Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

Validation of PATHFx 2.0: An open-source tool for estimating survival in patients undergoing pathologic fracture fixation

Treatment decisions in patients with metastatic bone disease rely on accurate survival estimation. We developed the original PATHFx models using expensive, proprietary software and now seek to provide a more cost-effective solution. Using open-source machine learning software to create PATHFx version 2.0, we asked whether PATHFx 2.0 could be created using open-source methods and externally validated in two unique patient populations. The training set of a well-characterized, database records of 189 patients and the bnlearn package within R Version 3.5.1 (R Foundation for Statistical Computing), was used to establish a series of Bayesian belief network models designed to predict survival at 1, 3, 6, 12, 18, and 24 months. Each was externally validated in both a Scandinavian (n = 815 patients) and a Japanese (n = 261 patients) data set. Brier scores and receiver operating characteristic curves to assessed discriminatory ability. Decision curve analysis (DCA) evaluated whether models should be used clinically. DCA showed that the model should be used clinically at all time points in the Scandinavian data set. For the 1-month time point, DCA of the Japanese data set suggested to expect better outcomes assuming all patients will survive greater than 1 month. Brier scores for each curve demonstrate that the models are accurate at each time point. Statement of Clinical Significance: we successfully transitioned to PATHFx 2.0 using open-source software and externally validated it in two unique patient populations, which can be used as a cost-effective option to guide surgical decisions in patients with metastatic bone disease.     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

Assessment of backward walking unmasks mobility impairments in post-stroke community ambulators

Background: While over half of stroke survivors recover the ability to walk without assistance, deficits persist in the performance of walking adaptations necessary for safe home and community mobility. One such adaptation is the ability to walk or step backward. Post-stroke rehabilitation rarely includes backward walking (BW) assessment and BW deficits have not been quantified in post-stroke community ambulators.

Objective: To quantify spatiotemporal and kinematic BW characteristics in post-stroke community ambulators and compare their performance to controls.

Methods: Individuals post-stroke (n = 15, 60.1 ± 12.9 years, forward speed: 1.13 ± 0.23 m/s) and healthy adults (n = 12, 61.2 ± 16.2 years, forward speed: 1.40 ± 0.13 m/s) performed forward walking (FW) and BW during a single session. Step characteristics and peak lower extremity joint angles were extracted using 3D motion analysis and analyzed with mixed-method ANOVAs (group, walking condition).

Results: The stroke group demonstrated greater reductions in speed, step length and cadence and a greater increase in double-support time during BW compared to FW (p < .01). Compared to FW, the post-stroke group demonstrated greater reductions in hip extension and knee flexion during BW (p < .05). The control group demonstrated decreased plantarflexion and increased dorsiflexion during BW, but these increases were attenuated in the post-stroke group (p < .05).

Conclusions: Assessment of BW can unmask post-stroke walking impairments not detected during typical FW. BW impairments may contribute to the mobility difficulties reported by adults post-stroke. Therefore, BW should be assessed when determining readiness for home and community ambulation.     

Stability of transverse expansion in the mandibular arch.

This was a retrospective, longitudinal cephalometric and cast study of 29 white patients at pretreatment, posttreatment, and an average of 6 years 3 months postretention. The goal was to assess changes with treatment and retention with the expanding mandibular lingual arch appliance in conjunction with fixed edgewise treatment. Seven mandibular cast measurements were assessed, including arch crowding, arch perimeter, arch length, and arch width at the permanent canines, first premolars, second premolars, and first molars. Cephalometric radiographs were digitized, and 16 cephalometric measurements were made. Repeated-measures analysis of variance and 2-sample t tests were used to determine statistically significant changes. It was found that the expanding lingual arch used for less than 6 months with the mandibular fixed edgewise appliance caused an increase in both the transverse and sagittal dimensions of the mandibular dental arch. Transverse expansion was more stable in the posterior region of the mandibular dental arch than in the anterior region. Mandibular intercanine width increase could be maintained only by fixed retention. Although the maxillary and mandibular incisors were advanced and proclined, lip protrusion did not occur.