Chronic gut inflammation impairs contextual control of fear.

Chronic inflammatory diseases are highly comorbid with anxiety in humans. The extent to which chronic inflammation is responsible for this relationship remains to be determined. We therefore tested the hypothesis that prolonged, but not brief, gut inflammation is sufficient to evoke anxiety-related behaviours in mice. We used the discriminative fear to context conditioning paradigm to assess fear generalization, which is a prominent feature of anxiety disorders. Gut inflammation was induced by exposure to dextran sodium sulfate (DSS) in the drinking water, a well-established rodent model of ulcerative colitis evoking prolonged inflammation. Neither acute (1 × 5 day cycle) nor chronic (3 × 5 day cycles) exposure to DSS affected fear responses when tested shortly after conditioning. Mice in all groups generated more fear responses (freezing) in a chamber previously paired with mild shock, as compared to a chamber with no pairing. This suggests DSS exposure had no effect on acquisition or expression of conditioned fear. Acute and control animals showed this same contextual control of freezing when tested 9 days later. In contrast, at this remote time point, the chronically treated animals exhibited increased freezing in the unpaired chamber such that freezing was equivalent in both contexts. These animals, however, showed intact preference for the unpaired chamber when allowed to freely move between chambers. These data suggest that some mnemonic process engaged after training, such as memory consolidation, is affected by past chronic inflammation so as to generalize negative associations and engage fearful responding in inappropriate contexts, despite intact knowledge that the chambers have different affective associations sufficient for place preference.

Dentate Update: Imaging Features of Entities That Affect the Dentate Nucleus.

The dentate nucleus is a cerebellar structure involved in voluntary motor function and cognition. There are relatively few entities that affect the dentate, and the clinical features of these conditions are often complex and nonspecific. Because these entities are rarely encountered, the formulation of a differential diagnosis can be difficult. Many of the conditions are reversible or treatable with early intervention. Therefore, it is important to recognize classic clinical presentations and their associated characteristic imaging findings. We provide a summary of entities that affect the dentate nucleus and a diagnostic workflow for approaching dentate nucleus imaging abnormalities.

Effect of Systemic Therapies on Outcomes following Vertebroplasty among Patients with Multiple Myeloma.

BACKGROUND AND PURPOSE: The role of vertebroplasty in patients with myeloma remains relatively undefined. Accordingly, we sought to better define the efficacy of vertebroplasty for myeloma-associated fractures and determine the effect of procedure timing relative to the initiation of systemic therapy on outcomes and complication rates. MATERIALS AND METHODS: Clinical, laboratory, and medication data were retrieved for 172 patients with multiple myeloma treated with vertebroplasty since October 2000. Quantitative outcome data (Roland-Morris Disability Questionnaire [scale, 0-24] and the Numeric Rating Scale [0-10] for pain at rest and with activity) were collected immediately pre- and postoperatively and at 1 week, 1 month, 6 months, and 1 year following vertebroplasty. Patients with ≥50% improvement on the Numeric Rating Scale and ≥40% improvement on the Roland-Morris Disability Questionnaire were classified as "responders." Peri- and postoperative complications were also collected. RESULTS: Significant median improvement in the Roland-Morris Disability and rest and activity Numeric Rating Scale scores (15, 2, and 6 points, respectively; P < .0001) persisted at 1 year without significant change from the immediate postoperative scores (P > .36). Patients on systemic therapy at the time of vertebroplasty were more likely to achieve "responder status," compared with patients not on systemic therapy, for the Numeric Rating Scale pain at rest score (P < .01) and the Roland-Morris Disability Questionnaire score (P < .003), with no difference in complication rates (χ2 = 0.17, P = .68). CONCLUSIONS: Vertebroplasty is an effective therapy for patients with myeloma with symptomatic compression fractures. Favorable outcomes are more likely to be achieved when spinal augmentation is performed after systemic therapy is initiated. Complication rates were not affected by the timing of systemic therapy.

Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and ß-amyloid.

Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aß) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aß25-35 injections, or both cholinergic depletion and Aß25-35 injections (Aß+ACh group). The Aß+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aß+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aß. These data suggest that cholinergic depletions and Aß injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology.

RNA-Sequencing Analysis of Messenger RNA/MicroRNA in a Rabbit Aneurysm Model Identifies Pathways and Genes of Interest.

