Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2−/−) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph+/−) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.

No abstract

Background: The survival of Fassier-Duval (FD) telescoping rods as compared with static implants in children affected by osteogenesis imperfecta is not well characterized. The purpose of this study was to compare risk of lower extremity implant failure in FD rods versus static implants. Methods: Data were retrospectively collected from patients with osteogenesis imperfecta who underwent surgical treatment using either FD rods or static implants (Rush rods, flexible nails, or Steinmann pins) between 1995 and 2015. The timing of implant failure was the primary outcome variable of interest. Comparisons were limited to limbs with no previous history of implants. Cox-proportional hazards regression analyses were used to compare the hazard of implant failure across implants. Negative binomial regression analyses were used to compare the incidence of surgical procedures in the 2 implant groups. Results: The final cohort consisted of 64 limbs (n=21 patients). The static implant group (n=38) consisted of 24 Rush rods (63%), 14 flexible nails (37%), and 2 Steinmann pins (5%). The hazard of implant failure in the static implant group was 13.2 times [95% confidence interval (CI), 2.5-69.6; P=0.0024] the hazard of implant failure in the FD rod group. The hazard of implant failure among females was 4.8 (95% CI, 1.4-16.7; P=0.0125) times the hazard of implant failure among males. The total surgery rate in the static implant group was 7.8 (95% CI, 1.8-33.0; P=0.0056) times the total surgery rate in the FD group. Conclusions: Among surgically naive limbs, FD rods were associated with significantly improved probability of survival compared with static implants. Level of Evidence: Level II—retrospective study.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal structural deformity that occurs in otherwise normal individuals. Although curve progression and severity vary amongst individuals, AIS can lead to significant cosmetic and functional deformity. AIS etiology has been determined to be genetic, however, exact genetic and biological processes underlying this disorder remain unknown. Vestibular structure and function have potentially been related to the etiopathogenesis of AIS. Here, we aimed to characterize the anatomy of the semicircular canals (SCC) within the vestibular system through a novel approach utilizing T2-weighted magnetic resonance images (MRI). Methods Three dimensional, MRI-based models of the SCCs were generated from AIS subjects (n = 20) and healthy control subjects (n = 19). Linear mixed models were used to compare SCC morphological measurements in the two groups. We compared side-to-side differences in the SCC measurements between groups (group*side interaction). Results Side-to-side differences in the lateral SCC were different between the two groups [false discovery rate adjusted p-value: 0.0107]. Orientation of right versus left lateral SCC was significantly different in the AIS group compared to the control group [mean side-to-side difference:-4.1˚, 95% CI:-6.4˚to-1.7˚]. Overall, among subjects in the AIS group, the left lateral SCC tended to be oriented in a more horizontal position than subjects in the control group. Significance Asymmetry within the SCCs of the vestibular system of individuals with AIS potentially results in abnormal efferent activity to postural muscles. Consequences of this muscular

Level II.