Bitschbundgaard4093

Objective To describe trends in mortality, major morbidity and perinatal care practices of VLBW infants born at Neocosur Neonatal Network centers from Jan 1 2001 through Dec 31 2016. Study design Retrospective analysis of prospectively collected data from all inborn infants with birthweight (BW) 500-1500 g and 23 - 35 weeks gestation. Results We examined data for 13,987 VLBW infants with mean BW 1,081±281 g and GA 28.8±2.9 weeks. Overall mortality was 26.8% without significant changes throughout the study period. Reductions in early-onset sepsis from 6.3% to 2.8% (P less then .001); late-onset sepsis from 21.1% to 19.5% (p = 0.002); retinopathy of prematurity from 21.3% to 13.8% (p less then 0.001); and hydrocephalus from 3.8% to 2.4% (p less then 0.001), were observed. The incidence for bronchopulmonary dysplasia decreased from 17.3% to 16% (p=0.043); incidence for severe intraventricular hemorrhage was 10.4%, necrotizing enterocolitis 11.1%, and periventricular leukomalacia 3.8% and did not change over the study period. Administration of antenatal corticosteroids increased from 70.2% to 82.3% and cesarean delivery from 65.9 to 75.4% (p less then 0.001). The use of conventional mechanical ventilation decreased from 67.7% to 63.9% (p less then 0.001) and CPAP increased from 41.3% to 64.3 % (p less then 0.001). Survival without major morbidity increased from 37.4% to 44.5% over the study period (p less then 0.001). Conclusion Progress in perinatal and neonatal care at network centers was associated with an improvement in survival without major morbidity of VLBW infants during a 16-year period. However, global mortality remained unchanged.Background & aims Although the healthy pancreas consists mostly of epithelial cells, pancreatic cancer and the precursor lesions known as pancreatic intraepithelial neoplasia, are characterized by an extensive accumulation of fibroinflammatory stroma that includes a substantial and heterogeneous fibroblast population. The cellular origin of fibroblasts within the stroma has not been determined. Here, we show that the Gli1 and Hoxb6 markers label distinct fibroblast populations in the healthy mouse pancreas. We then set out to determine whether these distinct fibroblast populations expanded during carcinogenesis. Methods We developed genetically engineered models using a dual-recombinase approach that allowed us to induce pancreatic cancer formation through FlpO-driven epithelial recombination of Kras while labeling Gli1+ or Hoxb6+ fibroblasts in an inducible manner. By using these models, we lineage-traced these 2 fibroblast populations during the process of carcinogenesis. Results Although in the healthy pancreas Gli1+ fibroblasts and Hoxb6+ fibroblasts are present in similar numbers, they contribute differently to the stroma in carcinogenesis. Namely, Gli1+ fibroblasts expand dramatically, whereas Hoxb6+ cells do not. Conclusions Fibroblasts present in the healthy pancreas expand during carcinogenesis, but with a different prevalence for different subtypes. Here, we compared Gli1+ and Hoxb6+ fibroblasts and found only Gli1+ expanded to contribute to the stroma during pancreatic carcinogenesis.Acid phosphatase (ACP) plays an important role in regulating phosphate nutrition in plants. Herein, for the first time, a novel ACP from Opuntia megacantha Salm-Dyck cladodes was purified to homogeneity and biochemically characterized. Specific activity of 8.78 U/mg was obtained with 11.29-fold purification and 15% yield. ACP was purified as monomer with molecular weight of 44 kDa as determined by SDS-PAGE under denaturing and nondenaturing conditions. Optimum pH and temperature for ACP activity was 5.5 and 60 °C, respectively. Thermodynamic parameters (Ea, ΔH, ΔG and ΔS) were also determined. selleck inhibitor ACP activity was stimulated by Ca2+, strongly inhibited by Cu2+ and Fe3+, and moderately inhibited by Mg2+ and Zn2+. Br-, CN-, F-, I- and N3- weakly inhibited ACP activity, where more than 70% of enzyme activity was remained at 5 mM. In addition, effect of β-ME, Cys, DTT, EDTA, H2O2, PMSF, SDS and TX-100 on ACP activity was investigated. km, Vmax, kcat and kcat/km of ACP for p-NPP were found to be 0.09 mM, 2.75 U/mL, 9.60 s-1 and 106.67 s-1 mM-1, respectively. The biochemical properties of ACP from Opuntia megacantha Salm-Dyck cladodes provide novel features with other plant ACPs and basic knowledge of ACP in Opuntia species.Donepezil (DPZ) is a well-known drug for Alzheimer's disease that inhibits acetylcholinesterase activity (AChE). In the present study, the inhibitory effect of DPZ on non-enzymatic glycated-AChE (GLY-AChE) was studied by different experimental and simulation techniques. The initial investigation revealed that glycation process could reduce AChE activity approximately 60% in the pure enzyme and 38% in the extracted crude AChE from neural cells cultured in the presence of high glucose (HG) concentration. It is suggested that glycation of lysine residues on the structure of AChE could change the conformation of the active site (Trp-86 and His-447) in a way that the orientation of acetylcholine interrupted. The further studies indicated that DPZ is although a strong inhibitor for the native enzyme, it is not able to affect the GLY-AChE activity. The KD values of AChE-DPZ and GLY-AChE-DPZ complexes were estimated to be 1.88 × 10-9 and 2.10 × 10-6, respectively. The stability assessment showed that AChE-DPZ complex is more stable than the glycated complex. Our results indicate that, glycation process could impact on the conformation of the residues involved in the DPZ binding cavity on α-helix domain. Therefore, DPZ is not able to bind its specific cavity to induce its inhibitory effects on GLY-AChE.Affinity for G-quadruplex (G4) structures may be a common feature of transcription-facilitating histone chaperons (HCs). This assumption is based on previous unmatched studies of HCs FACT, nucleolin (NCL), BRD3, and ATRX. We verified this assumption and considered its implications for the therapeutic applications of synthetic (exogenous) G4s and the biological significance of genomic G4s. First, we questioned whether exogenous G4s that recognize cell-surface NCL and could trap other HCs in the nucleus are usable as anticancer agents. We performed in vitro binding assays and selected leading multi-targeted G4s. They exhibited minor effects on cell viability. The presumed NCL-regulated intracellular transport of G4s was inefficient or insufficient for tumor-specific G4 delivery. Next, to clarify whether G4s in the human genome could recruit HCs, we compared available HC ChIP-seq data with G4-seq/G4-ChIP-seq data. Several G4s, including the well-known c-Myc quadruplex structure, were found to be colocalized with HC occupancy sites in cancer cell lines.