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Find video protocols related to scientific articles indexed in Pubmed.
Leukocytes as carriers for targeted cancer drug delivery.
Expert Opin Drug Deliv
PUBLISHED: 10-02-2014
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Introduction: Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. Areas covered: This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Expert opinion: Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues.
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Molecular basis and bleeding manifestations of factor XI deficiency in 11 Turkish families.
Blood Coagul. Fibrinolysis
PUBLISHED: 08-23-2014
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Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by variable bleeding tendency. In the present study, the gene encoding FXI (F11) was analyzed by direct sequencing in 33 individuals belonging to 11 unrelated Turkish families, and the bleeding tendency was quantitatively assessed by means of a bleeding questionnaire in 27 individuals with low FXI clotting activity and/or mutated F11 gene. We identified 10 distinct mutations (five missense, three nonsense and two splice site), four of which were novel. No mutation was found in one family. Of the four novel mutations, homozygosity for a c.89T>C (p.Phe30Ser) mutation and compound heterozygosity for a c.646G>A (p.Asp216Asn) mutation with the known c.403G>T (p.Glu135) type II Jewish mutation were associated with severe deficiency, whilst heterozygosity for the novel c.1655A>C (p.His552Arg) and c.1627G>A (p.Glu543Lys) mutations was associated with partial deficiency. p.Glu135 was found in 19% (5/27) of the mutated alleles. Bleeding score was positive in 57% (4/7) of individuals with severe and 39% (7/18) of those with partial deficiency. It was significantly correlated with clinical severity of bleeding (r?=?0.43, P?=?0.02), but not with FXI clotting activity (P?>?0.05). There was no optimal cut-off level of the bleeding score that could predict FXI deficiency. We conclude that the spectrum of mutations found in this study reflects the genetic heterogeneity of FXI deficiency in the Turkish population. Quantitative assessment of the bleeding symptoms by a bleeding questionnaire seems to be useful for evaluating the severity of bleeding episodes, but it can not be recommended as a screening tool for FXI deficiency.
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Patterns and Predictors of Sleep Quality Before, During, and After Hospitalization in Older Adults.
J Clin Sleep Med
PUBLISHED: 08-01-2014
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The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep.
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A microfluidic device to select for cells based on chemotactic phenotype.
Technology (Singap World Sci)
PUBLISHED: 07-08-2014
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In the search for biomarkers of metastasis, attention has been largely placed on ensemble-averaged measurements that screen for molecules or genes. However, individual molecular changes do not always result in disease, and population-based measurements can mask the molecular signatures of the cells responsible for disease. Here, we describe a device that selects for cells based on chemotactic behavior rather than based on molecular differences, enabling the most aggressive cells to be studied independently from the heterogeneous population.
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An Unusual Case of Severe Stenosis of the Coronary Sinus Ostium in Association With Double Inlet Left Ventricle.
World J Pediatr Congenit Heart Surg
PUBLISHED: 06-25-2014
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We present a patient with complex single ventricle physiology who was subsequently diagnosed with atresia of the coronary sinus ostium in the setting of myocardial dysfunction following operative palliation. Although a rare cardiac defect, awareness is important as the coronary venous system will often drain to a left superior vena cava (LSVC). If the LSVC is ligated without knowing of this defect, cardiac dysfunction and death can occur.
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Mouse Y-linked Zfy1 and Zfy2 are expressed during the male-specific interphase between meiosis I and meiosis II and promote the 2nd meiotic division.
PLoS Genet.
PUBLISHED: 06-01-2014
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Mouse Zfy1 and Zfy2 encode zinc finger transcription factors that map to the short arm of the Y chromosome (Yp). They have previously been shown to promote meiotic quality control during pachytene (Zfy1 and Zfy2) and at the first meiotic metaphase (Zfy2). However, from these previous studies additional roles for genes encoded on Yp during meiotic progression were inferred. In order to identify these genes and investigate their function in later stages of meiosis, we created three models with diminishing Yp and Zfy gene complements (but lacking the Y-long-arm). Since the Y-long-arm mediates pairing and exchange with the X via their pseudoautosomal regions (PARs) we added a minute PAR-bearing X chromosome derivative to enable formation of a sex bivalent, thus avoiding Zfy2-mediated meiotic metaphase I (MI) checkpoint responses to the unpaired (univalent) X chromosome. Using these models we obtained definitive evidence that genetic information on Yp promotes meiosis II, and by transgene addition identified Zfy1 and Zfy2 as the genes responsible. Zfy2 was substantially more effective and proved to have a much more potent transactivation domain than Zfy1. We previously established that only Zfy2 is required for the robust apoptotic elimination of MI spermatocytes in response to a univalent X; the finding that both genes potentiate meiosis II led us to ask whether there was de novo Zfy1 and Zfy2 transcription in the interphase between meiosis I and meiosis II, and this proved to be the case. X-encoded Zfx was also expressed at this stage and Zfx over-expression also potentiated meiosis II. An interphase between the meiotic divisions is male-specific and we previously hypothesised that this allows meiosis II critical X and Y gene reactivation following sex chromosome silencing in meiotic prophase. The interphase transcription and meiosis II function of Zfx, Zfy1 and Zfy2 validate this hypothesis.
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Are housestaff identifying malnourished hospitalized medicine patients?
Appl Physiol Nutr Metab
PUBLISHED: 05-30-2014
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Clinical nutrition and nutritional assessment are often a neglected component of medical school curriculums despite the high prevalence of malnutrition in hospitalized patients. This study found that medical housestaff performed nutritional assessments in only 4% of admitted patients despite a high rate of malnutrition (57%). Survey results show housestaff lack knowledge in the area of malnutrition. Medical schools and training programs must place greater emphasis of providing qualified physician nutrition specialists to implement effective nutrition instruction.
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Unnatural killer cells to prevent bloodborne metastasis: inspiration from biology and engineering.
Expert Rev Anticancer Ther
PUBLISHED: 05-05-2014
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Metastasis contributes to over 90% of cancer-related deaths. Many types of cancer metastasize via the bloodstream, where circulating tumor cells (CTCs) originating from the primary tumor can undergo selectin-mediated adhesion with the blood vessel wall and subsequently transmigrate to anatomically distant organs. In an effort to neutralize CTCs with the potential to form metastases, a new therapeutic approach has been developed in which circulating leukocytes are functionalized to target and kill cancer cells in the bloodstream. This approach mimics the cytotoxic activity of natural killer cells and the chemical engineering concept of a fluidized bed reactor, which increases the surface area for surface-catalyzed reactions. The resulting 'unnatural killer cells', proven effective in vitro with human blood and also in the living mouse, holds promise in neutralizing CTCs to interrupt the metastasis process.
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Dress codes and appearance policies: challenges under federal legislation, part 3: Title VII, the Americans with Disabilities Act, and the National Labor Relations Act.
Health Care Manag (Frederick)
PUBLISHED: 04-30-2014
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As more and more individuals express themselves with tattoos and body piercings and push the envelope on what is deemed appropriate in the workplace, employers have an increased need for creation and enforcement of reasonable dress codes and appearance policies. As with any employment policy or practice, an appearance policy must be implemented and enforced without regard to an individual's race, color, sex, national origin, religion, disability, age, or any other protected status. A policy governing dress and appearance based on the business needs of an employer that is applied fairly and consistently and does not have a disproportionate effect on any protected class will generally be upheld if challenged in court. By examining some of the more common legal challenges to dress codes and how courts have resolved the disputes, health care managers can avoid many potential problems. This article, the third part of a 3-part examination of dress codes and appearance policies, focuses on the issues of race and national origin under the Civil Rights Act, disability under the Americans With Disabilities Act, and employees' rights to engage in concerted activities under the National Labor Relations Act. Pertinent court cases that provide guidance for employers are addressed.
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Anterior tracheal suspension for tracheobronchomalacia in infants and children.
Ann. Thorac. Surg.
PUBLISHED: 04-27-2014
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Severe tracheobronchomalacia significantly complicates the postoperative course of infants and children with congenital heart disease, tracheoesophageal fistula, and tracheal stenosis. We have found that traditional approaches, including aortopexy, have been inconsistent in preventing acute life threatening events (ALTEs). In order to directly support the anterior tracheal wall, we have adopted the use of direct anterior tracheal suspension (ATS).
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Use of a HeartWare ventricular assist device in a patient with failed Fontan circulation.
Ann. Thorac. Surg.
PUBLISHED: 04-04-2014
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We present a successful case of the use of a HeartWare ventricular assist device as a bridge to transplantation in an 11-year-old with a hypoplastic left heart and failed Fontan circulation.
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Transposition of the great arteries--outcomes and time interval of early neonatal repair.
World J Pediatr Congenit Heart Surg
PUBLISHED: 03-27-2014
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This study evaluates the relationship of morbidity and resource utilization with the timing of early neonatal repair of transposition of the great arteries and intact ventricular septum (d-TGA/IVS).
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Fluid shear stress increases neutrophil activation via platelet-activating factor.
Biophys. J.
PUBLISHED: 03-20-2014
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Leukocyte exposure to hemodynamic shear forces is critical for physiological functions including initial adhesion to the endothelium, the formation of pseudopods, and migration into tissues. G-protein coupled receptors on neutrophils, which bind to chemoattractants and play a role in neutrophil chemotaxis, have been implicated as fluid shear stress sensors that control neutrophil activation. Recently, exposure to physiological fluid shear stresses observed in the microvasculature was shown to reduce neutrophil activation in the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine. Here, however, human neutrophil preexposure to uniform shear stress (0.1-2.75 dyn/cm(2)) in a cone-and-plate viscometer for 1-120 min was shown to increase, rather than decrease, neutrophil activation in the presence of platelet activating factor (PAF). Fluid shear stress exposure increased PAF-induced neutrophil activation in terms of L-selectin shedding, ?M?2 integrin activation, and morphological changes. Neutrophil activation via PAF was found to correlate with fluid shear stress exposure, as neutrophil activation increased in a shear stress magnitude- and time-dependent manner. These results indicate that fluid shear stress exposure increases neutrophil activation by PAF, and, taken together with previous observations, differentially controls how neutrophils respond to chemoattractants.
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General household emergency preparedness: a comparison between veterans and nonveterans.
Prehosp Disaster Med
PUBLISHED: 03-19-2014
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Despite federal and local efforts to educate the public to prepare for major emergencies, many US households remain unprepared for such occurrences. United States Armed Forces veterans are at particular risk during public health emergencies as they are more likely than the general population to have multiple health conditions.
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Dress codes and appearance policies: challenges under federal legislation, part 2: title VII of the civil rights act and gender.
Health Care Manag (Frederick)
PUBLISHED: 01-28-2014
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As more and more individuals express themselves with tattoos and body piercings and push the envelope on what is deemed appropriate in the workplace, employers have an increased need for creation and enforcement of reasonable dress codes and appearance policies. As with any employment policy or practice, an appearance policy must be implemented and enforced without regard to an individual's race, color, gender, national origin, religion, disability, age, or other protected status. A policy governing dress and appearance based on the business needs of an employer that is applied fairly and consistently and does not have a disproportionate effect on any protected class will generally be upheld if challenged in court. By examining some of the more common legal challenges to dress codes and how courts have resolved the disputes, health care managers can avoid many potential problems. This article, the second part of a 3-part examination of dress codes and appearance policies, focuses on the issue of gender under the Civil Rights Act of 1964. Pertinent court cases that provide guidance for employers are addressed.
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Repeated aortopulmonary shunt thrombosis in a neonatal patient with a low antithrombin level.
World J Pediatr Congenit Heart Surg
PUBLISHED: 01-10-2014
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A female infant with unbalanced right ventricular dominant atrioventricular septal defect with double-outlet right ventricle and pulmonary stenosis had recurrent aortopulmonary shunt thrombosis. She was found to have low antithrombin levels and was managed with antithrombin replacement in addition to unfractionated heparin. A subsequent aortopulmonary shunt was successfully placed, and patency was maintained. Her antithrombin levels normalized, and she was continued on low-molecular-weight heparin and aspirin until four months of age when a bidirectional superior cavopulmonary anastomosis was done. A prothrombotic evaluation at the time of the acute thrombosis and repeated at four months of age was negative except for the initially low antithrombin level. A repeat antithrombin level (off supplementation) at the time of the cavopulmonary anastomosis was normal making the diagnosis of congenital antithrombin deficiency unlikely. This case highlights the possibility of neonatal antithrombin deficiency as a cause of aortopulmonary shunt thrombosis and successful management with replacement therapy.
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TRAIL-coated leukocytes that kill cancer cells in the circulation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-06-2014
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Metastasis through the bloodstream contributes to poor prognosis in many types of cancer. Mounting evidence implicates selectin-based adhesive interactions between cancer cells and the blood vessel wall as facilitating this process, in a manner similar to leukocyte trafficking during inflammation. Here, we describe a unique approach to target and kill colon and prostate cancer cells in the blood that causes circulating leukocytes to present the cancer-specific TNF-related apoptosis inducing ligand (TRAIL) on their surface along with E-selectin adhesion receptor. This approach, demonstrated in vitro with human blood and also in mice, mimics the cytotoxic activity of natural killer cells and increases the surface area available for delivery of the receptor-mediated signal. The resulting "unnatural killer cells" hold promise as an effective means to neutralize circulating tumor cells that enter blood with the potential to form new metastases.
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Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage.
Proc. Biol. Sci.
PUBLISHED: 01-01-2014
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As duration of snow cover decreases owing to climate change, species undergoing seasonal colour moults can become colour mismatched with their background. The immediate adaptive solution to this mismatch is phenotypic plasticity, either in phenology of seasonal colour moults or in behaviours that reduce mismatch or its consequences. We observed nearly 200 snowshoe hares across a wide range of snow conditions and two study sites in Montana, USA, and found minimal plasticity in response to mismatch between coat colour and background. We found that moult phenology varied between study sites, likely due to differences in photoperiod and climate, but was largely fixed within study sites with only minimal plasticity to snow conditions during the spring white-to-brown moult. We also found no evidence that hares modify their behaviour in response to colour mismatch. Hiding and fleeing behaviours and resting spot preference of hares were more affected by variables related to season, site and concealment by vegetation, than by colour mismatch. We conclude that plasticity in moult phenology and behaviours in snowshoe hares is insufficient for adaptation to camouflage mismatch, suggesting that any future adaptation to climate change will require natural selection on moult phenology or behaviour.