BACKGROUND AND PURPOSE: Rabbit aneurysm models are used for the testing of embolization devices and elucidating the mechanisms of human intracranial aneurysm growth and healing. We used RNA-sequencing technology to identify genes relevant to induced rabbit aneurysm biology and to identify genes and pathways of potential clinical interest. This process included sequencing microRNAs, which are important regulatory noncoding RNAs. MATERIALS AND METHODS: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 6 rabbits. Messenger RNA and microRNA were isolated from the aneurysm and from the control left common carotid artery at 12 weeks and processed by using RNA-sequencing technology. The results from RNA sequencing were analyzed by using the Ingenuity Pathway Analysis tool. RESULTS: A total of 9396 genes were analyzed by using RNA sequencing, 648 (6.9%) of which were found to be significantly differentially expressed between the aneurysms and control tissues (P < .05; false-discovery rate, <0.01; fold change, >2 or <.5). Of these genes, 614 were mapped successfully, 143 were down-regulated, and 471 were up-regulated in the aneurysms as compared with controls. Using the same criteria for significance, 3 microRNAs were identified as down-regulated and 5 were identified as up-regulated. Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions and pathologies. CONCLUSIONS: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and antigen presentation. ANKRD1 and TACR1 were identified as genes of interest in the regulation of matrix metalloproteinases.

Strain and sex differences in puberty onset and the effects of THC administration on weight gain and brain volumes.

The use of recreational marijuana is widespread and frequently begins and persists through adolescence. Some research has shown negative consequences of adolescent marijuana use, but this is not seen across studies, and certain factors, like genetic background and sex, may influence the results. It is critical to identify which characteristics predispose an individual to be susceptible to the negative consequences of chronic exposure to marijuana in adolescence on brain health and behavior. To this end, using males and females of two strains of rats, Long-Evans hooded (LER) and Wistar (WR) rats, we explored whether these anatomically and behaviorally dimorphic strains demonstrated differences in puberty onset and strain-specific effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana. Daily 5 mg/kg treatment began on the day of puberty onset and continued for 14 days. Of particular interest were metrics of growth and volumetric estimates of brain areas involved in cognition that contain high densities of cannabinoid receptors, including the hippocampus and its subregions, the amygdala, and the frontal cortex. Brain volumetrics were analyzed immediately following the treatment period. LER and WR females started puberty at different ages, but no strain differences were observed in brain volumes. THC decreased weight gain throughout the treatment period for all groups. Only the hippocampus and some of its subregions were affected by THC, and increased volumes with THC administration was observed exclusively in females, regardless of strain. Long-term treatment of THC did not affect all individuals equally, and females displayed evidence of increased sensitivity to the effects of THC, and by extension, marijuana. Identifying differences in adolescent physiology of WR and LER rats could help determine the cause for strain and sex differences in brain and behavior of adults and help to refine the use of animal models in marijuana research.

Part III: Principal component analysis: bridging the gap between strain, sex and drug effects.

Previous work has identified the adolescent period as particularly sensitive to the short- and long-term effects of marijuana and its main psychoactive component Δ9-tetrahydrocannabinol (THC). However, other studies have identified certain backgrounds as more sensitive than others, including the sex of the individual or the strain of the rat used. Further, the effects of THC may be specific to certain behavioural tasks (e.g. measures of anxiety), and the consequences of THC are not seen equally across all behavioural measures. Here, data obtained from adolescent male and female Long-Evans and Wistar rats exposed to THC and tested as adults, which, using standard ANOVA testing, showed strain- and sex-specific effects of THC, was analyzed using principal component analysis (PCA). PCA allowed for the examination of the relative contribution of our variables of interest to the variance in the data obtained from multiple behavioural tasks, including the skilled reaching task, the Morris water task, the discriminative fear-conditioning to context task, the elevated plus maze task and the conditioned place preference task to a low dose of amphetamine, as well as volumetric estimates of brain volumes and cfos activation. We observed that early life experience accounted for a large proportion of variance across data sets, although its relative contribution varied across tasks. Additionally, THC accounted for a very small proportion of the variance across all behavioural tasks. We demonstrate here that by using PCA, we were able to describe the main variables of interest and demonstrate that THC exposure had a negligible effect on the variance in the data set.

Co-morbid beta-amyloid toxicity and stroke produce impairments in an ambiguous context task in rats without any impairment in spatial working memory.

