scholarly journals LGG-13. PILOCYTIC ASTROCYTOMAS WITH NOVEL BRAF FUSIONS DEMONSTRATE MAPK PATHWAY ACTIVATION

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i34-i34
Author(s):  
Hannah Chatwin ◽  
Katherine Lind ◽  
John DeSisto ◽  
Bridget Sanford ◽  
Ahmed Gilani ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Genetic Alterations ◽  
Positive Control ◽  
Negative Control ◽  
Gene Set Enrichment Analysis ◽  
Low Grade ◽  
Normal Brain ◽  
Pilocytic Astrocytomas ◽  
Negative Controls ◽  
Control Samples

Abstract Background Pilocytic astrocytomas (PAs) are the most common pediatric low-grade glioma subtype. Oftentimes, PAs demonstrate somatic genetic alterations, the most common being the BRAF-KIAA1549 fusion, which results in constitutive activation of the MAPK pathway. Better understanding of the effects of other RAF fusions is necessary to determine the potential utility of MAPK-targeting therapies. Methods Three patients presented to Children’s Hospital Colorado and were ultimately diagnosed with PAs harboring previously unreported gene fusions identified as FYCO-RAF1, CCTTNNBP2-BRAF, and SLC44A1-BRAF. Utilizing immunohistochemistry, we stained novel samples and controls for ERK and pERK (phosphorylated ERK) to assess the activation of the MAPK pathway. PAs with known BRAF-KIAA1549 fusions (4 samples) and normal brain tissue (5 samples) were used as positive and negative controls, respectively. We additionally performed RNA sequencing to better understand expression changes associated with these fusions, utilizing Metascape and GSEA (Gene Set Enrichment Analysis) for analysis. Results Immunohistochemistry of negative control samples demonstrated less p-ERK than ERK (ratios of 0.6–0.9, mean 0.8). All samples with novel fusions demonstrated statistically significantly higher p-ERK expression compared to negative controls (ratios of 1.3–1.7, mean 1.4). These experimental samples also all fell within the p-ERK to ERK expression range of the positive control samples, which demonstrated the widest range of expression (ratios of 1.1–4.5, mean 2.2). Our molecular analysis further confirmed these results, with GSEA demonstrating positively upregulated MAPK and ERK pathways in 2 positive controls and 1 novel fusion sample. Metascape analysis emphasized overall similar gene expression between these samples, demonstrating many shared genes and functional pathways. Conclusions We identified 3 previously unreported RAF fusions in PA that demonstrate activation of the MAPK pathway, although not as extensively as seen in some positive control samples with BRAF-KIAA1549 fusions. MEK inhibition may be a useful therapeutic strategy in these tumors if targeted therapy is indicated.

scholarly journals LGG-50. INTEGRATED MOLECULAR AND CLINICAL ANALYSIS OF 1,000 PEDIATRIC LOW-GRADE GLIOMAS UNCOVERS NOVEL SUBGROUPS FOR CLINICAL RISK STRATIFICATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii375-iii376
Author(s):  
Uri Tabori ◽  
Scott Ryall ◽  
Michal Zapotocky ◽  
Julie Bennett ◽  
Liana Nobre ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Clinical Presentation ◽  
Mapk Pathway ◽  
Clinical Analysis ◽  
Genetic Alterations ◽  
Low Grade ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Younger Age ◽  
Risk Categories

Abstract Pediatric low-grade gliomas (pLGG) are primarily driven by genetic alterations in the RAS/MAPK pathway, most commonly involving BRAF of NF1. Despite their molecular convergence, pLGG often show unexplained variability in their clinical outcome. To address this, we molecularly characterized a cohort of >1,000 clinically annotated pLGG. 84% of cases harbored a detectable driver mutation. The remaining 16% of patients nonetheless showed RAS/MAPK pathway up-regulation at the RNA level. The clinical presentation and outcome of pLGG appeared highly variable and linked to the alteration type: re-arrangement or SNV. Re-arrangement-driven tumors were diagnosed at a younger age (6.6 versus 10.9 years, p<0.0001), enriched for WHO grade I histology (88% versus 66%, p<0.0001), infrequently progressed (27% versus 46%, p<0.0001), and rarely resulted in death (3 versus 13%, p<0.0001) as compared to SNV-driven tumors. These included the rarest molecular drivers of pLGG, for which we now have the clinicopathologic features of including MYB, MYBL1, FGFR2 fusions, FGFR1-TACC1, FGFR1 SNVs, IDH1 p.R132H, and H3.3 p.K27M. Utilizing this information, we suggest novel risk categories of pLGG that effectively predicted patient outcome. Low-risk tumors progressed infrequently and rarely succumbed to their disease (10-year PFS of 71% and OS of 98%). Intermediate-risk pLGG had a 10-year PFS and OS of 35% and 90%, respectively. High risk pLGG almost invariably progressed (10-year PFS of 0%) and these patients often succumbed to their disease (10-year OS of 41%). These data highlight the biological and clinical differences between pLGG subtypes and offers molecular based risk stratification to these cancers.

