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.

Characteristics of Intestinal Flora in Pregnant Women with Mild Thalassemia Revealed by Metagenomics

Background: At present, there is no report that the intestinal flora of pregnant women with mild thalassemia is different from that of healthy pregnant women. Objectives: This study compared the composition and changes of the intestinal flora of pregnant women with mild thalassemia to those of healthy pregnant women using metagenomic sequencing technology and evaluated the potential microecological risk for pregnant women and the fetus. Methods: The present study was carried out on 14 mild thalassemia pregnant women with similar backgrounds in the Affiliated Hospital of Putian University, Fujian, China. In the same period, 6 healthy pregnant women were selected as the control group. The genomic deoxyribonucleic acid was extracted from the sable stool samples of pregnant women. Illumina HiSeq sequencing technology was adopted after library preparation. Prodigal software (ver 2.6.3, Salmon software (ver 1.6.0, and Kraken software (ver 2) were used to analyze the sequence data. Moreover, analysis of variance and Duncan’s multiple-comparison test or Wilcoxon rank-sum test were used as statistical methods. Results: The characteristics of the intestinal flora of pregnant women with mild thalassemia differed significantly from those of healthy pregnant women, showing an increase in some conditionally pathogenic bacteria (e.g., Prevotella stercorea rose and Escherichia coli) and a decrease in some probiotic bacteria, which might affect pregnant women and cause physiological function damage to their offspring by changing metabolic pathways; however, further validation is needed. Conclusions: The diversity and composition of intestinal flora in pregnant women with mild thalassemia vary significantly from those in healthy pregnant women, especially at the genus and species levels, representing more profound alterations in intestinal microecology.

A hydrogeochemical approach to evaluate groundwater quality in the vicinity of three tributaries of the Beas River, North-West India

The present study focused on the seasonal investigation of hydro-geochemical characteristics of groundwater samples collected from the vicinity of three tributaries of the Beas River, Punjab, India. Total 45 samples were analyzed during the pre- and post-monsoon season for physico-chemical parameters and heavy metals along with health risk assessment. Results revealed that the majority of samples were below the permissible limits set by the BIS and WHO. The relative abundance of major cations was Ca2+ > Mg2+ > Na+ > K+ and Ca2+ > Na+ > Mg2+ > K+, while that of the major anions was HCO3− > SO42− > Cl− > CO32− in the pre- and post-monsoon season, respectively. Groundwater was alkaline and hard in nature at most of the sites. Bicarbonate content exceeded the desirable limit having an average concentration of 337.26 mg/L and 391.48 mg/L, respectively, during the pre- and post-monsoon season. Tukey’s multiple comparison test was applied for finding significant differences among samples at p < 0.05. The dominant hydrochemical face of water was Ca–Mg–HCO3 type. US salinity (USSL) diagram indicated that during the pre-monsoon, 48.9% samples were C2S1 type and remaining 51.1% were C3S1 type while during the post-monsoon all samples were C3S1 type. It indicates that groundwater of the study area is at risk of salinity hazards in future and is not to be ignored. Such monitoring studies are recommended to design future safety plans to combat soil and human health risks.

Nutritional composition, nitrate and nitrite levels of Kikuyo grass and its influence on milk production.

Objetive. Establish variations of nutritional composition and the contents of nitrates and nitrites in the Kikuyo grass (Cenchrus clandestinus (Hochst. Ex Chiov.) Morrone) from four veredas in the municipality of San Miguel de Sema: Peña Blanca, Sirigay, Sabaneca, and Quintoque, during dry and rainy seasons. were dairy production is the most significant economic activity. Material and methods. Nutritional characterization parameters, were associated a two-way ANOVA, using Tukey's as a multiple comparison test. Results. The results revealed in dry matter a high average content of total protein (TP) (23.48% +/- 3.71), neutral detergent fiber (60.86% +/- 3.03), with important DM degradability values at different time points (62.97% +/- 3.74 after 48 Hours). The report indicated decreased values of lignin (4.25% +/- 0.5), non-structural carbohydrates (11.44% +/- 2.43) and of the ratio of non-structural carbohydrates: rumen degradable protein (NSC:RDP) of 0.84 +/- 0.16. The levels of nitrates reached an average of 2977 ppm +/- 2061, which differed significantly according to the seasons and veredas, for the dry season in the different veredas the level of nitrated remained at 4728 ppm, a value 3.9 higher in comparison to the rainy season. The levels of nitrites showed average contents of 2.97 pm of DM, contents highly decreased to be potentially toxic. Conclusions. These results allowed us to establish a difference in the protein:energy relation as the limiting factor for milk production. Nitrate levels indicated as potentially toxic.

