Cholesterol-dependent cytolysins: The outstanding questions.

The cholesterol-dependent cytolysins (CDCs) are a major family of bacterial pore-forming proteins secreted as virulence factors by Gram-positive bacterial species. CDCs are produced as soluble, monomeric proteins that bind specifically to cholesterol-rich membranes, where they oligomerize into ring-shaped pores of more than 30 monomers. Understanding the details of the steps the toxin undergoes in converting from monomer to a membrane-spanning pore is a continuing challenge. In this review we summarize what we know about CDCs and highlight the remaining outstanding questions that require answers to obtain a complete picture of how these toxins kill cells.

A single-institution experience with a brucellosis outbreak in the United States.

Human cases of brucellosis in the United States are primarily limited to imported infections or reservoirs. We describe a brucellosis outbreak involving 8 patients treated at a single hospital in the United States. Standardized precautionary microbiology processes and coordinated collaboration among hospital departments and local health departments assisted in optimally managing this disease at our institution.

Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR.

Obesity and diabetes are associated with increased breast cancer risk and worse disease progression once cancer is diagnosed; however, the exact etiology behind these observations remains to be fully elucidated. Due to the global obesity/diabetes pandemic, it is imperative to understand how these diseases promote and enhance breast cancer and other common cancers. In this study we demonstrate that hyperglycemia promotes breast cancer by altering leptin/IGF1R and AKT/mTOR signaling. To our knowledge, we show for the first time that in breast epithelial cells, hyperglycemia alone directly impacts leptin signaling. Hyperglycemia increased proliferation of both non-tumorigenic and malignant mammary epithelial cells. These observations coincided with increased leptin receptor and IGF1R receptor, as well as, increased levels of GRB2, pJAK2, pSTAT3, pIRS1/2, pAKT, and p-mTOR. Moreover, pJAK2 was almost completely colocalized with leptin receptor under high glucose conditions. These results demonstrate how hyperglycemia can potentially increase the risk of breast cancer in premalignant lesions and enhance cancer progression in malignant cells.

Optimal media for use in air sampling to detect cultivable bacteria and fungi in the pharmacy.

Current guidelines for air sampling for bacteria and fungi in compounding pharmacies require the use of a medium for each type of organism. U.S. Pharmacopeia (USP) chapter <797> (http://www.pbm.va.gov/linksotherresources/docs/USP797PharmaceuticalCompoundingSterileCompounding.pdf) calls for tryptic soy agar with polysorbate and lecithin (TSApl) for bacteria and malt extract agar (MEA) for fungi. In contrast, the Controlled Environment Testing Association (CETA), the professional organization for individuals who certify hoods and clean rooms, states in its 2012 certification application guide (http://www.cetainternational.org/reference/CAG-009v3.pdf?sid=1267) that a single-plate method is acceptable, implying that it is not always necessary to use an additional medium specifically for fungi. In this study, we reviewed 5.5 years of data from our laboratory to determine the utility of TSApl versus yeast malt extract agar (YMEA) for the isolation of fungi. Our findings, from 2,073 air samples obtained from compounding pharmacies, demonstrated that the YMEA yielded >2.5 times more fungal isolates than TSApl.