scholarly journals Evaluation of ionic degradation and slot corrosion of metallic brackets by the action of different dentifrices

2013 ◽  
Vol 18 (1) ◽  
pp. 86-93
Author(s):  
Gustavo Antônio Martins Brandão ◽  
Rafael Menezes Simas ◽  
Leandro Moreira de Almeida ◽  
Juliana Melo da Silva ◽  
Marcelo de Castro Meneghim ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Artificial Saliva ◽  
Positive Control ◽  
Negative Control ◽  
Sem Analysis ◽  
Wilcoxon Test ◽  
Surface Polishing ◽  
Aluminium Ion ◽  
Negative Controls

OBJECTIVE: To evaluate the in vitro ionic degradation and slot base corrosion of metallic brackets subjected to brushing with dentifrices, through analysis of chemical composition by Energy Dispersive Spectroscopy (EDS) and qualitative analysis by Scanning Electron Microscopy (SEM). METHODS: Thirty eight brackets were selected and randomly divided into four experimental groups (n = 7). Two groups (n = 5) worked as positive and negative controls. Simulated orthodontic braces were assembled using 0.019 x 0.025-in stainless steel wires and elastomeric rings. The groups were divided according to surface treatment: G1 (Máxima Proteção Anticáries®); G2 (Total 12®); G3 (Sensitive®); G4 (Branqueador®); Positive control (artificial saliva) and Negative control (no treatment). Twenty eight brushing cycles were performed and evaluations were made before (T0) and after (T1) experiment. RESULTS: The Wilcoxon test showed no difference in ionic concentrations of titanium (Ti), chromium (Cr), iron (Fe) and nickel (Ni) between groups. G2 presented significant reduction (p < 0.05) in the concentration of aluminium ion (Al). Groups G3 and G4 presented significant increase (p < 0.05) in the concentration of aluminium ion. The SEM analysis showed increased characteristics indicative of corrosion on groups G2, G3 and G4. CONCLUSION: The EDS analysis revealed that control groups and G1 did not suffer alterations on the chemical composition. G2 presented degradation in the amount of Al ion. G3 and G4 suffered increase in the concentration of Al. The immersion in artificial saliva and the dentifrice Máxima Proteção Anticáries® did not alter the surface polishing. The dentifrices Total 12®, Sensitive® and Branqueador® altered the surface polishing.

scholarly journals Effect of Sodium Carboxymethylcellulose and Sorbitol on Anti-Peptic Ulcer Activity of Anredera cordifolia Leaves Extract

2019 ◽  
Vol 4 (1) ◽  
pp. 16
Author(s):  
Maria Ulfah ◽  
Revika Rachmaniar ◽  
Egi MR. Sudrajat ◽  
Rida W. Fadla ◽  
Hary S. Pinuji
Keyword(s):  
Body Weight ◽  
Peptic Ulcer ◽  
Normal Control ◽  
Wistar Rat ◽  
Positive Control ◽  
Negative Control ◽  
Sodium Carboxymethylcellulose ◽  
Freeze Dried ◽  
Male Wistar Rats ◽  
Negative Controls

Anredera cordifolia or binahong is one of the Indonesian medicinal plants that is used to treat peptic ulcer. The purpose of this study was to evaluate the effect of the addition of sodium carboxymethylcellulose (CMC) and sorbitol on anti-peptic ulcer activity of A. cordifolia leaves extracts in male Wistar rats. The plants were extracted using decoction method and freeze dried. Three liquid formulas were used i.e., i) a combination of sodium CMC and sorbitol; ii) only sorbitol; iii) extract only. The rats were divided into 6 groups, i.e., positive control (sucralfate 35 mg/kg body weight); negative control (80% ethanol); normal control; and 3 formulas. After the administration of the liquid formula, all groups, except normal control, were given 80% ethanol (l5 ml/kg body weight) to induce peptic ulcer. Antipeptic ulcer activity was evaluated using direct observation on rats gastric mucosa, and histopathology assessment. The result showed that the strongest anti-peptic ulcer  was shown by sorbitol only (96.95% inhibition),  followed by the combination of sodium CMC and sorbitol (92.68% inhibition). The formula which only contained extract showed only  31.70% inhibition.  Statistical analysis showed significant differences between formula 1 and 2 with negative controls. In conclusion, A. cordifolia leaves extract with the addition of sorbitol showed the strongest anti-peptic ulcer activity. Keyword: Anredera cordifolia, peptic ulcer, suspense, Wistar rat.

