Investigating exposure to endocrine disruptors via hair analysis of pregnant women.

The aim of this study was the monitoring of the levels of parabens (PBs) and triclosan (TCS) in head hair samples of women collected during the first months of their pregnancy. Personal details concerning somatometric and demographic characteristics, dietary habits, use of personal care products and the medical and obstetrical history of the pregnant women as well as infants' somatometric characteristics and health condition were recorded through relevant questionnaires. Ninety five hair samples were collected, extracted by solid-liquid extraction and analysed using a liquid chromatography-mass spectrometry system (LC-MS). Analysis revealed high percentage of positive samples for all tested compounds (90-100% except from BePB (15.8%)). The mean concentration levels were 4501.2 pg/mg (17.6-27,437.0 pg/mg) for MePB; 510.1 pg/mg (11.0-4224.5 pg/mg) for EtPB; 22.9 pg/mg (2.1-66.6 pg/mg) for BePB; 237.1 pg/mg (1.8-2513.7 pg/mg) for BuPB and 245.0 pg/mg (8.8-8070.2 pg/mg) for TCS. Statistical analysis of both analytical results and questionnaires' data showed that the frequent use of personal care and hygiene products, such as makeup, hairspray and sunscreens, is correlated with higher levels of PBs in hair of the pregnant women. Additionally, positive correlation was observed between the BePB levels in hair and the infants' height. Finally, no other correlation was observed between endocrine disruptors' levels in maternal hair and infants' somatometric characteristics or health condition. Our study is the first one that determined PBs and TCS levels in hair samples, simultaneously. At the same time, correlation of the detected levels with the use of personal care products was accomplished, leading to significant association of BePB levels in hair of pregnant women with infants' height.

Biomonitoring of bisphenol A, triclosan and perfluorooctanoic acid in hair samples of children and adults.

Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry. Low levels of exposure to PFOA were detected for children and adults at concentrations below limit of quantification. The mean concentration of BPA in children and adults was 20.6 and 16.6 pg mg-1 , while for TCS 275.2 and 687.0 pg mg-1 , respectively. Children were highly exposed to BPA relative to adults (P = .011) although adults had greater exposure to TCS (P = .003). Hair from girls had a greater burden of BPA (P = .06) compared to boys. Moreover, higher TCS levels were depicted for females in both examined groups (children P = .200 and adults P = .213) compared to males, but no statistical differences were observed. Significant differences were also observed between age groups (P = .0007) for TCS. No correlations were found between BPA or TCS levels and body mass index or dietary habits for both children and adults. Children have a greater exposure to BPA compared to adults, whereas exposure of adults to TCS seems to be higher than that in children and elderly people. Exposure to BPA occurs mainly via ingestion whereas exposure to TCS mainly via dermal absorption.

Plasma biomarkers for the identification of women at risk for early-onset preeclampsia.

BACKGROUND: To identify potential biomarkers in the 1st trimester of pregnancy for the identification of women destined to develop early onset preeclampsia (EOPE). METHODS: Blood samples were obtained from pregnant women at 11-13 weeks of gestation. Women were followed up until delivery. Five samples from EOPE complicated pregnancies and 5 from unaffected ones were analysed using 2-DE and MALDI-TOF-TOF MS/MS. The altered expression of selected proteins was verified by ELISA in an extended sample cohort. RESULTS: Twelve proteins were differentially expressed in the plasma of women who subsequently developed EOPE as compared to controls. Alpha-1-antitrypsin (A1AT), CD5 antigen-like molecule (CD5L) Keratin, type I cytoskeletal 9 (K1C9), Myeloid cell nuclear differentiation antigen (MNDA), Transferrin (TRFE) and Vitamin D-binding protein (VTDB) were up-regulated with fold changes 3.14, 2.18, 1.53, 1.53, 4.26 3.38 respectively, whereas Alpha-2-HS-glycoprotein (FETUA), Beta-2-glycoprotein 1 (APOH), Complement factor B (CFAB), Haptoglobin (HPT), Vitronectin (VTNC) and Zinc-alpha-2-glycoprotein (ZA2G) were down-regulated with fold changes -0.38, -0.76, -0.24, -0.47, -0.23, and -0.50 respectively. The down-regulation of APOH, VTNC and HPT was verified using ELISA. CONCLUSIONS: The differentially expressed proteins represent potential biomarkers for the early screening for EOPE. Follow-up experiments however are necessary for evaluation.

Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

INTRODUCTION: Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship. MATERIALS AND METHODS: This is a narrative review of the current literature, following a search on MEDLINE and the Cochrane Library, from their inception until January 2012. Articles investigating gynecologic cancer (endometrial, ovarian, and breast) incidence in diabetic patients were extracted. RESULTS: The strong evidence for a positive association between diabetes mellitus and the risk for cancer indicates that energy intake in excess to energy expenditure, or the sequelae thereof, is involved in gynecological carcinogenesis. This risk may be further heightened by glucose which can directly promote the production of tumor cells by functioning as a source of energy. Insulin resistance accompanied by secondary hyperinsulinemia is hypothezised to have a mitogenic effect. Steroid hormones are in addition potent regulators of the balance between cellular differentiation, proliferation, and apoptosis. Inflammatory pathways may also be implicated, as a correlation seems to exist between diabetes mellitus and breast or endometrial carcinoma pathogenesis, although an analogous correlation with ovarian carcinoma is still under investigation. Antidiabetic agents have been correlated with elevated cancer risk, while metformin seems to lower the risk. CONCLUSION: Diabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.

Expression profile of CYP1A1 and CYP1B1 enzymes in endometrial tumors.

The cytochrome P450 CYP1A1 and CYP1B1 enzymes are phase I extrahepatic enzymes involved in the activation of pro-carcinogenic compounds to carcinogenic metabolites. Although differential overexpression of CYP1A1 and CYP1B1 has been documented at the messenger RNA (mRNA) and protein level, studies that have examined CYP1 expression by enzyme activity assays are limited. In the current study, the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of endometrial origin by quantitative reverse transcriptase PCR (qRT-PCR), Western blotting, and enzyme activity assays. The data revealed that approximately 36 % (5/14) and 43 % (6/14) of the endometrial tumors overexpressed CYP1A1 and CYP1B1 mRNA, whereas in 57 % of the endometrial tumors, CYP1 mRNA levels were downregulated. The mean mRNA levels of CYP1B1 and CYP1A1 in endometrial tumors did not show a significant difference compared to normal tissues (p > 0.05). Western blotting confirmed the qRT-PCR results and CYP1A1 and CYP1B1 proteins were shown to be downregulated in 7/14 (50 %) of the tumors and overexpressed in 4/14 (29 %) of the tumors. As regards to enzyme activity, 21 % (3/14) of the endometrial samples revealed elevated CYP1 activity levels across the tumor counterparts. Overall, the data suggest a putative downregulation of CYP1A1 and CYP1B1 expression in endometrial tumors, whereas overexpression of active CYP1 enzymes in 21 % of the tumors highlights the potential use of the latter enzymes as chemotherapeutic targets in endometrial cancer.

Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature.

BACKGROUND: Partial trisomy of the long arm of chromosome 1 (1q) is an exceptionally rare chromosomal abnormality and most of the prenatally diagnosed cases are associated with either complete (q11-qter) or large (q21-qter) duplications with pre- or perinatal demise of all reported cases. The most common sonographic findings associated with this karyotype abnormality include ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac abnormalities, craniofacial dysmorphism, and limb deformities. However, there is a wide spectrum of clinical manifestations due to the great variability in the extent of the duplication size and the possible contribution of additional genetic rearrangements in the final phenotype. CASE REPORT: We report on a female fetus with sole partial trisomy 1q presenting with multiple structural malformations in the second trimester scan. Standard karyotyping demonstrated a large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter→q31::q31→q12::q31→qter)] and further application of comparative genomic hybridization array confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSION: A fetus with nonmosaic partial trisomy 1q that was prenatally diagnosed upon multiple abnormal ultrasound findings is presented. A detailed review of the currently available literature on the prenatal diagnostic approach of partial trisomy 1q in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided. The use of novel molecular techniques such comparative genomic hybridization array could shed further light on the correlation between the genes identified in the chromosomal region of interest and the resultant phenotype.

