Fluorescent Imaging as a Component of Diagnosing Pyoderma Gangrenosum: A Case Report.

ABSTRACT: A 64-year-old White woman was admitted to the hospital with complaint of progressive right hip ulceration at the wound site following a total right hip arthroplasty. Initial history and physical examination gave a leading differential diagnosis of pyoderma gangrenosum. Until recently, the exclusion of infection for pyoderma gangrenosum has been largely clinical and supported by cultures/biopsies demonstrating the absence of infection. The MolecuLight i:X (MolecuLight, Toronto, Ontario, Canada) is a novel bedside fluorescent imaging device capable of determining the bacterial burden within a wound in real time. Fluorescent imaging excluded infection at the initial visit, and debridement was avoided. Subsequently, pathergy was avoided as well. The patient was started on topical clobetasol with hypochlorous acid-soaked dressings. She also received 80 mg daily of prednisone and high-dose vitamin D3 (10,000 IU). Recovery was complicated by a deep tunnel along the incisional line at 3 months postdiagnosis, which required slowing of the prednisone taper and the addition of colchicine. Repeat cultures grew Parvimonas, Pseudomonas, and Streptococcus species. Appropriate antibiotics were given. The patient was transitioned from prednisone to adalimumab and started on negative-pressure wound therapy. Negative-pressure wound therapy was discontinued at 5 months, and the wound resolved at 6 months.

Educational Case: Hypersensitivity Vasculitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, seehttp://journals.sagepub.com/doi/10.1177/2374289517715040. 1.

Hit and run versus long-term activation of PARP-1 by its different domains fine-tunes nuclear processes.

Poly(ADP-ribose) polymerase 1 (PARP-1) is a multidomain multifunctional nuclear enzyme involved in the regulation of the chromatin structure and transcription. PARP-1 consists of three functional domains: the N-terminal DNA-binding domain (DBD) containing three zinc fingers, the automodification domain (A), and the C-terminal domain, which includes the protein interacting WGR domain (W) and the catalytic (Cat) subdomain responsible for the poly(ADP ribosyl)ating reaction. The mechanisms coordinating the functions of these domains and determining the positioning of PARP-1 in chromatin remain unknown. Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as well as consisting of only one of those domains, we demonstrate that different functions of PARP-1 are coordinated by interactions among these domains and their targets. Interaction between the DBD and damaged DNA leads to a short-term binding and activation of PARP-1. This "hit and run" activation of PARP-1 initiates the DNA repair pathway at a specific point. The long-term chromatin loosening required to sustain transcription takes place when the C-terminal domain of PARP-1 binds to chromatin by interacting with histone H4 in the nucleosome. This long-term activation of PARP-1 results in a continuous accumulation of pADPr, which maintains chromatin in the loosened state around a certain locus so that the transcription machinery has continuous access to DNA. Cooperation between the DBD and C-terminal domain occurs in response to heat shock (HS), allowing PARP-1 to scan chromatin for specific binding sites.