Abstract 2819: Cross-correlation Analysis of Myocardial Velocity is Superior to Conventional Time-to-Peak Parameters for Quantifying Left Ventricular Dyssynchrony

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Brandon K Fornwalt ◽  
Takeshi Arita ◽  
Mohit Bhasin ◽  
George Voulgaris ◽  
John D Merlino ◽  
...  
Keyword(s):  
Cross Correlation ◽  
Positive Control ◽  
Negative Control ◽  
Left Ventricular ◽  
Left Ventricular Dyssynchrony ◽  
Control Group ◽  
Time To Peak ◽  
Data Points ◽  
Negative Controls ◽  
Threshold Line

Background- A recent study showed that the most commonly used Tissue Doppler imaging (TDI) parameters to diagnose left ventricular dyssynchrony agree only 50% of the time. Most of these parameters require calculation of the ``time-to-peak” myocardial velocity. This ``time-to-peak” based analysis utilizes only one of >100 data points collected per heart cycle. Methods- We developed and tested a new dyssynchrony parameter, cross-correlation delay (XCD), that utilizes all velocity data points from 3 consecutive beats (~420 points). We hypothesized that XCD would be superior to existing methods at diagnosing dyssynchrony. We tested XCD on 11 members of a positive control group (echocardiographic responders to cardiac resynchronization therapy) and 12 members of a negative control group (normal echocardiogram and 12-lead ECG). We compared XCD to septal-to-lateral delay in time-to-peak (SLD), maximum difference in the basal 2- or 4-chamber times-to-peak (MaxDiff) and standard deviation of the 12 basal and mid-wall times-to-peak (Ts-SD). Results- An XCD threshold of 31ms discriminated between positive and negative controls with 100% sensitivity and specificity (Figure 1 ). SLD, MaxDiff and Ts-SD showed sensitivities of 36, 55 and 100% and specificities of 50, 42 and 50%, respectively. ROC analysis showed XCD and Ts-SD were superior to SLD and MaxDiff in discriminating between positive and negative controls (p<0.01). XCD was the only parameter which decreased after resynchronization in the positive controls (from 160±88ms to 69±61ms, p=0.003). Conclusion- XCD is superior to existing parameters at discriminating patients with LV dyssynchrony from those with normal function. Figure 1. XCD shows the greatest discrimination between positive and negative controls. Dyssynchrony values for each positive control are shown as x’s and values for each negative control are shown as circels. Different dyssynchrony parameters are shown in each subplot (A-D). Threshold values to diagnose dyssynchrony are plotted as horizontal lines in each figure. Note that x’s above the threshold line represent false positives while circles below the threshold line represent false negatives.

scholarly journals Essential oils as tick repellents on clothing

2019 ◽  
Vol 79 (2) ◽  
pp. 209-219 ◽  
Author(s):  
Oliver Soutar ◽  
Freya Cohen ◽  
Richard Wall
Keyword(s):  
Essential Oils ◽  
No Reduction ◽  
Positive Control ◽  
Negative Control ◽  
Tick Abundance ◽  
Spearmint Oil ◽  
Oregano Oil ◽  
Negative Controls ◽  
Tick Repellents

Abstract Essential oils show promise as natural alternatives to synthetic tick repellents, but few studies have investigated their repellent efficacy in vivo or under field conditions. Here, blanket-drags and standardised walks were employed to evaluate tick acquisition by 1 m2 cotton blankets or cotton trousers, respectively, in woodland edge habitats of known high tick abundance. Blankets and trousers had been treated with one of 5% oregano, rosemary, spearmint or thyme oils, 20% DEET (N,N-diethyl-3-methylbenzamide) (positive control) or ethanol excipient-only (negative control). The number of ticks present on the blankets or trousers differed significantly between treatments: spearmint oil treatments resulted in significantly fewer ticks than the negative controls for both blankets and trousers and significantly fewer ticks were present on the oregano oil treated blankets. For ticks that did attach to the trousers, the rate of drop off within 3 min was significantly higher for trousers treated with spearmint oil or thyme oil than ethanol, oregano oil and rosemary oil. No reduction in repellence was detected over a 24 h period between treatment and testing. The results suggest that 5% oregano and spearmint oils exhibit potential as natural clothing repellents, with an effective equivalence to 20% DEET.

