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Find video protocols related to scientific articles indexed in Pubmed.
Nanoscale three-dimensional imaging of the human myocyte.
J. Struct. Biol.
PUBLISHED: 08-23-2014
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The ventricular human myocyte is spatially organized for optimal ATP and Ca(2+) delivery to sarcomeric myosin and ionic pumps during every excitation-contraction cycle. Comprehension of three-dimensional geometry of the tightly packed ultrastructure has been derived from discontinuous two-dimensional images, but has never been precisely reconstructed or analyzed in human myocardium. Using a focused ion beam scanning electron microscope, we created nanoscale resolution serial images to quantify the three-dimensional ultrastructure of a human left ventricular myocyte. Transverse tubules (t-tubule), lipid droplets, A-bands, and mitochondria occupy 1.8, 1.9, 10.8, and 27.9% of the myocyte volume, respectively. The complex t-tubule system has a small tortuosity (1.04±0.01), and is composed of long transverse segments with diameters of 317±24nm and short branches. Our data indicates that lipid droplets located well beneath the sarcolemma are proximal to t-tubules, where 59% (13 of 22) of lipid droplet centroids are within 0.50?m of a t-tubule. This spatial association could have an important implication in the development and treatment of heart failure because it connects two independently known pathophysiological alterations, a substrate switch from fatty acids to glucose and t-tubular derangement.
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Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.
Clin. Infect. Dis.
PUBLISHED: 06-27-2014
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Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD).
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In Vitro Activity of New Cephalosporins vs Streptococcus pneumoniae from the Canadian Bacterial Surveillance Network: 2008-2011.
Curr. Microbiol.
PUBLISHED: 02-27-2014
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Between 2008 and 2011, 6,895 Streptococcus pneumoniae isolates were submitted to the Canadian Bacterial Surveillance Network and underwent in vitro susceptibility testing. Fifteen percent of S. pneumoniae isolates were collected from pediatric patients (0-15 years old), 48.6 % of isolates were collected from adults between 16 and 64 years of age, and 36.1 % from adults aged ?65 years; age data were not available for 11 patients. Forty-five percent of S. pneumoniae isolates were recovered from sterile specimens, and 55 % of isolates were from nonsterile specimens. Overall, 0.4 % of isolates were resistant to penicillin, 0.4 % to ceftriaxone, 3 % to amoxicillin, 25 % to erythromycin, and 13 % to trimethoprim/sulfamethoxazole; 6.6 % of isolates were multidrug resistant (MDR). Among MDR isolates, resistance rates exceeded 95 % for erythromycin, tetracycline, and trimethoprim/sulfamethoxazole. The MIC90 of cethromycin, ceftaroline, and ceftobiprole against MDR isolates were 0.12, 0.25, and 1 mg/L, respectively. Ceftaroline, the active form of the prodrug ceftaroline fosamil, exhibited potent in vitro activity against the tested S. pneumoniae including all 456 multidrug-resistant strains. No ceftaroline-resistant isolates were identified.
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Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011.
Vaccine
PUBLISHED: 07-14-2013
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In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13).
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Have changing pneumococcal vaccination programmes impacted disease in Ontario?
Vaccine
PUBLISHED: 03-08-2013
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Publicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults ? 65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults ? 50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD).
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A unique strain of community-acquired Clostridium Difficile in severe complicated infection and death of a young adult.
BMC Infect. Dis.
PUBLISHED: 01-11-2013
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Clostridium difficile is the major cause of nosocomial antibiotic-associated diarrhoea with the potential risk of progressing to severe clinical outcomes including death. It is not unusual for Clostridium difficile infection to progress to complications of toxic megacolon, bowel perforation and even Gram-negative sepsis following pathological changes in the intestinal mucosa. These complications are however less commonly seen in community-acquired Clostridium difficile infection than in hospital-acquired Clostridium difficile infection. To the best of our knowledge, this was the first case of community-acquired Clostridium difficile infection of its type seen in Jamaica.
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Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada.
Antimicrob. Agents Chemother.
PUBLISHED: 05-31-2011
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Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ? 4 ?g/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at <2%. Multivariable analyses showed that prevalence of mutations known to be associated with reduced susceptibility to fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae.
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Effect of patterns of transferring patients among healthcare institutions on rates of nosocomial methicillin-resistant Staphylococcus aureus transmission: a Monte Carlo simulation.
Infect Control Hosp Epidemiol
PUBLISHED: 04-05-2011
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To determine the effect of the rate and pattern of patient transfers among institutions within a single metropolitan area on the rates of methicillin-resistant Staphylococcus aureus (MRSA) transmission among patients in hospitals and nursing homes.
