Deployment and transcriptional evaluation of nitisinone, an FDA-approved drug, to control bed bugs.

Bed bugs are blood-feeders that rapidly proliferate into large indoor infestations. Their bites can cause allergies, secondary infections and psychological stress, among other problems. Although several tactics for their management have been used, bed bugs continue to spread worldwide wherever humans reside. This is mainly due to human-mediated transport and their high resistance to several classes of insecticides. New treatment options with novel modes of action are required for their control. In this study, we evaluated the use of nitisinone (NTBC), an FDA-approved drug, for bed bug control in an insecticide-susceptible (HH) and an insecticide-resistant (CIN) population. Although NTBC was lethal to both populations when administered orally or applied topically in very low doses, we observed a slight but significant resistance in the CIN population. Transcriptomic analysis in both populations indicated that NTBC treatment elicited a broad suppression of genes associated with RNA post-transcriptional modifications, translation, endomembrane system, protein post-translational modifications and protein folding. The CIN population exhibited higher ATP production and xenobiotic detoxification. Feeding studies on a mouse model highlight that NTBC could be used as a control method of bed bugs by host treatment. The results demonstrate that NTBC can be used as a new active ingredient for bed bug control by topical or oral treatment and shed light on the molecular mechanisms of suppressed tyrosine metabolism following NTBC treatment.

Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy.

PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest-wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated.