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Find video protocols related to scientific articles indexed in Pubmed.
Downregulated miR-329 and miR-410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b.
Cancer Res.
PUBLISHED: 10-30-2014
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MicroRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR-329 and miR-410, which could potentially target Wnt-7b, an activator of the Wnt/?-catenin pathway, thereby attenuating the Wnt/?-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR-329 or miR-410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to re-express miR-329, miR-410 and Meg3 consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR-329, miR-410 and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contribute to oral carcinogenesis through epigenetic silencing of tumor suppressor miRNA which target Wnt/?-catenin signaling.
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A fly model for the CCUG-repeat expansion of myotonic dystrophy type 2 reveals a novel interaction with MBNL1.
Hum. Mol. Genet.
PUBLISHED: 10-09-2014
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Expanded non-coding RNA repeats of CUG and CCUG are the underlying genetic causes for myotonic dystrophy type 1 (DM1) and type 2 (DM2), respectively. A gain-of-function of these pathogenic repeat expansions is mediated at least in part by their abnormal interactions with RNA-binding proteins such as MBNL1 and resultant loss of activity of these proteins. To study pathogenic mechanisms of CCUG-repeat expansions in an animal model, we created a fly model of DM2 that expresses pure, uninterrupted CCUG-repeat expansions ranging from 16 to 720 repeats in length. We show that this fly model for DM2 recapitulates key features of human DM2 including RNA repeat-induced toxicity, ribonuclear foci formation and changes in alternative splicing. Interestingly, expression of two isoforms of MBNL1, MBNL135 and MBNL140, leads to cleavage and concurrent upregulation of the levels of the RNA-repeat transcripts, with MBNL140 having more significant effects than MBNL135. This property is shared with a fly CUG-repeat expansion model. Our results suggest a novel mechanism for interaction between the pathogenic RNA repeat expansions of myotonic dystrophy and MBNL1.
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Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma.
J. Oral Pathol. Med.
PUBLISHED: 09-04-2014
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This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC).
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A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.
PLoS ONE
PUBLISHED: 08-15-2014
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Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.
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Pronator Teres Transfer for Forearm and Wrist Deformity in Cerebral Palsy Children.
J Pediatr Orthop
PUBLISHED: 07-31-2014
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Forearm pronation and wrist flexion contracture can be a disability for daily living care and 2-hand function in cerebral palsy (CP) children. It may be beneficial to improve their posture and hand-grip power for better functional outcome. The purpose of our study was to investigate the outcome of pronator transfer in CP children.
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Zygotic expression of Exostosin1 (Ext1) is required for BMP signaling and establishment of dorsal-ventral pattern in Xenopus.
Int. J. Dev. Biol.
PUBLISHED: 05-28-2014
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Exostosin 1 (EXT1) is a glycosyltransferase that contributes to the biosynthesis of heparan sulfate proteoglycans (HSPG). Loss of ext1 function leads to the human genetic disorder hereditary multiple exostoses (HME) and inhibits development in mouse, zebrafish and Drosophila. In Xenopus, loss of maternal EXT1 leads to impaired wnt11 signaling, resulting in a loss of dorsal embryonic development (Tao et al., 2005), but the functions of zygotic ext1 have not been elucidated. In this study, morpholino oligonucleotides were used to generate a zygotic partial loss of function for ext1, in order to evaluate the requirements for ext1 function in gastrulation and paracrine signaling. Transcriptional profiling was carried out by microarray. Validation and subsequent analyses of gene expression were performed using Q-RT-PCR and in situ hybridization. Western blots were used to assess paracrine signaling pathway activity. Introduction of ext1 MO led to gastrulation defects, which were partially rescued by co-injection of ext1 mRNA. Microarray-based comparisons of gene expression in control vs. Ext1 MO embryos identified several developmentally significant genes that are dependent upon Ext1 function, including brachyury (Xbra). In addition, decreased Ext1 was shown to reduce the level of Wnt8 and BMP4 signaling and disrupt ventral-specific gene expression. Ext1 function is required for maintenance of normal levels of BMP and wnt, as well as their target genes. In addition, expression of xbra and the establishment of ventral mesoderm depend upon normal levels of Ext1. These findings suggest that ext1-dependent synthesis of HSPG is critical for wnt and BMP signaling, mesodermal identity, and ventral pattern.
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Results of a two-year pilot study of clinical outcome measures in collagen VI-related myopathy and LAMA2-related muscular dystrophy.
Neuromuscul. Disord.
PUBLISHED: 05-02-2014
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Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI related myopathy (COL6-RM) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RM and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL(TM) Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL(TM) scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RM and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes.
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Plasma growth arrest-specific protein 6 levels in premenopausal and postmenopausal women: the role of endogenous estrogen.
