Systemic high-dose dexamethasone treatment may modulate the efficacy of intratumoral viral oncolytic immunotherapy in glioblastoma models

BackgroundIntratumoral viral oncolytic immunotherapy is a promising new approach for the treatment of a variety of solid cancers. CAN-2409 is a replication-deficient adenovirus that delivers herpes simplex virus thymidine kinase to cancer cells, resulting in local conversion of ganciclovir or valacyclovir into a toxic metabolite. This leads to highly immunogenic cell death, followed by a local immune response against a variety of cancer neoantigens and, next, a systemic immune response against the injected tumor and uninjected distant metastases. CAN-2409 treatment has shown promising results in clinical studies in glioblastoma (GBM). Patients with GBM are usually given the corticosteroid dexamethasone to manage edema. Previous work has suggested that concurrent dexamethasone therapy may have a negative effect in patients treated with immune checkpoint inhibitors in patients with GBM. However, the effects of dexamethasone on the efficacy of CAN-2409 treatment have not been explored.MethodsIn vitro experiments included cell viability and neurosphere T-cell killing assays. Effects of dexamethasone on CAN-2409 in vivo were examined using a syngeneic murine GBM model; survival was assessed according to Kaplan-Meier; analyses of tumor-infiltrating lymphocytes were performed with mass cytometry (CyTOF - cytometry by time-of-flight). Data were analyzed using a general linear model, with one-way analysis of variance followed by Dunnett’s multiple comparison test, Kruskal-Wallis test, Dunn’s multiple comparison test or statistical significance analysis of microarrays.ResultsIn a mouse model of GBM, we found that high doses of dexamethasone combined with CAN-2409 led to significantly reduced median survival (29.0 days) compared with CAN-2409 treatment alone (39.5 days). CyTOF analyses of tumor-infiltrating immune cells demonstrated potent immune stimulation induced by CAN-2409 treatment. These effects were diminished when high-dose dexamethasone was used. Functional immune cell characterization suggested increased immune cell exhaustion and tumor promoting profiles after dexamethasone treatment.ConclusionOur data suggest that concurrent high-dose dexamethasone treatment may impair the efficacy of oncolytic viral immunotherapy of GBM, supporting the notion that dexamethasone use should be balanced between symptom control and impact on the therapeutic outcome.

Effect of Curing Time on the Bond Strength of Orthodontic Brackets Bonded by Light Cure Resin-Modified Glass Ionomer Cement: An In vitro Evaluation

This study was designed with the aim to evaluate the effect of curing time on the shear-bond strength of orthodontic brackets bonded using light cure Resin-Modified Glass Ionomer Cements (RMGIC). This class of cement when used for luting orthodontic brackets offers certain advantages when compared to the more commonly used resin cements. Intact natural teeth (premolars) extracted for therapeutic purposes as part of orthodontic treatment was sourced for use in this study. The teeth were equally divided into four groups four testing, Group 1 - brackets bonded with RMGIC and cured for 3 seconds, Group 2 - brackets bonded RMGIC and cured for 6 seconds, Group 3 - brackets bonded with RMGIC and cured for 9 seconds and Control group - brackets bonded with composite and cured for 15 seconds. A high intensity LED light source was used to cure the cements. The Shear-Bond strength of the brackets was evaluated using a universal testing machine. One-way ANOVA test and Tukey multiple comparison tests were done to compare the difference of Shear-Bond Strengths among the groups tested. The average Shear Bond Strength among study groups was 7.64±2.86 MPa. The ANOVA and Tukey multiple comparison tests could not identify a statistically significant difference in Shear-Bond Strengths among the groups. Curing time does not appear to have a statistically significant effect on the Shear Bond Strength of orthodontic brackets bonded using Resin-Modified Glass Ionomer Cements..

The application of orthogonal contrasts to determine homogeneous groups

The paper presents a modified approach to analysis of data obtained from experiments carried out according to classical factorial designs. Four examples were discussed in order to present details of proposed method. Modification of the analysis of variance presented here enables more effective use of information on how studied factors affect the means of dependent variable. The specificity of this approach is based on alternative multiple comparison procedure incorporating orthogonal contrasts to determine homogeneous groups.

PENGARUH TEPUNG BUAH NIPAH TERHADAP KARAKTERISTIK BISKUIT TINGGI SERAT

The amount of fibre consumption in Indonesia is lower than recommended by WHO. The use of nypa flour as wheat substitution in biscuit formulation is able to increase fibre content in biscuit. The aims of this research were to determine the effect of Nypa fruticans flour to the physicochemical and sensory properties of high-fiber biscuit. This research used a completely randomized design (CRD) with the concentration of Nypa fruticans flour (0, 10, 20, 30, 40, 50, and 60%) as the treatments. Data was analysed by ANOVA and DnMRT at 95% confidence level. The result showed that Nypa flour had 10% water content , 3,18% crude fiber content and color characteristic L * = 87,57; a * = -3,33; and b * = 20,17. The concentration of Nypa flour significantly affect water and crude fiber content, color characteristic, crispyness and grit, but did not significantly affect hardness, spread ratio, color (sensory), taste, aroma, overall acceptance and multiple comparison. The concentration of 40% nypa flour was the best treatment to produce high-fiber biscuit with 2,78% water content, 1,47% crude fiber content, hardness 1301,3 gF, spread ratio 5,15, color characteristic (L * = 75,51; a * = 0,18; b * = 30,00), color description (brownish yellow), slightly crunchy, rough, taste (rather liked), aroma (rather liked), and overall acceptance (rather liked). Multiple comparison tests showed that the biscuit favored by panelists similar to the reference biscuit.

1391. Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum

Background Leptin is an adipose tissue-derived cytokine that plays a role in energy regulation and immune functions. High leptin levels and obesity have been associated with decreased risk of developing active TB. We aimed to characterize the association between body mass index (BMI) and leptin levels in patients at different stages of tuberculosis (TB). Methods Data from a cross-sectional cardiovascular risk study of 40 to 70 years old individuals enrolled in Lima, Peru, and Cincinnati, US, were analyzed. Four categories based on TB and treatment status were defined: no TB infection (QuantiFERON-TB test negative; n= 31), latent TB infection (LTBI; QuantiFERON-TB test positive; n= 43), active TB on treatment (in the continuation TB treatment phase; n= 30), and post-TB (within one year of TB treatment completion; n=16). BMI and plasma leptin levels were compared among the four groups using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if differences were found in the Kruskal-Wallis test. Multivariate ordered logistic regression models were used to assess factors associated with leptin levels, adjusted for potential confounders. Results The median age was 53 years, and 51% were female. BMI was different between study groups (p< 0.01), with LTBI individuals having the highest BMI compared to other groups; see Figure 1A. Leptin levels were marginally low in the group with active TB on treatment, but no significant differences were found between groups (p=0.44; see Figure 1B). In multivariate analysis, leptin was associated with female sex (OR 23, 95%CI, 9-58), BMI (OR, 1.5, 95%CI, 1.2-1.7), and coronary plaque ≥25% stenosis (OR, 0.29, 95%CI, 0.08-0.99). Body mass index (BMI) and plasma leptin levels in participants with negative QuantiFERON-TB test (QFN-), latent tuberculosis infection (LTBI), active tuberculosis on treatment (ATBT), and post-TB treatment (TB-treated). Significance was determined using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if the Kruskal- Wallis test p-value was <0.05. Conclusion LTBI individuals had a higher BMI compared to persons with active TB on treatment and post-TB. Higher leptin levels were associated with higher BMI, but we found no association between leptin and TB status in our cohort. Disclosures All Authors: No reported disclosures

On the Convergence of the Benjamini–Hochberg Procedure

The Benjamini–Hochberg procedure is one of the most used scientific methods up to date. It is widely used in the field of genetics and other areas where the problem of multiple comparison arises frequently. In this paper we show that under fairly general assumptions for the distribution of the test statistic under the alternative hypothesis, when increasing the number of tests, the power of the Benjamini–Hochberg procedure has an exponential type of asymptotic convergence to a previously shown limit of the power. We give a theoretical lower bound for the probability that for a fixed number of tests the power is within a given interval around its limit together with a software routine that calculates these values. This result is important when planning costly experiments and estimating the achieved power after performing them.