JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Targeting high-risk employees may reduce cardiovascular racial disparities.
Am J Manag Care
PUBLISHED: 11-04-2014
Show Abstract
Hide Abstract
Objectives A possible remedy for health disparities is for employers to promote cardiovascular health among minority employees. We sought to quantify the financial return to employers of interventions to improve minority health, and to determine whether a race- or risk-targeted strategy was better. Study Design Retrospective claims-based cohort analysis. Methods Unconditional per-person costs attributable to stroke and myocardial infarction (MI) were estimated for University of Michigan employees from 2006 to 2009 using a 2-part model. The model was then used to predict the costs of cardiovascular disease to the University for 2 subgroups of employees-minorities and high-risk patients-and to calculate cost-savings thresholds: the point at which the costs of hypothetical interventions (eg, workplace fitness programs) would equal the cost savings from stroke/ MI prevention. Results Of the 38,314 enrollees, 10% were African American. Estimated unconditional payments for stroke/MI were almost the same in African Americans ($128 per employee per year; 95% CI, $79-$177) and whites ($128 per employee per year; 95% CI, $101- $156), including higher event rates and lower payments per event in African Americans. Targeting the highest risk decile with interventions to reduce stroke/MI would result in a substantially higher cost-savings threshold ($81) compared with targeting African Americans ($13). An unanticipated consequence of risk-based targeting is that African Americans would substantially benefit: an intervention targeted at the top risk decile would prevent 75% of the events in African Americans, just as would an intervention that exclusively targeted African Americans. Conclusions Targeting all high-risk employees for cardiovascular risk reduction may be a win-win-win situation for employers: improving health, decreasing costs, and reducing disparities.
Related JoVE Video
Dementia Risk After Traumatic Brain Injury vs Nonbrain Trauma: The Role of Age and Severity.
JAMA Neurol
PUBLISHED: 10-28-2014
Show Abstract
Hide Abstract
Epidemiologic evidence regarding the importance of traumatic brain injury (TBI) as a risk factor for dementia is conflicting. Few previous studies have used patients with non-TBI trauma (NTT) as controls to investigate the influence of age and TBI severity.
Related JoVE Video
The role of accommodations in poststroke disability management.
J Gerontol B Psychol Sci Soc Sci
PUBLISHED: 10-25-2014
Show Abstract
Hide Abstract
To explore use of assistive devices and personal assistance and unmet need for assistance among older stroke survivors and identify potentially modifiable factors to optimize self-care and mobility activities in this population.
Related JoVE Video
Is Physician Work in Procedure and Test Codes More Highly Valued Than That in Evaluation and Management Codes?
Ann. Surg.
PUBLISHED: 09-20-2014
Show Abstract
Hide Abstract
To determine whether the Centers for Medicare & Medicaid Services (CMS) Physician Fee Schedule confers higher value for physician work in procedure and test codes than in Evaluation and Management (E/M) codes.
Related JoVE Video
Effects of multiple genetic Loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.
Adam C Naj, Gyungah Jun, Christiane Reitz, Brian W Kunkle, William Perry, Yo Son Park, Gary W Beecham, Ruchita A Rajbhandary, Kara L Hamilton-Nelson, Li-San Wang, John S K Kauwe, Matthew J Huentelman, Amanda J Myers, Thomas D Bird, Bradley F Boeve, Clinton T Baldwin, Gail P Jarvik, Paul K Crane, Ekaterina Rogaeva, M Michael Barmada, F Yesim Demirci, Carlos Cruchaga, Patricia L Kramer, Nilüfer Ertekin-Taner, John Hardy, Neill R Graff-Radford, Robert C Green, Eric B Larson, Peter H St George-Hyslop, Joseph D Buxbaum, Denis A Evans, Julie A Schneider, Kathryn L Lunetta, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, Philip L De Jager, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Eden R Martin, Jonathan L Haines, Richard P Mayeux, Lindsay A Farrer, Gerard D Schellenberg, Margaret A Pericak-Vance, , Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Lisa L Barnes, Thomas G Beach, James T Becker, Duane Beekly, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Chris S Carlson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Helena C Chui, David G Clark, Jason Corneveaux, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M Laferla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Chiao-Feng Lin, Oscar L Lopez, Constantine G Lyketsos, Wendy J Mack, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Jill R Murrell, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Otto Valladares, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, Lei Yu.
JAMA Neurol
PUBLISHED: 09-10-2014
Show Abstract
Hide Abstract
Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants.
Related JoVE Video
Naturally Arising Strains of Polyomaviruses with Severely Attenuated MicroRNA Expression.
J. Virol.
PUBLISHED: 08-20-2014
Show Abstract
Hide Abstract
Several different polyomaviruses (PyVs) encode microRNAs (miRNAs) that regulate viral as well as host gene expression. However, the functions of polyomaviral miRNAs, particularly during in vivo infection, remain poorly understood. Here we identify rare naturally arising PyVs that are severely attenuated or null for miRNA expression. We identify hypomorphic or null strains for miRNA expression from rhesus macaque simian virus 40 (SV40) and human JC virus. These strains were isolated from immunocompromised hosts and derive from insertions or deletions in the viral DNA that preserve the amino acid reading frame of opposing-strand large T antigen gene. Characterization of the SV40 miRNA hypomorph, K661, shows that it is inhibited at the early miRNA biogenesis step of Drosha-mediated processing. Despite having a nonrearranged enhancer, which a previous study has shown renders some PyVs more susceptible to the autoregulatory activities of the miRNA, restoring miRNA expression to K661 has little effect on virus growth in either immortalized or primary monkey kidney cells. Thus, in addition to any effect of accompanying genomic elements, these results suggest that the cellular context also determines susceptibility to PyV miRNA-mediated effects. Combined, these results demonstrate that polyomaviruses lacking miRNAs can arise infrequently and that the functional importance of polyomaviral miRNAs is context dependent, consistent with an activity connected to the immune status of the host.
Related JoVE Video
The Connection Between Bayesian Estimation of a Gaussian Random Field and RKHS.