Endocrine
PUBLISHED: 03-01-2014
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Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein that interacts with receptor tyrosine kinases of the Tyro-3, AXL, Mer (TAM) family. The Gas6/TAM system contributes to the regulation of cell survival and proliferation, cell adhesion and migration, and inflammatory cytokines release. Plasma Gas6 plays an important role in the inflammatory process, and is involved in diverse human diseases. Few studies have investigated gender-specific variations in plasma Gas6 concentration. Hence, the aim of this study was to determine whether plasma Gas6 levels are associated with sex hormones in premenopausal and postmenopausal women. A total of 103 premenopausal and 135 postmenopausal women were recruited. Plasma Gas6 concentration, estradiol (E2), and sex hormone-binding globulin were assayed. The free estrogen index (FEI) was calculated. The results showed significantly lower Gas6 levels in the postmenopausal compared to the premenopausal women (P < 0.005). Plasma Gas6 levels were positively correlated with E2 levels in the pre- and postmenopausal women (r = 0.359, P < 0.001 and r = 0.261, P = 0.002, respectively). Gas6 levels were also correlated with FEI in the pre- and postmenopausal women (r = 0.234, P = 0.017 and r = 0.188, P = 0.029, respectively). After adjusting for confounders, the correlations still remained significant. In multiple stepwise regression analysis, only E2 in premenopausal and both age and E2 in postmenopausal women were independently correlated with the plasma Gas6 levels (all P < 0.001). These results suggest that plasma Gas6 is associated with sex hormones in both pre- and postmenopausal women, indicating a potential role of sex hormones in the Gas6/TAM system.
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Expression of growth arrest-specific protein 6 and Axl molecules in the left internal mammary artery of patients undergoing coronary artery bypass grafting.
J. Clin. Pathol.
PUBLISHED: 02-24-2014
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Studies have demonstrated that using a left internal mammary artery (LIMA) graft yields excellent long-term results in coronary artery bypass grafting (CABG). The growth arrest-specific 6 (Gas6) gene and its receptor, Axl, are crucial in vascular haemostasis and atherosclerosis. The objective of this study was to determine the expression of Gas6 and Axl molecules in the aorta and LIMA in patients undergoing CABG.
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High glucose induces human endothelial dysfunction through an Axl-dependent mechanism.
Cardiovasc Diabetol
PUBLISHED: 02-15-2014
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The receptor tyrosine kinase Axl and its ligand growth arrest-specific protein 6 (Gas6) are involved in the diabetic vascular disease. The aim of this study was to explore the role of Gas6/Axl system in high glucose (HG)-induced endothelial dysfunction.
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Enhanced anti-tumor activity of triptolide in combination with irradiation for the treatment of oral cancer.
Planta Med.
PUBLISHED: 02-07-2014
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Advanced oral cancer has a poor prognosis because of the lack of an effective treatment. We explored the efficiency of combined treatment with triptolide and ionizing radiation for treating oral cancer. Human tongue cancer cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation. Cell proliferation, cell cycle arrest, and apoptotic influences were analyzed by FACS and immunohistochemistry. Tumor potency was examined in an in vivo human tongue cancer cells xenograft mouse model. Our results demonstrated that triptolide caused a marked reduction in colony number that was further enhanced with increasing doses of ionizing radiation. Triptolide increased apoptosis and decreased the expression of anti-apoptotic proteins. In vivo, combination treatment synergistically reduced tumor weight and volume possibly via the induction of apoptosis and reduction in anti-apoptotic protein expression. In conclusion, triptolide plus ionizing radiation treatment had synergistic anti-tumor effects, especially in vivo, and may be a promising combined modality therapy for advanced oral cancer.
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The levels of plasma growth arrest-specific protein 6 is associated with insulin sensitivity and inflammation in women.
Diabetes Res. Clin. Pract.
PUBLISHED: 01-08-2014
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Vitamin K-dependent growth arrest-specific protein 6 (Gas6) and its receptors of the TAM (TYRO-3/Axl/Mer) family are ubiquitously expressed in immune, cardiovascular, and reproductive systems. They play pivotal roles of regulating tissue homeostasis via anti-inflammatory effects. Recent studies show that the Gas6/TAM system is involved in glucose tolerance-related metabolic disorders. Our aim was to investigate the link between Gas6 protein, insulin sensitivity and inflammatory cytokines in men and women.
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Effect of GAS6 and AXL Gene Polymorphisms on Adiposity, Systemic Inflammation, and Insulin Resistance in Adolescents.
Int J Endocrinol
PUBLISHED: 01-07-2014
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The present study was designed to explore the effects of GAS6 and AXL gene polymorphisms on adiposity, systemic inflammation, and insulin resistance in adolescents. After multistage sampling from the data of the Taipei Children Heart Study-III, we collected 358 boys and 369 girls with an average age of 13.3 years. We genotyped the adolescents' GAS6 rs8191973, GAS6 rs8191974, AXL rs4802113, and AXL rs2304232 polymorphisms. Significantly higher body mass index (BMI), waist circumference (WC), and hsCRP levels were found in boys with the GG genotype of GAS6 rs8191974 than A allele carriers; higher IL-6 and insulin levels and increased HOMA-IR were found in boys with the GG genotype of AXL rs2304232 than the A allele carriers. There was a significant difference in hsCRP levels of boys with the TT, TC, and CC genotypes of AXL rs4802113. Boys with both the GG genotype of GAS6 rs8191973 and the GG genotype of GAS6 rs8191974 exhibited higher BMI, WC, IL-6, and hsCRP levels than the boys carrying both the C allele of the GAS6 rs8191973 and the A allele of the GAS6 rs8191974. In conclusion, GAS6 and AXL polymorphisms are associated with adiposity, systemic inflammation, and insulin resistance in adolescents, especially in boys.
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Risk assessment of inferior alveolar nerve injury for immediate implant placement in the posterior mandible: a virtual implant placement study.
J Dent
PUBLISHED: 01-03-2014
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To investigate the prevalence and morphological parameters of lingual concavity, and whether these factors are related to a higher risk of inferior alveolar nerve (IAN) injury when performing an immediate implant surgery in posterior mandible region.
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A retrospective case-control analysis of the outpatient expenditures for western medicine and dental treatment modalities in CKD patients in Taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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To determine if expenditures for dentistry (DENT) correlate with severity of chronic kidney disease (CKD).
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Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-?B/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis.
Diabetologia
PUBLISHED: 08-06-2013
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Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1) were tested in a mouse model of type 2 diabetic nephropathy.
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Determinants of quality of life in children with cerebral palsy: A comprehensive biopsychosocial approach.
Res Dev Disabil
PUBLISHED: 07-23-2013
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This study investigated the determinants of quality of life (QOL) of children with cerebral palsy (CP) considering possible variables comprehensively from a biopsychosocial perspective by adopting the International Classification of Functioning, Disability and Health (ICF) and using a CP-specific QOL questionnaire. A total of 167 children with CP (mean age 9.06 years, SD 2.61 years) and their caregivers participated in this study. Childrens QOL was measured by the Cerebral Palsy Quality of Life for Children (CP QOL-Child) - primary caregiver proxy-report form. The potential determinants of QOL were collected based on all ICF dimensions. Results of seven multiple regression models showed that the determinants of QOL in children with CP were multidimensional and biopsychosocial in nature, i.e., encompassing the domains of health condition, body functions and structures, and contextual factors of the ICF. Childrens behavioral and emotional problems as well as caregivers psychological and family-related factors were important determinants of QOL in children with CP. Knowledge of the determinants of QOL could serve as a guide in a holistic approach to evaluation and intervention targeted at these determinants to improve the QOL of children with CP.
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A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells.
Carcinogenesis
PUBLISHED: 07-23-2013
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Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata. However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 = 0.75 ?M) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 ?M). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway.
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Determinants of school activity performance in children with cerebral palsy: a multidimensional approach using the ICF-CY as a framework.
Res Dev Disabil
PUBLISHED: 06-13-2013
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This study aimed to identify the determinants of activity performance in children with cerebral palsy (CP) in school by considering factors from the entire scope of the International Classification of Functioning, Disability, and Health for Child and Youth (ICF-CY). A sample of 167 school-aged children with CP and their caregivers were recruited in the study. Activity performance in school settings was assessed with part 3 of the School Functional Assessment - Chinese version, which divides activity performance into performance of physical activities and cognitive/behavioral activities. Possible determinants were collected according to all dimensions of the ICF-CY. Multiple regression analyses showed that the determinants of performance of physical activities were receiving speech therapy in school, diplegia, having a domestic helper, and severity of gross and fine motor impairments, explaining 83% of the total variance; the determinants of performance of cognitive/behavioral activities were intellectual impairment, prosocial behavior, having an assistant in school, educational placement, severity of fine motor impairment, accounting for 73% of the total variance. Results of the study provide clinicians a holistic understanding of factors influencing school activity performance, and enable clinicians to make appropriate evaluations and interventions targeted at the determinants to enhance childrens activity performance in school.
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A home-based program using patterned sensory enhancement improves resistance exercise effects for children with cerebral palsy: a randomized controlled trial.
Neurorehabil Neural Repair
PUBLISHED: 06-10-2013
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Neurologic music therapy has demonstrated improved walking performance in persons with neurologic disease; however, little evidence supports the use of music with functional resistance exercise to improve motor capacity and daily functions for children with cerebral palsy.
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Tumor-Associated Macrophages Promote Oral Cancer Progression Through Activation of the Axl Signaling Pathway.
Ann. Surg. Oncol.
