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All-sky assimilation of infrared (IR) radiances has not yet become operational at any weather forecasting centre, but it promises to bring new observations in sensitive areas and avoid the need for cloud detection. A new all-sky IR configuration gives results comparable to (and in some areas better than) clear-sky assimilation of the same data, meaning that operational implementation is now feasible. The impact of seven upper-tropospheric water vapour (WV) sounding channels from the Infrared Atmospheric Sounding Interferometer (IASI) is evaluated in both all-sky and clear-sky approaches. All-sky radiative transfer simulations (and the forecast model's cloud fields) are now sufficiently accurate that systematic errors are comparable to those of clear-sky assimilation outside of a few difficult areas such as deep convection. All-sky assimilation brings 65 % more data than clear-sky assimilation globally, with the biggest increases in midlatitude storm tracks and tropical convective areas. However, all-sky gives slightly less weight to any one observation than in the clear-sky approach. In the midlatitudes, all-sky and clear-sky assimilation have similarly beneficial impact on mid- and upper-tropospheric dynamical forecast fields. Here the addition of data in cloudy areas is offset by the slightly lower weight given to the observations. But in the tropics, all-sky assimilation is significantly more beneficial than clear-sky assimilation, with improved dynamical short-range forecasts throughout the troposphere and stratosphere.

The characterisation of errors and uncertainties in numerical weather prediction (NWP) model fields is a major challenge that is addressed as part of the Horizon 2020 Gap Analysis for Integrated Atmospheric ECV CLImate Monitoring (GAIA-CLIM) project. In that regard, observations from the GCOS (Global Climate Observing System) Reference Upper-Air Network (GRUAN) radiosondes are being used at the Met Office and European Centre for Medium-Range Weather Forecasts (ECMWF) to assess errors and uncertainties associated with model data. The software introduced in this study and referred to as the GRUAN processor has been developed to collocate GRUAN radiosonde profiles and NWP model fields, simulate top-of-atmosphere brightness temperature at frequencies used by space-borne instruments, and propagate GRUAN uncertainties in that simulation. A mathematical framework used to estimate and assess the uncertainty budget of the comparison of simulated brightness temperature is also proposed. A total of 1 year of GRUAN radiosondes and matching NWP fields from the Met Office and ECMWF have been processed and analysed for the purposes of demonstration of capability. We present preliminary results confirming the presence of known biases in the temperature and humidity profiles of both NWP centres. The night-time difference between GRUAN and Met Office (ECMWF) simulated brightness temperature at microwave frequencies predominantly sensitive to temperature is on average smaller than 0.1 K (0.4 K). Similarly, this difference is on average smaller than 0.5 K (0.4 K) at microwave frequencies predominantly sensitive to humidity. The uncertainty estimated for the Met Office–GRUAN difference ranges from 0.08 to 0.13 K for temperature-sensitive frequencies and from 1.6 to 2.5 K for humidity-sensitive frequencies. From the analysed sampling, 90 % of the comparisons are found to be in statistical agreement. This initial study has the potential to be extended to a larger collection of GRUAN profiles, covering multiple sites and years, with the aim of providing a robust estimation of both errors and uncertainties of NWP model fields in radiance space for a selection of key microwave and infrared frequencies.

