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Objective: We used machine learning to develop and validate a multivariable algorithm allowing the accurate and early prediction of postoperative hypocalcemia risk. Background: Postoperative hypocalcemia is frequent after total thyroidectomy. An early and accurate individualized prediction of the risk of hypocalcemia could guide the selective prescription of calcium supplementation only to patients most likely to present with hypocalcemia after total thyroidectomy. Methods: This retrospective study enrolled all patients undergoing total thyroidectomy in a single referral center between November 2019 and March 2022 (derivation cohort) and April 2022 and September 2022 (validation cohort). The primary study outcome was postoperative hypocalcemia (serum calcium under 80 mg/L). Exposures were multiple clinical and biological variables prospectively collected and analyzed with various machine learning methods to develop and validate a multivariable prediction algorithm. Results: Among 610/118 participants in the derivation/validation cohorts, 100 (16.4%)/26 (22%) presented postoperative hypocalcemia. The most accurate prediction algorithm was obtained with random forest and combined intraoperative parathyroid hormone measurements with 3 clinical variables (age, sex, and body mass index) to calculate a postoperative hypocalcemia risk for each patient. After multiple cross-validation, the area under the receiver operative characteristic curve was 0.902 (0.829--0.970) in the derivation cohort, and 0.928 (95% CI: 0.86; 0.97) in the validation cohort. Postoperative hypocalcemia risk values of 7% (low threshold) and 20% (high threshold) had, respectively, a sensitivity of 92%, a negative likelihood ratio of 0.11, a specificity of 90%, and a positive of 7.6 for the prediction of postoperative hypocalcemia. Conclusions: Using machine learning, we developed and validated a simple multivariable model that allowed the accurate prediction of postoperative hypocalcemia. The resulting algorithm could be used at the point of care to guide clinical management after total thyroidectomy. [ABSTRACT FROM AUTHOR]

Objective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases. Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management. Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers. Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n = 1203, 47.8%) and renal cancer (n = 555, 22.1%). One-year survival was 84.3% (n = 2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n = 32) and 29.9% (n = 753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates (P = 0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio = 0.64; P = 0.031) and incomplete resection ( ≥R1; hazard ratio = 0.41; P = 0.015). Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery. [ABSTRACT FROM AUTHOR]

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

Abstract A novel DNA methylation class of tumor within the central nervous system, the "neuroepithelial tumor (NET), PATZ1 fusion-positive” has recently been identified in the literature, characterized by EWSR1- and MN1-PATZ1 fusions. The cellular origin of this tumor type remains unknown, wavering between glioneuronal or mesenchymal (as round cell sarcomas with EWSR1-PATZ1 of the soft tissue). Because of the low number of reported cases, this tumor type will not be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS). Herein, we report one case of a CNS tumor classified by DNA methylation analysis as NET-PATZ1 but harboring a novel LARGE1-AFF2 fusion which has until now never been described in soft tissue or the CNS. We compare its clinical, histopathological, immunophenotypical, and genetic features with those previously described in NET-PATZ1. Interestingly, the current case presented histopathological (astroblastoma-like features, glioneuronal phenotype), clinical (with a favorable course), genetic (1p loss), and epigenetic (DNA-methylation profiling) similarities to previously reported cases of NET-PATZ1. Our results added data suggesting that different histomolecular tumor subtypes seem to be included within the methylation class “NET, PATZ1 fusion-positive”, including non PATZ1 fusions, and that further cases are needed to better characterize them.

