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Uterine dendritic cells (uDCs) are critical for endometrial function, yet their origin, molecular characteristics, and specific roles during the pre- and post-implantation periods in the human endometrium remain largely unknown. The complexity of the endometrial environment makes defining the contributions of uDCs subtypes challenging. We hypothesize that distinct uDC subsets carry out specialized functions, and that resident progenitor DCs generate these subtypes. Employing single-cell RNA sequencing on uterine tissues collected across different menstrual phases and during early pregnancy, we identify several uDCs subtypes, including resident progenitor DCs. CITE-seq was performed on endometrial single-cell suspensions to link surface protein expression with key genes identified by the RNAseq analysis. Our analysis revealed the developmental trajectory of the uDCs along with the distinct functional roles of each uDC subtype, including immune regulation, antigen presentation, and creating a conducive environment for embryo implantation. This study provides a comprehensive characterization of uDCs, serving as a foundational reference for future studies for better understanding female reproductive disorders such as infertility and pregnancy complications.

Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores ( p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 ( p = 0.033) and with pancreatic insufficiency ( p = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest.

A number of metathesis reactions were successfully conducted in 4-methyltetrahydropyran, including both standard model dienes, as well as more complex substrates, such as analogues of biologically active compounds and active pharmaceutical ingredients. To place this solvent in a context of pharmaceutical R + D, larger-scale syntheses of SUAM 1221, a prolyl endopeptidase inhibitor with potential application in Alzheimer disease treatment, and a derivative of sildenafil, an analogue of the popular Viagra drug, were executed. In the latter case, despite all the setup being made in air, the metathesis reaction at a 33 g scale proceeded very well with relatively low catalyst loading and without need of aqueous workup or column chromatography., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Background: Universal vitamin D supplementation is controversial. Preventative examinations and public health initiatives in former East Germany that included vitamin D prophylaxis for children were regulated by official recommendations and guidelines. The aim of this study is to analyse the impact of a standardised nationwide guideline for universal supplementation with 400 International Units (IU) vitamin D3/day during the first year of life on clinical and biochemical parameters and the influence of surrounding factors., Methods: This is a cross-sectional analysis looking at data from a field study of 3481 term-born children during their first year of life that was conducted in 1989., Results: There were no significant clinical signs of rickets. 25 hydroxyvitamin D (25(OH)D) (mean and SEM, total analyses n=572) after birth (n=28) was 36(7) nmol/L, at 1 month 64(4) nmol/L (n=70, p<0.0001), 91(5) nmol/L at 3 months (n=95, p<0.0001), 65(8) nmol/L at 8 months (n=21, p=0.005) and ranged between 33 and 109 nmol/L until 12 months. Less than 0.2% of analyses revealed pathological levels for calcium or phosphate. Alkaline phosphatase (ALP) levels (n=690) were >1500 U/L (95th percentile) in 3.6%. Participants were on breastmilk or vitamin D-free formula, with solids added from 6 months of age. There were seasonal variations in 25(OH)D levels with a rise during spring and autumn. Thus this analysis is unique as sun exposure and supplementation can be considered as the only vitamin D sources., Conclusions: We conclude that universal supplementation with 400 IU of vitamin D3 during the first year of life is safe and provides sufficient 25(OH)D levels in Germany.

Background: Insulin-like growth factor (IGF) system as regulator for cellular proliferation is of particular interest in search for new prognostic approaches in cancer treatment., Procedure: We analyzed the mRNA expression profile of IGF-I, -II, and IGFBP-2, -3 in 50 children with previously untreated AML (mean age 10.8 +/- 4.8 years; patients in CCR n = 20, patients with relapse during later course of disease n = 15). MNC samples from peripheral blood as well as bone marrow of healthy donors were used as controls., Results: IGFBP-2 expression was significantly higher in AML cells than in healthy cells of peripheral MNC (P < 0.001) and of bone marrow cells (P < 0.01). Conversely, AML cells showed significantly lower IGFBP-3 and IGF-I gene expression compared to controls (P = 0.02; P < 0.001). Patients with relapse (median +/- range: 0.0929 +/- 0.049) during later course of disease demonstrated higher IGFBP-2 expression compared to patients in CCR (0.0121 +/- 0.047; P = 0.06) at time of diagnosis. A multivariate analysis identified the IGFBP-2 mRNA expression as an independent factor for the prediction of relapse. Furthermore, the probability of relapse-free survival (RFS) in patients with IGFBP-2 mRNA level >0.1000 was 28%; whereas, the probability of RFS in patients with IGFBP-2 mRNA level <0.1000 was 62% (P = 0.04, log-rank test). No prognostic influence could be found for the other investigated genes., Conclusions: Results identified different expressions of IGF components between normal and AML cells. Patients with IGFBP-2 mRNA levels up to 0.1000 (relative to KG1 cell line) more likely developed a relapse. Identification of these patients at diagnosis may allow more individualized treatment., ((c) 2007 Wiley-Liss, Inc.)