PUBLISHED: 03-10-2013
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Recent studies suggest that tumor-associated macrophages (TAMs) promote tumor growth and metastasis. Our previous report demonstrated that Axl signaling promotes carcinogenesis and progression of oral squamous cell carcinoma (OSCC). This study aims to test the potential involvement of growth arrest-specific gene 6 (Gas6)/Axl signaling in the protumoral effect of TAMs.
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A preclinical evaluation of antimycin a as a potential antilung cancer stem cell agent.
Evid Based Complement Alternat Med
PUBLISHED: 03-10-2013
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Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs) as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP) method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs), was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA), was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, ? -catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress ? -catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate ? -catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.
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Concomitant horner and harlequin syndromes after inferior alveolar nerve block anesthesia.
J Endod
PUBLISHED: 02-14-2013
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Intraoral anesthesia is probably the most commonly used procedure in dentistry.
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Neuroimaging and electroencephalographic changes after vagus nerve stimulation in a boy with medically intractable myoclonic astatic epilepsy.
J. Formos. Med. Assoc.
PUBLISHED: 01-30-2013
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Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta-gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria-fornix, indicating improved diffusion of the white matter tract, and (18)F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social-emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria-fornix and glucose metabolism in MAE.
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Circulating growth arrest-specific 6 protein is associated with adiposity, systemic inflammation, and insulin resistance among overweight and obese adolescents.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-22-2013
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Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Preclinical studies indicate that Gas6 and its receptors of the TAM (Tyro-3, Axl, Mer) family may be involved in the pathogenesis of obesity and its complications, including systemic inflammation and insulin resistance. Until now, little has been known about the clinical significance of the Gas6/TAM system in childhood obesity.
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Factors affecting treatment decisions and outcomes of root-resected molars: a nationwide study.
J. Periodontol.
PUBLISHED: 01-17-2013
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Treatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset.
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Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-?B/microRNA 448 circuit.
Mol Nutr Food Res
PUBLISHED: 01-10-2013
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Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer.
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Logistic regression analyses for predicting clinically important differences in motor capacity, motor performance, and functional independence after constraint-induced therapy in children with cerebral palsy.
Res Dev Disabil
PUBLISHED: 01-03-2013
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Given the growing evidence for the effects of constraint-induced therapy (CIT) in children with cerebral palsy (CP), there is a need for investigating the characteristics of potential participants who may benefit most from this intervention. This study aimed to establish predictive models for the effects of pediatric CIT on motor and functional outcomes. Therapists administered CIT to 49 children (aged 3-11 years) with CP. Sessions were 1-3.5h a day, twice a week, for 3-4 weeks. Parents were asked to document the number of restraint hours outside of the therapy sessions. Domains of treatment outcomes included motor capacity (measured by the Peabody Developmental Motor Scales II), motor performance (measured by the Pediatric Motor Activity Log), and functional independence (measured by the Pediatric Functional Independence Measure). Potential predictors included age, affected side, compliance (measured by time of restraint), and the initial level of motor impairment severity. Tests were administered before, immediately after, and 3 months after the intervention. Logistic regression analyses showed that total amount of restraint time was the only significant predictor for improved motor capacity immediately after CIT. Younger children who restrained the less affected arm for a longer time had a greater chance to achieve clinically significant improvements in motor performance. For outcomes of functional independence in daily life, younger age was associated with clinically meaningful improvement in the self-care domain. Baseline motor abilities were significantly predictive of better improvement in mobility and cognition. Significant predictors varied according to the aspects of motor outcomes after 3 months of follow-up. The potential predictors identified in this study allow clinicians to target those children who may benefit most from CIT.
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The Cerebral Palsy Quality of Life for Children (CP QOL-Child): evidence of construct validity.
Res Dev Disabil
PUBLISHED: 01-02-2013
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The Cerebral Palsy Quality of Life for Children (CP QOL-Child) is the first health condition-specific questionnaire designed for measuring QOL in children with cerebral palsy (CP). However, its construct validity has not yet been confirmed by confirmatory factor analysis (CFA). Hence, this study assessed the construct validity of the caregiver proxy-report version of the Chinese version of the CP QOL-Child in children with CP using CFA. A total of 312 children with CP (mean age: 8.59 years, SD: 2.52 years) and their caregivers participated in this study. The Chinese version of the CP QOL-Child was completed by the caregivers of children with CP. Then, CFA was applied to evaluate the seven-factor measurement structure of the CP QOL-Child. The seven-factor CFA model had an adequate fit to our data as judged by ?(2) statistic and various goodness-of-fit (GOF) indices, including the root mean square error of approximation (RMSEA). This study provided empirical evidence of the construct validity of the CP QOL-Child to support its use with children with CP in the Chinese speaking society.
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Plasma concentrations predict aortic expression of growth-arrest-specific protein 6 in patients undergoing coronary artery bypass grafting.