IEEE Trans Neural Netw Learn Syst
PUBLISHED: 08-05-2014
Show Abstract
Hide Abstract
Reconstruction of a function from noisy data is key in machine learning and is often formulated as a regularized optimization problem over an infinite-dimensional reproducing kernel Hilbert space (RKHS). The solution suitably balances adherence to the observed data and the corresponding RKHS norm. When the data fit is measured using a quadratic loss, this estimator has a known statistical interpretation. Given the noisy measurements, the RKHS estimate represents the posterior mean (minimum variance estimate) of a Gaussian random field with covariance proportional to the kernel associated with the RKHS. In this brief, we provide a statistical interpretation when more general losses are used, such as absolute value, Vapnik or Huber. Specifically, for any finite set of sampling locations (that includes where the data were collected), the maximum a posteriori estimate for the signal samples is given by the RKHS estimate evaluated at the sampling locations. This connection establishes a firm statistical foundation for several stochastic approaches used to estimate unknown regularization parameters. To illustrate this, we develop a numerical scheme that implements a Bayesian estimator with an absolute value loss. This estimator is used to learn a function from measurements contaminated by outliers.
Related JoVE Video
Loss of the Mexican American survival advantage after ischemic stroke.
Stroke
PUBLISHED: 07-29-2014
Show Abstract
Hide Abstract
Mexican Americans (MAs) were previously found to have lower mortality after ischemic stroke than non-Hispanic whites. We studied mortality trends in a population-based design.
Related JoVE Video
Impact of state Medicaid coverage on utilization of inpatient rehabilitation facilities among patients with stroke.
Stroke
PUBLISHED: 07-08-2014
Show Abstract
Hide Abstract
Poststroke rehabilitation is associated with improved outcomes. Medicaid coverage of inpatient rehabilitation facility (IRF) admissions varies by state. We explored the role of state Medicaid IRF coverage on IRF utilization among patients with stroke.
Related JoVE Video
The effect of pre-Affordable Care Act (ACA) Medicaid eligibility expansion in New York State on access to specialty surgical care.
Med Care
PUBLISHED: 07-02-2014
Show Abstract
Hide Abstract
Critics argue that expanding health insurance coverage through Medicaid may not result in improved access to care. The Affordable Care Act provides reimbursement incentives aimed at improving access to primary care services for new Medicaid beneficiaries; however, there are no such incentives for specialty services. Using the natural experiment of Medicaid expansion in New York (NY) State in October 2001, we examined whether Medicaid expansion increased access to common musculoskeletal procedures for Medicaid beneficiaries.
Related JoVE Video
Racial differences in disability after stroke: results from a nationwide study.
Neurology
PUBLISHED: 06-27-2014
Show Abstract
Hide Abstract
We sought to characterize racial differences in disability among older stroke survivors.
Related JoVE Video
Minorities, men, and unmarried amyotrophic lateral sclerosis patients are more likely to die in an acute care facility.
Amyotroph Lateral Scler Frontotemporal Degener
PUBLISHED: 06-12-2014
Show Abstract
Hide Abstract
Studies suggest that dying at home is a more favorable experience. This study investigated where amyotrophic lateral sclerosis (ALS) patients die and the patient demographics associated with dying in an acute care facility or nursing home compared to home or hospice. Centers for Disease Control and Prevention Multiple Cause Mortality Files from 2005 to 2010 were used to identify ALS patients and to classify place of death. Multinomial logistic regression was used to determine the association between patient demographics and place of death. Between 2005 and 2010, 40,911 patients died of ALS in the United States. Place of death was as follows: home or hospice facility 20,231 (50%), acute care facility (25%), and nursing home (20%). African Americans (adjusted multinomial odds ratio (aMOR) 2.56, CI 2.32-2.83), Hispanics (aMOR 1.44, CI 1.30-1.62), and Asians (aMOR 1.87, CI 1.57-2.22) were more likely to die in an acute care facility, whereas females (aMOR 0.76, CI 0.72-0.80) and married individuals were less likely. Hispanics (aMOR 0.68, CI 0.58-0.79) and married individuals were less likely to die in a nursing home. In conclusion, minorities, men, and unmarried individuals are more likely to die in an acute care facility. Further studies are needed to better understand place of death preferences.
Related JoVE Video
A central role for the primary microRNA stem in guiding the position and efficiency of Drosha processing of a viral pri-miRNA.
RNA
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
Processing of primary microRNA (pri-miRNA) stem-loops by the Drosha-DGCR8 complex is the initial step in miRNA maturation and crucial for miRNA function. Nonetheless, the underlying mechanism that determines the Drosha cleavage site of pri-miRNAs has remained unclear. Two prevalent but seemingly conflicting models propose that Drosha-DGCR8 anchors to and directs cleavage a fixed distance from either the basal single-stranded (ssRNA) or the terminal loop. However, recent studies suggest that the basal ssRNA and/or the terminal loop may influence the Drosha cleavage site dependent upon the sequence/structure of individual pri-miRNAs. Here, using a panel of closely related pri-miRNA variants, we further examine the role of pri-miRNA structures on Drosha cleavage site selection in cells. Our data reveal that both the basal ssRNA and terminal loop influence the Drosha cleavage site within three pri-miRNAs, the Simian Virus 40 (SV40) pri-miRNA, pri-miR-30a, and pri-miR-16. In addition to the flanking ssRNA regions, we show that an internal loop within the SV40 pri-miRNA stem strongly influences Drosha cleavage position and efficiency. We further demonstrate that the positions of the internal loop, basal ssRNA, and the terminal loop of the SV40 pri-miRNA cooperatively coordinate Drosha cleavage position and efficiency. Based on these observations, we propose that the pri-miRNA stem, defined by internal and flanking structural elements, guides the binding position of Drosha-DGCR8, which consequently determines the cleavage site. This study provides mechanistic insight into pri-miRNA processing in cells that has numerous biological implications and will assist in refining Drosha-dependent shRNA design.
Related JoVE Video
Influence of hospital-level practices on readmission after ischemic stroke.
Neurology
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
To inform stroke quality improvement initiatives by determining the relationship between hospital-level stroke practices and readmission after accounting for patient-level factors.
Related JoVE Video
Intracerebral hemorrhage mortality is not changing despite declining incidence.
