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Find video protocols related to scientific articles indexed in Pubmed.
Effects of cactus fiber on the excretion of dietary fat in healthy subjects: a double blind, randomized, placebo-controlled, crossover clinical investigation.
Curr Ther Res Clin Exp
PUBLISHED: 12-01-2014
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Cactus (Opuntia ficus-indica) fiber was shown to promote weight loss in a 3-month clinical investigation. As demonstrated by in vitro studies, cactus fiber binds to dietary fat and its use results in reduced absorption, which in turn leads to reduced energy absorption and ultimately the reduction of body weight.
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Smooth muscle architecture within cell-dense vascular tissues influences functional contractility.
Integr Biol (Camb)
PUBLISHED: 11-04-2014
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The role of vascular smooth muscle architecture in the function of healthy and dysfunctional vessels is poorly understood. We aimed at determining the relationship between vascular smooth muscle architecture and contractile output using engineered vascular tissues. We utilized microcontact printing and a microfluidic cell seeding technique to provide three different initial seeding conditions, with the aim of influencing the cellular architecture within the tissue. Cells seeded in each condition formed confluent and aligned tissues but within the tissues, the cellular architecture varied. Tissues with a more elongated cellular architecture had significantly elevated basal stress and produced more contractile stress in response to endothelin-1 stimulation. We also found a correlation between the contractile phenotype marker expression and the cellular architecture, contrary to our previous findings in non-confluent tissues. Taken with previous results, these data suggest that within cell-dense vascular tissues, smooth muscle contractility is strongly influenced by cell and tissue architectures.
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Assessing 3rd year medical students' interprofessional collaborative practice behaviors during a standardized patient encounter: A multi-institutional, cross-sectional study.
Med Teach
PUBLISHED: 10-15-2014
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Abstract Background: To understand how third-year medical student interprofessional collaborative practice (IPCP) is affected by self-efficacy and interprofessional experiences (extracurricular experiences and formal curricula). Methods: The authors measured learner IPCP using an objective structured clinical examination (OSCE) with a standardized nurse (SN) and standardized patient (SP) during a statewide clinical performance examination. At four California medical schools from April to August 2012, SPs and SNs rated learner IPCP (10 items, range 0-100) and patient-centered communication (10 items, range 0-100). Post-OSCE, students reported their interprofessional self-efficacy (16 items, 2 factors, range 1-10) and prior extracurricular interprofessional experiences (3 items). School representatives shared their interprofessional curricula during guided interviews. Results: Four hundred sixty-four of 530 eligible medical students (88%) participated. Mean IPCP performance was 79.6?±?14.1 and mean self-efficacy scores were 7.9 (interprofessional teamwork) and 7.1 (interprofessional feedback and evaluation). Seventy percent of students reported prior extracurricular interprofessional experiences; all schools offered formal interprofessional curricula. IPCP was associated with self-efficacy for interprofessional teamwork (??=?1.6, 95% CI [0.1, 3.1], p?=?0.04) and patient-centered communication (??=?12.5, 95% CI [2.7, 22.3], p?=?0.01). Conclusions: Medical student IPCP performance was associated with self-efficacy for interprofessional teamwork and patient-centered communication. Increasing interprofessional opportunities that influence medical students' self-efficacy may increase engagement in IPCP.
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A High Efficiency Induction of Dopaminergic Cells from Human Umbilical Mesenchymal Stem Cells for the Treatment of Hemiparkinsonian Rats.
Cell Transplant
PUBLISHED: 10-08-2014
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Background The success rate in previous attempts at transforming human mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord to dopaminergic cells was a mere 12.7 %. The present study was therefore initiated to establish a more effective procedure for better yield of dopaminergic cells in such transformation for more effective HUMSC-based therapy for Parkinsonism. Methods To examine, in vitro, the effects of enhanced Nurr1 expression in HUMSCs on their differentiation, cells were processed through the three-stage differentiation protocol. The capacity of such cells to synthesize and release dopamine was measured by HPLC. The therapeutic effects of Nurr1-overexppressed HUMSCs were examined in 6-hydroxydopamine-lesioned rats by quantification of rotations in response to amphetamine. Results Enhanced Nurr1 expression in HUMSCs promoted the transformation into dopaminergic cells in vitro through stepwise culturing in sonic hedgehog, and fibroblast growth factor-8, neuron-conditioned medium. The success rate was about 71%, as determined by immunostaining for tyrosine hydroxylase, and around 94 nM dopamine synthesis (intracellular and released into the culture medium), as measured by HPLC. Additionally, transplantation of such cells into the striatum of hemiparkinsonian rats resulted in improvement of their behavioral deficits, as indicated by amphetamine-evoked rotation scores. Viability of the transplanted cells lasted for at least 3 months as verified by positive staining for tyrosine hydroxylase. Conclusions Nurr1, FGF8, Shh and NCM can synergistically enhance the differentiation of HUMSCs into dopaminergic cells, and may pave the way for HUMSCs-based treatments for Parkinson's disease.
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Long-term vascular contractility assay using genipin-modified muscular thin films.
Biofabrication
PUBLISHED: 09-24-2014
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Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss. To achieve this, we developed a microfluidic delivery system to pattern genipin and extracellular matrix proteins on PDMS prior to cell seeding. Tissues constructed using this method showed improved viability and maintenance of in vivo-like lamellar structure. Functional contractility of tissues fabricated on genipin-modified substrates remained consistent throughout two weeks in culture. These results suggest that muscular thin films with genipin-modified PDMS substrates are a viable method for conducting functional studies of arterial growth and remodeling in vascular diseases.
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Bloodstream infections at a tertiary referral hospital in Yangon, Myanmar.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 09-23-2014
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Data regarding characteristics of bloodstream infections in Myanmar are limited.
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FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells.
Oncotarget
PUBLISHED: 09-20-2014
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Several reports suggest that malignant cells generate phenotypic diversity through fusion with various types of stromal cells within the tumor microenvironment. Mesenchymal stem cell (MSC) is one of the critical components in the tumor microenvironment and a promising fusogenic candidate, but the underlying functions of MSC fusion with malignant cell have not been fully examined. Here, we demonstrate that MSCs fuse spontaneously with lung cancer cells, and the latter is reprogrammed to slow growth and stem-like state. Transcriptome profiles reveal that lung cancer cells are reprogrammed to a more benign state upon MSC fusion. We further identified FOXF1 as a reprogramming mediator that contributes not only to the reprogramming toward stemness but also to the p21-regulated growth suppression in fusion progeny. Collectively, MSC fusion does not enhance the intrinsic malignancy of lung cancer cells. The anti-malignant effects of MSC fusion-induced reprogramming on lung cancer cells were accomplished by complementation of tumorigenic defects, including restoration of p21 function and normal terminal differentiation pathways as well as up-regulation of FOXF1, a putative tumor suppressor. Such fusion process raises the therapeutic potential that MSC fusion can be utilized to reverse cellular phenotypes in cancer.
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History of Atrial Fibrillation as a Risk Factor in Patients With Heart Failure and Preserved Ejection Fraction.
Circ Heart Fail
PUBLISHED: 09-15-2014
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-Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established.