scholarly journals Antimicrobial Activity of an Amnion-Chorion Membrane to Oral Microbes

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Haroon Ashraf ◽  
Kerri Font ◽  
Charles Powell ◽  
Michael Schurr
Keyword(s):  
Bacterial Species ◽  
Healing Process ◽  
Antimicrobial Properties ◽  
Positive Control ◽  
Negative Control ◽  
Collagen Membrane ◽  
Wound Healing Process ◽  
Bacterial Strains ◽  
Oral Microbes ◽  
Negative Controls

Objective. The aim of this study was to evaluate wound biomodification by assessing antimicrobial properties present within a human-derived composite amnion-chorion membrane (ACM). Methods. Membranes analyzed were the human-derived ACM BioXclude™ and the porcine-derived collagen membrane Bio-Gide®. Paper discs with and without tetracycline served as positive and negative controls, respectively. The same number of colony-forming units per milliliter for each bacterial species (Aggregatibacter actinomycetemcomitans, Streptococcus mutans, and Streptococcus oralis) was inoculated on each of the discs. Discs from each group were removed at 12 and 24 hours and sonicated to remove the bacteria off the membranes. A serial dilution was performed to quantify bacterial growth. Results. The ACM inhibited growth at all time points, with all bacterial strains, identical to the negative control tetracycline discs. The collagen membrane and positive controls did not inhibit growth of any of the bacterial species throughout the 24-hour study period. P<0.05 for microbial growth on ACM or negative control vs. either collagen membrane or positive control. Conclusion. ACM was proven to be as bactericidal as paper discs inoculated with tetracycline at its minimum bactericidal concentration. The ACM bactericidal property may be beneficial in the early wound healing process.

scholarly journals KULIT BUAH JERUK LIMAU (Citrus amblycarpa (Hassk.) Osche) SEBAGAI ANALGESIK

Jurnal Kimia ◽  
2020 ◽  
pp. 24
Author(s):  
R. A. I. K. Maharani ◽  
N. K. Cahyaningsih ◽  
M. D. Abimanyu ◽  
K. W. Astuti
Keyword(s):  
Body Weight ◽  
Analgesic Activity ◽  
Treatment Options ◽  
Ethanol Extract ◽  
Positive Control ◽  
Negative Control ◽  
Fruit Peel ◽  
Hot Plate ◽  
Inflammatory Drugs ◽  
Negative Controls

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the treatment options for relieving pain. However, long-term use can trigger gastrointestinal bleeding. Therefore, alternative analgesics which have the same therapeutic effect with lower side effects are needed. Limau (Citrus amblycarpa) is an empirical drug for tingling and cramping. The aim of the study is to determine the analgesic activity of ethanol extract of C. amblycarpa fruit peel. The method used in testing analgesic activity is the Hot Plate method. The study was conducted by dividing 30 mice into 6 groups. The group given CMC-Na 1% was used as a negative control, the group given suspension of sodium diclofenac dose of 6.5 mg/kg of body weight was used as a positive control, and the group given suspension of ethanol extract of C. amblycarpa fruit peel with dose variations 100, 300 and 600 mg/kg of body weight. The test animals were placed on top of the Hot Plate with a temperature of 70°C at 30 minutes after giving suspension test and the response time of mice to heat was observed every 30 minutes for 3 hours with cut off time 15 second. Based on the test results, it can be concluded that the administration of ethanol extract of C. amblycarpa fruit peel with 100, 300 and 600 mg/kg of body weight gave analgesic activity on mice compared to the negative controls (CMC-Na 1%).   Keywords: C. amblycarpa, Fruit Peel, Analgesics, Hot Plate 

scholarly journals Indonesian Strain of Lactobacillus reuteri Probiotic Reduces the Initial Biofilm Colonization

2020 ◽  
Vol 14 (1) ◽  
pp. 544-553
Author(s):  
Armelia Sari Widyarman ◽  
Triska Ramajayanti ◽  
Citra Fragrantia Theodorea
Keyword(s):  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Lactobacillus Reuteri ◽  
Positive Control ◽  
Negative Control ◽  
Microbial Biofilms ◽  
Incubation Periods ◽  
Negative Controls ◽  
Initial Biofilm

