Search

Objectives: The primary aim of the study was to evaluate the prevalence of fetal heart tumors in a single tertiary referral center over a period of 15 years. The secondary aim was to confirm the presence of tuberous sclerosis complex (TSC) through the evaluation of germline mutation in TSC1 / TSC2 and assess the outcomes in affected fetuses and newborns. Methods: A retrospective study was conducted between 2003 and 2017. Fetal echocardiography was performed in the second trimester of pregnancy in the study population. The identification of heart tumors and further follow-up were performed by a pediatric cardiologist. Molecular genetic analysis was conducted on fetuses and children in cases where TSC was suspected. Results: In total, 39,018 fetuses were examined between 2003 and 2017. Heart tumors were detected in nine fetuses and were diagnosed as rhabdomyoma in all cases. We identified mutations in one of the TSC1 or TSC2 genes in all cases with multiple rhabdomyomas (8/9). In all born children (5/9), the genetically confirmed diagnosis of TSC was established, and clinically pathological deposits in the brain were found. Conclusion: Fetal heart tumors are usually represented by rhabdomyomas having a good cardiac prognosis. However, rhabdomyoma is usually the first symptom of TSC with a subsequent brain disorder and impaired neurological development.

Introduction: Worldwide, there are more lesbians who chose to have children in the context of a same-sex relationship than ever before. The Czech studies focusing on this issue, including the analysis of methods of conception, are limited., Aim: We aimed to examine the changes over time in the desire of Czech lesbian women for children and to analyze their chosen methods of conception., Methods: We analyzed retrospectively the personal history of lesbian patients who visited our clinic in the period from 2009 to 2017. Our sample (n = 318) was divided into 2 groups: Group A - our patients between 2009 and 2013, whereas group B comprised our patients from 2013 to 2017., Main Outcome Measures: The outcome of this study is comparing groups A and B, regarding factors associated to parenthood, such as desire to have a child and preferences in methods of conception., Results: We compared group A and group B and obtained the following results: The percentage of homosexual women who did not desire to have a child decreased (22.5% vs 15.6%). Regarding the changes in the preferences in methods of conception among group A and group B, the findings are as follows: a child from a previous relationship (31.2% vs 27.4%), clinically assisted reproduction with an anonymous donor (19.6% vs 30.1%), home intrauterine insemmination with a known donor (24.6% vs 19.2%), clinically assisted reproduction with a known donor (13.1% vs 9.6%), coitus outside the relationship for the purpose of a child conception (9.8% vs 5.5%), home intrauterine insemmination by sperm from an anonymous donor (1.6% vs 4.1%), assisted reproduction performed abroad was selected only in group B (2.7%)., Conclusions: We confirm that the percentage of Czech lesbians who have a child or want to have a child has increased and that several variables regarding the desire for parenthood in the Czech lesbian community are changing over time (eg, methods of conception) mostly in concordance with other Western European countries. Turcan P, Prochazka M, Prochazka P, et al. Desire for Parenthood and Associated Trends in Czech Lesbian Women. Sex Med 2020;8:650-659., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Noninvasive fetal RHD genotyping is an important tool for predicting RhD incompatibility between a pregnant woman and a fetus. This study aimed to assess a methodological approach other than the commonly used one for noninvasive fetal RHD genotyping on a representative set of RhD-negative pregnant women. The methodology must be accurate, reliable, and broadly available for implementation into routine clinical practice. A total of 337 RhD-negative pregnant women from the Czech Republic region were tested in this study. The fetal RHD genotype was assessed using two methods: real-time PCR and endpoint quantitative fluorescent (QF) PCR. We used exon-7-specific primers from the RHD gene, along with internal controls. Plasma samples were analyzed and measured in four/two parallel reactions to determine the accuracy of the RHD genotyping. The RHD genotype was verified using DNA analysis from a newborn buccal swab. Both methods showed an excellent ability to predict the RHD genotype. Real-time PCR achieved its greatest accuracy of 98.6% (97.1% sensitivity and 100% specificity (95% CI)) if all four PCRs were positive/negative. The QF PCR method also achieved its greatest accuracy of 99.4% (100% sensitivity and 98.6% specificity (95% CI)) if all the measurements were positive/negative. Both real-time PCR and QF PCR were reliable methods for precisely assessing the fetal RHD allele from the plasma of RhD-negative pregnant women.

A lack of nurses in the Czech Republic is an issue that has been under discussion for several years. The aim of this paper is to analyze the lack and need of general nurses and midwives in the Hradec Kralove region where the shortage is higher than the national average. The used methods are quantitative research and structured interviews, to determine the number of nurses in healthcare institutions. The study uses data obtained from publicly available sources, i.e., Czech Statistical Office (CSO) and the National Institute of Education (NIE). The shortage of nurses in the Hradec Kralove region can be expected by 2030 to be in the range between 647.6 and 667.1 nurses while maintaining the existing conditions, that is, five times more than at present. In addition to the commonly considered measures that appear in the country's strategies-such as improving the quality of conditions during studies and during employment, specifying or adjusting the role and competency of nurses and midwives in the healthcare system, or unifying employment standards- a focus on promoting the nursing profession can be recommended. Schools and ministries should be encouraged to focus on and invest in the promotion of this profession, so as to play a key role in recruiting new students for the nursing field of study at a time when the nursing profession is perceived positively, as an embodiment of solidarity and selflessness., Competing Interests: The authors declare no conflict of interest.

Soil-transmitted helminthiases (STH) are one of 17 neglected tropical diseases (NTDs) earmarked for control or elimination by 2020 in the WHO's Roadmap on NTDs. Deworming programs for STH have thus far been focused on treating pre-school and school-aged children; however, there is a growing consensus that to achieve elimination of STH transmission, programs must also target adults, potentially through community-wide mass drug administration (MDA). There is currently a gap in the literature on what components are required to deliver community-wide MDA for STH in order to achieve high intervention reach and uptake. Nested within the TUMIKIA Project, a cluster randomized trial in Kenya evaluating the effectiveness of school-based deworming versus community-wide MDA, we collected qualitative data from program implementers and recipients in eight clusters where community-wide MDA was delivered. Data collection included semi-structured in-depth interviews (n = 72) and focus group discussions (n = 32). A conceptual framework for drug distribution was constructed to help build an analysis codebook. Case memos were developed for each top-level theme. Community-wide MDA for STH was perceived as a complex intervention with key administrative and social mobilization domains. Key actionable themes included: (1) developing an efficient strategy to allocate reasonable workload for implementers to cover all targeted households; (2) maximizing community drug distributors' motivation through promoting belief in the effectiveness of the intervention and providing sufficient financial incentives; (3) developing effective capacity building strategies for implementers; and (4) implementing a context-adapted community engagement strategy that leverages existing community structures and takes into consideration past community experiences of MDAs. Transitioning from STH control to elimination goals requires significant planning and action to ensure community-wide MDA is delivered with sufficient reach and uptake. We present findings that can inform national deworming programs to increase intervention delivery capacity., Competing Interests: The authors have declared that no competing interests exist.

