Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

In Vitro Models of Cell Senescence: A Systematic Review on Musculoskeletal Tissues and Cells.

Ageing is an irreversible and inevitable biological process and a significant risk factor for the development of various diseases, also affecting the musculoskeletal system, resulting from the accumulation of cell senescence. The aim of this systematic review was to collect the in vitro studies conducted over the past decade in which cell senescence was induced through various methods, with the purpose of evaluating the molecular and cellular mechanisms underlying senescence and to identify treatments capable of delaying senescence. Through three electronic databases, 22 in vitro studies were identified and included in this systematic review. Disc, cartilage, or muscle cells or tissues and mesenchymal stem cells were employed to set-up in vitro models of senescence. The most common technique used to induce cell senescence was the addition to the culture medium of tumor necrosis factor (TNF)α and/or interleukin (IL)1ß, followed by irradiation, compression, hydrogen peroxide (H2O2), microgravity, in vitro expansion up to passage 10, and cells harvested from damaged areas of explants. Few studies evaluated possible treatments to anti-senescence effects. The included studies used in vitro models of senescence in musculoskeletal tissues, providing powerful tools to evaluate age-related changes and pathologies, also contributing to the development of new therapeutic approaches.

The Complex Interplay between the Gut Microbiome and Osteoarthritis: A Systematic Review on Potential Correlations and Therapeutic Approaches.

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.

Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review.

Musculoskeletal frailty-a common and debilitating condition linked to aging and chronic diseases-presents a major public health issue. In vivo models have become a key tool for researchers as they investigate the condition's underlying mechanisms and develop effective interventions. This systematic review examines the current body of research on in vivo models of musculoskeletal frailty, without any time constraints. To achieve this aim, we utilized three electronic databases and incorporated a total of 11 studies. Our investigation delves into varied animal models that simulate specific features of musculoskeletal frailty, including muscle loss, bone density reduction, and functional decline. Furthermore, we examine the translational prospects of these models in augmenting our comprehension of musculoskeletal frailty and streamlining the production of groundbreaking therapeutic approaches. This review provides significant insights and guidance for healthcare researchers and practitioners who aim to combat musculoskeletal frailty, ultimately enhancing the quality of life for older adults and individuals affected by this condition.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.

BACKGROUND: Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. METHODS: Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. RESULTS: We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). CONCLUSIONS: In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy.

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.

Preliminary Characterization of the Epigenetic Modulation in the Human Mesenchymal Stem Cells during Chondrogenic Process.

Regenerative medicine represents a growing hot topic in biomedical sciences, aiming at setting out novel therapeutic strategies to repair or regenerate damaged tissues and organs. For this perspective, human mesenchymal stem cells (hMSCs) play a key role in tissue regeneration, having the potential to differentiate into many cell types, including chondrocytes. Accordingly, in the last few years, researchers have focused on several in vitro strategies to optimize hMSC differentiation protocols, including those relying on epigenetic manipulations that, in turn, lead to the modulation of gene expression patterns. Therefore, in the present study, we investigated the role of the class II histone deacetylase (HDAC) inhibitor, MC1568, in the hMSCs-derived chondrogenesis. The hMSCs we used for this work were the hMSCs obtained from the amniotic fluid, given their greater differentiation capacity. Our preliminary data documented that MC1568 drove both the improvement and acceleration of hMSCs chondrogenic differentiation in vitro, since the differentiation process in MC1568-treated cells took place in about seven days, much less than that normally observed, namely 21 days. Collectively, these preliminary data might shed light on the validity of such a new differentiative protocol, in order to better assess the potential role of the epigenetic modulation in the process of the hypertrophic cartilage formation, which represents the starting point for endochondral ossification.

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19.

Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-ß, IL-2 and IL-10, ß-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-ß, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of "protection of the fetus" from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother's body is responding to the viral attack. These results allow us to hypothesize a mechanism of "trafficking" of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress.

Functional brain network topology across the menstrual cycle is estradiol dependent and correlates with individual well-being.

