A preliminary approach to embryonic development of Austrolebias wolterstorffi, an endangered neotropical annual fish species.

Annual fish live exclusively in temporary wetlands and are among the shortest-lived vertebrates in the world. These fish persist in these habitats due to drought-resistant eggs, that which, through diapauses are able to detect stimuli from the environment to start the development processes. They are also able to direct their embryonic development in different trajectories with different development times. Our objective in this paper was to describe the different stages of embryonic development of Austrolebias wolterstorffi, a critically endangered annual fish. A total of 27 stages of embryonic development were identified for the two observed developmental pathways (direct and diapause 2). Of these 27 developmental stages observed, 24 were identical between the two types of trajectories and three different. A total of 90% of the embryos that completed their development proceeded normally, without pauses. One embryo had a different development from the others, entering diapause 2, with a pause in development for 48 h. Although the embryonic development of A. wolterstorffi is similar to that of other Neotropical annual fish species, the diapause 2 occurs when the embryo has a large body size and a well-developed brain, indicating that the lack of embryonic information of the genus Austrolebias may hide characteristics still undescribed or even different survival strategies than what has been observed for other annual fish.

Non-invasive fetal monitoring: Fetal Heart Rate multimodal estimation from abdominal electrocardiography and phonocardiography.

BACKGROUND: Fetal cardiac well-being is essential during labor as the delivery is at risk for fetal distress. Continuous monitoring by cardiotocography (CTG) is daily used to record the fetal heart rate (FHR) but this technique has important drawbacks in clinical use. OBJECTIVES: We propose to monitor FHR with a non-invasive technique, using multimodal recordings of the fetus cardiac activity, associating electrocardiographic (ECG) and phonocardiographic (PCG) sensors. The aim of this study is to evaluate the quality of these multimodal FHR estimations by comparison with CTG, based on clinical criteria. METHODS: A clinical protocol was established and a prospective open label study was carried out in the University Hospital of Grenoble. The objective was to record thoracic and abdominal PCG and ECG signals on pregnant women over 37 WG (weeks of gestation), simultaneously with CTG recordings. Adapted signal processing algorithms were then applied on abdominal PCG and ECG signals to extract FHR. Quantitative evaluation was carried out on FHR estimations compared with FHR extracted from CTG. RESULTS: A total of 40 recordings were performed. Due to technical mistakes the analysis was made possible for 38. 35 recordings allowed a FHR follow-up by ECG or PCG, 30 recordings allowed a FHR follow-up by PCG only, 25 recordings allowed a FHR follow-up by ECG only and 20 recordings allowed a FHR follow-up by both ECG and PCG. CONCLUSION: Reliable multimodal recording of FHR associating ECG and PCG sensors is possible during the last month of pregnancy. These positive results encourage the study of multimodal FHR recording during labor and delivery.

Femoral fracture during breech vaginal delivery: A case report.

Femoral fracture is a rare but significant foetal injury, more frequent and likely to happen when the foetus is malpositioned or in a breech presentation. Cesarian section does not appear to be protective and all recent publications report cases occurring during cesarian section. We report a case that occurred in a vaginal delivery of a single footling breech presentation. This complication allows us to remind that femur fracture is a complication of breech delivery whatever the modality. The prognosis is good with early diagnosis.

[Giant condyloma acuminatum in pregnancy]. / La tumeur de Buschke Lowenstein chez la femme enceinte.

Buschke Lownestein's tumour is a giant acuminate condyloma characterised by its degenerative potential, its invasive nature and its recurrence after treatment. It is a rare condition, transmitted mainly by sexual transmission and induced by to the human papillomavirus (HPV). The discussion will be illustrated by a clinical case The treatment is still under discussion but surgery seems to be the best option. Management during pregnancy is more complex since it must take into account the mother and her fetus. The delivery route is still debated. The post-treatment evolution was satisfactory and without recurrence until the delivery which, due to the antecedent of 3 caesarean sections, was carried out by cesarean section. HPV vaccination, sex education and early treatment of condyloma lesions should prevent and in any case improve the prognosis of this disease.