PLoS ONE
PUBLISHED: 01-01-2013
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The tyrosine kinase receptor Axl is expressed in the vasculature, and growth arrest-specific protein 6 (Gas6) is its ligand. Plasma Gas6 levels have been shown to be associated with endothelial dysfunction markers and cardiovascular events. We set out to determine the plasma Gas6 levels in patients undergoing coronary artery bypass grafting (CABG) and investigate the expression of Gas6 and Axl in the aorta.
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LIA5 is required for nuclear reorganization and programmed DNA rearrangements occurring during tetrahymena macronuclear differentiation.
PLoS ONE
PUBLISHED: 01-01-2013
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During macronuclear differentiation of the ciliate Tetrahymena thermophila, genome-wide DNA rearrangements eliminate nearly 50 Mbp of germline derived DNA, creating a streamlined somatic genome. The transposon-like and other repetitive sequences to be eliminated are identified using a piRNA pathway and packaged as heterochromatin prior to their removal. In this study, we show that LIA5, which encodes a zinc-finger protein likely of transposon origin, is required for both chromosome fragmentation and DNA elimination events. Lia5p acts after the establishment of RNAi-directed heterochromatin modifications, but prior to the excision of the modified sequences. In ?LIA5 cells, DNA elimination foci, large nuclear sub-structures containing the sequences to be eliminated and the essential chromodomain protein Pdd1p, do not form. Lia5p, unlike Pdd1p, is not stably associated with these structures, but is required for their formation. In the absence of Lia5p, we could recover foci formation by ectopically inducing DNA damage by UV treatment. Foci in both wild-type or UV-treated ?LIA5 cells contain dephosphorylated Pdd1p. These studies of LIA5 reveal that DNA elimination foci form after the excision of germ-line limited sequences occurs and indicate that Pdd1p reorganization is likely mediated through a DNA damage response.
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Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.
Hum. Mol. Genet.
PUBLISHED: 09-20-2011
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Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.
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The growth arrest-specific 6 (Gas6) gene polymorphism c.834+7G>A is associated with type 2 diabetes.
Diabetes Res. Clin. Pract.
PUBLISHED: 06-24-2011
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The plasma protein growth arrest-specific 6 (Gas6) is important to the inflammatory process and involved in the development of diabetic renal and vascular complications. Recently, Gas6 protein also represents a novel independent risk factor of type 2 diabetes. We further investigated the association of c.843+7G>A Gas6 polymorphism and type 2 diabetes.
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Axl is a prognostic marker in oral squamous cell carcinoma.
Ann. Surg. Oncol.
PUBLISHED: 04-22-2011
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Overexpression of the receptor tyrosine kinase Axl is implicated in several diseases. The present study was conducted to determine the biologic and clinical significance of Axl in oral squamous cell carcinoma (OSCC).
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Gay and lesbian couple relationship commitment in taiwan: a preliminary study.
J Homosex
PUBLISHED: 11-09-2010
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Due to the traditional values on marriage and heterosexual relationships, gay and lesbian couple relationships were long ignored in Taiwan. This study attempted to look at gay and lesbian couple relationship commitment. Questionnaires were used in this study. Due to the difficulties of getting gays and lesbians to participate in research, snowballing method was used. The sample included 218 participants in a stable couple relationship for at least six months. Through multiple regression analyses, the result showed that the influencing factors of gay and lesbian couples commitment fit Rusbults Investment Model closely.
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Defining genetic factors that modulate intergenerational CAG repeat instability in Drosophila melanogaster.
Genetics
PUBLISHED: 11-01-2010
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Trinucleotide repeat instability underlies >20 human hereditary disorders. These diseases include many neurological and neurodegenerative situations, such as those caused by pathogenic polyglutamine (polyQ) domains encoded by expanded CAG repeats. Although mechanisms of instability have been intensely studied, our knowledge remains limited in part due to the lack of unbiased genome-wide screens in multicellular eukaryotes. Drosophila melanogaster displays triplet repeat instability with features that recapitulate repeat instability seen in patients with disease. Here we report an enhanced fly model with substantial instability based on a noncoding 270 CAG (UAS-CAG(270)) repeat construct under control of a germline-specific promoter. We find that expression of pathogenic polyQ protein modulates repeat instability of CAG(270) in trans, indicating that pathogenic-length polyQ proteins may globally modulate repeat instability in the genome in vivo. We further performed an unbiased genetic screen for novel modifiers of instability. These studies indicate that different aspects of repeat instability are under independent genetic control, and identify CG15262, a protein with a NOT2/3/5 conserved domain, as a modifier of CAG repeat instability in vivo.
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The determinants of daily function in children with cerebral palsy.
