Citations

AbstractIntroductionUnderstanding clinical reasoning is essential for patient care and medical education. Dual‐processing theory suggests that nonanalytic reasoning is an essential aspect of expertise; however, assessing nonanalytic reasoning is challenging because it is believed to occur on the subconscious level. This assumption makes concurrent verbal protocols less reliable assessment tools.MethodsFunctional magnetic resonance imaging was used to explore the neural basis of nonanalytic reasoning in internal medicine interns (novices) and board‐certified staff internists (experts) while completing United States Medical Licensing Examination and American Board of Internal Medicine multiple‐choice questions.ResultsThe results demonstrated that novices and experts share a common neural network in addition to nonoverlapping neural resources. However, experts manifested greater neural processing efficiency in regions such as the prefrontal cortex during nonanalytical reasoning.ConclusionsThese findings reveal a multinetwork system that supports the dual‐process mode of expert clinical reasoning during medical evaluation.

Abstract Cigarette smoking is a major risk factor in the development of non–small cell lung cancer (NSCLC), which accounts for 80% of all lung cancers. Nicotine, the major addictive component of tobacco smoke, can induce proliferation, invasion, and epithelial-to-mesenchymal transition (EMT) in NSCLC cell lines and promote metastasis of NSCLC in mice. Here, we demonstrate that the scaffolding protein β-arrestin-1 is necessary for nicotine-mediated induction of mesenchymal genes vimentin and fibronectin as well as EMT regulators ZEB1 and ZEB2. Nicotine induced changes in cell morphology and ablate tight junctions consistent with EMT; β-arrestin-1, but not β-arrestin-2, was required for these changes. β-Arrestin-1 promoted the expression of the mesenchymal genes, as well as ZEB1 and ZEB2, through the mediation of the E2F1 transcription factor; this required Src kinase activity. Stimulation of multiple NSCLC cell lines with nicotine led to enhanced recruitment of β-arrestin-1 and E2F1 on vimentin, fibronectin, and ZEB1 and ZEB2 promoters. Furthermore, there was significantly more β-arrestin-1 and E2F1 associated with these promoters in human NSCLC tumors, and β-arrestin-1 levels correlated with vimentin and fibronectin levels in human NSCLC samples. A549-luciferase cells lacking β-arrestin-1 showed a significantly reduced capacity for tumor growth and metastasis when orthotopically implanted into the lungs of SCID-beige mice. Taken together, these studies reveal a novel role for β-arrestin-1 in the growth and metastasis of NSCLC. Cancer Res; 75(6); 1009–20. ©2015 AACR.

ObjectiveAmyotrophic lateral sclerosis/parkinsonism–dementia complex has been described in Guam, Western Papua, and the Kii Peninsula of Japan. The etiology and pathogenesis of this complex neurodegenerative disease remains enigmatic.MethodsIn this study, we have used targeted genomic sequencing to evaluate the contribution of genetic variability in the pathogenesis of amyotrophic lateral sclerosis, parkinsonism, and dementia in Guamanian Chamorros.ResultsGenes previously linked to or associated with amyotrophic lateral sclerosis, parkinsonism, dementia, and related neurodegenerative syndromes were sequenced in Chamorro subjects living in the Mariana Islands. Homozygous PINK1 p.L347P, heterozygous DCTN1 p.T54I, FUS p.P431L, and HTT (42 CAG repeats) were identified as pathogenic mutations.InterpretationThe findings explain the clinical, pathologic, and genetic heterogeneity observed in some multi‐incident families and contribute to the excess incidence of neurodegeneration previously reported on Guam. Ann Neurol 2015;77:458–468

OBJECT Motocross racing is a popular sport; however, its impact on the growing/developing pediatric spine is unknown. Using a retrospective cohort model, the authors compared the degree of advanced degenerative findings in young motocross racers with findings in age-matched controls. METHODS Patients who had been treated for motocross-related injury at the authors' institution between 2000 and 2007 and had been under 18 years of age at the time of injury and had undergone plain radiographic or CT examination of any spinal region were eligible for inclusion. Imaging was reviewed in a blinded fashion by 3 physicians for degenerative findings, including endplate abnormalities, loss of vertebral body height, wedging, and malalignment. Acute pathological segments were excluded. Spine radiographs from age-matched controls were similarly reviewed and the findings were compared. RESULTS The motocross cohort consisted of 29 riders (mean age 14.7 years; 82% male); the control cohort consisted of 45 adolescents (mean age 14.3 years; 71% male). In the cervical spine, the motocross cohort had 55 abnormalities in 203 segments (average 1.90 abnormalities/patient) compared with 20 abnormalities in 213 segments in the controls (average 0.65/patient) (p = 0.006, Student t-test). In the thoracic spine, the motocross riders had 51 abnormalities in 292 segments (average 2.04 abnormalities/patient) compared with 25 abnormalities in 299 segments in the controls (average 1.00/patient) (p = 0.045). In the lumbar spine, the motocross cohort had 11 abnormalities in 123 segments (average 0.44 abnormalities/patient) compared with 15 abnormalities in 150 segments in the controls (average 0.50/patient) (p = 0.197). CONCLUSIONS Increased degenerative changes in the cervical and thoracic spine were identified in adolescent motocross racers compared with age-matched controls. The long-term consequences of these changes are unknown; however, athletes and parents should be counseled accordingly about participation in motocross activities.

