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.
Cranial and spinal oligodendrogliomatosis: a case report and review of the literature.
Childs Nerv Syst
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
Oligodendrogliomatosis is a rarely reported entity in literature associated with poor prognosis in terms of length and quality of life. In this paper, we describe oligodendrogliomatosis in a 15-year-old male who initially presented with altered mental status due to diabetic ketoacidosis.
Related JoVE Video
Evidence-based management of deep wound infection after spinal instrumentation.
J Clin Neurosci
PUBLISHED: 07-14-2014
Show Abstract
Hide Abstract
In this study, evidence-based medicine is used to assess optimal surgical and medical management of patients with post-operative deep wound infection following spinal instrumentation. A computerized literature search of the PubMed database was performed. Twenty pertinent studies were identified. Studies were separated into publications addressing instrumentation retention versus removal and publications addressing antibiotic therapy regimen. The findings were classified based on level of evidence (I-III) and findings were summarized into evidentiary tables. No level I or II evidence was identified. With regards to surgical management, five studies support instrumentation retention in the setting of early deep infection. In contrast, for delayed infection, the evidence favors removal of instrumentation at the time of initial debridement. Surgeons should be aware that for deformity patients, even if solid fusion is observed, removal of instrumentation may be associated with significant loss of correction. A course of intravenous antibiotics followed by long-term oral suppressive therapy should be pursued if instrumentation is retained. A shorter treatment course may be appropriate if hardware is removed.
Related JoVE Video
Use of candidate gene markers to guide antipsychotic dosage adjustment.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 05-23-2014
Show Abstract
Hide Abstract
To improve antipsychotic treatment in schizophrenia patients, many studies have investigated genetic polymorphisms associated with antipsychotic metabolizing enzymes and receptors. While these studies have typically focused on drug response, few have investigated genetic influences on antipsychotic dosage. This study set out to analyze the association between 134 SNPs in 38 candidate genes and antipsychotic dosage in schizophrenia patients.
Related JoVE Video
Minimally invasive lateral transpsoas approach to the lumbar spine: pitfalls and complication avoidance.
Neurosurg. Clin. N. Am.
PUBLISHED: 04-08-2014
Show Abstract
Hide Abstract
The lateral transpsoas approach to the lumbar spine has become an increasingly popular method to achieve fusion. Although this approach requires less tissue dissection, a smaller incision, decreased operative time, reduced blood loss and postoperative pain, and shorter hospital stay, it carries the potential for serious neurologic and visceral complications. This article reviews these complications in detail and proposes mechanisms for their avoidance.
Related JoVE Video
Induction of social behavior in zebrafish: live versus computer animated fish as stimuli.
Zebrafish
PUBLISHED: 02-27-2014
Show Abstract
Hide Abstract
The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish.
Related JoVE Video
Thoracic spinal cord intramedullary aspergillus invasion and abscess.
J Clin Neurosci
PUBLISHED: 02-21-2014
Show Abstract
Hide Abstract
Invasive central nervous system aspergillosis is a rare form of fungal infection that presents most commonly in immunocompromised individuals. There have been multiple previous reports of aspergillus vertebral osteomyelitis and spinal epidural aspergillus abscess; however to our knowledge there are no reports of intramedullary aspergillus infection. We present a 19-year-old woman with active acute lymphoblastic leukemia who presented with several weeks of fevers and bilateral lower extremity weakness. She was found to have an intramedullary aspergillus abscess at T12-L1 resulting from adjacent vertebral osteomyelitis and underwent surgical debridement with ultra-sound guided aspiration and aggressive intravenous voriconazole therapy. To our knowledge this is the first reported case of spinal aspergillosis invading the intramedullary cavity. Though rare, this entity should be included in the differential for immunocompromised patients presenting with fevers and neurologic deficit. Early recognition with aggressive neurosurgical intervention and antifungal therapy may improve outcomes in future cases.
Related JoVE Video
Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF): surgical technique, long-term 4-year prospective outcomes, and complications compared with an open TLIF cohort.
Neurosurg. Clin. N. Am.
PUBLISHED: 02-18-2014
Show Abstract
Hide Abstract
Transforaminal lumbar interbody fusion (TLIF) is an important surgical option for the treatment of back pain and radiculopathy. The minimally invasive TLIF (MI-TLIF) technique is increasingly used to achieve neural element decompression, restoration of segmental alignment and lordosis, and bony fusion. This article reviews the surgical technique, outcomes, and complications in a series of 144 consecutive 1- and 2-level MI-TLIFs in comparison with an institutional control group of 54 open traditional TLIF procedures with a mean of 46 months' follow-up. The evidence base suggests that MI-TLIF can be performed safely with excellent long-term outcomes.
Related JoVE Video
Complications associated with posterior approaches in minimally invasive spine decompression.
Neurosurg. Clin. N. Am.
PUBLISHED: 01-25-2014
Show Abstract
Hide Abstract
Posterior approaches for decompression in minimally invasive spine surgery are increasingly used for a wide range of pathology. Surgeons and patients must understand these risks in order to identify, manage, and ideally prevent complications. Technical intraoperative complications, recurrences and reoperations, infections, and medical complications associated with the surgery are considered for common posterior minimally invasive decompression procedures of the cervical and lumbar spine. Methods of possibly avoiding these complications are also discussed. This article then aggregates the relevant data to allow concise understanding of the complications associated with these procedures.
Related JoVE Video
Bilateral neurological deficits following unilateral minimally invasive TLIF: A review of four patients.
Surg Neurol Int
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is commonly used for the treatment of degenerative lumbar spinal disorders. The rate of postoperative neurological deficits is traditionally low. New neurological postoperative complications may be underreported. We report our infrequent rate of MI-TLIF procedures complicated by postoperative weakness.
Related JoVE Video
Isolation and functional analysis of CONSTANS-LIKE genes suggests that a central role for CONSTANS in flowering time control is not evolutionarily conserved in Medicago truncatula.
Front Plant Sci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The zinc finger transcription factor CONSTANS has a well-established central role in the mechanism for photoperiod sensing in Arabidopsis, integrating light and circadian clock signals to upregulate the florigen gene FT under long-day but not short-day conditions. Although CONSTANS-LIKE (COL) genes in other species have also been shown to regulate flowering time, it is not clear how widely this central role in photoperiod sensing is conserved. Legumes are a major plant group and various legume species show significant natural variation for photoperiod responsive flowering. Orthologs of several Arabidopsis genes have been shown to participate in photoperiodic flowering in legumes, but the possible function of COL genes as integrators of the photoperiod response has not yet been examined in detail. Here we characterize the COL family in the temperate long-day legume Medicago truncatula, using expression analyses, reverse genetics, transient activation assays and Arabidopsis transformation. Our results provide several lines of evidence suggesting that COL genes are unlikely to have a central role in the photoperiod response mechanism in this species.
