Scedosporium Sinusitis: A Rare Opportunistic Infection.

Scedosporium sinusitis is an opportunistic fungal infection that is difficult to treat due to its inherent resistance to many antifungal agents. Infections may cause both localized or disseminated disease usually in skin and soft tissues. Immunocompetent persons are typically unaffected and disseminated disease occurs in immunocompromised hosts. Scedosporiumis a common hyaline mold causing sinopulmonary disease in those with hematologic malignancies and neutropenia. A 38-year-old Caucasian male with a medical history significant for HIV with intermittent treatment compliance, high-grade diffuse large B cell lymphoma (DLBCL) on chemotherapy, and hemophagocytic lymphohistiocytosis (HLH) presented with right-sided facial pain and fever. Maxillofacial computed tomography (CT) showed thickening and opacification of the sphenoid and maxillary sinuses concerning for fungal sinusitis. Endoscopic transsphenoidal debridement showed fungal growth of Scedosporium and the patient's blood cultures were ultimately negative. The patient underwent debridement of fungal sinusitis as well as right medial maxillectomy and ethmoidectomy. A three-month course of voriconazole was started and completed with weekly liver enzyme tests to monitor medication side effects. He has since been observed well as an outpatient with his oncologist after three months loss to follow-up and his infection has resolved.

Boosting NAD ameliorates hematopoietic impairment linked to short telomeres in vivo.

Short telomeres are a defining feature of telomere biology disorders (TBDs), including dyskeratosis congenita (DC), for which there is no effective general cure. Patients with TBDs often experience bone marrow failure. NAD, an essential metabolic coenzyme, is decreased in models of DC. Herein, using telomerase reverse transcriptase null (Tert-/-) mice with critically short telomeres, we investigated the effect of NAD supplementation with the NAD precursor, nicotinamide riboside (NR), on features of health span disrupted by telomere impairment. Our results revealed that NR ameliorated body weight loss in Tert-/- mice and improved telomere integrity and telomere dysfunction-induced systemic inflammation. NR supplementation also mitigated myeloid skewing of Tert-/- hematopoietic stem cells. Furthermore, NR alleviated villous atrophy and inflammation in the small intestine of Tert-/- transplant recipient mice. Altogether, our findings support NAD intervention as a potential therapeutic strategy to enhance aspects of health span compromised by telomere attrition.

Detection of DNA Damage in Hematopoietic Stem Cells.

Single-cell gel electrophoresis (SCGE or Comet assay) and the Fast Halo assay, also known as the Halo assay, are powerful tools to generate DNA damage measurements with single-cell resolution. Though these techniques are prone to have variability, they can be robust tools for quantifying DNA damage when planned and executed carefully. Here, we present both assays and highlight each technique's advantages and challenges in measuring DNA damage in cells with limiting cell number, such as hematopoietic stem cells (HSCs). The Comet assay is highly sensitive at the cost of increased variability. The Halo assay attenuates some of the effects of variability present in the Comet assay but does not eliminate them entirely and is less sensitive. Overall, the Comet and Halo assays are powerful means of directly measuring DNA damage. We recommend the below methods for detecting damage in hematopoietic stem cells, but the methods can easily be adjusted for measuring damage in any type of single cells in suspension.