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Rising Incidence of Early-Onset Colorectal Cancer in Australia over Two Decades: Report and Review.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-12-2014
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The average age at diagnosis for colorectal cancer in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilised or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of colorectal cancer in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries which share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for colorectal cancer under age 50 years, and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding colorectal cancer in young adults, to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol and sedentary lifestyles, and to identify the questions remaining to be addressed. Though absolute numbers might not justify a population screening approach, the dispersal of young adults with colorectal cancer across the primary healthcare system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of colorectal cancers or by removal of advanced polyps.
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Bilateral diffuse fluorodeoxyglucose uptake in thyroid gland diagnosed by fluorodeoxyglucose-positron emission tomography/computed tomography.
World J Nucl Med
PUBLISHED: 09-06-2014
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Our patient is a female who was first diagnosed with breast cancer at the age of 23. A follow-up fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) at age 44 revealed diffuse high FDG uptake in an enlarged thyroid gland. Fine-needle aspiration (FNA) of the thyroid mass revealed estrogen receptor/progesterone receptor negative, human epidermal growth factor receptor 2+ breast cancer. To the best of our knowledge, this is the first case to report breast cancer metastasis to the thyroid in a diffuse pattern on FDG-PET/CT. Bilateral diffuse uptake of FDG in thyroid is the most commonly associated with benign conditions. However, FNA biopsies need to be done to rule out metastatic disease in thyroid lesions with diffuse high FDG uptake, especially for patients with history of cancer.
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Use of NaF-18-Positron Emission Tomography/Computed Tomography in the Detection of Bone Metastasis from Papillary Renal Cell Carcinoma.
World J Nucl Med
PUBLISHED: 09-06-2014
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We present a case of a 60-year-old white male with a history of papillary renal cell carcinoma (PRCC) status postpartial nepherectomy. He was followed-up annually with abdominal computed tomography (CT) scans to monitor for tumor recurrence. A solitary metastatic bony lesion was detected by CT 4 years after partial nephrectomy and it was confirmed by NaF-positron emission tomography (PET)/CT and magnetic resonance imaging. He underwent external beam radiation therapy (XRT) for solitary metastasis to L1 vertebra. The L1 lesion was treated with XRT, which exhibited no fluorodeoxyglucose activity after the treatment. This is the first case report to mention the use of NaF-18-PET/CT in the detection of bone metastasis from PRCC. Our case once again emphasizes the usefulness of NaF-18-PET/CT in RCC follow-up.
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Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.
Biomaterials
PUBLISHED: 08-28-2014
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Osteoarthritis (OA) is a common disease associated with tissue inflammation, physical disability and imbalanced homeostasis in cartilage. For advanced treatments, biological approaches are currently focused on tissue regeneration and anti-inflammation. This study was undertaken to evaluate the therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) (HA+PRP) on OA. Articular chondrocytes were obtained from five OA patients. The optimal HA and PRP concentrations were evaluated by MTT assay. The expressions of chondrogenic and inflammatory genes were analyzed by RT-PCR. Signaling pathway was examined by immunoblotting and the expressions of OA pathology-related chemokines and cytokines was demonstrated by real-time PCR-based SuperArray. The therapeutic efficacies of HA+PRP were then demonstrated in 3D arthritic neo-cartilage and ACLT-OA model. Here we showed that HA+PRP could greatly retrieve pro-inflammatory cytokines-reduced articular chondrocytes proliferation and chondrogenic phenotypes, the mechanism of which involve the sequential activation of specific receptors CD44 and TGF-?RII, downstream mediators Smad2/3 and Erk1/2, and the chondrogenic transcription factor SOX9. The real-time PCR-based SuperArray results also indicated that OA pathology-related chemokines and cytokines could be efficiently suppressed by HA+PRP. Moreover, the cartilaginous ECM could be retrieved from inflammation-induced degradation by HA+PRP in both 2D monolayer and 3D neo-cartilage model. Finally, the intra-articular injection of HA+PRP could strongly rescue the meniscus tear and cartilage breakdown and then decrease OA-related immune cells. The combination of HA+PRP can synergistically promote cartilage regeneration and inhibit OA inflammation. This study might offer an advanced and alternative OA treatment based on detailed regenerative mechanisms.
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HAS-BLED and CHA2DS2-VASc Scores as Predictors of Bleeding and Thrombotic Risk after Continuous-Flow Ventricular Assist Device Implantation.
J. Card. Fail.
PUBLISHED: 08-21-2014
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HAS-BLED and CHA2DS2-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation.
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Factors Affecting Uptake of NaF-18 by the Normal Skeleton.
J Clin Med Res
PUBLISHED: 07-31-2014
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The primary aim of this study was to examine if factors such as renal function, height, weight and age could affect the uptake of sodium fluoride-18 (NaF-18) by the normal bone. This is the first study to examine the possible factors that can influence NaF-18 uptake in the normal bone.
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Evaluation of Polymeric Nanoparticle Formulations by Effective Imaging and Quantitation of Cellular Uptake for Controlled Delivery of Doxorubicin.
Small
PUBLISHED: 07-15-2014
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Various polymeric nanoparticles have been extensively engineered for applications in controlled drug release delivery in the last decades. Currently, there is a great demand to develop a strategy to qualitatively and quantitatively evaluate these polymeric nanoparticle formulations for producing innovative delivery systems. In this work, a screening platform is developed using luminescent quantum dots as drug model and imaging label to evaluate nanoparticle formulations incorporating either hydrophilic or hydrophobic drugs and imaging agents. It is validated that there is no influence of the incorporated entities on the cellular uptake profile. The use of quantum dots enables efficient detection and precise quantitation of cellular uptake of particles which occupy 25% of the cell volume. The correlation of quantum dot- and doxorubicin-incorporated nanoparticles is useful to develop an evaluation platform for nanoparticle formulations through imaging and quantitation. This platform is also used to observe the surface properties effect of other polymers such as chitosan and poly(ethylene) glycol on the cellular interaction and uptake. Moreover, quantum dots can be used to study microparticle theranostic delivery formulations by deliberately incorporating as visible ring surrounding the microparticles for their easy identifying and tracing in diagnostic and chemotherapeutic applications.
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Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.
Biomaterials
PUBLISHED: 06-30-2014
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Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation.
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Renal Cell Carcinoma Metastasis to the Gallbladder Detected by FDG-PET/CT.
J Clin Med Res
PUBLISHED: 06-27-2014
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A 62-year-old male presented to the ER with three episodes of diffuse abdominal pain which occurred after eating. He had a history of renal cell carcinoma (RCC), prostate cancer and bladder cancer. FDG-PET/CT scan showed a hypermetabolic soft tissue density within the fundus of the gallbladder. The patient underwent laparoscopic cholecystectomy and surgical pathology revealed clear cell type RCC. This is the first report that features PET/CT imaging to detect RCC metastasis to the gallbladder. Lesions within the gall bladder and their clinical manifestations can be non-specific and PET/CT can help characterize them. RCC metastasis to the gallbladder is very rare but it should be included in the differential diagnosis, especially in patients with a history of RCC.
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Effect of fixed-dose combination of isosorbide dinitrate and hydralazine on all hospitalizations and on 30-day readmission rates in patients with heart failure: results from the African-American Heart Failure Trial.
Circ Heart Fail
PUBLISHED: 06-26-2014
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Fixed-dose combination of isosorbide dinitrate and hydralazine (FDC-I/H) reduced mortality by 43% and death or first hospitalization for heart failure (HF) by 37% in the African-American Heart Failure Trial (A-HeFT). Reduction in mortality makes it difficult to determine the effect on hospitalizations unless the analysis adjusts for death as a competing risk.