Neurology
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
To determine trends in incidence and mortality of intracerebral hemorrhage (ICH) in a rigorous population-based study.
Related JoVE Video
Subcutaneous venous-access device removal: a cost analysis.
Obstet Gynecol
PUBLISHED: 04-29-2014
Show Abstract
Hide Abstract
Most patients being treated for gynecologic malignancies have vascular-access devices for chemotherapy administration. After treatment is completed, the device is removed. However, the ideal setting for removal has not been shown. This study performed a cost analysis of outpatient-clinic removal with local anesthesia compared with outpatient-operating room removal with various forms of sedation while controlling for postprocedure complications.
Related JoVE Video
Stroke risk after nonstroke emergency department dizziness presentations: a population-based cohort study.
Ann. Neurol.
PUBLISHED: 04-26-2014
Show Abstract
Hide Abstract
Acute stroke is a serious concern in emergency department (ED) dizziness presentations. Prior studies, however, suggest that stroke is actually an unlikely cause of these presentations. Lacking are data on short- and long-term follow-up from population-based studies to establish stroke risk after presumed nonstroke ED dizziness presentations.
Related JoVE Video
Cost and utility in the diagnostic evaluation of stroke.
Continuum (Minneap Minn)
PUBLISHED: 04-05-2014
Show Abstract
Hide Abstract
The diagnostic evaluation in a patient presenting with acute stroke has several purposes depending on the clinical circumstances. These include identifying stroke mimics, differentiating ischemic stroke from intracerebral hemorrhage in the acute setting, clarifying stroke localization, and determining the stroke mechanism to guide secondary prevention. The neurologist needs to be aware of the cost implications of different approaches to the diagnostic evaluation.
Related JoVE Video
Specialist participation in healthcare delivery transformation: influence of patient self-referral.
Am J Manag Care
PUBLISHED: 03-28-2014
Show Abstract
Hide Abstract
Improving coordination of care and containing healthcare costs are prominent goals of healthcare reform. Specialist involvement in healthcare delivery transformation efforts like Accountable Care Organizations (ACOs) is necessary to achieve these goals. However, patients’ self-referrals to specialists may undermine care coordination and incur unnecessary costs if patients frequently receive care from specialists not engaged in such healthcare delivery transformation efforts. Additionally, frequent self-referrals may also diminish the incentive for specialist participation in reform endeavors like ACOs to get access to a referral base.
Related JoVE Video
Variation in do-not-resuscitate orders for patients with ischemic stroke: implications for national hospital comparisons.
Stroke
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
Decisions on life-sustaining treatments and the use of do-not-resuscitate (DNR) orders can affect early mortality after stroke. We investigated the variation in early DNR use after stroke among hospitals in California and the effect of this variation on mortality-based hospital classifications.
Related JoVE Video
Ocular pharmacokinetics of intravitreally administered brimonidine and dexamethasone in animal models with and without blood-retinal barrier breakdown.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-23-2014
Show Abstract
Hide Abstract
We compared ocular and systemic pharmacokinetics of brimonidine and dexamethasone following a single intravitreal dose in animals with blood-retinal barrier (BRB) breakdown and in healthy controls.
Related JoVE Video
The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.
Alzheimers Dement
PUBLISHED: 01-15-2014
Show Abstract
Hide Abstract
We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL, very long based on the number of T residues.
Related JoVE Video
A systematic review and critical appraisal of quality measures for the emergency care of acute ischemic stroke.
Ann Emerg Med
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Acute stroke is an important focus of quality improvement efforts. There are many organizations involved in quality measurement for acute stroke, and a complex landscape of quality measures exists. Our objective is to describe and evaluate existing US quality measures for the emergency care of acute ischemic stroke patients in the emergency department (ED) setting. We performed a systematic review of the literature to identify the existing quality measures for the emergency care of acute ischemic stroke. We then convened a panel of experts to appraise how well the measures satisfy the American College of Cardiology/American Heart Association (ACC/AHA) criteria for performance measure development (strength of the underlying evidence, clinical importance, magnitude of the relationship between performance and outcome, and cost-effectiveness). We identified 7 quality measures relevant to the emergency care of acute ischemic stroke that fall into 4 main categories: brain imaging, thrombolytic administration, dysphagia screening, and mortality. Three of the 7 measures met all 4 of the ACC/AHA evaluation criteria: brain imaging within 24 hours, thrombolytic therapy within 3 hours of symptom onset, and thrombolytic therapy within 60 minutes of hospital arrival. Measures not satisfying all evaluation criteria were brain imaging report within 45 minutes, consideration for thrombolytic therapy, dysphagia screening, and mortality rate. There remains room for improvement in the development and use of measures that reflect high-quality emergency care of acute ischemic stroke patients in the United States.
Related JoVE Video
Using internally developed risk models to assess heterogeneity in treatment effects in clinical trials.
Circ Cardiovasc Qual Outcomes
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Recent proposals suggest that risk-stratified analyses of clinical trials be routinely performed to better enable tailoring of treatment decisions to individuals. Trial data can be stratified using externally developed risk models (eg, Framingham risk score), but such models are not always available. We sought to determine whether internally developed risk models, developed directly on trial data, introduce bias compared with external models.
Related JoVE Video
Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study.
Gynecol. Oncol.
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma.
Related JoVE Video
Consumer Demand for Online Dizziness Information: If You Build it, They may Come.
Front Neurol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Dizziness is a common reason patients present to doctors, but effective diagnostic tests and treatments for dizziness are underused. The internet is a way to disseminate medical information and is emerging as an intervention platform. The objective of this study was to describe internet searches for dizziness terms to assess the possible consumer demand for internet-based dizziness diagnostic and treatment tools.
Related JoVE Video
Purine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors for autoimmune diseases.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development.
Related JoVE Video
A Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signaling.
PLoS Pathog.