Background. The incidence of diabetes mellitus (both pregestational and gestational) is increasing worldwide, and hyperglycemia during pregnancy is associated with adverse pregnancy outcomes. Evidence on the safety and efficacy of metformin during pregnancy has accumulated resulting in an increase in its prescription in many reports. Aims. We aimed to determine the prevalence of antidiabetic drug use (insulins and blood glucose-lowering drugs) before and during pregnancy in Switzerland and the changes therein during pregnancy and over time. Methods. We conducted a descriptive study using Swiss health insurance claims (2012-2019). We established the MAMA cohort by identifying deliveries and estimating the last menstrual period. We identified claims for any antidiabetic medication (ADM), insulins, blood glucose-lowering drugs, and individual substances within each class. We defined three groups of pattern use based on timing of dispensation: (1) dispensation of at least one ADM in the prepregnancy period and in or after trimester 2 (T2) (pregestational diabetes); (2) dispensation for the first time in or after T2 (GDM); and (3) dispensation in the prepregnancy period and no dispensation in or after T2 (discontinuers). Within the pregestational diabetes group, we further defined continuers (dispensation for the same group of ADM) and switchers (different ADM group dispensed in the prepregnancy period and in or after T2). Results. MAMA included 104,098 deliveries with a mean maternal age at delivery of 31.7. Antidiabetic dispensations among pregnancies with pregestational and gestational diabetes increased over time. Insulin was the most dispensed medication for both diseases. Between 2017 and 2019, less than 10% of pregnancies treated for pregestational diabetes continued metformin rather than switching to insulin. Metformin was offered to less than 2% of pregnancies to treat gestational diabetes (2017-2019). Conclusion. Despite its position in the guidelines and the attractive alternative that metformin represents to patients who may encounter barriers with insulin therapy, there was reluctance to prescribe it.

The architectural study of the inner castle of Belvoir revealed a construction site that was built from the outer wall. The stones used came from local quarries. Although only the ground floor of the fortification remains, it is possible to reconstruct part of the first floor and more specifically the location of the chapel. The castle was built quickly and several retouches are clearly visible, showing an evolving architectural project. Two elements have been identified on the ground floor: the small cistern dug in the inner courtyard, connected to the large cistern in the outer enclosure, and the room reserved for the ovens, kitchen or sugar refinery.

Objective To evaluate whether urine output (UO), rarely assessed in the literature, is associated with relevant neonatal outcomes in very preterm infants, and which UO threshold may be the most clinically relevant.Design Retrospective cohort study.Setting Two Level IV neonatal intensive care units.Patients Very preterm infants born between 240/7 and 296/7 weeks of gestation documented with eight UO measurements per day between postnatal day 1 and day 7.Main outcome measures Composite outcome defined as death before discharge, or moderate to severe bronchopulmonary dysplasia, or severe brain lesions. The association between this outcome and UO was studied using several UO thresholds.Results Among 532 infants studied, UO

BackgroundInterictal epileptiform discharges are an important biomarker for localization of focal epilepsy, especially in patients who undergo chronic intracranial monitoring. Manual detection of these pathophysiological events is cumbersome, but is still superior to current rule-based approaches in most automated algorithms.ObjectiveTo develop an unsupervised machine-learning algorithm for the improved, automated detection and localization of interictal epileptiform discharges based on spatiotemporal pattern recognition.MethodsWe decomposed 24 h of intracranial electroencephalography signals into basis functions and activation vectors using non-negative matrix factorization (NNMF). Thresholding the activation vector and the basis function of interest detected interictal epileptiform discharges in time and space (specific electrodes), respectively. We used convolutive NNMF, a refined algorithm, to add a temporal dimension to basis functions.ResultsThe receiver operating characteristics for NNMF-based detection are close to the gold standard of human visual-based detection and superior to currently available alternative automated approaches (93% sensitivity and 97% specificity). The algorithm successfully identified thousands of interictal epileptiform discharges across a full day of neurophysiological recording and accurately summarized their localization into a single map. Adding a temporal window allowed for visualization of the archetypal propagation network of these epileptiform discharges.ConclusionUnsupervised learning offers a powerful approach towards automated identification of recurrent pathological neurophysiological signals, which may have important implications for precise, quantitative, and individualized evaluation of focal epilepsy.

Epilepsy is defined by the seemingly random occurrence of spontaneous seizures. The ability to anticipate seizures would enable preventative treatment strategies. A central but unresolved question concerns the relationship of seizure timing to fluctuating rates of interictal epileptiform discharges (here termed interictal epileptiform activity, IEA), a marker of brain irritability observed between seizures by electroencephalography (EEG). Here, in 37 subjects with an implanted brain stimulation device that detects IEA and seizures over years, we find that IEA oscillates with circadian and subject-specific multidien (multi-day) periods. Multidien periodicities, most commonly 20-30 days in duration, are robust and relatively stable for up to 10 years in men and women. We show that seizures occur preferentially during the rising phase of multidien IEA rhythms. Combining phase information from circadian and multidien IEA rhythms provides a novel biomarker for determining relative seizure risk with a large effect size in most subjects.