The menstrual cycle (MC) is a sex hormone-related phenomenon that repeats itself cyclically during the woman's reproductive life. In this explorative study, we hypothesized that coordinated variations of multiple sex hormones may affect the large-scale organization of the brain functional network and that, in turn, such changes might have psychological correlates, even in the absence of overt clinical signs of anxiety and/or depression. To test our hypothesis, we investigated longitudinally, across the MC, the relationship between the sex hormones and both brain network and psychological changes. We enrolled 24 naturally cycling women and, at the early-follicular, peri-ovulatory, and mid-luteal phases of the MC, we performed: (a) sex hormone dosage, (b) magnetoencephalography recording to study the brain network topology, and (c) psychological questionnaires to quantify anxiety, depression, self-esteem, and well-being. We showed that during the peri-ovulatory phase, in the alpha band, the leaf fraction and the tree hierarchy of the brain network were reduced, while the betweenness centrality (BC) of the right posterior cingulate gyrus (rPCG) was increased. Furthermore, the increase in BC was predicted by estradiol levels. Moreover, during the luteal phase, the variation of estradiol correlated positively with the variations of both the topological change and environmental mastery dimension of the well-being test, which, in turn, was related to the increase in the BC of rPCG. Our results highlight the effects of sex hormones on the large-scale brain network organization as well as on their possible relationship with the psychological state across the MC. Moreover, the fact that physiological changes in the brain topology occur throughout the MC has widespread implications for neuroimaging studies.

Noninvasive screening for congenital heart defects using a serum metabolomics approach.

OBJECTIVE: Heart anomalies represent nearly one-third of all congenital anomalies. They are currently diagnosed using ultrasound. However, there is a strong need for a more accurate and less operator-dependent screening method. Here we report a metabolomics characterization of maternal serum in order to describe a metabolomic fingerprint representative of heart congenital anomalies. METHODS: Metabolomic profiles were obtained from serum of 350 mothers (280 controls and 70 cases). Nine classification models were built and optimized. An ensemble model was built based on the results from the individual models. RESULTS: The ensemble machine learning model correctly classified all cases and controls. Malonic, 3-hydroxybutyric and methyl glutaric acid, urea, androstenedione, fructose, tocopherol, leucine, and putrescine were determined as the most relevant metabolites in class separation. CONCLUSION: The metabolomic signature of second trimester maternal serum from pregnancies affected by a fetal heart anomaly is quantifiably different from that of a normal pregnancy. Maternal serum metabolomics is a promising tool for the accurate and sensitive screening of such congenital defects. Moreover, the revelation of the associated metabolites and their respective biochemical pathways allows a better understanding of the overall pathophysiology of affected pregnancies.

Differences between influenza and pertussis vaccination uptake in pregnancy: a multi-center survey study in Italy.

BACKGROUND: A suboptimal maternal vaccination coverage in 2017-18 has been reported in Italy. The study aims were to (i) assess changes in maternal influenza and tetanus, diphtheria and acellular pertussis vaccination coverage during 2018-19 influenza season compared to the previous season (ii) estimate influenza vaccine coverage among maternal care providers (MCPs) and (iii) explore the characteristics of vaccine delivery to pregnant women. METHODS: We conducted a cross-sectional survey among pregnant women and MCPs about influenza and pertussis immunization during pregnancy. We also collected information regarding prenatal care characteristics and vaccine delivery among four centers in Italy. RESULTS: We recruited 483 pregnant women and 452 MCPs. The influenza and pertussis vaccine uptake among pregnant women for the season 2018-19 was 14.9% and 60.9%, respectively. MCPs' influenza vaccine uptake was 33.6%. Knowing that the flu vaccine was safe for mothers and their infants and being vaccinated in the previous influenza season were associated with higher vaccine uptake. Regarding pertussis, being a housewife was associated to lower vaccine uptake, while knowing the vaccine is effective and safe for mothers and newborns were associated with higher pertussis vaccine uptake. The single most important factor associated to higher coverage of both influenza and pertussis vaccines was receiving a health-care provider's vaccine advice. Most pregnant women (69.4%) stated that they preferred to be vaccinated in their same prenatal care setting. CONCLUSIONS: Receiving a health-care provider's vaccine advice and the availability of vaccines during prenatal care visits might improve vaccination coverage among pregnant women.