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Incidence and Outcome of Pediatric Patients With Intracranial Hemorrhage While Supported on Ventricular Assist Devices.
Artif Organs
PUBLISHED: 11-21-2013
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Pediatric patients supported on ventricular assist devices (VADs) require systemic anticoagulation and are at risk for intracranial hemorrhage (ICH). Little is known about the incidence or outcomes of pediatric patients with ICH while supported on a VAD. A retrospective chart review of all patients receiving VAD support was completed. Patients diagnosed with ICH while supported on a VAD were identified. Significant factors prior to diagnosis of ICH, medical/surgical treatment of ICH, and patient outcomes were assessed. Five of 30 (17%) patients supported on a VAD from January 2000 to November 2012 were diagnosed with an ICH. Four patients had an identified cerebral thromboembolic injury prior to the ICH. Four patients required interruption in their anticoagulation regimen due to other bleeding concerns prior to ICH. Neurosurgical intervention consisted of evacuation of hemorrhage in one, whereas two others required management of hydrocephalus with external ventricular drainage. Three of the five patients died on VAD support. Two deaths were directly related to ICH, whereas the third was unrelated. Two patients were successfully transplanted; one remains with a significant neurological impairment, and the other has recovered with minimal residual impairment following neurosurgical evacuation of a large subdural hematoma. ICH is a devastating complication of VAD support. Prior ischemic infarcts and interruptions to anticoagulation may put a patient at risk for ICH. Prompt neurosurgical evaluation/intervention can result in positive outcomes.
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Dress codes and appearance policies: challenges under federal legislation, part 1: title VII of the civil rights act and religion.
Health Care Manag (Frederick)
PUBLISHED: 10-31-2013
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As more and more individuals choose to express themselves and their religious beliefs with headwear, jewelry, dress, tattoos, and body piercings and push the envelope on what is deemed appropriate in the workplace, employers have an increased need for creation and enforcement of reasonable dress codes and appearance policies. As with any employment policy or practice, an appearance policy must be implemented and enforced without regard to an individuals race, color, sex, national origin, religion, disability, age, or any other protected status. A policy governing dress and appearance based on the business needs of an employer that is applied fairly and consistently and does not have a disproportionate effect on any protected class will generally be upheld if challenged in court. By examining some of the more common legal challenges to dress codes and how courts have resolved the disputes, health care managers can avoid many potential problems. This article addresses the issue of religious discrimination focusing on dress and appearance and some of the court cases that provide guidance for employers.
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Biomarker-Based Predictive Models for Prognosis in Amyotrophic Lateral Sclerosis.
JAMA Neurol
PUBLISHED: 10-23-2013
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IMPORTANCE Although median survival in amyotrophic lateral sclerosis (ALS) is 2 to 4 years, survival ranges from months to decades, creating prognostic uncertainty. Strategies to predict prognosis would benefit clinical management and outcomes assessments of clinical trials. OBJECTIVE To identify biomarkers in plasma and cerebrospinal fluid (CSF) of patients with ALS that can predict prognosis. DESIGN, PARTICIPANTS, AND SETTING We conducted a retrospective study of plasma (n?=?29) and CSF (n?=?33) biomarkers identified in samples collected between March 16, 2005, and August 22, 2007, from patients with ALS at an academic tertiary care center. Participants included patients who were undergoing diagnostic evaluation in the neurology outpatient clinic and were eventually identified as having definite, probable, laboratory-supported probable, or possible ALS as defined by revised El-Escorial criteria. All were white and none had a family history of ALS. Clinical information extended from initial presentation to death. Genotyping for hemochromatosis (HFE) gene status was performed. Multiplex and immunoassay analysis of plasma and CSF was used to measure levels of 35 biomarkers. Statistical modeling was used to identify biomarker panels that could predict total disease duration. MAIN OUTCOMES AND MEASURES Total disease duration, defined as the time from symptom onset to death, was the main outcome. The hypothesis being tested was formulated after data collection. RESULTS Multivariable models for total disease duration using biomarkers from plasma, CSF, and plasma and CSF combined incorporated 7, 6, and 6 biomarkers to achieve goodness-of-fit R2 values of 0.769, 0.617, and 0.962, respectively. After classification into prognostic categories, actual and predicted values achieved moderate to good agreement, with Cohen ? values of 0.526, 0.515, and 0.930 for plasma, CSF, and plasma and CSF combined models, respectively. Inflammatory biomarkers, including select interleukins, growth factors such as granulocyte colony-stimulating factor, and l-ferritin, had predictive value. CONCLUSIONS AND RELEVANCE This study provides proof-of-concept for a novel multivariable modeling strategy to predict ALS prognosis. These results support unbiased biomarker discovery efforts in larger patient cohorts with detailed longitudinal follow-up.
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Theme: Physical Biology in Cancer. 3. The role of cell glycocalyx in vascular transport of circulating tumor cells.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 10-16-2013
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Circulating tumor cells (CTCs) in blood are known to adhere to the luminal surface of the microvasculature via receptor-mediated adhesion, which contributes to the spread of cancer metastasis to anatomically distant organs. Such interactions between ligands on CTCs and endothelial cell (EC)-bound surface receptors are sensitive to receptor-ligand distances at the nanoscale. The sugar-rich coating on the cell surface known as the glycocalyx, expressed both on the surface of CTCs and ECs, serves as a physical structure that can control the spacing and thus the availability of such receptor-ligand interactions. The cancer cell glycocalyx can also regulate the ability of therapeutic ligands to bind to CTCs in the bloodstream. Here, we review the role of cell glycocalyx on the adhesion and therapeutic treatment of CTCs in the bloodstream.
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Community Fall Prevention Programs: Comparing Three InSTEP Models by Levels of Intensity.
J Aging Phys Act
PUBLISHED: 08-12-2013
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The Fall Prevention Center of Excellence designed three progressive intensity fall prevention program models, Increasing Stability Through Evaluation and Practice (INSTEP) to reduce risk in community-dwelling older adults. Each model included physical activity, medical risk and home safety components and was implemented as a 12-week program for small class sizes (12-15 persons) in community and senior centers. Change in fall rates and fall risk factors was assessed using a battery of performance tests, self-reports of function and fall diaries in a three-group within-subjects (n=200) design measured at baseline, immediately post intervention, and at 3- and 9-months post-intervention. Overall, participants experienced a reduction in falls, improved self-perception of gait and balance, and improved dynamic gait functional. The medium intensity InSTEP model significantly (p = .003) reduced self-reported falls in comparison to the other models. InSTEP is a feasible model for addressing fall risk reduction in community-dwelling older adults.
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Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A.
Blood
PUBLISHED: 08-07-2013
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Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44?800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.
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Design and development of ankle-foot prosthesis with delayed release of plantarflexion.
J Rehabil Res Dev
PUBLISHED: 07-25-2013
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A computer-controlled mechanism that fits a standard ankle-foot prosthesis was designed to capture the absorbed energy in the ankle and delay its release until specific times in the gait cycle. This mechanism used a direct current motor to take up and hold the compression of a carbon-fiber ankle joint. Based on the timing of the contact forces between the foot and the ground, a microprocessor released the spring at preset times later in the gait cycle. This mechanism was added to a Talux prosthetic foot and was employed by a user of a conventional energy-storage ankle-foot prosthesis. His gait was recorded using a motion analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on separate days, and the standard kinematic and kinetic gait data were recorded. The user reported some settings were more comfortable than others. When these preferences were tested with a randomized double-blind trial, the preferences were not consistent. A second user showed a preference for the 55 ms delay. The modifications to the device resulted in changes to the gait of the subjects, including increased cadence and kinematics of the unaffected joints and a longer, slower push from the ankle, which was noticed by both of the subjects.
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Explaining differences in hepatitis C between U.S. veterans and nonveterans in treatment for substance abuse: results from a regression decomposition.
Subst Use Misuse
PUBLISHED: 07-23-2013
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Hepatitis C virus (HCV) infection is common among people with substance abuse histories and a burden for U.S. veterans in particular. This study compares self-reported HCV between 1,652 veterans and 48,013 nonveterans who received public-sector substance abuse treatment in Los Angeles between 2006 and 2010. A higher percentage of veterans than nonveterans reported HCV (6.5% vs. 3.8%, p < .0001). Homelessness and mental illness explained, respectively, 8.6% and 7.1% of the difference in HCV between the two groups, adjusting for other variables. Reducing homelessness and mental illness among veterans may also help reduce the excess burden of HCV in this population.
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Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma.
Sensors (Basel)
PUBLISHED: 07-16-2013
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The isolation of hematopoietic stem and progenitor cells (HSPCs) is critical for transplantation therapy and HSPC research, however current isolation techniques can be prohibitively expensive, time-consuming, and produce variable results. Selectin-coated microtubes have shown promise in rapidly isolating HSPCs from human bone marrow, but further purification of HSPCs remains a challenge. Herein, a biomimetic device for HSPC isolation is presented to mimic the acidic vascular microenvironment during trauma, which can enhance the binding frequency between L-selectin and its counter-receptor PSGL-1 and HSPCs. Under acidic pH conditions, L-selectin coated microtubes enhanced CD34+ HSPC adhesion, as evidenced by decreased cell rolling velocity and increased rolling flux. Dynamic light scattering was utilized as a novel sensor to confirm an L-selectin conformational change under acidic conditions, as previously predicted by molecular dynamics. These results suggest that mimicking the acidic conditions of trauma can induce a conformational extension of L-selectin, which can be utilized for flow-based, clinical isolation of HSPCs.
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Outcomes of systemic to pulmonary artery shunts in patients weighing less than 3 kg: Analysis of shunt type, size, and surgical approach.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 06-28-2013
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To evaluate outcomes of systemic to pulmonary artery shunts (SPS) in patients weighing less than 3 kg with regard to shunt type, shunt size, and surgical approach.
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Comparison of the Use of H1N1 and seasonal influenza vaccinations between veterans and non-veterans in the United States, 2010.
BMC Public Health
PUBLISHED: 05-30-2013
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Veterans of the U.S. armed forces tend to be older and have more chronic health problems than the general adult population, which may place them at greater risk of complications from influenza. Despite Centers for Disease Control and Prevention (CDC) recommendations, seasonal influenza vaccination rates for the general adult population remain well below the national goal of 80%. Achieving this goal would be facilitated by a clearer understanding of which factors influence vaccination.
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Bilateral pulmonary artery banding as rescue intervention in high-risk neonates.
Ann. Thorac. Surg.
PUBLISHED: 01-30-2013
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Presentation in shock and preoperative infection remain risk factors for neonatal cardiac surgery. This report describes bilateral pulmonary artery banding (bPAB) in ductal-dependent lesions with systemic outflow obstruction as rescue intervention before surgery with cardiopulmonary bypass in these high-risk neonates.
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Using exercises to identify Veterans Health Administration priorities for disaster response: findings from the New Madrid Earthquake training exercise.
J Public Health Manag Pract
PUBLISHED: 01-30-2013
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Emergency managers are often charged with prioritizing the relative importance of key issues and tasks associated with disaster response. However, little work has been done to identify specific ways that the decision-making process can be improved. This exercise was conducted with 220 employees of the US Department of Veterans Affairs, who were asked to assign priority rankings to a list of possible options of the most important issues to address after a hypothetical disaster scenario impacting a Veterans Affairs Medical Center. We found that groups that were assigned to represent perspectives farther from the impacted site had less agreement in their identification of the top priorities than those assigned to the impacted facility. These findings suggest that greater geographic and administrative proximity to the impacted site may generate greater clarity and certainty about priority setting. Given the complex structure of many organizations, and the multiple levels of group decision making and coordination likely to be needed during disasters, research to better understand training needs with respect to decision making is essential to improve preparedness. Relatively simple modifications to exercises, as outlined here, could provide valuable information to better understand emergency management decision making across multiple organizational levels.
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Mechanical support as failure intervention in patients with cavopulmonary shunts (MFICS): rationale and aims of a new registry of mechanical circulatory support in single ventricle patients.
Congenit Heart Dis
PUBLISHED: 01-24-2013
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It is now recognized that a majority of single ventricle patients, those with functionally univentricular hearts, who have survived palliative cavopulmonary connection will experience circulatory failure and end-organ dysfunction due to intrinsic inadequacies of a circulation supported by a single ventricle. Thus, there are an increasing number of patients with functional single ventricles presenting with failing circulations that may benefit from mechanical circulatory support (MCS). The paucity of experience with MCS in this population, even at high volume cardiac centers, contributes to limited available data to guide MCS device selection and management. Thus, a registry of MCS in this population would be beneficial to the field. A conference was convened in January 2012 of pediatric and adult cardiologists, pediatric cardiac intensivists, congenital heart surgeons, and adult cardiothoracic surgeons to discuss the current state of MCS, ventricular assist device, and total artificial heart therapy for patients who have undergone cavopulmonary connection, either superior cavopulmonary connection or total cavopulmonary connection. Specifically, individual experience and challenges with VAD therapy in this population was reviewed and creation of a multiinstitutional registry of MCS/ventricular assist device in this population was proposed. This document reflects the consensus from the meeting and provides a descriptive overview of the registry referred to as Mechanical Support as Failure Intervention in Patients with Cavopulmonary Shunts.
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MRI validated echocardiographic technique to measure total cardiac volume: a tool for donor-recipient size matching in pediatric heart transplantation.
Pediatr Transplant
PUBLISHED: 01-24-2013
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Our aim is to develop and validate an accurate method for estimating TCV using standard echocardiographic imaging that can be easily employed to aid in donor-recipient size matching in pediatric heart transplantation. Thirty patients who underwent Echo and cardiac magnetic resonance imaging (cMRI) were identified. TCV was measured on cMRI. TCV was determined echocardiographically by two methods: a volume measurement using the modified Simpsons method on a four-chamber view of the heart; and a calculated volume measurement which assumed a true-elliptical shape of the heart. These two methods where compared with the value obtained by cMRI using the concordance correlation coefficient (CCC). TCV by method 1 correlated well with cMRI (CCC = 0.98%, CI = 0.97, 0.99). TCV by method 2 had a CCC = 0.90 (CI = 0.9464, 0.9716) when compared to cMRI. Left ventricular end-diastolic volume (LVEDV) also correlated as a predictor of TCV in patients with structurally normal hearts and could be described by the equation: TCV = 6.6 (LVEDV) + 12 (R(2)  = 0.97). Echocardiographic assessment of TCV for recipients and their potential donors is a simple process and can be prospectively applied as part of donor evaluation.
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Patterns of sleep quality during and after postacute rehabilitation in older adults: a latent class analysis approach.
J Sleep Res
PUBLISHED: 01-17-2013
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Sleep quality is related to emotional, physical, psychological and cognitive functioning and functional independence in later life. After acute health events, older adults are likely to utilize postacute rehabilitation services to improve functioning and facilitate return to independent living. Patterns of how sleep changes with postacute rehabilitation, and predictors of such patterns, are unknown. The current investigation employed latent class analysis (LCA) methods to classify older adults (n = 233) into groups based on patterns of self-reported sleep quality pre-illness, during postacute rehabilitation and up to 1 year following postacute rehabilitation. Using LCA, older adults were grouped into (1) consistently good sleepers (46%), (2) good sleepers who transitioned into poor sleepers (34%), (3) consistently poor sleepers (14%) and (4) poor sleepers who transitioned into good sleepers (6%). In three planned analyses, pain was an independent predictor of membership in classes 1 or 2 (good pre-illness sleep quality) versus classes 3 or 4 (poor pre-illness sleep quality), and of membership in class 1 (consistently good sleep) versus class 2 (good sleep that transitioned to poor sleep). A lower Mini-Mental State Examination score was a predictor of membership in class 1 versus class 2. There were no statistically significant predictors of membership in class 3 versus class 4. Demographics, comorbidities and depressive symptoms were not significant predictors of class membership. These findings have implications for identification of older adults at risk for developing poor sleep associated with changes in health and postacute rehabilitation. The findings also suggest that pain symptoms should be targeted to improve sleep during postacute rehabilitation.
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Computational and experimental models of cancer cell response to fluid shear stress.
Front Oncol
PUBLISHED: 01-15-2013
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It has become evident that mechanical forces play a key role in cancer metastasis, a complex series of steps that is responsible for the majority of cancer-related deaths. One such force is fluid shear stress, exerted on circulating tumor cells by blood flow in the vascular microenvironment, and also on tumor cells exposed to slow interstitial flows in the tumor microenvironment. Computational and experimental models have the potential to elucidate metastatic behavior of cells exposed to such forces. Here, we review the fluid-generated forces that tumor cells are exposed to in the vascular and tumor microenvironments, and discuss recent computational and experimental models that have revealed mechanotransduction phenomena that may play a role in the metastatic process.
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Determining Occurrence Dynamics when False Positives Occur: Estimating the Range Dynamics of Wolves from Public Survey Data.
PLoS ONE
PUBLISHED: 01-01-2013
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Large-scale presence-absence monitoring programs have great promise for many conservation applications. Their value can be limited by potential incorrect inferences owing to observational errors, especially when data are collected by the public. To combat this, previous analytical methods have focused on addressing non-detection from public survey data. Misclassification errors have received less attention but are also likely to be a common component of public surveys, as well as many other data types. We derive estimators for dynamic occupancy parameters (extinction and colonization), focusing on the case where certainty can be assumed for a subset of detections. We demonstrate how to simultaneously account for non-detection (false negatives) and misclassification (false positives) when estimating occurrence parameters for gray wolves in northern Montana from 2007-2010. Our primary data source for the analysis was observations by deer and elk hunters, reported as part of the states annual hunter survey. This data was supplemented with data from known locations of radio-collared wolves. We found that occupancy was relatively stable during the years of the study and wolves were largely restricted to the highest quality habitats in the study area. Transitions in the occupancy status of sites were rare, as occupied sites almost always remained occupied and unoccupied sites remained unoccupied. Failing to account for false positives led to over estimation of both the area inhabited by wolves and the frequency of turnover. The ability to properly account for both false negatives and false positives is an important step to improve inferences for conservation from large-scale public surveys. The approach we propose will improve our understanding of the status of wolf populations and is relevant to many other data types where false positives are a component of observations.
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Emergency department crowding is associated with decreased quality of analgesia delivery for children with pain related to acute, isolated, long-bone fractures.
Acad Emerg Med
PUBLISHED: 12-16-2011
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The authors sought to determine which quality measures of analgesia delivery are most influenced by emergency department (ED) crowding for pediatric patients with long-bone fractures.
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HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation.
Hum. Reprod.
PUBLISHED: 12-08-2011
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Recurrent AZFb deletions on the human Y chromosome are associated with an absence of ejaculated spermatozoa consequent to a meiotic maturation arrest that prevents the progression of germ cells to haploid stages. The extreme rarity of partial deletions has hampered the identification of the AZFb genes required for normal meiotic stages. The critical interval, refined by two overlapping deletions associated with full spermatogenesis (AZFc and b1/b3), measures over 4 Mb and contains 13 coding genes: CDY2, XKRY, HSFY1, HSFY2, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2 and four copies of RBMY.
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Poor self-reported sleep quality predicts mortality within one year of inpatient post-acute rehabilitation among older adults.
Sleep
PUBLISHED: 12-02-2011
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To evaluate the association between self-reported sleep quality among older adults during inpatient post-acute rehabilitation and one-year survival.
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Do correlates of dual use by American Indian and Alaska Native Veterans operate uniformly across the Veterans Health Administration and the Indian Health Service?
J Gen Intern Med
PUBLISHED: 10-13-2011
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To determine if the combined effects of patient-level (demographic and clinical characteristics) and organizational-level (structure and strategies to improve access) factors are uniformly associated with utilization of Indian Health Service (IHS) and/or Veterans Health Administration (VHA) by American Indian and Alaska Native (AIAN) Veterans to inform policy which promotes dual use.
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Coarctectomy combined with an interdigitating arch reconstruction results in a lower incidence of recurrent arch obstruction after the Norwood procedure than coarctectomy alone.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 09-05-2011
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Recurrent aortic arch obstruction after the Norwood procedure continues to be a source of morbidity. We sought to determine if a modified interdigitating technique for aortic arch reconstruction during the Norwood procedure decreased recurrent arch obstruction.
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ContextProvider: Context awareness for medical monitoring applications.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 08-29-2011
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Smartphones are sensor-rich and Internet-enabled. With their on-board sensors, web services, social media, and external biosensors, smartphones can provide contextual information about the device, user, and environment, thereby enabling the creation of rich, biologically driven applications. We introduce ContextProvider, a framework that offers a unified, query-able interface to contextual data on the device. Unlike other context-based frameworks, ContextProvider offers interactive user feedback, self-adaptive sensor polling, and minimal reliance on third-party infrastructure. ContextProvider also allows for rapid development of new context and bio-aware applications. Evaluation of ContextProvider shows the incorporation of an additional monitoring sensor into the framework with fewer than 100 lines of Java code. With adaptive sensor monitoring, power consumption per sensor can be reduced down to 1% overhead. Finally, through the use of context, accuracy of data interpretation can be improved by up to 80%.
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Creation and implementation of a prospective pediatric clinical outcomes registry.
J Registry Manag
PUBLISHED: 06-01-2011
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To build a pediatric clinical outcomes registry (COR) using a contemporary information system designed to support research and outcome studies and to improve patient care and quality of life.
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Aortic exclusion: a method of handling aortic insufficiency in the pediatric population needing mechanical circulatory support.
Pediatr Cardiol
PUBLISHED: 05-25-2011
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Aortic insufficiency (AI) is generally regarded as a contraindication for mechanical circulatory support in children. In the current Berlin EXCOR trial, moderate to severe AI is an exclusion criterion. There are reports in the literature of successful mechanical circulatory support (MCS) in adult patients with significant AI via "aortic exclusion" or bioprosthetic aortic valve replacement. We report the first case of aortic exclusion in an infant with moderate to severe aortic insufficiency in need of MCS.
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Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle.
Circulation
PUBLISHED: 05-16-2011
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We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle.
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Aortopulmonary window.
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu
PUBLISHED: 03-30-2011
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Aortopulmonary window is a rare defect caused by failure of fusion of the two opposing conotruncal ridges that are responsible for separating the truncus arteriosus into the aorta and pulmonary artery. Aortopulmonary window may occur as an isolated lesion or it can be associated with other cardiac abnormalities in one third to one half of cases. The most common associated lesions are arch abnormalities, specifically interrupted aortic arch and coarctation of the aorta. Antenatal diagnosis is rare. In the current era, early mortality following repair of simple aortopulmonary window approaches zero and depends on the presence of associated lesions, especially interrupted aortic arch. Long-term outcome should be excellent. Early morbidity includes pulmonary artery stenosis and residual aortopulmonary septal defects. Long-term follow-up is indicated to look for recurrent lesions such as the development of branch pulmonary artery stenosis and arch obstruction.
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The coming of the Greeks to Provence and Corsica: Y-chromosome models of archaic Greek colonization of the western Mediterranean.
BMC Evol. Biol.
PUBLISHED: 03-14-2011
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The process of Greek colonization of the central and western Mediterranean during the Archaic and Classical Eras has been understudied from the perspective of population genetics. To investigate the Y chromosomal demography of Greek colonization in the western Mediterranean, Y-chromosome data consisting of 29 YSNPs and 37 YSTRs were compared from 51 subjects from Provence, 58 subjects from Smyrna and 31 subjects whose paternal ancestry derives from Asia Minor Phokaia, the ancestral embarkation port to the 6th century BCE Greek colonies of Massalia (Marseilles) and Alalie (Aleria, Corsica).
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Dithiothreitol causes HIV-1 integrase dimer dissociation while agents interacting with the integrase dimer interface promote dimer formation.
Biochemistry
PUBLISHED: 02-21-2011
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We have developed a homogeneous time-resolved fluorescence resonance energy transfer (FRET)-based assay that detects the formation of HIV-1 integrase (IN) dimers. The assay utilizes IN monomers that express two different epitope tags that are recognized by their respective antibodies, coupled to distinct fluorophores. Surprisingly, we found that dithiothreitol (DTT), a reducing agent essential for in vitro enzymatic activity of IN, weakened the interaction between IN monomers. This effect of DTT on IN is dependent on its thiol groups, since the related chemical threitol, which contains hydroxyls in place of thiols, had no effect on IN dimer formation. By studying mutants of IN, we determined that cysteines in IN appear to be dispensable for the dimer dissociation effect of DTT. Peptides derived from the IN binding domain (IBD) of lens epithelium derived growth factor/transcriptional coactivator p75 (LEDGF), a cellular cofactor that interacts with the IN dimer interface, were tested in this IN dimerization assay. These peptides, which compete with LEDGF for binding to IN, displayed an intriguing equilibrium binding dose-response curve characterized by a plateau rising to a peak, then descending to a second plateau. Mathematical modeling of this binding system revealed that these LEDGF-derived peptides promote IN dimerization and block subunit exchange between IN dimers. This dose-response behavior was also observed with a small molecule that interacts with the IN dimer interface and inhibits LEDGF binding to IN. In conclusion, this novel IN dimerization assay revealed that peptide and small molecule inhibitors of the IN-LEDGF interaction also stabilize IN dimers and promote their formation.
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The Y-encoded gene zfy2 acts to remove cells with unpaired chromosomes at the first meiotic metaphase in male mice.
Curr. Biol.
PUBLISHED: 01-31-2011
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During male but not female mammalian meiosis, there is efficient apoptotic elimination of cells with unpaired (univalent) chromosomes at the first meiotic metaphase (MI) [1]. Apoptotic elimination of MI spermatocytes is seen in response to the univalent X chromosome of XSxr(a)O male mice [2], in which the X chromosome carries Sxr(a) [3, 4], the Y-chromosome-derived sex-reversal factor that includes the testis determinant Sry. Sxr(b) is an Sxr(a)-derived variant in which a deletion has removed six Y short-arm genes and created a Zfy2/Zfy1 fusion gene spanning the deletion breakpoint [4, 5]. XSxr(b)O males have spermatogonial arrest that can be overcome by the re-addition of Eif2s3y from the deletion as a transgene; however, XSxr(b)OEif2s3y transgenic males do not show the expected elimination of MI spermatocytes in response to the univalent [6]. Here we show that these XSxr(b)OEif2s3y males have an impaired apoptotic response with completion of the first meiotic division, but there is no second meiotic division. We then show that Zfy2 (but not the closely related Zfy1) is sufficient to reinstate the apoptotic response to the X univalent. These findings provide further insight into the basis for the much lower transmission of chromosomal errors originating at the first meiotic division in men than in women [7].
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Association of smoking and chronic pain syndromes in Kentucky women.
J Pain
PUBLISHED: 01-18-2011
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The objective of this project was to determine the relationship between cigarette smoking and the reporting of chronic pain syndromes among participants in the Kentucky Womens Health Registry. Data was analyzed on 6,092 women over 18 years of age who responded to survey questions on pain and smoking. The chronic pain syndromes included in the analysis were fibromyalgia, sciatica, chronic neck pain, chronic back pain, joint pain, chronic head pain, nerve problems, and pain all over the body. Analyses controlled for age, body mass index, and Appalachian versus non-Appalachian county of residence. Results showed that women who were daily smokers reported more chronic pain (defined as the presence of any reported chronic pain syndromes) than women who were never smokers (adjusted odds ratio [aOR] = 2.04 and 95% confidence interval [CI] 1.67, 2.49). An increased risk was also seen for "some-day" smokers (aOR 1.68, 95% CI 1.24, 2.27), and former smokers (aOR 1.20, 95% CI 1.06, 1.37), though with less of an association in the latter group. This study provides evidence of an association between chronic pain and cigarette smoking that is reduced in former smokers.
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Surgery and critical care for anomalous coronary artery from the pulmonary artery.