Sporadic Alzheimer's disease (AD) accounts for a high proportion of AD cases. Therefore, it is of importance to investigate other factors that contribute to the etiology and progression of AD. AD is characterized by decreased cholinergic tone, tau hyperphosphorylation and beta-amyloid (Aß) accumulation. In addition to the hallmark pathology, other factors have been identified that increase the risk of AD, including stroke. This study examined the combined effects of beta-amyloid administration and unilateral stroke in an animal model of AD. Adult rats were given a sham surgery, bilateral intraventricular infusion of 10 µL of 50n mol Aß(25-35), a unilateral injection of endothelin-1 into the right striatum, or Aß and endothelin-1 administration in combination. Following a recovery period, rats were tested in the 1-trial place learning variant of the Morris water task followed by an ambiguous discriminative fear-conditioning to context task. After behavioural assessment, rats were euthanized, and representative sections of the medial septum were analyzed for differences in choline-acetyltransferase (ChAT) immunohistochemistry. No differences were observed in spatial working memory, but the combined effect of Aß and stroke resulted in deficits in the discriminative fear-conditioning to context task. A trend towards decreased ChAT-positive staining in the medial septum was observed. This study indicates that Aß and stroke in combination produce worse functional consequences than when experienced alone, furthering the concept of AD as a disease with multiple and complex etiologies.

Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult brain and behaviour: Variants of learning, anxiety and volumetric estimates.

Marijuana is one of the most highly used psychoactive substances in the world, and its use typically begins during adolescence, a period of substantial brain development. Females across species appear to be more susceptible to the long-term consequences of marijuana use. Despite the identification of inherent differences between rat strains including measures of anatomy, genetics and behaviour, no studies to our knowledge have examined the long-term consequences of adolescent exposure to marijuana or its main psychoactive component, Δ(9)-tetrahydrocannabinol (THC), in males and females of two widely used rat strains: Long-Evans hooded (LER) and Wistar (WR) rats. THC was administered for 14 consecutive days following puberty onset, and once they reached adulthood, changes in behaviour and in the volume of associated brain areas were quantified. Rats were assessed in behavioural tests of motor, spatial and contextual learning, and anxiety. Some tasks showed effects of injection, since handled and vehicle groups were included as controls. Performance on all tasks, except motor learning, and the volume of associated brain areas were altered with injection or THC administration, although these effects varied by strain and sex group. Finally, analysis revealed treatment-specific correlations between performance and brain volumes. This study is the first of its kind to directly compare males and females of two rat strains for the long-term consequences of adolescent THC exposure. It highlights the importance of considering strain and identifies certain rat strains as susceptible or resilient to the effects of THC.

Strain and sex differences in brain and behaviour of adult rats: Learning and memory, anxiety and volumetric estimates.

Alterations in behaviour can arise through a number of factors, including strain and sex. Here, we explored strain and sex differences between Long-Evans (LER) and Wistar (WR) male and female rats that had been trained in a myriad of behavioural tasks. Tests included those assessing motor learning (skilled reaching task), spatial learning and memory (Morris water task), contextual learning (discriminative fear-conditioning to context) and anxiety behaviour (elevated plus maze). Following behavioural assessment, associated brain areas were examined for volumetric differences, including the hippocampus and its subregions, prefrontal cortex areas and the amygdala. LER and WR differed in their rates of performance in the skilled reaching task throughout the training period. Overall, LER outperformed WR in tasks related to contextual and spatial learning, although this was not accompanied by larger volumes of associated brain areas. Males outperformed females in spatial learning, and females outperformed males in the contextual fear-conditioning task and had an associated larger amygdalar volume, although these sexual dimorphisms were only observed within the LER strain. Overall, this study highlights differences between these two rat strains as well as highlights that larger volumetric estimates of brain areas do not always confer improved function of associated behaviours.

Developing injury indicators for First Nations and Inuit children and youth in Canada: a modified Delphi approach.

INTRODUCTION: The purpose of this research was to take the initial step in developing valid indicators that reflect the injury issues facing First Nations and Inuit children and youth in Canada. METHODS: Using a modified-Delphi process, relevant expert and community stakeholders rated each indicator on its perceived usefulness and ability to prompt action to reduce injury among children and youth in indigenous communities. The Delphi process included 5 phases and resulted in a refined set of 27 indicators. RESULTS: Indicators related to motorized vehicle collisions, mortality and hospitalization rates were rated the most useful and most likely to prompt action. These were followed by indicators for community injury prevention training and response systems, violent and inflicted injury, burns and falls, and suicide. CONCLUSION: The results suggest that a broad-based modified-Delphi process is a practical and appropriate method, within the OCAP™ (Ownership, Control, Access and Possession) principles, for developing a proposed set of indicators for injury prevention activity focused on First Nations and Inuit children and youth. Following additional work to validate and populate the indicators, it is anticipated that communities will utilize them to monitor injury and prompt decisions and action to reduce injuries among children and youth.

TITRE: Élaboration d'indicateurs de blessures chez les enfants et les jeunes des Premières nations et inuits au Canada grâce à une méthode de Delphes modifiée. INTRODUCTION: Le but de cette recherche était de franchir la première étape de l'élaboration d'indicateurs valides et représentatifs des blessures chez les enfants et les jeunes des Premières nations et Inuits du Canada. MÉTHODOLOGIE: À l'aide d'une méthode de Delphes modifiée, des intervenants des collectivités et des experts ont évalué chaque indicateur en fonction de son utilité perçue et de sa capacité à inciter à l'action dans le but de réduire les blessures chez les enfants et les jeunes des collectivités autochtones. Le processus s'est déroulé en 5 étapes et a permis d'obtenir un ensemble de 27 indicateurs. RÉSULTATS: Les indicateurs évalués comme étant les plus utiles et les plus susceptibles d'inciter à l'action ont été ceux liés au taux de collision de véhicules à moteur, au taux de mortalité et au taux d'hospitalisation. Ont été sélectionnés ensuite les indicateurs de la formation en prévention des blessures et programmes communautaires d'intervention, ceux des blessures intentionnelles, ceux des brûlures et des chutes et enfin ceux du suicide. CONCLUSION: Les résultats indiquent qu'utiliser une méthode de Delphes modifiée avec participation élargie est efficace et pertinent pour élaborer un ensemble d'indicateurs visant à guider les activités de prévention des blessures chez les enfants et les jeunes des Premières nations et Inuits, tout en respectant les principes PCAP™ (propriété, contrôle, accès et possession). Une fois achevés les travaux complémentaires de validation des indicateurs et la collecte des données associées, ces indicateurs vont pouvoir servir aux collectivités pour la surveillance des blessures et pour la prise de décisions et de mesures efficaces de réduction des blessures chez les enfants et les jeunes.

The effect of exercise on carbohydrate preference in female rats.

Exercise has a myriad of health benefits, including positive effects against heart disease, diabetes, and dementia. Cognitive performance improves following chronic exercise, both in animal models and humans. Studies have examined the effect of exercise on feeding, demonstrating a preference towards increased food consumption. Further, sex differences exist such that females tend to prefer carbohydrates over other macronutrients following exercise. However, no clear effect of exercise on macronutrient or carbohydrate selection has been described in animal or human studies. This research project sought to determine the effect of voluntary exercise on carbohydrate selection in female rats. Preference for a complex (starch) versus a simple (dextrose) carbohydrate was assessed using a discriminative preference to context paradigm in non-exercising and voluntarily exercising female rats. In addition, fasting blood glucose and performance in the Morris water task was examined in order to verify the effects of exercise on performance in this task. Female rats given access to running wheels preferred a context previously associated with starch, whereas females with no running wheel access preferred a context previously associated with dextrose. No changes in blood glucose were observed. However, cognitive differences in the Morris water task were observed such that voluntary exercise allowed rats to find a new location of a hidden platform following 4 days of training to an old platform location. These results suggest that voluntary exercise may decrease preservative behaviors in a spatial navigation task through the facilitation of plasticity mechanisms. This study is the first of its kind to demonstrate the influence of exercise on taste preference for complex and simple carbohydrates with this context conditioning paradigm.

Comparative effectiveness of ruptured cerebral aneurysm therapies: propensity score analysis of clipping versus coiling.

BACKGROUND AND PURPOSE: The relative merits of treating ruptured aneurysms with clipping versus coiling continue to be a topic of debate. We evaluated a national, multihospital patient data base to examine recent trends in ruptured aneurysm therapies and to compare peri-procedural outcomes between clipping and coiling treatments. MATERIALS AND METHODS: The Premier Perspective data base was used to identify patients hospitalized between 2006-2011 for ruptured aneurysm who underwent clipping or coiling therapy. A propensity score model, representing the probability of receiving clipping, was generated for each patient by use of relevant patient and hospital variables. After Greedy-type matching of the propensity score, the risk of in-hospital mortality and morbidity was compared between clipping and coiling cohorts. RESULTS: A total of 5229 patients with ruptured aneurysm (1228 clipping, 4001 coiling) treated at 125 hospitals were identified. Clipping therapy frequency decreased from 27% in 2006 to 21% in 2011. After propensity score adjustment, in-hospital mortality risk was similar between groups (OR = 0.94 [95% CI, 0.73-1.21]; P = .62). However, unfavorable outcomes were more common after clipping compared with coiling, including discharge to long-term care (OR = 1.32 [95% CI, 1.12-1.56]; P = .0006), ischemic complications (OR = 1.51 [95% CI, 1.24-1.83]; P = .0009), neurologic complications (OR = 1.64 [95% CI, 1.18-2.27]; P = .0018), and other surgical complications (OR = 1.55 [95% CI, 1.05-2.33]; P = .0240). CONCLUSIONS: This study of a data base of multiple hospitals in the United States demonstrates that clipping of ruptured cerebral aneurysms resulted in greater adjusted morbidity compared with coiling.

Retrospective review of rapid pediatric brain MR imaging at an academic institution including practice trends and factors affecting scan times.

BACKGROUND AND PURPOSE: In an effort to reduce radiation exposure in children requiring regular follow up for shunted hydrocephalus, our institution implemented a rapid brain MR imaging protocol. The purpose of this study was to review an academic practice experience with pediatric rapid brain MR imaging without patient sedation in the evaluation of hydrocephalus and a limited group of other conditions. MATERIALS AND METHODS: We retrospectively analyzed limited-sequence, rapid brain MR imaging scans performed in nonsedated patients younger than 14 years between April 2009 and December 2011. So-called failed examinations were determined by consensus of 2 authors as insufficiently diagnostic for evaluation of ventricular size. CT and MR imaging quarterly volumes for hydrocephalus-related indications were determined from 2005-2012. Multivariable logistic regression analysis was performed to elucidate factors potentially affecting scan durations including examination indication and patient age, sex, inpatient status, and clinical conditions. RESULTS: A total of 398 examinations were performed on 168 patients (103 boys, 65 girls; median age, 13 months). None were deemed to be failed examinations. Median scan duration was 4.43 minutes (interquartile range, 4.42 minutes-5.88 minutes; SD, 2.42 minutes). Examination indication of altered mental status was the only factor associated with increased scan duration (+1.77 minutes; P = .0021). Hydrocephalus-related imaging volumes approximately doubled in the 7 years reviewed, but rapid MR imaging introduced in 2009 is quickly replacing CT scanning for these indications, accounting for nearly 7 of every 8 examinations at the end of the study period. CONCLUSIONS: In every case of initial work-up and follow-up, rapid brain MR imaging effectively evaluated ventricular size and/or intracranial fluid and represents a viable alternative to CT scanning, irrespective of a child's age or clinical condition. For this indication and patient group, MR imaging is now the predominant imaging method in our practice.

Subarachnoid hemorrhage incidence in the United States does not vary with season or temperature.

BACKGROUND AND PURPOSE: Previous studies have suggested seasonal variations in rates of spontaneous rupture of intracranial aneurysms, leading to potentially devastating SAH. In an effort to identify a seasonal effect, variation in SAH incidence and in-hospital mortality rates were examined as they relate to admission month, temperature, and climate using HCUP's Nationwide Inpatient Sample. MATERIALS AND METHODS: Cases of nontraumatic SAH and subsequent in-hospital mortality were extracted from the 2001-2008 NIS and associated with month of occurrence, local average monthly temperatures, and USDA climate zone. Multivariate regression analysis was used to study how admission month, temperature, and climate affected SAH admission and mortality rates. RESULTS: Among 57,663,486 hospital admissions from the 2001-2008 NIS, 52,379 cases of spontaneous SAH (ICD-9-CM 430) and 13,272 cases of subsequent in-hospital mortality were identified. SAH incidence and in-hospital mortality rates were not significantly correlated with a monthly/seasonal effect (incidence, χ(2) = 2.94, P = .99; mortality, χ(2) = 6.91, P = .81). However, SAH incidence significantly varied with climate (P < .0001, zones 11 and 7) but not with temperature (P = .1453), whereas average monthly temperature and climate had no significant correlation with in-hospital mortality (temperature, P = .3005; climate, P = .0863). CONCLUSIONS: We identified no significant monthly or temperature-related effect in the incidence of SAH. Our data suggest that certain climate zones within the United States may be associated with significantly different SAH incidence, but the origins of these differences remain unclear and are probably unrelated to meteorologic variables.

Comparison of hospitalization costs and Medicare payments for carotid endarterectomy and carotid stenting in asymptomatic patients.

BACKGROUND AND PURPOSE: Hospitals struggle to provide care for elderly patients based on Medicare payments. Amid concerns of inadequate reimbursement, we sought to evaluate the hospitalization costs for recipients of CEA and CAS placement, identify variables associated with increased costs, and compare these costs with Medicare reimbursements. MATERIALS AND METHODS: All CEA and CAS procedures were extracted from the 2001-2008 NIS. Average CMS reimbursement rates for CEA and CAS were obtained from www.CMS.gov. Annual trends in hospital costs were analyzed by Sen slope analysis. Associations between LOS and hospital costs with respect to sex, age, discharge status, complication type, and comorbidity were analyzed by using the Wilcoxon rank sum test. Least-squares regression models were used to predict which variables had the greatest impact on LOS and hospital costs. RESULTS: The 2001-2008 NIS contained 181,200 CEA and 12,485 CAS procedures. Age and sex were not predictive of costs for either procedure. Among favorable outcomes, CAS was associated with significantly higher costs compared with CEA (P < .0001). Average Medicare payments were $1,318 less than costs for CEA and $3,241 less than costs for CAS among favorable outcomes. Greater payment-to-cost disparities were noted for both CEA and CAS in patients who had unfavorable outcomes. CONCLUSIONS: The 2008 Medicare hospitalization payments were substantially less than median hospital costs for both CAS and CEA. Efforts to decrease hospitalization costs and/or increase payments will be necessary to make these carotid revascularization procedures economically viable for hospitals in the long term.

Mortality in the vertebroplasty population.

BACKGROUND AND PURPOSE: Vertebroplasty is an effective treatment for painful compression fractures refractory to conservative management. Because there are limited data regarding the survival characteristics of this patient population, we compared the survival of a treated with an untreated vertebral fracture cohort to determine whether vertebroplasty affects mortality rates. MATERIALS AND METHODS: The survival of a treated cohort, comprising 524 vertebroplasty recipients with refractory osteoporotic vertebral compression fractures, was compared with a separate historical cohort of 589 subjects with fractures not treated by vertebroplasty who were identified from the Rochester Epidemiology Project. Mortality was compared between cohorts by using Cox proportional hazards models adjusting for age, sex, and Charlson indices of comorbidity. Mortality was also correlated with pre-, peri-, and postprocedural clinical metrics (eg, cement volume use, RDQ score, analog pain scales, frequency of narcotic use, and improvement in mobility) within the treated cohort. RESULTS: Vertebroplasty recipients demonstrated 77% of the survival expected for individuals of similar age, ethnicity, and sex within the US population. Compared with individuals with both symptomatic and asymptomatic untreated vertebral fractures, vertebroplasty recipients retained a 17% greater mortality risk. However, compared with symptomatic untreated vertebral fractures, vertebroplasty recipients had no increased mortality following adjustment for differences in age, sex, and comorbidity (HR, 1.02; 95% CI, 0.82-1.25). In addition, no clinical metrics used to assess the efficacy of vertebroplasty were predictive of survival. CONCLUSIONS: Vertebroplasty recipients have mortality rates similar to those of individuals with untreated symptomatic fractures but have worse mortality compared with those with asymptomatic vertebral fractures.

Retrograde amnesia for fear-potentiated startle in rats after complete, but not partial, hippocampal damage.