Background: The benefits of probiotics for human health have long been proven. Probiotic Lactobacillus reuteri, can produce a beneficial broad-spectrum antibacterial compound called reuterin by metabolizing glycerol. Objective: The aim of the study was to investigate the effect of the Indonesian strain of L. reuteri LC382415 on mono- and dual-species Streptococcus mutans and Streptococcus sanguinis biofilms in vitro. Methods: Streptococcus mutans and S. sanguinis were cultured in BHI broth. Lactobacillus reuteri LC382415 was inoculated on MRS agar. The different concentrations effect of L. reuteri (1×104, 1×106, and 1×108 CFU/mL) with and without glycerol supplementation on microbial biofilms were examined using a biofilm assay after incubation for 1,3,6, and 24-h. The biofilm mass optical density was measured with a microplate spectrophotometer at 490 nm. Chlorhexidine gluconate (0.2%) was used as a positive control, and wells without treatment were used as negative controls. Results: A significant reduction in mono- and dual-species S. mutans and S. sanguinis biofilm formation was observed after treatment with all concentrations of L.reuteri and after all incubation periods (p<0.05) with or without glycerol supplementation. The concentration of 1×104 CFU/mL after 3-h incubation was the most effective in inhibiting biofilm formation, with 87.8% S. mutans, 95.9% S. sanguinis, and 80.4% dual-species biofilm reduction compared to the negative control (p<0.05). Conclusion: The Indonesian strain of L. reuteri effectively reduces mono- and dual-species S.mutans and S. sanguinis biofilms. This suggests that it may be useful in preventing biofilm formation in oral cavities. Future studies on the mechanism of action of this active component are warranted.

scholarly journals Thermographic examination of prick test reactions with local anesthetic

2019 ◽  
Vol 140 (1) ◽  
pp. 225-231
Author(s):  
Evgeni Stanev ◽  
Maria Dencheva ◽  
Maya Lyapina ◽  
Payam Forghani
Keyword(s):  
Allergic Inflammation ◽  
Positive Control ◽  
Negative Control ◽  
Diagnostic Process ◽  
Thermal Camera ◽  
Men And Women ◽  
Temperature Changes ◽  
Prick Test ◽  
Test Reactions ◽  
Negative Controls

Abstract In allergology, skin diagnostic tests are divided into epicutaneous, cutaneous and intracutaneous. The prick test is one of the cutaneous tests used most often for the diagnosis of hypersensitivity to local anesthetics. In the case of hypersensitivity to the examined anesthetic and reaction to the histamine-containing solution (positive control), inflammation appears with an increase in the local temperature. This warming can be detected objectively with a thermal camera and can be used in the diagnostic process. This study was used to examine the capabilities of the infrared thermography application, in the prick test of both men and women, by comparing temperature changes and the intensity of allergic inflammation in the positive and negative controls in addition with a negative reaction to an allergen. A group of 115 patients—55 male (52%) and 60 female (48%), are included. All are examined for hypersensitivity to Mepivastesin, together with the positive and negative control. Skin temperature changes of the skin were examined with FLIR A320 thermal camera and the FLIR Reporter Professional software 2013—application used to process the thermal camera images and data. The statistical analysis shows a marked temperature difference between men and women. Similarities in temperature values are detected between the negative reactions to dental anesthetic and the negative control. However, the latter substantially differs from the data obtained with the positive control. Results of the research indicate the possible applications of the thermography diagnostics in evaluation of the prick test results.

Novel RAF Fusions in Pediatric Low-Grade Gliomas Demonstrate MAPK Pathway Activation

2021 ◽  
Author(s):  
Katherine T Lind ◽  
Hannah V Chatwin ◽  
John DeSisto ◽  
Philip Coleman ◽  
Bridget Sanford ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Immunofluorescent Staining ◽  
Low Grade ◽  
Normal Brain ◽  
Mapk Activation ◽  
Low Grade Gliomas ◽  
Pathway Activation ◽  
Mitogen Activated Protein

Abstract Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) are the most common childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, and SLC44A1-BRAF. We hypothesized that these tumors would show molecular similarity to the canonical KIAA1549-BRAF fusion that is the most widely seen alteration in pilocytic astrocytoma (PA), the most common pediatric LGG variant, and that this similarity would include mitogen-activated protein kinase (MAPK) pathway activation. To test our hypothesis, we utilized immunofluorescent imaging and RNA-sequencing in normal brain, KIAA1549-BRAF-harboring tumors, and our 3 tumors with novel fusions. We performed immunofluorescent staining of ERK and phosphorylated ERK (p-ERK), identifying increased p-ERK expression in KIAA1549-BRAF fused PA and the novel fusion samples, indicative of MAPK pathway activation. Geneset enrichment analysis further confirmed upregulated downstream MAPK activation. These results suggest that MAPK activation is the oncogenic mechanism in noncanonical RAF fusion-driven LGG. Similarity in the oncogenic mechanism suggests that LGGs with noncanonical RAF fusions are likely to respond to MEK inhibitors.

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