Intersexual Twins due to Tetragametic Chimerism.

Disorders of or differences in sexual development (DSD) are defined by congenital conditions in which development of chromosomal, gonadal, or anatomic sex are atypical. Here, we report on monochorionic diamniotic twins delivered by caesarean section in the 36th week of pregnancy. Monochorionic twins are usually monozygous and thus should have the same sexual differentiation.

The First Neocentric, Discontinuous, and Complex Small Supernumerary Marker Chromosome Composed of 7 Euchromatic Blocks Derived from 5 Different Chromosomes.

Background: The majority of small supernumerary marker chromosomes (sSMCs) are derived from one single chromosome. Complex sSMCs instead consist of two to three genomic segments, originating from different chromosomes. Additionally, discontinuous sSMCs have been seen; however, all of them are derived from one single chromosome.

Laparoscopic Bilateral Cervicosacropexy and Vaginosacropexy: New Surgical Treatment Option in Women with Pelvic Organ Prolapse and Urinary Incontinence.

Objective: Sacrocolpopexy (SCP) is the gold standard for apical prolapse treatment. However, the technical performance of each SCP is strongly dependent on the surgeon's own discretion and comparison of clinical outcomes with respect to urinary incontinence (UI) is difficult. We developed a comprehensible laparoscopic surgical technique for the treatment of apical prolapse with UI.

TOT 8/4: A Way to Standardize the Surgical Procedure of a Transobturator Tape.

Suburethral tapes are placed "tension-free" below the urethra. Several studies reported considerable differences of the distance between urethra and tape. These distances ranged from 1 to 10 mm amongst different patients.

Suspicious Prenasal Skin Thickness-to-Nasal Bone Length Ratio: Prevalence and Correlation with Other Markers in Second and Third Trimester Fetuses with Down Syndrome.

Purpose: To assess the prevalence and value of a suspicious prenasal skin thickness-to-nasal bone length ratio (PT/NB ratio) in comparison to other established markers in a large population of Down syndrome (DS) fetuses.

Materials And Methods: This was a retrospective study of 139 DS fetuses and 530 normal fetuses scanned after 14 + 0 weeks of gestation. To characterize diagnostic performance, we used the ROC curve approach.

Consanguinity and pregnancy outcomes in a multi-ethnic, metropolitan European population.

Objective: The aim of the present study was to assess the risk of major anomalies in the offspring of consanguineous couples, including data on the prenatal situation.

Methods: Over 20 years (1993-2012), 35,391 fetuses were examined by prenatal sonography. In 675 cases (1.

Fetal Aneuploidy Detection by Cell-Free DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twins.

Non-invasive prenatal testing (NIPT) by random massively parallel sequencing of maternal plasma DNA for multiple pregnancies is a promising new option for prenatal care since conventional non-invasive screening for fetal trisomies 21, 18 and 13 has limitations and invasive diagnostic methods bear a higher risk for procedure related fetal losses in the case of multiple gestations compared to singletons. In this study, in a retrospective blinded analysis of stored twin samples, all 16 samples have been determined correctly, with four trisomy 21 positive and 12 trisomy negative samples. In the prospective part of the study, 40 blood samples from women with multiple pregnancies have been analyzed (two triplets and 38 twins), with two correctly identified trisomy 21 cases, confirmed by karyotyping.

[Prenatal diagnostics: current medical aspects].

During the last few years, there has been a rapid development in prenatal diagnosis. Due to the improvements in sonographic examinations and the introduction of first-trimester screening, the number of invasive prenatal diagnostic procedures has dropped by more than 50 %. Recently, noninvasive prenatal diagnostic tests with cell-free fetal DNA from maternal blood have also become available and will further enhance this development.

Diagnostic accuracy of random massively parallel sequencing for non-invasive prenatal detection of common autosomal aneuploidies: a collaborative study in Europe.

Objective: The objective of this study is to validate the diagnostic accuracy of a non-invasive prenatal test for detecting trisomies 13, 18, and 21 for a population in Germany and Switzerland.

Methods: Random massively parallel sequencing was applied using Illumina sequencing platform HiSeq2000. Fetal aneuploidies were identified using a median absolute deviation based z-score equation.

Genomic chondrocyte culture profiling by array-CGH, interphase-FISH and RT-PCR.

Objective: In vitro expansion is an important step to acquire sufficient cells in human tissue engineering technologies. The high number of chondrocytes needed for human articular cartilage implants requires in vitro expansion of the primary cells, bearing a theoretical risk of in vitro induced changes in the genomes. To gain more insights into this situation, model cultures were prepared and analyzed.