Related JoVE Video
Ligand-gated ion channel interacting proteins and their role in neuroprotection.
Front Cell Neurosci
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Ion channel receptors are a vital component of nervous system signaling, allowing rapid and direct conversion of a chemical neurotransmitter message to an electrical current. In recent decades, it has become apparent that ionotropic receptors are regulated by protein-protein interactions with other ion channels, G-protein coupled receptors and intracellular proteins. These other proteins can also be modulated by these interactions with ion channel receptors. This bidirectional functional cross-talk is important for critical cellular functions such as excitotoxicity in pathological and disease states like stroke, and for the basic dynamics of activity-dependent synaptic plasticity. Protein interactions with ion channel receptors can therefore increase the computational capacity of neuronal signaling cascades and also represent a novel target for therapeutic intervention in neuropsychiatric disease. This review will highlight some examples of ion channel receptor interactions and their potential clinical utility for neuroprotection.
Related JoVE Video
Targeting a Glioblastoma Cancer Stem Cell Population Defined by EGF Receptor Variant III.
Cancer Res.
PUBLISHED: 12-23-2013
Show Abstract
Hide Abstract
The relationship between mutated proteins and the cancer stem cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is highly co-expressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells with the highest degree of self-renewal and tumor initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers while markers of differentiation are found in EGFRvIII- cells. EGFRvIII expression is lost in standard cell culture but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ co-expression and self-renewal and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population.
Related JoVE Video
Risk factors and long-term survival in adult patients with primary malignant spinal cord astrocytomas.
J. Neurooncol.
PUBLISHED: 10-26-2013
Show Abstract
Hide Abstract
Primary intramedullary spinal cord tumors are a rare entity, comprising 4–10 %of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973–2008), and evaluates the impact of demographic and treatment factors on survival. Eighty nine adults were evaluated (mean age of 43 years); 49 % of patients had anaplastic astrocytoma and 51 % of patients had glioblastoma.88 % of patients had surgical intervention and 85 % of patients had radiotherapy. In univariate analysis, male gender (HR = 0.50, CI: 0.29–0.86, P = 0.01), surgical treatment (HR = 0.37, CI: 0.15–0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06–3.18, P = 0.03) were significant predictors of survival. Results remained significant or marginally significant after multivariate adjustment analyses. Adjuvant radiotherapy and age at diagnosis did not have a significant influence on survival. Future prospective studies from collaborative institutions combining richer detail in perioperative treatment, radiotherapy dosing, chemotherapy treatment, neurologic examinations, functional outcomes, and quality of life measures would contribute to more concrete, evidence-based treatment protocols for adult patients with primary malignant spinal cord astrocytomas.
Related JoVE Video
Comparison of Symptomatic Cerebral Spinal Fluid Leak Between Patients Undergoing Minimally Invasive versus Open Lumbar Foraminotomy, Discectomy, or Laminectomy.
World Neurosurg
PUBLISHED: 09-10-2013
Show Abstract
Hide Abstract
Minimally invasive spine surgery (MISS) techniques have similar long-term outcomes compared to open surgery for patients undergoing 1- or 2-level discectomy, foraminotomy, or laminectomy. However, the rate of cerebrospinal fluid (CSF) leaks with both techniques has not been well established in the literature. This study sought to compare the rate and clinical impact of CSF leak in open lumbar foraminotomy, discectomy, or laminectomy with comparable MISS approaches.
Related JoVE Video
Determinants and protective behaviours regarding tick bites among school children in the Netherlands: a cross-sectional study.
BMC Public Health
PUBLISHED: 08-29-2013
Show Abstract
Hide Abstract
Lyme borreliosis (LB) is the most common tick-borne disease in the United States and Europe. The incidence is 13.4 per 100,000 inhabitants in the United States and more than 300 per 100,000 inhabitants in Europe. Children are at highest risk of LB. In the Netherlands in 2007, the incidence of tick bites in children between 10-14 years varied from 7,000 -11,000 per 100,000, depending on age. This study among Dutch school children aimed to examine the knowledge, perceived threat, and perceived importance of protective behaviour in relation to tick bites and their potential consequences.
Related JoVE Video
Outcome following unilateral versus bilateral instrumentation in patients undergoing minimally invasive transforaminal lumbar interbody fusion: a single-center randomized prospective study.
Neurosurg Focus
PUBLISHED: 08-03-2013
Show Abstract
Hide Abstract
Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is used to treat a wide variety of lumbar degenerative disorders. Although there are some reports showing efficacy of unilateral instrumentation during MIS-TLIF, a controlled randomized prospective study has not been done.
Related JoVE Video
The Effect of Surgical Level on Self-Reported Clinical Outcomes After Minimally Invasive Transforaminal Lumbar Interbody Fusion: L4-L5 Versus L5-S1.
World Neurosurg
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
The anatomic and biomechanical aspects of the L5-S1 level present unique operative challenges compared with the L4-L5 level. However, it has not been determined if self-reported outcomes and complications are different between patients treated with a minimally invasive transforaminal lumbar interbody fusion at these specific levels.
Related JoVE Video
Minimally invasive thoracic decompression for multi-level thoracic pathologies.
J Clin Neurosci
PUBLISHED: 07-15-2013
Show Abstract
Hide Abstract
We describe our experience using a minimal access approach for multi-level dorsal decompression of the thoracic spine that may limit approach-related soft-tissue injury and spinal destabilization. Additionally, three patients, each with unique compressive thoracic pathology, are discussed. A single minimal access technique, using multi-level hemilaminotomies, was used to address these unique pathologies via a similar approach. The three patients in this study had a mean age of 49.3years (range: 45-55years), mean estimated blood loss of 750cc (range: 350-1000cc), mean operative time of 3.8hours (range: 3-5hours), and a mean post-operative hospital stay of 2.3days (range: 2-3days). Complete decompression was achieved with resolution of symptoms in all patients. Long-term follow-up averaged 26.7months (range: 15-36months). Radiographic decompression was demonstrated in all patients. Minimal access techniques using muscle-splitting tubular retractor systems can effectively treat multi-level dorsal compression of the thoracic cord, while potentially limiting morbidity and long-term spinal instability.
Related JoVE Video
Microendoscopic decompression for cervical spondylotic myelopathy.
Neurosurg Focus
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
Cervical spondylotic myelopathy (CSM) is a common cervical degenerative disease that affects the elderly population. Spinal cord decompression is achieved through various anterior and posterior approaches including anterior cervical decompression and fusion, laminectomy, laminoplasty, and combined approaches. The authors describe another option, minimally invasive endoscopically assisted decompression of stenosis (MEDS), which obviates the need for muscle dissection and disruption of the posterior tension band, a cause of postlaminectomy kyphosis.
Related JoVE Video
Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice.
J. Neurosci.
PUBLISHED: 05-03-2013
Show Abstract
Hide Abstract
Schizophrenia is thought to result from interactions between susceptible genotypes and environmental risk factors. DISC1 is an important gene for schizophrenia and mood disorders based on both human and animal studies. In the present study we sought to investigate interactions between two distinct point mutations in the mouse Disc1 gene (L100P and Q31L) and maternal immune activation (MIA) during pregnancy with polyinosinic:polycytidylic acid (polyI:C). PolyI:C given at 5 mg/kg impaired cognitive and social behavior in both wild-type (WT) and Disc1-Q31L(+/-) offspring, and reduced prepulse inhibition at 16 but not 8 weeks of age. Disc1-L100P(+/-) mutants were more sensitive to MIA than WT or Disc1-Q31L(+/-) mice. Interleukin-6 (IL-6) is a critical cytokine for mediating the behavioral and transcriptional effects of polyI:C. We found a more pronounced increase of IL-6 in response to polyI:C in fetal brain in Disc1-L100P(+/-) mice compared with WT or Disc1-Q31L(+/-) mice. Coadministration of an anti-IL-6 antibody with polyI:C reversed schizophrenia-related behavioral phenotypes in Disc1-L100P(+/-) mice. In summary, we found specific interactions between discrete genetic (Disc1-L100P(+/-)) and environmental factors (MIA) that exacerbate schizophrenia-related phenotypes. IL-6 may be important in the pathophysiology of this interaction.
Related JoVE Video
Analysis of CpG SNPs in 34 genes: association test with suicide attempt in schizophrenia.
Schizophr. Res.
PUBLISHED: 04-13-2013
Show Abstract
Hide Abstract
Suicide is the act of intentionally causing ones own death. The lifetime suicide risk in schizophrenia is 4.9% and 20% to 50% of patients with SCZ will attempt suicide during their life. The other risk factors for suicidal behavior in schizophrenia include prior history of suicide attempts, active psychosis, depression and substance abuse. To date, there are no robust genetic or epigenetic predictors of suicide or suicide attempt in this specific population.
Related JoVE Video
Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.
PLoS Genet.
PUBLISHED: 04-01-2013
Show Abstract
Hide Abstract
Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a "breakpoint analysis" pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis.
Related JoVE Video
Using rodents to model schizophrenia and substance use comorbidity.
Neurosci Biobehav Rev
PUBLISHED: 03-28-2013
Show Abstract
Hide Abstract
Schizophrenia and substance use disorders (SUD) often occur together, yet it is unclear why this is the case or how best to manage dual diagnosis. Rodent models are well suited to study how genes and environment interact to impact neurodevelopment, brain function and behaviors relevant to dual diagnosis. Indeed a variety of rodent models for schizophrenia display behavioral and physiological features relevant to SUD including: neurodevelopmental models, models of a rare variant (Disc1), to models of common variants (neurexin, dysbindin and neuregulin), and models of various gene-drug interactions. Thus it may be worthwhile to probe models of schizophrenia for insights relevant to SUD and dual diagnosis. However, future studies on dual diagnosis should involve characterization beyond measuring locomotor responses to self-administration tasks, include drug classes other than psychostimulants, and dissect the neuroadaptations that underlie risk for dual diagnosis.
Related JoVE Video
Risk factors and long-term survival in adult patients with primary malignant spinal cord astrocytomas.
J. Neurooncol.
PUBLISHED: 03-19-2013
Show Abstract
Hide Abstract
Primary intramedullary spinal cord tumors are a rare entity, comprising 4-10 % of all spinal cord tumors. The current report presents data on intramedullary spinal cord anaplastic astrocytomas and glioblastomas in adults using the national surveillance, epidemiology, and end results database (1973-2008), and evaluates the impact of demographic and treatment factors on survival. Eighty nine adults were evaluated (mean age of 43 years); 49 % of patients had anaplastic astrocytoma and 51 % of patients had glioblastoma. 88 % of patients had surgical intervention and 85 % of patients had radiotherapy. In univariate analysis, male gender (HR = 0.50, CI: 0.29-0.86, P = 0.01), surgical treatment (HR = 0.37, CI: 0.15-0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06-3.18, P = 0.03) were significant predictors of survival. Results remained significant or marginally significant after multivariate adjustment analyses. Adjuvant radiotherapy and age at diagnosis did not have a significant influence on survival. Future prospective studies from collaborative institutions combining richer detail in perioperative treatment, radiotherapy dosing, chemotherapy treatment, neurologic examinations, functional outcomes, and quality of life measures would contribute to more concrete, evidence-based treatment protocols for adult patients with primary malignant spinal cord astrocytomas.
Related JoVE Video
Abnormal interneuron development in disrupted-in-schizophrenia-1 L100P mutant mice.
Mol Brain
PUBLISHED: 03-19-2013
Show Abstract
Hide Abstract
Interneuron deficits are one of the most consistent findings in post-mortem studies of schizophrenia patients and are likely important in the cognitive deficits associated with schizophrenia. Disrupted-in-Schizophrenia 1 (DISC1), a strong susceptibility gene for schizophrenia and other mental illnesses, is involved in neurodevelopment, including that of interneurons. However, the mechanism by which DISC1 regulates interneuron development remains unknown. In this study, we analyzed interneuron histology in the Disc1-L100P single point mutation mouse, that was previously shown to have behavioral abnormalities and cortical developmental defects related to schizophrenia.
Related JoVE Video
Persistent mental health disturbances during the 10 years after a disaster: four-wave longitudinal comparative study.
Psychiatry Clin. Neurosci.
PUBLISHED: 02-27-2013
Show Abstract
Hide Abstract
Although some studies have examined the long-term effects of disasters, very little is known about severe persistent symptoms following disasters. The aim of the present study was to examine persistent mental health problems and to what extent disaster exposure predicts long-term persistent disturbances.
Related JoVE Video
Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma.
J Hematol Oncol
PUBLISHED: 02-19-2013
Show Abstract
Hide Abstract
Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain.
Related JoVE Video
Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation.
Front Behav Neurosci
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia and that would also complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogs. Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience, and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position. Results: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets, and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively) with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning. Conclusion: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.
Related JoVE Video
Measuring surgical outcomes in cervical spondylotic myelopathy patients undergoing anterior cervical discectomy and fusion: assessment of minimum clinically important difference.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
The concept of minimum clinically important difference (MCID) has been used to measure the threshold by which the effect of a specific treatment can be considered clinically meaningful. MCID has previously been studied in surgical patients, however few studies have assessed its role in spinal surgery. The goal of this study was to assess the role of MCID in patients undergoing anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM).
Related JoVE Video
The disabling effect of diseases: a study on trends in diseases, activity limitations, and their interrelationships.