In this paper ensembles of forecasts (of up to six hours) are studied from a convection-permitting model with a representation of model error due to unresolved processes. The ensemble prediction system (EPS) used is an experimental convection-permitting version of the UK Met Office's 24-member Global and Regional Ensemble Prediction System (MOGREPS). The method of representing model error variability, which perturbs parameters within the model's parameterisation schemes, has been modified and we investigate the impact of applying this scheme in different ways. These are: a control ensemble where all ensemble members have the same parameter values; an ensemble where the parameters are different between members, but fixed in time; and ensembles where the parameters are updated randomly every 30 or 60 min. The choice of parameters and their ranges of variability have been determined from expert opinion and parameter sensitivity tests. A case of frontal rain over the southern UK has been chosen, which has a multi-banded rainfall structure. The consequences of including model error variability in the case studied are mixed and are summarised as follows. The multiple banding, evident in the radar, is not captured for any single member. However, the single band is positioned in some members where a secondary band is present in the radar. This is found for all ensembles studied. Adding model error variability with fixed parameters in time does increase the ensemble spread for near-surface variables like wind and temperature, but can actually decrease the spread of the rainfall. Perturbing the parameters periodically throughout the forecast does not further increase the spread and exhibits "jumpiness" in the spread at times when the parameters are perturbed. Adding model error variability gives an improvement in forecast skill after the first 2–3 h of the forecast for near-surface temperature and relative humidity. For precipitation skill scores, adding model error variability has the effect of improving the skill in the first 1–2 h of the forecast, but then of reducing the skill after that. Complementary experiments were performed where the only difference between members was the set of parameter values (i.e. no initial condition variability). The resulting spread was found to be significantly less than the spread from initial condition variability alone.

A huge amount of geographical datasets are becoming available in distributed environments like Spatial Data Infrastructures (SDI). These datasets are very heterogeneous since they come from different independent sources and surveys and are structured in different formats. In the context of a national SDI that needs to assure an adequate quality level of the data it provides, it is necessary to face the problem of data validation in an uniform way independently from the chosen implementation technology. In this paper we present the tools and methodology for data validation which have been developed to support the construction of the Italian SDI. These tools are conformant to the relevant ISO 19100 and Open Geospatial Consortium (OGC) standards.

Purpose: To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI signs., Method: Our retrospective study included patients with PP from two institutions. All patients underwent US and MRI examinations for suspicion of PAS. CRF consisting of maternal age, cesarean section number, smoking and hypertension were retrieved. US and MRI signs suggestive of PAS were evaluated. Logistic regression analysis was performed to identify CRF and/or US and MRI signs associated with PAS considering histology as the reference standard. A nomogram was created using significant CRF and imaging signs at multivariate analysis, and its diagnostic accuracy was measured using the area under the binomial ROC curve (AUC), and the cut-off point was determined by Youden's J statistic., Results: A total of 171 patients were enrolled from two institutions. Independent predictors of PAS included in the nomogram were: 1) smoking and number of previous CS among CRF; 2) loss of the retroplacental clear space at US; 3) intraplacental dark bands, focal interruption of the myometrial border and placental bulging at MRI. A PAS-prediction nomogram was built including these parameters and an optimal cut-off of 14.5 points was identified, showing the highest sensitivity (91%) and specificity (88%) with an AUC value of 0.95 (AUC of 0.80 in the external validation cohort)., Conclusion: A nomogram-based model combining CRF with US and MRI signs might help to predict PAS in PP patients, with MRI contributing more than US as imaging evaluation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the era of massive sharing of information, the term social provenance is used to denote the ownership, source or origin of a piece of information which has been propagated through social media. Tracking the provenance of information is becoming increasingly important as social platforms acquire more relevance as source of news. In this scenario, Twitter is considered one of the most important social networks for information sharing and dissemination which can be accelerated through the use of retweets and quotes. However, the Twitter API does not provide a complete tracking of the retweet chains, since only the connection between a retweet and the original post is stored, while all the intermediate connections are lost. This can limit the ability to track the diffusion of information as well as the estimation of the importance of specific users, who can rapidly become influencers, in the news dissemination. This paper proposes an innovative approach for rebuilding the possible chains of retweets and also providing an estimation of the contributions given by each user in the information spread. For this purpose, we define the concept of Provenance Constraint Network and a modified version of the Path Consistency Algorithm. An application of the proposed technique to a real-world dataset is presented at the end of the paper., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2023.)

