQ5vs.Q1 =1.79 (1.26-2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut-offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon-rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.