PUBLISHED: 12-01-2013
Show Abstract
Hide Abstract
Torque teno viruses (TTVs) are a group of viruses with small, circular DNA genomes. Members of this family are thought to ubiquitously infect humans, although causal disease associations are currently lacking. At present, there is no understanding of how infection with this diverse group of viruses is so prevalent. Using a combined computational and synthetic approach, we predict and identify miRNA-coding regions in diverse human TTVs and provide evidence for TTV miRNA production in vivo. The TTV miRNAs are transcribed by RNA polymerase II, processed by Drosha and Dicer, and are active in RISC. A TTV mutant defective for miRNA production replicates as well as wild type virus genome; demonstrating that the TTV miRNA is dispensable for genome replication in a cell culture model. We demonstrate that a recombinant TTV genome is capable of expressing an exogenous miRNA, indicating the potential utility of TTV as a small RNA vector. Gene expression profiling of host cells identifies N-myc (and STAT) interactor (NMI) as a target of a TTV miRNA. NMI transcripts are directly regulated through a binding site in the 3UTR. SiRNA knockdown of NMI contributes to a decreased response to interferon signaling. Consistent with this, we show that a TTV miRNA mediates a decreased response to IFN and increased cellular proliferation in the presence of IFN. Thus, we add Annelloviridae to the growing list of virus families that encode miRNAs, and suggest that miRNA-mediated immune evasion can contribute to the pervasiveness associated with some of these viruses.
Related JoVE Video
Understanding stroke survivorship: expanding the concept of poststroke disability.
Stroke
PUBLISHED: 11-26-2013
Show Abstract
Hide Abstract
Limitations in essential daily activities are common among older adults after stroke, but little is known about restrictions in their ability to participate in valued social activities. We sought to broaden our understanding of disability after stroke by characterizing poststroke participation restrictions and investigating the extent to which they are accounted for by differences in physical and cognitive capacity, aphasia/dysarthria, depressive, and anxiety symptoms.
Related JoVE Video
Time to Brain Imaging in Acute Stroke Is Improving: Secondary Analysis of the INSTINCT Trial.
Stroke
PUBLISHED: 11-14-2013
Show Abstract
Hide Abstract
Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors.
Related JoVE Video
Expenditures in the elderly with peripheral neuropathy: Where should we focus cost-control efforts?
Neurol Clin Pract
PUBLISHED: 11-01-2013
Show Abstract
Hide Abstract
To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts.
Related JoVE Video
Shared Vision, Collective Impact, and Persistent Challenges: The First Decade of Georgias Oncology Research Network.
J Oncol Pract
PUBLISHED: 10-15-2013
Show Abstract
Hide Abstract
Ten years ago, Georgia was lauded for dedicating a portion of tobacco settlement funds to the Georgia Cancer Coalition (GCC). The plan championed by then-Governor Roy E. Barnes was designed to make Georgia a leader in prevention, treatment, and research. This plan called for the expansion of clinical trials to ensure Georgians had access to the highest quality care based on the most current treatments and discoveries. As a result, oncologists in the state were engaged in a planning process that resulted in a shared vision to improve the quality of cancer care through research and the formation of a new organization: the Georgia Center for Oncology Research and Education.
Related JoVE Video
Comprehensive mapping and analysis of Kaposis sarcoma-associated herpesvirus 3 UTRs identify differential posttranscriptional control of gene expression in lytic versus latent infection.
J. Virol.
PUBLISHED: 09-25-2013
Show Abstract
Hide Abstract
3 untranslated regions (UTRs) are known to play an important role in posttranscriptional regulation of gene expression. Here we map the 3 UTRs of Kaposis sarcoma-associated herpesvirus (KSHV) using next-generation RNA sequencing, 3 rapid amplification of cDNA ends (RACE), and tiled microarray analyses. Chimeric reporters containing the KSHV 3 UTRs show a general trend toward reduced gene expression under conditions of latent infection. Those 3 UTRs with a higher GC content are more likely to be associated with reduced gene expression. KSHV transcripts display an extensive use of shared polyadenylation sites allowing for partially overlapping 3 UTRs and regulatory activities. In addition, a subset of KSHV 3 UTRs is sufficient to convey increased gene expression under conditions of lytic infection. These results suggest a role for viral 3 UTRs in contributing to differential gene expression during latent versus lytic infection.
Related JoVE Video
Research participation by low-income and racial/ethnic minority groups: how payment may change the balance.
Clin Transl Sci
PUBLISHED: 07-29-2013
Show Abstract
Hide Abstract
Minorities are underenrolled in clinical research trials, and one-third of trials are underenrolled overall. The role of payment has not been studied at the national level as an explanation for enrollment patterns. Our objective was to examine the distribution of self-reported previous research participation across different sociodemographic groups; to assess the publics perception of fair payment for a low-risk medicine trial and the association between requested payment and sociodemographic characteristics; to estimate the amount of payment for a medication trial to achieve proportional representation of minorities and different socioeconomic groups. This was a cross-sectional study with nationally representative data collected in 2011 by the C.S. Mott Childrens Hospital National Poll on Childrens Health. To determine the relationship between perceived fair payment and individual-level characteristics, we used multivariable linear regression. With 60% participation rate, in a sample of 2,150 respondents 11% (n = 221) of the sample had previously participated in medical research. Requested payment differed significantly by racial/ethnic group with Hispanics requesting more payment than non-Hispanic whites (0.37 [95%CI 0.02, 0.72]) In contrast to payment at $49, $149, and $249, payment at $349 yielded proportional representation of racial/ethnic minority groups. Hispanics requested higher payment for research participation, suggesting a possible explanation for their underenrollment.
Related JoVE Video
Pre-clinical Cognitive Phenotypes for Alzheimer Disease: A Latent Profile Approach.
Am J Geriatr Psychiatry
PUBLISHED: 07-29-2013
Show Abstract
Hide Abstract
Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline.
Related JoVE Video
Association between hospital case volume and the use of bronchoscopy and esophagoscopy during head and neck cancer diagnostic evaluation.
Cancer
PUBLISHED: 07-25-2013
Show Abstract
Hide Abstract
There are no clinical guidelines on best practices for the use of bronchoscopy and esophagoscopy in diagnosing head and neck cancer. This retrospective cohort study examined variation in the use of bronchoscopy and esophagoscopy across hospitals in Michigan.
Related JoVE Video
Assessment of the differences in pharmacokinetics and pharmacodynamics between four distinct formulations of triamcinolone acetonide.