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Time series analysis of demographic and temporal trends of tuberculosis in Singapore.
BMC Public Health
PUBLISHED: 06-25-2014
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Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore.
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Family history of colorectal cancer is not associated with colorectal cancer survival regardless of microsatellite instability status.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-02-2014
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Individuals with a family history of colorectal cancer in first-degree relatives have an elevated risk of developing colorectal cancer themselves, particularly colorectal cancer exhibiting high microsatellite instability (MSI-high). Given that MSI-high colorectal cancer is associated with a favorable prognosis, it is plausible that having a family history of colorectal cancer could, in turn, be favorably associated with colorectal cancer survival.
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Decreased orthostatic adrenergic reactivity in non-dipping postural tachycardia syndrome.
Auton Neurosci
PUBLISHED: 05-19-2014
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Whether non-dipping - the loss of the physiologic nocturnal drop in blood pressure - among patients with postural tachycardia syndrome (POTS) is secondary to autonomic neuropathy, a hyperadrenergic state, or other factors remains to be determined. In 51 patients with POTS (44 females), we retrospectively analyzed 24-hour ambulatory blood pressure recordings, laboratory indices of autonomic function, orthostatic norepinephrine response, 24-hour natriuresis and peak exercise oxygen consumption. Non-dipping (<10% day-night drop in systolic blood pressure) was found in 55% (n=28). Dippers and non-dippers did not differ in: 1) baseline characteristics including demographic and clinical profile, sleep duration, daytime blood pressure, 24-hour natriuresis, and peak exercise oxygen consumption; 2) severity of laboratory autonomic deficits (sudomotor, cardiovagal and adrenergic); 3) frequency of autonomic neuropathy (7/23 vs. 8/28, P=0.885); 4) supine resting heart rate (75.3±14.0bpm vs. 74.0±13.8bpm, P=0.532); or 5) supine plasma norepinephrine level (250.0±94.9pg/ml vs. 207.0±86.8pg/ml, P=0.08). However, dippers differed significantly from non-dippers in that they had significantly greater orthostatic heart rate increment (43±16bpm vs. 35±10bpm, P=0.007) and significantly greater orthostatic plasma norepinephrine increase (293±136.6pg/ml vs. 209±91.1pg/ml, P=0.028). Our data indicate that in patients with POTS, a non-dipping blood pressure profile is associated with a reduced orthostatic sympathetic reactivity not accounted for by autonomic neuropathy.
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Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis.
Hum. Mol. Genet.
PUBLISHED: 04-15-2014
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To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10(-11)]. We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genome-wide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 × 10(-10)) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10(-8)). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.
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A rare nonvalvular left ventricular papillary fibroelastoma: A case report.
J Cardiol Cases
PUBLISHED: 04-15-2014
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Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. We report the case of a 66-year-old Caucasian male with acute bilateral basal ganglia infarctions found to have a mass adherent to the left ventricular septum by transesophageal echocardiography. The mass was identified as a rare nonvalvular cardiac papillary fibroelastoma based on echogenicity, pedunculated nature, and typical motion. Tissue characterization by cardiac magnetic resonance imaging demonstrated homogeneously hypo-intense signal on T2 weighted imaging and signal hyperintensity after administration of gadolinium contrast, confirming the fibroelastic nature of the mass. Surgical excision was performed via ventriculotomy and histopathologic examination was pathognomonic of a papillary fibroelastoma. We conclude that transesophageal echocardiography provides high diagnostic certainty in patients with cardiac papillary fibroelastomas and can reliably identify atypical locations of these tumors on nonvalvular surfaces. A multimodality imaging approach is not necessarily indicated in all patients with this condition.
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Frequency, origin, and outcome of ventricular premature complexes in patients with or without heart diseases.
Am. J. Cardiol.
PUBLISHED: 04-14-2014
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The objective of the present study was to investigate the relation of ventricular premature complex (VPC) burden, origin, and electrocardiographic characteristics with left ventricular function and survival. Of 1,589 study patients, 388 (25%), 610 (38%), and 591 (37%) had low (<1,000/24 hours), moderate (1,000 to 10,000/24 hours), and high (>10,000/24 hours) VPC burden, respectively. Twenty-three percent of study patients had a left ventricular (LV) ejection fraction <50% (8% in low-, 20% in moderate-, and 36% in high-VPC-burden groups, p <0.001). High VPC burden was associated with lower LV ejection fraction in the presence (r = -0.17, p <0.001) and absence (r = -0.20, p <0.001) of heart diseases. The Kaplan-Meier survival estimates showed a significant difference among the 3 VPC burden groups (p = 0.046). The survival rates were significantly lower for patients with a VPC coupling interval of ?480 ms than those with a VPC coupling interval of <480 ms (p = 0.002) and lower for those with a VPC QRS duration of ?150 ms than those with a VPC QRS duration of <150 ms (p <0.001). In conclusion, high VPC burden is detrimental to LV systolic function. Broader VPC QRS duration and longer VPC coupling interval adversely impact on long-term survival.
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Geographic factors are associated with increased risk for out-of hospital cardiac arrests and provision of bystander cardio-pulmonary resuscitation in Singapore.
Resuscitation
PUBLISHED: 04-04-2014
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Bystander Cardio-Pulmonary Resuscitation (BCPR) can improve survival for Out-of-Hospital Cardiac Arrest (OHCA). This study aimed to investigate the geographic variation of BCPR provision and survival to discharge outcomes among residential OHCA cases, evaluate this variation with individual and population characteristics and identify high-risk residential areas with low relative risk (RR) of BCPR and high RR of OHCA at the development guide plan (DGP) census tract levels in Singapore.
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Extracellular matrix-regulated neural differentiation of human multipotent marrow progenitor cells enhances functional recovery after spinal cord injury.
Spine J
PUBLISHED: 04-01-2014
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Recent advanced studies have demonstrated that cytokines and extracellular matrix (ECM) could trigger various types of neural differentiation. However, the efficacy of differentiation and in vivo transplantation has not yet thoroughly been investigated.
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Measurement of perceptions of educational environment in evidence-based medicine.
Evid Based Med
PUBLISHED: 03-31-2014
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In recent years, there has been a renewed interest in measuring perceptions regarding different aspects of the medical educational environment. A reliable tool was developed for measuring perceptions of the educational environment as it relates to evidence-based medicine as part of a multicountry randomised controlled trial to evaluate the effectiveness of a clinically integrated evidence-based medicine course. Participants from 10 specialties completed the questionnaire. A working dataset of 518 observations was available. Two independent subsets of data were created for conducting an exploratory factor analysis (n=244) and a confirmatory factor analysis (n=274), respectively. The exploratory factor analysis yielded five 67-item definitive instruments, with five to nine dimensions; all resulted in acceptable explanations of the total variance (range 56.6-65.9%). In the confirmatory factor analysis phase, all goodness of-fit measures were acceptable for all models (root mean square error of approximation ? 0.047; comparative fit index ? 0.980; normed ?(2) ? 1.647; Bentler-Bonett normed fit index ? 0.951). The authors selected the factorisation with seven dimensions (factor-7 instrument) as the most useful on pragmatic grounds and named it Evidence-Based Medicine Educational Environment Measure 67 (EBMEEM-67). Cronbach's ? for subscales ranged between 0.81 and 0.93. The subscales are: 'Knowledge and learning materials'; 'Learner support'; 'General relationships and support'; 'Institutional focus on EBM'; 'Education, training and supervision'; 'EBM application opportunities'; and 'Affirmation of EBM environment'. The EBMEEM-67 can be a useful diagnostic and benchmarking tool for evaluating the perceptions of residents of the environment in which evidence-based medicine education takes place.
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Fertility and apparent genetic anticipation in Lynch syndrome.
Fam. Cancer
PUBLISHED: 03-29-2014
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Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.
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IQP-GC-101 reduces body weight and body fat mass: a randomized, double-blind, placebo-controlled study.
Phytother Res
PUBLISHED: 03-06-2014
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IQP-GC-101 is a patented blend of the standardized extracts of Garcinia cambogia, Camellia sinensis, unroasted Coffea arabica, and Lagerstroemia speciosa. These individual ingredients of IQP-GC-101 have each shown promise in promoting weight loss; however, the efficacy of the blend has not been established. This randomized, placebo-controlled, double-blind, parallel group study conducted over 14?weeks (including a 2-week run-in phase) aimed to investigate the efficacy and safety of IQP-GC-101 in reducing body weight and body fat mass in overweight Caucasian adults. Subjects took three IQP-GC-101 or placebo tablets, twice a day, 30?min before main meals. All subjects also adhered to a 500?kcal/day energy deficit diet with 30% of energy from fat. Ninety-one overweight and mildly obese subjects (46 in the IQP-GC-101 group, 45 in the placebo group) completed the study. After 12-week intervention, IQP-GC-101 resulted in a mean (±SD) weight loss of 2.26?±?2.37?kg compared with 0.56?±?2.34?kg for placebo (pU ?=?0.002). There was also significantly more reduction in body fat mass, waist circumference, and hip circumference in the IQP-GC-101 group. No serious adverse events were reported. The use of IQP-GC-101 has been shown to result in body weight and body fat reduction in the current study, with good tolerability.
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Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?
Gynecol. Oncol.
PUBLISHED: 03-03-2014
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To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.
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Priorities for Emergency Department Syncope Research.
Ann Emerg Med
PUBLISHED: 02-25-2014
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There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research.
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Regulation of large conductance Ca2+-activated K+ (BK) channel ?1 subunit expression by muscle RING finger protein 1 in diabetic vessels.
J. Biol. Chem.
PUBLISHED: 02-25-2014
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The large conductance Ca(2+)-activated K(+) (BK) channel, expressed abundantly in vascular smooth muscle cells (SMCs), is a key determinant of vascular tone. BK channel activity is tightly regulated by its accessory ?1 subunit (BK-?1). However, BK channel function is impaired in diabetic vessels by increased ubiquitin/proteasome-dependent BK-?1 protein degradation. Muscle RING finger protein 1 (MuRF1), a muscle-specific ubiquitin ligase, is implicated in many cardiac and skeletal muscle diseases. However, the role of MuRF1 in the regulation of vascular BK channel and coronary function has not been examined. In this study, we hypothesized that MuRF1 participated in BK-?1 proteolysis, leading to the down-regulation of BK channel activation and impaired coronary function in diabetes. Combining patch clamp and molecular biological approaches, we found that MuRF1 expression was enhanced, accompanied by reduced BK-?1 expression, in high glucose-cultured human coronary SMCs and in diabetic vessels. Knockdown of MuRF1 by siRNA in cultured human SMCs attenuated BK-?1 ubiquitination and increased BK-?1 expression, whereas adenoviral expression of MuRF1 in mouse coronary arteries reduced BK-?1 expression and diminished BK channel-mediated vasodilation. Physical interaction between the N terminus of BK-?1 and the coiled-coil domain of MuRF1 was demonstrated by pulldown assay. Moreover, MuRF1 expression was regulated by NF-?B. Most importantly, pharmacological inhibition of proteasome and NF-?B activities preserved BK-?1 expression and BK-channel-mediated coronary vasodilation in diabetic mice. Hence, our results provide the first evidence that the up-regulation of NF-?B-dependent MuRF1 expression is a novel mechanism that leads to BK channelopathy and vasculopathy in diabetes.
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Frequent attenders to the ED: patients who present with repeated asthma exacerbations.
Am J Emerg Med
PUBLISHED: 02-11-2014
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Asthma has been reported as one of the main causes of frequent attendance to the emergency department (ED), and many of those visits are potentially preventable. Understanding the characteristics of frequent attender (FA) patients with asthmatic exacerbations will help to identify factors associated with frequent attendance and improve case management. The aim of this study is to describe the characteristics of FA who present multiple times to the ED for asthma exacerbations.
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A Review of the Efficacy and Safety of Litramine IQP-G-002AS, an Opuntia ficus-indica Derived Fiber for Weight Management.
Evid Based Complement Alternat Med
PUBLISHED: 02-10-2014
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Sedentary lifestyle and caloric overconsumption are the key determinants of the escalating obesity prevalence. Reducing dietary fat absorption may help to induce a negative energy balance and thus help in managing weight problem. Apart from approved drug therapies, weight problems may also be aided with alternative and natural treatments. This paper compiled and reviewed the efficacy and safety of Litramine IQP-G-002AS, an Opuntia ficus-indica (OFI) derived fiber, in reducing dietary fat absorption and promoting weight loss. Evidence reviewed shows that Litramine IQP-G-002AS displays efficacy in promoting fat excretion and weight loss in four randomized, placebo-controlled clinical studies (including an unpublished pilot study). With a daily dosage of 3?g over a seven-day period, Litramine IQP-G-002AS showed an increased faecal fat excretion compared with placebo (15.8% (SD 5.8%) versus 4.6% (SD 3.1%); P < 0.001). In a 12-week study, significant greater weight loss (3.8?kg (SD 1.8?kg) versus 1.4?kg (SD 2.6?kg); P < 0.001) was observed in overweight and obese subjects treated with Litramine IQP-G-002AS as compared to placebo. No relevant gastrointestinal side effects have been reported for Litramine IQP-G-002AS at the dosages studied.
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Colorectal cancer and self-reported tooth agenesis.
Hered Cancer Clin Pract
PUBLISHED: 01-21-2014
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Germline mutations in APC and AXIN2 are both associated with colon neoplasia as well as anomalous dental development. We tested the hypothesis that congenitally missing teeth may occur more commonly in individuals diagnosed with colorectal cancer than in individuals without this diagnosis.
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Effects of atrioventricular and interventricular delays on gas exchange during exercise in patients with heart failure.
J. Heart Lung Transplant.
PUBLISHED: 01-17-2014
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Cardiac resynchronization therapy (CRT) has been an important treatment for heart failure. However, it is controversial as to whether an individualized approach to altering AV and VV timing intervals would improve outcomes. Changes in respiratory patterns and gas exchange are dynamic and may be influenced by timing delays. Light exercise enhances the heart and lung interactions. Thus, in this study we investigated changes in non-invasive gas exchange by altering AV and VV timing intervals during light exercise.
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Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system.