Aims: To determine the frequency of pregnancy terminations due to prenatal congenital heart defect (CHD) and assess the agreement fetal echocardiography (FECHO) and autopsy findings., Methods: The data were retrospectively assessed between 2008 and 2017 in a population of 116 698 live births. The correlations between the FECHO and autopsy findings were classified into five levels of agreement: complete, partial, altered diagnosis, disagreement, and unfeasible autopsy., Results: Totally, 293 CHDs were identified and 49% of families (143/293) decided to terminate the pregnancy. In 1% (2/143) of cases, the autopsy could not be performed, for the other 99% (141/143), the pathologist confirmed the presence of CHDs. Complete agreement between FECHO and autopsy was achieved in 85% (122/143). In 10% (14/143) of cases, the pathologist found minor findings, which were not described in the FECHO. In 4% (5/143) of cases, the pathologist changed the main diagnosis., Conclusion: Altogether, the results indicated that FECHO is a highly sensitive method for the prenatal detection of CHD but is incapable of detecting the complete spectrum of cardiac defects. Autopsies verified the diagnosis, confirmed the overall impairment in the fetus, and provided data for further counselling of the affected family.

Background: Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them., Methods: To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers., Findings: The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as 'intertwined': related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services., Significance: Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases., Competing Interests: The authors declare that they have no competing interests.

An electrochemical study was performed on the behavior of Ti 3 C 2 T x MXenes prepared by using either HF (MXene1) or LiF/HCl as etchants (MXene2). The use of two redox probes indicates the presence of a higher negative charge density on MXene2 in comparison to MXene1. The characterization of two nanomaterials shows that titanium and fluoride are present higher by one order of magnitude at the interface of MXene2, compared to MXene1. The high Ti and F content is accompanied by a 82-fold larger (249 μA·cm -2 vs. 5.64 μA·cm -2 ) anodic peak at the peak potential near 0.4 V (vs. Ag/AgCl). Similarly, the peak current on MXene2 is 317-fold higher for the oxygen reduction at pH 7.0 (at a voltage of -0.84 V) and 215-fold higher for the reduction of H 2 O 2 at -0.89 V, when compared to MXene1. Graphical abstractDifference in electrochemical behavior of MXene prepared by HF (MXene1) and LiF/HCl (MXene2) as etchants.

Background: Autism spectrum disorders (ASD) and intellectual disabilities (ID) are heterogeneous and complex developmental diseases with significant genetic backgrounds and overlaps of genetic susceptibility loci. Copy number variants (CNVs) are known to be frequent causes of these impairments. However, the clinical heterogeneity of both disorders causes the diagnostic efficacy of CNV analysis to be modest. This could be resolved by stratifying patients according to their clinical features., Aim: First, we sought to assess the significance of particular clinical features for the detection of pathogenic CNVs in separate groups of ID and ASD patients and determine whether and how these groups differ from each other in the significance of these variables. Second, we aimed to create a statistical model showing how particular clinical features affect the probability of pathogenic CNV findings., Method: We tested a cohort of 204 patients with ID ( N  = 90) and ASD ( N  = 114) for the presence of pathogenic CNVs. We stratified both groups according to their clinical features. Fisher's exact test was used to determine the significance of these variables for pathogenic CNV findings. Logistic regression was used to create a statistical model of pathogenic CNV findings., Results: The frequency of pathogenic CNV was significantly higher in the ID group than in the ASD group: 18 (19.78%) versus 8 (7%) ( p  < 0.004). Microcephaly showed a significant association with pathogenic findings in ID patients ( p  < 0.01) according to Fisher's exact test, whereas epilepsy showed a significant association with pathogenic findings in ASD patients ( p  < 0.01). The probability of pathogenic CNV findings when epilepsy occurred in ASD patients was more than two times higher than if epilepsy co-occurred with ID (29.6%/14.0%). Facial dysmorphism was a significant variable for detecting pathogenic CNVs in both groups (ID p = 0.05, ASD p = 0.01). However, dysmorphism increased the probability of pathogenic CNV detection in the ID group nearly twofold compared to the ASD group (44.4%/23.7%). The presence of macrocephaly in the ASD group showed a 25% probability of pathogenic CNV findings by logistic regression, but this was insignificant according to Fisher's exact test. The probability of detecting pathogenic CNVs decreases up to 1% in the absence of dysmorphism, macrocephaly, and epilepsy in the ASD group., Conclusion: Dysmorphism, microcephaly, and epilepsy increase the probability of pathogenic CNV findings in ID and ASD patients. The significance of each feature as a predictor for pathogenic CNV detection differs depending on whether the patient has only ASD or ID. The probability of pathogenic CNV findings without dysmorphism, macrocephaly, or epilepsy in ASD patients is low. Therefore the efficacy of CNV analysis is limited in these patients., Competing Interests: Vera Becvarova and Marie Trkova are employed by Gennet, s. r. o. The authors declare there are no competing interests., (©2019 Capkova et al.)

Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD. Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history. Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p  < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3-9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5-5.2) were found to be independent risk factors of CHDs. Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.

Aim: The therapeutic potential of adipose-derived stem cell conditioned medium (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI)., Methods: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle tissue was collected 35 days after ischemia induction. Ischemic changes were evaluated in hematoxylin-eosin stained tissues for early (necrotic lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The expression of proangiogenic miR-126 was also evaluated using in situ hybridization. The levels of cytokines, insulin, and C-peptide were measured in blood., Results: Early repair phases were observed more often in placebo-treated samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was not statistically significant. We demonstrated a statistically significant positive correlation between the early healing phases in tissue samples and C-peptide levels in peripheral blood. The expression of proangiogenic miR-126 was also shown in a number of structures in all phases of ischemic tissue healing., Conclusion: Based on our results, we believe that treatment with ASC-CM has the potential to accelerate the healing process in ischemic tissues in the rabbit model of CLI. The whole healing process was accompanied by miR-126 tissue expression. C-peptide could be used to monitor the course of the tissue healing process.

Aim: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases., Methods: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation., Results: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]., Conclusion: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.