Retina (Philadelphia, Pa.)
PUBLISHED: 07-05-2013
Show Abstract
Hide Abstract
To compare the durability of Kenalog, Trivaris, Triesence, and compounding pharmacy preservative-free triamcinolone acetonide in pigmented rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and pharmacokinetics.
Related JoVE Video
Traumatic brain injury may be an independent risk factor for stroke.
Neurology
PUBLISHED: 06-26-2013
Show Abstract
Hide Abstract
To explore whether traumatic brain injury (TBI) may be a risk factor for subsequent ischemic stroke.
Related JoVE Video
Altering Electromyography Studies: Importance of the Electromyographers Perception of Patient Pain.
Arch Phys Med Rehabil
PUBLISHED: 06-17-2013
Show Abstract
Hide Abstract
To determine the relation between the patients actual pain, the electromyographers perception of patient pain, and whether an electromyogram (EMG) is altered.
Related JoVE Video
Does a claims diagnosis of autism mean a true case?
Autism
PUBLISHED: 06-05-2013
Show Abstract
Hide Abstract
The purpose of this study was to validate autism spectrum disorder cases identified through claims-based case identification algorithms against a clinical review of medical charts. Charts were reviewed for 432 children who fell into one of the three following groups: (a) more than or equal to two claims with an autism spectrum disorder diagnosis code (n = 182), (b) one claim with an autism spectrum disorder diagnosis code (n = 190), and (c) those who had no claims for autism spectrum disorder but had claims for other developmental or neurological conditions (n = 60). The algorithm-based diagnoses were compared with documented autism spectrum disorders in the medical charts. The algorithm requiring more than or equal to two claims for autism spectrum disorder generated a positive predictive value of 87.4%, which suggests that such an algorithm is a valid means to identify true autism spectrum disorder cases in claims data.
Related JoVE Video
Impact of (18)F-florbetapir PET imaging of ?-amyloid neuritic plaque density on clinical decision-making.
Neurocase
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
(18)F-florbetapir positron emission tomography (PET) imaging of the brain is now approved by the Food and Drug Administration (FDA) approved for estimation of ?-amyloid neuritic plaque density when evaluating patients with cognitive impairment. However, its impact on clinical decision-making is not known. We present 11 cases (age range 67-84) of cognitively impaired subjects in whom clinician surveys were done before and after PET scanning to document the theoretical impact of amyloid imaging on the diagnosis and treatment plan of cognitively impaired subjects. Subjects have been clinically followed for about 5 months after the PET scan. Negative scans occurred in five cases, leading to a change in diagnosis for four patients and a change in treatment plan for two of these cases. Positive scans occurred in six cases, leading to a change in diagnosis for four patients and a change in treatment plan for three of these cases. Following the scan, only one case had indeterminate diagnosis. Our series suggests that both positive and negative florbetapir PET scans may enhance diagnostic certainty and impact clinical decision-making. Controlled longitudinal studies are needed to confirm our data and determine best practices.
Related JoVE Video
The impact of diabetes counseling and education: clinical and cost outcomes from a large population of US managed care patients with type 2 diabetes.
Diabetes Educ
PUBLISHED: 05-02-2013
Show Abstract
Hide Abstract
The purpose of this study is to examine outcomes in adult patients with type 2 diabetes mellitus who received diabetes counseling and education (C/E) services compared with those who did not.
Related JoVE Video
The influence of procedure delay on resource use: a national study of patients with open tibial fracture.
Plast. Reconstr. Surg.
PUBLISHED: 04-23-2013
Show Abstract
Hide Abstract
The purpose of this study was to (1) understand national variation in delay of emergency procedures in patients with open tibial fracture at the hospital level and (2) compare length of stay and cost in patients cared for at the best- and worst-performing hospitals for delay.
Related JoVE Video
Characterization of mineral phosphate solubilization traits from a barley rhizosphere soil functional metagenome.
Microbiologyopen
PUBLISHED: 04-15-2013
Show Abstract
Hide Abstract
Mineral phosphate solubilization (MPS) microorganisms are important for their provision of orthophosphate anions for plant growth promotion activity in soil. In this study, we applied a functional metagenomic approach to identify this trait directly from the microbiome in barley rhizosphere soil that had not received P fertilizer over a 15-year period. A fosmid system was used to clone the metagenome of which 18,000 clones (~666 Mb of DNA) was screened for MPS. Functional assays and High Performance Liquid Chromatography analysis recognized gluconic acid production and MPS activity in the range 24.8-77.1 mmol/L and 27.6-38.16 ?g/mL, respectively, when screened in an Escherichia coli host (at frequency of one MPS-positive clone hit per 114 Mb DNA tested). The MPS clones (with average insert size of ~37 kb) were analysed by 454 Roche sequencing and annotated. A number of genes/operons with homology to Phosphorous (P) uptake, regulatory and solubilization mechanisms were identified, linking the MPS function to the uncultivated microbiome present in barley rhizosphere soil.
Related JoVE Video
Assessing mild cognitive impairment with amyloid and dopamine terminal molecular imaging.
J. Nucl. Med.
PUBLISHED: 04-09-2013
Show Abstract
Hide Abstract
We evaluated PET-based classification of neurodegenerative pathology in mild cognitive impairment (MCI).
Related JoVE Video
Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases.
Neurotherapeutics
PUBLISHED: 03-19-2013
Show Abstract
Hide Abstract
Protein misfolding and aggregation in the brain have been recognized to be crucial in the pathogenesis of various neurodegenerative diseases, including Alzheimers, Parkinsons, and the polyglutamine (polyQ) diseases, which are collectively called the "protein misfolding diseases". In the polyQ diseases, an abnormally expanded polyQ stretch in the responsible proteins causes the proteins to misfold and aggregate, eventually resulting in neurodegeneration. Hypothesizing that polyQ protein misfolding and aggregation could be inhibited by molecules specifically binding to the expanded polyQ stretch, we identified polyQ binding peptide 1 (QBP1). We show that QBP1 does, indeed, inhibit misfolding and aggregation of the expanded polyQ protein in vitro. Furthermore overexpression of QBP1 by the crossing of transgenic animals inhibits neurodegeneration in Drosophila models of the polyQ diseases. We also introduce our attempts to deliver QBP1 into the brain by administration using viral vectors and protein transduction domains. Interestingly, recent data suggest that QBP1 can also inhibit the misfolding/aggregation of proteins responsible for other protein misfolding diseases, highlighting the potential of QBP1 as a general therapeutic molecule for a wide range of neurodegenerative diseases. We hope that in the near future, aggregation inhibitor-based drugs will be developed and bring relief to patients suffering from these currently intractable protein misfolding diseases.