Biomaterials
PUBLISHED: 01-17-2014
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Chemotherapy for brain cancer tumors remains a big challenge for clinical medicine due to the inability to transport sufficient drug across the blood-brain barrier (BBB) and the poor penetration of drug into the tumors. To effectively treat brain tumors and reduce side effects on normal tissues, both des-octanoyl ghrelin and folate conjugated with polymersomal doxorubicin (GFP-D) was developed in this study to help transport across the BBB and target the tumor as well. The size measurements revealed that this BBB-penetrating cancer cell-targeting GFP-D was about 85 nm. In-vitro experiments with a BBB model and C6 glioma cells demonstrated that GFP-D owned a robust penetrating-targeting function for drug delivery. In C6 cell viability tests, GFP-D exhibited an inhibitory effect significantly different from the unmodified polymersomal doxorubicin (P-D). In-vivo antitumor experiments showed that GFP-D performed a much better anti-glioma effect and presented a significant improvement in the overall survival of the tumor-bearing mice as compared to the treatments with free doxorubicin (Dox), liposomal doxorubicin (L-D), P-D, or single ligand conjugated P-D. In addition, Cy 5.5 was used as a probe to investigate the delivery property of this penetrating-targeting delivery system. The overall experimental results indicate that this BBB-penetrating cancer cell-targeting GFP is a highly potential nanocarrier for the treatment of brain tumors.
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Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-14-2014
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It has been controversial that men carrying a DNA mismatch repair (MMR) gene mutation (Lynch syndrome) are at heightened risk of prostate cancer given that an increased risk is likely to be modest and the prevalence of prostate cancer is high. We used PubMed to search for "molecular studies" that reported MMR-deficiency status of prostate cancer tumors in men with an MMR gene mutation, and "risk studies" that reported prostate cancer risk for men known or suspected to have an MMR gene mutation relative to that for noncarriers or the general population. Of the six molecular studies, 32 of 44 [73%, 95% confidence intervals (CI), 57%-85%] prostate cancer tumors in carriers were MMR deficient, which equates to carriers having a 3.67-fold increased risk of prostate cancer (95% CI, 2.32-6.67). Of the 12 risk studies, we estimated a 2.13-fold increased risk of prostate cancer (95% CI, 1.45-2.80) for male carriers in clinic-based retrospective cohorts, 2.11 (95% CI, 1.27-2.95) for male carriers with a prior diagnosis of colorectal cancer, and 2.28 (95% CI, 1.37-3.19) for all men from mutation-carrying families. The combination of evidence from molecular and risk studies in the current literature supports consideration of prostate cancer as part of Lynch syndrome.
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Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer.
Gastroenterology
PUBLISHED: 01-10-2014
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We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population.
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Impact of a social franchising program on uptake of oral rehydration solution plus zinc for childhood diarrhea in myanmar: a community-level randomized controlled trial.
J. Trop. Pediatr.
PUBLISHED: 01-08-2014
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Diarrhea's impact on childhood morbidity can be reduced by administering oral rehydration solution (ORS) with zinc; challenges to wider use are changing health-seeking behavior and ensuring access.
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Initial Experience of Utilizing Real-Time Intra-Procedural PET/CT Biopsy.
J Clin Imaging Sci
PUBLISHED: 01-01-2014
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Nonreal-time Positron Emission Tomography/Computed Tomography (PET/CT) biopsies that use the image co-registration of a prior PET with an intra-procedural CT have been reported. The aim of this study was to report the initial experience of performing real-time intra-procedural PET/CT-guided biopsies.
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Omental Nodular Deposits of Recurrent Chromophobe Renal Cell Carcinoma Seen on FDG-PET/CT.
J Clin Imaging Sci
PUBLISHED: 01-01-2014
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We present the case of a 69-year-old male with chromophobe renal cell carcinoma (RCC). Chromophobe RCC accounts for only 4% of renal cancers and it is the least aggressive type. Omental nodular deposits due to RCC metastasis are very rare and it is reported only in more aggressive forms of RCC. This is the first report that shows FluoroDeoxyGlucose - Positron Emission Tomography/Computed Tomgraphy (FDG-PET/CT) images of omental nodular deposits from chromophobe RCC. FDG-PET/CT is becoming very useful in restaging RCC with distant metastases.
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Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).
Appl Clin Genet
PUBLISHED: 01-01-2014
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Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic inactivation. Determining the underlying cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely to reshape the current triaging schemes used to identify germline MMR gene mutations in cancer-affected individuals and their relatives.
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Human resources for health: task shifting to promote basic health service delivery among internally displaced people in ethnic health program service areas in eastern Burma/Myanmar.
Glob Health Action
PUBLISHED: 01-01-2014
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Burma/Myanmar was controlled by a military regime for over 50 years. Many basic social and protection services have been neglected, specifically in the ethnic areas. Development in these areas was led by the ethnic non-state actors to ensure care and the availability of health services for the communities living in the border ethnic-controlled areas. Political changes in Burma/Myanmar have been ongoing since the end of 2010. Given the ethnic diversity of Burma/Myanmar, many challenges in ensuring health service coverage among all ethnic groups lie ahead.
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Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers.
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Retention and risk factors for attrition in a large public health ART program in Myanmar: a retrospective cohort analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The outcomes from an antiretroviral treatment (ART) program within the public sector in Myanmar have not been reported. This study documents retention and the risk factors for attrition in a large ART public health program in Myanmar.
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Normal SUV values measured from NaF18- PET/CT bone scan studies.
PLoS ONE
PUBLISHED: 01-01-2014
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Cancer and metabolic bone diseases can alter the SUV. SUV values have never been measured from healthy skeletons in NaF18-PET/CT bone scans. The primary aim of this study was to measure the SUV values from normal skeletons in NaF18-PET/CT bone scans.
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Targeted delivery of erythropoietin by transcranial focused ultrasound for neuroprotection against ischemia/reperfusion-induced neuronal injury: a long-term and short-term study.
PLoS ONE
PUBLISHED: 01-01-2014
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Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permeability. In this study, we investigated the effects of MBs/FUS on extending the therapeutic time window of EPO and its neuroprotective effects in both acute and chronic phases. Male Wistar rats were firstly subjected to two common carotid arteries and right middle cerebral artery occlusion (three vessels occlusion, 3VO) for 50 min, and then the rats were treated with hEPO (human recombinant EPO, 5000 IU/kg) with or without MBs/FUS at 5 h after occlusion/reperfusion. Acute phase investigation (I/R, I/R+MBs/FUS, I/R+hEPO, and I/R+hEPO+MBs/FUS) was performed 24 h after I/R; chronic tests including cylinder test and gait analysis were performed one month after I/R. The experimental results showed that MBs/FUS significantly increased the cerebral content of EPO by bettering vascular permeability. In acute phase, both significant improvement of neurological score and reduction of infarct volume were found in the I/R+hEPO+MBs/FUS group, as compared with I/R and I/R+hEPO groups. In chronic phase, long-term behavioral recovery and neuronal loss in brain cortex after I/R injury was significantly improved in the I/R+hEPO+MBs/FUS group. This study indicates that hEPO administration with MBs/FUS sonication even at 5 h after occlusion/reperfusion can produce a significant neuroprotection.
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Reducing Ambulance Response Times Using Discrete Event Simulation.
Prehosp Emerg Care
PUBLISHED: 10-17-2013
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Abstract Objectives. The objectives of this study are to develop a discrete-event simulation (DES) model for the Singapore Emergency Medical Services (EMS), and to demonstrate the utility of this DES model for the evaluation of different policy alternatives to improve ambulance response times. Methods. A DES model was developed based on retrospective emergency call data over a continuous 6-month period in Singapore. The main outcome measure is the distribution of response times. The secondary outcome measure is ambulance utilization levels based on unit hour utilization (UHU) ratios. The DES model was used to evaluate different policy options in order to improve the response times, while maintaining reasonable fleet utilization. Results. Three policy alternatives looking at the reallocation of ambulances, the addition of new ambulances, and alternative dispatch policies were evaluated. Modifications of dispatch policy combined with the reallocation of existing ambulances were able to achieve response time performance equivalent to that of adding 10 ambulances. The median (90th percentile) response time was 7.08 minutes (12.69 minutes). Overall, this combined strategy managed to narrow the gap between the ideal and existing response time distribution by 11-13%. Furthermore, the median UHU under this combined strategy was 0.324 with an interquartile range (IQR) of 0.047 versus a median utilization of 0.285 (IQR of 0.051) resulting from the introduction of additional ambulances. Conclusions. Response times were shown to be improved via a more effective reallocation of ambulances and dispatch policy. More importantly, the response time improvements were achieved without a reduction in the utilization levels and additional costs associated with the addition of ambulances. We demonstrated the effective use of DES as a versatile platform to model the dynamic system complexities of Singapores national EMS systems for the evaluation of operational strategies to improve ambulance response times.
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MRI-compatible ultrasound heating system with ring-shaped phased arrays for breast tumor thermal therapy.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Therapeutic ultrasound transducers can carry out precise and efficient power deposition for tumor thermal therapy under the guidance of magnetic resonance imaging. For a better heating, organ-specific ultrasound transducers with precision location control system should be developed for tumors located at various organs. It is feasible to perform a better heating for breast tumor thermal therapy with a ring-shaped ultrasound phased-array transducer. In this study, we developed ring-shaped phased-array ultrasound transducers with 1.0 and 2.5 MHz and a precision location control system to drive the transducers to the desired location to sonicate the designated region. Both thermo-sensitive hydrogel phantom and ex vivo fresh pork were used to evaluate the heating performance of the transducers. The results showed that the ring-shaped phased array ultrasound transducers were very promising for breast tumor heating with the variation of heating patterns and without overheating the ribs.
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Differential effects of phosphate binders on pre-dialysis serum bicarbonate in end-stage kidney disease patients on maintenance haemodialysis.
BMC Nephrol
PUBLISHED: 09-25-2013
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Phosphate binders constituents have alkalotic or acidotic properties and may contribute to acid base balance in haemodialysis patients. This study aimed to investigate the differential effects of phosphate binders on pre-dialysis serum bicarbonate in End Stage Kidney Disease patients on maintenance haemodialysis.
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Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues.
Biomaterials
PUBLISHED: 08-31-2013
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The effective protection of the blood-brain barrier (BBB) from tight junctions and efflux transport systems ultimately results in the limited entry of 95% of drug/gene candidates, which are potentially beneficial for central nervous system (CNS) diseases. In order to enhance the brain-specific delivery, in this study we developed a targeting carrier system, which consists of poly(carboxyl ethylene glycol-g-glutamate)-co-poly(distearin-g-glutamate) (CPEGGM-PDSGM) polymersomes with the conjugation of des-octanoyl ghrelin. Des-octanoyl ghrelin across the BBB was reported to be unidirectional (blood-to-brain direction). However, there is no report about the conjugation of des-octanoyl ghrelin to a drug carrier system to confer the BBB targeting property through des-octanoyl ghrelin binding sites mediated endocytosis. To qualitatively and quantitatively investigate this carriers properties, coumarin 6, Cy5.5 and met-enkephalin were individually encapsulated in these polymersomes. The experimental results showed that the cellular uptake was significantly higher for des-octanoyl ghrelin-conjugated polymersomes (GPs) than unconjugated polymersomes when co-incubated with the BBB cells. In addition, an enhanced accumulation in brain together with a reduced accumulation in liver and spleen was observed in animal study, indicating better brain selectivity for the GPs. In a hot-plate test, a significant inhibition of nociceptive response could be achieved for an intravenous injection of GPs encapsulated with met-enkephalin. The overall results demonstrated that GPs own a great potential for targeting delivery of drug across the BBB to treat CNS diseases.
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Criteria and prediction models for mismatch repair gene mutations: a review.
J. Med. Genet.
PUBLISHED: 08-16-2013
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One of the strongest predictors of colorectal cancer risk is carrying a germline mutation in a DNA mismatch repair (MMR) gene. Once identified, mutation carriers can be recommended for intensive screening that will substantially reduce their high colorectal cancer risk. Conversely, the relatives of carriers identified as non-carriers can be relieved of the burden of intensive screening. Criteria and prediction models that identify likely mutation carriers are needed for cost-effective, targeted, germline testing for MMR gene mutation. We reviewed 12 criteria/guidelines and 8 prediction models (Leiden, Amsterdam-plus, Amsterdam-alternative, MMRpro, PREMM1,2,6, MMRpredict, Associazione Italiana per lo studio della Familiarità ed Ereditarietà dei tumori Gastrointestinali (AIFEG) and the Myriad Genetics Prevalence table) for identifying mutation carriers. While criteria are only used to identify individuals with colorectal cancer (yes/no for screening followed by germline testing), all prediction models except MMRpredict and Myriad tables can predict the probability of carrying mutations for individuals with or without colorectal cancer. We conducted a meta-analysis of the discrimination performance of 17 studies that validated the prediction models. The pooled estimate for the area under curve was 0.80 (95% CI 0.72 to 0.88) for MMRpro, 0.81 (95% CI 0.73 to 0.88) for MMRpredict, 0.84 (95% CI 0.81 to 0.88) for PREMM, and 0.85 (95% CI 0.78 to 0.91) for Leiden model. Given the high degree of overlap in the CIs, we cannot state that one model has a higher discrimination than any of the others. Overall, the existing statistical models have been shown to be sensitive and specific (at a 5% cut-off) in predicting MMR gene mutation carriers. Future models may need to: provide prediction of PMS2 mutations, take into account a wider range of Lynch syndrome-associated cancers when assessing family history, and be applicable to all people irrespective of any cancer diagnosis.
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Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: A single-center retrospective study.
Heart Rhythm
PUBLISHED: 08-07-2013
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It is unknown whether radiofrequency ablation (RFA) or antiarrhythmic therapy is superior when treating patients with symptomatic premature ventricular contractions (PVCs).
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Establishment of a promising human nucleus pulposus cell line for intervertebral disc tissue engineering.
