Fetal Doppler changes one week after endoscopic equatorial laser for twin-to-twin transfusion syndrome: a longitudinal study

Objective: To investigate sequential Doppler changes in donors and recipients before and 1 week after endoscopic laser for twin\u2010to\u2010twin transfusion syndrome (TTTS) and to examine factors that may be associated with such changes. Methods: In TTTS pregnancies undergoing laser treatment, we examined fetal Doppler changes before and 1 week postintervention. Intrauterine death rates and preoperative factors were analyzed in relation to Doppler changes. Results: Among 129 (85.4%) donors surviving at 1 week after laser, there was normalization of umbilical artery flow in 26 (72.2%) of 36 cases with preoperative abnormal Dopplers. In the remaining 10 (27.8%) fetuses, abnormal findings persisted. The rate of later intrauterine death was significantly higher in the latter group (6 of 10, 60.0%) compared with fetuses in which Doppler findings normalized (4 of 26, 15.4%; P < .05), with no difference in the rate of severe donor growth restriction between the 2 groups (80.0% vs 65.4%, respectively; P = .688). Conclusions: In about 70% of TTTS donors with preoperative abnormal umbilical artery Doppler, there was normalization 1 week after endoscopic laser. The incidence of fetal growth restriction was not significantly different in donors with persistence of Doppler abnormalities compared with those with normalized findings

Development of a Three-Dimensional In Vitro Model for Longitudinal Observation of Cell Behavior: Monitoring by Magnetic Resonance Imaging and Optical Imaging

Purpose: The aim of this study is the development of a three-dimensional multicellular spheroid cell culture model for the longitudinal comparative and large-scale screening of cancer cell proliferation with noninvasive molecular imaging techniques under controlled and quantifiable conditions. Procedures: The human glioblastoma cell line Gli36ΔEGFR was genetically modified to constitutively express the fluorescence protein mCherry, and additionally labeled with iron oxide nanoparticles for high-field MRI detection. The proliferation of aggregates was longitudinally monitored with fluorescence imaging and correlated with aggregate size by light microscopy, while MRI measurements served localization in 3D space. Irradiation with γ-rays was used to detect proliferational response. Results: Cell proliferation in the stationary three-dimensonal model can be observed over days with high accuracy. A linear relationship of fluorescence intensity with cell aggregate size was found, allowing absolute quantitation of cells in a wide range of cell amounts. Glioblastoma cells showed pronounced suppression of proliferation for several days following high-dose γ-irradiation. Conclusions: Through the combination of two-dimensional optical imaging and 3D MRI, the position of individual cell aggregates and their corresponding light emission can be detected. This allows an exact quantification of cell proliferation, with a focus on very small cell amounts (below 100 cells) using high resolution noninvasive techniques as a well-controlled basis for further cell transplantation studies

Ascorbic acid, a vitamin, is observed by in vivo 13C nuclear magnetic resonance spectroscopy of rat liver

The first in vivo detection of a vitamin with nuclear magnetic resonance (NMR) is reported for mammalian liver. Vitamin C, also known as ascorbic acid, was monitored noninvasively in rat liver by "whole body" 13C NMR spectroscopy at high field after infusion of [1,2-13C2]glucose into anesthetized rats. Generally, the carbon resonances of ascorbic acid overlap with those of other highly abundant cellular metabolites, thus precluding their observation in situ. This problem was resolved by taking advantage of the 13C-13C spin couplings introduced by the two covalently bound 13C nuclei in [1,2-13C2]glucose. During glucose metabolism, [5,6-13C2]ascorbic acid was synthesized, which also exhibited characteristic 13C homonuclear spin couplings. This feature enabled the spectral discrimination of ascorbic acid from overlapping singlet resonances of other metabolites. Quantitative analysis of the spin-coupling patterns provided an estimate of the turnover rate of hepatic ascorbic acid in vivo (1.9 +/- 0.4 nmol.min-1.g-1) and a novel approach toward a better understanding of optimal ascorbic acid requirements in humans. The results obtained in vivo were confirmed with high-resolution proton and 13C NMR spectroscopy of liver extracts

Revision der Theologie - Reform der Kirche

John E. Thiel is a contributing author, Naming the Heterodox: Interconfessional Polemics as a Context for Drey’s Theology, pp.114-139

Increased levetiracetam clearance and breakthrough seizure in a pregnant patient successfully handled by intensive therapeutic drug monitoring

We report a 36-year-old pregnant patient with subtherapeutic trough plasma levels of levetiracetam (LVT) and a breakthrough nocturnal seizure while assuming 3 times a day dosing of the drug. An intensive pharmacokinetic study was performed from immediately before to 11 hours after the morning LVT dose administration and suggested that the patient was not adequately exposed to the drug during the night. After changing the dosing of LVT to 4 times a day, the patient experienced no seizures and delivered a healthy newborn without complications. Afterward, trough plasma levels of LVT remained always within the therapeutic range until delivery, and no major increase of the drug daily dose was required

What Is Known and Unknown About the Association Between Endometriosis and Sexual Functioning : A Systematic Review of the Literature

It is well known that endometriosis is associated with an increase in the risk of deep dyspareunia, with potential negative effects on global female sexual functioning and couple relationship. The aims of this study were to review the literature on the impact of endometriosis on female sexual functioning and to suggest new avenues for future research and treatment strategies. An electronic database research was performed to identify all the studies on the relation between endometriosis and sexual functioning published in the period 2000 to 2016. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After the screening process, a total of 9 studies investigating the relation between endometriosis and female sexual functioning were considered. Overall, these studies indicated that around two thirds of women with endometriosis have some form of sexual dysfunction not limited to deep dyspareunia. These findings suggest that the global sexual impact of endometriosis requires further investigation, focusing not only on pain during intercourse but also on psychological and relational dimensions, including partner's sexual functioning. Because sexual functioning is a complex, multidimensional phenomenon, the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team composed of gynecologists, sexologists, and psychologists/psychotherapists

Similarity and Differences in Sexual Violence Against Adolescents and Adult Women : The Need to Focus on Adolescent Victims

Study Objective: To explore whether there are differences in characteristics, clinical findings and management in cases of sexual violence in adolescent and adult women. Design: Retrospective study. Setting: SVSeD–Service for Sexual and Domestic Violence, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. Participants: Female victims of sexual violence aged 10 years and older. Two study groups were analysed: an adolescent group and an adult group. Interventions: None; this was an observational study. Main Outcome Measures: Characteristics of the perpetrator, time spent between the episode of sexual violence and the access to SVSeD, presence of genital and/or extragenital injuries; tests for sexually transmitted diseases, spermatozoa research; and toxicological screening; Results: Adolescent victims of sexual violence requested help later than the adult victims. The majority of the perpetrators were well known to the victims in both groups. In both groups, we observed genital injuries in 1 of 3 patients. We found a strong association between the presence of genital injuries and a positive screening test for sexually transmitted diseases, in particular with regard to the adolescent victims. Conclusion: Adolescents’ delayed disclosure of sexual violence may affect the ability to properly manage these crimes. Prevention programs and public awareness campaigns should be implemented to highlight the importance of a prompt disclosure after sexual assault has occurred. Gynecologists should be made increasingly aware of this delicate issue, to better assist victims of sexual violence, especially adolescent victims

Loss of the novel Vcp (valosin containing protein) interactor Washc4 interferes with autophagy-mediated proteostasis in striated muscle and leads to myopathy in vivo

VCP/p97 (valosin containing protein) is a key regulator of cellular proteostasis. It orchestrates protein turnover and quality control in vivo, processes fundamental for proper cell function. In humans, mutations in VCP lead to severe myo- and neuro-degenerative disorders such as inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD), amyotrophic lateral sclerosis (ALS) or and hereditary spastic paraplegia (HSP). We analyzed here the in vivo role of Vcp and its novel interactor Washc4/Swip (WASH complex subunit 4) in the vertebrate model zebrafish (Danio rerio). We found that targeted inactivation of either Vcp or Washc4, led to progressive impairment of cardiac and skeletal muscle function, structure and cytoarchitecture without interfering with the differentiation of both organ systems. Notably, loss of Vcp resulted in compromised protein degradation via the proteasome and the macroautophagy/autophagy machinery, whereas Washc4 deficiency did not affect the function of the ubiquitin-proteasome system (UPS) but caused ER stress and interfered with autophagy function in vivo. In summary, our findings provide novel insights into the in vivo functions of Vcp and its novel interactor Washc4 and their particular and distinct roles during proteostasis in striated muscle cells

Intimate Partner Violence and Post Traumatic Stress Disorder: seeking epigenetic markers associated with violence against women

Introduction: Violence against women is a significant health and social problem and includes many different forms such as the Intimate Partner Violence (IPV). The consequences range among morbidity, mortality, physical and psychological health problems, including Post Traumatic Stress Disorder (PTSD). The interactions between genome and environmental factors, such as IPV, represent one of the major challenges in molecular medicine. The major focus of our research project, named epiREVAMP (from the Latin REpellere Vulnera Ad Mulierem et Puerum), is the identification of epigenetic markers of the IPV disorder that distinguish between people at high and low risk of developing PTSD, in order to better target evidence-based interventions in high risk groups. The first steps of this study are the definition of the samples to be collected (i.e. which type of victims), the completion of a standardised questionnaire by the victims and the set up of a biobank storing the collected samples until the definition of the final laboratory protocols. Materials and Methods We expect to study 600 subjects/year in the SINIACA-IDB (Security in Domestic Environment National surveillance Project) surveillance. The evaluation of a possible psychological therapy will be carried out by analysing a cohort of 200 women who suffered violence and 400 matched controls of women who did not suffer violence. DNA and RNA samples will be collected, stored and processed and the epigenome will be analysed using the array Infinium HumanMethylation450 BeadChip (Illumina,USA). The differentially methylated regions will be identified using GenomeStudio software and the laboratory results will be analysed along with the information collected in the questionnaire. Results Both early detection of post-traumatic distress in women and the identification of epigenomic factors are the prioritised areas of this research which is focused not only on the susceptibility but also on the resilience or not resilience to PTSD. This innovative approach represents a shift in the understanding of genetics from a gene-centric view to the phenotypic plasticity of a given genotype producing different phenotypes in response to different environmental conditions