Horizons in Endometriosis: Proceedings of the Montreux Reproductive Summit, 14-15 July 2023.

Endometriosis is a complex and chronic gynaecological disorder that affects millions of women worldwide, leading to significant morbidity and impacting reproductive health. This condition affects up to 10% of women of reproductive age and is characterised by the presence of endometrial-like tissue outside the uterus, potentially leading to symptoms such as chronic pelvic pain, dysmenorrhoea, dyspareunia, and infertility. The Montreux summit brought a number of experts in this field together to provide a platform for discussion and exchange of ideas. These proceedings summarise the six main topics that were discussed at this summit to shed light on future directions of endometriosis classification, diagnosis, and therapeutical management. The first question addressed the possibility of preventing endometriosis in the future by identifying risk factors, genetic predispositions, and further understanding of the pathophysiology of the condition to develop targeted interventions. The clinical presentation of endometriosis is varied, and the correlation between symptoms severity and disease extent is unclear. While there is currently no universally accepted optimal classification system for endometriosis, several attempts striving towards its optimisation - each with its own advantages and limitations - were discussed. The ideal classification should be able to reconcile disease status based on the various diagnostic tools, and prognosis to guide proper patient tailored management. Regarding diagnosis, we focused on future tools and critically discussed emerging approaches aimed at reducing diagnostic delay. Preserving fertility in endometriosis patients was another debatable aspect of management that was reviewed. Moreover, besides current treatment modalities, potential novel medical therapies that can target underlying mechanisms, provide effective symptom relief, and minimise side effects in endometriotic patients were considered, including hormonal therapies, immunomodulation, and regenerative medicine. Finally, the question of hormonal substitution therapy after radical treatment for endometriosis was debated, weighing the benefits of hormone replacement.

Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. RESULTS: Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis.

BACKGROUND: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. METHODS: Spinal multimodal MRI was performed shortly after diagnosis in 41 ALS patients and 12 healthy participants as part of a prospective multicenter cohort study, the PULSE study (NCT00002013-A00969-36). Motor capacity was assessed using ALSFRS-R scores. Multiple stepwise linear regression models were constructed to predict motor capacity at 3 and 6 months from diagnosis, based on clinical variables, structural MRI measurements, including spinal cord cross-sectional area (CSA), anterior-posterior, and left-to-right cross-section diameters at vertebral levels from C1 to T4, and diffusion parameters in the lateral corticospinal tracts (LCSTs) and dorsal columns. RESULTS: Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. And as early as 3 months from diagnosis, structural MRI measurements fit the best multiple linear regression model to predict the total ALSFRS-R (R2 = 0.70, p value = 0.0001) and arm sub-score (R2 = 0.69, p value = 0.0002), and combined with DTI metric in the LCST and clinical factors fit the best multiple linear regression model to predict leg sub-score (R2 = 0.73, p value = 0.0002). CONCLUSIONS: Spinal multimodal MRI could be promising as a tool to enhance prognostic accuracy and serve as a motor function proxy in ALS.

COVID-19 reinfection after pregnancy.

BACKGROUND: There have been reports of COVID-19 reinfections, but the immunological characterization of these cases is partial. We report a case of reinfection with SARS-CoV-2, where the first infection occurred in the course of late pregnancy. CASE PRESENTATION: On May 27, 2020, a 37-year-old woman gave birth at full term, 3 hours after full dilatation. She developed fever (38.3°C) after delivery. Mild biological anomalies compatible with COVID-19 were observed: lymphopenia, thrombocytopenia, elevated D-Dimers, CRP, and LDH. At 6-month follow-up, she reported having contracted COVID-19 with high fever, rhinorrhea, hand frostbites, cough, headache, dysgeusia and anosmia. CONCLUSIONS: We report a case of COVID-19 reinfection with a first mild infection during late pregnancy and a more aggressive second infection 5 months later.

Oxford-AstraZeneca COVID-19 vaccine: need of a reasoned and effective vaccine campaign.

OBJECTIVES: A strong COVID-19 vaccine campaign is needed to reach the herd immunity and reduce this pandemic infection. STUDY DESIGN: In the Foch Hospital, France, in February 2021, 451 healthcare workers were vaccinated by a first dose of AstraZeneca vaccine. METHODS: Adverse effects were reported to our pharmaco-vigilance circuit, by an online and anonymous questionnaire following the first weeks of the vaccinal campaign to healthcare workers. RESULTS: Two hundred seventy-four (60.8%) of them reported multiple adverse effects. Main adverse effects reported were feverish state/chills (65.7%), fatigue/physical discomfort (62.4%), arthralgia/muscle pain (61.0%) and fever (44.5%). CONCLUSIONS: On March 2021 many European countries suspended AstraZeneca vaccine for one week due to safety uncertainty. Thus, confidence in its efficacy is undermined. However, the benefit/risk balance is clearly in favor of vaccination.

One-pot synthesis of a new generation of hybrid bisphosphonate polyoxometalate gold nanoparticles as antibiofilm agents.

A reduced polyoxovanadate functionalized with bisphosphonate molecules was synthesized and used to prepare in one step hybrid organic-inorganic polyoxometalate decorated gold nanoparticles. These new composites were shown to strongly inhibit P. aeruginosa and S. epidermidis biofilm growth, with the three components constituting the nanoparticles (Au0 core, vanadium and alendronate) acting synergistically.

Correction: One-pot synthesis of a new generation of hybrid bisphosphonate polyoxometalate gold nanoparticles as antibiofilm agents.

[This corrects the article DOI: 10.1039/C9NA00401G.].

Added Value of Spectroscopy to Perfusion MRI in the Differential Diagnostic Performance of Common Malignant Brain Tumors.

BACKGROUND AND PURPOSE: Perfusion and spectroscopic MR imaging provide noninvasive physiologic and metabolic characterization of tissues, which can help in differentiating brain tumors. We investigated the diagnostic role of perfusion and spectroscopic MR imaging using individual and combined classifiers of these modalities and assessed the added performance value that spectroscopy can provide to perfusion using optimal combined classifiers that have the highest differential diagnostic performance to discriminate lymphomas, glioblastomas, and metastases. MATERIALS AND METHODS: From January 2013 to January 2016, fifty-five consecutive patients with histopathologically proved lymphomas, glioblastomas, and metastases were included after undergoing MR imaging. The perfusion parameters (maximum relative CBV, maximum percentage of signal intensity recovery) and spectroscopic concentration ratios (lactate/Cr, Cho/NAA, Cho/Cr, and lipids/Cr) were analyzed individually and in optimal combinations. Differences among tumor groups, differential diagnostic performance, and differences in discriminatory performance of models with quantification of the added performance value of spectroscopy to perfusion were tested using 1-way ANOVA models, receiver operating characteristic analysis, and comparisons between receiver operating characteristic analysis curves using a bivariate χ2, respectively. RESULTS: The highest differential diagnostic performance was obtained with the following combined classifiers: maximum percentage of signal intensity recovery-Cho/NAA to discriminate lymphomas from glioblastomas and metastases, significantly increasing the sensitivity from 82.1% to 95.7%; relative CBV-Cho/NAA to discriminate glioblastomas from lymphomas and metastases, significantly increasing the specificity from 92.7% to 100%; and maximum percentage of signal intensity recovery-lactate/Cr and maximum percentage of signal intensity recovery-Cho/Cr to discriminate metastases from lymphomas and glioblastomas, significantly increasing the specificity from 83.3% to 97.0% and 100%, respectively. CONCLUSIONS: Spectroscopy yielded an added performance value to perfusion using optimal combined classifiers of these modalities, significantly increasing the differential diagnostic performances for these common brain tumors.

Anti-infectious properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 on enterotoxigenic E. coli (ETEC) strain H10407.

Enterotoxigenic Escherichia coli (ETEC) are major food-borne pathogens responsible for traveler's diarrhea. The production of adhesins and the secretion of enterotoxins constitute the major virulence traits of the bacteria. Treatments are mainly symptomatic and can involve antibiotherapy. However, given the rise of antibiotic resistance worldwide, there is an urgent need for the development of new preventive strategies for the control of ETEC infections. Among them, a promising approach is the use of probiotics. The aim of this study was to investigate, using complementary in vitro and in vivo approaches, the inhibitory potential of the yeast Saccharomyces cerevisiae CNCM I-3856 against the human ETEC reference strain H10407. In conventional culture media, S. cerevisiae significantly reduced ETEC growth and toxin production. The yeast also inhibited bacterial adhesion to mucin-agar and intestinal Caco-2/TC7 cells in a dose-dependent manner. Lastly, pre-treatment with S. cerevisiae inhibited interleukin-8 production by ETEC-infected intestinal cells. In streptomycin-treated mice, the probiotic yeast decreased bacterial colonization, mainly in the ileum, the main site of ETEC pathogenesis. For the first time, this study shows that the probiotic yeast S. cerevisiae CNCM I-3856 can exert an anti-infectious activity against a human ETEC strain through a multi-targeted approach, including inhibition of bacterial growth and toxin production, reduction of bacterial adhesion to mucins and intestinal epithelial cells, and suppression of ETEC-induced inflammation. Interestingly, the highest activity was obtained with a prophylactic treatment. Further studies will aim to assess the effect of the yeast on ETEC survival and virulence under human simulated digestive conditions.