This document presents the recommendations developed by the IOC Medical and Scientific Commission and several international federations (IF) on the protection of athletes competing in the heat. It is based on a working group, meetings, field experience and a Delphi process. The first section presents recommendations for event organisers to monitor environmental conditions before and during an event; to provide sufficient ice, shading and cooling; and to work with the IF to remove regulatory and logistical limitations. The second section summarises recommendations that are directly associated with athletes' behaviours, which include the role and methods for heat acclimation; the management of hydration; and adaptation to the warm-up and clothing. The third section explains the specific medical management of exertional heat stroke (EHS) from the field of play triage to the prehospital management in a dedicated heat deck, complementing the usual medical services. The fourth section provides an example for developing an environmental heat risk analysis for sport competitions across all IFs. In summary, while EHS is one of the leading life-threatening conditions for athletes, it is preventable and treatable with the proper risk mitigation and medical response. The protection of athletes competing in the heat involves the close cooperation of the local organising committee, the national and international federations, the athletes and their entourages and the medical team., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although current guidelines recommend that mothers with suspected or confirmed SARS-CoV-2 infection should be encouraged to initiate and continue breastfeeding, up-to-date literature shows conflicting data regarding breastfeeding experiences in infected women. This survey aimed to report on the psychological impact of SARS-CoV-2 infection on breastfeeding practice and medical counselling in a single tertiary center in Southern Italy. Methods: One-hundred breastfeeding women with SARS-CoV-2 infection at delivery were given an anonymous questionnaire regarding breastfeeding and women’s perception of the impact of COVID-19 on breastfeeding. Results: 75% of women reported they had difficulty breastfeeding; among them, 66 (66%) declared that separation from their babies after delivery affected their ability to breastfeed. Incidence of reported difficulties in breastfeeding was higher in women who underwent caesarean section compared to women with vaginal delivery (56/65, 86.2% vs. 19/35, 54.3%, χ2 = 12.322, p < 0.001) and in women with a hospital stay of more than 5 days (48/57, 84.2% vs. 23/37, 62.2%, χ2 = 5.902, p = 0.015). Furthermore, the incidence of difficulties in breastfeeding was higher in women who subsequently decided to use exclusively infant formula compared to women who mixed maternal milk with infant formula and women who breastfed exclusively with maternal milk (48/49, 98% vs. 20/25, 80% vs. 7/26, 26.9%, χ2 = 46.160, p < 0.001). Conclusions: Our survey highlights the importance of healthcare support and information on hygiene practices to decrease the perceived stress related to breastfeeding for infected mothers under restrictions, especially in women undergoing cesarean section and with a long hospital stay.

Background: The optimal gestational age at delivery for stable women with suspected placenta accreta is still subject of debate., Objective: To estimate the likelihood of vaginal bleeding necessitating expedited delivery in women with placenta accreta according to gestational age at planned cesarean hysterectomy., Study Design: This was a multicenter cohort study. Singleton pregnancies at risk of placenta accreta because of placenta previa in the setting of prior cesarean delivery were included. Outcomes were compared in cohort of women who had planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks versus at 35 0/7 - 35 6/7 weeks. The primary outcome was incidence of vaginal bleeding severe enough to necessitate delivery., Results: 118 singleton pregnancies with placenta previa in the setting of prior cesarean delivery, and confirmed placenta accreta at the time of delivery were included in the study. Women who had planned cesarean hysterectomy at 34 weeks had lower episodes of vaginal bleeding severe enough to necessitate immediate or emergency delivery (20.6% vs 38.0%; odds ratio (OR) 0.42, 95% confidence interval (CI) 0.19 to 0.96). Eight women (11.8%) in the 34 weeks group and 6 women (12.0%) in the 35 weeks group delivered before the planned date due to onset of spontaneous labor (OR 0.98, 95% CI 0.32 to 3.02)., Conclusion: In singleton gestations with suspected placenta accreta, planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks was associated with a decreased chance of unscheduled delivery due to severe vaginal bleeding., Condensation: In case of placenta accreta, planned cesarean hysterectomy at 34 weeks was associated with decreased chance of unscheduled delivery due to severe vaginal bleeding.