[Introduction of the Couder manoeuvre and perineal injuries]. / Introduction de la manœuvre de Couder et évolution des lésions périnéales.

OBJECTIVE: To analyse the introduction of the Couder manoeuvre in our level 3 maternity unit shortly after its introduction in 2019. Then, to evaluate and compare the rate of perineal injuries between 2017, when the manoeuvre was not performed at all, and 2020. MATERIALS AND METHOD: A single-centre retrospective study of patients who delivered a singleton eutociously at term from 1 January to 31 December 2017 and 2020. RESULTS: In total, 2930 records were analysed. The Couder manoeuvre rate was 32.12% in 2020. A change in the distribution of perineal lesions was observed: the rate of intact perineum increased (P<0.001), while 2nd degree lesions decreased between 2017 and 2020 (P<0.05). The 1st degree perineum and obstetric anal sphincter injuries remained stable. The rate of episiotomy decreased significantly by almost a factor of 7. CONCLUSION: The practice of the Couder manoeuvre can be implemented fairly quickly after training of the actors with nearly a third of normal deliveries at term concerned one year after its introduction. This manoeuvre seems, in our practice, to have contributed to the reduction, as previously reported, of the rate of second degree perineal injuries.

Spider silk nerve graft promotes axonal regeneration on long distance nerve defect in a sheep model.

Peripheral nerve injuries with substantial tissue loss require autologous nerve transplantation or alternatively reconstruction with nerve conduits. Axonal elongation after nerve transection is about 1 mm/day. The precise time course of axonal regeneration on an ultrastructural level in nerve gap repair using either autologous or artificial implants has not been described. As peripheral nerve regeneration is a highly time critical process due to deterioration of the neuromuscular junction, this in vivo examination in a large animal model was performed in order to investigate axonal elongation rates and spider silk material degradation in a narrowly delimited time series (20, 30, 40, 50, 90, 120, 150 and 180 days) by using a novel spider silk based artificial nerve graft as a critical prerequisite for clinical translation. Autologous nerves or artificial nerve conduits based on spider silk of the spider species Trichonephila edulis were transplanted in a 6.0 cm nerve defect model in the black headed mutton. At each of the post-implant time point, electrophysiology recordings were performed to assess functional reinnervation of axonal fibers into the implants. Samples were analyzed by histology and immunofluorescence in order to verify the timeline of axonal regeneration including axonal regeneration rates of the spider silk implant and the autologous transplant groups. Spider silk was degraded within 3 month by a light immune response mainly mediated by Langhans Giant cells. In conjunction with behavioral analysis and electrophysiological measurements, the results indicate that the spider silk nerve implant supported an axonal regeneration comparable to an autologous nerve graft which is the current gold standard in nerve repair surgery. These findings indicate that a biomaterial based spider silk nerve conduit is as effective as autologous nerve implants and may be an important approach for long nerve defects.

[IVOM quality assurance in Westfalen-Lippe : Structure of quality assurance and results of the pilot study Q-VERA]. / Intravitreale operative Medikamenteneingabe (IVOM) ­ Qualitätssicherung in Westfalen-Lippe : Aufbau der Qualitätssicherung und Ergebnisse der Pilotstudie Q-VERA.

BACKGROUND: The KVWL-QS assists ophthalmologists in the transfer for good clinical praxis into real life. In addition the QS-commission initiated a pilotstudy "Qualitäts-Versorgung bei AMD" (Q­VERA) in order to test new instruments for improvements. It was analized, if Reading Center (RC) based controls in combination with specific case-management modules can improve the results of IVOM treatment. PATIENTS AND METHODS: In 5 treatment centers 878 consecutive patients with newly diagnosed AMD (Neu-Patienten) were included, who were treated with the IVAN-scheme. Initial FA and OCT images were transferred electronically to the RC. Also 781 retreatment patients (mean 20.7 IVOM before) with retreatment due to lesion activity were observed. RESULTS: In 5% of the 878 newly treated patients a discrepancy between RC and treatment center was recorded. In this group the 481 patients, who finished up to the analysis date the 12-month follow-up, the visual function (increase in BCVA) and SD-OCT (reduction in central retinal thickness) results were comparable with large prospective cohorts. This was achieved with 6.5 injections and 10.6 visits over 12 months. In the group of 781 patients with repeated injections the number of injections over 12 months was 7.7 and the number of visits 11.6. CONCLUSION: Quality assessment can improve the efficacy of IVOM therapy for AMD patients in real life. In addition to existing structures, electronical exchange by a RC assisted evaluation can further improve the quality by reducing the number of unnecessary treatment visits. The case-management with adherence control, re-call-system and specific information for patients and relatives can specifically increase the long-term adherence and thus the success of the therapy.