Background: Early glucosteroid treatment in preterm infants has a negative impact on physical growth and development. So far, data on dexamethasone effect on the GH/IGF axis and the clinical outcome are conflicting., Objective: Therefore, we studied the effect of dexamethasone treatment on parameters of somatic growth and on the secretion of insulin like growth factors (IGFs) and insulin like growth factors binding proteins (IGFBPs) in preterm infants., Methods: In 75 preterm infants somatic development was assessed at birth and after 3 months of corrected age. IGF-I/II and IGFBP-1-3 were measured at the same time. According to their treatment regime the infants were assigned to the dexamethasone treated or the non-treated group., Results: At 3 months the 13 infants with dexamethasone had a lower body weight, slightly lower body length and a lower head circumference. IGF-II (464.4 +/- 97.4 vs 638 +/- 201.4 mug/l, p = 0.001) and IGFBP-3 (1800 +/- 426 vs 2105 +/- 547 mug/l, p = 0.045) were significantly reduced under the influence of glucocorticoids, whereas IGFBP-1 was elevated (59.6 +/- 61.0 vs 21.1 +/- 21.7 mug/l, p = 0.002). The ratio IGFBP-3/(IGFBP-1 + 2) was reduced in the dexamethasone group (1.827 +/- 0.868 vs 3.098 +/- 1.898 mug/l, p = 0.016), implying a significant retardation in the somatic development., Conclusion: Dexamethasone impairs IGF and IGFBP secretion and stimulates IGFBP-1, an inhibitor of IGF-I. These pathways might contribute to alterations of the GH/IGF axis, particularly the ratio IGFBP-3/(IGFBP-1 + 2).

Background: Previous studies have suggested a possible influence of ghrelin on foetal growth. After birth, the regulation of this newly discovered orexigenic peptide is largely unknown., Objective: To study the relationship between circulating levels of ghrelin and enteral nutritional state in preterm infants during the first months of life., Methods: Ghrelin levels were measured in a cross-sectional study by radioimmunoassay on the second day after birth (n = 51), at 3 months (n = 63) and at 6 months (n = 53) of corrected postnatal age. Complete data sets of auxological parameters, biochemical values, perinatal diseases, nutritional management and therapy were determined., Results: All infants showed levels of ghrelin in postnatal serum. In correlation analyses and multivariable linear regression models, ghrelin was strongly related to enteral caloric intake on the second day after birth (all P < 0.01). At 6 months of corrected postnatal age, infants who were exclusively breastfed/formula fed had significantly lower ghrelin levels than infants with solid foods (Mann-Whitney U-test: P = 0.027)., Conclusion: Ghrelin levels were positively correlated with the enteral nutritional state in preterm infants on the second day after birth. The introduction of solid foods increased the ghrelin levels in a group of preterm infants at 6 months of corrected postnatal age.

Objectives: To analyse IGFs in respect to somatic growth and neonatal diseases during the first 6 months of life., Methods: IGF-I, IGF-II and IGF binding proteins (IGFBP-1, -2, -3) were determined by immunoassays in neonatal patients after birth (n = 67) and at 3 (3 mo; n = 75) and 6 months (6 mo; n = 47) of corrected postnatal age. Data on growth were tested for associations to the gestational age, birth weight (bw) SDS (/-2 SDS), neonatal morbidity and therapeutic strategies., Results: All IGFs and IGFBPs changed significantly between birth and 3 mo of corrected age (p < 0.05). Perinatal respiratory diseases influenced IGF-II at 3 mo, and bronchopulmonary dysplasia IGF-II at 3 and 6 mo (all p < 0.05). IGF-I differed between the subgroups bw /-2 SDS (p < 0.05). At 3 mo, IGFBP-1 was significantly increased in infants with glucocorticoid administration during the first four weeks of life., Conclusion: The first months of life are characterised by a pole reversal of the somatotropic axis: IGFBP-1 and -2 decrease and IGFBP-3 increases. Respiratory diseases with an origin in the neonatal period, glucocorticoid therapy and low birth weight have an impact on the IGF pattern up to 6 mo. Prospective studies are necessary to investigate, whether the described link between the IGF/IGFBP axis and respiratory morbidity in neonatal patients has an impact on development in later infancy.

Background: Loss of bone mass is a known complication of chronic inflammatory bowel disease (IBD) in children. The gold standard in the evaluation of bone mineral density (BMD) is dual energy X-ray absorptiometry (DXA)., Objective: In this preliminary study we evaluated digital X-ray radiogrammetry (DXR) which estimates BMD (DXR-BMD) from hand radiographs in children with IBD., Materials and Methods: A total of 26 children with IBD (10 girls, 16 boys; age range 10-18 years) underwent DXR for the calculation of DXR-BMD and metacarpal index (DXR-MCI) using the Pronosco X-posure system. The results were compared with a local reference database and correlated with the results of DXA., Results: DXR-BMD was 0.36-0.56 g/cm(2) (median 0.46 g/cm(2)) in Crohn disease patients and 0.38-0.63 g/cm(2) (median 0.48 g/cm(2)) in ulcerative colitis patients. DXR-MCI was 0.29-0.49 in Crohn disease patients and 0.28-0.53 in ulcerative colitis patients. The Z-scores were reduced to <-1 SD in five Crohn disease patients and in six ulcerative colitis patients. The coefficients (r) for the correlations between DXR-BMD and DXA-BMD were 0.78 for the lumbar spine and 0.61 for the proximal femur (P<0.01), and between DXR-MCI and DXA-BMD were 0.78 for the lumbar spine and 0.51 for the proximal femur (P<0.01)., Conclusions: DXR seems to be able to estimate cortical osteopenia in children with chronic IBD. The DXR results showed a positive correlation with DXA results.

Background: Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels., Objectives: To study endocrine factors in RBC transfusions that might be of importance for ROP., Methods: IGF-1, IGF-2 and their binding proteins 1-3 (IGFBP-1-3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP >or= stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP