Previous studies have shown that retinal melatonin plays an important role in the regulation of retinal daily and circadian rhythms. Melatonin exerts its influence by binding to G-protein coupled receptors named melatonin receptor type 1 and type 2 and both receptors are present in the mouse retina. Earlier studies have shown that clock genes are rhythmically expressed in the mouse retina and melatonin signaling may be implicated in the modulation of clock gene expression in this tissue. In this study we determined the daily and circadian expression patterns of Per1, Per2, Bmal1, Dbp, Nampt and c-fos in the retina and in the photoreceptor layer (using laser capture microdissection) in C3H-f+/+ and in melatonin receptors of knockout (MT1 and MT2) of the same genetic background using real-time quantitative RT-PCR. Our data indicated that clock and clock-controlled genes are rhythmically expressed in the retina and in the photoreceptor layer. Removal of melatonin signaling significantly affected the pattern of expression in the retina whereas in the photoreceptor layer only the Bmal1 circadian pattern of expression was affected by melatonin signaling removal. In conclusion, our data further support the notion that melatonin signaling may be important for the regulation of clock gene expression in the inner or ganglion cells layer, but not in photoreceptors.

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Up to 10% of hospitalized patients report an allergy to penicillin (PCN). However, over 90% of patients with a reported PCN allergy do not have a true allergy. False reporting can lead to overuse of non-preferred broad-spectrum antibiotics and poorer clinical outcomes. We developed a multidisciplinary protocol for PCN skin testing for hospitalized patients with a documented PCN allergy. Feasibility and impact of this protocol were assessed to determine the necessary resources for broader implementation. METHODS: A pilot study was conducted at Michigan Medicine from July 2018 to January 2019. Patients with PCN allergy were identified from hospitalist and infectious disease services. PCN skin test was performed after screening. Patients' outpatient pharmacies and PCPs were notified of the result and rates of penicillin allergy re-labeling were monitored. RESULTS: 5 of 56 patients tested had negative PCN skin test results. Of those, 16 (29%) switched antibiotics, 19 (35%) were not on antibiotics, 17 (31%) were on appropriate antibiotics, and 3 (5.4%) were not switched due to other factors. 4 PICC lines were avoided. 15 additional patients had the PCN allergy label removed without testing based on prior use. Out of 115 pharmacists contacted, 72 (62.6%) pharmacists deleted the PCN allergy in the pharmacy record. All but 2 patients' PCPs were contacted via EMR, letter or fax. Only 3 of 55 patients (5.45%) were re-labeled with a PCN allergy after six months. CONCLUSIONS: An inpatient PCN testing program was designed and successfully executed to optimize current antibiotic stewardship practices and prevent PCN allergy re-labels.