Reaction of Chlorine Dioxide with Saturated Nitrogen-Containing Heterocycles and Comparison with the Micropollutant Behavior in a Real Water Matrix.

Chlorine dioxide (ClO2) is a very selective oxidant that reacts with electron-rich moieties such as activated amines and thus can degrade specific N-containing micropollutants. N-containing heterocycles (NCHs) are among the most frequent moieties of pharmaceuticals. In this study, the reactions of ClO2 with ritalinic acid and cetirizine, two abundant micropollutants, and model compounds representing their NCH moiety were investigated. The pH-dependent apparent reaction rates of all NCHs with ClO2 were measured and modeled. This model showed that neutral amines are the most important species having reaction rates between 800 and 3200 M-1 s-1, while cationic amines are not reactive. Ritalinic acid, cetirizine, and their representative model compounds showed a high stoichiometric ratio of ≈5 moles ClO2 consumption per degraded ritalinic acid and ≈4 moles ClO2 consumption per degraded cetirizine, respectively. Investigation of chlorine-containing byproducts of ClO2 showed that all investigated NCHs mostly react by electron transfer and form above 80% chlorite. The reactions of the model compounds were well comparable with cetirizine and ritalinic acid, indicating that the model compounds indeed represented the reaction centers of cetirizine and ritalinic acid. Using the calculated apparent reaction rate constants, micropollutant degradation during ClO2 treatment of surface water was predicted for ritalinic acid and cetirizine with -8 to -15% and 13 to -22% error, respectively. The results indicate that in ClO2-based treatment, piperidine-containing micropollutants such as ritalinic acid can be considered not degradable, while piperazine-containing compounds such as cetirizine can be moderately degraded. This shows that NCH model compounds could be used to predict micropollutant degradation.

Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours.

AIMS: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.

Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice.

Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. In this form, free oligosaccharides can be transferred into the lysosomes to be degraded completely. α-Mannosidase (MAN2C1) is the enzyme responsible for the partial demannosylation occurring in the cytosol. It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. These findings confirm the key role played by Man2c1 in the catabolism of free oligosaccharides.

Marker-free phenotyping of tumor cells by fractal analysis of reflection interference contrast microscopy images.

Phenotyping of tumor cells by marker-free quantification is important for cancer diagnostics. For the first time, fractal analysis of reflection interference contrast microscopy images of single living cells was employed as a new method to distinguish between different nanoscopic membrane features of tumor cells. Since tumor progression correlates with a higher degree of chaos within the cell, it can be quantified mathematically by fractality. Our results show a high accuracy in identifying malignant cells with a failure chance of 3%, which is far better than today's applied methods.

Lysosomal di-N-acetylchitobiase-deficient mouse tissues accumulate Man2GlcNAc2 and Man3GlcNAc2.

Most lysosomal storage diseases are caused by defects in genes encoding for acidic hydrolases. Deficiency of an enzyme involved in the catabolic pathway of N-linked glycans leads to the accumulation of the respective substrate and consequently to the onset of a specific storage disorder. Di-N-acetylchitobiase and core specific α1-6mannosidase represent the only exception. In fact, to date no lysosomal disease has been correlated to the deficiency of these enzymes. We generated di-N-acetylchitobiase-deficient mice by gene targeting of the Ctbs gene in murine embryonic stem cells. Accumulation of Man2GlcNAc2 and Man3GlcNAc2 was evaluated in all analyzed tissues and the tetrasaccharide was detected in urines. Multilamellar inclusion bodies reminiscent of polar lipids were present in epithelia of a scattered subset of proximal tubules in the kidney. Less constantly, enlarged Kupffer cells were observed in liver, filled with phagocytic material resembling partly digested red blood cells. These findings confirm an important role for lysosomal di-N-acetylchitobiase in glycans degradation and suggest that its deficiency could be the cause of a not yet described lysosomal storage disease.

Hepatoma-derived growth factor and nucleolin exist in the same ribonucleoprotein complex.