Background: Autism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNVs). Microarray-based whole-genome approaches for CNV detection are widely accepted. However, the clinical significance of most CNV is poorly understood, so results obtained using such methods are sometimes ambiguous. We therefore evaluated a targeted approach based on multiplex ligation-dependent probe amplification (MLPA) using selected probemixes to detect clinically relevant variants for diagnostic testing of ASD patients. We compare the reliability and efficiency of this test to those of chromosomal microarray analysis (CMA) and other tests available to our laboratory. In addition, we identify new candidate genes for ASD identified in a cohort of ASD-diagnosed patients., Method: We describe the use of MLPA, CMA, and karyotyping to detect CNV in 92 ASD patients and evaluate their clinical significance., Result: Pathogenic and likely pathogenic mutations were identified by CMA in eight (8.07% of the studied cohort) and 12 (13.04%) ASD patients, respectively, and in eight (8.07%) and four (4.35%) patients, respectively, by MLPA. The detected mutations include the 22q13.3 deletion, which was attributed to ring chromosome 22 formation based on karyotyping. CMA revealed a total of 91 rare CNV in 55 patients: eight pathogenic, 15 designated variants of unknown significance (VOUS)-likely pathogenic, 10 VOUS-uncertain, and 58 VOUS-likely benign or benign. MLPA revealed 18 CNV in 18 individuals: eight pathogenic, four designated as VOUS-likely pathogenic, and six designated as VOUS-likely benign/benign. Rare CNVs were detected in 17 (58.62%) out of 29 females and 38 (60.32%) out of 63 males in the cohort. Two genes, DOCK8 and PARK2 , were found to be overlapped by CNV designated pathogenic, VOUS-likely pathogenic, or VOUS-uncertain in multiple patients. Moreover, the studied ASD cohort exhibited significant ( p < 0.05) enrichment of duplications encompassing DOCK8 ., Conclusion: Multiplex ligation-dependent probe amplification and CMA yielded concordant results for 12 patients bearing CNV designated pathogenic or VOUS-likely pathogenic. Unambiguous diagnoses were achieved for eight patients (corresponding to 8.7% of the total studied population) by both MLPA and CMA, for one (1.09%) patient by karyotyping, and for one (1.09%) patient by FRAXA testing. MLPA and CMA thus achieved identical reliability with respect to clinically relevant findings. As such, MLPA could be useful as a fast and inexpensive test in patients with syndromic autism. The detection rate of potentially pathogenic variants (VOUS-likely pathogenic) achieved by CMA was higher than that for MLPA (13.04% vs. 4.35%). However, there was no corresponding difference in the rate of unambiguous diagnoses of ASD patients. In addition, the results obtained suggest that DOCK8 may play a role in the etiology of ASD., Competing Interests: The authors declare that they have no competing interests. Vera Becvarova and Marie Trkova are employed by Gennet, s. r. o.

A common Authentication and Authorisation Infrastructure (AAI) that would allow single sign-on to services has been identified as a key enabler for European bioinformatics. ELIXIR AAI is an ELIXIR service portfolio for authenticating researchers to ELIXIR services and assisting these services on user privileges during research usage. It relieves the scientific service providers from managing the user identities and authorisation themselves, enables the researcher to have a single set of credentials to all ELIXIR services and supports meeting the requirements imposed by the data protection laws. ELIXIR AAI was launched in late 2016 and is part of the ELIXIR Compute platform portfolio. By the end of 2017 the number of users reached 1000, while the number of relying scientific services was 36. This paper presents the requirements and design of the ELIXIR AAI and the policies related to its use, and how it can be used for serving some example services, such as document management, social media, data discovery, human data access, cloud compute and training services., Competing Interests: No competing interests were disclosed.

Patient-nominated supporters can potentially improve the continuum of HIV care. We retrospectively determined factors associated with having a patient-nominated supporter among people living with HIV (PLWH), and its association with retention in care and viral suppression. We analysed registries of adults evaluated by social workers (n = 1345) at a referral hospital in Peru between 2011-2014. Nondisclosure of HIV status was associated with lacking supporters (aPR: 5.41, 95% CI: 3.83-7.64). Retention in care was 76.4% and 34.2% after one and two years of enrolment, respectively. PLWH with supporters were more likely to be retained in care after two years (aRR = 1.36, 95% CI: 1.02-1.81), but not after one year (aRR = 1.10, 95% CI: 0.98-1.23) compared to PLWH without supporters. Having supporters who were parents or friends was associated with an increased probability of being retained in care after one and two years of enrolment. Viral suppression after one year of enrolment was 58.7%. Having a supporter was not associated with viral suppression (aRR = 1.18, 95% CI: 0.99-1.41), but PLWH with supporters were more likely to have viral load measurements (p = 0.005). Patient-nominated supporters appear beneficial for engagement in HIV care; these benefits may be related to the nature of their relationship with PLWH.

Objective: To demonstrate the advantage of using weighted Cox regression to analyze nested case-control data in overcoming limitations encountered with traditional conditional logistic regression., Study Design and Setting: We analyzed data from 1,051 women who were sampled in a case-control study of lung cancer nested within a cohort of breast cancer patients. We investigated how lung cancer risk is associated with radiation therapy and modified by smoking, with both conditional logistic regression and weighted Cox regression models., Results: In contrast to logistic regression, weighted Cox regression exploited the information regarding radiation dose received by each individual lung. The weighted method also mitigated a problem of overmatching apparent in the data and revealed that the risk of radiotherapy-associated lung cancer was modified by smoking (P = 0.026) with a hazard ratio of 4.09 (2.31, 7.24) in unexposed smokers and 8.63 (5.04, 14.79) in smokers receiving doses >13 Gy. The cumulative risk of lung cancer increased steadily with increasing radiotherapy dose in smokers, whereas no such effect was found in nonsmokers., Conclusion: The weighted Cox regression makes optimal and versatile use of the information in a nested case-control design, allowing dose-response analysis of exposure to paired organs and enabling the estimation of cumulative risk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder resulting from mutations in the PHOX2B gene located on chromosome 4p12.3, characterized by hypoventilation secondary to missing responses to both hypercapnia and hypoxia., Case Report: Proband. A girl, hospitalised 5 times for respiratory failure from 6 weeks old, presented at 4 years of age severe cyanosis related to pneumonia. Tracheostomy was done, and she was discharged home using a portable positive pressure ventilator during sleep. Proband's father: The father was retrospectively found out to suffer from severe headache and excessive daytime sleepiness. Molecular genetic evaluation of PHOX2B gene was performed and casual polyalanine repeat expansion mutation c.741&#95;755dup15 in exon 3 was found both in proband and her father in heterozygous form. The proband's grandmother died of respiratory failure after administration of benzodiazepine at the age of fifty years. Considering the grandmother's history, she is highly suspected of having had CCHS as well., Conclusion: Repeated respiratory failure of girl was explained by PHOX2B mutation and Ondina curse. Proband´s father has incompletely penetrated PHOX2B heterozygous mutation as well and proband´s grandmother died probably from the consequences of drug interaction with PHOX2B mutated background as well. Both daughter and father currently require overnight mechanical ventilatory support. Although most PHOX2B mutations occur de novo, our case is a rare three generation family affected by autosomal dominant inheritance with incomplete penetrance manifested as the late-form of CCHS and proven PHOX2B mutation in two generations.