OBJECT Off-road motorcycling is a very popular sport practiced by countless people worldwide. Despite its popularity, not much has been published on the severity and distribution of central nervous system–related injuries associated with this activity in the pediatric population. The purpose of this study was to confirm, characterize, and document the rate of head and spine injuries associated with off-road motorcycling in this population. METHODS All patients aged 18 years or less who were treated for a motorbike injury at the authors' institution (a Level 1 regional trauma center) between 2000 and 2007 were identified through in-house surgical and trauma registries. Type, mechanism, and severity of CNS-related injuries were assessed, including: incidence of traumatic brain injury (TBI), loss of consciousness (LOC), Glasgow Coma Scale (GCS) score, head CT findings, neurological deficits, spinal fractures, cervical strain, and use of protective gear, including helmets. RESULTS During the 8-year period of study, 298 accidents were evaluated in 248 patients. The patients' mean age at the time of injury was 14.2 ± 2.7 years. Head injury or TBI was identified in 60 (20.1%) of 298 cases (involving 58 of 248 patients). Fifty-seven cases were associated with LOC, and abnormalities were identified on head CT in 10 patients; these abnormalities included skull fractures and epidural, subdural, subarachnoid, and intraparenchymal hemorrhages. The GCS score was abnormal in 11 cases and ranged from 3 to 15, with an overall mean of 14.5. No patients required cranial surgery. Helmet use was confirmed in 43 (71.6%) of the cases involving TBI. Spine fractures were identified in 13 patients (4.3%) and 5 required surgical fixation for their injury. CONCLUSIONS The authors found a high occurrence of head injuries following pediatric off-road motorcycle riding or motocross accidents despite the use of helmets. Additionally, this study severely underestimates the rate of mild TBIs in this patient population. Our data indicate that motocross is a high-risk sport despite the use of protective gear. Riders and parents should be counseled accordingly about the risks prior to participation.

OBJECT Action motorsports, including motocross, have been gaining popularity among children and adolescents, raising concerns for increased risk of concussions in participating youth. The authors undertook this study to test the following hypotheses: 1) that there is a high rate of concussion symptoms associated with a number of preventable or adjustable risk factors, and 2) that a high percentage of these symptoms are not be reported to adults and medical personnel. METHODS The authors identified all motocross riders under the age of 18 at a regional racetrack during the riding season between May and October 2010. The participants completed questionnaires pertaining to demographic characteristics and variables associated with motocross. The questionnaire results were compared with the incidence of self-reported concussion symptoms. RESULTS Two hundred two riders were identified who met the criteria for participation in the study, and 139 of them completed the study questionnaire. Of these 139 riders, 67 (48%) reported at least 1 concussion symptom during the season. The majority of riders (98%) reported “always” wearing a helmet, and 72% received professional help with fitting of their helmets. Proper helmet fitting was associated with a 41% decreased risk of concussion symptoms (RR 0.59, 95% CI 0.44–0.81, p < 0.01). Sixty-six riders (47%) reported having received sponsor support for motocross participation. Sponsor support conferred a relative risk for concussion symptoms of 1.48 (95% CI 1.05–2.08, p = 0.02). CONCLUSIONS Nearly half of all motocross competitors under the age of 18 reported concussion symptoms. Preventive measures are necessary to limit the negative impact from concussions. The risk of concussive injury can be decreased for pediatric motocross riders if they receive professional help with proper helmet fitting and through implementation of stricter guidelines regarding sponsorship.

OBJECT Recently, aggressive surgical techniques and a push toward en bloc resections of certain tumors have resulted in a need for creative spinal column reconstruction. Iatrogenic instability following these resections requires a thoughtful approach to adequately transfer load-bearing forces from the skull and upper cervical spine to the subaxial spine. METHODS The authors present a series of 7 cases in which lateral mass reconstruction with a cage or fibular strut graft was used to provide load-bearing support, including 1 case of bilateral cage placement. RESULTS The authors discuss the surgical nuances of en bloc resection of high cervical tumors and explain their technique for lateral mass cage placement. Additionally, they provide their rationale for the use of these constructs throughout the craniocervical junction and subaxial spine. CONCLUSIONS Lateral mass reconstruction provides a potential alternative or adjuvant method of restoring the load-bearing capabilities of the cervical spine.

ABSTRACT Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load. IMPORTANCE This study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.

Endovascular repair has become the first line of treatment in most patients with blunt aortic injury. The most common mechanism is deceleration injury affecting the aortic isthmus distal to the origin of the left subclavian artery. Injuries of the distal thoracic aorta are uncommon. We report the case of a 25-year-old male patient who presented with paraplegia and distal thoracic aortic pseudoaneurysm associated with severe thoracolumbar vertebral fracture and displacement after a motocross accident. Endovascular repair was performed using total percutaneous technique and conformable C-TAG thoracic stent-graft (WL Gore, Flagstaff, AZ). Following stent-graft placement and angiographic confirmation of absence of endoleak, thoracolumbar spinal fixation was performed in the same operative procedure. This case illustrates a multispecialty approach to complex aortic and vertebral injury and the high conformability of newer thoracic stent-grafts to adapt to tortuous anatomy.