We assessed the involvement of the hippocampus in recall of learned fear of a discrete visual stimulus using a fear-potentiated startle (FPS) procedure. Recall was measured by an increase in acoustic startle in the presence of a light that was paired with footshock. In Experiment 1, rats either received sham, dorsal, ventral, or complete (dorsal and ventral) NMDA-induced damage of the hippocampus following FPS acquisition. During the post-surgery retention test, only the rats with complete hippocampal damage showed a significant FPS deficit. In Experiment 2, we examined whether recent and remote memory for FPS would be differentially affected by complete hippocampal damage. Rats received sham or complete hippocampal damage 1- or 4-wk after FPS acquisition. During the retention test, sham rats exhibited significant FPS, whereas rats with hippocampal damage showed a large FPS deficit that was equivalent for recent and remote memories. In Experiment 3, we found that rats with complete hippocampal damage induced before conditioning showed levels of FPS that did not significantly differ from sham rats. Combined, these findings suggest that extensive damage to the hippocampus causes retrograde amnesia for a memory involving a light-shock association that is not temporally graded. The same damage does not cause anterograde amnesia in the same memory task. Partial damage of the hippocampus, whether of the dorsal or ventral region, was insufficient to cause retrograde amnesia. Thus, the hippocampus normally has a critical and long-lasting role enabling recall of fear conditioning to a discrete visual stimulus. In the absence of the hippocampus other memory systems support new learning.

Fate of manuscripts previously rejected by the American Journal of Neuroradiology: a follow-up analysis.

BACKGROUND AND PURPOSE: This is a follow-up article to "Fate of Submitted Manuscripts Rejected from the American Journal of Neuroradiology: Outcomes and Commentary." The purpose of this study was to quantify differences in citation frequency between manuscripts published in the American Journal of Neuroradiology (AJNR) and those published after AJNR rejection and to understand citation frequency differences among rejected manuscripts. MATERIALS AND METHODS: In this study, a MEDLINE search identified all manuscripts published in AJNR in 2005 and those initially rejected by AJNR in 2004 but subsequently published elsewhere. Once identified, the citation frequencies of both groups were determined by using SCOPUS. Citation data were used in comparative studies between AJNR rejected and accepted articles and in studies comparing citation frequency differences among rejected manuscripts as a function of journal and/or publication classifications. RESULTS: Among 315 subsequently published rejections from AJNR in 2004, 696 citations accumulated between 2005 and 2007 (2.4 citations/journal year), whereas 441 AJNR articles published in 2005 accumulated 2490 citations between 2005 and 2007 (6.4 citations/journal year, P < .0001). One-way analysis of variance suggested that rejected manuscripts classified as technical reports and/or published in journals classified as either neuroradiology or general radiology had significantly higher citation frequencies than other submission types and journal classifications. Nonparametric analysis of citation frequency showed significant correlations with impact factors of respective publishing journals (rho = 0.444). CONCLUSION: Results from this study suggest that publications initially rejected from AJNR have a significantly lower citation frequency than those accepted by AJNR. Among rejected manuscripts, citations frequencies were highest in technical reports and among journals close to the neuroradiologic discipline.

Post-training CB1 cannabinoid receptor agonist activation disrupts long-term consolidation of spatial memories in the hippocampus.

Cannabinoids have long been associated with mnemonic deficits. However, existing evidence has generally focused on the effect of cannabinoids when they are delivered prior to task-training, and such findings are confounded by possible drug effects on sensory, motor, and/or motivational systems that support the acquisition and the expression of learning. The present study investigated the effects of the CB1-receptor agonist WIN 55,212-2 (WIN) on memory consolidation in the Morris water maze. In experiment 1, systemic injections of either WIN or DMSO vehicle were given daily following each training day (post-training), and rats were probe-tested 1 week or 4 weeks later. Rats injected with 1 mg/kg and 3 mg/kg of WIN spent significantly less time in the target quadrant compared with controls 4 weeks later, while no difference was observed at 1-week retention. In experiment 2, intrahippocampal injections of WIN were administered to the dorsal hippocampus following each training day and rats were again probe-tested 1 week or 4 weeks later. Rats bilaterally infused with WIN at 2.5 microg and 5 microg (per side) during training spent significantly less time in the target quadrant than vehicle controls on probe trial 4 weeks later, while no difference was seen at 1-week retention. Taken together, our results showed that post-training activation of CB1 receptors in the hippocampus disrupts long-term memory consolidation but has no effect on acquisition and short-term retention. Plausible pharmacological interactions between cannabinoids and other neurotransmitter systems and associated plasticity mechanisms are discussed.