Prenatal greenspace exposure and cord blood cortisol levels : A cross-sectional study in a middle-income country

Exposure to greenspace has been associated with reduced stress; however, the available evidence on such an association for the fetus is still very scarce. We, for the first time, investigated the association between maternal greenspace exposure and the level of cortisol, a stress hormone, in the cord blood. Our study was based on a cohort of 150 pregnant women in Sabzevar, Iran (2018). We comprehensively assessed greenspace exposure for each participant through (i) residential surrounding greenspace (using two satellite-derived vegetation indices), (ii) residential proximity to green spaces, (iii) maternal visual access to greenspace, (iv) use of public and private green spaces, (v) having a private garden, and (vi) the number of plant pots at home. Linear regression models were developed to assess the association of each indicator of greenspace exposure with cord blood cortisol levels, controlled for the relevant covariates. We observed that a higher residential surrounding greenspace (100 m buffer), having a window with greenspace view, window greenspace coverage of more than 50%, frequently looking at greenspace through window, residential proximity to large green spaces, and more time spent in green spaces were associated with lower cortisol levels in the cord blood. The findings for residential surrounding greenspace at 300 m and 500 m buffers, residential proximity to any green space regardless of its size, having a private garden, and number of plant pots at home were not conclusive. While about one-third of the association between residential surrounding greenspace (100 m buffer) could be mediated through reduction in exposure to air pollution, we did not observe any strong evidence for such a mediatory role for the visual access to greenspace. The findings stratified for parental education and housing type showed mixed patterns. Our findings suggest that more greenspace exposure might reduce cortisol level in the cord blood

Longitudinal Behavior of Left-Ventricular Strain in Fetal Growth Restriction

Fetal growth restriction (FGR) is associated with an increased risk of adverse outcomes resulting from adaptive cardiovascular changes in conditions of placental insufficiency, leading to cardiac deformation and dysfunction, which can be evaluated with 2D speckle tracking echocardiography (2D-STE). The aim of the present study was to evaluate whether reduced fetal growth is associated with cardiac left-ventricle (LV) dysfunction, using 2D-STE software widely used in postnatal echocardiography. A prospective longitudinal cohort study was performed, and global (GLO) and segmental LV longitudinal strain was measured offline and compared between FGR and appropriate-for-gestational-age (AGA) fetuses throughout gestation. All cases of FGR fetuses were paired 1:2 to AGA fetuses, and linear mixed model analysis was performed to compare behavior differences between groups throughout pregnancy. Our study shows LV fetal longitudinal strain in FGR and AGA fetuses differed upon diagnosis and behaved differently throughout gestation. FGR fetuses had lower LV strain values, both global and segmental, in comparison to AGA, suggesting subclinical cardiac dysfunction. Our study provides more data regarding fetal cardiac function in cases of placental dysfunction, as well as highlights the potential use of 2D-STE in the follow-up of cardiac function in these fetuses

Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg) : A structured summary of a study protocol for a randomised placebo controlled trial

Objectives: The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. Trial design: Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. Participants: Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. •Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact*of a SARS-CoV-2 confirmed or suspected case in the past 14 days •More than 12 weeks of gestation (dated by ultrasonography) •Agreement to deliver in the study hospitals Exclusion criteria •Known hypersensitivity to HCQ or other 4-amonoquinoline compounds •History of retinopathy of any aetiology •Concomitant use of digoxin, cyclosporine, cimetidine •Known liver disease •Clinical history of cardiac pathology including known long QT syndrome •Unable to cooperate with the requirements of the study •Participating in other intervention studies •Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: •SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) •SARS-CoV-2 PCR negative pregnant women in contact*with a SARS-CoV-2-infected confirmed or suspected case (n=514).*The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. Intervention and comparator: Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). Main outcomes: The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). Randomisation: Allocation of participants to study arms will be done centrally by the trial's Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. Blinding (masking): Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. Numbers to be randomised (sample size): This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. Trial Status: Protocol version 1.0, from May 8th, 2020. Recruitment is ongoing (first patient recruited the 19th May 2020 and recruitment end anticipated by December 2020). Trial registration: EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562, retrospectively registered 1 June 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol

Nano-based approved pharmaceuticals for cancer treatment : present and future challenges

Altres ajuts: RICORS RD21/0012/0001 (co-funded by the European Regional Development Fund, "A way to make Europe"); Fundación Mutua Madrileña (FMMA) through the project "Targeted therapy for selective elimination of metastatic stem cells CXCR4+ in endometrial cancer" (AP1666942017); Asociación Española contra el cancer (AECC) through the project "Development of an antitumor protein delivery system into ovarian cancer cells using the subcellular vault" (IDEAS18038BENI)Cancer is one of the main causes of death worldwide. To date, and despite the advances in conventional treatment options, therapy in cancer is still far from optimal due to the non-specific systemic biodistribution of antitumor agents. The inadequate drug concentrations at the tumor site led to an increased incidence of multiple drug resistance and the appearance of many severe unde-sirable side effects. Nanotechnology, through the development of nanoscale-based pharmaceuticals, has emerged to provide new and innovative drugs to overcome these limitations. In this review, we provide an overview of the approved nanomedicine for cancer treatment and the rationale behind their designs and applications. We also highlight the new approaches that are currently under investigation and the perspectives and challenges for nanopharmaceuticals, focusing on the tumor microenvironment and tumor disseminate cells as the most attractive and effective strategies for cancer treatments

Neural plasticity of the uterus : New targets for endometrial cancer?

Altres ajuts: European Regional Development Fund (FEDER); FMMA grant (AP166942017); European Social Fund (ESF 'Investing in Your Future').Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle. Therefore, a precise understanding of nerve-cancer crosstalk and the contribution of the organ-intrinsic neuroplasticity, mediated by estrogen and progesterone, of the uterine is urgently needed. The development of new and innovative medicines for patients with endometrial cancer would increase their quality of life and health. This review compiles information on the architecture and function of autonomous uterine neural innervations and the influence of hormone-dependent nerves in normal uterus and tumor progression. It also explores new therapeutic possibilities for endometrial cancer using these endocrine and neural advantages

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors : Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). , identifier: NCT04767438

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia : the ANGIOCOR prospective cohort study protocol

Background: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. Methods: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. Discussion: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. Trial registration: NCT04162236