Tissue Eng Part C Methods
PUBLISHED: 07-13-2013
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Low-back pain caused by intervertebral disc degeneration could be recovered by the regeneration of the nucleus pulposus (NP). This study aimed to establish a chondrogenic recovery model with promising a human NP (hNP) cell line, an immortalized hNP (ihNP), which could be a screening platform to identify regenerative drugs. The ihNP cells were created from primary human NP cells transfected with a retroviral vector-driven HPV16 E6/E7. Growth properties and characteristics of ihNP were evaluated by comparing with parental NP cells. Successful immortalization of ihNP cells stably expressed HPV 16 E6/E7 mRNA. The doubling time of ihNP was shortened to 53.16±2.63?h compared with parental hNP-P1. Cell cycle regulators, including p53, p21, and pRB were downregulated compared to parental hNP-P1. The in vivo neoplastic forming assay also demonstrated that the ihNP was nontumorigenic. After 25 generations of cell cultures, the ihNP cells, yet stably expressed chondrogenic genes, including (SOX9), type II collagen (Col II), aggrecan, decorin, biglycan, and versican. Higher expressions of chondrogenic proteins, including Col II, phosphorylated SOX9 (p-SOX9), and CD44 were also determined. Under the stressful inflammatory conditions induced by lipopolysaccharides (LPS), the regenerative and anti-inflammatory potentials of ihNP in two-dimensional culture with the presence of platelet-rich plasma (PRP) were evaluated by reverse transcriptase polymerase chain reaction. PRP showed significant effects on restoring diminished chondrogenic markers and deleterious inflammatory responses induced by LPS in ihNP. The therapeutic potentials of ihNP in three-dimensional neocartilage model could also be exerted by PRP using histological evaluation and immunological staining. Hence, the established ihNP cells can provide a chondrogenic recovery model as a regenerative drug screening tool for further regenerative drug discovery and development.
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Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.
Dis. Colon Rectum
PUBLISHED: 07-11-2013
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Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability.
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BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome.
Am. J. Surg. Pathol.
PUBLISHED: 06-26-2013
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BRAFV600E mutation in microsatellite-unstable (MSI) colorectal carcinomas (CRCs) virtually excludes Lynch syndrome (LS). In microsatellite-stable (MSS) CRCs it predicts poor prognosis. We propose a universal CRC LS screening algorithm using concurrent reflex immunohistochemistry (IHC) for BRAFV600E and mismatch-repair (MMR) proteins. We compared BRAFV600E IHC with multiplex polymerase chain reaction (PCR) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry in 216 consecutive CRCs from 2011. Discordant cases were resolved with real-time PCR. BRAFV600E IHC was performed on 51 CRCs from the Australasian Colorectal Cancer Family Registry (ACCFR), which were fully characterized for BRAF mutation by allele-specific PCR, MMR status (MMR IHC and MSI), MLH1 promoter methylation, and germline MLH1 mutation. We then assessed MMR and BRAFV600E IHC on 1403 consecutive CRCs. By matrix-assisted laser desorption/ionization-time of flight mass spectrometry 15 cases did not yield a BRAF result, whereas 38/201 (19%) were positive. By IHC 45/216 (20%) were positive. Of the 7 discordant cases, real-time PCR confirmed the IHC result in 6. In the 51 CRCs from the ACCFR, IHC was concordant with allele-specific PCR in 50 cases. BRAFV600E and MSI IHC on 1403 CRCs demonstrated the following phenotypes: BRAF/MSS (1029 cases, 73%), BRAF/MSS (98, 7%), BRAF/MSI (183, 13%), and BRAF/MSI (93, 7%). All 11/1403 cancers associated with proven LS were BRAF/MSI. We conclude that BRAF IHC is highly concordant with 2 commonly used PCR-based BRAFV600E assays; it performed well in identifying MLH1 mutation carriers from the ACCFR and identified all cases of proven LS among the 1403 CRCs. Reflex BRAFV600E and MMR IHC are simple cheap tests that facilitate universal LS screening and identify the poor prognosis of the BRAFV600E-mutant MSS CRC phenotype.
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Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer.
Epigenetics
PUBLISHED: 06-17-2013
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Changes in the methylation levels of DNA from white blood cells (WBCs) are putatively associated with an elevated risk for several cancers. The aim of this study was to investigate the association between colorectal cancer (CRC) and the methylation status of three DNA repetitive elements in DNA from peripheral blood. WBC DNA from 539 CRC cases diagnosed before 60 years of age and 242 sex and age frequency-matched healthy controls from the Australasian Colorectal Cancer Family Registry were assessed for methylation across DNA repetitive elements Alu, LINE-1 and Sat2 using MethyLight. The percentage of methylated reference (PMR) of cases and controls was calculated for each marker. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression adjusted for potential confounders. CRC cases demonstrated a significantly higher median PMR for LINE-1 (p < 0.001), Sat2 (p < 0.001) and Alu repeats (p = 0.02) when compared with controls. For each of the DNA repetitive elements, individuals with PMR values in the highest quartile were significantly more likely to have CRC compared with those in the lowest quartile (LINE-1 OR = 2.34, 95%CI = 1.48-3.70; p < 0.001, Alu OR = 1.83, 95%CI = 1.17-2.86; p = 0.01, Sat2 OR = 1.72, 95%CI = 1.10-2.71; p = 0.02). When comparing the OR for the PMR of each marker across subgroups of CRC, only the Alu marker showed a significant difference in the 5-fluoruracil treated and nodal involvement subgroups (both p = 0.002). This association between increasing methylation levels of three DNA repetitive elements in WBC DNA and early-onset CRC is novel and may represent a potential epigenetic biomarker for early CRC detection.
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Perceived Versus Predicted Risks of Colorectal Cancer and Self-Reported Colonoscopies by Members of Mismatch Repair Gene Mutation-Carrying Families Who Have Declined Genetic Testing.
J Genet Couns
PUBLISHED: 05-22-2013
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People carrying germline mutations in mismatch repair genes are at high risk of colorectal cancer (CRC), yet about half of people from mutation-carrying families decline genetic counselling and/or testing to identify mutation status. We studied the association of quantitative measures of risk perception, risk prediction and self-reported screening colonoscopy in this elusive yet high-risk group. The sample of 26 participants (mean age 43.1 years, 14 women) in the Australasian Colorectal Cancer Family Registry were relatives of mutation carriers; had not been diagnosed with any cancer at the time of recruitment and had declined an invitation to attend genetic counselling and/or testing. A structured elicitation protocol captured perceived CRC risk over the next 10 years. Self-reported colonoscopy screening was elicited during a 45-minute semi-structured interview. Predicted 10-year CRC risk based on age, gender, known mutation status and family history was calculated using "MMRpro." Mean perceived 10-year risk of CRC was 31 % [95 % CI 21, 40], compared with mean predicted risk of 4 % [2, 7] (p?
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Frequent periodic leg movement during sleep is associated with left ventricular hypertrophy and adverse cardiovascular outcomes.
J Am Soc Echocardiogr
PUBLISHED: 04-24-2013
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Sleep disturbance caused by obstructive sleep apnea is recognized as a contributing factor to adverse cardiovascular outcomes. However, the effect of restless legs syndrome, another common cause of fragmented sleep, on cardiac structure, function, and long-term outcomes is not known. The aim of this study was to assess the effect of frequent leg movement during sleep on cardiac structure and outcomes in patients with restless legs syndrome.
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Weight reduction and maintenance with IQP-PV-101: A 12-week randomized controlled study with a 24-week open label period.
Obesity (Silver Spring)
PUBLISHED: 04-18-2013
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The safety and efficacy of IQP-PV-101, a proprietary extract of Phaseolus vulgaris, on weight management in two phases was evaluated here. The weight loss (WL) phase was conducted over 12 weeks and the weight maintenance (WM) phase took 24 weeks.
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Multiplicity and molecular heterogeneity of colorectal carcinomas in individuals with serrated polyposis.
Am. J. Surg. Pathol.