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When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto.
Crit Care
PUBLISHED: 03-22-2011
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There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection.
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Self-collected mid-turbinate swabs for the detection of respiratory viruses in adults with acute respiratory illnesses.
PLoS ONE
PUBLISHED: 03-17-2011
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The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs.
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Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia.
Exp. Neurol.
PUBLISHED: 02-28-2011
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The Akita mouse is a robust model of diabetic autonomic neuropathy which develops severe diabetes following beta cell death, which occurs reproducibly at 3-4 weeks of age, and maintains the diabetic state without therapy for as long as 11 additional months. Neuritic dystrophy and neuronopathy involving prevertebral sympathetic superior mesenteric and celiac ganglia begin to develop within the first two months of onset of diabetes and are progressive with time. We have examined the effect of insulin implants resulting in normoglycemia and injections of ARA290, a small erythropoietin peptide which has no effect on glycemic parameters, on the reversal of established neuritic dystrophy and neuronopathy. We have found that 4 weeks of insulin therapy beginning at 2 months of diabetes resulted in normalization of blood glucose, body weight and HbA1c. Insulin therapy successfully reversed established neuritic dystrophy and neuronopathy to control levels. Numbers of sympathetic neurons were not significantly changed in either 3 month diabetic or insulin-treated Akita mice. Treatment with ARA290 for 7 weeks beginning at 4 months of diabetes did not result in altered metabolic severity of diabetes as measured by blood glucose, body weight or HbA1c levels. ARA290 treatment was able to decrease neuritic dystrophy by 55-74% compared to untreated diabetics or in comparison to a separate group of diabetic animals representing the 4 month treatment onset point. Surprisingly, there was no effect of ARA290 on ganglionic neuron number or ongoing neuronopathy (pale/degenerating neurons) in diabetic Akita mice during this time period. The development of neuroprotective EPO-like peptides may provide a possible future therapy for this debilitating complication of diabetes; however, it appears that discrete elements may be differentially targeted by the diabetic state and may require selective therapy.
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Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada.
PLoS ONE
PUBLISHED: 04-19-2010
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In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.
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Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-08-2010
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Understanding the fine-structure molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research. We used short-read-length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of distinct clonally related complexes. We discovered that each epidemic is dominated by micro- and macrobursts of multiple emergent clones, some with distinct strain genotype-patient phenotype relationships. On average, strains were differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent of SNPs are strain specific; that is, each strain has a unique genome sequence. We identified nonrandom temporal-spatial patterns of strain distribution within and between the epidemic peaks. The extensive full-genome data permitted us to identify genes with significantly increased rates of nonsynonymous (amino acid-altering) nucleotide polymorphisms, thereby providing clues about selective forces operative in the host. Comparative expression microarray analysis revealed that closely related strains differentiated by seemingly modest genetic changes can have significantly divergent transcriptomes. We conclude that enhanced understanding of bacterial epidemics requires a deep-sequencing, geographically centric, comparative pathogenomics strategy.
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Molecular epidemiology of multidrug resistant extended spectrum beta-lactamase producing Klebsiella pneumoniae at a Jamaican hospital, 2000-2004.
BMC Microbiol.
PUBLISHED: 01-28-2010
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The accurate identification of a pathogen beyond the species level is critical in epidemiological studies and investigations of nosocomial outbreaks of infection. The clonal relatedness of 66 multidrug resistant (MDR) strains of extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolated from clinical specimens from hospitalized patients at a Jamaican hospital during a 5 year period were determined by pulsed field gel electrophoresis (PFGE).
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Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada.
Ann. Clin. Microbiol. Antimicrob.
PUBLISHED: 01-18-2010
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The objective of this study was to examine Streptococcus pneumoniae isolates collected from a longitudinal surveillance program in order to determine their susceptibility to currently used fluoroquinolones and of the frequency and type of mutations in the quinolone-resistant determining regions (QRDRs) of their parC and gyrA genes.
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Genetic ablation of calcium-independent phospholipase A2{gamma} leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy, and cognitive dysfunction.