ObjectiveThe mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.MethodsWe retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.ResultsWe found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (

Abstract The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a $$p

Prematurity is a major risk factor for perinatal stress and neonatal complications leading to systemic inflammation and abnormal mother–infant interactions. Oxytocin (OT) is a neuropeptide regulating the inflammatory response and promoting mother–infant bonding. The release of this hormone might be influenced by either vocal or tactile stimulation. The main objective of the current randomized, crossover, clinical trial was to assess the salivary OT/cortisol balance in mothers following the exposure of their baby born preterm to two types of sensorial interventions: maternal voice without or with contingent tactile stimulation provided by the mother to her infant. Among the 26 mothers enrolled, maternal voice intervention alone had no effect on OT and cortisol levels in the mothers, but when associated with tactile stimulation, it induced a significant increase in maternal saliva oxytocin (38.26 ± 30.26 pg/mL before vs 53.91 ± 48.84 pg/mL after, p = 0.02), particularly in the mothers who delivered a female neonate. Maternal voice intervention induced a significant reduction in cortisol and an increase in OT levels in mothers when the maternal voice with a tactile stimulation intervention was performed first. In conclusion, exposure to the maternal voice with a contingent tactile stimulation was associated with subtle changes in the maternal hormonal balance between OT and cortisol. These findings need to be confirmed in a larger sample size and may ultimately guide caregivers in providing the best intervention to reduce parental stress following preterm delivery.

Cosechar para el mundo, pastar para la región. Una historia de globalización en los Montes de María (1850-1917), by Santiago Colmenares Guerra, Universidad Nacional de Colombia, 2023

Abstract Background Many lower-limb exoskeletons have been developed to assist gait, exhibiting a large range of control methods. The goal of this paper is to review and classify these control strategies, that determine how these devices interact with the user. Methods In addition to covering the recent publications on the control of lower-limb exoskeletons for gait assistance, an effort has been made to review the controllers independently of the hardware and implementation aspects. The common 3-level structure (high, middle, and low levels) is first used to separate the continuous behavior (mid-level) from the implementation of position/torque control (low-level) and the detection of the terrain or user’s intention (high-level). Within these levels, different approaches (functional units) have been identified and combined to describe each considered controller. Results 291 references have been considered and sorted by the proposed classification. The methods identified in the high-level are manual user input, brain interfaces, or automatic mode detection based on the terrain or user’s movements. In the mid-level, the synchronization is most often based on manual triggers by the user, discrete events (followed by state machines or time-based progression), or continuous estimations using state variables. The desired action is determined based on position/torque profiles, model-based calculations, or other custom functions of the sensory signals. In the low-level, position or torque controllers are used to carry out the desired actions. In addition to a more detailed description of these methods, the variants of implementation within each one are also compared and discussed in the paper. Conclusions By listing and comparing the features of the reviewed controllers, this work can help in understanding the numerous techniques found in the literature. The main identified trends are the use of pre-defined trajectories for full-mobilization and event-triggered (or adaptive-frequency-oscillator-synchronized) torque profiles for partial assistance. More recently, advanced methods to adapt the position/torque profiles online and automatically detect terrains or locomotion modes have become more common, but these are largely still limited to laboratory settings. An analysis of the possible underlying reasons of the identified trends is also carried out and opportunities for further studies are discussed.

Abstract Background The phenotype of an individual can be affected not only by the individual’s own genotypes, known as direct genetic effects (DGE), but also by genotypes of interacting partners, indirect genetic effects (IGE). IGE have been detected using polygenic models in multiple species, including laboratory mice and humans. However, the underlying mechanisms remain largely unknown. Genome-wide association studies of IGE (igeGWAS) can point to IGE genes, but have not yet been applied to non-familial IGE arising from “peers” and affecting biomedical phenotypes. In addition, the extent to which igeGWAS will identify loci not identified by dgeGWAS remains an open question. Finally, findings from igeGWAS have not been confirmed by experimental manipulation. Results We leverage a dataset of 170 behavioral, physiological, and morphological phenotypes measured in 1812 genetically heterogeneous laboratory mice to study IGE arising between same-sex, adult, unrelated mice housed in the same cage. We develop and apply methods for igeGWAS in this context and identify 24 significant IGE loci for 17 phenotypes (FDR

Abstract Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9–9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0–7.0] and diabetes [aOR2.2, 95% CI 1.1–4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.

