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Find video protocols related to scientific articles indexed in Pubmed.
Academy of Medicine-Ministry of Health clinical practice guidelines: attention deficit hyperactivity disorder.
Singapore Med J
PUBLISHED: 09-06-2014
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The Academy of Medicine (AMS) and the Ministry of Health (MOH) have developed the clinical practice guidelines on Attention Deficit Hyperactivity Disorder (ADHD) to provide doctors and patients in Singapore with evidence-based treatment for ADHD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on ADHD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.
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Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore.
BMC Infect. Dis.
PUBLISHED: 04-06-2014
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The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain.
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Development and control of a lower extremity assistive device (LEAD) for gait rehabilitation.
IEEE Int Conf Rehabil Robot
PUBLISHED: 11-05-2013
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This research developed a wearable lower extremity assistive device intended to aid stroke patient during rehabilitation. The device specifically aims to assist the patient in sit-to-stand, stand-to-sit, and level-walking tasks in order to promote active gait rehabilitation exercises. The device adopts an anthropomorphic structure with hip and knee joint actuated in sagittal plane. A finite state machine strategy was proposed to control the device. At different states, appropriate assist torque is added to each joint. EMG signals are used to assess the assist performance. Tests on an able-bodied subject show that the device could successfully detect and transit between states. In sit-to-stand tasks, the integrated EMG (iEMG) of the Vastus Medialis for standing up with 11 Nm of assistance torque were found to be significantly less (P = 0.00187) than the iEMG of without assistance for standing up which indicate reduced muscle effort with the device assistance. Results show the device could potentially assist stroke patient in similar tasks.
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Muscle force estimation with surface EMG during dynamic muscle contractions: A wavelet and ANN based approach.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Human muscle force estimation is important in biomechanics studies, sports and assistive devices fields. Therefore, it is essential to develop an efficient algorithm to estimate force exerted by muscles. The purpose of this study is to predict force/torque exerted by muscles under dynamic muscle contractions based on continuous wavelet transform (CWT) and artificial neural networks (ANN) approaches. Mean frequency (MF) of the surface electromyography (EMG) signals power spectrum was calculated from CWT. ANN models were trained to derive the MF-force relationships from the subset of EMG signals and the measured forces. Then we use the networks to predict the individual muscle forces for different muscle groups. Fourteen healthy subjects (10 males and 4 females) were voluntarily recruited in this study. EMG signals were collected from the biceps brachii, triceps, hamstring and quadriceps femoris muscles to evaluate the proposed method. Root mean square errors (RMSE) and correlation coefficients between the predicted forces and measured actual forces were calculated.
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A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
Hum. Mol. Genet.
PUBLISHED: 06-04-2013
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Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
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Factors influencing infection by pandemic influenza A(H1N1)pdm09 over three epidemic waves in Singapore.
Influenza Other Respir Viruses
PUBLISHED: 05-05-2013
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Previous influenza pandemics had second and on occasion third waves in many countries that were at times more severe than the initial pandemic waves.
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Autism spectrum disorder in Chinese populations: a brief review.
Asia Pac Psychiatry
PUBLISHED: 03-12-2013
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This review summarizes the published work on the prevalence and incidence rates of autism spectrum disorder (ASD) in Chinese populations. The authors searched MEDLINE, Web of Science and the PsycINFO database and identified seven studies that were published in the English language. In mainland China, Li and colleagues reported an autism prevalence rate of 2.38/10,000 but admitted the possibility of underestimation. A higher prevalence of 11/10,000 was reported by Zhang and Ji based on a survey that was conducted in Tianjin, China. In Taiwan, Chien and colleagues reported that the cumulative prevalence of ASD increased from 1.79 to 28.72/10,000 from 1996 to 2005 and the annual incidence rate increased from 0.91 to 4.41/10,000 per year from 1997 to 2005. Another study based on the Taiwan national health insurance database reported a high prevalence rate of 122.8/10,000 for the year 2007. Two studies based on the Taiwan national disability registry data reported an increasing trend of ASD for the period 2000-2007 and 2004-2010, respectively. In Hong Kong, Wong and colleagues estimated that the incidence of ASD was 5.49/10,000 and the average prevalence over the 1986-2005 period was 16.1/10,000. We identified 12 studies through the searching of Chinese databases. The prevalences among these studies varied from 2.8 to 29.5/10,000. While existing data appear to suggest, it remains unclear whether there is a true rise in the prevalence of ASD in ethnic Chinese population across geographic sites. More collaborative research on this topic should be conducted in the future.