Am J Public Health
PUBLISHED: 11-28-2011
Show Abstract
Hide Abstract
Data from the Netherlands indicate a recent increase in prevalence of chronic diseases and a stable prevalence of disability, suggesting that diseases have become less disabling. We studied the association between chronic diseases and activity limitations in the Netherlands from 1990 to 2008.
Related JoVE Video
Medical innovation and age-specific trends in health care utilization: findings and implications.
Soc Sci Med
PUBLISHED: 10-22-2011
Show Abstract
Hide Abstract
Health care utilization is expected to rise in the coming decades. Not only will the aggregate need for health care grow by changing demographics, so too will per capita utilization. It has been suggested that trends in health care utilization may be age-specific. In this paper, age-specific trends in health care utilization are presented for different health care sectors in the Netherlands, for the period 1981-2009. For the hospital sector we also explore the link between these trends and the state of medical technology. Using aggregated data from a Dutch health survey and a nationwide hospital register, regression analysis was used to examine age-specific trends in the probability of utilizing health care. To determine the influence of medical technology, the growth in age-specific probabilities of hospital care was regressed on the number of medical patents while adjusting for confounders related to demographics, health status, supply and institutional factors. The findings suggest that for most health care sectors, the trend in the probability of health care utilization is highest for ages 65 and up. Larger advances in medical technology are found to be significantly associated with a higher growth of hospitalization probability, particularly for the higher ages. Age-specific trends will raise questions on the sustainability of intergenerational solidarity in health care, as solidarity will not only be strained by the ageing population, but also might find itself under additional pressure as the gap in health care utilization between elderly and non-elderly grows over time. For hospital care utilization, this process might well be accelerated by advances in medical technology.
Related JoVE Video
Case report: anxiety and fear in a patient with meningioma compressing the left amygdala.
Neurocase
PUBLISHED: 10-20-2011
Show Abstract
Hide Abstract
The amygdalae are an important part of fear and anxiety circuits in the mammalian brain, involved in the encoding and storage of fear memories. In this case report we discuss a 26-year-old male patient with a temporal lobe meningioma that presented with unilateral abducens palsy, deep-seated headaches, and persistent psychiatric symptoms including depression and anticipatory anxiety. The patients psychiatric symptoms and clinical diagnosis provided the impetus for the eventual diagnostic imaging and discovery of the intracranial lesion.
Related JoVE Video
Hypnosis in the laboratory creates a window on psychopathology.
Int J Clin Exp Hypn
PUBLISHED: 08-27-2011
Show Abstract
Hide Abstract
The authors describe 3 studies in which hypnosis itself is not studied but instead used to create anomalous states in the laboratory that can be studied under controlled conditions. The 1st article is a comprehensive review of programmatic research using hypnosis to elicit and study clinically relevant delusions. The 2nd article reviews studies comparing the brain activity of hysterical/dissociative patients with nonpatients hypnotized and given suggestions for sensory-motor and cognitive anomalies typical of the clinical syndromes. The authors conclude that the hypnosis analogues are relevant and revealing. The 3rd article describes a single experiment using hypnosis to elicit distressing and intrusive memories, typical of acute anxiety disorders. Findings with hypnotic subjects are in keeping with those from patients suffering intrusive memories. Across all 3 papers, hypnosis is shown to be a viable and helpful tool for experimental psychopathology.
Related JoVE Video
The role of BDNF in the pathophysiology and treatment of schizophrenia.
J Psychiatr Res
PUBLISHED: 07-09-2011
Show Abstract
Hide Abstract
Brain derived neurotrophic factor (BDNF) has been associated with the pathophysiology of schizophrenia (SCZ). However, it remains unclear whether alterations in BDNF observed in patients with SCZ are a core part of disease neurobiology or a consequence of treatment. In this manuscript we review existing knowledge relating the function of BDNF to synaptic transmission and neural plasticity and the relationship between BDNF and both pharmacological and non-pharmacological treatments for SCZ. With regards to synaptic transmission, exposure to BDNF or lack of this neurotrophin results in alteration to both excitatory and inhibitory synapses. Many authors have also evaluated the effects of both pharmacological and non-pharmacological treatments for SCZ in BDNF and despite some controversial results, it seems that medicated and non-medicated patients present with lower levels of BDNF when compared to controls. Further data suggests that typical antipsychotics may decrease BDNF expression whereas mixed results have been obtained with atypical antipsychotics. The authors found few studies reporting changes in BDNF after non-pharmacological treatments for SCZ, so the existing evidence in this area is limited. Although the study of BDNF provides some new insights into understanding of the pathophysiology and treatment of SCZ, additional work in this area is needed.
Related JoVE Video
Standardizing the inclusion of indirect medical costs in economic evaluations.
Pharmacoeconomics
PUBLISHED: 06-08-2011
Show Abstract
Hide Abstract
A shortcoming of many economic evaluations is that they do not include all medical costs in life-years gained (also termed indirect medical costs). One of the reasons for this is the practical difficulties in the estimation of these costs. While some methods have been proposed to estimate indirect medical costs in a standardized manner, these methods fail to take into account that not all costs in life-years gained can be estimated in such a way. Costs in life-years gained caused by diseases related to the intervention are difficult to estimate in a standardized manner and should always be explicitly modelled. However, costs of all other (unrelated) diseases in life-years gained can be estimated in such a way. We propose a conceptual model of how to estimate costs of unrelated diseases in life-years gained in a standardized manner. Furthermore, we describe how we estimated the parameters of this conceptual model using various data sources and studies conducted in the Netherlands. Results of the estimates are embedded in a software package called Practical Application to Include future Disease costs (PAID 1.0). PAID 1.0 is available as a Microsoft® Excel tool (available as Supplemental Digital Content via a link in this article) and enables researchers to switch off those disease categories that were already included in their own analysis and to estimate future healthcare costs of all other diseases for incorporation in their economic evaluations. We assumed that total healthcare expenditure can be explained by age, sex and time to death, while the relationship between costs and these three variables differs per disease. To estimate values for age- and sex-specific per capita health expenditure per disease and healthcare provider stratified by time to death we used Dutch cost-of-illness (COI) data for the year 2005 as a backbone. The COI data consisted of age- and sex-specific per capita health expenditure uniquely attributed to 107 disease categories and eight healthcare provider categories. Since the Dutch COI figures do not distinguish between costs of those who die at a certain age (decedents) and those who survive that age (survivors), we decomposed average per capita expenditure into parts that are attributable to decedents and survivors, respectively, using other data sources.
Related JoVE Video
BTI1, an azoreductase with pH-dependent substrate specificity.
Appl. Environ. Microbiol.
PUBLISHED: 04-29-2011
Show Abstract
Hide Abstract
The group II azoreductase BTI1 utilizes NADPH to directly cleave azo bonds in water-soluble azo dyes, including quenchers of fluorescence. Unexpectedly, optimal reduction was dye specific, ranging from a pH of <5.5 for Janus green B, to pH 6.0 for methyl red, methyl orange, and BHQ-10, to pH >8.3 for flame orange.