Related JoVE Video
Related JoVE Video
Neuropsychological predictors of dementia in late-life major depressive disorder.
Am J Geriatr Psychiatry
PUBLISHED: 02-12-2013
Show Abstract
Hide Abstract
Major depressive disorder is a likely risk factor for dementia, but some cases of major depressive disorder in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores to predict conversion to dementia in a sample of depressed older adults diagnosed as nondemented at the time of neuropsychological testing.
Related JoVE Video
Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.
Nat. Med.
PUBLISHED: 02-10-2013
Show Abstract
Hide Abstract
Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n=30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P=0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.
Related JoVE Video
Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans.
Cancer Res.
PUBLISHED: 02-07-2013
Show Abstract
Hide Abstract
Efforts to selectively target and disrupt established tumor vasculature have largely failed to date. We hypothesized that a vaccinia virus engineered to target cells with activation of the ras/MAPK signaling pathway (JX-594) could specifically infect and express transgenes (hGM-CSF, ?-galactosidase) in tumor-associated vascular endothelial cells in humans. Efficient replication and transgene expression in normal human endothelial cells in vitro required either VEGF or FGF-2 stimulation. Intravenous infusion in mice resulted in virus replication in tumor-associated endothelial cells, disruption of tumor blood flow, and hypoxia within 48 hours; massive tumor necrosis ensued within 5 days. Normal vessels were not affected. In patients treated with intravenous JX-594 in a phase I clinical trial, we showed dose-dependent endothelial cell infection and transgene expression in tumor biopsies of diverse histologies. Finally, patients with advanced hepatocellular carcinoma, a hypervascular and VEGF-rich tumor type, were treated with JX-594 on phase II clinical trials. JX-594 treatment caused disruption of tumor perfusion as early as 5 days in both VEGF receptor inhibitor-naïve and -refractory patients. Toxicities to normal blood vessels or to wound healing were not evident clinically or on MRI scans. This platform technology opens up the possibility of multifunctional engineered vaccinia products that selectively target and infect tumor-associated endothelial cells, as well as cancer cells, resulting in transgene expression, vasculature disruption, and tumor destruction in humans systemically.
Related JoVE Video
Reciprocal inhibition between intracellular antiviral signaling and the RNAi machinery in mammalian cells.
Cell Host Microbe
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
RNA interference (RNAi) is an established antiviral defense mechanism in plants and invertebrates. Whether RNAi serves a similar function in mammalian cells remains unresolved. We find that in some cell types, mammalian RNAi activity is reduced shortly after viral infection via poly-ADP-ribosylation of the RNA-induced silencing complex (RISC), a core component of RNAi. Well-established antiviral signaling pathways, including RIG-I/MAVS and RNaseL, contribute to inhibition of RISC. In the absence of virus infection, microRNAs repress interferon-stimulated genes (ISGs) associated with cell death and proliferation, thus maintaining homeostasis. Upon detection of intracellular pathogen-associated molecular patterns, RISC activity decreases, contributing to increased expression of ISGs. Our results suggest that, unlike in lower eukaryotes, mammalian RISC is not antiviral in some contexts, but rather RISC has been co-opted to negatively regulate toxic host antiviral effectors via microRNAs.
Related JoVE Video
Choosing Wisely: highest-cost tests in outpatient neurology.
Ann. Neurol.
PUBLISHED: 01-09-2013
Show Abstract
Hide Abstract
Identifying the tests/procedures ordered by neurologists that contribute most to health care expenditures is a critical step in the process of creating the neurology top 5 list for the Choosing Wisely initiative. Using data from the 2007-2010 National Ambulatory Care Medical Survey, we found that $13.3 billion (95% confidence interval = $10.1-$16.5 billion) was spent on tests ordered at neurologist visits. The tests/procedures with the highest expenditures were magnetic resonance imaging (MRI; 51% of total expenditures; $7.5 billion), electromyography (EMG; 20% of expenditures; $2.6 billion), and electroencephalography (EEG; 8% of expenditures; $1.1 billion). MRI, EMG, and EEG should receive close scrutiny in the development of the neurology top 5 list.
Related JoVE Video
Topical application of 0.005% latanoprost increases episcleral venous pressure in normal dogs.
Vet Ophthalmol
PUBLISHED: 11-30-2011
Show Abstract
Hide Abstract
Episcleral venous pressure (EVP) has an important role in intraocular pressure (IOP) homeostasis and accounts for more than 70% of the IOP in the normal dog. A frequently used species in glaucoma research is the normotensive dog especially when evaluating the efficacy of prostaglandin analogues and prostamides; however, aqueous humor dynamic studies in normal dogs are lacking, and the effect of 0.005% latanoprost on canine EVP is not known. We sought to determine the effects to the EVP of topically applied 0.005% latanoprost in the normotensive beagle dog.
Related JoVE Video
X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase.
Chem Biol Drug Des
PUBLISHED: 09-21-2011
Show Abstract
Hide Abstract
Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Brutons tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 Å resolution and PP2 at 1.9 Å resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.
Related JoVE Video
Novel tricyclic inhibitors of IKK2: discovery and SAR leading to the identification of 2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl)pyridin-2-yl)methyl)acetamide (BMS-066).
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-22-2011
Show Abstract
Hide Abstract
The synthesis, structure-activity relationships (SAR), and biological results of pyridyl-substituted azaindole based tricyclic inhibitors of IKK2 are described. Compound 4m demonstrated potent in vitro potency, acceptable pharmacokinetic and physicochemical properties, and efficacy when dosed orally in a mouse model of inflammatory bowel disease.
Related JoVE Video
An international perspective on advanced neuroimaging: cometh the hour or ivory tower?