Cell­free fetal DNA at 11­13 weeks of gestation is not altered in complicated pregnancies.

Non-invasive maternal cell-free fetal DNA (cffDNA) is a promising biomarker for screening common genetic syndromes. Alterations in the expression levels of cffDNA in the maternal circulation have been demonstrated in abnormal pregnancies. However, the results are conflicting. The present study aimed to investigate whether cffDNA levels are associated with pregnancy complications. The study group comprised pregnant women who presented with pregnancy complications, such as preterm birth, gestational hypertension, intrauterine growth retardation, gestational diabetes, polyhydramnios, oligohydramnios, vaginal bleeding and placental abruption. The control group comprised women who had a normal pregnancy course. Blood samples were obtained from 500 pregnant women between 11-13 weeks of gestation. cffDNA was amplified, sequenced and analyzed using the next-generation aneuploidy test of a Panorama-Natera kit. Nuchal translucency (NT) thickness as well as pregnancy associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were also assessed. Statistical analysis was performed in 494 out of the 500 samples collected with SPSS v.26 using non-parametric methods. The parameters were normalized by the multiples of median (MoM) method. The expression levels of PAPP-A, ß-hCG, and the NT mean MoM values were significantly different between the study and control groups (P=0.005, P<0.001 and P=0.007, respectively). However, the expression levels of cffDNA and the mean MoM values were not significantly different between these two groups (P=0.687). The findings of the present study support the conclusion that cffDNA expression is not altered in a series of pregnancy complications. The prognostic value of cffDNA in predicting adverse pregnancy outcomes requires further investigation.

Prognostic value of tgfb1 protein in endometrioid adenocarcinoma.

BACKGROUND: Angiogenesis is a prerequisite for tumour development, progression and metastasis; however, its underlying molecular mechanisms in endometrial carcinoma are poorly understood. DESIGN: In this study, the mRNA and protein expression profiles of two key regulators of angiogenesis, vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGFB1), were evaluated by real-time PCR and western blot analysis in 23 endometrial cancer tissue-paired specimens (malignant vs. adjacent normal tissues). We aimed to investigate whether VEGF and TGFB1 serve as markers of the malignant transformation of the endometrium and whether VEGF or TGFB1 expression can constitute a useful prognostic marker of survival in patients with endometrial carcinoma. RESULTS: Tissue-pair analysis revealed VEGF transcriptional up-regulation and TGFB1 mRNA down-regulation as the most frequent transcriptional features. VEGF and TGFB1 mRNA were positively correlated (P < 0·001). VEGF protein levels were higher in endometrioid-type tissue pairs (P = 0·047). TGFB1 protein and mRNA levels were negatively correlated (P = 0·042). TGFB1 protein expression was related to survival only in patients with endometrioid adenocarcinoma (P = 0·045). CONCLUSIONS: Tissue-pair mRNA and protein analysis reveals VEGF transcriptional up-regulation and TGFB1 down-regulation that are correlated with the malignant transformation of the endometrium, while post-transcriptional mechanisms control VEGF and TGFB1 protein. TGFB1 protein demonstrated a prognostic value only in endometrioid adenocarcinoma.

Therapeutic management of fetal anemia: review of standard practice and alternative treatment options.

Fetal anemia, mainly due to red cell alloimmunization, is still a significant cause of fetal and neonatal mortality and morbidity. The focus of current clinical research has shifted from an invasive approach to non-invasive management and treatment of affected pregnancies, and the progress in this field is associated with a major improvement in perinatal outcome. During the last 50 years, intrauterine red cells transfusion (IUT), fi rst via the intraperitoneal route and later directly to fetal circulation, is the standard practice in most centers, with survival rates that exceed 90 % , particularly if anemia is diagnosed early and treated in a timely manner. In addition, plasmapheresis and intravenous administration of highdose immunoglobulin have been implicated in the treatment of pregnancies complicated with early-onset severe red cell alloimmunization, alone or in combination with IUTs before the 20(th) week of pregnancy, but there are still issues to be clarified further. This review article aims to provide an overview of the current standard therapeutic management and alternative treatment modalities in pregnancies complicated by fetal anemia.

Predictive value of the sFlt­1/PlGF ratio in women with suspected preeclampsia: An update (Review).

Preeclampsia (PE) is a major complication of pregnancy with an incidence rate of 2­8% and is a leading cause of maternal mortality and morbidity. The various consequences of severe preeclampsia for the fetus, neonate and child include intrauterine growth retardation (IUGR), fetal hypoxia, oligohydramnios, intrauterine fetal demise, increased perinatal mortality and morbidity, neurodevelopmental disorders and even irreversible brain damage (cerebral palsy). A number of studies have demonstrated that differences in maternal serum concentrations of angiogenic factors between preeclampsia and normotensive pregnancies can be used as biomarkers, either alone or in combination with other markers, to predict the development of PE. The presence in the maternal circulation of two proteins of placental origin, placental growth factor (PlGF) and soluble fms­like tyrosine kinase 1 (sFlt­1), has been shown to be of clinical value, as the sFlt­1/PlGF ratio appears to be the optimal predictive tool for the development of PE. The measurement of their concentration in maternal serum in screening models, serves as predictive marker for the development of PE or IUGR later in gestation. However, further research is required to improve its clinical applicability and provide guidelines for its use worldwide to achieve more consistent clinical management of women with PE.

Bacterial Vaginosis and Post-Operative Pelvic Infections.

Bacterial vaginosis (BV) represents a condition in which the normal protective Lactobacilli, especially those that produce H2O2, are replaced by high quantities of facultative anaerobes, leading to gynecologic and obstetric post-operative complications. BV is an important cause of obstetric and gynecological adverse sequelae and it could lead to an increased risk of contracting sexually transmitted infections such as gonorrhea, genital herpes, Chlamydia, Trichomonas, and human immunodeficiency virus. Herein, we reviewed bacterial vaginosis and its association with post-operative pelvic infections. In Obstetrics, BV has been associated with increased risk of preterm delivery, first-trimester miscarriage in women undergoing in vitro fertilization, preterm premature rupture of membranes, chorioamnionitis, amniotic fluid infections, postpartum and postabortal endomyometritis as well as postabortal pelvic inflammatory disease (PID). In gynecology, BV increases the risk of post-hysterectomy infections such as vaginal cuff cellulitis, pelvic cellulitis, pelvic abscess, and PID. BV is often asymptomatic, can resolve spontaneously, and often relapses with or without treatment. The American College of Obstetricians and Gynecologists recommends testing for BV in women having an increased risk for preterm delivery. Women with symptoms should be evaluated and treated. Women with BV undergoing gynecological surgeries must be treated to reduce the frequency of post-operative pelvic infections. Metronidazole and clindamycin are the mainstays of therapy. Currently, there is no consensus on pre-surgery screening for BV; decisions are made on a case-by-case basis.

Rare case of XX/XY mosaicism and trisomy 13 in early prenatal diagnosis.

Coexistence of XX/XY sex mosaicism and autosomal trisomy in prenatal diagnosis is particularly rare. Herein, we report the first, to our knowledge, case of a fetus with cyclopia, ambiguous genitalia and a 47,XX,+13,inv9[47]/47,XY,+13[13] karyotype detected at 13 weeks of gestation after chorionic villus sampling. Molecular analysis after prenatal diagnosis suggests that this is a case of sex mosaicism coexisting with trisomy 13, rather than chimera.

Familial Pelizaeus-Merzbacher disease caused by a 320.6-kb Xq22.2 duplication and the pathological findings of a male fetus.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) is a recessive, X-linked leukoencephalopathy attributed to impaired myelination during central nervous system development, caused by defects in the proteolipid protein 1 (PLP1) gene. PMD presents clinical variability, ranging from the severe connatal form to the classic form. CASES: We report the clinical and molecular findings of two affected males, three carrier females, and an aborted male fetus with familial PMD. The two male probands presented with severe PMD phenotype and intellectual disability. High-resolution oligonucleotide-based array comparative genomic hybridization (aCGH) identified an Xq22.2 duplication of 320.6 kb (102641391-102961998, hg18), including the PLP1 gene and surrounding chromosomal region. Postmortem examination of the aborted fetus at 25 weeks' gestation showed focal subcortical white matter degeneration, focal gliosis, and cerebellar atrophy. CONCLUSIONS: Genotype-phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the PLP1 gene has a more complex role in human brain development, exceeding its structural function in myelin formation.

Immune aspects and myometrial actions of progesterone and CRH in labor.

Progesterone and corticotropin-releasing hormone (CRH) have a critical role in pregnancy and labor, as changes related to these hormones are crucial for the transition from myometrial quiescence to contractility. The mechanisms related to their effect differ between humans and other species, thus, despite extensive research, many questions remain to be answered regarding their mediation in human labor. Immune responses to progesterone and CRH are important for labor. Progesterone acts as an immunomodulator which controls many immune actions during pregnancy, and its withdrawal releases the inhibitory action on inflammatory pathways. In humans, a "functional" progesterone withdrawal occurs with onset of labor through changes in progesterone metabolism, progesterone receptors, and other molecules that either facilitate or antagonize progesterone function. Placental CRH acts on the fetal pituitary-adrenal axis to stimulate adrenal production of androgens and cortisol and also acts directly on myometrial cells via its receptors. CRH also affects inflammatory signals and vice versa. Interactions between progesterone and CRH additionally occur during labor. We describe the role of these two hormones in human myometrium and their interactions with the immune system during labor.

Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities. Evaluation of 13,500 cases with consideration of using QF-PCR as a stand-alone test according to referral indications.

OBJECTIVE: Evaluate the results obtained from Quantitative Fluorescent (QF)-PCR and conventional karyotype analysis to determine the advantages and disadvantages of dual testing in prenatal diagnosis. METHODS: From 1 June 2006 to 1 June 2010, dual testing by QF-PCR and karyotype analysis was performed in 13,500 prenatal samples. The rates of concordant results between the two methods were evaluated and the rates of clinically significant chromosomal abnormalities undetected by QF-PCR were assessed. RESULTS: Abnormal karyotype was found in 320 out of 13,500 cases (2.37%, 95% confidence interval (CI) 2.11-2.63%). From these, QF-PCR did not detect the abnormality in 70 cases (0.52%, 95% CI 0.4-0.64%), whereas 34 had a high/unknown risk of adverse outcome (0.25%, 95% CI 0.17-0.33%). By selectively applying dual testing only at cases with ultrasound findings and/or genetic history, 13 cases of high/unknown risk would have been missed (0.1%, 95% CI 0.05-0.15%). CONCLUSION: Selective dual testing is expected to achieve a serious beneficial economical outcome and reduce parental anxiety produced by ambiguous cytogenetic findings. However, the percentage of 0.1% undetected clinically significant abnormalities cannot be ignored. A suggestion would include the offering of a choice to the pregnant women, undergoing prenatal screening, by informing them about different approaches and various complications.

Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights.

The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.

Fetal longitudinal myocardial function assessment by anatomic M-mode.

AIM: To evaluate the feasibility of offline anatomic M-mode (AMM) to study fetal atrioventricular annulus long-axis displacement (LAD) and compare its performance against real-time conventional M-mode (MM). MATERIAL AND METHODS: Paired AMM and MM LAD studies were recorded prospectively in 54 fetuses, and performance was compared. Insonation angles were less than 30° in all but 4 cases. The overall feasibility of AMM was tested in a composite total sample of 91 normal singleton pregnancies (median gestational age 23⁺6 weeks, range 12-36). AMM LAD was measured by placement of a virtual M-mode line on digitally stored raw data of fetal 4-chamber video loops. We studied annulus LAD at the lateral mitral (left ventricle; LV), proximal mitral (intraventricular septum; IVS), and lateral tricuspid (right ventricle; RV) myocardial segments. We compared LAD and its regression with gestational age measured using both methods in paired studies and AMM in the whole cohort. RESULTS: Annulus LAD was measured using AMM, in all cases and segments, irrespective of cardiac axis alignment to the ultrasound beam. Good correlation existed between AMM and MM (RV r = 0.901, LV r = 0.899, IVS r = 0.815, p < 0.001). AMM recorded higher LAD values than MM in RV [mean 6.17 (SD 1.46) vs. 5.82 (SD 1.74) mm, p = 0.002] and LV [mean 4.18 (SD 1.11) vs. 3.98 (SD 1.12), p = 0.007]. Both methods showed LAD in RV > LV > IVS and a significant gestational increase in LAD values in all segments (p < 0.001) CONCLUSIONS: AMM permits offline evaluation of fetal longitudinal myocardial function in routinely obtained 2D fetal heart images with similar values to conventional MM in paired studies recorded <30°.