Related JoVE Video
Longitudinal administrative data can be used to examine multimorbidity, provided false discoveries are controlled for.
J Clin Epidemiol
PUBLISHED: 03-31-2011
Show Abstract
Hide Abstract
This article presents methods for using administrative data to study multimorbidity in hospitalized individuals and indicates how the findings can be used to gain a deeper understanding of hospital multimorbidity.
Related JoVE Video
Finasteride-associated cataract and intraoperative floppy-iris syndrome.
J Cataract Refract Surg
PUBLISHED: 03-15-2011
Show Abstract
Hide Abstract
A 47-year-old man who had been using finasteride for male pattern alopecia for 4 years complained of progressive bilateral blurring of vision. His general health had been good, and he was not on any other long-term medication. Examination showed bilateral anterior subcapsular cataracts. Phacoemulsification and insertion of intraocular lenses were performed, and both eyes showed features of intraoperative floppy-iris syndrome (IFIS), including undulation and billowing of the iris, iris prolapse, and pupil constriction. We believe the use of finasteride can be associated with cataract formation and IFIS. Ophthalmologists and physicians prescribing finasteride should be aware of this possible association.
Related JoVE Video
Disc1 point mutations in mice affect development of the cerebral cortex.
J. Neurosci.
PUBLISHED: 03-04-2011
Show Abstract
Hide Abstract
Disrupted-in-Schizophrenia 1 (DISC1) is a strong candidate gene for schizophrenia and other mental disorders. DISC1 regulates neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth, and neurotransmitter signaling. Abnormal neuronal morphology and cortical architecture are seen in human postmortem brain from patients with schizophrenia. However, the etiology and development of these histological abnormalities remain unclear. We analyzed the histology of two Disc1 mutant mice with point mutations (Q31L and L100P) and found a relative reduction in neuron number, decreased neurogenesis, and altered neuron distribution compared to wild-type littermates. Frontal cortical neurons have shorter dendrites and decreased surface area and spine density. Overall, the histology of Disc1 mutant mouse cortex is reminiscent of the findings in schizophrenia. These results provide further evidence that Disc1 participates in cortical development, including neurogenesis and neuron migration.
Related JoVE Video
Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-01-2011
Show Abstract
Hide Abstract
Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.
Related JoVE Video
Complications of open compared to minimally invasive lumbar spine decompression.
J Clin Neurosci
PUBLISHED: 02-16-2011
Show Abstract
Hide Abstract
Minimally invasive modalities have demonstrated efficacy in the treatment of neurogenic claudication. Direct comparisons, however, between complication rates of these newer techniques with open surgical techniques for lumbar decompression are lacking. This single-institution study examined neurogenic claudicants between August 2007 and June 2009. A total of 26 patients received open surgical decompression, and 23 patients microendoscopic decompression. Baseline demographic characteristics, peri-operative morbidity and mortality, length of hospital stay, and final disposition following hospitalization were recorded. Morbidity was divided into major and minor categories as defined by degree of requisite intervention and adverse impact on hospital stay. Average age, number of surgical levels, and pre-operative American Society of Anesthesiologists Physical Status Index scores were similar in each group (p>0.05). While minimally invasive surgery may be associated with slightly longer operative times, there is decreased blood loss, shorter hospital stays, and likely decreased requirements for ancillary support services upon discharge.
Related JoVE Video
Malignant eyelid tumors in Hong Kong 1997-2009.
Jpn. J. Ophthalmol.
PUBLISHED: 02-15-2011
Show Abstract
Hide Abstract
To determine the epidemiologic and clinical characteristics of patients with malignant eyelid tumors in Hong Kong.
Related JoVE Video
Trends in activity limitations: the Dutch older population between 1990 and 2007.
Int J Epidemiol
PUBLISHED: 02-15-2011
Show Abstract
Hide Abstract
It is not clear whether recent increases in life expectancy are accompanied by a concurrent postponement of activity limitations. The objective of this study was to give best estimates of the trend in the prevalence of activity limitations among the non-institutionalized population aged 55-84 years over the period 1990-2007 in The Netherlands.
Related JoVE Video
Genetic inactivation of GSK3? rescues spine deficits in Disc1-L100P mutant mice.
Schizophr. Res.
PUBLISHED: 02-01-2011
Show Abstract
Hide Abstract
Disrupted-in-Schizophrenia 1 (DISC1), a strong candidate gene for schizophrenia and other mental disorders, regulates neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth and spine development. Glycogen synthase kinase-3 (GSK3) directly interacts with DISC1 and also plays a role in neurodevelopment. Recently, our group showed that the Disc1-L100P mutant protein has reduced interaction with both GSK3? and ?. Genetic and pharmacological inhibition of GSK3 activity rescued behavioral abnormalities in Disc1-L100P mutant mice. However, the cellular mechanisms mediating these effects of GSK3 inhibition in Disc1 mutant mice remain unclear. We sought to investigate the effects of genetic inactivation of GSK3? on frontal cortical neuron morphology in Disc1 L100P mutant mice using Golgi staining. We found a significant decrease in dendritic length and surface area in Disc1-L100P, GSK3? null and L100P/GSK3? double mutants. Dendritic spine density was significantly reduced only in Disc1-L100P and L100P/GSK3? +/- mice when compared to wild-type littermates. There was no difference in dendritic arborization between the various genotypes. No significant rescue in dendritic length and surface area was observed in L100P/GSK3? mutants versus L100P mice, but spine density in L100P/GSK3? mice was comparable to wild-type. Neurite outgrowth and spine development abnormalities induced by Disc1 mutation may be partially corrected through GSK3? inactivation, which also normalizes behavior. However, many of the other dendritic abnormalities in the Disc1-L100P mutant mice were not corrected by GSK3? inactivation, suggesting that only some of the anatomical defects have observable behavioral effects. These findings suggest novel treatment approaches for schizophrenia, and identify a histological read-out for testing other therapeutic interventions.
Related JoVE Video
Parent of origin effect and allelic expression imbalance of the serotonin transporter in bipolar disorder and suicidal behaviour.