Res Dev Disabil
PUBLISHED: 09-20-2010
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The aim of this study was to identify determinants of daily function in a population-based sample of children with cerebral palsy (CP). The study took into consideration factors from the entire scope of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, the determinants of daily function were examined from the perspectives of capacity and performance respectively. A total of 216 children with CP (mean age 8.19 years, SD 3.39 years) and their caregivers participated in the study. The potential determinants of daily function from the dimensions of health condition, body functions and structures, environmental and personal factors of the ICF were collected. Stepwise multiple regression models showed that childs age, grade, preferred hand, educational placement, severity of gross and fine motor impairment, and prosocial behavior were important determinants, accounting for 88.29% of the variance of daily capacity. The aforementioned variables together with birth order were determinants of performance of daily function, and accounted for 89.53% of the variance in that performance. Knowledge of determinants of daily function helps clinicians and educators to plan intervention and educational programs targeted at these determinants to improve capacity and performance in daily function for children with CP.
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Intratumoral macrophage counts correlate with tumor progression in colorectal cancer.
J Surg Oncol
PUBLISHED: 08-27-2010
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The role of intratumoral tumor-associated macrophages (TAMs) in colorectal cancer (CRC) is not clear. We aim to examine the relationships of TAMs and the clinicopathologic features of CRC and the expression of matrix metalloproteinases (MMP)-2 and MMP-9.
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Plasma protein growth arrest-specific 6 levels are associated with altered glucose tolerance, inflammation, and endothelial dysfunction.
Diabetes Care
PUBLISHED: 05-26-2010
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Plasma protein growth arrest-specific 6 (Gas6) is important to the inflammatory process and is involved in the development of diabetic renal and vascular complications. We set out to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammation, and endothelial dysfunction.
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Continued root formation after replantation and root canal treatment in an avulsed immature permanent tooth: a case report.
Dent Traumatol
PUBLISHED: 05-22-2010
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This case report describes the continued root formation following replantation and conventional root canal therapy of a traumatically avulsed open-apex tooth with suppurative apical periodontitis. A 7-year-old male patient had an avulsed upper left central incisor (tooth 21) replanted approximately 50 min after traumatic avulsion. A root canal procedure was initiated due to pulp necrosis and periapical abscess detected in the follow-up period. After endodontic treatment with calcium hydroxide (Ca(OH)(2)) dressing, a normal root length developed including an apical segment beyond the hard tissue barrier. Regeneration of the root occurred without pathology or ankylosis at 1-year of follow up.
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The conjugation-specific Die5 protein is required for development of the somatic nucleus in both Paramecium and Tetrahymena.
Eukaryotic Cell
PUBLISHED: 05-21-2010
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Development in ciliated protozoa involves extensive genome reorganization within differentiating macronuclei, which shapes the somatic genome of the next vegetative generation. Major events of macronuclear differentiation include excision of internal eliminated sequences (IESs), chromosome fragmentation, and genome amplification. Proteins required for these events include those with homology throughout eukaryotes as well as proteins apparently unique to ciliates. In this study, we identified the ciliate-specific Defective in IES Excision 5 (DIE5) genes of Paramecium tetraurelia (PtDIE5) and Tetrahymena thermophila (TtDIE5) as orthologs that encode nuclear proteins expressed exclusively during development. Abrogation of PtDie5 protein (PtDie5p) function by RNA interference (RNAi)-mediated silencing or TtDie5p by gene disruption resulted in the failure of developing macronuclei to differentiate into new somatic nuclei. Tetrahymena DeltaDIE5 cells arrested late in development and failed to complete genome amplification, whereas RNAi-treated Paramecium cells highly amplified new macronuclear DNA before the failure in differentiation, findings that highlight clear differences in the biology of these distantly related species. Nevertheless, IES excision and chromosome fragmentation failed to occur in either ciliate, which strongly supports that Die5p is a critical player in these processes. In Tetrahymena, loss of zygotic expression during development was sufficient to block nuclear differentiation. This observation, together with the finding that knockdown of Die5p in Paramecium still allows genome amplification, indicates that this protein acts late in macronuclear development. Even though DNA rearrangements in these two ciliates look to be quite distinct, analysis of DIE5 establishes the action of a conserved mechanism within the genome reorganization pathway.
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Human chorionic gonadotropin up-regulates expression of myeloid cell leukemia-1 protein in human granulosa-lutein cells: implication of corpus luteum rescue and ovarian hyperstimulation syndrome.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-05-2010
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The corpus luteum is a dynamic endocrine structure with periodic development and regression during menstrual cycles. Its lifespan can be prolonged by human chorionic gonadotropin (hCG). However, the signal mechanisms of this phenomenon remain unclear.
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Power Doppler presentation of shoulders with biceps disorder.
Arch Phys Med Rehabil
PUBLISHED: 04-13-2010
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To investigate the patterns of power Doppler signals on the long head of the biceps tendon at asymptomatic controls and shoulders with clinically diagnosed biceps disorder.
