Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development.

Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis.

Efficacy of a non-invasive middle ear aeration device in children with recurrent otitis media: A randomized controlled trial protocol.

Acute otitis media (AOM) represents a significant disease burden in the pediatric population. Besides vaccinations, there are no robust measures of reducing incidence of AOM in this age-group. This is a randomized controlled clinical trial evaluating the efficacy of a non-invasive middle ear aeration device, the EarPopper device (EP). We aim to investigate the reduction of episodes AOM in children with recurrent otitis media. The control arm will be observational. The intervention arm will have the EP used. The primary endpoint is incidence of AOM. The secondary endpoints are hazard ratio of time to AOM, proportion without AOM and antibiotics use, quality of life (OMO-22 Form), and adherence to treatment. Sample size is a minimum of 150 patients. The inclusion criteria is ages 4-11, with history of recurrent Acute Otitis Media (AOM).

Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio.

Objective We aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in patients with head and neck cancer (HNC) undergoing major surgery. Study Design Retrospective cohort study. Setting Academic tertiary hospital from 2011 to 2017. Subjects and Methods Patients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including Caprini score, age, sex, smoking, body mass index, prior VTE, and anticoagulation, were also recorded. Risk factors were screened in univariate analysis using Wilcoxon's rank sum test and χ2 test (Bonferroni corrected). Significant covariates were included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CIs). Results There were 306 patients enrolled with 7 cases of VTE (6 deep vein thromboses and 1 pulmonary embolism. On univariate analysis, length of stay ( P = .0026), length of surgery ( P = .0029), and PLR ( P = .0002) were found to have significant associations with VTE. A receiver operator characteristic (ROC) curve was constructed that yielded an area under the ROC of 0.905 (95% CI, 0.82-0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (ß 95% CI, 0.0001-0.0006; P = .0056) and PLR (ß 95% CI, 5.3256-5.3868; P < .0001) were significant independent predictors of VTE. Conclusion This exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.