PUBLISHED: 04-10-2013
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Serrated polyposis (SP) is a clinically defined syndrome characterized by the occurrence of multiple serrated polyps in the large intestine. Individuals with SP and their relatives are at increased risk of colorectal carcinoma (CRC). We aimed to determine the pathologic and molecular profiles of CRCs in individuals fulfilling World Health Organization criteria for SP. A total of 45 CRCs were obtained from 38 individuals with SP (27 female and 11 male patients; median age at CRC diagnosis, 58.5 y) attending genetics clinics. Tumor samples were pathologically reviewed, screened for somatic BRAF and KRAS mutations, and analyzed immunohistochemically for mismatch repair protein (MMR) expression. Tumors were spread throughout the large intestine, with 64% located in the proximal colon. Mutations in BRAF and KRAS and immunohistochemical evidence of MMR deficiency were found in 46%, 5%, and 38%, respectively. Nearly half of CRCs were BRAF/KRAS wild type, and these were associated with distal location (63%) and MMR proficiency (84%). Overexpression of p53 and/or evidence of ?-catenin activation were identified in 13 CRCs. Ten patients (26%) had synchronous or metachronous CRCs. In conclusion, the majority of CRCs arising in individuals with SP do not harbor molecular hallmarks of serrated pathway CRCs but show a diverse range of molecular profiles. The high proportion of multiple CRCs suggests that individuals with SP would benefit from frequent colonoscopic surveillance and from a consideration of a more extensive colectomy at the time of CRC diagnosis.
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A natural fiber complex reduces body weight in the overweight and obese: a double-blind, randomized, placebo-controlled study.
Obesity (Silver Spring)
PUBLISHED: 03-19-2013
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A proprietary natural fiber complex (Litramine IQP G-002AS) derived from Opuntia ficus-indica, and standardized on lipophilic activity, was previously shown in preclinical and human studies to reduce dietary fat absorption through gastrointestinal (GI) fat binding. Here, we investigated the efficacy and safety of IQP G-002AS in body weight reduction.
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Risk of breast cancer in Lynch syndrome: a systematic review.
Breast Cancer Res.
PUBLISHED: 03-18-2013
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INTRODUCTION: Lynch syndrome is an autosomal dominantly inherited disorder of cancer susceptibility caused by germline mutations in the DNA mismatch repair (MMR) genes. Mutation carriers have a substantial burden of increased risks of cancers of the colon, rectum, endometrium and several other organs which generally occur at younger ages than for the general population. The issue of whether breast cancer risk is increased for MMR gene mutation carriers has been debated with evidence for and against this association. METHODS: Using the PUBMED, we identified all relevant studies of breast cancer associated with Lynch syndrome that were published by 15 December 2012. In the review, we included: (i) molecular studies that reported microsatellite instability and/or immunohistochemistry in breast cancer tumors of MMR gene mutation carriers; and (ii) risk studies that investigated risk of breast cancer for confirmed MMR gene mutation carriers or families or clinically and/or pathologically defined Lynch syndrome families. RESULTS: We identified 15 molecular studies and, when combined, observed 62 of 122 (51%; 95% CI 42 to 60%) breast cancers in MMR gene mutation carriers were MMR-deficient. Of the 21 risk studies identified, 13 did not observe statistical evidence for an association of breast cancer risk with Lynch syndrome while 8 studies found an increased risk of breast cancer ranging from 2- to 18-fold compared with the general population (or non-carriers). There is only one prospective study demonstrating an elevated risk of breast cancer for MMR gene mutation carriers compared with the general population (standardized incidence ratio 3.95; 95% CI 1.59, 8.13). CONCLUSIONS: Since breast cancer is a relatively common disease in the general population, more precise estimates of risk and gene-specific risks will need to utilize large prospective cohort studies with a long follow-up. While current data are inconclusive at a population level, individual tumor testing results suggest that MMR deficiency is involved with breast cancers in some individuals with Lynch syndrome.
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Surface-functionalized nanoparticles for biosensing and imaging-guided therapeutics.
Nanoscale
PUBLISHED: 03-11-2013
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In this article, the very recent progress of various functional inorganic nanomaterials is reviewed including their unique properties, surface functionalization strategies, and applications in biosensing and imaging-guided therapeutics. The proper surface functionalization renders them with stability, biocompatibility and functionality in physiological environments, and further enables their targeted use in bioapplications after bioconjugation via selective and specific recognition. The surface-functionalized nanoprobes using the most actively studied nanoparticles (i.e., gold nanoparticles, quantum dots, upconversion nanoparticles, and magnetic nanoparticles) make them an excellent platform for a wide range of bioapplications. With more efforts in recent years, they have been widely developed as labeling probes to detect various biological species such as proteins, nucleic acids and ions, and extensively employed as imaging probes to guide therapeutics such as drug/gene delivery and photothermal/photodynamic therapy.
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Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome.
Transl Res
PUBLISHED: 03-10-2013
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Lipid rafts are specialized plasma membrane microdomains that serve as platforms for integrating cellular signal transductions. We have recently reported that autoantibodies against cardiac membrane proteins are present in patients with postural orthostatic tachycardia syndrome (POTS). In this study, we examined the presence of autoimmunoreactive IgGs against lipid raft proteins in these patients. IgGs were purified from the sera of 10 patients and 7 normal controls. Cardiac lipid raft preparations were isolated from normal human heart tissue. The lipid raft-associated proteins were resolved by 2-dimensional gel electrophoresis and immunoblotted against IgGs from each subject. Protein spots that reacted specifically with patient IgGs were identified by nano-liquid chromatography-mass spectrometry/mass spectrometry. Thirty-four such protein spots, and 72 unique proteins were identified. The targets of autoimmunoreactive IgGs include proteins associated with caveolae structure, adrenergic signaling, calcium signaling, cytostructures, chaperone and energy metabolism. Multiple pathways were involved including those that regulate caveolae-mediated signaling, oxidative phosphorylation, fatty acid metabolism, protein ubiquitination, and cardiac ?-adrenergic signaling. Our results suggest that cardiac lipid raft-associated proteins are targets of autoimmunoreactive IgGs from patients with POTS. Autoimmunity may play a role in the pathogenesis of POTS.
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Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines.
Biomaterials
PUBLISHED: 03-06-2013
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Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs) therapy. However, MSCs from different origins might exhibit distinct differentiation capacities. This study was undertaken to compare the therapeutic efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM-MSCs were first characterized. The coculture commitment system was subsequently utilized for comparing the patterned molecules in stage-specific chondrogenesis of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs and BM-MSCs were encapsulated in neo-cartilage and subjected into pro-inflammatory cytokine environment. Finally, chondrogenic and inflammatory cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both negative for hematopoietic markers and positive for adhesion and mesenchymal cell markers. The CB-MSCs showed a markedly higher chondrogenic potential and relatively lower osteogenic and adipogenic capacities than BM-MSCs. During chondrogenesis, the committed CB-MSCs also showed significant increases in cell proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific gene expressions in a coculture system. For the therapeutic efficacies, the committed CB-MSCs could strongly recover the pro-inflammatory cytokines diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL-10, ICAM-1 and TGF-?1 were also up-regulated in committed CB-MSCs analyzed by using cytokine profiling. Our data demonstrate that CB-MSCs possess specific advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better therapeutic potential that can contribute to advanced cell-based transplantation for clinical OA therapy.
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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.

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

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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.