Abstract This study intend to compare the long-term psychological impact (depression, post-traumatic stress disorder) on both partners between patients that underwent uterine artery embolization (UAE) for post-partum hemorrhage (PPH) and uneventful deliveries. Women who experienced severe PPH treated by UAE in our institution between 2003 and 2013 were identified in our obstetrical database. These cases were matched to controls with uneventful deliveries. Matching criteria were maternal age, parity, ethnicity, year of delivery, birthweight, gestational age and mode of delivery. Patients and their partners completed validated questionnaires measuring post-traumatic stress (TSQ), as well as depression symptoms (MINI). A total of 63 cases of PPH and 189 matched controls (1:3) participated in a study exploring gynecological and obstetrical outcomes. With a mean of 8 years post-index delivery, patients after PPH showed increased risk of depression (p = 0.015) and post-traumatic stress disorder (22.2% versus 4.8%, p

Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.

Humans are adept at understanding speech despite the fact that our natural listening environment is often filled with interference. An example of this capacity is phoneme restoration, in which part of a word is completely replaced by noise, yet listeners report hearing the whole word. The neurological basis for this unconscious fill-in phenomenon is unknown, despite being a fundamental characteristic of human hearing. Here, using direct cortical recordings in humans, we demonstrate that missing speech is restored at the acoustic-phonetic level in bilateral auditory cortex, in real-time. This restoration is preceded by specific neural activity patterns in a separate language area, left frontal cortex, which predicts the word that participants later report hearing. These results demonstrate that during speech perception, missing acoustic content is synthesized online from the integration of incoming sensory cues and the internal neural dynamics that bias word-level expectation and prediction.

The diet and age of mice can modulate how different genetic variants impact body weight, demonstrating the need to take context into account when performing genetic studies.

Summary: Background: Pregnant individuals with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease, prematurity, and stillbirth. In March 2021, vaccination for at risk pregnant women was recommended in Switzerland, expanding this to all pregnant women in May 2021. Our aim was to assess the safety of mRNA COVID-19 vaccines in pregnancy. Methods: This multicentre prospective cohort study describes early adverse events and perinatal outcomes in pregnant women who received at least one dose of mRNA vaccine between March 1st and December 27th, 2021 in Switzerland, using the COVI-PREG registry. Early adverse events were collected at least one month following vaccine administration. Pregnancy and neonatal outcomes were extracted from medical records using the maternity discharge letters providing follow-up information up to 5 days after birth. Findings: Of 1012 vaccinated women, 894 (88·3%) received both injections during pregnancy, with BNT162b2 (n = 271) or mRNA-1273 (n = 623) vaccines. Local events (mainly local pain) were reported in 81·3% and 80·5% after the first and second doses. Rates of systemic reactions (mainly fatigue and headache) were similar after the first dose and most frequent after the second dose of mRNA-1273. Of the 1012 women, four (0·4%; 95%CI [0·1-1·0]) severe early adverse events occurred: pulmonary embolism, preterm premature rupture of membranes, isolated fever with hospitalisation, and herpes zoster. Of 107 patients vaccinated before 14 weeks, one (0·9%; 95%CI [0·0-5·1]) early spontaneous abortions was reported (8 weeks). Of 228 vaccinated before 20 weeks one (0·4%; 95%CI [0·0-2·4]) late spontaneous abortion was reported (16 weeks). Of 513 women exposed before 37 weeks, 33 (6·4%; 95%CI [4·5-8·9]) delivered preterm. Among 530 patients exposed in pregnancy, no stillbirth was reported and 25 (4·7%; 95%CI [3·0-6·8]) neonates were admitted to intensive care unit. Interpretation: Frequent local and systemic effects were described after exposure to mRNA COVID-19 vaccines during pregnancy but severe events were rare. Women vaccinated during pregnancy did not experience higher adverse pregnancy or neonatal outcomes when compared to historical data on background risks in the obstetric population. Funding: This research was funded by a grant from the Swiss Federal Office of Public Health and the CHUV Foundation.