A pilot study of next generation sequencing-liquid biopsy on cell-free DNA as a novel non-invasive diagnostic tool for Klippel-Trenaunay syndrome.

OBJECTIVES: Somatic mosaicism of PIK3CA gene is currently recognized as the molecular driver of Klippel-Trenaunay syndrome. However, given the limitation of the current technologies, PIK3CA somatic mutations are detected only in a limited proportion of Klippel-Trenaunay syndrome cases and tissue biopsy remains an invasive high risky, sometimes life-threatening, diagnostic procedure. Next generation sequencing liquid biopsy using cell-free DNA has emerged as an innovative non-invasive approach for early detection and monitoring of cancer. This approach, overcoming the space-time profile constraint of tissue biopsies, opens a new scenario also for others diseases caused by somatic mutations. METHODS: In the present study, we performed a comprehensive analysis of seven patients (four females and three males) with Klippel-Trenaunay syndrome. Blood samples from both peripheral and efferent vein from malformation were collected and cell-free DNA was extracted from plasma. Tissue biopsies from vascular lesions were also collected when available. Cell-free DNA libraries were performed using Oncomine™ Pan-Cancer Cell-Free Assay. Ion Proton for sequencing and Ion Reporter Software for analysis were used (Life Technologies, Carlsbad, CA, USA). RESULTS: Cell-free circulating DNA analysis revealed pathogenic mutations in PIK3CA gene in all patients. The mutational load was higher in plasma obtained from the efferent vein at lesional site (0.81%) than in the peripheral vein (0.64%) leading to conclude for a causative role of the identified variants. Tissue analysis, available for one amputated patient, confirmed the presence of the mutation at the malformation site at a high molecular frequency (14-25%), confirming its causative role. CONCLUSIONS: Our data prove for the first time that the cell-free DNA-next generation sequencing-liquid biopsy, which is currently used exclusively in an oncologic setting, is indeed the most effective tool for Klippel-Trenaunay syndrome diagnosis and tailored personalized treatment.

Prediction of placenta accreta spectrum in patients with placenta previa using clinical risk factors, ultrasound and magnetic resonance imaging findings.

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.

Variations in sleep associated with different types of hormonal contraceptives.

Progesterone and some of its metabolites are neuroactive steroids that affect sleep by increasing melatonin secretion and stimulating GABA-A receptors. The effect of progestogens in hormonal contraceptives on sleep has not been thoroughly investigated. This observational study assessed possible associations in sleep changes induced by estrogen-progestogens in contraceptives in 108 women between the ages of 20 and 50 years. We assessed mean nightly sleep time with a 31-day sleep diary, and subjective sleep quality with the five subjective subscores of the Pittsburgh Sleep Quality Index (PSQI). Included women were of childbearing age, healthy, sexually active and had been using a hormonal contraceptive method (pill, intrauterine system (IUS), subcutaneous implant, vaginal ring) for at least six months. Results were compared to a matched control group that did not use hormonal contraceptives. The longest mean nightly sleep time, compared to control (450 min), occurred in women who used progestogen-only oral contraception (510 min), followed by IUS delivery of levonorgestrel 13.5 mg (480 min) and oral ethinylestradiol 0.02/0.03 mg plus gestodene 0.075 mg (475 min). Global subjective sleep quality was influenced most by the administration of etonorgestrel 0.120 mg/ethinylestradiol 0.015 mg via the vaginal route. Our results show that low-doses of progestins affect various aspects of sleep, and that this is influenced by the route of administration.

First trimester detection of fetal open spina bifida using BS/BSOB ratio.