Background: In this part of the study, where we determined the causes of preeclampsia and other obstetric complications, we focused on the role of tissue factor (TF) in the activation of these pathophysiological processes. Recent findings attribute a significant part of the activation of coagulation creation of autoantibodies. Once this mechanism is activated, the antibodies induce expression of tissue factor (TF, CD142) on monocytes and vascular endothelial cells., Methods: We have proposed a monitor activation model of the coagulation system in preeclampsia and other pregnancy complications using TF expression on monocytes by flow cytometry and simultaneous determination the TF-induced thrombin generation in plasma. To determine expression of tissue factor (CD142) on monocytes, we proposed a method of multicolor flow cytometry using anti CD45 PerCP, anti CD14 APC, anti CD16b FITC, and anti CD142 PE antibodies and the corresponding isotype controls., Results: We verified the model on patients with severe antiphospholipid syndrome, which is a high expression of antibodies, in particular against beta-2GPI., Conclusions: We demonstrated complete inhibition of TF expression on monocytes and a significant reduction of thrombin generation in plasma.

Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk.The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression.The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratified analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected.This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.

Background: Monozygotic twinning is associated with increased perinatal morbidity and mortality. There is evidence that the number of monozygotic twins increases after assisted reproductive techniques., Methods: We searched PUBMED, MEDLINE, and Scopus from 1987 to 2015 for studies analyzing the incidence and possible etiology of monozygotic twinning in infertility patients and critically reviewed the current state of knowledge., Results and Conclusions: Monozygotic twinning is a rare in natural conception but occurs around twice the normal rate after assisted reproduction. Factors associated with this phenomenon remain speculative, though there is some evidence that micromanipulation techniques, prolonged culture, and genetics are involved. In view of the possible complications, adequate pre-conception counselling is advocated.

Supramolecular surface nanostructures have application potential as functional devices. The complex combination of thiolated cyclodextrin, chemisorbed on an Au surface (Au-S-CD), with deposited Fe species is studied by secondary ion mass spectrometry. The Fe species are prepared by pulsed laser ablation in water and thermal effusion in vacuum. Using laser ablation in water, the solution of Fe species is dropped on Au-S-CD, where mass peaks at 1227 m/z, 1243 m/z, and 1260 m/z are observed and assigned to C42 H68 O34 SNa-Fe(+) , C42 H68 O34 SK-Fe(+) together with C42 H68 O34 SNa-FeO(+) , and C42 H68 O34 SK-FeO(+) , respectively. On the other hand, laser ablation directly linked to the Au-S-CD surface results in desorption of CD-S. Thermal effusion, even with a cooled surface, was negative with respect to the complex observation. Laser ablation results in the formation of a supramolecular host-guest complex of the form Au-S-CD-Fe, and in the formation of an adduct of the form Au-S-CD-FeO., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery., Methods: We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2-4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score <7; umbilical artery pH), anesthesia complications, and subjective patient complaints 24 hours after surgery., Results: We enrolled 240 parturients. The mean time to tracheal intubation was 2.9 seconds longer in the ROC group (95% confidence interval, -5.3 to 11.2 seconds), noninferior compared with the SUX group. Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups (ROC, 87.5%; SUX, 74.2%; P = 0.019), but there were no differences in vocal cord position (P = 0.45) or intubation response (P = 0.31) between groups. No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found (10-minute Apgar score <7, P = 0.07; umbilical artery pH, P = 0.43). The incidence of postpartum myalgia was greater in the SUX group (ROC 0%; SUX 6.7%; P = 0.007). The incidence of subjective complaints was lower in the ROC group (ROC, 21.4%; SUX, 37.5%; P = 0.007)., Conclusions: We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

Objective: We compared the incidence and type of levator ani avulsion diagnosed by translabial ultrasound evaluation in primiparous women six months after vacuum-assisted or spontaneous vaginal delivery., Material and Methods: This retrospective observational study was performed between January 2011 and December 2013. Primiparous women six months after vacuum-assisted vaginal delivery and after spontaneous vaginal delivery underwent translabial ultrasound evaluation. The distance between the urethra and fibers of the musculus levator ani puborectalis (levator-urethra gap) was measured. A levator-urethra gap >25 mm was considered a musculus levator ani avulsion., Results: In total, 184 women participated in the study. Among them, 92 had vacuum extraction and 92 had uncomplicated spontaneous delivery. A longer levator-urethra gap on both sides of the pubic bone was found in women after vacuum-assisted vaginal delivery (p < 0.0001 for both sides). Musculus levator ani avulsion was identified in 20 women (unilateral in 16 cases and bilateral in four cases). No difference in an incidence of musculus levator ani avulsion was identified in women after vacuum-assisted vaginal delivery [11/92 (12%)] compared to spontaneous delivery [9/92 (10%); p = 0.81]., Conclusion: Vacuum-assisted vaginal delivery in primiparous women is associated with a longer levator-urethra gap but not with a higher frequency of avulsion of the musculus levator ani.

Background: The clinical importance of assessing the fetal KEL genotype is to exclude 'K'-positive fetuses (genotype KEL1/KEL2) in 'K'-alloimmunized pregnant women (genotype KEL2/KEL2). Noninvasive assessment of the fetal KEL genotype is not yet available in the Czech Republic., Objective: The aim of this study was to assess the fetal KEL1/KEL2 genotype from cell-free fetal DNA in the plasma of KEL2/KEL2 pregnant women., Methods: The fetal genotype was assessed by minisequencing (a dilution series including control samples). A total of 138 pregnant women (between the 8th and 23rd gestational week) were tested by minisequencing. The fetal genotype was further verified by analysis of a buccal swab from the newborn., Results: Minisequencing proved to be a reliable method. In 2.2% (3/138) of the examined women, plasma sample testing failed; 94.8% (128/135) had the KEL2/KEL2 genotype, and a total of 3.1% of fetuses (4/128) had the KEL1/KEL2 genotype. Sensitivity and specificity reached 100% (p < 0.0001)., Conclusion: Minisequencing is a reliable method for the assessment of the fetal KEL1 allele from the plasma of KEL2/KEL2 pregnant women., (© 2015 S. Karger AG, Basel.)

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To determine amniotic fluid total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substances (TBARS), markers of oxidative stress, in pregnancies complicated by preterm prelabor rupture of membranes (pPROM) and their correlation to microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA)., Methods: One-hundred thirty-eight women with singleton pregnancies complicated by pPROM were included in this study. Amniotic fluid was collected by transabdominal amniocentesis at the time of admission and amniotic fluid concentrations of TAC, FRAP and TBARS were measured., Result: The presence of MIAC and/or HCA did not show any significant differences in the amniotic fluid TAC, FRAP and TBARS concentrations. Positive correlations between gestational age at sampling and amniotic fluid TAC and FRAP concentrations were found (TAC: rho = 0.32; p = 0.0002; FRAP: rho = 0.36; p < 0.0001). A negative correlation between gestation age at sampling and amniotic fluid TBARS concentrations was identified (rho = -0.25; p = 0.004)., Conclusions: Oxidative stress is associated with pPROM as indicated by the presence of markers tested in the amniotic fluid; however, oxidative stress markers tested are not influenced by the presence of MIAC or HCA.