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Routine spinal navigation for thoraco-lumbar pedicle screw insertion using the O-arm three-dimensional imaging system improves placement accuracy.
J Clin Neurosci
PUBLISHED: 02-16-2013
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Modern image-guided spinal navigation employs high-quality intra-operative three dimensional (3D) images to improve the accuracy of spinal surgery. This study aimed to assess the accuracy of thoraco-lumbar pedicle screw insertion using the O-arm (Breakaway Imaging, LLC, Littleton, MA, USA) 3D imaging system. Ninety-two patients underwent insertion of thoraco-lumbar pedicle screws guided by O-arm navigation over a 27month period. Intra-operative scans were retrospectively reviewed for pedicle breach. The operative time of patients where O-arm navigation was used was compared to a matched control group where fluoroscopy was used. A total of 467 pedicle screws were inserted. Four hundred and forty-five screws (95.3%) were placed within the pedicle without any breach (Gertzbein classification grade 0). Sixteen screws (3.4%) had a pedicle breach of less than 2mm (Gertzbein classification grade 1), and six screws (1.3%) had a pedicle breach between 2mm and 4mm (Gertzbein classification grade 2). The grade 2 screws were revised intra-operatively. There was no incidence of neurovascular injury in this series of patients. The mean operative time for O-arm patients was 5.25hours. In a matched control group of fluoroscopy patients, the mean operative time was 4.75hours. The difference in the mean operative time between the two groups was not statistically significant (p=0.15, paired t-test). Stereotactic navigation based on intra-operative O-arm 3D imaging resulted in high accuracy in thoraco-lumbar pedicle screw insertion.
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Super, red palm and palm oleins improve the blood pressure, heart size, aortic media thickness and lipid profile in spontaneously hypertensive rats.
PLoS ONE
PUBLISHED: 01-04-2013
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Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension.
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Place of death and its determinants for patients with cancer in Singapore: an analysis of data from the Singapore Cancer Registry, 2000-2009.
J Palliat Med
PUBLISHED: 10-03-2011
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To describe the place of death for patients with cancer in Singapore from 2000 to 2009, and determinants of death at home and in in-patient hospice compared to death in hospital.
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The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore.
BMC Infect. Dis.
PUBLISHED: 06-11-2011
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Enterovirus 71 (EV71) has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997.
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Effects of cognitive-behavioral therapy on anxiety in children with autism spectrum disorders: a randomized controlled trial.
Child Psychiatry Hum Dev
PUBLISHED: 06-11-2011
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We compared the effects of a 16-week Cognitive-Behavioral Therapy (CBT) program and a Social Recreational (SR) program on anxiety in children with Autism Spectrum Disorders (ASD). Seventy children (9-16 years old) were randomly assigned to either of the programs (n (CBT) = 36; n (SR) = 34). Measures on childs anxiety using the Spence Child Anxiety Scale--Child (SCAS-C) and the Clinical Global Impression-Severity scale (CGI--S) were administered at pre-, post-treatment, and follow-ups (3- and 6-month). Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as "Normal" and "Borderline" for both programs. Findings from the present study suggest factors such as regular sessions in a structured setting, consistent therapists, social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD.
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Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
PLoS Genet.