Improving tissue characterization, differentiation and diagnosis in gynecology with the narrow-band imaging technique: A systematic review.

Narrow-band imaging (NBI), an on-demand, real-time endoscopic imaging technique, was developed to enhance visualization of the mucosal vascular network and surface texture. The present article provides a systematic review of studies that assessed the use of NBI in gynecological endoscopy. The following electronic databases were searched: PubMed (1950-2020), Google Scholar (2004-2020) and Cochrane Library (2010-2020). In the initial search, 3,836 entries were identified, of which 31 were finally included in the systematic review. Of the selected studies, 10 (32%) were case reports, 19 (61.2%) were prospective studies and 2 (6.4%) were randomized controlled trials with control groups. The selected studies reported on the use of NBI in hysteroscopy, laparoscopy and colposcopy. It was revealed that NBI utilization in hysteroscopy increased the accuracy, sensitivity and specificity in detecting malignant and premalignant lesions. NBI improved the specificity and sensitivity in the detection of endometriotic lesions and cervical lesions. Conventional white light endoscopy in gynecology may be significantly improved by the use of NBI. Further studies with larger cohorts and improved design are required to achieve more reliable results. It is of special interest that utilization of this method requires apparatus which is expensive; concerns are the long training and experience of staff required and the long learning curve.

Effectiveness of Non-Pharmacological Methods, Such as Breastfeeding, to Mitigate Pain in NICU Infants.

Neonates do experience pain and its management is necessary in order to prevent long-term, as well as, short-term effects. The most common source of pain in the neonatal intensive care unit (NICU) is caused by medically invasive procedures. NICU patients have to endure trauma, medical adhesive related skin injuries, heel lance, venipuncture and intramuscular injection as well as nasogastric catheterization besides surgery. A cornerstone in pain assessment is the use of scales such as COMFORT, PIPP-R, NIPS and N-PASS. This narrative review provides an up to date account of neonate pain management used in NICUs worldwide focusing on non-pharmacological methods. Non-steroidal anti-inflammatory drugs have well established adverse side effects and opioids are addictive thus pharmacological methods should be avoided if possible at least for mild pain management. Non-pharmacological interventions, particularly breastfeeding and non-nutritive sucking as primary strategies for pain management in neonates are useful strategies to consider. The best non-pharmacological methods are breastfeeding followed by non-nutritive sucking coupled with sucrose sucking. Regrettably most parents used only physical methods and should be trained and involved for best results. Further research in NICU is essential as the developmental knowledge changes and neonate physiology is further uncovered together with its connection to pain.

CNS imaging is a key diagnostic tool in the evaluation of patients with CFC syndrome: two cases and literature review.

Cardio-facio-cutaneous (CFC) syndrome is characterized by a variable degree of cognitive impairment, and multiple congenital anomalies including characteristic facies, cardiac, and ectodermal abnormalities. CFC syndrome is caused by mutations in the genes BRAF, MEK1, or MEK2. Here we provide a follow-up report on two patients presenting distinct facial appearance and other features of the syndrome, and we present the first molecular evidence of paternal origin for a CFC-causing germline mutation. Brain imaging revealed a lipoma of the corpus callosum and periventricular leukoencephalopathy as well as a hypoplastic corpus callosum, and defects in myelinization, in each patient, respectively. A review of the literature showed that, although non-specific, ventriculomegaly, hydrocephalus, and cortical atrophy represent the most frequent imaging findings of brain anomalies in CFC syndrome. CNS abnormalities are significant diagnostic features of CFC syndrome and a brain MRI is recommended in individuals diagnosed with CFC or suspected of having CFC syndrome.