Complex fractures of the acetabulum: Should the enlarged iliofemoral approach be abandoned? Results at 20 years' follow-up.

INTRODUCTION: Among the various options for internal fixation of acetabular fractures, the enlarged iliofemoral approach is less often used, being more invasive, although providing greater exposure enabling control of all components in complex fractures. Even so, the impact of its invasiveness has not been confirmed, and long-term results are not known. We therefore performed a retrospective study, aiming: to assess long-term functional outcome, and; to assess associated morbidity. HYPOTHESIS: The enlarged iliofemoral approach allows precise reduction, with favorable long-term outcome. MATERIAL AND METHODS: Between 1992 and 1997, 15 patients were operated on for complex acetabular fracture by a single surgeon using an enlarged iliofemoral approach. Two patients were excluded due to lack of follow-up data, leaving 13 patients for analysis: 3 simple transverse fractures, 4 transverse+posterior wall fractures, 4 anterior column+posterior hemi-transverse fractures, one T-shaped fracture and one 2-column fracture. There were 4 cases of posterior dislocation of the hip, and 8 of intrapelvic protrusion. Surgical morbidity was assessed in terms of operative time, number of packed red blood cell transfusions, iatrogenic lesions or postoperative complications, rehabilitation time, and hospital stay. Functional assessment at follow-up used the WOMAC index and Harris score; radiologic assessment used the Kellgren-Lawrence score for osteoarthritis and Brooker score for ossification. RESULTS: Reduction was in all cases anatomic. There were no intra- or post-operative complications. Median number of packed red blood cell transfusions was 5 [range, 3-10]. Median operative time was 4hours [3-6]. Median hospital stay was 6 weeks [6-8], to allow systematic traction with early postoperative mobilization. Weight-bearing was resumed at a median 8 weeks [8-12]. At a median 22 years' follow-up [20-24], median Harris score was 83.5 [63-92] and median WOMAC index 24.5 [1-52]. All patients showed Brooker 1 or 2 ectopic ossification and moderate osteoarthritis. Two underwent subsequent arthroplasty (at 1 and 11 years after the index procedure). DISCUSSION: The enlarged iliofemoral approach allowed anatomic reduction of acetabular fracture. It provided very good long-term results, without excessive morbidity. LEVEL OF EVIDENCE: IV, retrospective non-controlled study.

Genome-wide association study for behavior, type traits, and muscular development in Charolais beef cattle.

Behavior, type traits, and muscular development are of interest for beef cattle breeding. Genome-wide association studies (GWAS) enable the identification of candidate genes, which enables gene-based selection and provides insight in the genetic architecture of these traits. The objective of the current study was to perform a GWAS for 3 behavior traits, 12 type traits, and muscular development in Charolais cattle. Behavior traits, including aggressiveness at parturition, aggressiveness during gestation period, and maternal care, were scored by farmers. Type traits, including udder conformation, teat, feet and legs, and locomotion, were scored by trained classifiers. Data used in the GWAS consisted of 3,274 cows with phenotypic records and genotyping information for 44,930 SNP. When SNP had a false discovery rate (FDR) smaller than 0.05, they were referred to as significant. When SNP had a FDR between 0.05 and 0.20, they were referred to as suggestive. Four significant and 12 suggestive regions were detected for aggressiveness during gestation, maternal care, udder balance, teat thinness, teat length, foot angle, foot depth, and locomotion. These 4 significant and 12 suggestive regions were not supported by other significant SNP in close proximity. No SNP with major effects were detected for behavior and type traits, and SNP associations for these traits were spread across the genome, suggesting that behavior and type traits were influenced by many genes, each explaining a small part of genetic variance. The GWAS identified 1 region on chromosome 2 significantly associated with muscular development, which included the myostatin gene (), which is known to affect muscularity. No other regions associated with muscular development were found. Results showed that the myostatin region associated with muscular development had pleiotropic effects on udder volume, teat thinness, rear leg, and leg angle.

[Osteo-cutaneous Mycobacterium marinum infection of the elbow and reconstruction with radial collateral artery perforator-based propeller flap]. / Infection ostéo-cutanée du coude à Mycobacterium marinum et reconstruction par un lambeau en hélice basé sur une perforante de l'artère collatérale radiale postérieure.

