Suicidal ideation may be uniquely associated with inflammation in depressed patients.

An agar-plate assay was adapted to examine aspects of quinolone structure that restrict the emergence of quinolone-mediated quinolone resistance. When Escherichia coli was applied to agar containing nalidixic acid, the number of quinolone-resistant mutants arising during incubation was decreased by raising the drug concentration and by mutations expected to block the induction of the SOS response (recA, lexA); the mutant number was increased by a mutator mutation (ung). The examination of four related fluoroquinolones then revealed that a C-8 methoxy group and an N-ethyl piperazine substituent at C-7 reduced mutant acquisition more effectively than C-8 H and C-7 C-ethyl piperazine groups. The fluoroquinolone that was most effective at restricting mutant acquisition was the most active when lethal activity was measured on agar plates or in liquid medium (as minimal bactericidal concentration). It also exhibited the lowest ratio of mutant MIC to wild-type MIC when it was tested with a set of isogenic gyrase mutants, and it had a low mutant prevention concentration (MPC) relative to MIC. However, a low MPC was less likely to be important in restricting the induced mutant accumulation because a fluoroquinolone N-ethyl piperazine substituent was more effective than a C-ethyl piperazine substituent at reducing mutant accumulation but was less effective at lowering the MPC. An 8-methoxy-quinazoline-2,4-dione was also effective at restricting the accumulation of resistant mutants on agar. Collectively, these data characterize a simple assay for detection of drug-mediated resistance that is sensitive to the structures of GyrA inhibitors. The assay provides a new method for screening quinolones and quinolone-like molecules that complements MPC-based tests for restricting the emergence of resistance.Members of the quinolone class of antibacterial agents are becoming increasingly popular as resistance to other compounds grows. Unfortunately, quinolone-containing therapies are also threatened by the emergence of bacterial resistance, which is likely to occur in two ways. One is through the spontaneous presence of resistant mutants prior to therapy, followed by enrichment and amplification of the mutants during therapy. The second is through the generation of resistant mutants during treatment via error-prone repair processes, such as those known to be part of the SOS response (17). In previous work we developed strategies for identifying compounds that would restrict the selective amplification of resistant mutant subpopulations present prior to therapy (6, 10). An approach for identifying agents that restrict the acquisition of resistant mutants generated (induced) by the compounds during drug exposure has not been reported.Accumulation of quinolone-induced quinolone-resistant mutants can be observed by applying large numbers of bacteria to quinolone-containing agar and then scoring the number of colonies arising during incubation (2, 3). An important feature of this assay is that the generation of individual mutants is not...

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Background: Heart failure (HF), the leading cause of hospitalization in adults over the age of 65, is a difficult-to-treat syndrome associated with high morbidity and mortality. Home-monitoring programs may help reduce HF-associated morbidity, but can be difficult to establish in smaller clinical settings. In this quality improvement project, we identified local patients at high risk of HF-related morbidity and hospitalizations, then implemented a medical student-based constant-contact program to encourage their follow-through on self-care.   Methods: Between June 2012 and September 2014, our clinic treated 197 patients for systolic or diastolic HF. These patients’ baseline characteristics were evaluated for trends that increased their risk for hospitalization. Of the high-risk patients identified (n=80), 12 (15%) were enrolled in the project. An 8-week constant-contact intervention was initiated through weekly calls. Patients’ health statuses were recorded and the importance of self-care was reiterated.   Results: High-risk HF patients were identified based on >10 clinic visits during the study period; 3 were lost to follow-up. Each patient completed two questionnaires at the study’s beginning and conclusion, with response rates of 67% (6/9) and 56% (5/9). Most participants reported symptom improvement and increased knowledge about their conditions.   Conclusion: Our preliminary population-guided, medical-student initiated intervention in a small clinical setting was designed to increase patient understanding and compliance and to improve HF symptoms. Although the study was limited by its low participation rate, drastic improvements in self-reported outcomes were noted among participants. A larger study with similar positive outcomes could ultimately influence follow-up methods.