J. Biol. Chem.
PUBLISHED: 10-19-2009
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Genetic ablation of calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) results in profound alterations in hippocampal phospholipid metabolism and mitochondrial phospholipid homeostasis resulting in enlarged and degenerating mitochondria leading to autophagy and cognitive dysfunction. Shotgun lipidomics demonstrated multiple alterations in hippocampal lipid metabolism in iPLA(2)gamma(-/-) mice including: 1) a markedly elevated hippocampal cardiolipin content with an altered molecular species composition characterized by a shift to shorter chain length molecular species; 2) alterations in both choline and ethanolamine glycerophospholipids, including a decreased plasmenylethanolamine content; 3) increased oxidized phosphatidylethanolamine molecular species; and 4) an increased content of ceramides. Electron microscopic examination demonstrated the presence of enlarged heteromorphic lamellar structures undergoing degeneration accompanied by the presence of ubiquitin positive spheroid inclusion bodies. Purification of these enlarged heteromorphic lamellar structures by buoyant density centrifugation and subsequent SDS-PAGE and proteomics identified them as degenerating mitochondria. Collectively, these results identify the obligatory role of iPLA(2)gamma in neuronal mitochondrial lipid metabolism and membrane structure demonstrating that iPLA(2)gamma loss of function results in a mitochondrial neurodegenerative disorder characterized by degenerating mitochondria, autophagy, and cognitive dysfunction.
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Genome-wide dissection of globally emergent multi-drug resistant serotype 19A Streptococcus pneumoniae.
BMC Genomics
PUBLISHED: 09-16-2009
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Emergence of multi-drug resistant (MDR) serotype 19A Streptococcus pneumoniae (SPN) is well-documented but causal factors remain unclear. Canadian SPN isolates (1993-2008, n = 11,083) were serotyped and in vitro susceptibility tested. A subset of MDR 19A were multi-locus sequence typed (MLST) and representative isolates whole genomes sequenced.
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Autophagy regulates pancreatic beta cell death in response to Pdx1 deficiency and nutrient deprivation.
J. Biol. Chem.
PUBLISHED: 08-04-2009
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There are three types of cell death; apoptosis, necrosis, and autophagy. The possibility that activation of the macroautophagy (autophagy) pathway may increase beta cell death is addressed in this study. Increased autophagy was present in pancreatic islets from Pdx1(+/-) mice with reduced insulin secretion and beta cell mass. Pdx1 expression was reduced in mouse insulinoma 6 (MIN6) cells by delivering small hairpin RNAs using a lentiviral vector. The MIN6 cells died after 7 days of Pdx1 deficiency, and autophagy was evident prior to the onset of cell death. Inhibition of autophagy prolonged cell survival and delayed cell death. Nutrient deprivation increased autophagy in MIN6 cells and mouse and human islets after starvation. Autophagy inhibition partly prevented amino acid starvation-induced MIN6 cell death. The in vivo effects of reduced autophagy were studied by crossing Pdx1(+/-) mice to Becn1(+/-) mice. After 1 week on a high fat diet, 4-week-old Pdx1(+/-) Becn1(+/-) mice showed normal glucose tolerance, preserved beta cell function, and increased beta cell mass compared with Pdx1(+/-) mice. This protective effect of reduced autophagy had worn off after 7 weeks on a high fat diet. Increased autophagy contributes to pancreatic beta cell death in Pdx1 deficiency and following nutrient deprivation. The role of autophagy should be considered in studies of pancreatic beta cell death and diabetes and as a target for novel therapeutic intervention.
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Insulin pump therapy: guidelines for successful outcomes.
Diabetes Educ
PUBLISHED: 03-26-2009
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Current forms of insulin delivery used in the treatment of diabetes mellitus (diabetes) include syringes, pens, and insulin pumps. Technical advantages of insulin pump therapy, or continuous subcutaneous insulin delivery (CSII), include precise and flexible insulin dosing. In the context of intensive diabetes management, insulin pumps can facilitate improved long-term glycemic control and reduce the risk for diabetes complications, with improved lifestyle flexibility for patients and their families. Comprehensive patient education, carbohydrate counting, and frequent self-monitoring of blood glucose or continuous glucose monitoring are necessary components of successful insulin pump therapy. Technological advances have increased the appeal of pump therapy to patients and clinicians. Physically, current insulin pumps are discreet, ergonomic, and water resistant. Meanwhile, software improvements have yielded smart pumps with features that support pump users in their daily diabetes management. Robust data analysis software packages allow patients and clinicians unprecedented insight into the quality of diabetes control. Furthermore, widespread insurance reimbursement for CSII has expanded access to therapy.
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Neuritic dystrophy and neuronopathy in Akita (Ins2(Akita)) diabetic mouse sympathetic ganglia.
Exp. Neurol.