BACKGROUND: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect. OBJECTIVE: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound. METHODS: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves. RESULTS: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649. CONCLUSION: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida.

Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Sexual intercourse during pregnancy is commonly believed to trigger the onset of contractions and, therefore, labor. However, in low-risk pregnancies, there is neither association with preterm birth, premature rupture of membranes, or low birth weight, nor with spontaneous onset of labor at term. AIM: To evaluate the effectiveness of sexual intercourse for spontaneous onset of labor at term in singleton pregnancies. METHODS: The systematic search was conducted using electronic databases from inception of each database to June 2019. Review of articles also included the abstracts of all references retrieved from the search. Inclusion criteria were randomized controlled trials comparing sexual intercourse in singleton low-risk pregnancies at term with controls (either reduced number of coitus or no coitus) for spontaneous onset of labor. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME MEASURES: The primary outcome was the incidence of spontaneous onset of labor. The summary measures were reported as summary relative risk with 95% CI using the random-effects model of DerSimonian and Laird. RESULTS: Data extracted from 3 trials, including 1,483 women with singleton pregnancy at term and cephalic presentation, were analyzed. Women who were randomized in the sexual intercourse group had similar incidence of spontaneous onset of labor compared with control subjects (0.82% vs 0.80%; relative risk 1.02, 95% CI 0.98-1.07). CLINICAL IMPLICATION: Sexual intercourse should not be restricted in low-risk term pregnancies. Further studies are needed to properly evaluate the impact of orgasm, penetration, condom use, frequency of intercourse and other factors on induction of labor at term. STRENGTH & LIMITATIONS: Our study has several strengths. The three included trials had low risk of allocation bias; intention-to-treat analysis was used; this is the first meta-analysis on this issue so far. Limitations mainly depend on the design of the included studies. Firstly, compliance to the protocol relied on self-reporting by patients; in addition, not all the features of sexual intercourse could be adequately assessed (orgasm, nipple stimulation, sexual positions, etc.). CONCLUSION: In women with singleton, cephalic, low-risk pregnancies, sexual intercourse at term does not significantly increase the incidence of spontaneous onset of labor. Carbone L, De Vivo V, Saccone G, et al. Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Sex Med 2019;16:1787-1795.

Serum metallome in pregnant women and the relationship with congenital malformations of the central nervous system: a case-control study.

BACKGROUND: Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. METHODS: Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. RESULTS: We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 µg/L Vs 1.44 ± 4.21 µg/L, p < 0.0006) and to Controls (i.e. mothers carrying a normally-developed fetus) (6.45 ± 15.15 µg/L Vs 0.11 ± 0.51 µg/L, p < 0.0006). Moreover, Aluminum abundances were below the limit of detection in the majority of control samples. CONCLUSION: CAluminum may play a role in the onset of central nervous system malformations, although the exact Aluminum species and related specific type of malformation needs further elucidation.

Metabolomic Signature of Endometrial Cancer.

Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed countries. At the moment, no effective screening system is available. Here, we evaluate the diagnostic performance of a serum metabolomic signature. Two enrollments were carried out, one consisting of 168 subjects: 88 with EC and 80 healthy women, was used for building the classification models. The second (used to establish the performance of the classification algorithm) was consisted of 120 subjects: 30 with EC, 30 with ovarian cancer, 10 with benign endometrial disease, and 50 healthy controls. Two ensemble models were built, one with all EC versus controls (Model I) and one in which EC patients were aggregated according to their histotype (Model II). Serum metabolomic analysis was conducted via gas chromatography-mass spectrometry, while classification was done by an ensemble learning machine. Accuracy ranged from 62% to 99% for the Model I and from 67% to 100% for the Model II. Ensemble model showed an accuracy of 100% both for Model I and II. The most important metabolites in class separation were lactic acid, progesterone, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, and valine. The serum metabolomics signature of endometrial cancer patients is peculiar because it differs from that of healthy controls and from that of benign endometrial disease and from other gynecological cancers (such as ovarian cancer).