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Factors predicting clinically significant fatigue in women following treatment for primary breast cancer.
Support Care Cancer
PUBLISHED: 03-29-2010
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Cancer-related fatigue is common, complex, and distressing. It affects 70-100% of patients receiving chemotherapy and a significant number who have completed their treatments. We assessed a number of variables in women newly diagnosed with primary breast cancer (BrCa) to determine whether biological and/or functional measures are likely to be associated with the development of clinically significant fatigue (CSF). Two hundred twenty-three women participated in a study designed to document the impact of the diagnosis and treatment of primary breast cancer on function. Forty-four had complete data on all variables of interest at the time of confirmed diagnosis but prior to treatment (baseline) and ? 9 months post-diagnosis. Objective measures and descriptive variables included history, physical examination, limb volume, hemoglobin, white blood cell count, and glucose. Patient-reported outcomes included a verbal numerical rating of fatigue (0-10, a score of ? 4 was CSF), five subscales of the SF-36, Physical Activity Survey, and Sleep Questionnaire. At baseline, the entire cohort (n = 223) and the subset (n = 44) were not significantly different for demographic, biological, and self-reported data, except for younger age (p = 0.03) and ER+ (p = 0.01). Forty-five percent had body mass index (BMI)?? 25, 52% were post-menopause, and 52% received modified radical mastectomy, 39% lumpectomy, 52% chemotherapy, 68% radiation, and 86% hormonal therapy. Number of patients with CSF increased from 1 at baseline to 11 at ? 9 months of follow-up. CSF at ? 9 months significantly correlated with BMI ? 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05). Fatigue increases significantly following the treatment of BrCa. Predictors of CSF include high BMI and WBC count, increase in limb volume, and low level of physical activity. These are remediable.
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Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer.
Mol. Cancer
PUBLISHED: 03-19-2010
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Many cancerous cells accumulate beta-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of beta-catenin in the nuclei of oral cancer cells.
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Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands.
Ann. Surg. Oncol.
PUBLISHED: 02-17-2010
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Cytoplasmic and nuclear accumulation of beta-catenin in mucoepidermoid carcinoma (MEC) is frequently noted, but the mechanism is unknown.
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The involvement of promoter methylation and DNA methyltransferase-1 in the regulation of EpCAM expression in oral squamous cell carcinoma.
Oral Oncol.
PUBLISHED: 09-17-2009
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Epithelial cell adhesion molecule (EpCAM) is important for cell proliferation and differentiation but mechanisms regulating their expression are unclear. Because EpCAM may play a role in carcinogenesis, we investigated the clinicopathologic significance of its expression in oral squamous cell carcinoma (OSCC) and the involvement of DNA methylation machinery in regulation of EpCAM expression during tumorigenesis. Immunohistochemical staining for EpCAM expression and DNA methyltransferase-1 (DNMT1) was done in 112 OSCC cases. Tumor genomic DNA was extracted and EpCAM promoter methylation was examined by methylation-specific polymerase chain reaction in 72 OSCC specimens. Immunoreactivity and methylation were correlated with clinicopathologic features. EpCAM expression was undetectable in normal epithelium; high expression was observed in 51% (57/112) of OSCC. Heterogeneity and plasticity of EpCAM expression was observed during tumor development. Allele methylation was found in 51% (37/72) of OSCC cases analyzed. EpCAM expression was associated with promoter methylation (p = 0.008). However, EpCAM expression and promoter methylation did not correlate with clinicopathologic OSCC variables. DNMT1 expression was occasionally observed in basal cells of normal epithelium; high expression was observed in 47% (53/112) of OSCC. DNMT1 did not correlate with EpCAM expression or methylation status. High DNMT1 expression correlated with tumor size (p < 0.0001) histologic differentiation (p = 0.012) and clinical stage (p < 0.0001) of OSCC. EpCAM expression increased during development of OSCC. EpCAM promoter methylation is associated with EpCAM expression levels in OSCC, suggesting an epigenetically mediated regulation of EpCAM expression. Increased DNMT1 protein expression may be involved in histogenesis and progression of OSCC.
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Management of crown-root fracture tooth by intra-alveolar transplantation with 180-degree rotation and suture fixation.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
PUBLISHED: 08-19-2009
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Teeth with traumatic crown-root fractures extending subgingivally and involving the entire width of the tooth may have problems in endodontic isolation, periodontal maintenance, and restoration. A number of techniques, such as crown lengthening, and orthodontic or surgical extrusion, have been described for treatment of crown-root fractures. However, all of these techniques have limitations in terms of the extended time required for treatment, cost, and esthetic considerations. Intra-alveolar transplantation is an alternative treatment option in the management of complicated crown-root fractures. We describe a case of intra-alveolar transplantation with 180( degrees ) rotation and suture fixation. At 1-year follow-up, the replanted tooth has normal function and no obvious inflammatory root resorption on radiographic examination.