Antiphospholipid Antibody Syndrome (APS) is a systemic autoimmune disease characterized by acquired hypercoagulability with the possible development of venous, arterial, and microvascular thrombosis. We report a rare case of Libman-Sacks tricuspid valve endocarditis in a 38-year-old pregnant woman at 15 weeks gestation with unknown primary antiphospholipid syndrome. During a routine cardiac examination and echocardiography performed for a previous episode of pleuropericarditis, a large, mobile mass with irregular edges was found at the level of the tricuspid valve. Three main differential diagnoses for intramyocardial mass were examined: tumor, infective endocarditis, and nonbacterial thrombotic endocarditis (NTBE). Cardiac magnetic resonance imaging (CMR) with contrast raised the suspicion of a thrombus. The woman was hospitalized urgently at the Cardiac Intensive Care Unit of the Federico II University Hospital, and anticoagulant and antiplatelet therapy were started. The thrombophilic screening performed and medical history confirmed the diagnosis of primary antibody syndrome (APS). A multidisciplinary consultation with obstetricians, cardiologists, anesthetists, and cardiac surgeons was required. The patient decided not to terminate the pregnancy despite the risk to her health and to undergo cardiac surgery during pregnancy. Histological examination confirmed the presence of nonbacterial thrombotic endocarditis. Weekly obstetric scans were performed after surgery to verify fetal well-being. An emergency cesarean section was performed at the 35th week of gestation due to repeated deceleration and abnormal short-term variability on c-CTG in a pregnancy complicated by fetal growth restriction and gestational hypertension. A newborn weighing 1290 g was born. She was hospitalized in Neonatal Intensive Care and discharged after two months; currently, she enjoys good health. The management of patients with antiphospholipid antibody syndrome has not yet been standardized, but there is a general consensus that patients who do not have thrombocytopenia, thromboembolic phenomena, or pregnancy should not undergo any treatment or should take only low doses of acetylsalicylic acid. In the presence of any of the above conditions, various treatment regimens have been used based on the severity and individuality of the case.

Background: The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March-May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions., Methods: Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March-May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI)., Results: Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of - 101.3 (95% CI - 103.5 to - 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of - 19.7 (95% CI - 23.8 to - 15.6; p < 0.0001)., Conclusion: A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric-gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures., (© 2021. The Author(s).)

In the course of infection and intense endotoxemia processes, induction of a catabolic state leading to weight loss is observed in mice and humans. However, the late effects of acute inflammation on energy homeostasis, regulation of body weight and glucose metabolism are yet to be elucidated. Here, we addressed whether serial intense endotoxemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to weight gain and associated metabolic complications. Male Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (10 mg/kg LPS), followed by 10 weeks on a high-fat diet (HFD). LPS-treated mice did not show changes in weight when fed standard chow. However, when challenged by a high-fat diet, LPS-treated mice showed greater weight gain, with larger fat depot areas, increased serum leptin and insulin levels and impaired insulin sensitivity when compared to mice on HFD only. Acute endotoxemia caused a long-lasting increase in mRNA expression of inflammatory markers such as TLR-4, CD14 and serum amyloid A (SAA) in the adipose tissue, which may represent the key factors connecting inflammation to increased susceptibility to weight gain and impaired glucose homeostasis. In an independent experimental model, and using publicly available microarray data from adipose tissue from mice infected with Gram-negative bacteria, we performed gene set enrichment analysis and confirmed upregulation of a set of genes responsible for cell proliferation and inflammation, including TLR-4 and SAA. Together, we showed that conditions leading to intense and recurring endotoxemia, such as common childhood bacterial infections, may resound for a long time and aggravate the effects of a western diet. If confirmed in humans, infections should be considered an additional factor contributing to obesity and type 2 diabetes epidemics.