Eur Arch Psychiatry Clin Neurosci
PUBLISHED: 01-19-2011
Show Abstract
Hide Abstract
Suicide and suicidal behaviour are a major health concern worldwide particularly in patients with mood disorders. Family, adoption and twin studies show that genetics influences suicidal behaviour. The serotonin transporter (5HTT) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since 5HTT binding is decreased in the brain of suicide completers. Because the effect of genomic imprinting in the 5HTT gene on suicidal behaviour has not been investigated, we analysed the parent-of-origin effect (POE) of four 5HTT markers and the differential expression of the 5HTT G2651T (rs1042173) alleles in suicide attempters affected by bipolar disorder. We performed a family based association study and ETDT/QTDT analyses of the rs25531, HTTLPR, VNTR-2 and G2651T polymorphisms in 312 nuclear families with at least one subject affected by bipolar disorder. The main outcomes investigated in this study are bipolar disorder diagnosis, suicide attempts, suicidal behaviour severity and age at onset of bipolar disorder. We also compared the allele-specific mRNA levels in lymphoblastoid cells from 13 bipolar suicide attempters and 8 bipolar non-suicide attempters. Allele 2651T was transmitted significantly more often to bipolar patients (P = 0.042). There was no significant difference between maternal and paternal transmission ratios. Furthermore, there was no significant difference in the ratio of T/G-specific mRNA expression between bipolar attempters and non-attempters. These data do not support a role for differential allelic expression of 5HTT for suicidal behaviour in bipolar disorder. Small sample size and the fact that RNA was obtained from lymphoblastoid cell lines were some of the limitations of this study.
Related JoVE Video
Contributions of the D-serine pathway to schizophrenia.
Neuropharmacology
PUBLISHED: 01-16-2011
Show Abstract
Hide Abstract
The glutamate neurotransmitter system is one of the major candidate pathways for the pathophysiology of schizophrenia, and increased understanding of the pharmacology, molecular biology and biochemistry of this system may lead to novel treatments. Glutamatergic hypofunction, particularly at the NMDA receptor, has been hypothesized to underlie many of the symptoms of schizophrenia, including psychosis, negative symptoms and cognitive impairment. This review will focus on D-serine, a co-agonist at the NMDA receptor that in combination with glutamate, is required for full activation of this ion channel receptor. Evidence implicating D-serine, NMDA receptors and related molecules, such as D-amino acid oxidase (DAO), G72 and serine racemase (SRR), in the etiology or pathophysiology of schizophrenia is discussed, including knowledge gained from mouse models with altered D-serine pathway genes and from preliminary clinical trials with D-serine itself or compounds modulating the D-serine pathway. Abnormalities in D-serine availability may underlie glutamatergic dysfunction in schizophrenia, and the development of new treatments acting through the D-serine pathway may significantly improve outcomes for many schizophrenia patients.
Related JoVE Video
Using molecular epidemiology to trace transmission of nosocomial norovirus infection.
J. Clin. Microbiol.
PUBLISHED: 12-15-2010
Show Abstract
Hide Abstract
Nosocomial norovirus (NoV) infection is common and may lead to complications in vulnerable hospitalized patients. Understanding sources and modes of transmission of noroviruses within health care settings will support the design of evidence-based strategies for reducing introduction and further spread. We sequenced a highly variable segment of the genome to identify possible clusters in patients with and without acute gastroenteritis who were hospitalized in the period 2002-2007. Admission and sampling dates were used to separate patients with nosocomial infection from those without nosocomial infection. Epidemiological clustering retrieved 22 clusters, defined as ? 2 patients with nosocomial infection on the same ward within 5 days. In total, 264 patients (of 2,458 tested) were diagnosed with NoV infection, and 61% of the patient strains could be genotyped. Of those, 51% (n = 82) belonged to GII.4, 34% (n = 54) belonged to GII.3, and 15% (n = 24) belonged to other genotypes (GI.6B, GII.17, GII.7, and GII.2). In childrens wards, GII.3 strains were associated with nosocomial spread more often than other viruses were, whereas in adults this was the case for GII.4 strains. Sequence alignment recognized 11 new clusters based on identical P2 domains (4 GII.3 and 7 GII.4 clusters), involving patients in different wards. This increased the total number of recognized clusters by 50%. Five of these clusters involved at least one outpatient, providing a possible target for improvement of infection control. We concluded that the use of sequence-based typing should be considered for identifying hidden nosocomial clusters of NoV infections within health care settings.
Related JoVE Video
Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme.
Curr. Opin. Mol. Ther.
PUBLISHED: 12-15-2010
Show Abstract
Hide Abstract
Celldex Therapeutics is developing rindopepimut (CDX-110), a 14-mer injectable peptide vaccine for the potential treatment of glioblastoma multiforme (GBM). Rindopepimut specifically targets a novel junctional epitope of the EGFR deletion mutant EGFRvIII, which is a constitutively active receptor that is expressed in approximately 60 to 70% of patients with GBM. EGFRvIII expression is correlated with worse prognosis and reduced overall survival. Importantly, EGFRvIII is not expressed in normal brain tissue, making it an excellent therapeutic target. Preclinical studies demonstrated lasting tumor regression and increased survival times, as well as efficient generation of EGFRvIII-specific humoral and cellular immune responses, in animals expressing EGFRvIII and vaccinated with rindopepimut. Phase I and II clinical trials in patients with GBM demonstrated significantly increased median time to progression and overall survival time in those vaccinated with rindopepimut compared with matched historical controls. Only limited side effects have been observed in patients. Given these results, rindopepimut is an extremely promising therapy for patients with GBM. Phase I and II clinical trials in patients with GBM were ongoing at the time of publication. In the future, it may be beneficial to combine rindopepimut with other treatment modalities to further prolong survival.
Related JoVE Video
Measuring the constitutive activation of c-Jun N-terminal kinase isoforms.
Meth. Enzymol.
PUBLISHED: 11-02-2010
Show Abstract
Hide Abstract
The c-Jun N-terminal kinases (JNK) are important regulators of cell growth, proliferation, and apoptosis. JNKs are typically activated by a sequence of events that include phosphorylation of its T-P-Y motif by an upstream kinase, followed by homodimerization and translocation to the nucleus. Constitutive activation of JNK has been found in a variety of cancers including non-small cell lung carcinomas, gliomas, and mantle cell lymphoma. In vitro studies show that constitutive activation of JNK induces a transformed phenotype in fibroblasts and enhances tumorigenicity in a variety of cell lines. Interestingly, a subset of JNK isoforms was recently found to autoactivate rendering the proteins constitutively active. These constitutively active JNK proteins were found to play a pivotal role in activating transcription factors that increase cellular growth and tumor formation in mice. In this chapter, we describe techniques and methods that have been successfully used to study the three components of JNK activation. Use of these techniques may lead to a better understanding of the components of JNK pathways and how JNK is activated in cancer cells.
Related JoVE Video
Successful treatment of Pseudallescheria boydii keratitis with topical natamycin as monotherapy.
J Ocul Pharmacol Ther
PUBLISHED: 10-08-2010
Show Abstract
Hide Abstract
To report a case of Pseudallescheria boydii keratitis successfully treated with topical natamycin as monotherapy.
Related JoVE Video
Parent of origin effect and differential allelic expression of BDNF Val66Met in suicidal behaviour.
World J. Biol. Psychiatry
PUBLISHED: 08-23-2010
Show Abstract
Hide Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since BDNF levels are decreased in brain and plasma of suicide victims. Because the differential allelic expression of Val66Met BDNF gene on suicidal behaviour has not been investigated, we analyzed the parent-of-origin effect (POE) in suicide attempters and the differential expression of BDNF Val66Met alleles in suicide victims.