Obstetric outcomes associated with induction of labour after caesarean section.

PURPOSE: To evaluate the efficiency and safety of inducing labour with oxytocin in women with a single prior Caesarean section, with particular focus on the Bishop score. METHODS: Between January 1, 2013 and March 31, 2017, we included all women with a singleton full-term pregnancy and single prior Caesarean section in this monocentric retrospective observational study. Women for whom vaginal delivery was not recommended and those who went into spontaneous labour were excluded. The choice between induction of labour and caesarean section was made by the obstetrician and the patient, taking into account both the patient's personal medical history and the clinical observations on admission to hospital. The primary outcome was the rate of vaginal delivery. RESULTS: Out of 966 women with no contraindication to trial of labour after previous caesarean delivery (TOLAC), 248 were induced, with a vaginal delivery rate of 58.5% (95% CI [52.06; 64.67]). This rate was 81.7% (67/82) among women with Bishop ≥6 and 47% (78/166) if Bishop was <6. Eight cases of uterine rupture were reported in the induction of labour group. Regarding maternal morbidity, this was the main difference between the caesarean section and the induction of labour groups (p=0.049). Neonatal morbidity was low in both groups. CONCLUSIONS: The rate of vaginal delivery after induction of labour with oxytocin infusion was satisfactory. Nevertheless, maternal morbidity and especially the risk of uterine rupture were not minor. It is thus essential before inducing labour to inform the woman about the rate of success of TOLAC and the risks of uterine rupture.

Non-invasive fetal monitoring using electrocardiography and phonocardiography: A preliminary study.

BACKGROUND: Continuous fetal monitoring is commonly used during pregnancy and labor to assess fetal wellbeing. The most often used technology is cardiotocography (CTG), but this technique has major drawbacks in clinical use. OBJECTIVES: Our aim is to test a non-invasive multimodal technique of fetal monitoring using phonocardiography (PCG) and electrocardiography (ECG) and to evaluate its feasibility in clinical practice, by comparison with CTG. METHODS: This prospective open label study took place in a French university hospital. PCG and ECG signals were recorded using abdominal and thoracic sensors from antepartum women during the second half of pregnancy, simultaneously with CTG recording. Signals were then processed to extract fetal PCG and ECG and estimate fetal heart rate (FHR). RESULTS: A total of 9 sets of recordings were evaluated. Very accurate fetal ECG and fetal PCG signals were recorded, enabling us to obtain FHR for several subjects. The FHR calculated from ECG was highly correlated with the FHR from the CTG reference (from 74% to 84% of correlation). CONCLUSION: This work with preliminary signal processing algorithms proves the feasibility of the approach and constitutes the beginnings of a unique database that is needed to improve and validate the signal processing algorithms.

[Use of hydroxychloroquine and prednisone in the presence of serum autoimmunity in female infertility]. / Utilisation de l'hydroxychloroquine et de la prednisone en présence d'une auto-immunité sérique dans l'infertilité féminine.

OBJECTIVE: Presence of non-specific autoimmunity (antinuclear antibodies without antigenic specificities and/or antiphospholipid antibodies without criteria of antiphospholipid syndrome) seems to be associated with unexplained female infertility. The objective is to study the characteristics of patients who undergone treatment for non-specific antibodies in Medically Assisted Procreation (MAP). METHODS: Ten patients were prospectively followed at MAP center of Grenoble University Hospital. Patient characteristics were collected and evaluated. All patients had a consultation in internal medicine unit as well as an autoimmune assessment (antinuclear antibodies, APL especially) in search of defined autoimmune disease (exclusion criterion). The treatments undertaken were at clinician' discretion. RESULTS: One patient received quadritherapy (heparin, platelet antiaggregant, prednisone and hydroxychloroquine), 5 received triple therapy, 3 had dual therapy, and one patient had prednisone only. The 10 patients had a pregnancy under treatment, 8 of which were completed without complications. The control of autoimmunity under treatment appears to show a decrease in serum antibody levels. Tolerance was good (delayed hypersensitivity to hydrochloroquine resulted in discontinuation of therapy in only one patient). CONCLUSION: The presence of non-specific serum autoimmunity in a context of infertility appears to be pathogenic and immunomodulatory treatments are clinically and/or biologically effective. A prospective and interventional study with a larger number of patients is needed to assess the efficacy of such treatments in patients with unexplained infertility.

Integration of Murine and Human Studies for Mapping Periodontitis Susceptibility.

Periodontitis is one of the most common inflammatory human diseases with a strong genetic component. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWASs) of chronic periodontitis (CP) have largely been unsuccessful in identifying common susceptibility factors. A combination of quantitative trait loci (QTL) mapping in mice with association studies in humans has the potential to discover novel risk loci. To this end, we assessed alveolar bone loss in response to experimental periodontal infection in 25 lines (286 mice) from the Collaborative Cross (CC) mouse population using micro-computed tomography (µCT) analysis. The orthologous human chromosomal regions of the significant QTL were analyzed for association using imputed genotype data (OmniExpress BeadChip arrays) derived from case-control samples of aggressive periodontitis (AgP; 896 cases, 7,104 controls) and chronic periodontitis (CP; 2,746 cases, 1,864 controls) of northwest European and European American descent, respectively. In the mouse genome, QTL mapping revealed 2 significant loci (-log P = 5.3; false discovery rate = 0.06) on chromosomes 1 ( Perio3) and 14 ( Perio4). The mapping resolution ranged from ~1.5 to 3 Mb. Perio3 overlaps with a previously reported QTL associated with residual bone volume in F2 cross and includes the murine gene Ccdc121. Its human orthologue showed previously a nominal significant association with CP in humans. Use of variation data from the genomes of the CC founder strains further refined the QTL and suggested 7 candidate genes ( CAPN8, DUSP23, PCDH17, SNORA17, PCDH9, LECT1, and LECT2). We found no evidence of association of these candidates with the human orthologues. In conclusion, the CC populations enabled mapping of confined QTL that confer susceptibility to alveolar bone loss in mice and larger human phenotype-genotype samples and additional expression data from gingival tissues are likely required to identify true positive signals.

Whole angiosperms Wolffia columbiana disperse by gut passage through wildfowl in South America.

For the first time to our knowledge, we demonstrate that whole angiosperm individuals can survive gut passage through birds, and that this occurs in the field. Floating plants of the genus Wolffia are the smallest of all flowering plants. Fresh droppings of white-faced whistling duck Dendrocygna viduata ( n = 49) and coscoroba swan Coscoroba coscoroba ( n = 22) were collected from Brazilian wetlands. Intact Wolffia columbiana were recovered from 16% of D. viduata and 32% of Coscoroba samples (total = 164 plantlets). The viability of plants was tested, and asexual reproduction was confirmed. Wolffia columbiana is an expanding alien in Europe. Avian endozoochory of asexual angiosperm propagules may be an important, overlooked dispersal means for aquatic plants, and may contribute to the invasive character of alien species.

[CAVE - A checklist system for preoperative risk evaluation : Guideline-conform cardiopulmonary diagnostics before general and visceral surgical interventions]. / CAVE ­ Ein Checklistensystem zur präoperativen Risikoevaluation : Leitliniengerechte kardiopulmonale Diagnostik vor allgemein- und viszeralchirurgischen Eingriffen.

BACKGROUND: Preoperative evaluation of patient risk is an essential component of patient preparation before surgery. Guidelines provide evidence-based algorithms for preoperative assessment of cardiac risk; however, even experienced physicians correctly apply evidence-based algorithms in only 50% of all cases or less. OBJECTIVE: A checklist system for guideline-based cardiopulmonary risk evaluation in adult patients undergoing abdominal or visceral surgery (CAVE checklists) was created to assist in preoperative cardiopulmonary risk assessment and increase correct application of evidence-based algorithms before elective visceral surgery. MATERIAL UND METHODS: International guidelines were transformed into a checklist system. These checklists were than evaluated in a department of general and visceral surgery. The main goal was to determine whether preoperative examinations, such as electrocardiograph (ECG), chest-x-ray, spirometry and advanced assessment by a cardiologist, are performed according to evidence-based guidelines. The frequency of recommended as well as unnecessary and missed examinations was assessed. RESULTS: In this study 541 patients with a median age of 64.5 years (interquartile range: 52-73 years) were examined using the checklist system. Of the patients 90.4% underwent ECG and 98.5% chest-X-ray as recommended in the guidelines. Spirometry was not recommended in any patient and not performed in any case. Advanced assessment by a cardiologist was performed in 45.5% of cases as recommended in the guidelines. When guidelines did not recommend ECG, x­ray, spirometry or advanced cardiac assessment, 69.4%, 99.6%, 99.3% and 99.8% of patients, respectively, actually did not receive these examinations. Only 2.8% of all patients did not receive an examination that was recommended by the guidelines: 1.5% ECG, 0.2% x­ray and 1.1% advanced cardiological assessment. None of these patients suffered from postoperative cardiopulmonary complications. CONCLUSION: These simple checklists are easy to use and provide a higher degree of evidence-based preoperative cardiopulmonary risk evaluation than previously reported in the literature. Adaptation of the checklists to changing guidelines is easy to perform. Whether the application of these checklists will result in a reduction of morbidity and costs have to be determined in further clinical trials.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Applications of Mass Spectrometry Imaging to Cancer.

Pathologists play an essential role in the diagnosis and prognosis of benign and cancerous tumors. Clinicians provide tissue samples, for example, from a biopsy, which are then processed and thin sections are placed onto glass slides, followed by staining of the tissue with visible dyes. Upon processing and microscopic examination, a pathology report is provided, which relies on the pathologist's interpretation of the phenotypical presentation of the tissue. Targeted analysis of single proteins provide further insight and together with clinical data these results influence clinical decision making. Recent developments in mass spectrometry facilitate the collection of molecular information about such tissue specimens. These relatively new techniques generate label-free mass spectra across tissue sections providing nonbiased, nontargeted molecular information. At each pixel with spatial coordinates (x/y) a mass spectrum is acquired. The acquired mass spectrums can be visualized as intensity maps displaying the distribution of single m/z values of interest. Based on the sample preparation, proteins, peptides, lipids, small molecules, or glycans can be analyzed. The generated intensity maps/images allow new insights into tumor tissues. The technique has the ability to detect and characterize tumor cells and their environment in a spatial context and combined with histological staining, can be used to aid pathologists and clinicians in the diagnosis and management of cancer. Moreover, such data may help classify patients to aid therapy decisions and predict outcomes. The novel complementary mass spectrometry-based methods described in this chapter will contribute to the transformation of pathology services around the world.

Altered immune reconstitution of B and T cells precedes the onset of clinical symptoms of chronic graft-versus-host disease and is influenced by the type of onset.

We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/µl; 136/µl, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/µl; 54.3/µl) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/µl) compared to those in pts without (1.25% and 9.06/µl) or with quiescent onset of cGVHD (1.15% and 6.91/µl). Finally, relative B cell counts, including naïve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.

Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma.

Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used. For AL amyloidosis, single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at P<10-5 with homogeneity of results from the 3 sample sets; some of these were previously documented to influence MM risk, including the SNP at the IRF4 binding site. In AL amyloidosis, rs9344 at the splice site of cyclin D1, promoting translocation (11;14), reached the highest significance, P=7.80 × 10-11; the SNP was only marginally significant in MM. SNP rs79419269 close to gene SMARCD3 involved in chromatin remodeling was also significant (P=5.2 × 10-8). These data provide evidence for common genetic susceptibility to AL amyloidosis and MM. Cyclin D1 is a more prominent driver in AL amyloidosis than in MM, but the links to aggregation of light chains need to be demonstrated.