Preterm intraventricular hemorrhage in vitro: Modeling the cytopathology of the ventricular zone

BACKGROUND: Severe intraventricular hemorrhage (IVH) is one of the most devastating neurological complications in preterm infants, with the majority suffering long-term neurological morbidity and up to 50% developing post-hemorrhagic hydrocephalus (PHH). Despite the importance of this disease, its cytopathological mechanisms are not well known. An in vitro model of IVH is required to investigate the effects of blood and its components on the developing ventricular zone (VZ) and its stem cell niche. To address this need, we developed a protocol from our accepted in vitro model to mimic the cytopathological conditions of IVH in the preterm infant. METHODS: Maturing neuroepithelial cells from the VZ were harvested from the entire lateral ventricles of wild type C57BL/6 mice at 1-4 days of age and expanded in proliferation media for 3-5 days. At confluence, cells were re-plated onto 24-well plates in differentiation media to generate ependymal cells (EC). At approximately 3-5 days, which corresponded to the onset of EC differentiation based on the appearance of multiciliated cells, phosphate-buffered saline for controls or syngeneic whole blood for IVH was added to the EC surface. The cells were examined for the expression of EC markers of differentiation and maturation to qualitatively and quantitatively assess the effect of blood exposure on VZ transition from neuroepithelial cells to EC. DISCUSSION: This protocol will allow investigators to test cytopathological mechanisms contributing to the pathology of IVH with high temporal resolution and query the impact of injury to the maturation of the VZ. This technique recapitulates features of normal maturation of the VZ in vitro, offering the capacity to investigate the developmental features of VZ biogenesis

Investigating the Impact of Crohn's Disease on the Bioaccessibility of a Lipid-Based Formulation with an in Vitro Dynamic Gastrointestinal Model

The aim of the study was to investigate the impact of Crohn's disease (CD) on the performance of a lipid-based formulation of ciprofloxacin in a complex gastrointestinal simulator (TIM-1, TNO) and to compare the luminal environment in terms of bile salt and lipid composition in CD and healthy conditions. CD conditions were simulated in the TIM-1 system with a reduced concentration of porcine pancreatin and porcine bile. The bioaccessibility of ciprofloxacin was similar in simulated CD and healthy conditions considering its extent as well as its time course in the jejunum and ileum filtrate. Differences were observed in terms of the luminal concentration of triglycerides, monoglycerides, and fatty acids in the different TIM-1 compartments, indicating a reduction and delay in the lipolysis of formulation excipients in CD. The quantitative analysis of bile salts revealed higher concentrations for healthy conditions (standard TIM-1 fasted-state protocol) in the duodenum and jejunum TIM-1 compartments compared to published data in human intestinal fluids of healthy subjects. The reduced concentrations of bile salts in simulated CD conditions correspond to the levels observed in human intestinal fluids of healthy subjects in the fasted state.A lipidomics approach with ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) has proven to be a time-efficient method to semiquantitatively analyze differences in fatty acid and bile salt levels between healthy and CD conditions. The dynamic luminal environment in CD and healthy conditions after administration of a lipid-based formulation can be simulated using the TIM-1 system. For ciprofloxacin, an altered luminal lipid composition had no impact on its performance indicating a low risk of altered performance in CD patients. </p

Dynamical Fine Tuning in Brane Inflation

We investigate a novel mechanism of dynamical tuning of a flat potential in the open string landscape within the context of warped brane-antibrane inflation in type IIB string theory. Because of competing effects between interactions with the moduli stabilizing D7-branes in the warped throat and anti-D3-branes at the tip, a stack of branes gives rise to a local minimum of the potential, holding the branes high up in the throat. As branes successively tunnel out of the local minimum to the bottom of the throat the potential barrier becomes lower and is eventually replaced by a flat inflection point, around which the remaining branes easily inflate. This dynamical flattening of the inflaton potential reduces the need to fine tune the potential by hand, and also leads to successful inflation for a larger range of inflaton initial conditions, due to trapping in the local minimum.Comment: 23 pages, 9 figures. v2: Updated D3-dependence in potential, small changes to numerical result

Lectures in Honor of the Alexander Campbell Bicentennial

In 1984, the Disciples of Christ Historical Society set forth a program to celebrate the 200th birthday of Alexander Campbell. This book launched a renewed interest in Stone-Campbell history and inspired research that shaped numerous historical projects. Contributors include T. Dwight Bozeman, Robert O. Fife, Richard L. Harrison, Samuel S. Hill, Thomas Olbricht, William J. Richardson, D. Newell Williams, Eva Jean Wrather, and Barbara Brown Zickmund.https://digitalcommons.acu.edu/acu_library_books/1018/thumbnail.jp

