Search

Human brain development is a complex process that begins in the third week of gestation. During early development, the fetal brain undergoes dynamic morphological changes. These changes result from events such as neurogenesis, neuronal migration, synapse formation, axonal growth and myelination. Disruption of any of these processes is thought to be responsible for a wide array of different pathologies. Recent advances in magnetic resonance imaging, especially diffusion-weighted imaging and diffusion tensor imaging (DTI), have enabled characterization and evaluation of brain development in utero. In this review, aimed at practitioners involved in fetal medicine and high-risk pregnancies, we provide a comprehensive overview of fetal DTI studies focusing on characterization of early normal brain development as well as evaluation of brain pathology in utero. We also discuss the reliability and limitations of fetal brain DTI. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies.A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9).Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances.According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

International audience; BackgroundAntenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome.MethodsWe designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks’ gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076.FindingsBetween Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI –0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI –0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3–4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.InterpretationBecause non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction.

To assess the contribution and impact of fetal magnetic resonance imaging (MRI) in managing fetal gastroschisis.We conducted an observational retrospective study of gastroschisis patients at three fetal medicine centers from 2008 to 2019. The primary endpoint was the number of cases in which the MRI provided relevant information related to gastroschisis.A total of 189 patients were included, and our study group included 38 patients who underwent MRI. For the eight patients with suspected gastroschisis, MRI confirmed the diagnosis. In six cases, it provided additional relevant information (spiral turn, intestine ischemia, and bowel size discrepancy). For the 17 patients with ultrasound signs of additional gastrointestinal anomalies, MRI detected one case of unidentified complex gastroschisis on sonography. For the 13 patients undergoing routine MRI, no significant information was obtained. One termination of pregnancy and one fetoscopy were performed a few days after the MRI results. There was no subsequent follow-up or additional bowel complications to support management.Although MRI did not change the management of pregnancies complicated by fetal gastroschisis, patients presenting with fetal gastroschisis with intraabdominal bowel dilatation could benefit from MRI to allow for more precise prenatal counseling to predict postnatal intestinal complications before birth.

Pregnancy outcomes; Vaccine effectiveness; Omicron Resultados del embarazo; Efectividad de la vacuna; Omicron Resultats de l'embaràs; Eficàcia de la vacuna; Omicron Background In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. Methods INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. Findings We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0–38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03–1·31]) and SPMMI (RR 1·21 [95% CI 1·00–1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88–1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12–1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84–3·43]), perinatal complications (RR 1·84 [95% CI 1·02–3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67–20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02–4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44–41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22–65) and 76% (47–89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose. Interpretation COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority.

Teleconsultation has become a new means of using care which has taken off significantly since the COVID crisis, The pooling of the technological environment within the TC makes it possible to set up practice reviews by reusing the data collected. Our aim was to evaluate the relevance of antibiotic therapy during teleconsultations carried out on the national teleconsultation platform "Qare" in 4 common infections. 143,428 TCs with structured prescriptions were analyzed, with an appropriate prescription in more than 82% of cases, higher than in the literature. The use of data makes it possible to quickly assess practices and inform doctors to improve their practices.

Teleconsultation has become a new means of using care which has taken off significantly since the COVID crisis, The pooling of the technological environment within the TC makes it possible to set up practice reviews by reusing the data collected. Our aim was to evaluate the relevance of antibiotic therapy during teleconsultations carried out on the national teleconsultation platform “Qare” in 4 common infections. 143,428 TCs with structured prescriptions were analyzed, with an appropriate prescription in more than 82% of cases, higher than in the literature. The use of data makes it possible to quickly assess practices and inform doctors to improve their practices.

Orthogonal Frequency-Division Multiplexing with Random multiple access (OFDRMA) is discussed for uplink communications, whereby several active users send information towards a single base-station (BS), while all other users are dormant. Originally, uplink communication methods included sharing the frequency resources among the active users in an orthogonal fashion, i.e., a central unit is required to dynamically allocate the resources. More recently, non-orthogonal methods have arisen, meaning that several active users share the same frequency bins, but they still do require a central unit to dynamically allocate the resources in a uniform (as possible) manner over the available bandwidth. The task and overhead required for managing the frequency allocations among the users can be quite cumbersome. In OFDRMA, the frequency allocations for any user are independent of the frequency allocations for the other users, and independent of which of the other users are currently active. Rather, OFDRMA relies on random, yet predetermined, allocation of frequency bins for each user, known only to that user and the BS. A multi-user detection approach is presented based on a graphical representation of the system. It is shown to provide robustness against the forced randomness of the scheme. Capacity of OFDRMA and its optimization are analyzed and provided in detail. Simulation results are provided for demonstrating the performance attainable with OFDRMA and the proposed detection scheme. Both the capacity and the simulations are compared with modern multi-user multiple-input multiple-output (MU-MIMO) schemes.

SUMMARY The seismic response of the Santiago City, the capital of Chile with more than 5.5 million inhabitants, is controlled by the properties of the shallower quaternary deposits and the impedance contrast with the underlying Abanico Formation, among other factors. In this study, we process continuous records of ambient seismic noise to perform an ambient seismic noise tomography with the aim of defining the shallower structure of the Abanico Formation underneath the densely populated metropolitan area of Santiago, Chile. The seismic signals were recorded by a network consisting of 29 broad-band seismological stations and 12 accelerograph stations, located in a 35 × 35 km2 quadrant. We used the average coherency of the vertical components to calculate dispersion curves from 0.1 to 5 Hz and Bootstrap resampling to estimate the variance of the traveltimes. The reliable frequency band of the dispersion curves was defined by an empirical method based on sign normalization of the coherency real part. The ambient noise tomography was solved on a domain discretized into 256 2 × 2 km2 cells. Using a regularized weighted least-squares inversion, we inverted the observed traveltimes between stations, assuming straight ray paths, in order to obtain 2-D phase velocity maps from 0.2 to 1.1 Hz, linearly spaced every 0.05 Hz, in 157 of the 256 square cells of the domain. In each square cell with information, dispersion curves were assembled and used to invert shear wave velocity profiles, which were interpolated using the ordinary Kriging method to obtain a 3-D shear wave velocity model valid from 0.6 to 5 km depth. The 3-D velocity model shows that the Abanico Formation is stiffer in the south of the study area with larger velocity anomalies towards the shallower part of the model. The value of the shear wave velocity narrows with depth, reaching an average value of 3.5 km s–1 from 3 to 5 km depth.

Chagas disease is a serious parasitic infection caused by Trypanosoma cruzi. Unfortunately, the current chemotherapeutic tools are not enough to combat the infection. The aim of this study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles during the acute phase of Chagas infection in an experimental murine model. Microparticles were prepared by spray-drying using copolymers derived from esters of acrylic and methacrylic acids as carriers. Dissolution efficiency of the formulations was up to 3.80-fold greater than that of raw benznidazole. Stability assay showed no significant difference (P > 0.05) in the loading capacity of microparticles for 3 years. Cell cultures showed no visible morphological changes or destabilization of the cell membrane nor haemolysis was observed in defibrinated human blood after microparticles treatment. Mice with acute lethal infection survived 100% after 30 days of treatment with benznidazole microparticles (50 mg kg−1 day−1). Furthermore, no detectable parasite load measured by quantitative polymerase chain reaction and lower levels of T. cruzi-specific antibodies by enzyme-linked immunosorbent assay were found in those mice. A significant decrease in the inflammation of heart tissue after treatment with these microparticles was observed, in comparison with the inflammatory damage observed in both infected mice treated with raw benznidazole and untreated infected mice. Therefore, these polymeric formulations are an attractive approach to treat Chagas disease.

Orthogonal frequency-division multiplexing with random multiple access (OFDRMA) is discussed for down-link communications, whereby a single base-station transmits information towards several active users. Current methods for down-link communication partition the frequency resources among the active users in an orthogonal fashion, i.e. a central unit (typically the base-station itself) dynamically allocates the resources such that each user is allocated a fixed and exclusive set of sub-bands (a.k.a. bins, or subcarriers). The task and overhead required for orchestrating the frequency sub-bands allocations among the users in an optimal fashion can be quite cumbersome, and typically involves increased computational complexity, latency and bandwidth resources. The main purpose we address in this paper is to avoid the task and overhead required in the state-of-the-art OFDM systems in both the base-station and the users, while sacrificing as little as possible in terms of users side error rate performance. This is of particular importance in multi-user multiple-input multiple-output systems, which become increasingly popular these recent years. In OFDRMA a user is assumed to be allocated with a predetermined, randomly selected frequency bins. A multi-antenna multi-user delivery approach is presented based on pre-coding and multi-cast transmission. It is shown to provide robustness against the forced randomness of the scheme. Simulation results are provided for demonstrating the performance attainable with OFDRMA and the proposed transmission scheme.

Background Benznidazole and nifurtimox are effective drugs used to treat Chagas’ disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. Objectives To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. Methods Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. Results Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. Conclusions In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas’ disease.

Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies.This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies.This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements.Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P.05 for all comparisons).Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Chagas disease is a neglected tropical disease affecting the American continent and also some regions of Europe. Benznidazole, approved by FDA, is a drug of choice but its poor aqueous solubility may lead to a low bioavailability and efficacy. Therefore, the aim of this study was to formulate nanoparticles of benznidazole for improving its solubility, dissolution and permeability. A Plackett-Burman design was applied to identify the effect of 5 factors over 4 responses. Then, a Central Composite design was applied to estimate the values of the most important factors leading to the best compromise between highest nanoprecipitation efficiency, drug solubility and lower particle size. The optimized nanoparticles were evaluated for in vitro drug release in biorelevant media, stability studies and transmission electron microscopy. Biocompatibility and permeability of nanoparticles were evaluated on the Caco-2 cell line. The findings of the optimization process indicated that concentration of drug and stabilizer influenced significantly the particle size while concentration of stabilizer and organic/water phase volume ratio mainly influenced the drug solubility. Stability studies suggested that benznidazole nanoparticles were stable after 12 months at different temperatures. Minimal interactions of those nanoparticles and mucin glycoproteins suggested favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of the optimized formulation and showed an increased permeation through the Caco-2 cells. Thus, this study confirmed the suitability of the design of experiment and optimization approach to elucidate critical parameters influencing the quality of benznidazole nanoparticles, which could lead to a more efficient management of Chagas disease by oral route.

Breast cancer-related lymphedema (BCRL) is a lifelong condition that can impact the quality of life, affecting approximately 20% of breast cancer patients. Risk factors for the development of BCRL after mastectomy in rural populations have not been studied. Retrospective review of mastectomy patients from 2017 to 2021 was performed at a single institution. Statistical analysis included logistic and linear regression models. 475 patients were included, and 40 (8.4%) patients were diagnosed with BCRL. Increased odds of developing BCRL were significantly associated with tumor-involved lymph nodes, radiation therapy, axillary lymphadenectomy, adjuvant chemotherapy, and endocrine therapy. Postmastectomy reconstruction significantly reduced the odds of developing BCRL. There was no significant association in our population with age, body mass index, diabetes, tobacco use, cancer type, or complications. This study demonstrates that individuals underrepresented in the literature, such as patients in largely rural communities, have some differences in risk factors for developing BCRL when compared to national studies.