Hfq-binding small RNAs (sRNAs) in bacteria modulate the stability and translational efficiency of target mRNAs through limited base-pairing interactions. While these sRNAs are known to regulate numerous mRNAs as part of stress responses, what distinguishes targets and non-targets among the mRNAs predicted to base pair with Hfq-binding sRNAs is poorly understood. Using the Hfq-binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions using only the three unstructured regions of Spot 42 substantially improved the identification of previously known and novel Spot 42 targets. Furthermore, increasing the extent of base-pairing in single or multiple base-pairing regions improved the strength of regulation, but only for the unstructured regions of Spot 42. We also found that non-targets predicted to base pair with Spot 42 lacked an Hfq-binding site, folded into a secondary structure that occluded the Spot 42 targeting site, or had overlapping Hfq-binding and targeting sites. By modifying these features, we could impart Spot 42 regulation on non-target mRNAs. Our results thus provide valuable insights into the requirements for target selection by sRNAs.

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Purpose Interferon alpha 2b (IFN-α2b) has been used as an adjunctive agent to treat conjunctival melanoma (CM), however its efficacy is unproved due to a paucity of data. We present 5 cases of incompletely excised CM lesions to inform clinical decision making regarding the adjunctive use of IFN-α2b. Observations We identified all biopsy proven CM cases treated between 1997 and 2017 at the University of Iowa. Of these, we analyzed cases in which topical IFN-α2b drops were prescribed after the initial excision to treat surgical margins that were positive for primary acquired melanosis [PAM] with or without atypia or invasive CM. We noted the origin of CM (nevus, PAM, or de novo), presence and location of margins positive for residual melanoma, duration of IFN-α2b treatment, recurrences, time to recurrence, and outcome at last follow-up. Topical IFN-α2b drops (1 million IU/mL 4 times daily for 3–6 months) were used as adjunctive therapy in 5 cases following incomplete surgical excision of CM. The preceding lesion was PAM in 4 cases and compound nevus in 1 case. In 2 cases, margins were positive for PAM with atypia and both resulted in remission of melanoma at 54 and 33 months, respectively. However, in 3 cases, margins were positive for invasive melanoma and all 3 developed recurrence of melanoma despite IFN-α2b use. Conclusions and Importance There are limited data regarding the efficacy of IFN-α2b as adjunctive therapy for incomplete excision of CM lesions. In this series, adjunctive topical IFN-α2b did not prevent recurrence in cases with surgical margins positive for invasive melanoma. Our results indicate that caution should be exercised when considering adjunctive IFN-α2b to treat CM lesions not excised completely.

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Purpose To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. Methods All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. Results Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90–1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). Conclusions DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity.

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