Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are linked to impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.Author summaryThe primary cilium is a microtubule-based membranous projection on the cell that is involved in multiple physiological functions. Patients who have cilia dysfunction commonly have intellectual disability. However, it is not known how cilia affect learning and memory. Studying mouse models of a cilia-based intellectual disability can provide insight into learning and memory. One such cilia-based intellectual disability is Bardet-Biedl Syndrome (BBS), which is caused by homozygous and compound heterozygous mutations of BBS genes. We found that a mouse model of BBS (Bbs1M390R/M390R mice) has learning and memory defects. In addition, we found that other mouse models of BBS have similar learning and memory defects. These BBS mouse models have difficulty associating an environment with an aversive stimulus, a task designed to test context fear memory. This type of memory involves the hippocampus. We found that Bbs1M390R/M390R mice have decreased cell production in the hippocampus. Treating Bbs1M390R/M390R mice with a compound (lithium) that increases cell production in the hippocampus improved the learning and memory deficits. Our results demonstrate a potential role for cilia in learning and memory, and indicate that lithium is a potential treatment, requiring further study, for the intellectual disability phenotype of BBS.

OBJECTIVE: Changes in electronic health record (EHR) default settings have been shown to affect provider behavior. Opioids are not routinely prescribed at our institution for postpartum care after vaginal deliveries. We sought to determine whether an adjustment made to a post-vaginal delivery order set was associated with opioid prescribing patterns at discharge. STUDY DESIGN: This is a retrospective before-after study of all vaginal deliveries (VD) at a single tertiary care center from Dec 2014-May 2015 (prior to EHR change) and Dec 2015-May 2016 (after EHR change). The EHR change was the addition of a pre-checked order for oxycodone as a second-line agent for pain. Medical records were queried for demographic and clinical data, including postpartum inpatient pain medication use and opioid prescription information. This was also collected for women undergoing cesarean delivery (CD) as the post-cesarean delivery order set did not undergo alterations during the study period. Descriptive and univariate data analyses were performed. RESULTS: A total of 558 VD patients before and 542 patients after the EHR change were included. There were no significant differences in demographic characteristics between the groups aside from lacerations. The likelihood of oxycodone use during postpartum stay after VD increased after the EHR change (OR 6.94, CI 5.20-9.27, p <.0001). However, the likelihood of receiving an oxycodone prescription and the number of tablets prescribed were not significantly different (OR 1.28, CI 0.91-1.80, p¼0.16; OR 1.60, CI 1.13-2.27, p¼0.20). For patients who underwent CD during the same time periods, there was no difference in oxycodone use during postpartum admission (OR 0.95, CI 0.70-1.30, p¼0.75) or in oxycodone prescription at discharge (OR 0.93, CI 0.57-1.50, p¼0.75). CONCLUSION: A pre-checked order for oxycodone in an EHR order set increased use of oxycodone during postpartum admission after VD, but did not significantly increase the likelihood of oxycodone prescriptions at discharge.

INTRODUCTION: Opioids are not routinely prescribed at our institution for postpartum care after vaginal deliveries (VD). We sought to determine a model to predict need for opioid prescription refill after a VD. METHODS: This is an IRB-approved secondary analysis retrospective cohort study of all VD at a single tertiary care center from Dec 2014 to May 2015 and Dec 2015 to May 2016. Medical records were queried for demographic and clinical data. Multivariable logistic regression modeling was performed to determine the most relevant predictors for receiving an opioid prescription refill within 30 days of discharge. The performance of the prediction model was assessed by using the Akaike information criterion (AIC). RESULTS: Of the total 1100 VD patients included, 24 (2.2%) received an opioid prescription refill within 30 days of discharge. Factors included in the top model according to AIC were last pain score (OR 1.267, CI 1.01-1.60, P=.045) and age (OR 1.10, CI 1.00-1.21, P=.044). Predictors that were not included in the top model according to AIC were BMI, race, postpartum tubal ligation, gravidity, gestational age, tobacco use, psychiatric diagnoses and insurance. CONCLUSION: Last pain score is a significant modifiable predictor for patients requiring a refill for opioid pain medications after a VD. Better control of pain prior to discharge may help decrease the need for opioid refills within 30 days of discharge after a VD.

Background: Acoustic neuromas are a common sequela of neurofibromatosis type 2 and have been shown to grow at an increased rate during pregnancy.Case: 21-year-old female, gravida 1 para 0, with history of neurofibromatosis type 2 presented for prenatal care following new onset seizures and progressive deafness. She was found to have bilateral slow-growing acoustic neuromas. Over the course of her pregnancy, her acoustic neuroma began growing and she became completely deaf. She underwent surgical decompression during her pregnancy and had a late preterm vaginal delivery due to preeclampsia with severe features. She subsequently had further operative and medical treatment of her neuromas. Conclusion:Acoustic neuromas during pregnancy are exceedingly rare, but can be managed successfully with an interdisciplinary team approach tailored to the patients' specific clinical presentation.