BACKGROUND: Hepatoma-derived growth factor (HDGF) is a protein which is highly expressed in a variety of tumours. HDGF has mitogenic, angiogenic, neurotrophic and antiapoptotic activity but the molecular mechanisms by which it exerts these activities are largely unknown nor has its biological function in tumours been elucidated. Mass spectrometry was performed to analyse the HDGFStrep-tag interactome. By Pull-down-experiments using different protein and nucleic acid constructs the interaction of HDGF and nucleolin was investigated further. RESULTS: A number of HDGFStrep-tag copurifying proteins were identified which interact with RNA or are involved in the cellular DNA repair machinery. The most abundant protein, however, copurifying with HDGF in this approach was nucleolin. Therefore we focus on the characterization of the interaction of HDGF and nucleolin in this study. We show that expression of a cytosolic variant of HDGF causes a redistribution of nucleolin into the cytoplasm. Furthermore, formation of HDGF/nucleolin complexes depends on bcl-2 mRNA. Overexpression of full length bcl-2 mRNA increases the number of HDGF/nucleolin complexes whereas expression of only the bcl-2 coding sequence abolishes interaction completely. Further examination reveals that the coding sequence of bcl-2 mRNA together with either the 5' or 3' UTR is sufficient for formation of HDGF/nucleolin complexes. When bcl-2 coding sequence within the full length cDNA is replaced by a sequence coding for secretory alkaline phosphatase complex formation is not enhanced. CONCLUSION: The results provide evidence for the existence of HDGF and nucleolin containing nucleoprotein complexes which formation depends on the presence of specific mRNAs. The nature of these RNAs and other components of the complexes should be investigated in future.

[What is a public health intervention? Results of a Delphi process in German-speaking countries]. / Was wird unter einer Public-Health-Intervention verstanden? Ergebnisse eines Delphi-Prozesses im deutschsprachigen Raum.

BACKGROUND: Internationally, a variety of definitions for public health interventions (PHI) exist. In the German-speaking countries, however, a definition is still outstanding. Therefore, the aim of this study was to derive consensus criteria for the definition of PHI from the expert perspective of science and practice. METHODS: A Delphi survey with two online rounds was conducted from December 2022 to February 2023. Six criteria were formulated by a working group and posed for consensus: 1) the intention of the intervention, 2) potential conflicts of interest of the initiators of the intervention, 3) primary vs. secondary/tertiary prevention, 4) costs, 5) targeting, and 6) the reach of the intervention. In both Delphi rounds, experts from academia and practice were recruited through relevant networks and associations throughout the German-speaking world. The judgments were asked about standardized rating scales with the possibility of open justification. RESULTS: In the first Delphi round, n = 52 and in the second round n = 43 experts from research, care and administration/management in health care participated. Consensus was reached on four of the six criteria after the second Delphi round: the intention of the intervention, possible conflicts of interest of the initiators of the intervention, primary vs. secondary/tertiary prevention, and the scope of the intervention. From the perspective of the experts interviewed, these are the criteria that distinguish PHI. DISCUSSION AND CONCLUSION: Based on the consensus criteria, PHI can be defined more concretely. Thus, the results contribute to a better inter- and transdisciplinary understanding. Ideally, the criteria will make it easier to assign interventions to the public health sector in the future, even if a precise examination will be necessary in individual cases, among other things because the experts disagreed on the criteria of costs and how to address the target group.

Paradigmatic Approach to Support Personalized Counseling With Digital Health (iKNOW).

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee's data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine.

Label-free live-cell imaging with confocal Raman microscopy.

Confocal Raman spectroscopy is a noninvasive alternative to established cell imaging methods because it does not require chemical fixation, the use of fluorescent markers, or genetic engineering. In particular, single live-cell, high-resolution imaging by confocal Raman microscopy is desirable because it allows further experiments concerning the individually investigated cells. However, to derive meaningful images from the spectroscopic data, one must identify cell components within the dataset. Using immunofluorescence images as a reference, we derive Raman spectral signatures by means of information measures to identify cell components such as the nucleus, the endoplasmic reticulum, the Golgi apparatus, and mitochondria. The extracted signatures allow us to generate representations equivalent to conventional (immuno)fluorescence images with more than three cell components at a time, exploiting the Raman spectral information alone.

