Cyclic di-GMP Positively Regulates DNA Repair in Vibrio cholerae.

In Vibrio cholerae, high intracellular cyclic di-GMP (c-di-GMP) concentration are associated with a biofilm lifestyle, while low intracellular c-di-GMP concentrations are associated with a motile lifestyle. c-di-GMP also regulates other behaviors, such as acetoin production and type II secretion; however, the extent of phenotypes regulated by c-di-GMP is not fully understood. We recently determined that the sequence upstream of the DNA repair gene encoding 3-methyladenine glycosylase (tag) was positively induced by c-di-GMP, suggesting that this signaling system might impact DNA repair pathways. We identified a DNA region upstream of tag that is required for transcriptional induction by c-di-GMP. We further showed that c-di-GMP induction of tag expression was dependent on the c-di-GMP-dependent biofilm regulators VpsT and VpsR. In vitro binding assays and heterologous host expression studies show that VpsT acts directly at the tag promoter in response to c-di-GMP to induce tag expression. Last, we determined that strains with high c-di-GMP concentrations are more tolerant of the DNA-damaging agent methyl methanesulfonate. Our results indicate that the regulatory network of c-di-GMP in V. cholerae extends beyond biofilm formation and motility to regulate DNA repair through the VpsR/VpsT c-di-GMP-dependent cascade.IMPORTANCEVibrio cholerae is a prominent human pathogen that is currently causing a pandemic outbreak in Haiti, Yemen, and Ethiopia. The second messenger molecule cyclic di-GMP (c-di-GMP) mediates the transitions in V. cholerae between a sessile biofilm-forming state and a motile lifestyle, both of which are important during V. cholerae environmental persistence and human infections. Here, we report that in V. cholerae c-di-GMP also controls DNA repair. We elucidate the regulatory pathway by which c-di-GMP increases DNA repair, allowing this bacterium to tolerate high concentrations of mutagens at high intracellular levels of c-di-GMP. Our work suggests that DNA repair and biofilm formation may be linked in V. cholerae.

Presentation and outcomes of patients with clinically T1-2, N0 supraglottic squamous cell carcinoma: The role of definitive radiotherapy compared to primary partial laryngectomy.

BACKGROUND: Early-stage supraglottic squamous cell carcinoma (SCC) is usually treated with a single modality. The aim of this study is to examine the role of radiotherapy (RT) versus partial laryngectomy (open, robotic-assisted, or endoscopic) with elective neck dissection (PL + END). METHODS: A retrospective analysis of the National Cancer Database, 2010-2016. The study population included adult patients with clinically T1-2, N0 supraglottic SCC. RESULTS: 3301 patients were included. RT was performed in 93.52%, open PL + END in 2.64%, robotic-assisted PL + END in 1.33%, and endoscopic surgical resection in 2.51%. In the surgery group, T was upstaged in 23.36% and N was upstage in 16.36%. Five-year survival in the primary surgery group compared to RT group was 61.89% versus 77.46% (HR: 0.56, 95%CI: 0.43, 0.72). CONCLUSIONS: T was upstaged in 23% of surgical patients. This accurate staging is likely missed in patients who undergo RT and possibly contributes to lower overall survival of this treatment group.

A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma.

IMPORTANCE: Mammary Analogue Secretory Carcinoma (MASC) is a newly characterized salivary gland carcinoma resembling secretory carcinoma of the breast. Prior to being described, MASC was most commonly misdiagnosed as Acinic Cell Carcinoma. Though MASC is predominantly an adult neoplasm, cases have been reported in the pediatric population. Reporting and summarizing of known cases is imperative to understand the prognosis and clinical behavior of MASC. OBJECTIVE: EVIDENCE REVIEW: Web of Science, Medline, EMBASE, and The Cochrane Library were searched for studies that included pediatric cases of MASC. Data on clinical presentation, diagnosis and management, and pathology were collected from all pediatric cases. FINDINGS: CONCLUSIONS AND RELEVANCE: Since the first case of MASC in the pediatric population was described in 2011, only 12 cases, including this one, have been described in the literature. With this paucity of information, much remains unknown regarding this new pathologic diagnosis. The collection of clinical outcomes data of children with MASC is needed to better understand the behavior of this malignancy as well as determine optimal treatment regimens.