Background: Tissue factor (TF) is a key element for normal gestation, especially in the first trimester. TF levels are hence raised in pregnancy, producing an adaptive hypercoagulable state. Potentiated hypercoagulability however, is associated with disorders of pregnancy such as pre-eclampsia but the results of TF and its inhibitor, tissue factor pathway inhibitor (TFPI), measurement, in pre eclampsic women are ambiguous and the data conflicting. This review covers the current knowledge status of the role of TF assessment in pregnancy with a focus on its diagnostic utility., Methods: A review of the literature using the following key words: tissue factor, thrombosis, inflammation, pregnancy, preeclampsia., Results: The published literature shows raised and unchanged TF levels in various studies of pre-eclampsia along with equally conflicting data for TFPI. The various study designs and methods used in these studies makes valid comparison difficult. Meta analysis of 34 randomized trials showed that low-dose aspirin in early phases of gravidity (starting from the 16th week or earlier) significantly reduces the incidence of preeclampsia., Conclusions: Overall, the results of the literature search together with knowledge of the structure and biological effects of TF, suggest that measuring the level of plasma TF/TFPI is not ideal for determining the actual levels of TF in the uteroplacental circulation. The current view that endothelial dysfunction is the trigger for preeclampsia, suggests that aspirin may be an effective prophylaxis. Further research will be necessary: measuring the expression of tissue factor on monocytes using flowcytometry and comparing the development of this expression during normal pregnancy and pregnancy complicated by preeclampsia, for example. Another possibility is immunohistochemical determination of the level of TF expression directly in placental tissue.

Objective: To determine the vaginal fluid interleukin (IL)-6 and IL-8 concentrations in pregnancies complicated by preterm prelabor rupture of membranes and their correlation to microbial invasion of the amniotic cavity (MIAC) as well as histological chorioamnionitis (HCA)., Methods: Sixty-eight women with singleton pregnancies were included in this study. Vaginal fluid was collected at the time of admission. IL-6 and IL-8 concentrations in the vaginal fluid were determined using ELISA., Result: Women with MIAC had higher vaginal fluid IL-6 levels compared to those without MIAC (with MIAC: median 374 pg/mL versus without MIAC: median 174 pg/mL; p = 0.03). IL-8 levels were higher in women with MIAC only in the crude analysis but not after adjustment for gestational age. There was no difference in the IL-6 and IL-8 concentrations between those with and without HCA. Women with both MIAC and HCA had higher IL-6 vaginal fluid levels than those without both MIAC and HCA (with MIAC and HCA: median 466 pg/mL versus without MIAC and HCA: median 178 pg/mL; p = 0.02). IL-8 levels were higher in women with MIAC and HCA only in the crude analysis but not after adjustment for gestational age., Conclusions: Vaginal fluid IL-6 but not IL-8 levels reflect the presence of MIAC and both MIAC and HCA.

The possible effect of radiofrequency exposure from mobile phones on tumor risk has been studied since the late 1990s. Yet, empirical information about recall of the start of mobile phone use among adult cases and controls has never been reported. Limited knowledge about recall errors hampers interpretations of the epidemiological evidence. We used network operator data to validate the self-reported start year of mobile phone use in a case-control study of mobile phone use and acoustic neuroma risk. The answers of 96 (29%) cases and 111 (22%) controls could be included in the validation. The larger proportion of cases reflects a more complete and detailed reporting of subscription history. Misclassification was substantial, with large random errors, small systematic errors, and no significant differences between cases and controls. The average difference between self-reported and operator start year was -0.62 (95% confidence interval: -1.42, 0.17) years for cases and -0.71 (-1.50, 0.07) years for controls, standard deviations were 3.92 and 4.17 years, respectively. Agreement between self-reported and operator-recorded data categorized into short, intermediate and long-term use was moderate (kappa statistic: 0.42). Should an association exist, dilution of risk estimates and distortion of exposure-response patterns for time since first mobile phone use could result from the large random errors in self-reported start year. Retrospective collection of operator data likely leads to a selection of "good reporters", with a higher proportion of cases. Thus, differential recall cannot be entirely excluded.

Unlabelled: Abstract Objective: To determine the cervical fluid interleukin (IL)-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and the association of these interleukins with microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA)., Methods: Sixty women with singleton pregnancies were included in this study. Cervical fluid was sampled at the time of admission using Dacron polyester swabs, which were placed into the endocervical canal for 20 s. IL-6 and IL-8 levels were determined by ELISA. The management of PPROM was active management (except for in pregnancies <28 weeks of gestation) and occurs not later than 72 h after the rupture of membranes., Result: The women with MIAC had higher IL-6 and IL-8 levels than did the women without MIAC (IL-6: p=0.01; IL-8: p=0.003). There was no difference in IL-6 levels between women with and without HCA (p=0.37). The women with HCA had higher IL-8 levels only in the crude analysis (p=0.01) but not after adjustment for gestational age (p=0.06). The women with both MIAC and HCA had higher levels of IL-6 and IL-8 than did the other women (IL-6: p=0.003; IL-8: p=0.001). IL-8 level of 2653 pg/mL was found to be the best cut-off point in the identification of PPROM pregnancies complicated by both MIAC and HCA with a likelihood ratio of 24., Conclusions: The presence of MIAC is the most important factor impacting the local cervical inflammatory response, which is determined by IL-6 and IL-8 levels in the cervical fluid. IL-8 levels seem to be a promising non-invasive marker for the prediction of pregnancies complicated by the presence of both MIAC and HCA.

Background: The study aimed at finding a laboratory approach to detect endothelial damage in normal pregnancy as well as in pregnancy complicated by preeclampsia using selected markers of endothelial activation., Materials: A total of 403 healthy pregnant women without a history of deep vein thrombosis and/or hypertension were prospectively studied. From all women, venous blood was collected before the end of the 1st trimester, between weeks 24 and 28 of gestation, and in the 3rd trimester (weeks 34-36). Assays of tissue plasminogen activator, plasminogen activator inhibitor-1, von Willebrand factor activity and antigen, thrombomodulin, endothelial protein C receptor, and endothelial microparticles activated by TF were performed., Results: When comparing women who developed preeclampsia during pregnancy (the average levels were 23.41 μg/L, 34.33 μg/L, and 53.56 μg/L in the 1st, 2nd, and 3rd trimesters, respectively) with healthy pregnant women (the average levels were 19.05 μg/L, 28.47 μg/L, and 39.86 μg/L in the 1st, 2nd, and 3rd trimesters, respectively) significant differences in the levels of thrombomodulin were found in all three trimesters. By contrast, no statistically significant differences in the levels of vWF (both antigen and activity), t-PA, EPCR, EMPs, MMP-2, MMP-9, and TIMP-9 were found in any trimesters in the same group., Conclusions: Pregnancy and preeclampsia strongly influence the levels of studied markers. The findings of this work confirm the possible predictive potential of thrombomodulin and PA-1.