Identification of oncostatin M as a STAT5-dependent mediator of bone marrow remodeling in KIT D816V-positive systemic mastocytosis.

Systemic mastocytosis is a neoplastic disease of mast cells harboring the activating KIT mutation D816V. In most patients, mast cell infiltration in the bone marrow is accompanied by marked microenvironment alterations, including increased angiogenesis, osteosclerosis, and sometimes fibrosis. Little is known about the mast cell-derived molecules contributing to these bone marrow alterations. We show here that neoplastic mast cells in patients with systemic mastocytosis express oncostatin M (OSM), a profibrogenic and angiogenic modulator. To study the regulation of OSM expression, KIT D816V was inducibly expressed in Ba/F3 cells and was found to up-regulate OSM mRNA and protein levels, suggesting that OSM is a KIT D816V-dependent mediator. Correspondingly, KIT D816V(+) HMC-1.2 cells expressed significantly higher amounts of OSM than the KIT D816V(-) HMC-1.1 subclone. RNA interference-induced knockdown of STAT5, a key transcription factor in KIT D816V(+) mast cells, inhibited OSM expression in HMC-1 cells, whereas a constitutively activated STAT5 mutant induced OSM expression. Finally, OSM secreted from KIT D816V(+) mast cells stimulated growth of endothelial cells, fibroblasts, and osteoblasts, suggesting that mast cell-derived OSM may serve as a key modulator of the marrow microenvironment and thus contribute to the pathology of systemic mastocytosis.

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data.

OBJECTIVE: To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN: Individual patient data metaanalysis of randomized controlled trials. RESULTS: Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION: Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Maternal smoking and fetal lung signals--an in utero MRI investigation.

OBJECTIVE: To investigate whether fetal lung signals and fetal lung signal progression over gestation observed on magnetic resonance imaging are different in mothers who reported smoking during pregnancy compared with nonsmoking controls. METHOD: Cross-sectional retrospective study of 100 consecutive singleton pregnancies that underwent magnetic resonance imaging. Fetal lung-liver signal intensity ratios of 18 fetuses of mothers who reported smoking during pregnancy were compared with 82 fetuses of nonsmoking controls. RESULTS: Average gestational age at magnetic resonance imaging was 26.4 ± 5.2 weeks (Range 18.4-38.2 weeks). Cases reported smoking between 2 and 15 cigarettes per day. The mean number of cigarettes per day for cases was 9.2 ± 3.4. Mean fetal lung-liver signal intensity ratios did not differ significantly between the two groups (p = 0.8). They showed a linear increase with gestational age (r(2) = 0.3). Multiple regression analysis of lung-liver signal intensity ratios using gestational age and smoking status as predictors revealed a significant influence of gestational age (p < 0.0001) but not maternal smoking status (p = 0.8) on fetal lung-liver signal intensity ratios. CONCLUSIONS: Fetuses of mothers who reported smoking during pregnancy show similar lung signals and lung signal progression over gestation on magnetic resonance imaging as nonsmoking controls.

Are fetuses with isolated echogenic bowel at higher risk for an adverse pregnancy outcome? Experiences from a tertiary referral center.