Cardiol Young
PUBLISHED: 11-20-2010
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Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital cardiac malformation that accounts for 0.25-0.50% of children with congenital cardiac disease and can cause myocardial dysfunction in young infants. In any infant presenting with ventricular dysfunction, the diagnosis of anomalous origin of the left coronary artery from the pulmonary artery must be suspected and the origin of the coronary arteries must be confirmed. The diagnosis of anomalous origin of the left coronary artery from the pulmonary artery is an indication for surgical repair. A two-coronary arterial system is the goal and is almost always achievable. The goal of surgical therapy is the creation of a two-coronary arterial system, which appears to provide better long-term survival and protection from left ventricular dysfunction and mitral valvar regurgitation than does simple ligation of the anomalous coronary artery. Direct reimplantation of the anomalous coronary artery is the procedure of choice. It is straightforward and borrows from well-practised techniques commonly used in other procedures such as the arterial switch operation. For the rare patient in whom direct reimplantation is not possible, strategies to lengthen the anomalous coronary artery, or baffle it within the pulmonary root, are available. Mitral valvar regurgitation is common at presentation, but following the establishment of a two-coronary arterial system and satisfactory myocardial perfusion, regurgitation of the mitral valve resolves in the vast majority. Therefore, mitral valvuloplasty at the time of initial surgery for anomalous origin of the left coronary artery from the pulmonary artery is not indicated. Post-operative care requires careful manipulation of inotropic support and reduction of afterload. Mechanical support, with either extracorporeal membrane oxygenation or left ventricular assist device, should be available for use if necessary.
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A survey-based assessment of United States clinical laboratory response to the 2009 H1N1 influenza outbreak.
Arch. Pathol. Lab. Med.
PUBLISHED: 11-04-2010
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The recent outbreak of pandemic influenza created enormous economic, logistical, and analytical challenges for clinical laboratories. Laboratory response represented a critical element in the care of affected patients, but little has been published regarding this aspect of the pandemic.
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Humoral rejection after pediatric heart transplantation: a case report.
Prog Transplant
PUBLISHED: 10-09-2010
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Humoral rejection was observed 2 years after heart transplantation in a 10-year-old African American girl with sickle cell disease. Hemodynamic compromise developed, and the patient started treatment with extracorporeal membrane oxygenation within 24 hours of admission. With cellular rejection initially believed to be the cause, administration of thymoglobulin and high-dose steroids was initiated. Human leukocyte antigen antibody analysis revealed high titers of donor-specific class I and II antibodies. Aggressive treatment for antibody-mediated rejection was started with plasmapheresis and administration of intravenous immune globulin and rituximab. The patient displayed clinical signs of infection and was treated with antimicrobial, antiviral, and antifungal agents. Computed tomography of the chest suggested asperigillous infection. The patient underwent a left upper lobectomy. The patient recovered and has done well, now 4 years after having received the heart transplant. Antibody-mediated rejection should be considered early in heart transplant patients presenting with hemodynamic compromise and may respond to aggressive antibody and B cell-directed therapy. Vigilance for secondary infections, especially during treatment for rejection, is crucial.
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A review of sentinel laboratory performance: identification and notification of bioterrorism agents.
Arch. Pathol. Lab. Med.
PUBLISHED: 10-07-2010
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The anthrax incident of 2001 in the United States prompted the College of American Pathologists (CAP), the Association of Public Health Laboratories, and the Centers for Disease Control and Prevention to develop exercises for Laboratory Response Network (LRN) sentinel laboratories.
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Fibroblast growth factor-10 signals development of von Brunns nests in the exstrophic bladder.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 08-18-2010
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von Brunns nests have long been recognized as precursors of benign lesions of the urinary bladder mucosa. We report here that von Brunns nests are especially prevalent in the exstrophic bladder, a birth defect that predisposes the patient to formation of bladder cancer. Cells of von Brunns nest were found to coalesce into a stratified, polarized epithelium which surrounds itself with a capsule-like structure rich in types I, III, and IV collagen. Histocytochemical analysis and keratin profiling demonstrated that nested cells exhibited a phenotype similar, but not identical, to that of urothelial cells of transitional epithelium. Immunostaining and in situ hybridization analysis of exstrophic tissue demonstrated that the FGF-10 receptor is synthesized and retained by cells of von Brunns nest. In contrast, FGF-10 is synthesized and secreted by mesenchymal fibroblasts via a paracrine pathway that targets basal epithelial cells of von Brunns nests. Small clusters of 10pRp cells, positive for both FGF-10 and its receptor, were observed both proximal to and inside blood vessels in the lamina propria. The collective evidence points to a mechanism where von Brunns nests develop under the control of the FGF-10 signal transduction system and suggests that 10pRp cells may be the original source of nested cells.
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Complete deletion of the AZFb interval from the Y chromosome in an oligozoospermic man.
Hum. Reprod.
PUBLISHED: 08-17-2010
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Deletion of the entire AZFb interval from the Y chromosome is strictly associated with azoospermia arising from maturation arrest during meiosis. Here, we describe the exceptional case of an oligozoospermic man, 13-1217, with an AZFb + c (P5/distal-P1) deletion. Through the characterization of this patient, and two AZFb (P5/proximal-P1) patients with maturation arrest, we have explored three possible explanations for his exceptionally progressive spermatogenesis.
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Genetic diversity on the Comoros Islands shows early seafaring as major determinant of human biocultural evolution in the Western Indian Ocean.
Eur. J. Hum. Genet.
PUBLISHED: 08-11-2010
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The Comoros Islands are situated off the coast of East Africa, at the northern entrance of the channel of Mozambique. Contemporary Comoros society displays linguistic, cultural and religious features that are indicators of interactions between African, Middle Eastern and Southeast Asian (SEA) populations. Influences came from the north, brought by the Arab and Persian traders whose maritime routes extended to Madagascar by 700-900 AD. Influences also came from the Far East, with the long-distance colonisation by Austronesian seafarers that reached Madagascar 1500 years ago. Indeed, strong genetic evidence for a SEA, but not a Middle Eastern, contribution has been found on Madagascar, but no genetic trace of either migration has been shown to exist in mainland Africa. Studying genetic diversity on the Comoros Islands could therefore provide new insights into human movement in the Indian Ocean. Here, we describe Y chromosomal and mitochondrial genetic variation in 577 Comorian islanders. We have defined 28 Y chromosomal and 9 mitochondrial lineages. We show the Comoros population to be a genetic mosaic, the result of tripartite gene flow from Africa, the Middle East and Southeast Asia. A distinctive profile of African haplogroups, shared with Madagascar, may be characteristic of coastal sub-Saharan East Africa. Finally, the absence of any maternal contribution from Western Eurasia strongly implicates male-dominated trade and religion as the drivers of gene flow from the North. The Comoros provides a first view of the genetic makeup of coastal East Africa.
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Your workers may be contingent but your liability for them is certain: Part III: other employment issues.
Health Care Manag (Frederick)
PUBLISHED: 08-06-2010
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Hiring contingent workers can significantly help health care employers reduce labor costs while maintaining the staff required for quality patient care. However, a number of federal laws create legal land mines that await the unsuspecting employer. This article, the concluding part of a 3-part examination of contingent employment, addresses additional issues including benefits, tax implications, workers compensation, contract considerations, and the screening of potential staffing partners.
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Candidate urinary biomarker discovery in ureteropelvic junction obstruction: a proteomic approach.
J. Urol.
PUBLISHED: 07-20-2010
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Ureteropelvic junction obstruction may either worsen and require surgery, improve or remain stable. It may take upward of 3 years for the natural history to unfold. Urinary proteome analysis using capillary electrophoresis mass spectrometry has been shown to differentiate between normal infants and those with ureteropelvic junction obstruction. We sought to confirm these findings using liquid chromatography/nano-spray mass spectrometry to examine the urinary proteome in patients with unilateral grade IV ureteropelvic junction obstruction compared to age matched healthy infants.
