Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.

DNA methylation, a key epigenetic driver of transcriptional silencing, is universally dysregulated in cancer. Reversal of DNA methylation by hypomethylating agents, such as the cytidine analogs decitabine or azacytidine, has demonstrated clinical benefit in hematologic malignancies. These nucleoside analogs are incorporated into replicating DNA where they inhibit DNA cytosine methyltransferases DNMT1, DNMT3A and DNMT3B through irreversible covalent interactions.

Skull base osteomyelitis imaging.

Purpose Of Review: Skull base osteomyelitis (SBO) is a challenging entity to diagnose and treat. The goal of this review is to summarize the imaging findings of SBO and present these in the context of recent studies on imaging of SBO.

Recent Findings: This review discusses the clinical presentation, pathophysiology and imaging appearances of SBO.

Neuroimaging of the Pituitary Gland: Practical Anatomy and Pathology.

The pituitary gland is a small endocrine organ located within the sella turcica. Various pathologic conditions affect the pituitary gland and produce endocrinologic and neurologic abnormalities. The most common lesion of the pituitary gland is the adenoma, a benign neoplasm.

Heavily calcified parapharyngeal space mesenchymal chondrosarcoma: Imaging and pathological findings and a review of the literature.

Parapharyngeal space (PPS) masses are relatively rare lesions of the head and neck, and account for 0.5-1.5% of head and neck lesions.

Critical illness-associated cerebral microbleed in a patient with sickle cell disease: A case report and review of the literature.

Critical illness-associated cerebral microbleed (CICM) is a relatively rare and newly described condition. It can occur in critically ill ICU patients and can be secondary to many underlying etiologies. CICM is associated with high mortality and permanent neurologic deficits in surviving patients.

Pseudohypoxic Brain Swelling: Report of 2 Cases and Introduction of the Lentiform Rim Sign as Potential MRI Marker.

Background: A rare but important complication related to otherwise uneventful brain and spine surgery is becoming more recognized and more frequently reported in the medical literature. This has been variably labeled as pseudohypoxic brain swelling or postoperative hypotension-associated venous congestion. This poorly understood condition occurs in the setting of surgical intervention and is thought to be related to cerebrospinal fluid leak or evacuation, decreased intracranial pressure, and subsequent development of deep venous congestion affecting the basal ganglia, thalami, and cerebellum.

Spontaneous "pneumo-apoplexy" as a presentation of pituitary adenoma.

Cases of spontaneous CSF leak associated with pituitary tumor apoplexy are uncommon in the literature with pneumocephalus or pneumosella being rare, especially spontaneous occurrence of pneumocephalus being extremely rare. We present a case of pituitary macroadenoma apoplexy resulting in spontaneous CSF leak and a large volume of intra-tumoral gas. A 65-year-old female presented with severe headache, profuse rhinorrhea and acute vision loss and was found to have a large sellar and suprasellar lesion with air and hemorrhage with mild peripheral enhancement.

Global transcriptomic analysis of the arcuate nucleus following chronic glucocorticoid treatment.

Objective: Glucocorticoids (GCs) are widely prescribed medications that are well recognized to cause adverse metabolic effects including hyperphagia, obesity, and hyperglycemia. These effects have been recapitulated in a murine model of GC excess, and we hypothesize that they are mediated, in part, through central mechanisms. This study aimed to identify genes in the hypothalamic arcuate nucleus (ARC) that are altered with GC treatment and evaluate their contribution to GC-induced metabolic abnormalities.

Imaging of Inflammatory Disorders of Salivary Glands.

Sialadenitis is among the most common conditions that affect the salivary glands. Inflammation of the salivary glands occurs as the end result of a variety of pathologic conditions, including infectious, autoimmune, and idiopathic causes. Clinically, inflammation of the salivary gland causes pain and localized swelling.

Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review.

The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example.

: An R package for the dose response analysis of live cell imaging data.

We present , an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time.

The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors.

Prolonged treatment with bevacizumab is associated with brain atrophy: a pilot study in patients with high-grade gliomas.

Bevacizumab is widely used for treatment of high-grade gliomas and other malignancies. Because bevacizumab has been shown to be associated with neurocognitive decline, this study is designed to investigate whether prolonged treatment with bevacizumab is also associated with brain atrophy. We identified 12 high-grade glioma patients who received bevacizumab for 12 months at the first recurrence and 13 matched controls and blindly compared the volumes of the contralateral hemispheres and contralateral ventricle in these two groups at baseline and after 12 ± 2 months of the baseline scan by two independent analyses.

Neurodegeneration with Brain Iron Accumulation: Clinicoradiological Approach to Diagnosis.

Discovery of genetic abnormalities associated with neurodegeneration with brain iron accumulation (NBIA) has led to use of a genetic-based NBIA classification schema. Most NBIA subtypes demonstrate characteristic imaging abnormalities. While clinical diagnosis of NBIA is difficult, analysis of both clinical findings and characteristic imaging abnormalities allows accurate diagnosis of most of the NBIA subtypes.

Practical imaging of the parotid gland.

The parotid gland may be affected by numerous pathologies, and physicians from many different medical and surgical specialties request parotid imaging. Mastering the typical imaging features of various types of parotid pathology is facilitated by understanding how various diseases produce their characteristic imaging findings. In this review article, we present succinct overviews of the normal anatomy and the common pathologies of the parotid gland and recommend a practical approach to differential diagnosis that can be easily implemented in day-to-day radiology practice.

Observer reliability of arteriovenous malformations grading scales using current imaging modalities.

Object: The aim of this study was to examine observer reliability of frequently used arteriovenous malformation (AVM) grading scales, including the 5-tier Spetzler-Martin scale, the 3-tier Spetzler-Ponce scale, and the Pollock-Flickinger radiosurgery-based scale, using current imaging modalities in a setting closely resembling routine clinical practice.

Methods: Five experienced raters, including 1 vascular neurosurgeon, 2 neuroradiologists, and 2 senior neurosurgical residents independently reviewed 15 MRI studies, 15 CT angiograms, and 15 digital subtraction angiograms obtained at the time of initial diagnosis. Assessments of 5 scans of each imaging modality were repeated for measurement of intrarater reliability.

Vascular lesions of the central skull base region.

The arterial and venous structures of the central skull base region form complex anatomical relationships with each other and with adjacent osseous and neural structures. Vascular structures including the cavernous sinuses and internal carotid arteries can be displaced, encased, or invaded by neoplastic, inflammatory, or infectious lesions of the central skull base. Consequently, the vascular structures have a unique role in determining the imaging appearance, clinical significance, and therapeutic options of lesions occurring in the central skull base.

Neuroimaging: intrinsic lesions of the central skull base region.

The sphenoid bone is the osseous foundation of the central skull base. The body of the sphenoid is cuboid in shape and its posterior margin is joined to the basilar occipital bone (basiocciput) via a synchondrosis to form the complete clivus. Traditionally, radiologic discussions of intrinsic disease of the central skull base emphasize marrow space-occupying lesions including metastatic disease, myeloma, and chordoma.