The IOC recently published its framework on fairness, inclusion and non-discrimination based on gender identity and sex variations. This framework is drafted mainly from a human rights perspective, with less consideration for medical/scientific issues. The framework places the onus for gender eligibility and classification entirely on the International Federations (IFs), even though most will not have the capacity to implement the framework. The position of no presumption of advantage is contrary to the 2015 IOC consensus. Implementation of the 2021 framework will be a major challenge for IFs that have already recognised the inclusion of trans and women athletes with differences of sexual development (DSD) using a scientific/medical solution. The potential consequences for sports that need to prioritise fairness or safety could be one of two extremes (1) exclusion of all transgender or DSD athletes on the grounds of advantage or (2) self-identification that essentially equates to no eligibility rules. Exclusion of all transgender or DSD athletes is contrary to the Olympic charter and unlawful in many countries. While having no gender eligibility rules, sport loses its meaning and near-universal support. Athletes should not be under pressure to undergo medical procedures or treatment to meet eligibility criteria. However, if an athlete is fully informed and consents, then it is their free choice to undergo carefully considered or necessary interventions for gender classification for sport to compete fairly and safely in their chosen gender. Free choice is a fundamental human right, but so is the right to fair and safe competition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Singleton pregnancies obtained by assisted reproductive technology (ART) are at increased risk of adverse pregnancy outcome. Aim of this pilot study was to compare maternal hemodynamic profile in ART and spontaneous singleton pregnancies. Patients were enrollered during a third trimester routine obstetric examination. Maternal haemodynamic assessment was carried out by a single trained operator using an UltraSonic Cardiac Output Monitor in standardized conditions. Our pilot data suggests that women conceived after ART may have significantly lower Cardiac Output and significantly higher Systemic Vascular Resistance when compared to those conceiving spontaneously. These differences, if confirmed in larger studies, might explain the increased prevalence of adverse outcome, especially hypertensive disorders of pregnancy, in singleton ART pregnancies., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objectives: To predict placental accreta spectrum (PAS) in patients with placenta previa (PP) evaluating clinical risk factors (CRF), ultrasound (US) and magnetic resonance imaging (MRI) findings., Methods: Seventy patients with PP were retrospectively selected. CRF were retrieved from medical records. US and MRI images were evaluated to detect imaging signs suggestive of PAS. Univariable analysis was performed to identify CRF, US and MRI signs associated with PAS considering histology as standard of reference. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) was calculated. Multivariable analysis was also performed., Results: At univariable analysis, the number of previous cesarean section, smoking, loss of the retroplacental clear space, myometrial thinning < 1 mm, placental lacunae, intraplacental dark bands (IDB), focal interruption of myometrial border (FIMB) and abnormal vascularity were statistically significant. The AUC in predicting PAS progressively increased using CRF, US and MRI signs (0.69, 0.79 and 0.94, respectively; p < 0.05); the accuracy of MRI alone was similar to that obtained combining CRF, US and MRI variables (AUC = 0.97) and was significantly higher (p < 0.05) than that combining CRF and US (AUC = 0.83). Multivariable analysis showed that only IDB (p = 0.012) and FIMB (p = 0.029) were independently associated with PAS., Conclusions: MRI is the best modality to predict PAS in patients with PP independently from CRF and/or US finding. It is reasonable to propose the combined assessment of CRF and US as the first diagnostic level to predict PAS, sparing MRI for selected cases in which US findings are uncertain for PAS., (© 2021. Italian Society of Medical Radiology.)

Background: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision., Objective: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy., Study Design: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020)., Results: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P<.001), even if a very large percentage declared to be generally in favor of vaccines (128 [90.1%] vs 14 [9.9%]; chi-square test=6.091; P=.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75 [52.8%] vs 67 [47.2%]; chi-square test=10.996; P=.001)., Conclusion: Urgent data are needed on the safety, efficacy, and toxicology of severe acute respiratory syndrome coronavirus 2 vaccines during pregnancy to modify this trend and to help obstetricians during the counseling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. Methods: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 34 0 -35 6 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. Results: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p  = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. Conclusion: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.

Competing Interests: Competing interests: WD reports grants from IOC Research Centers Grant, other from IPC Travel Support, grants from World Rugby, grants from AXA, grants from Ossur, outside the submitted work.

