SummaryThe osteogenic and oncogenic transcription factor RUNX2 downregulates the RNA polymerase I (RNA Pol I)-mediated transcription of rRNAs and changes histone modifications associated with the rDNA repeat. However, the mechanisms by which RUNX2 suppresses rRNA transcription are not well understood. RUNX2 cofactors such as histone deacetylases (HDACs) play a key role in chromatin remodeling and regulation of gene transcription. Here, we show that RUNX2 recruits HDAC1 to the rDNA repeats in osseous cells. This recruitment alters the histone modifications associated with active rRNA-encoding genes and causes deacetylation of the protein upstream binding factor (UBF, also known as UBTF). Downregulation of RUNX2 expression reduces the localization of HDAC1 to the nucleolar periphery and also decreases the association between HDAC1 and UBF. Functionally, depletion of HDAC1 relieves the RUNX2-mediated repression of rRNA-encoding genes and concomitantly increases cell proliferation and global protein synthesis in osseous cells. Our findings collectively identify a RUNX2-HDAC1-dependent mechanism for the regulation of rRNA-encoding genes and suggest that there is plasticity to RUNX2-mediated epigenetic control, which is mediated through selective mitotic exclusion of co-regulatory factors.

Vascular access has been a major problem in the management of end stage renal disease (ESRD) patients on chronic hemodialysis (HD). Native arteriovenous fistulas (AVFs) are the preferred vascular access for ESRD patients on HD. Multiple factors have been evaluated as causes for poor AVF rates. The purpose of this retrospective analysis was to assess the impact of training of nephrologist in interventional nephrology (IN) on vascular access outcomes. We studied the rates of different types of vascular access amongst patients on chronic HD under the care of two nephrology groups over 25 months in a community dialysis unit. In group A, all vascular access were managed directly by an interventional nephrologist, while in group B they were managed by general nephrologist with no exposure to IN during their training. A total of 129 patients received dialysis for at least 4 months at the unit during those 25 months. The rate of AVFs in group A was 56.6%, while in group B the rate of AVFs was 40.8% (p = 0.059). The rate of AVGs in group A was 22.9% and in group B it was 27.6% (p = 0.647). The tunneled HD catheter rate in group A was 20.4% and in group B it was 31.6% (p = 0.098). The results of this study demonstrate that training of nephrologists in IN leads to increased use of AVF as HD vascular access. We suggest that training programs in nephrology should consider incorporating IN into their programs to increase the prevalence of AVFs.

Amiodarone is an antiarrhythmic drug that has been commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. Especially, its main metabolically active metabolite desethylamiodarone can adversely affect many organs. A very well-known severe complication of amiodarone therapy is the amiodarone-induced pulmonary toxicity. This article presents the case study of an 82-year-old male patient with acute amiodarone-induced pulmonary toxicity. The patient underwent endovascular aneurysm repair for rapidly increasing abdominal aortic aneurysm. During the postoperative period the patient developed rapid atrial fibrillation and amiodarone therapy was initiated. Subsequently, the patient went into acute respiratory failure and was requiring high supplemental oxygen support and a chest X-ray revealed bilateral pulmonary infiltrates. During the hospital course the patient required mechanical ventilator support. With discontinuation of amiodarone, supportive therapy and steroid treatment patient symptoms significantly improved. Amiodarone-induced pulmonary toxicity must be considered in the differential diagnosis of all patients on the medication with progressive or acute respiratory symptoms. Early discontinuation of amiodarone and aggressive corticosteroid therapy should be considered as a viable treatment strategy.

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