The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A number of epidemiological studies indicate an inverse association between atopy and brain tumors in adults, particularly gliomas. We investigated the association between atopic disorders and intracranial brain tumors in children and adolescents, using international collaborative CEFALO data., Patients and Methods: CEFALO is a population-based case-control study conducted in Denmark, Norway, Sweden, and Switzerland, including all children and adolescents in the age range 7-19 years diagnosed with a primary brain tumor between 2004 and 2008. Two controls per case were randomly selected from population registers matched on age, sex, and geographic region. Information about atopic conditions and potential confounders was collected through personal interviews., Results: In total, 352 cases (83%) and 646 controls (71%) participated in the study. For all brain tumors combined, there was no association between ever having had an atopic disorder and brain tumor risk [odds ratio 1.03; 95% confidence interval (CI) 0.70-1.34]. The OR was 0.76 (95% CI 0.53-1.11) for a current atopic condition (in the year before diagnosis) and 1.22 (95% CI 0.86-1.74) for an atopic condition in the past. Similar results were observed for glioma., Conclusions: There was no association between atopic conditions and risk of all brain tumors combined or of glioma in particular. Stratification on current or past atopic conditions suggested the possibility of reverse causality, but may also the result of random variation because of small numbers in subgroups. In addition, an ongoing tumor treatment may affect the manifestation of atopic conditions, which could possibly affect recall when reporting about a history of atopic diseases. Only a few studies on atopic conditions and pediatric brain tumors are currently available, and the evidence is conflicting.

Background: There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited., Methods: We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%)., Results: Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses., Conclusions: The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

Objective: To determine the amniotic fluid nucleosome concentrations in pregnancies that are complicated by preterm prelabor rupture of membranes and their correlation to microbial invasion of the amniotic cavity (MIAC), histologic chorioamnionitis (HCA), and their association with neonatal outcomes., Methods: Eighty-nine women with singleton pregnancies were included in this study. Amniotic fluid was collected, and nucleosome concentration in the amniotic fluid was determined using enzyme-linked immunosorbent assay., Result: There were no differences observed in the amniotic fluid nucleosome concentrations in women with or without MIAC. The presence of HCA (with chorioamnionitis: median 0.5; without chorioamnionitis: median 0.21; p = 0.01) and funisitis (with funisitis: median 0.85; without funisitis: median 0.22; p = 0.0008) was associated with higher nucleosome concentrations using crude analysis; however, this was not significant after adjusting for gestational age (p = 0.12 for both). A negative correlation was observed between amniotic fluid nucleosome concentrations and gestational age (ρ = -0.52; p < 0.0001). There was no association identified between amniotic fluid nucleosome concentration and neonatal morbidity., Conclusions: Amniotic fluid nucleosome concentrations remained a stable physiologic constituent in pregnancies complicated by preterm prelabor rupture of membranes, and these concentrations were gestational age dependent. Neither MIAC nor HCA significantly affected amniotic fluid nucleosome concentrations.

Background: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence., Methods: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7-19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls., Results: The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number of childhours at daycare, attending baby groups, birth order or living with other children. Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7-19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95% confidence interval: 1.57-5.50) and 4.21 (95% confidence interval: 1.24-14.30)., Interpretation: There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.

Objective: To determine amniotic fluid soluble Toll-like receptor 2 (sTLR2) levels in PPROM according to the presence of microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis (HCA), and both these conditions. To test the cutoff level of 222.7 ng/mL, as proposed in our previous study, in order to distinguish women with both MIAC and HCA., Methods: 169 women with a gestational age between 24+0 and 36+6 weeks were included in a prospective cohort study. Amniocenteses were performed, and sTLR2 in the amniotic fluid were determined using ELISA., Results: Women with MIAC had higher sTLR2 levels (median 113.2 ng/mL) than those without MIAC (median 47.1 ng/mL; p < 0.0001). Women with HCA did not have a higher sTLR2 level (median 52.6 ng/mL) compared with women without HCA (median 47.1 ng/mL; p = 0.23). Women with both MIAC and HCA had higher sTLR2 levels (median: 311.3 ng/mL) than other women (17.5 ng/mL; p < 0.0001). The cutoff level 222.7 ng/mL had a sensitivity of 63%, a specificity of 98%, and a likelihood ratio of 40.3 for the prediction of both MIAC and HCA., Conclusions: Amniotic fluid sTLR2 is a promising predictor of both MIAC and HCA with high specificity in PPROM.

Aims: The aim of this study was to assess the feasibility and accuracy of fetal gender assignment by transabdominal ultrasound at 12-14 weeks of gestation., Methods: Fetal gender assessment was performed in 1222 singleton pregnancies. In all fetuses the crown-rump length (CRL) was measured and the genital area of the fetus was examined in the mid-sagittal plane. The result of ultrasound examination was compared to the phenotypic sex of the newborn after delivery., Results: The feasibility as well as accuracy in determining gender increased with growing fetal CRL. At CRL < 50 mm (gestational age < 11+4) the feasibility was 39.1% and accuracy 30.5% (40.9% in male gender vs 24.3% in female gender). At CRL 50-54.9 mm (gestational age 11+4 to 12+0) the feasibility was 63.5% and accuracy 75.0% (89.1% in male gender vs 66.7% in female gender). At CRL 55-59.9 mm (gestational age 12+0 to 12+2) the feasibility was 90.5% and accuracy 96.6% (99.1% in male gender vs 93.5% in female gender). At CRL ≥ 60 mm (gestational age ≥ 12+2) the feasibility was 97.4% and accuracy 100.0% (100.0% in male gender vs 100.0% in female gender)., Conclusions: Fetal gender may reliably be determined when CRL ≥ 60 mm (gestational age ≥ 12+2). Male gender may already be reliably determined when CRL ≥ 55 mm (gestational age ≥ 12+0). If CRL < 50 mm (gestational age < 11+4) the gender cannot be reliably predicted.