PUBLISHED: 05-25-2011
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The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P?=?2.32×10(-12), OR?=?0.75). Also, rs12540874 in GRB10 gene (P?=?1.27 × 10(-6), OR?=?1.15) and rs11047102 in SOX5 gene (P?=?1.39×10(-7), OR?=?1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P?=?1.79×10(-61), OR?=?2.48), in the HLA-DPA1/B1 loci with ATA (P?=?4.57×10(-76), OR?=?8.84), and in NOTCH4 with ACA P?=?8.84×10(-21), OR?=?0.55) and ATA (P?=?1.14×10(-8), OR?=?0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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Development of live attenuated Bordetella pertussis strains expressing the universal influenza vaccine candidate M2e.
Vaccine
PUBLISHED: 03-25-2011
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The attenuated Bordetella pertussis BPZE1 vaccine strain represents an attractive platform for the delivery of heterologous vaccine candidates via the nasal route. The filamentous hemagglutinin (FHA) has been used to secrete or expose the foreign antigens at the bacterial surface. In this study, one, two and three copies of the Cys-containing ectodomain of matrix protein 2 (M2e) from influenza A virus were genetically fused to full length FHA and expressed in BPZE1. The secretion efficacy of the FHA-(M2e)(1,2,3) chimera in the extracellular milieu and the ability of the recombinant bacteria to colonize the mouse lungs inversely correlated with the number of M2e copies fused to FHA. Nevertheless FHA-(M2e)(3)-producing bacteria (BPLR3) triggered the highest systemic anti-M2e antibody response upon nasal administration to BALB/c mice. Nasal immunization with BPLR3 bacteria resulted in a significant reduction in the viral loads upon challenge with H1N1/PR8 influenza A virus, but did not improve the survival rate compared to BPZE1-immunized mice. Furthermore, since previous work reported that disulfide bond formation in Cys-containing passenger antigens affects the secretion efficacy of the FHA chimera, the dsbA gene encoding a periplasmic disulfide isomerase was deleted in the FHA-(M2e)(3)-producing strain. Despite improving significantly the secretion efficacy of the FHA-(M2e)(3) chimera, the dsbA deletion did not result in higher anti-M2e antibody titers in mice, due to impaired bacterial fitness and colonization ability.
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Ovarian choriocarcinoma as the first manifestation of 46,XY pure gonadal dysgenesis.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 02-22-2011
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We report a case of 46,XY pure gonadal dysgenesis (Swyer syndrome) in a phenotypically normal 12-year-old girl with a history of vaginal bleeding and early breast development, with ovarian choriocarcinoma as the first manifestation. The clues leading to the diagnosis included the failure to establish any relationship between normal menstrual cycles postoperatively and a small remaining contralateral ovary. The correct diagnosis is important for cancer prophylaxis and hormonal replacement therapy. Prepubertal and peripubertal girls presenting with gonadal germ cell tumors should be carefully evaluated for the possibility of underlying gonadal dysgenesis. A history of vaginal bleeding or early signs of puberty does not exclude the diagnosis.
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Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis.
Am. J. Pathol.
PUBLISHED: 02-11-2011
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Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-?, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.
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Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans.
