Ischemic preconditioning induces cortical microglial proliferation and a transcriptomic program of robust cell cycle activation.

Ischemic preconditioning (IPC) is an experimental phenomenon in which a subthreshold ischemic insult applied to the brain reduces damage caused by a subsequent more severe ischemic episode. Identifying key molecular and cellular mediators of IPC will provide critical information needed to develop novel therapies for stroke. Here we report that the transcriptomic response of acutely isolated preconditioned cortical microglia is dominated by marked upregulation of genes involved in cell cycle activation and cellular proliferation. Notably, this transcriptional response occurs in the absence of cortical infarction. We employed ex vivo flow cytometry, immunofluorescent microscopy, and quantitative stereology methods on brain tissue to evaluate microglia proliferation following IPC. Using cellular colocalization of microglial (Iba1) and proliferation (Ki67 and BrdU) markers, we observed a localized increase in the number of microglia and proliferating microglia within the preconditioned hemicortex at 72, but not 24, hours post-IPC. Our quantification demonstrated that the IPC-induced increase in total microglia was due entirely to proliferation. Furthermore, microglia in the preconditioned hemisphere had altered morphology and increased soma volumes, indicative of an activated phenotype. Using transgenic mouse models with either fractalkine receptor (CX3CR1)-haploinsufficiency or systemic type I interferon signaling loss, we determined that microglial proliferation after IPC is dependent on fractalkine signaling but independent of type I interferon signaling. These findings suggest there are multiple distinct targetable signaling pathways in microglia, including CX3CR1-dependent proliferation that may be involved in IPC-mediated protection.

Speech and Surgical Outcomes in Children With Veau Types III and IV Cleft Palate: A Comparison of Internationally Adopted and Nonadopted Children.

OBJECTIVE: This study compares speech and surgical outcomes in internationally adopted and nonadopted patients undergoing cleft palate repair, and examines the influence of age at initial palatoplasty. DESIGN: Retrospective cohort study setting: Tertiary Care Children's Hospital. PATIENTS: 70 international adoptees and 211 nonadoptees with Veau type III and IV clefts (without associated syndrome) repaired at our institution. OUTCOME MEASURES: Outcomes included VPI, compensatory misarticulations, intelligibility, nasal air emission, oronasal fistula, and secondary speech surgery. Speech evaluations completed near 5 years of age were gathered from a prospectively collected database. RESULTS: Adoptees underwent palatoplasty 5.2 months after arrival, a mean of 10.4 months later than nonadoptees. Adoptees were significantly more likely to develop moderate/severe VPI and trended toward more frequent need for secondary speech surgery. Oronasal fistula occurred at similar rates. Increased age at initial palatoplasty was a significant predictor of moderate to severe VPI, and need for secondary speech surgery. CONCLUSIONS: International adoptees undergo palatoplasty 10.4 months later than nonadoptees and are significantly more likely to develop moderate/severe VPI, with a trend toward increased secondary speech surgery. An association between treatment delay and moderate/severe VPI and secondary speech surgery has been demonstrated. While a causal relationship between delayed repair and inferior outcomes in international adoptees has not been proven, this data suggests that surgical intervention upon unrepaired cleft palates soon after adoption may be beneficial. The opportunity for a change in practice exists, as half of the 10.4-month relative delay in palate repair occurs postadoption.

Fireworks type, injury pattern, and permanent impairment following severe fireworks-related injuries.

BACKGROUND: There is a paucity of clinical data on severe fireworks-related injuries, and the relationship between firework types, injury patterns, and magnitude of impairment is not well understood. Our objective was to describe the relationship between fireworks type, injury patterns, and impairment. METHODS: Retrospective case series (2005-2015) of patients who sustained consumer fireworks-related injuries requiring hospital admission and/or an operation at a Level 1 Trauma/Burn Center. Fireworks types, injury patterns (body region, injury type), operation, and permanent impairment were examined. RESULTS: Data from 294 patients 1 to 61years of age (mean 24years) were examined. The majority (90%) were male. 119 (40%) patients were admitted who did not undergo surgery, 163 (55%) patients required both admission and surgery, and 12 (5%) patients underwent outpatient surgery. The greatest proportion of injuries was related to shells/mortars (39%). There were proportionally more rocket injuries in children (44%), more homemade firework injuries in teens (34%), and more shell/mortar injuries in adults (86%). Brain, face, and hand injuries were disproportionately represented in the shells/mortars group. Seventy percent of globe-injured patients experienced partial or complete permanent vision loss. Thirty-seven percent of hand-injured patients required at least one partial or whole finger/hand amputation. The greatest proportion of eye and hand injuries resulting in permanent impairment was in the shells/mortars group, followed by homemade fireworks. Two patients died. CONCLUSIONS: Severe fireworks-related injuries from homemade fireworks and shells/mortars have specific injury patterns. Shells/mortars disproportionately cause permanent impairment from eye and hand injury.

Flipped classroom approach to global outreach: cross-cultural teaching of horizontal strabismus to Chinese ophthalmology residents.

AIM: To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States. METHODS: Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018. Residents were instructed to watch a pre-class video lecture prior to the in-class-case-based activity. Content tests (5 Ophthalmic Knowledge Assessment Program style questions) and surveys were administered before and after the classroom sessions (100% response rate). These results were compared to that of an American cohort who were taught the same content. RESULTS: The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents (92% vs 55%, P=0.04) and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style (P-values between 0.008 and <0.001). In both Chinese and American cohorts, we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session (P=0.025 for Chinese residents; P=0.001 for US residents), whereas scores in both groups for the esotropia course did not significantly improve. CONCLUSION: This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting. The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge. Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings. Finally, the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19, although such a format requires further study.