Summary: We present a protocol to generate an advanced ex vivo model of human placenta. We use a vibrating tissue slicer to obtain precision-cut slices representative of the entire thickness of human placenta. This approach delivers standardized cultures with a preserved microstructure and cellular composition comparable to the native tissue. We applied this system to study SARS-CoV-2 infection at the maternal-fetal interface. Moreover, this system can be used to investigate the basic functions of the human placenta in health and disease.For complete details on the use and execution of this protocol, please refer to Fahmi et al. (2021).

Abstract High‐throughput sequencing of amplicons (HTSA) has been proposed as an effective approach to evaluate taxonomic and genetic diversity at the same time. However, there are still uncertainties as to how the results produced by different bioinformatics treatments impact the conclusions drawn on biodiversity and population genetics indices. We evaluated the ability of six bioinformatics pipelines to recover taxonomic and genetic diversity from HTSA data obtained from controlled assemblages. To that end, 20 assemblages were produced using 354 colonies of Botrylloides spp., sampled in the wild in ten marinas around Brittany (France). We used DNA extracted from preservative ethanol (ebDNA) after various time of storage (3, 6, and 12 months), and from a bulk of preserved specimens (bulkDNA). DNA was amplified with primers designed for targeting this ascidian genus. Results obtained from HTSA data were compared with Sanger sequencing on individual zooids (i.e., individual barcoding). Species identification and relative abundance determined with HTSA data from either ebDNA or bulkDNA were similar to those obtained with traditional individual barcoding. However, after 12 months of storage, the correlation between HTSA and individual‐based data was lower than after shorter durations. The six bioinformatics pipelines were able to depict accurately the genetic diversity using standard population genetics indices (HS and FST), despite producing false positives and missing rare haplotypes. However, they did not perform equally and dada2 was the only pipeline able to retrieve all expected haplotypes. This study showed that ebDNA is a nondestructive alternative for both species identification and haplotype recovery, providing storage does not last more than 6 months before DNA extraction. Choosing the bioinformatics pipeline is a matter of compromise, aiming to retrieve all true haplotypes while avoiding false positives. We here recommend to process HTSA data using dada2, including a chimera‐removal step. Even if the possibility to use multiplexed primer sets deserves further investigation to expand the taxonomic coverage in future similar studies, we showed that primers targeting a particular genus allowed to reliably analyze this genus within a complex community.

Abstract This study aims to evaluate the feasibility and clinical interest of shear wave elastography, by quantitatively estimating the baseline stiffness of the myometrium before and after placental expulsion. We conducted a prospective cohort study of women at term, without known risk factors for postpartum hemorrhage, who gave birth via spontaneous labor in our tertiary center. Myometrium tonicity was evaluated based on measurements of shear wave speed (SWS) in the anterior uterine corpus. All data points were collected by a single operator. Measurements were carried out at three different time points: after fetal delivery (T1), after placental delivery (T2) and 30 min after placental delivery (T3). Our primary objective was to assess the feasibility of this new imaging technique. Ten valid SWS measurements obtained at each of the three different time points were considered as a positive primary outcome. Our secondary objectives were to evaluate the difference in median myometrial shear wave velocity between each time point, as well as to determine the correlation between myometrial shear wave velocity and patients’ characteristics. 38 women were recruited during the study period, of whom 34 met the study criteria. 1017 SWS measurements were obtained. The median time to perform measurements was 16 s for one value, and 2 min 56 s for ten. For 11 women (32%) it was not possible to achieve ten SWS at T1 as placental expulsion immediately followed the birth of the newborn. One patient experienced placental retention and only measurements at T1 were performed. For all other patients, we were successfully able to obtain all measures as intended. There was no difference in the mean shear wave speed between the three time points. After adjustments for confounders, we observed a significant correlation for total blood loss (correlation coefficient = − 0.26, p

Deep brain stimulation and epidural electrical stimulation of the spinal cord enable locomotion in humans with spinal cord injury (SCI) but the potential synergy between both approaches is unclear. The authors show that a complex technological approach is required to enable volitional walking in rats with SCI.

With COVID-19 vaccination hesitancy at around 50% in the obstetric population, it is critical to identify which women should be addressed and how. Our study aimed to assess COVID-19 vaccination willingness among pregnant and postpartum women in Europe and to investigate associated determinants. This study was a cross-sectional, web-based survey conducted in Belgium, Norway, Switzerland, The Netherlands, and United Kingdom (UK) in June–August 2021. Among 3194 pregnant women, the proportions of women vaccinated or willing to be vaccinated ranged from 80.5% in Belgium to 21.5% in Norway. The associated characteristics were country of residence, chronic illness, history of flu vaccine, trimester of pregnancy, belief that COVID-19 is more severe during pregnancy, and belief that the COVID-19 vaccine is effective and safe during pregnancy. Among 1659 postpartum women, the proportions of women vaccinated or willing to be vaccinated ranged from 86.0% in the UK to 58.6% in Switzerland. The associated determinants were country of residence, chronic illness, history of flu vaccine, breastfeeding, and belief that the COVID-19 vaccine is safe during breastfeeding. Vaccine hesitancy in the obstetric population depends on medical history and especially on the opinion that the vaccine is safe and on the country of residence.

The human body is vastly colonised by microorganisms, whose impact on health is increasingly recognised. The human genital tract hosts a diverse microbiota, and an increasing number of studies on the male genital tract microbiota suggest that bacteria have a role in male infertility and pathological conditions, such as prostate cancer. Nevertheless, this research field remains understudied. The study of bacterial colonisation of the male genital tract is highly impacted by the invasive nature of sampling and the low abundance of the microbiota. Therefore, most studies relied on the analysis of semen microbiota to describe the colonisation of the male genital tract (MGT), which was thought to be sterile. The aim of this narrative review is to present the results of studies that used next-generation sequencing (NGS) to profile the bacterial colonisation patterns of different male genital tract anatomical compartments and critically highlight their findings and their weaknesses. Moreover, we identified potential research axes that may be crucial for our understanding of the male genital tract microbiota and its impact on male infertility and pathophysiology.

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Inhaled nitric oxide (iNO) is a therapy used in neonates with pulmonary hypertension. Some evidence of its neuroprotective properties has been reported in both mature and immature brains subjected to injury. NO is a key mediator of the VEGF pathway, and angiogenesis may be involved in the reduced vulnerability to injury of white matter and the cortex conferred by iNO. Here, we report the effect of iNO on angiogenesis in the developing brain and its potential effectors. We found that iNO promotes angiogenesis in the developing white matter and cortex during a critical window in P14 rat pups. This shift in the developmental program of brain angiogenesis was not related to a regulation of NO synthases by exogenous NO exposure, nor the VEGF pathway or other angiogenic factors. The effects of iNO on brain angiogenesis were found to be mimicked by circulating nitrate/nitrite, suggesting that these carriers may play a role in transporting NO to the brain. Finally, our data show that the soluble guanylate cyclase/cGMP signaling pathway is likely to be involved in the pro-angiogenetic effect of iNO through thrombospondin-1, a glycoprotein of the extracellular matrix, inhibiting soluble guanylate cyclase through CD42 and CD36. In conclusion, this study provides new insights into the biological basis of the effect of iNO in the developing brain.

Background. Sequestration of vancomycin in ST® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST® interaction was assessed using the in vitro NeckEpur® technology. Method. ST150® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were assessed in duplicate: (i) continuous diafiltration (CDF): 4 L/h, (ii) continuous dialysis (CD): 2.5 L/h post-filtration. Results. The mean initial vancomycin concentration in the central compartment (CC) was 51.4 +/− 5.0 mg/L. The mean percentage eliminated from the CC over 6 h was 91 +/− 4%. The mean clearances from the CC by CDF and CD were 2.8 and 1.9 L/h, respectively. The mean clearances assessed using cumulative effluents were 4.4 and 2.2 L/h, respectively. The mean percentages of the initial dose eliminated in the effluents from the CC by CDF and CD were 114 and 108% with no detectable sequestration of vancomycin in both modes of elimination. Discussion. Significant sequestration adds a clearance to that provided by CDF and CD. The study provides multiple evidence from the CC, the filter, and the effluents of the lack of an increase in total clearance in comparison with the flow rates without significant sequestration in the ST® filter comparing cumulative effluents to the initial dose in the CC. Conclusions. There is no evidence ST® filters directly sequestrate vancomycin.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal–fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus–infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January–July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9–57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0–15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9–5.5]).