Related JoVE Video
Development of an EGFRvIII specific recombinant antibody.
BMC Biotechnol.
PUBLISHED: 06-09-2010
Show Abstract
Hide Abstract
EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM), breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community.
Related JoVE Video
Predictors of long-term care utilization by Dutch hospital patients aged 65+.
BMC Health Serv Res
PUBLISHED: 05-06-2010
Show Abstract
Hide Abstract
Long-term care is often associated with high health care expenditures. In the Netherlands, an ageing population will likely increase the demand for long-term care within the near future. The development of risk profiles will not only be useful for projecting future demand, but also for providing clues that may prevent or delay long-term care utilization. Here, we report our identification of predictors of long-term care utilization in a cohort of hospital patients aged 65+ following their discharge from hospital discharge and who, prior to hospital admission, were living at home.
Related JoVE Video
Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.
Int Clin Psychopharmacol
PUBLISHED: 05-04-2010
Show Abstract
Hide Abstract
Phosphodiesterase 4B (PDE4B) has been evaluated as a genetic risk factor for schizophrenia. Selective PDE4 inhibitor drugs have antipsychotic-like effects and reduce tardive dyskinesia-like movements in animal models. We investigated whether PDE4B genetic variants are associated with antipsychotic-induced tardive dyskinesia incidence and severity in schizophrenia patients. Our sample consisted of 169 Caucasian patients taking typical antipsychotic medication for at least 1 year. We found two PDE4B gene variants to be nominally associated with tardive dyskinesia (rs1338719 and rs7528545) in the overall population and two other variants nominally associated with the presence of tardive dyskinesia and severity in female patients (rs1890196 and rs783036). None of these results survived correction for multiple testing. Overall, our results do not support a genetic association between tardive dyskinesia and PDE4B.
Related JoVE Video
Pineal parenchymal tumor of intermediate differentiation: clinicopathological report and analysis of epidermal growth factor receptor variant III expression.
Neurosurgery
PUBLISHED: 04-21-2010
Show Abstract
Hide Abstract
Epidermal growth factor receptor (EGF) receptor gene amplification is commonly seen in cancer and is the target of many therapies. EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor and has been detected in a large percentage of patients with glioblastoma multiforme but not in normal brain. Therapies targeting EGFRvIII are currently being investigated in clinical and preclinical trials.
Related JoVE Video
Quantitative modeling of the high-throughput production and in vivo kinetics of (drug-encapsulating) liposomes.
PLoS ONE
PUBLISHED: 03-29-2010
Show Abstract
Hide Abstract
In developing liposomes for in vivo use, it is important to design the liposomes to have optimal in vivo kinetics, and it is also necessary to identify optimal high-throughput production conditions for these liposomes. Previous work has not definitively established the general relationship between liposomes configuration and composition, and their in vivo kinetics. Also, no straightforward method exists to calculate optimal liposome high-throughput production conditions for specific liposome compositions. This work presents first-principles quantitative correlations describing liposomes in vivo drug leakage and vascular mass transfer kinetics. This work further presents a simple quantitative model relating specific liposome compositions to ideal high-throughput production parameters. The results have implications for the identification of promising liposome compositions via high-throughput screening methodologies, as well as the design and optimization of high-throughput reactors for liposome production.
Related JoVE Video
Lack of association of NALCN genetic variants with schizophrenia.
Psychiatry Res
PUBLISHED: 03-19-2010
Show Abstract
Hide Abstract
NALCN (sodium leak channel, non-selective) is located on chromosome 13q (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464 schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We observed nominal association with rs9518320 and rs9518331, suggesting that NALCN is not related to schizophrenia risk.
Related JoVE Video
Glial cell line-derived neurotrophic factor receptor alpha 2 (GFRA2) gene is associated with tardive dyskinesia.
Psychopharmacology (Berl.)
PUBLISHED: 02-07-2010
Show Abstract
Hide Abstract
Tardive dyskinesia (TD) has a pharmacogenetic component in which the interaction of antipsychotic exposure with individual genetic variation mediates risk. The glial cell line-derived neurotrophic factor (GDNF) signalling pathway has been associated with neuroprotective effects in central dopaminergic neurons and spinal motor neurons. Clinical trials have also investigated whether GDNF may ameliorate Parkinsons disease symptoms.
Related JoVE Video
Clinical evaluation of the intraoperative refraction technique for intraocular lens power calculation.
Ophthalmology
PUBLISHED: 01-25-2010
Show Abstract
Hide Abstract
To evaluate clinically the intraoperative refraction technique for intraocular lens (IOL) power calculation using 2 existing formulas proposed by Ianchulev and Leccisotti and to derive alternative formulas for this technique.
Related JoVE Video
Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response.
J Psychiatr Res
PUBLISHED: 01-06-2010
Show Abstract
Hide Abstract
GDNF (glial-cell-line derived neurotrophic factor) is a potent neurotrophic factor for dopaminergic neurons. Neuropsychiatric diseases and their treatments are associated with alterations in the levels of both GDNF and its receptor family (GDNF family receptor alpha or GFRA). GFRA1, GFRA2 and GFRA3 are located in chromosomal regions with suggestive linkage to schizophrenia. In this study we analyzed polymorphisms located in all four known GFRA genes and examined association with schizophrenia and clozapine response. We examined SNPs across the genes GFRA1-4 in 219 matched case-control subjects, 85 small nuclear families and 140 schizophrenia patients taking clozapine for 6months. We observed that GFRA3 rs11242417 and GFRA1 rs11197557 variants were significantly associated with schizophrenia after combining results from both schizophrenia samples. Furthermore, we found an overtransmission of the G-C GFRA1 rs7920934-rs730357 haplotype to subjects with schizophrenia and association of A-T-G-G GFRA3 rs10036665-rs10952-rs11242417-rs7726580 with schizophrenia in the case-control sample. On the other hand, GFRA2 variants were not associated with schizophrenia diagnosis but subjects carrying T-G-G rs1128397-rs13250096-rs4567028 haplotype were more likely to respond to clozapine treatment. The statistical significance of results survived permutation testing but not Bonferroni correction. We also found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia.
Related JoVE Video
Modified epidermal growth factor receptor (EGFR)-bearing liposomes (MRBLs) are sensitive to EGF in solution.