Background: The objective was to determine the incidence and volume of fetomaternal hemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these variables would enable optimalization of guidelines for D alloimmunization prophylaxis., Study Design and Methods: In a prospective cohort study, a total of 3457 examinations were performed, 2413 after normal vaginal delivery and 1044 after cesarean delivery. FMH was assessed by flow cytometry. (FMH is fetal red blood cell [RBC] volume; fetal blood volume is double [expected fetal hematocrit is 50%].), Results: The fetal RBC volume diagnosed in maternal circulation after delivery ranged from insignificant FMH of not more than 0.1 mL to excessive FMH of 65.9 mL (median, 0.7; mean, 0.78; SD, 1.48). FMH of more than 2.5 mL (immunoglobulin [Ig] G anti-D insufficient dose 50 µg) was observed in 1.4% (49/3457) and excessive volumes of FMH of more than 5 mL (insufficient dose, 100 µg) in 0.29% (10/3457). Delivery by cesarean section presented a higher risk of incidence of FMH of more than 2.5 mL (odds ratio, 2.2; p = 0.004) when compared with normal vaginal delivery. It did not, however, present a significant risk factor for the incidence of excessive volumes of FMH of more than 5 mL., Conclusion: During normal vaginal delivery as well as during delivery by cesarean section, FMH of less than 5 mL occurs in the great majority of cases, and thus for the prevention of D alloimmunization, an IgG anti-D dose of 100 µg should be sufficient. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor., (© 2012 American Association of Blood Banks.)

Objectives: The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs), since infectious agents may pose a risk factor and a proposed mechanism is transferral of infectious agents from animals to humans., Methods: The case-control study conducted in Denmark, Norway, Sweden, and Switzerland included brain tumor cases diagnosed from 2004 to 2008 aged 7-19 years at diagnosis. Three hundred and fifty-two cases (83 % participation rate) were matched to 646 population-based controls (71 % participation rate). Conditional logistic regression was used to estimate odds ratios., Results: Maternal farm residence during pregnancy was inversely related to all CBTs combined (adjusted odds ratio (aOR) = 0.40, 95 % confidence interval (CI) = 0.19-0.88), as was the child's farm residence but not statistically significantly so (aOR = 0.57, 95 % CI = 0.28-1.17). Exposure to animals was in general not related to CBT risk except postnatal contact with birds showing reduced aORs of all CBTs (0.67, 95 % CI = 0.46-0.97) and primitive neuroectodermal tumor (0.28, 95 % CI = 0.10-0.83). Sensitivity analyses focusing on early exposure of the child did not change the associations observed for the entire exposure period with the exception of exposure to goats and sheep which was associated with reduced risks of both all CBTs (aOR = 0.48, 95 % CI = 0.24-0.97) and astrocytomas (aOR = 0.29, 95 % CI = 0.10-0.87)., Conclusion: Altogether, our data indicate an inverse association between the mother during pregnancy or the child living on a farm and CBT risk, which contrasts with the existing literature and merits further attention. With respect to exposure to animals, we did not observe any systematic pattern. This suggests that a potential protective effect of farm residence is mediated by some other factor than animal contact.

Two previous studies suggest that cigarette smoking reduces acoustic neuroma risk; however, an association between use of snuff tobacco and acoustic neuroma has not been investigated previously. The authors conducted a case-control study in Sweden from 2002 to 2007, in which 451 cases and 710 population-based controls completed questionnaires. Cases and controls were matched on gender, region, and age within 5 years. The authors estimated odds ratios using conditional logistic regression analyses, adjusted for education and tobacco use (snuff use in the smoking analysis and smoking in the snuff analysis). The risk of acoustic neuroma was greatly reduced in male current smokers (odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23, 0.74) and moderately reduced in female current smokers (OR = 0.70, 95% CI: 0.40, 1.23). In contrast, current snuff use among males was not associated with risk of acoustic neuroma (OR = 0.94, 95% CI: 0.57, 1.55). The authors' findings are consistent with previous reports of lower acoustic neuroma risk among current cigarette smokers than among never smokers. The absence of an association between snuff use and acoustic neuroma suggests that some constituent of tobacco smoke other than nicotine may confer protection against acoustic neuroma.

Objective: Determine the influence of maternal age, parity, gestational age and birth weight on the volume of fetal erythrocytes which enter the maternal circulation during spontaneous delivery. Determining these parameters would enable improving the guidelines for RhD alloimmunization prophylaxis., Design: Prospective clinical study., Setting: Department of Obstetrics and Gynecology, University Hospital, Olomouc., Methods: A total of 2413 examinations were performed. The amount of fetal erythrocytes entering maternal circulation during uncomplicated spontaneous delivery of one fetus was determined by flow cytometry using the BDFACSCanto cytometer (Becton Dickonson International). Laboratory processing: Fetal Cell Count kit (Diagnosis of Feto-maternal transfusion by flow cytometry), IQ Products, IQP-379. Calculation of total volume of fetal erythrocytes entering maternal circulation: Scientific Subcommittee of the Australian and New Zealand Society of Blood Transfusion. Guidelines for laboratory assessment of fetomaternal haemorrhage. 1st ed. Sydney: ANZSBT, 2002: 3-12., Results: The average maternal age when FMH 1.8 ml (95 perc) was 29.4 years vs. 29.1 years when FMH > 1.8 ml, median 30 years in both groups, the difference was not statistically significant (p = 0.501). The average gestational age when FMH 1.8 ml (95 perc) was 275.3 days vs. 276.9 days when FMH > 1.8 ml, median 278 days (39 weeks +5 days) vs. 276 days (39 weeks + 3 days), the difference was not statistically significant (p = 0.849). The average birth weight when FMH 1.8 ml (95 perc) was 3312 g vs. 3353 g when FMH > 1.8 ml, median 3340 g vs. 3330 g, the difference was not statistically significant (p = 0.743). FMH > 1.8 ml (5 perc) was present in 4.1% of primiparas (42/1023), in 4.2% of secundiparas (44/1050) and in 5.3% of multiparas (18/340), the difference was not statistically significant (p = 0.607). The difference in maternal age, parity, gestational age and birth weight were also not statistically significant for fetomaternal hemorrhage FMH > 2.1 ml (2.5 perc), FMH > 2.5 ml (n = 25), FMH > 5 ml (n = 5)., Conclusion: Maternal age, parity, gestational age and birth weight does not present a risk factor for excessive fetomaternal hemorrhage during spontaneous delivery.