OBJECTIVE: The purpose of this study was to determine the risk of poor perinatal outcome in normal karyotype second-trimester fetuses with the sonographic finding of isolated echogenic bowel. METHOD: Medical records, ultrasonographic findings and outcome details were reviewed for 97 cases of isolated fetal echogenic bowel, after excluding cases of aneuploidy and major congenital anomalies, and compared with a cohort of 400 fetuses without pathologic intra-abdominal findings. RESULTS: The incidence of echogenic bowel during the 14-year study period was 0.8%. Eighty (82.5%) pregnancies resulted in healthy, live-born infants. Congenital infection and cystic fibrosis was reported in 6.2% and 4.4%, respectively. The incidence of intrauterine growth restriction and intrauterine fetal demise was significantly higher in the group of isolated echogenic bowels compared with the control group (9.9% versus 1.3%, p ≤ 0.001; 8.9% versus 0.5% p ≤ 0.001). CONCLUSION: Echogenic bowel is a risk factor for an adverse pregnancy outcome, even in normal karyotype fetuses without congenital anomalies. This information should be considered when counseling patients after midtrimester echogenic bowel is diagnosed.

Maxillary dental arch biometry: assessment with fetal MR imaging.

OBJECTIVE: To define normal growth of the fetal maxillary dental arch using magnetic resonance imaging. METHOD: Four hundred twenty-four consecutive fetuses (18 to 37 weeks) with a morphologically normal anatomy or only minor malformations, not affecting bone growth and face anatomy were included. On axial T2-weighted images the dental arch length and width were measured. The measurements were correlated with gestational age and the biparietal diameter (BPD) of the fetal head using correlation and regression analysis. RESULTS: A linear growth relationship was observed between the dental arch length and gestational age (r = 0.86; p = < 0.0001; y = -1.85 + 0.75 × gestational age) and the dental arch width and gestational age (r = 0.92; p = < 0.0001; y = -2.19 + 1.05 × gestational age). A significant correlation was found between the dental arch length and the BPD (r = 0.903; p = < 0.0001) and the dental arch width and the BPD (r = 0.927; p = < 0.0001). The interobserver variability showed good agreement for the dental arch length (intraclass coefficient 0.981; r = 0.963) and width (intraclass coefficient 0.987; r = 0.974), respectively. CONCLUSION: We present a nomogram for the in utero assessment of the fetal dental arch. These data may help in the early detection of abnormal dental arch development.

Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials.

BACKGROUND: Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death. METHODS/DESIGN: We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups. DISCUSSION: Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

What Causes Cancer in Women with a gBRCA Pathogenic Variant? Counselees' Causal Attributions and Associations with Perceived Control.

Laypersons have a strong need to explain critical life events, such as the development of an illness. Expert explanations do not always match the beliefs of patients. We therefore assessed causal attributions made by women with a pathogenic germline variant in BRCA1/2 (gBRCA1/2-PV), both with and without a cancer diagnosis. We assumed that attributions would be associated with the control experience. We conducted a cross-sectional study of N = 101 women with a gBRCA1/2-PV (mean age 43.3 ± 10.9). Women answered self-report questionnaires on perceived causes and control. Most women (97%) named genes as a causal factor for the development of cancer. Surprisingly, the majority of women also named stress and health behavior (both 81%), environment (80%), and personality (61%). Women with a cancer diagnosis tended to endorse more causes. The attributions to personality (ρ = 0.39, p < 0.01) health behavior (ρ = 0.44, p < 0.01), and environment (ρ = 0.22, p < 0.05) were significantly associated with personal control, whereas attribution to genes showed a small, albeit significant association with treatment control (ρ = 0.20, p < 0.05). Discussing causal beliefs in clinical counseling may provide a "window of opportunity" in which risk factors and health behaviors could be better addressed and individually targeted.

Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D3.

In addition to its role in bone metabolism, vitamin D3 exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D3 levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity. We studied the seasonal fluctuation of γδ T cells, the possible influence of vitamin D3, and the effect of the active metabolite 1α,25(OH)2D3 on the in vitro activation of human γδ T cells. In a retrospective analysis with 2625 samples of random blood donors, we observed higher proportions of γδ T cells in winter when compared with summer. In a prospective study over one year with a small cohort of healthy adults who did or did not take oral vitamin D3 supplementation, higher proportions of γδ T cells were present in donors without oral vitamin D3 uptake, particularly in spring. However, γδ T cell frequency in blood did not directly correlate with serum levels of 25(OH)D3. The active metabolite 1α,25(OH)2D3 inhibited the in vitro activation of γδ T cells at the level of proliferation, cytotoxicity, and interferon-γ production. Our study reveals novel insights into the seasonal fluctuation of γδ T cells and the immunomodulatory effects of vitamin D3.