PLoS ONE
PUBLISHED: 06-25-2009
Show Abstract
Hide Abstract
Cancers often overexpress EGF and other growth factors to promote cell replication and migration. Previous work has not produced targeted drug carriers sensitive to abnormal amounts of growth factors. This work demonstrates that liposomes bearing EGF receptors covalently crosslinked to p-toluic acid or methyl-PEO(4)-NHS ester (or, in short, MRBLs) exhibit an increased rate of release of encapsulated drug compounds when EGF is present in solution. Furthermore, the modified EGF receptors retain the abilities to form dimers in the presence of EGF and bind specifically to EGF. These results demonstrate that MRBLs are sensitive to EGF in solution and indicate that MRBL-reconstituted modified EGF receptors, in the presence of EGF in solution, form dimers which increase MRBL permeability to encapsulated compounds.
Related JoVE Video
Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model.
Hum. Mol. Genet.
PUBLISHED: 05-30-2009
Show Abstract
Hide Abstract
Abnormal N-methyl-d-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. d-serine is an important NMDAR modulator, and to elucidate the role of the d-serine synthesis enzyme serine racemase (Srr) in schizophrenia, we identified and characterized mice with an ENU-induced mutation that results in a complete loss of Srr activity and dramatically reduced d-serine levels. Mutant mice displayed behaviors relevant to schizophrenia, including impairments in prepulse inhibition, sociability and spatial discrimination. Behavioral deficits were exacerbated by an NMDAR antagonist and ameliorated by d-serine or the atypical antipsychotic clozapine. Expression profiling revealed that the Srr mutation influenced several genes that have been linked to schizophrenia and cognitive ability. Transcript levels altered by the Srr mutation were also normalized by d-serine or clozapine treatment. Furthermore, analysis of SRR genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant Srr function and diminished d-serine may contribute to schizophrenia pathogenesis.
Related JoVE Video
Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: analysis of suicidality in major psychosis.
J Psychiatr Res
PUBLISHED: 04-25-2009
Show Abstract
Hide Abstract
Suicide is an act deliberately initiated and performed by a person with full knowledge that a fatal outcome is probable. The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behaviour by a genetic association between the 5-HT2A T102C silent polymorphism and suicidality in patients with mood disorders and schizophrenia. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific methylation of the 5-HT2A gene, and found that the methylation of the C allele in the pre-frontal cortex of heterozygous suicide victims (n=10) was not significantly different in comparison with the non-suicide group (n=10) (p=0.084). We also analyzed methylation of the C allele in white blood cell DNA from bipolar and schizophrenic attempters and found a significant difference in the schizophrenic attempters (p=0.00013) but not in the bipolar attempters (p=0.616). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect inheritance of suicidal behaviour. Thus, we examined the parental origin of specific alleles for genetic association in a genetic family-based sample of major psychoses in which information on suicidal behaviour was available. This result suggests that methylation of the 102C allele does not influence completed suicide.
Related JoVE Video
Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry.
Am J Med Genet C Semin Med Genet
PUBLISHED: 04-21-2009
Show Abstract
Hide Abstract
Classical twin studies in the field of psychiatry generally fall into one of two categories: (1) those designed to identify environmental risk factors causing discordance in monozygotic (MZ) twins and (2) those geared towards identifying genetic risk factors. However, neither environment nor differences in DNA sequence can fully account for phenotypic discordance among MZ twins. The field of epigenetics--DNA modifications that can affect gene expression--offers new models to understand discordance in MZ twins. In the past, MZ twins were regarded as genetically-identical controls for differing environmental conditions. In contrast, the evolving current concept is that epigenetic differences between MZ twins may modulate differences in diverse phenotype, from disease to personality. In this article, we review some twin studies, and discuss the dynamic interactions between stochastic, environmental, and epigenetic variables that influence neurobiological phenotypes.
Related JoVE Video
Genetic association and post-mortem brain mRNA analysis of DISC1 and related genes in schizophrenia.
Schizophr. Res.
PUBLISHED: 03-04-2009
Show Abstract
Hide Abstract
Convergent evidence from genetic linkage, genetic association and biological studies implicates the Disrupted in schizophrenia 1 (DISC1) gene in the etiology and pathophysiology of schizophrenia. We conducted genetic association studies in matched case-control and family sample sets (N=117 families; N=210 case-control pairs), testing polymorphisms across DISC1 and DISC1 interacting genes: LIS1, NUDEL, FEZ1 and PDE4B. We found that DISC1 variants, particularly in the exon 9/intron 9/intron 10 region of the gene, may be associated with risk for schizophrenia in our sample population. There was no strong evidence for association with LIS1, NUDEL, FEZ1 and PDE4B. Gene-gene interaction analyses and mRNA quantification in post-mortem brains from schizophrenia patients and control subjects did not reveal significant differences.
Related JoVE Video
DNA methylation profiles in monozygotic and dizygotic twins.
Nat. Genet.
PUBLISHED: 01-18-2009
Show Abstract
Hide Abstract
Twin studies have provided the basis for genetic and epidemiological studies in human complex traits. As epigenetic factors can contribute to phenotypic outcomes, we conducted a DNA methylation analysis in white blood cells (WBC), buccal epithelial cells and gut biopsies of 114 monozygotic (MZ) twins as well as WBC and buccal epithelial cells of 80 dizygotic (DZ) twins using 12K CpG island microarrays. Here we provide the first annotation of epigenetic metastability of approximately 6,000 unique genomic regions in MZ twins. An intraclass correlation (ICC)-based comparison of matched MZ and DZ twins showed significantly higher epigenetic difference in buccal cells of DZ co-twins (P = 1.2 x 10(-294)). Although such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and animal studies favor the hypothesis that it is due to epigenomic differences in the zygotes, suggesting that molecular mechanisms of heritability may not be limited to DNA sequence differences.
Related JoVE Video
FoxO proteins and cardiac pathology.
Adv. Exp. Med. Biol.
PUBLISHED: 01-01-2009
Show Abstract
Hide Abstract
The FoxO family of transcription factors mediate a wide range of cellular responses from cell death to cell survival, growth inhibition and glucose utilization. This complex array of responses is regulated by an equally complex regulatory system, involving phosphorylation, ubiquitinization and acetylation, in addition to interactions with other transcription factors and transcriptional modifiers. In heart, FoxO proteins have been shown to be involved in development in limiting hypertrophic growth responses and in cardioprotection provided by silent information regulator 1 (Sirt1). However, the range of responses mediated by FoxO proteins and the clear evidence for involvement of FoxO regulators in cardiac pathology, suggest that further pathological actions of FoxO family members remain to be elucidated.
Related JoVE Video
Prophylactic valproic acid treatment prevents schizophrenia-related behaviour in Disc1-L100P mutant mice.
PLoS ONE
Show Abstract
Hide Abstract
Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood.
Related JoVE Video
Preseptal cellulitis in a child caused by Megacopta centrosignatum.
J AAPOS
Show Abstract
Hide Abstract
Preseptal cellulitis in children can be caused by a reaction to embedded insects, their body parts, or secretions. We report the case of a 2-year-old girl who presented with preseptal cellulitis caused by an insect identified as Megacopta centrosignatum in her superior fornix.
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.