Aim: The aim of this study was to assess coagulation markers of endothelial damage and examine new markers of endothelial activation such as matrix metalloproteinases (MMPs) in a group of healthy pregnant women. Matrix metalloproteinase (MMP)-2, in particular, plays a major role in the degradation of the extracellular matrix confirming its essential function in both the survival (angiogenesis) and death of endothelial cells. Detection of specific coagulation factors, mainly released from the vascular endothelium such as vWF, sTM (soluble thrombomodulin) and ePCR (endothelial protein C receptor) and factors dependent on endothelial activation such as t-PA and PAI-1, could provide information on possible endothelial dysfunction and help differentiate pregnant patients with an altered thrombotic state., Methods: Healthy pregnant women underwent complete assessment for endothelial damage (as vWF, vWF activity, sTM, ePCR, EMP, MMP-2, MMP-9 and TIMP-2) using the ELISA and other methods., Results and Conclusions: The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage and typically characterized by higher levels of both coagulation endothelial markers and MMPs. In pregnancy, changes in extracellular matrix composition and matrix metalloproteinase activity also occur and promote vascular remodeling but, only in the uterus. Predisposing risk factors for epithelial dysfunction, and vascular mediators associated with vascular remodeling must be assessed from concentrations in whole blood. The levels of MMPs are not increased in the circulation and the local situation in the uterus cannot be monitored this way. However, MMP-2 processes and modulates the functions of many other vasoactive and pro-inflammatory molecules including adrenomedullin, big endothelin-1, calcitonin gene-related peptide, CCL7/MCP-3, CXCL12/SDF-1, galectin-3, IGFBP-3, IL-1 Beta, S100A8, and S100A9. These molecules represent new potential molecular markers of endothelial damage during pregnancy.

A growing body of literature addresses possible health effects of mobile phone use in children and adolescents by relying on the study participants' retrospective reconstruction of mobile phone use. In this study, we used data from the international case-control study CEFALO to compare self-reported with objectively operator-recorded mobile phone use. The aim of the study was to assess predictors of level of mobile phone use as well as factors that are associated with overestimating own mobile phone use. For cumulative number and duration of calls as well as for time since first subscription we calculated the ratio of self-reported to operator-recorded mobile phone use. We used multiple linear regression models to assess possible predictors of the average number and duration of calls per day and logistic regression models to assess possible predictors of overestimation. The cumulative number and duration of calls as well as the time since first subscription of mobile phones were overestimated on average by the study participants. Likelihood to overestimate number and duration of calls was not significantly different for controls compared to cases (OR=1.1, 95%-CI: 0.5 to 2.5 and OR=1.9, 95%-CI: 0.85 to 4.3, respectively). However, likelihood to overestimate was associated with other health related factors such as age and sex. As a consequence, such factors act as confounders in studies relying solely on self-reported mobile phone use and have to be considered in the analysis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents., Methods: CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models., Results: Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure., Conclusion: The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents., (Copyright © 2011 Wiley-Liss, Inc.)

Background: An anatomic study., Objective: To point out the risk of bleeding during retropubic surgery in females., Methods: A pelvic dissection, preparation of vessels and photodocumentation in colour., Results: A detailed representation of topographic vessel relations in pelvic and retropubic regions is presented. This could be used as an authentic visual aid for postgraduate training in urogynaecological surgery., Conclusion: This study highlights the risk of vascular lesions common to all suspensory surgical procedures for female stress urinary incontinence. Apart from paraurethral vessels, the vessels of the urinary bladder, the paravesical plexuses, the retropubic anastomosis and the external iliac vessles can be injured in surgery. Preceeded by training at an accredited urogynaecologic centre, TVT can be considered a safe method. Introduction of other modifications such as the transobturator system (namely the + "inside-out" method) makes all urogynaecological surgical procedures much safer.

Objectives: Acoustic neuroma is a benign tumour accounting for approximately 6-10% of all intracranial tumours and occurs mainly in patients aged ≥50 years. Our aim was to investigate a wide range of occupational exposures, individual occupational titles and socioeconomic status (SES) as potential risk factors for acoustic neuroma., Methods: We conducted a population-based case-control study of 793 acoustic neuroma cases identified through the Swedish Cancer Registry and 101,762 randomly selected controls. Information on SES and occupation was obtained from censuses and linked to job-exposure matrices. Logistic regression was used to estimate ORs and calculate 95% CIs., Results: An increased OR was seen for mercury exposure <10 years before the reference year (OR 2.9; 95% CI 1.2 to 6.8), and a more modest association for benzene exposure (OR 1.8; 95% CI: 1.0 to 3.2) ≥10 years before the reference year. We observed a threefold increased risk for females working as tailors and dressmakers ≥10 years before the reference year, and a more than threefold significantly elevated OR for those working as truck and conveyor operators <10 years before the reference year. We found no convincing evidence that SES is related to disease development., Conclusion: We observed an increased risk of acoustic neuroma associated with occupational exposure to mercury, benzene and textile dust. Men working as truck and conveyor operators <10 years before the reference year had the highest increased risk of acoustic neuroma, but it is unclear what in those occupations might contribute to disease development. Our study also suggested an association between acoustic neuroma and being a class teacher or policeman. However, these findings should be further investigated to exclude the possibility of detection bias.

Purpose: Studies have shown that women who survive breast cancer have an increased risk of a future primary lung cancer, though many are based only on data recorded in tumor registries and none have conducted pathological confirmation. Previous studies and future use of large registries may be affected by misdiagnosis., Methods: Pathological analysis was conducted on tumors from 110 women with breast cancer followed by lung cancer using morphology, Estrogen Receptor-alpha (ER), and Thyroid Transcription Factor-1 (TTF1). We developed an algorithm to classify lung tumors as unlikely lung cancer (score=1) to likely lung cancer (score=5)., Results: Mean time to diagnosis of lung cancer after breast cancer was 13 years. 76% of breast tumors and 20% of lung tumors were positive for ER and 51% of lung tumors were positive for TTF-1. 86% of the lung tumors were probable primaries, 7% were probable metastases from the breast, and 7% were of undetermined status. 70% of probable metastases had a latency of longer than 10 years., Conclusion: Prior studies identifying the association of breast cancer and breast cancer treatments with lung cancer are likely to reflect true associations not confounded by misdiagnosis, as evidenced by the low rate of misclassification detected in this study. Analysis of the years of diagnosis suggests that latency may not be an accurate criterion for assignment of primary status, which could be significant in a clinical setting. These data may also benefit future retrospective studies using large registries., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: For more than 20 years, infection with the human papillomavirus (HPV) has been of a matter of interest not only to gynecologists but also to maxillofacial surgeons and othorhinolaryngologists. HPV is generally known to be involved in cervical cancer. Recently, there are many clinical studies pointed out the potentially dangerous connection between HPV infection and head and neck carcinomas (HNC). HPV infection was identified as a possible etiological factor in 15-30% of HNC., Methods: Aim of this article is to summarize the recent knowledge about the HPV infection with regards to etiology of head and neck cancer., Results: It has been proven that HPV infection is related to development of head and neck cancer and that the sexual behavior has played an important role in the viral transmission. HNC of viral etiology have been observed mostly in younger people; their curability is difficult and prognosis serious., Conclusion: Beside the well known correlation between developing of new head and neck cancer and bad habits (smoking, alcohol abuse, poor oral hygiene etc.) we should take into consideration the sexual promiscuity and alternative sexual practices. Vaccination against cervical cancer, recommended to young women, should be extended to their male partners to prevent the virus transmission and decrease the HNC incidence.