PUBLISHED: 03-21-2009
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Diabetic autonomic neuropathy is a debilitating, poorly studied complication of diabetes. Our previous studies of non-obese diabetic (NOD) and related mouse models identified rapidly developing, dramatic pathology in prevertebral sympathetic ganglia; however, once diabetic, the mice did not survive for extended periods needed to examine the ability of therapeutic agents to correct established neuropathy. In the current manuscript we show that the Akita (Ins2(Akita)) mouse is a robust model of diabetic sympathetic autonomic neuropathy with unambiguous, spontaneous, rapidly-developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man. Akita mice diabetic for 2, 4 or 8 months of diabetes progressively developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric (SMG) and celiac ganglia (CG). Comparable changes failed to develop in the superior cervical ganglia (SCG) of the Akita mouse or in any ganglia of non-diabetic mice. Morphometric studies demonstrate an overall increase in presynaptic axon terminal cross sectional area, including those without any ultrastructural features of dystrophy. Neurons in Akita mouse prevertebral sympathetic ganglia show an unusual perikaryal alteration characterized by the accumulation of membranous aggregates and minute mitochondria and loss of rough endoplasmic reticulum. These changes result in the loss of a third of neurons in the CG over the course of 8 months of diabetes. The extended survival of diabetic mice and robust pathologic findings provide a clinically relevant paradigm that will facilitate the analysis of novel therapeutic agents on the reversal of autonomic neuropathy.
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Impact of a mandatory infection control education program on nosocomial acquisition of methicillin-resistant Staphylococcus aureus.
Infect Control Hosp Epidemiol
PUBLISHED: 02-10-2009
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To assess the impact of an institution-wide infection control education program on the rate of transmission of methicillin-resistant Staphylococcus aureus (MRSA).
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Predicting patient discharge disposition after total joint arthroplasty in the United States.
J Arthroplasty
PUBLISHED: 01-20-2009
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The purpose of this study was to develop an easily administered tool to preoperatively predict patient discharge disposition after total joint arthroplasty in the United States. Data were collected in a retrospective review of 517 medical charts and analyzed using logistic regression to develop a model for predicting the likelihood that a patient will not be discharged directly home. The resulting regression model was the basis for the nomogram, named the Predicting Location after Arthroplasty Nomogram. This model demonstrated a bootstrap-corrected concordance index of 0.867, excellent calibration, and external validation as demonstrated by a concordance index of 0.861. Preoperative knowledge that a patient is likely to require an extended care facility allows the clinical care team to make appropriate arrangements and avoid potential delays in patient discharge.
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Population-based surveillance for invasive pneumococcal disease in homeless adults in Toronto.
PLoS ONE
PUBLISHED: 01-13-2009
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Identification of high-risk populations for serious infection due to S. pneumoniae will permit appropriately targeted prevention programs.
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Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits.
PLoS ONE
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Regulated protein degradation by the proteasome plays an essential role in the enhancement and suppression of signaling pathways in the nervous system. Proteasome-associated factors are pivotal in ensuring appropriate protein degradation, and we have previously demonstrated that alterations in one of these factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 (Usp14), can lead to proteasome dysfunction and neurological disease. Recent studies in cell culture have shown that Usp14 can also stabilize the expression of over-expressed, disease-associated proteins such as tau and ataxin-3. Using Usp14-deficient ax(J) mice, we investigated if loss of Usp14 results in decreased levels of endogenous tau and ataxin-3 in the nervous system of mice. Although loss of Usp14 did not alter the overall neuronal levels of tau and ataxin-3, we found increased levels of phosphorylated tau that correlated with the onset of axonal varicosities in the Usp14-deficient mice. These changes in tau phosphorylation were accompanied by increased levels of activated phospho-Akt, phosphorylated MAPKs, and inactivated phospho-GSK3?. However, genetic ablation of tau did not alter any of the neurological deficits in the Usp14-deficient mice, demonstrating that increased levels of phosphorylated tau do not necessarily lead to neurological disease. Due to the widespread activation of intracellular signaling pathways induced by the loss of Usp14, a better understanding of the cellular pathways regulated by the proteasome is required before effective proteasomal-based therapies can be used to treat chronic neurological diseases.
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Staphylococcus aureus pneumonia and dengue virus co-infection and review of implications of coinfection.
BMJ Case Rep
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Dengue fever is an important public health problem in Jamaica and has various serious manifestations, which if not identified and treated at the appropriate time can lead to dire consequences. Bacterial co-infections have been seen in clinical practice but may be thought of as simply coincidental. This review highlights the importance of bacteria in exacerbating dengue infections and the importance of looking for co-infection in patients with certain clinical manifestations. It also provides the reader with a scientific understanding of the immune pathogenesis of dengue and bacterial co-infections.
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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.