Mycobacterium marinum is an atypical and non-tuberculosis mycobacterium that mainly leads to cutaneous infections. Infections occur through inoculation of the organism through injury to the skin in the presence of contaminated water or fish. The patient often presents with unspecific symptoms and the evolution, in the absence of adequate treatment, is characterized by an expansion of the cutaneous lesion and a spread to deep structures. Infections of tendon sheaths and joints are described, rarely osteomyelitis. Sure diagnosis is hard to obtain and is established from the medical history and microbiological examination. There are no specific therapeutic guidelines. Double or triple antibiotherapy is often effective and should be continued several months after complete resolution of clinical signs. Surgical debridement is required in cases of invasive or resistant infections. We report the case of a young immunocompetent fishmonger with a rare osteocutaneous M. marinum infection of the elbow. Treatment included large surgical excision of infected skin and bone areas and a triple antibiotics administration. Reconstruction have been ensured by a radial collateral artery perforator-based propeller flap, satisfying appropriates functional and cosmetical concerns of this anatomical region. Surgery and appropriate antibiotics treatment were effective and allowed healing of an invasive cutaneous and bone M. marinum infection.

Genetic parameters for large-scale behavior traits and type traits in Charolais beef cows.

In the last decades, beef cattle breeding mainly focused on improving production and reproduction traits. Nowadays, there is a growing interest to include behavior and type traits in the breeding goal. There is an interest in behavior as it is associated with human safety and workability and in type traits as they might be associated with longevity of cows. The objective of the current study was to estimate the heritability for behavior and type traits in Charolais and to estimate the genetic correlations among these traits. Behavior traits, including aggressiveness at parturition, aggressiveness during gestation period, and maternal care, were scored by farmers using an on-farm recording system to enable large-scale collection of phenotypes. Type traits, including udder traits ( = 3), teat traits (3), feet and leg traits (5), and locomotion (1), were scored by 10 trained classifiers. Data was available on 6,649 cows in parity 1 to 12 and located in 380 herds. Results showed that differences between herds explained up to 23% of the total phenotypic variance in behavior traits. This might be due to differences in management or to consistent differences in scoring between farmers. Aggressiveness at parturition had higher heritability (0.19) and higher genetic coefficient of variation (CV = 11%) than aggressiveness during gestation ( = 0.06 and CV = 4%) and maternal care ( = 0.02 and CV = 2%). Heritabilities for udder traits (0.14 to 0.20) and teat traits (0.17 to 0.35) were higher than for feet and leg traits (0.02 to 0.19). Genetic coefficients of variation for udder and teat traits were also higher (up to 21%) than for feet and leg traits (up to 11%). Strong genetic correlations were found between behavior traits (with absolute values from 0.71 to 0.98). The genetic correlations indicate that it is difficulty to simultaneously improve maternal care and reduce aggressiveness. We concluded that there are good opportunities to implement selection for improved udder and teat traits and against aggressiveness at parturition using a simple on-farm recording system of behavior.

Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in motor rehabilitation after stroke: an update.

Stroke is a leading cause of adult motor disability. The number of stroke survivors is increasing in industrialized countries, and despite available treatments used in rehabilitation, the recovery of motor functions after stroke is often incomplete. Studies in the 1980s showed that non-invasive brain stimulation (mainly repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) could modulate cortical excitability and induce plasticity in healthy humans. These findings have opened the way to the therapeutic use of the 2 techniques for stroke. The mechanisms underlying the cortical effect of rTMS and tDCS differ. This paper summarizes data obtained in healthy subjects and gives a general review of the use of rTMS and tDCS in stroke patients with altered motor functions. From 1988 to 2012, approximately 1400 publications were devoted to the study of non-invasive brain stimulation in humans. However, for stroke patients with limb motor deficit, only 141 publications have been devoted to the effects of rTMS and 132 to those of tDCS. The Cochrane review devoted to the effects of rTMS found 19 randomized controlled trials involving 588 patients, and that devoted to tDCS found 18 randomized controlled trials involving 450 patients. Without doubt, rTMS and tDCS contribute to physiological and pathophysiological studies in motor control. However, despite the increasing number of studies devoted to the possible therapeutic use of non-invasive brain stimulation to improve motor recovery after stroke, further studies will be necessary to specify their use in rehabilitation.

Reducible valgus flat-foot: assessment of posterior subtalar joint surface displacement by posterior arthroscopy during sinus tarsi expansion screwing.