Exerc Immunol Rev
PUBLISHED: 09-16-2010
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Acute bouts of aerobic exercise are known to mobilize antigen-experienced CD8+ T-cells expressing the cell surface marker of senescence, KLRG1, into the blood. It is not known; however if this is due to a selective mobilization of terminally differentiated T-cells (i.e., KLRG1 +/CD28-/CD57+) or a population of effector memory T-cells (i.e., KLRG1+/CD28+/CD57-) that have not reached terminal differentiation. The aim of this study was to further characterize KLRG1 + T-cells mobilized by acute exercise by assessing the co-expression of KLRG1 with CD28 or CD57 and to determine telomere lengths in the CD4+ and CD8+ T-cell subsets. Nine moderately trained male subjects completed an exhaustive treadmill running protocol at 80%. Blood lymphocytes isolated before, immediately after and 1h after exercise were labelled with antibodies against KLRG1, CD28 or CD57, CD4 or CD8 and CD3 for 4-color flow cytometry analysis. Telomere lengths in CD3+, CD4+ and CD8+ T-cells were determined using Q-PCR. The relative proportion of KLRG1 + cells among the CD8+ T-cells increased by 40% immediately after exercise, returning to baseline 1h later. This was due to a mobilization of KLRG1+/CD28- (61% increase), KLRG1+/CD57+ (56% increase) and to a lesser extent, KLRG1+/CD57- cells (24% increase). Telomeres in CD8+ T-cells displayed an increased relative length immediately after exercise, whereas no change occurred for CD4+ or the overall CD3+ T-cells. In conclusion, the increased frequency of KLRG1 +/CD8+ T-cells in blood after acute exercise is predominantly due to a selective mobilization of terminally differentiated T-cells. The increased relative telomere length in CD8+ T-cells after exercise might indicate that KLRG1+ cells mobilized by exercise are under stress or aberrant signaling-induced senescence (STASIS). We postulate that a frequent mobilization of these cells by acute exercise might eventually allow naïve T-cells to occupy the "vacant" immune space and increase the naïve T-cell repertoire.
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Attenuated Bordetella pertussis protects against highly pathogenic influenza A viruses by dampening the cytokine storm.
J. Virol.
PUBLISHED: 05-05-2010
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The threat of a pandemic spread of highly virulent influenza A viruses currently represents a top global public health problem. Mass vaccination remains the most effective way to combat influenza virus. However, current vaccination strategies face the challenge to meet the demands in a pandemic situation. In a mouse model of severe influenza virus-induced pneumonitis, we observed that prior nasal administration of an attenuated strain of Bordetella pertussis (BPZE1) provided effective and sustained protection against lethal challenge with two different influenza A virus subtypes. In contrast to most cross-protective effects reported so far, the protective window offered upon nasal treatment with BPZE1 lasted up to at least 12 weeks, suggesting a unique mechanism(s) involved in the protection. No significant differences in viral loads were observed between BPZE1-treated and control mice, indicating that the cross-protective mechanism(s) does not directly target the viral particles and/or infected cells. This was further confirmed by the absence of cross-reactive antibodies and T cells in serum transfer and in vitro restimulation experiments, respectively. Instead, compared to infected control mice, BPZE1-treated animals displayed markedly reduced lung inflammation and tissue damage, decreased neutrophil infiltration, and strong suppression of the production of major proinflammatory mediators in their bronchoalveolar fluids (BALFs). Our findings thus indicate that protection against influenza virus-induced severe pneumonitis can be achieved through attenuation of exaggerated cytokine-mediated inflammation. Furthermore, nasal treatment with live attenuated B. pertussis offers a potential alternative to conventional approaches in the fight against one of the most frightening current global public health threats.
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Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
Nat. Genet.
PUBLISHED: 01-04-2010
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Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
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Coupled UASB-activated sludge process for COD and nitrogen removals in municipal sewage treatment in warm climate.
Water Sci. Technol.
PUBLISHED: 11-26-2009
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A laboratory-scale system consisting of an upflow anaerobic sludge blanket (UASB) reactor followed by a modified Ludzack-Ettinger (MLE) activated sludge process was adopted to investigate COD and nitrogen removals in municipal sewage treatment in warm climate. The COD, SCOD, acetic acid (HAc), NH4+-N and PO4(3-)-P conversions in the UASB reactor were investigated. A 35% reduction in volatile suspended solid (VSS) was achieved in the UASB process. The net methane (CH4) production was 0.06 l (g COD(removed))(-1). Acids accumulation was not observed. In the MLE activated sludge process, nitrification was almost complete while denitrification was modest. Little excess sludge was produced as the bulk of the COD was removed in the UASB reactor, which reduced the COD mass load to the activated sludge process. The average COD and SCOD of the final effluent of the activated sludge process were 51 and 25 mg l(-1), respectively and the average NH4+-N concentration of the final effluent was 3.1 mg N l(-1). The results illustrated that the coupled process is feasible for COD and nitrogen removals in municipal sewage treatment in warm climate. However, the low pH of the final effluent (<6 on average) remains an issue to be solved.
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Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury.
Am. J. Pathol.
PUBLISHED: 09-03-2009
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Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in either PKD1 or PKD2 and accounts for 10% of all patients on renal replacement therapy. The kidney disease phenotype is primarily characterized by cyst formation, but there are also prominent interstitial changes (inflammation, apoptosis, proliferation, and fibrosis). Using a model of unilateral ischemia-reperfusion injury, we tested the hypothesis that Pkd2 heterozygous kidneys are more sensitive to injury and that this could lead to interstitial inflammation and fibrosis. Baseline tubular proliferation in heterozygous kidneys was twofold higher than in wild-type kidneys. The magnitude and duration of tubular and interstitial proliferative responses was consistently greater in injured heterozygous compared with wild-type kidneys at all time points. Conversely, tubular p21 expression in heterozygotes was lower at baseline and following injury at all time points. Significantly more neutrophils and macrophages were detected in injured Pkd2 heterozygous kidneys at 2 days, correlating with increased expression of the cytokines interleukin (IL)-1beta and keratinocyte-derived chemokine and resulting in interstitial fibrosis at 28 days. We conclude that Pkd2 dosage influences both susceptibility and nature of the repair responses following injury. Polycystin-2 is therefore likely to play multiple roles in regulating tubular cell viability, repair, and remodeling in the mature kidney.
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Suicidal and help-seeking behavior in Xiamen, south China.
Asia Pac Psychiatry
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The aim of this study is to examine the association between suicidal behavior and mental health status of south Chinese people, and explore the mediating effect of help-seeking behaviors.
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Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore.
BMC Infect. Dis.
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Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools.
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Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up.
Hum. Mol. Genet.
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Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value = 5.04 × 10(-12), odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 × 10(-7), OR = 1.36) and NFKB1 (P-value = 1.03 × 10(-6), OR = 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones.
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In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection.
J. Gen. Virol.
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Influenza A virus has caused a number of pandemics in past decades, including the recent H1N1-2009 pandemic. Viperin is an interferon (IFN)-inducible protein of innate immunity, and acts as a broad-spectrum antiviral protein. We explored the antiviral activities and mechanisms of viperin during influenza virus (IFV) infection in vitro and in vivo. Wild-type (WT) HeLa and viperin-expressing HeLa cells were infected with influenza A/WSN/33/H1N1 (WSN33) virus, and subjected to virological, light and electron microscopic analyses. Viperin expression reduced virus replication and titres, and restricted viral budding. Young and old viperin-knockout (KO) mice and WT control animals were challenged with influenza WSN33 at lethal doses of 10(3) and 10(4) p.f.u. via the intratracheal route. Lungs were subjected to histopathological, virological and molecular studies. Upon lethal IFV challenge, both WT and KO mice revealed similar trends of infection and recovery with similar mortality rates. Viral quantification assay and histopathological evaluation of lungs from different time points showed no significant difference in viral loads and lung damage scores between the two groups of mice. Although the in vitro studies demonstrated the ability of viperin to restrict influenza H1N1 virus replication, the viperin-deficient mouse model indicated that absence of viperin enhanced neither the viral load nor pulmonary damage in the lungs of infected mice. This may be due to the compensation of IFN-stimulated genes in the lungs and/or the influenza non-structural protein 1-mediated IFN antagonism dampening the IFN response, thereby rendering the loss of viperin insignificant. Nevertheless, further investigations that exploit the antiviral mechanisms of viperin as prophylaxis are still warranted.
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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.