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The interpretation of habitat preference metrics under use-availability designs.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 06-23-2010
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Models of habitat preference are widely used to quantify animal-habitat relationships, to describe and predict differential space use by animals, and to identify habitat that is important to an animal (i.e. that is assumed to influence fitness). Quantifying habitat preference involves the statistical comparison of samples of habitat use and availability. Preference is therefore contingent upon both of these samples. The inferences that can be made from use versus availability designs are influenced by subjectivity in defining what is available to the animal, the problem of quantifying the accessibility of available resources and the framework in which preference is modelled. Here, we describe these issues, document the conditional nature of preference and establish the limits of inferences that can be drawn from these analyses. We argue that preference is not interpretable as reflecting the intrinsic behavioural motivations of the animal, that estimates of preference are not directly comparable among different samples of availability and that preference is not necessarily correlated with the value of habitat to the animal. We also suggest that preference is context-dependent and that functional responses in preference resulting from changing availability are expected. We conclude by describing advances in analytical methods that begin to resolve these issues.
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The home-range concept: are traditional estimators still relevant with modern telemetry technology?
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 06-23-2010
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Recent advances in animal tracking and telemetry technology have allowed the collection of location data at an ever-increasing rate and accuracy, and these advances have been accompanied by the development of new methods of data analysis for portraying space use, home ranges and utilization distributions. New statistical approaches include data-intensive techniques such as kriging and nonlinear generalized regression models for habitat use. In addition, mechanistic home-range models, derived from models of animal movement behaviour, promise to offer new insights into how home ranges emerge as the result of specific patterns of movements by individuals in response to their environment. Traditional methods such as kernel density estimators are likely to remain popular because of their ease of use. Large datasets make it possible to apply these methods over relatively short periods of time such as weeks or months, and these estimates may be analysed using mixed effects models, offering another approach to studying temporal variation in space-use patterns. Although new technologies open new avenues in ecological research, our knowledge of why animals use space in the ways we observe will only advance by researchers using these new technologies and asking new and innovative questions about the empirical patterns they observe.
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Spica casting compared to Bryants traction after complete primary repair of exstrophy: safe and effective in a longitudinal cohort study.
J. Urol.
PUBLISHED: 06-19-2010
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Bryants traction is the most commonly used method for immobilization after bladder exstrophy repair. We hypothesized that spica casting is a safe and effective alternative to Bryants traction after complete primary repair of exstrophy.
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Multiplexed quantitative real-time PCR to detect 22q11.2 deletion in patients with congenital heart disease.
Physiol. Genomics
PUBLISHED: 06-15-2010
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22q11.2 Deletion syndrome (22q11.2 DS) [DiGeorge syndrome type 1 (DGS1)] occurs in ?1:3,000 live births; 75% of children with DGS1 have severe congenital heart disease requiring early intervention. The gold standard for detection of DGS1 is fluorescence in situ hybridization (FISH) with a probe at the TUPLE1 gene. However, FISH is costly and is typically ordered in conjunction with a karyotype analysis that takes several days. Therefore, FISH is underutilized and the diagnosis of 22q11.2 DS is frequently delayed, often resulting in profound clinical consequences. Our goal was to determine whether multiplexed, quantitative real-time PCR (MQPCR) could be used to detect the haploinsufficiency characteristic of 22q11.2 DS. A retrospective blinded study was performed on 382 subjects who had undergone congenital heart surgery. MQPCR was performed with a probe localized to the TBX1 gene on human chromosome 22, a gene typically deleted in 22q11.2 DS. Cycle threshold (C(t)) was used to calculate the relative gene copy number (rGCN). Confirmation analysis was performed with the Affymetrix 6.0 Genome-Wide SNP Array. With MQPCR, 361 subjects were identified as nondeleted with an rGCN near 1.0 and 21 subjects were identified as deleted with an rGCN near 0.5, indicative of a hemizygous deletion. The sensitivity (21/21) and specificity (361/361) of MQPCR to detect 22q11.2 deletions was 100% at an rGCN value drawn at 0.7. One of 21 subjects with a prior clinical (not genetically confirmed) DGS1 diagnosis was found not to carry the deletion, while another subject, not previously identified as DGS1, was detected as deleted and subsequently confirmed via microarray. The MQPCR assay is a rapid, inexpensive, sensitive, and specific assay that can be used to screen for 22q11.2 deletion syndrome. The assay is readily adaptable to high throughput.
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Forecasting Hotspots - A Predictive Analytics Approach.
IEEE Trans Vis Comput Graph
PUBLISHED: 05-26-2010
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In spatiotemporal data, analysts are searching for regions of space and time with unusually high incidences of events (hotspots). In the cases that hotspots are found, analysts would like to predict how these regions may grow in order to plan resource allocation and preventative measures. Furthermore, analysts would also like to predict where future hotspots may occur. To facilitate such forecasting, we have created a predictive visual analytics toolkit that provides analysts with linked spatiotemporal and statistical analytic views. Our system models spatiotemporal events through the combination of kernel density estimation for event distribution and seasonal trend decomposition by loess smoothing for temporal predictions. We provide analysts with estimates of error in our modeling, along with spatial and temporal alerts to indicate the occurrence of statistically significant hotspots. Spatial data is distributed based on a modeling of previous event locations, thereby maintaining a temporal coherence with past events. Such tools allow analysts to perform real-time hypothesis testing, plan intervention strategies, and allocate resources to correspond to perceived threats.
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Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms.
PLoS ONE
PUBLISHED: 05-07-2010
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Screening tests for Trisomy 21 (T21), also known as Down syndrome, are routinely performed for the majority of pregnant women. However, current tests rely on either evaluating non-specific markers, which lead to false negative and false positive results, or on invasive tests, which while highly accurate, are expensive and carry a risk of fetal loss. We outline a novel, rapid, highly sensitive, and targeted approach to non-invasively detect fetal T21 using maternal plasma DNA.
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Your workers may be contingent, but your liability for them is certain: part II: Issues under federal employment and labor legislation.
Health Care Manag (Frederick)
PUBLISHED: 05-04-2010
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Hiring contingent workers can significantly help health care employers reduce labor costs while maintaining the staff required for quality patient care. However, a number of federal laws create legal land mines that await the unsuspecting employer. This article, the second part of a 3-part examination of contingent employment, addresses the effects of several key pieces of employment and labor legislation on the employment of contingent workers.
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Perioperative monitoring in high-risk infants after stage 1 palliation of univentricular congenital heart disease.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 04-19-2010
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Survival of high-risk patients with univentricular heart disease after Norwood palliation is reduced. We hypothesized that early goal-directed monitoring with venous oximetry and near-infrared spectroscopy would offset their increased vulnerability and improve survival.
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Intraclass correlation estimates for cancer screening outcomes: estimates and applications in the design of group-randomized cancer screening studies.
J. Natl. Cancer Inst. Monographs
PUBLISHED: 04-14-2010
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Screening has become one of our best tools for early detection and prevention of cancer. The group-randomized trial is the most rigorous experimental design for evaluating multilevel interventions. However, identifying the proper sample size for a group-randomized trial requires reliable estimates of intraclass correlation (ICC) for screening outcomes, which are not available to researchers. We present crude and adjusted ICC estimates for cancer screening outcomes for various levels of aggregation (physician, clinic, and county) and provide an example of how these ICC estimates may be used in the design of a future trial.
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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.