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Floating retained root lesion mimicking apical periodontitis.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
PUBLISHED: 04-29-2009
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A case of a retained root tip simulating apical periodontitis on radiographic examination is described. The retained root tip, originating from the left lower first molar, floated under the left lower second premolar apical region mimicking apical periodontitis. It appeared as an ill-defined periapical radiolucency containing a smaller radiodense mass on radiograph. The differential diagnosis included focal sclerosing osteomyelitis (condensing osteitis) and ossifying fibroma. Upon exicisional biopsy, a retained root associated with granulation tissue was found. After 1-year follow-up, the patient was asymptomatic and the periradicular lesion was healing. Meanwhile, the associated tooth showed a normal response to stimulation testing.
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Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands.
Ann. Surg. Oncol.
PUBLISHED: 01-01-2009
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There is considerable controversy about whether tumor-associated macrophages (TAMs) promote or inhibit tumor progression. The present study examined the clinicopathologic significance of TAMs and their association with tumor angiogenesis, cell proliferation, and apoptosis in mucoepidermoid carcinoma (MEC). The potential effect of TAMs on cancer cells was also investigated.
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Diacerein: a potential therapeutic drug for periodontal disease.
Med. Hypotheses
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Periodontal diseases are chronic inflammatory diseases characterized by the destruction of the tooth-supporting structures. They are the most prevalent form of bone pathology in humans and act as a modifying factor of the systemic health of patients. Accumulating evidence has provided insight into mechanisms of periodontal inflammation revealing that oral pathogens induce inflammatory cascades, including a variety of cytokines produced by different cell types, which promotes host-mediated tissue destruction. Cytokine networks established in diseased periodontal tissues are extremely complex, and substances regulating immuno-inflammatory reactions and signaling pathways, in addition to traditional periodontal treatment, could potentially be targeted as an approach for prevention and treatment of periodontal diseases. Diacerein, a purified anthraquinone derivative, was derived originally from plants with profound anti-inflammatory and analgesic activities. Its wide range of biological activities have been applied and discussed for several decades; however, studies of diacerein have mainly concentrated on effects on joint-derived tissues/cells, which suggest a beneficial role in osteoarthritis treatment. Diacerein reduces association of the IL-1 receptor to form heterodimer complexes, repressing IL-1 and its related downstream events and impairing active IL-1 release due to the inhibition of the IL-1-converting enzyme (ICE). To date, there are no reports describing the therapeutic effect of diacerein for treatment of periodontitis. Given the involvement of inflammation and occurrence of tissue destruction in periodontal disease, we propose that diacerein might be a promising biological drug for periodontal disease due to its therapeutic advantages. In addition, we hypothesize that the underlying mechanisms might involve the capacity of diacerein to selectively inhibit signal transduction to affect the cytokine profiles and, consequently, produce the outcome of ameliorating disease breakdown.
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Predictors of functional shoulder recovery at 1 and 12 months after breast cancer surgery.
Breast Cancer Res. Treat.
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The objective of this study are (1) to determine if upper extremity function, as represented by shoulder ROM, self-reported symptoms and upper extremity functional limitations in activities of daily living could be predictively related to demographic and cancer characteristics post-surgery for breast cancer. And (2) to examine if variables related to early onset impairment contribute to late onset impairments in women after breast cancer surgery. Subjects were assessed preoperatively and 1, 3, 6, 9, and 12+ months post breast cancer surgery for impairments and symptoms and at 12+ months for shoulder functional limitations using a physical therapy surveillance model. Body weight, shoulder ROM, manual muscle testing, and upper limb volume were recorded. At 12+ months, the Harvard Alumni Health Study Physical Activity Questionnaire, and an Upper Limb Disability Questionnaire were administered. Symptoms and ROM impairments were compared by functional limitations. Characteristics significantly associated with early ROM impairment (but not later impairment) were axillary lymph node dissection, removal of ?15 nodes, mastectomy surgery and stage II breast cancer. Positive nodes, older age, and BMI?25 were significantly associated with reduced shoulder ROM at 12+ months. At 12+ months, only 10 % of the patients experienced ROM impairments while rates of self-reported symptoms in the affected upper extremity at 12+ months were as follows: pain-49%, weakness-47.1%, numbness-55.9%, feeling tired-42.5%. The majority of patients used the affected upper extremity for reaching without limitation, but ?35% reported limitation with household chores, carrying and lifting. Difficulty carrying and lifting could be predicted by BMI?25 and use of the dominant affected upper limb. Different factors are associated with early versus later ROM loss. Symptoms reported by breast cancer survivors are frequently associated with functional limitations in upper extremity tasks and warrant intervention. Physical therapy using a prospective surveillance model of care may reduce severity of ROM loss, symptoms and functional upper extremity limitations 1 year after breast cancer surgery.
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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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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.