INTRODUCTION: Subtalar arthroereisis corrects childhood and adult reducible valgus flat-foot in certain indications. Inserting an expansion screw in the sinus tarsi simultaneously corrects the calcaneal valgus of the talocalcaneal divergence and first-ray pronation if these are reducible. The displacement induced in the posterior subtalar joint (decoaptation, translation, rotation) is, however, poorly known. The present study involved arthroscopic assessment of posterior subtalar joint surface displacement during insertion of a talocalcaneal arthroereisis screw, with the hypothesis that displacement varies in three dimensions according to screw size. MATERIAL AND METHOD: Eight specimens were used for the study. All ankles were supple, taken from adult subjects. A 4.5-mm arthroscope was used and measurements were taken with a graduated palpator in the posterior subtalar joint. Three sinus tarsi expansion screws of incremental diameter were assessed. Before and after insertion measurements were made of posterolateral and posteromedial talar exposure on the calcaneus, anteroposterior and lateromedial translation, and talocalcaneal joint-line opening. RESULTS: Medial rotation, varization and anterior translation of the calcaneus were comparable in all cases. Mean lateral opening of the posterior subtalar joint was 0.88 mm with 8-mm screws and 1.25 mm with 16-mm screws. Significant differences between 8 and 16 mm screws were found for lateral subtalar joint opening (P=0.028) and for lateromedial translation (P=0.004). CONCLUSION: Sinus tarsi expansion screwing corrects hindfoot valgus and talocalcaneal divergence by inducing medial translation of the calcaneus under the talus and talar medial rotation and varization, proportional to screw size (medial translation and lateral opening of the subtalar joint). LEVEL OF EVIDENCE: III.

Accuracy of genomic prediction when combining two related crossbred populations.

Charolais bulls are selected for their crossbreed performance when mated to Montbéliard or Holstein dams. To implement genomic prediction, one could build a reference population for each crossbred population independently. An alternative could be to combine both crossbred populations into a single reference population to increase size and accuracy of prediction. The objective of this study was to investigate the accuracy of genomic prediction by combining different crossbred populations. Three scenarios were considered: 1) using 1 crossbred population as reference to predict phenotype of animals from the same crossbred population, 2) combining the 2 crossbred populations into 1 reference to predict phenotype of animals from 1 crossbred population, and 3) using 1 crossbred population as reference to predict phenotype of animals from the other crossbred population. Traits studied were bone thinness, height, and muscular development. Phenotypes and 45,117 SNP genotypes were available for 1,764 Montbéliard × Charolais calves and 447 Holstein × Charolais calves. The population was randomly spilt into 10 subgroups, which were assigned to the validation one by one. To allow fair comparison between scenarios, size of the reference population was kept constant for all scenarios. Breeding values were estimated with BLUP and genomic BLUP. Accuracy of prediction was calculated as the correlation between the EBV and the phenotypic values of the calves in the validation divided by the square root of the heritability. Genomic BLUP showed higher accuracies (between 0.281 and 0.473) than BLUP (between 0.197 and 0.452). Accuracies tended to be highest when prediction was within 1 crossbred population, intermediate when populations were combined into the reference population, and lowest when prediction was across populations. Decrease in accuracy from a prediction within 1 population to a prediction across populations was more pronounced for bone thinness (-27%) and height (-29%) than for muscular development (-14%). Genetic correlation between the 2 crossbred populations was estimated using pedigree relationships. It was 0.70 for bone thinness, 0.80 for height, and 0.99 for muscular development. Genetic correlation indicates the expected gain in accuracy of prediction when combining different populations into 1 reference population. The larger the genetic correlation is, the larger the benefit is to combine populations for genomic prediction.

Alumina-zirconia composites functionalized with laminin-1 and laminin-5 for dentistry: effect of protein adsorption on cellular response.

The present paper describes a study on laminin interaction with the surface of two alumina-zirconia composites with different percentages of ZrO2, both with submicrometric grain size. As major molecules within the basement membrane (BM), laminins are important protein fragments for epithelial cell adhesion and migration. On the other hand, alumina-zirconia composites are very attractive materials for dental applications due to their esthetic and mechanical properties. X-Ray photoelectron spectroscopy and atomic force microscopy were used to study the adsorption of two types of laminin, laminin-1 (Ln-1) and laminin-5 (Ln-5), onto the ceramics surfaces. The in vitro cell response was determined by intracellular phosphorylation of major kinases. Ceramics samples functionalized with laminins showed better cellular activation than untreated specimens; furthermore, cellular activation was found to be greater for the composite with higher percentage in zirconia when functionalized with Ln-5, whereas the adsorption of Ln-1 resulted in a greater activation for the alumina-rich oxide.