Noninvasive prenatal detection of chromosomal aneuploidies using different next generation sequencing strategies and algorithms.

Objective: Here we describe the successful application of massively parallel sequencing for noninvasive prenatal detection of trisomy 21. In addition, for the detection of a broader spectrum of fetal aneuploidies, a target enrichment approach was successfully tested.

Methods: The circulating cell-free DNA was prepared from 53 maternal blood samples and analysed using Illumina's sequencing systems Genome Analyzer(IIx) and HiSeq2000, respectively.

'Normal' nuchal translucency: a justification to refrain from detailed scan? Analysis of 6858 cases with special reference to ethical aspects.

Objective: To assess the prevalence and detection rate of major anomalies (MAs) by applying first trimester anomaly scan (FTAS) including first trimester fetal echocardiography (FTFE) to all fetuses and discuss ethical implications.

Methods: The study group included 6879 consecutive fetuses with known outcome of pregnancy (follow-up: 98%), 6565 with 'normal' nuchal translucency (NT) (≤ P95), 314 with 'increased' NT (> P95). All fetuses received FTAS/FTFE.

Validation of a postfixation tissue storage and transport medium to preserve histopathology and molecular pathology analyses (total and phosphoactivated proteins, and FISH).

Tumor biomarker studies are integral to oncology clinical trials but may yield artifactual results owing to variation in sample procurement and processing. Ethanol, 70% vol/vol, was validated as a sample transport medium using markers of the PI3K/Akt/mTOR pathway. BT474 tumor xenografts were excised and slices were immediately placed into formaldehyde and fixed for 24 hours.

MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest.

Mutations in the MCPH1 gene cause primary microcephaly associated with a unique cellular phenotype of misregulated chromosome condensation. The encoded protein contains three BRCT domains, and accumulating data show that MCPH1 is involved in the DNA damage response. However, most of this evidence has been generated by experiments using RNA interference (RNAi) and cells from non-human model organisms.

The impact of first trimester screening and early fetal anomaly scan on invasive testing rates in women with advanced maternal age.

Purpose: To evaluate the acceptance of noninvasive screening for trisomy 13, 18, 21 and the impact on invasive testing rates in women at an age≥35 years.

Materials And Methods: In a retrospective analysis from 2003-2006 including 13 268 women≥35 years old with singleton pregnancies and 3133 invasive procedures, we evaluated the prenatal detection rate of aneuploidies in two cohorts. Group 1: advanced maternal age as sole indication, group 2: additional abnormalities and/or suspicious maternal serum parameters.

A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset.

Objective: (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach.

Methods: Database query, viable singletons [crown-rump length (CRL) 45-84 mm corresponding to 11-13(+6) weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied.

Results: Seventy-four of 4171 were lost to follow-up (1.

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma.

B-RAF is the most frequently mutated protein kinase in human cancers. The finding that oncogenic mutations in BRAF are common in melanoma, followed by the demonstration that these tumours are dependent on the RAF/MEK/ERK pathway, offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity.

Anti-Angiogenic/Vascular Effects of the mTOR Inhibitor Everolimus Are Not Detectable by FDG/FLT-PET.

Noninvasive functional imaging of tumors can provide valuable early-response biomarkers, in particular, for targeted chemotherapy. Using various experimental tumor models, we have investigated the ability of positron emission tomography (PET) measurements of 2-deoxy-2-[(18)F]fluoro-glucose (FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) to detect response to the allosteric mammalian target of rapamycin (mTOR) inhibitor everolimus. Tumor models were declared sensitive (murine melanoma B16/BL6 and human lung H596) or relatively insensitive (human colon HCT116 and cervical KB31), according to the IC(50) values (concentration inhibiting cell growth by 50%) for inhibition of proliferation in vitro (<10 nM and >1 microM, respectively).

Small supernumerary marker chromosomes 1 with a normal phenotype.

Small supernumerary marker chromosomes (sSMCs) are a major problem in prenatal cytogenetic diagnostics. Over two-thirds of cases carrying an sSMC derived from chromosome 1 are associated with clinical abnormalities. We report 3 further cases of such sSMCs that did not show any clinical abnormalities.

First-trimester prenatal diagnosis of Okihiro syndrome.

A case of Okihiro syndrome (OS) detected by 2- and confirmed by 3-dimensional ultrasound at 13+2 gestational weeks is reported. While the pregnant woman affected by the OS presented with limb anomalies, the fetus showed severe thoracoabdominal and skeletal anomalies. Termination of pregnancy was performed at 14+1 gestational weeks and confirmed the sonographically detected symptoms.