Objective: To compare women's experience of first-trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell-free DNA (cfDNA) analysis., Methods: This was single-center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first-trimester risk assessment based on FTCS, or to a policy of first-trimester risk assessment based on ultrasound findings and cfDNA. FTCS included ultrasound evaluation with crown-rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP-A and free beta hCG). In this group, invasive diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first-trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, invasive diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre-test and post-test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post-test reassurance, defined as mean score of reassurance post-test questionnaire. The effect of the assigned screening test on the mean of each outcome was quantified as mean difference (MD) with 95% confidence interval (CI)., Results: Forty women with singleton gestations were enrolled in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre-test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post-test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfaction and lower mean anxiety score as assessed in the STAI pre-test questionnaire., Conclusions: First-trimester risk assessment for fetal aneuploidy with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal reassurance and better maternal satisfaction compared to the standard first-trimester combined screening with nuchal translucency, and biochemistry., Trial Registration: Clinicaltrials.gov NCT04077060., (© 2020 John Wiley & Sons Ltd.)

Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFNγ) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to evaluate the incidence of toxoplasmosis infection during pregnancy and to describe the characteristics of the serological status, management, follow-up and treatment., Material and Methods: This is a population-based cohort study of women referred for suspected toxoplasmosis during pregnancy from January, 2001 to December, 2012. Suspected toxoplasmosis was defined as positive IgM antibody during pregnancy. Women with suspected toxoplasmosis during pregnancy were classified into three groups: seroconversion, suspected infection, or no infection in pregnancy. Women in the first and second group were treated according to local protocol, and amniocentesis with toxoplasmosis PCR detection and serial detailed ultrasound scans were offered. Neonates were investigated for congenital toxoplasmosis at birth and were monitored for at least one year after birth., Results: During the study period, there were 738,588 deliveries in Campania. Of them 1159 (0.2%) were referred to our Institution for suspected toxoplasmosis during pregnancy: 183 (15.8%) women were classified as seroconversion, 381 (32.9%) were suspected infection, and 595 (51.3%) were not infected in pregnancy. Neonatal outcome was available for 476 pregnancies, including 479 neonates (3 twins, 473 singletons), out of the 564 pregnancies with seroconversion or suspected infection. 384 (80.2%) babies were not infected at birth and at follow-up, 67 (14.0%) had congenital toxoplasmosis, 10 (2.1%) were voluntary induced termination of pregnancy, 15 (3.1%) were spontaneous miscarriage, and 4 (0.8%) were stillbirth (of which one counted already in the infected cohort). Considering cases of congenital toxoplasmosis, the transmission rate in women with seroconversion was 32.9% (52/158), and in women with suspected infection was 4.7% (15/321)., Conclusions: Toxoplasmosis is uncommon in pregnancy with overall incidence of seroconversion and suspected infection in pregnancy of 0.8 per 1000 live births and incidence of congenital toxoplasmosis 0.1 per 1000 live births when applying a strict protocol of screening, follow-up, and treatment. 51.3% (595/1159) of women referred to our center for suspected infection were actually considered not infected., (Copyright © 2019. Published by Elsevier B.V.)