Int Psychogeriatr
PUBLISHED: 08-17-2011
Show Abstract
Hide Abstract
Over the past five to ten years, neuroimaging capability for neurodegenerative diseases has made remarkable progress. However, debate remains as to the true clinical utility of these advanced and costly investigations. Not only is the place of these tests in diagnostic algorithms unclear, but the access to them varies both within and between countries. We sought to gather informed opinion from recognized leaders in the field who can combine both an academic and a clinical perspective on the use of neuroimaging in their own countries. Opinion is presented from Scotland, Argentina, the Czech Republic, France, the USA and Australia. The emerging consensus was one of ongoing caution. While in most countries there was a sense that the use of more advanced imaging techniques was growing, their hour has not yet cometh. However, these techniques, rather than falling from the Ivory Tower, should descend slowly step by step onto fertile and receptive clinics from where better clinical guidelines will emerge.
Related JoVE Video
A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma.
Mol. Ther.
PUBLISHED: 07-19-2011
Show Abstract
Hide Abstract
JX-594 is a targeted and granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In order to study the mechanisms-of-action (MOA) of JX-594 in humans, a mechanistic proof-of-concept clinical trial was performed at a low dose equivalent to ?10% of the maximum-tolerated dose (MTD) in other clinical trials. Ten patients with previously treated stage IV melanoma were enrolled. Tumors were injected weekly for up to nine total treatments. Blood samples and tumor biopsies were analyzed for evidence of transgene activity, virus replication, and immune stimulation. The ?-galactosidase (?-gal) transgene was expressed in all patients as evidenced by antibody induction. Six patients had significant induction of GM-CSF-responsive white blood cell (WBC) subsets such as neutrophils (25-300% increase). JX-594 replication and subsequent shedding into blood was detectable in five patients after cycles 1-9. Tumor biopsies demonstrated JX-594 replication, perivascular lymphocytic infiltration, and diffuse tumor necrosis. Mild flu-like symptoms were the most common adverse events. In sum, JX-594 replication, oncolysis, and expression of both transgenes were demonstrated; replication was still evident after multiple cycles. These findings have implications for further clinical development of JX-594 and other transgene-armed oncolytic viruses.
Related JoVE Video
A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study.
Gynecol. Oncol.
PUBLISHED: 06-30-2011
Show Abstract
Hide Abstract
To estimate activity and safety of trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (1 cycle) in uterine leiomyosarcoma.
Related JoVE Video
Health care costs in patients with painful diabetic peripheral neuropathy prescribed pregabalin or duloxetine.
Pain Pract
PUBLISHED: 06-16-2011
Show Abstract
Hide Abstract
Pregabalin and duloxetine are two FDA-approved medications for the treatment of pain associated with diabetic peripheral neuropathy (pDPN). The objective of this study was to compare changes in all-cause and pDPN-related health care costs in patients with pDPN initiated on pregabalin or duloxetine.
Related JoVE Video
Health care costs in patients with fibromyalgia on pregabalin vs. duloxetine.
Pain Pract
PUBLISHED: 05-26-2011
Show Abstract
Hide Abstract
The economic burden associated with fibromyalgia in the U.S. is substantial. The objective of this study was to compare changes in health care costs in fibromyalgia patients initiated on pregabalin and duloxetine in real-world settings.
Related JoVE Video
Risk factors and preventive interventions for Alzheimer disease: state of the science.
Arch. Neurol.
PUBLISHED: 05-09-2011
Show Abstract
Hide Abstract
Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD.
Related JoVE Video
Assessment of mild dementia with amyloid and dopamine terminal positron emission tomography.
Brain
PUBLISHED: 05-09-2011
Show Abstract
Hide Abstract
We assessed the relationship between consensus clinical diagnostic classification and neurochemical positron emission tomography imaging of striatal vesicular monoamine transporters and cerebrocortical deposition of a?-amyloid in mild dementia. Seventy-five subjects with mild dementia (Mini-Mental State Examination score?18) underwent a conventional clinical evaluation followed by 11C-dihydrotetrabenazine positron emission tomography imaging of striatal vesicular monoamine transporters and 11C-Pittsburgh compound-B positron emission tomography imaging of cerebrocortical a?-amyloid deposition. Clinical classifications were assigned by consensus of an experienced clinician panel. Neuroimaging classifications were assigned as Alzheimers disease, frontotemporal dementia or dementia with Lewy bodies on the basis of the combined 11C-dihydrotetrabenazine and 11C-Pittsburgh compound-B results. Thirty-six subjects were classified clinically as having Alzheimers disease, 25 as having frontotemporal dementia and 14 as having dementia with Lewy bodies. Forty-seven subjects were classified by positron emission tomography neuroimaging as having Alzheimers disease, 15 as having dementia with Lewy bodies and 13 as having frontotemporal dementia. There was only moderate agreement between clinical consensus and neuroimaging classifications across all dementia subtypes, with discordant classifications in ?35% of subjects (Cohens ?=0.39). Discordant classifications were least frequent in clinical consensus Alzheimers disease (17%), followed by dementia with Lewy bodies (29%) and were most common in frontotemporal dementia (64%). Accurate clinical classification of mild neurodegenerative dementia is challenging. Though additional post-mortem correlations are required, positron emission tomography imaging likely distinguishes subgroups corresponding to neurochemically defined pathologies. Use of these positron emission tomography imaging methods may augment clinical classifications and allow selection of more uniform subject groups in disease-modifying therapeutic trials and other prospective research involving subjects in the early stages of dementia.
Related JoVE Video
Prognostic significance of neurologic examination findings in Wilson disease.
Parkinsonism Relat. Disord.
PUBLISHED: 05-02-2011
Show Abstract
Hide Abstract
Wilson disease patients present with any of several neurologic phenotypes, and their treated outcomes vary widely. Our goal was to determine whether presenting clinical features of neurologic Wilson disease (WD) predict longer term neurologic outcomes in patients receiving anticopper treatment.
Related JoVE Video
The maxillary sinus: challenges and treatments for implant placement.