Sensory processing difficulties in psychiatric disorders: A meta-analysis.

In clinical practice, many individuals with psychiatric disorders report difficulties in sensory processing, including increased awareness or sensitivity to external stimuli. In this meta-analysis, we examined the sensory processing patterns of adolescent and adult individuals with a broad spectrum of different psychiatric conditions. A systematic search in various databases resulted in the inclusion of 33 studies (N=2008), all using the Adolescent/Adult Sensory Profile (AASP). By comparing diagnostic subgroups to the corresponding reference group of the AASP, we detected a general pattern of sensory processing, indicating elevated levels of low registration, sensory sensitivity and sensory avoiding and lowered sensory seeking behavior in patients with different types of psychiatric disorders. The majority of effect sizes were large to very large. In conclusion, sensory processing difficulties can be considered as a non-specific transdiagnostic phenotype associated with a broad spectrum of psychiatric conditions. Further research into the relevance and role of sensory processing difficulties in psychiatric disorders may improve long-term prognosis and treatment.

Mean, lowest, and highest pulsatility index of the uterine artery and adverse pregnancy outcome in twin pregnancies.

OBJECTIVE: The objective of the study was to assess the use of mean, lowest, and highest pulsatility index (PI) of the uterine arteries to screen for adverse pregnany outcome in twin pregnancies. STUDY DESIGN: This was a screening study of 423 twin pregnancies. Relationship between PI at 20-22 weeks and adverse pregnancy outcome was evaluated. RESULTS: Mean, lowest, and highest PI above the 95th centile were significant risk factors for preeclampsia and adverse pregnancy outcome in monochorionic and dichorionic twins. We calculated a sensitivity for preeclampsia for mean, highest, and lowest PI of 35%, 29%, and 27%, respectively. CONCLUSION: Increased mean, lowest, and highest PI is associated with a higher risk of preeclampsia and adverse pregnancy outcome in twins. We observed the highest sensitivity and specificity by using highest PI. The high incidence of preeclampsia in twins makes it attractive to use the PI of the uterine artery for risk stratification in twins.

Quantification of the subcutaneous fat layer with MRI in fetuses of healthy mothers with no underlying metabolic disease vs. fetuses of diabetic and obese mothers.

OBJECTIVE: To assess the age-dependent fetal subcutaneous fat layer (SCFL) of non-diabetic, normal-weight mothers and fetuses of mothers with gestational diabetes (GDM) and normal body weight or obesity. METHODS: In a prospective study, we evaluated 115 MRI examinations of fetuses with no history of (maternal) metabolic disease [gestational week (GW) 29 to 39/40] and 50 examinations of mothers with GDM and normal body weight or obesity. The SCFL was measured at predetermined anatomical landmarks. Measurements were correlated with the maternal body mass index (BMI) and glycated hemoglobin A1c (HbA1c)-values in diabetic mothers. RESULTS: In fetuses of non-diabetic, normal-weight mothers, measurements showed high consistency within the respective GW and ranged from 2 mm at GW 29 at all measured points, up to 4.5 mm at the trunk and 6.0 mm at the extremities at GW 39/40. In 47/50 fetuses of mothers with GDM, the SCFL was within the range of fetuses of mothers with no metabolic disease. In three patients with GDM and BMI<30, the SCFL-thickness was decreased. No fetuses showed an increased SCFL-thickness. CONCLUSION: The SCFL of normally developed fetuses is easily detectable from GW 29 on T1-weighted images (T1-W), and increases with gestational age. The presented data provide physiological benchmarks to evaluate developmental status and may help in the prenatal diagnosis of abnormal growth and macrosomia. In pregnant women with well-controlled GDM, an increase of the SCFL is not expected.