Platelet‐Derived Growth Factor Stimulates Bone Fill and Rate of Attachment Level Gain: Results of a Large Multicenter Randomized Controlled Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141430/1/jper2205.pd

Kinetic viscoelasticity modeling applied to degradation during carbon–carbon composite processing

Kinetic viscoelasticity modeling has been successfully utilized to describe phenomena during cure of thermoset based carbon fiber reinforced matrices. The basic difference from classic viscoelasticity is that the fundamental material descriptors change as a result of reaction kinetics. Accordingly, we can apply the same concept for different kinetic phenomena with simultaneous curing and degradation. The application of this concept can easily be utilized in processing and manufacturing of carbon–carbon composites, where phenolic resin matrices are cured degraded and reinfused in a carbon fiber bed. This work provides a major step towards understanding complex viscoelastic phenomena that go beyond simple thermomechanical descriptors.United States. Air Force Office of Scientific ResearchNational Science Foundation (U.S.) (Joint U.S.-Greece Program

Platelet‐Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36‐Month Extension Results From a Randomized, Controlled, Double‐Masked Clinical Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141092/1/jper0456.pd

Clinical determinants of plasma cardiac biomarkers in patients with stable chest pain

Objective: Troponin and B-type natriuretic peptide (BNP) concentrations are associated with cardiovascular risk in stable patients. Understanding their determinants and identifying modifiable clinical targets may improve outcomes. We aimed to establish clinical and cardiac determinants of these biomarkers. Methods: This was a prespecified substudy from the randomised Scottish Computed Tomography of the Heart trial, which enrolled patients 18–75 years with suspected stable angina between 2010 and 2014 (NCT01149590). We included patients from six centres in whom high-sensitivity troponin I and BNP were measured (Singulex Erenna). Patients with troponin &gt;99th centile upper reference limit (10.2 ng/L) or BNP ≥400 ng/L were excluded to avoid inclusion of patients with myocardial injury or heart failure. Multivariable linear regression models were constructed with troponin and BNP as dependent variables. Results: In total, 885 patients were included; 881 (99%) and 847 (96%) had troponin and BNP concentrations above the limit of detection, respectively. Participants had a slight male preponderance (n=513; 56.1%), and the median age was 59.0 (IQR 51.0–65.0) years. The median troponin and BNP concentrations were 1.4 (IQR 0.90–2.1) ng/L and 29.1 (IQR 14.0–54.0) ng/L, respectively. Age and atherosclerotic burden were independent predictors of both biomarkers. Male sex, left ventricular mass and systolic blood pressure were independent predictors of increased troponin. In contrast, female sex and left ventricular volume were independent predictors of increased BNP. Conclusions: Troponin and BNP are associated with coronary atherosclerosis but have important sex differences and distinct and contrasting associations with CT-determined left ventricular mass and volume

The Prevalence and Influence of the Combination of Humor and Violence in Super Bowl Commercials

The growing concern over violence in the media has led to vast amounts of research examining the effects of violent media on viewers. An important subset of this research looks at how humor affects this relationship. While research has considered this subset in television programming, almost no research has explored this in the context of advertising. This paper builds on the little research that exists by examining the effects of combining humor and violence, as well as the theoretical approaches that underlie these effects. A content analysis is conducted to identify the prevalence of violence, humor, and the combination of these elements in a longitudinal sample of Super Bowl commercials (2005, 2007, and 2009). Further, we investigate the relationship between the joint occurrence of humor and violence in ads and ad popularity. We conclude that violent acts are rampant in these commercials and that many acts are camouflaged by the simultaneous presence of humor, especially in the most popular ads

Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy

Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn2+-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal- free and metal-bound PsaA have provided the first insights into the mechanism of PsaA-facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations to study the relative flexibility of the structural domains in metal-free PsaA and its distribution of conformations in solution. The results show that the crystal structure of the metal-free PsaA is a good representation of the dominant conformation in solution, but the protein also samples structurally distinct conformations that are not captured by the crystal structure. Further, these results suggest that the metal binding site is larger and more solvent exposed than indicated by the metal-free crystal structure. Collectively, this study provides atomic-resolution insight into the conformational dynamics of PsaA prior to metal binding and lays the groundwork for future EPR and MD based studies of PsaA in solution