MR1 overexpression correlates with poor clinical prognosis in glioma patients.

BACKGROUND: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. METHODS: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression. RESULTS: MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. CONCLUSIONS: Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.

An Unusual Case of Actinomucor elegans: A Challenging Diagnosis.

BACKGROUND Actinomucor elegans is an unusual cause of mucormycosis and can be difficult to identify by conventional methods. Mucormycosis has a very high mortality rate, especially among immunocompromised individuals. Due to the morbid and progressive nature of opportunistic fungal infections, early diagnosis is paramount for effective disease management. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI) and Sanger sequencing are useful methods for rapid diagnosis of unusual fungal pathogens. CASE REPORT We report a fatal case of mucormycosis caused by A. elegans in an immunocompromised man. The pathogen was isolated from a large nasal septal black eschar that developed rapidly during tooth extraction in a patient with myelodysplastic syndrome and diabetes mellitus. After unsuccessful identification by conventional methods, A. elegans was identified using MALDI and Sanger sequencing. CONCLUSIONS Diagnosing fungal organisms poses many difficulties, but amidst the technological evolution in pathogen identification, there are useful methods for rapid identification, including MALDI and sequencing. With these powerful tools, earlier diagnosis will give health professionals an advantage against potentially fatal fungal infections.

Macrolide and Clindamycin Resistance in Group a Streptococci Isolated From Children With Pharyngitis.

Group A streptococcus (GAS) is responsible for 15%-30% of cases of acute pharyngitis in children. Macrolides such as azithromycin have become popular for treating GAS pharyngitis. We report macrolide resistance rates in a primary care setting in our geographic area over the past 5 years and discuss the implications of resistance in making treatment decisions. Throat swabs were collected from children with pharyngitis from May 2011 to May 2015 in a primary care setting in Madison, Wisconsin. Susceptibility testing was performed for erythromycin and clindamycin using the Kirby-Bauer disk diffusion method. GAS was identified on 143 throat cultures. Overall, 15% of GAS isolates demonstrated nonsusceptibility for both clindamycin and erythromycin. Inducible resistance (positive D-test) was detected in 17 isolates (12%). The rate of detection of nonsusceptibility in each year of the study did not change over time. Azithromycin should only be used for patients with pharyngitis and substantial manifestations of penicillin hypersensitivity and when used, susceptibility testing should always be performed.