Mass participation endurance sports events are popular but a large number of participants are older and may be at risk of medical complications during events. Medical encounters (defined fully in the statement) include those traditionally considered 'musculoskeletal' (eg, strains) and those due to 'illness' (eg, cardiac, respiratory, endocrine). The rate of sudden death during mass endurance events (running, cycling and triathlon) is between 0.4 and 3.3 per 100 000 entrants. The rate of other serious medical encounters (eg, exertional heat stroke, hyponatraemia) is rarely reported; in runners it can be up to 100 times higher than that of sudden death, that is, between 16 and 155 per 100 000 race entrants. This consensus statement has two goals. It (1) defines terms for injury and illness-related medical encounters, severity and timing of medical encounters, and diagnostic categories of medical encounters, and (2) describes the methods for recording data at mass participation endurance sports events and reporting results to authorities and for publication. This unifying consensus statement will allow data from various events to be compared and aggregated. This will inform athlete/patient management, and thus make endurance events safer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Early-onset preeclampsia is a form of preeclampsia requiring delivery before 34 weeks of gestation. The etiology is unknown, but placental dysfunction appears crucial. We evaluated the immunohistochemical expression of the antiapoptotic protein Bcl-2, the angiogenetic factors VEGF and PlGF, and the epithelial factors HGF, c-Met and STAT3 in placental samples of pregnancies complicated by early-onset preeclampsia., Materials and Methods: Placental sections were obtained from 41 women with early-onset preeclampsia (cases) and from 31 uncomplicated pregnancies (controls). A standard haematoxylin and eosin stain was used to assess histological structure. Immunohistochemical expression of Bcl-2, VEGF, PlGF, HGF, c-Met and STAT3 was analyzed., Results: Mean gestational age was 32 weeks in cases and 39 weeks in controls. Microscopically, sections from women with preeclampsia showed a disorder of villous development as a distal villous hypoplasia with placental undergrowth. The immunoistochemical expression of Bcl-2 (p < 0.0001), VEGF (p = 0.0323), PlGF (p = 0.002), HGF (p < 0.0001), c-Met (p < 0.0001) and STAT3 (p = 0.0004) were significantly lower in placentas of complicated pregnancies compared to uncomplicated ones., Conclusions: Early-onset preeclampsia is associated with a disorder of villous development. Apoptotic, angiogenetic and epithelial mechanisms are simultaneously impaired and contribute to placental dysfunctions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims/hypothesis: Pre-adipocytes and adipocytes are responsive to the acute phase protein serum amyloid A (SAA). The combined effects triggered by SAA encompass an increase in pre-adipocyte proliferation, an induction of TNF-α and IL-6 release and a decrease in glucose uptake in mature adipocytes, strongly supporting a role for SAA in obesity and related comorbidities. This study addressed whether SAA depletion modulates weight gain and insulin resistance induced by a high-fat diet (HFD)., Methods: Male Swiss Webster mice were fed an HFD for 10 weeks under an SAA-targeted antisense oligonucleotide (ASOSAA) treatment in order to evaluate the role of SAA in weight gain., Results: With ASOSAA treatment, mice receiving an HFD did not differ in energy intake when compared with their controls, but were prevented from gaining weight and developing insulin resistance. The phenotype was characterised by a lack of adipose tissue expansion, with low accumulation of epididymal, retroperitoneal and subcutaneous fat content and decreased inflammatory markers, such as SAA3 and toll-like receptor (TLR)-4 expression, as well as macrophage infiltration into the adipose tissue. Furthermore, a metabolic status similar to chow-fed mice counterparts could be observed, with equivalent levels of leptin, adiponectin, IGF-I, SAA, fasting glucose and insulin, and remarkable improvement in glucose and insulin tolerance test profiles. Surprisingly, the expected HFD-induced metabolic endotoxaemia was also prevented by the ASOSAA treatment., Conclusions/interpretation: This study provides further evidence of the role of SAA in weight gain and insulin resistance. Moreover, we also suggest that beyond its proliferative and inflammatory effects, SAA is part of the lipopolysaccharide signalling pathway that links inflammation to obesity and insulin resistance.

The practice of inhaling liquefied petroleum gas (LPG) to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication.

Objective: Epidemiological studies show the association of sleep restriction (SR) with obesity and insulin resistance. Experimental studies are limited to the concurrent or short-term effects of SR. Here, we examined the late effects of SR regarding weight gain and metabolic alterations induced by a high-fat diet (HFD)., Methods: C57BL/6 mice were subjected to a multiple platform method of SR for 15 days, 21 h daily, followed by 6 weeks of a 30% HFD., Results: Just after SR, serum insulin and resistin concentrations were increased and glycerol content decreased. In addition, resistin, TNF-α, and IL-6 mRNA expression were notably increased in epididymal fat. At the end of the HFD period, mice previously submitted to SR gained more weight (32.3 ± 1.0 vs. 29.4 ± 0.7 g) with increased subcutaneous fat mass, had increments in the expression of the adipogenic genes PPARγ, C/EBPα, and C/EBPβ, and had macrophage infiltration in the epididymal adipose tissue. Furthermore, enhanced glucose tolerance and insulin resistance were also observed., Conclusions: The consequences of SR may last for a long period, characterizing SR as a predisposing factor for weight gain and insulin resistance. Metabolic changes during SR seem to prime adipose tissue, aggravating the harmful effects of diet-induced obesity., (© 2014 The Obesity Society.)

