Echocardiographic Features of the Ductus Arteriosus and the Foramen Ovale in a Hospital-Based Population of Neonatal Foals.

The ductus arteriosus (DA) and foramen ovale (FO), including the septum primum (SP) and septum secundum (SS), are important structures in fetal circulation and are unexplored in neonatal equids. The objective of this study is to describe echocardiographic characteristics in a hospital-based population of neonatal foals. On days 2, 5 and 10 after parturition, cardiac ultrasound was performed, and clinical data were collected in healthy and diseased Warmblood foals.

Prevalence and characteristics of ventricular septal defects in a non-racehorse equine population (2008-2019).

Background: Ventricular septal defects (VSDs) are the most common congenital cardiac defect in horses.

Objectives: To identify prevalence, age, breed, and sex distribution of VSD and to describe associated clinical and ultrasonographic findings.

Animals: Hospital-based population of 21 136 horses presented to the equine internal medicine department.

Dichotomous Impact of Myc on rRNA Gene Activation and Silencing in B Cell Lymphomagenesis.

A major transcriptional output of cells is ribosomal RNA (rRNA), synthesized by RNA polymerase I (Pol I) from multicopy rRNA genes (rDNA). Constitutive silencing of an rDNA fraction by promoter CpG methylation contributes to the stabilization of these otherwise highly active loci. In cancers driven by the oncoprotein Myc, excessive Myc directly stimulates rDNA transcription.

IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma.

In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma.

Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition.

In the current study we examined the combination of SAHA and SBE13 in cancer and non-cancer cells. HeLa cells displayed a synergistically reduced cell proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells. Cell cycle distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells.

Vanillin-derived antiproliferative compounds influence Plk1 activity.

We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure.

Combinatorial inhibition of Plk1 and PKCβ in cancer cells with different p53 status.

PKCβ and Plk1 are fascinating targets in cancer therapy. Therefore, we combined Enzastaurin targeting PKCβ and SBE13 targeting Plk1 to test synergistic effects in cells with different p53 status. We analyzed cell proliferation and apoptosis induction, and did Western blot and FACScan analyses to examine the combined PKCβ and Plk1 inhibition.

Do injection drug users have more adverse events during procedural sedation and analgesia for incision and drainage of cutaneous abscesses?

Objective: Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) in the emergency department (ED). We compared adverse events (AEs) for IDUs to those for non-IDUs receiving PSA for incision and drainage of cutaneous abscesses.

Methods: This was a retrospective analysis of a PSA safety audit.

Drugs by numbers: reaction-driven de novo design of potent and selective anticancer leads.

A potent and selective inhibitor of the anticancer target Polo-like kinase 1 was found by computer-based molecular design. This type II kinase inhibitor was synthesized as suggested by the design software DOGS and exhibited significant antiproliferative effects against HeLa cells without affecting nontransformed cells. The study provides a proof-of-concept for reaction-based de novo design as a leading tool for drug discovery.