Compend Contin Educ Dent
PUBLISHED: 04-06-2011
Show Abstract
Hide Abstract
Standard implant placement in the posterior maxilla is often limited by the lack of vertical bone height due to the pneumatization of the sinus cavity. Several techniques have been developed to enter this cavity and elevate the membrane to enable implant placement. These methods may involve the use of bone grafts and membranes, as well as concurrent implant placement. This article reviews the clinical situations in which to apply these sinus lift techniques, complications, and success rates.
Related JoVE Video
PPP2R1A mutations are common in the serous type of endometrial cancer.
Mol. Carcinog.
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
Recently unbiased sequencing efforts identified PPP2R1A mutations in clear cell ovarian cancers (OCC). Similar mutations were also noted with high frequency in uterine serous carcinoma. Because the endometrium develops from the same developmental precursors we further examined the hypothesis that PPP2R1A mutations might also occur in diverse histologic subtypes of uterine cancer. We sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary cancers. We found no mutations in the cell lines originally derived from endometrioid (n?=?13), undifferentiated (n?=?3), clear cell (n?=?1), and carcinosarcoma (n?=?3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon 179 mutation in the ACI-158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu) in a primary serous carcinoma as well as a CGC (Arg) to CAC (His) codon 258 mutation in a poorly differentiated endometrioid cancer. We sequenced a large panel of endometrial malignancies (n?=?181) and found 12 mutants. Importantly, we confirmed a high frequency of mutation in 8 of 25 (32%) serous carcinomas a subtype with well-recognized poor prognosis. Mutations were infrequent in endometrioid cancer and absent in clear cell and carcinosarcoma subtypes. The PPP2R1A mutation regions are conserved among species and known to interact with the regulatory subunits of the PP2A enzyme. PPP2R1A mutant endometrial cancers may represent good candidates for personalized drug therapies particularly for women with the lethal serous histologic variant of uterine cancer.
Related JoVE Video
Metabolomics in early Alzheimers disease: identification of altered plasma sphingolipidome using shotgun lipidomics.
PLoS ONE
PUBLISHED: 03-29-2011
Show Abstract
Hide Abstract
The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimers disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility.
Related JoVE Video
Incidence of dementia and cognitive impairment, not dementia in the United States.
Ann. Neurol.
PUBLISHED: 03-18-2011
Show Abstract
Hide Abstract
Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia and CIND.
Related JoVE Video
Acute care and long-term mortality among elderly patients with intracerebral hemorrhage who undergo chronic life-sustaining procedures.
J Stroke Cerebrovasc Dis
PUBLISHED: 03-17-2011
Show Abstract
Hide Abstract
Little is known about patients with intracerebral hemorrhage (ICH) who undergo chronic life-sustaining procedures. We sought to explore variations in treatment, Medicare payments, and mortality among elderly patients with ICH who received a feeding tube, a tracheostomy, or neither chronic life-sustaining procedure. Medicare Provider Analysis and Review files from 2004 linked to Center for Medicaid and Medicare Services denominator files through January 2005 were analyzed. Patients over age 65 years with a primary diagnosis of ICH based on discharge code (ICD-9-CM 431) were divided into those who underwent tracheostomy, those who underwent feeding tube placement but not tracheostomy, and those who underwent neither procedure. Thirty-day and 1-year survival rates were estimated using Kaplan-Meier methods. Among the 32,210 patients studied, 6% underwent feeding tube placement, and 2.5% underwent tracheostomy. Compared with the patients who did not undergo a chronic life-sustaining procedure, those who underwent tracheostomy had a longer length of stay (median, 25 days vs 4 days; P < .01) and greater Medicare spending (median, $81,479 vs $6,008; P < .01) during their initial hospitalization. The 30-day and 1-year cumulative mortality risks were 47% and 59%, respectively, in patients who did not undergo a chronic life-sustaining procedure, 21% and 53% in patients who underwent feeding tube placement, and 19% and 65% in those who underwent tracheostomy (P < .01, log-rank test across the 3 groups). Our findings show high 1-year mortality among elderly patients with ICH, even in those who undergo chronic life-sustaining procedures. Medicare payments for patients who undergo tracheostomy are substantial. More information about functional outcomes is needed.
Related JoVE Video
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimers disease.
Adam C Naj, Gyungah Jun, Gary W Beecham, Li-San Wang, Badri Narayan Vardarajan, Jacqueline Buros, Paul J Gallins, Joseph D Buxbaum, Gail P Jarvik, Paul K Crane, Eric B Larson, Thomas D Bird, Bradley F Boeve, Neill R Graff-Radford, Philip L De Jager, Denis Evans, Julie A Schneider, Minerva M Carrasquillo, Nilüfer Ertekin-Taner, Steven G Younkin, Carlos Cruchaga, John S K Kauwe, Petra Nowotny, Patricia Kramer, John Hardy, Matthew J Huentelman, Amanda J Myers, Michael M Barmada, F Yesim Demirci, Clinton T Baldwin, Robert C Green, Ekaterina Rogaeva, Peter St George-Hyslop, Steven E Arnold, Robert Barber, Thomas Beach, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Chris S Carlson, Regina M Carney, Steven L Carroll, Helena C Chui, David G Clark, Jason Corneveaux, Carl W Cotman, Jeffrey L Cummings, Charles DeCarli, Steven T DeKosky, Ramon Diaz-Arrastia, Malcolm Dick, Dennis W Dickson, William G Ellis, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Sid Gilman, Bruno Giordani, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Nancy Johnson, Jason Karlawish, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, James J Lah, Allan I Levey, Andrew P Lieberman, Oscar L Lopez, Wendy J Mack, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Joseph E Parisi, Daniel P Perl, Elaine Peskind, Ronald C Petersen, Wayne W Poon, Joseph F Quinn, Ruchita A Rajbhandary, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Roger N Rosenberg, Mary Sano, Lon S Schneider, William Seeley, Michael L Shelanski, Michael A Slifer, Charles D Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Randall L Woltjer, Laura B Cantwell, Beth A Dombroski, Duane Beekly, Kathryn L Lunetta, Eden R Martin, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Gerard D Schellenberg.
Nat. Genet.
PUBLISHED: 03-10-2011
Show Abstract
Hide Abstract
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimers disease susceptibility.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.