Indoleamine 2,3-dioxygenase (IDO) is an interferon-γ (IFN-γ)-induced tryptophan-degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originated from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N-dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non-competitive inhibitors, with Ki values of 156 and 506 μM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN-γ-induced IDO in the A172 human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co-culture assays. We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor-reactive response by the PBMCs., (Copyright © 2013 John Wiley & Sons, Ltd.)

Our data suggest that impaired activity of myeloperoxidase (MPO) may play an important role in the dysfunction of neutrophils from hyperglycemic rats. Neutrophil biochemical pathways include the NADPH oxidase system and the MPO enzyme. They both play important role in the killing function of neutrophils. The effect of hyperglycemia on the activity of these enzymes and the consequences with regard to Candida albicans phagocytosis and the microbicidal property of rat peritoneal neutrophils is evaluated here. The NADPH oxidase system activity was measured using chemiluminescence and cytochrome C reduction assays. MPO activity was measured by monitoring HOCl production, and MPO protein expression was analysed using Western blot and immunofluorescence. C. albicans phagocytosis and death were evaluated by optical microscopy using the May-Grunwald-Giemsa staining method. ROS generation kinetic was slightly delayed in the diabetic group. MPO expression levels were higher in diabetic neutrophils; however, MPO activity was decreased in these same neutrophils compared with the controls. C. albicans phagocytosis and killing were lower in the diabetic neutrophils. Based on our experimental model, the phagocytic and killing functions of neutrophil phagocytosis are impaired in diabetic rats because of the decreased production of HOCl, highlighting the importance of MPO in the microbicidal function of neutrophils., (Copyright © 2012 John Wiley & Sons, Ltd.)

Although many elite sporting events occur in climate-controlled venues, some athletes train and compete in environments that can potentially pose a risk to the athlete's health. In particular, athletes in aquatics, track and field, tennis, football and triathlon can be exposed to extreme heat during competition or while training. The International Federations responsible for these sports are aware of these health risks and have implemented measures to help protect the health of their athletes. This review paper outlines the sport-specific environmental health risks and the safety standards implemented to safeguard athlete health.

The experiment, aimed to evaluate the distracting effect of television, was carried out on 122 children, divided into three groups. All groups performed the auditory vigilance test (AVT) to assess reaction time (RT) to an auditory stimulus and the number of errors in responding to the stimulus. Children in group 1 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a black and white cartoon (BW test). Children in group 2 performed the AVT while in front of a blank TV set and listening to the soundtrack of a movie (SO test), then watching a color cartoon (CC test). Group 3 performed SO, BW, and CC tests consecutively. RT and the number and type of errors were measured. In each group, 30 days separated one session from the following. A significant increase of median RTs (more than 10%) and errors (twice and more) was observed both in the case of BW and CC tests with respect to SO test. RT increased throughout all tests. During SO test, errors are mainly "false reactions", but in BW and CC tests, errors are more numerous, and they are mainly "omissions". TV movies have a significant distracting and attention-capturing effect, which increases throughout the vision of the show. No advantage in decreasing this effect is offered by removing color from the movie.

To detect electrocochleographic (ECochG) potentials generated by the cochlea in response to auditory stimuli, either transtympanic or tympanic/extratympanic electrodes are currently used. The first are invasive, while the second are arranged in contact or very close to the tympanic membrane (TM). To avoid the discomfort and the risks inherent to the application of such conventional electrodes, this Letter presents an alternative technique. A conducting liquid is inserted into the ear canal to act as a distributed electrical interface between the TM and an external electrode. Thus, ECochG potentials are detected without any direct contact between the solid electrode and the sensitive TM. This technique was tested on ten volunteers with single-click auditory stimuli. Results showed its efficacy to noninvasively detect useful ECochG responses, with accurate morphology and significant amplitude. The technique is comfortable, sedation/anesthesia-free, inherently safe, and easy to perform. It also favors improvements of contact stability, reductions of contact impedance, and relative tolerance to misplacements. As a contraindication, the liquid prevents use on subjects affected by tympanic perforation. All these features encourage further investigations on this technique as a possible additional tool for the ECochG practice.