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&lt; 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 &lt;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

Synthesis of starch-carrageenan bio-thermoplastic composites on the type and concentration of thermoplastic forming materials as packaging materials

Plastic waste is one of the primary environmental pollutants; in addition to being very large in number, it is also complicated to be degraded by microbes. One of the efforts to overcome plastic pollution is to develop biodegradable thermoplastic (bio-thermoplastic), namely plastic that is easy to form and melts at high temperatures and is easily degraded. This study aims to determine the effect of the type and concentration of thermoplastic forming materials (glycerol and castor oil) on bioplastic composites made from cassava starch with carrageenan. Another goal is to get the best characteristics of the treatment. This study used a randomized block design with 12 treatments derived from 2 types (glycerol and castor oil) and six concentrations (1, 2, 3, 4, 5, 6%) of thermoplastic forming materials. The treatments were grouped into two based on the time of the research. The data obtained were analyzed for diversity, and if it had a significant effect, it was continued with Duncan’s multiple comparison test. The observed variables included mechanical properties, swelling, WVTR, and biodegradation. The results showed that the type and concentration of the thermostatic forming material had a significant effect on tensile strength, elongation, elasticity, WVTR and had no effect on swelling and biodegradation. The bio-thermoplastic composite with the best characteristics was made from starch and carrageenan in a ratio of 25:75 using 1% glycerol with a tensile strength of 33.98 MPa and 1% castor oil with a tensile strength of 35.71 MPa.

Red blood cells and their releasates compromise bone marrow-derived human mesenchymal stem/stromal cell survival in vitro

Purpose The use of bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMC) in the treatment of inflammatory orthopedic conditions has become a common practice. The therapeutic effect of BMA/BMC is thought to revolve primarily around the mesenchymal stem/stromal cell (MSC) population residing within the nucleated cell fraction. MSCs have the unique ability to respond to site of injury via the secretion of immunomodulating factors, resolving inflammation in diseased joints. Recently, the importance of hematocrit (HCT) in BMC has been debated, as the potential impact on MSC function is unknown. In the present study, we investigate MSC health over a short time-course following exposure to a range of HCT and red blood cell releasate (RBCrel) conditions. Methods Bone marrow-derived human MSCs in early passage were grown under conditions of 0%, 2.5%, 5%, 10%, 20% and 40% HCT and RBCrel conditions for 3 days. At each day, the percentage of viable, apoptotic and necrotic MSCs was determined via flow cytometry. Relative viable MSC counts in each condition was determined to account for dynamic changes in overall MSC densities over the time-course. Statistical analysis was performed using a one-way ANOVA comparing test conditions to the control followed by a Dunnett’s multiple comparison test. Results Significant reductions in viable MSCs concurrent with an increase in necrotic MSCs in high HCT and RBCrel conditions was observed within 24 h. At each successive timepoint, the percent and relative number of viable MSCs were reduced, becoming significant in multiple HCT and RBCrel conditions by Day 3. Necrosis appears to be the initial mode of MSC death following exposure to HCT and RBCrel, followed by apoptosis in surviving MSC fractions. Conclusion Various levels of HCT and RBCrel severely compromise MSC health within 3 days and HCT should be controlled in the preparation of BMC products. Further, HCT of BMCs should be routinely recorded and tracked with patient outcomes along with routine metrics (e.g. nucleated cell counts, fibroblast-colony forming units). Differences in HCT may account for the inconsistencies in the efficacy of BMC reported when treating orthopedic conditions.

PROTECTIVE EFFECT OF CURCUMIN RIMPANG CURCUMA LONGA LINN. EXTRACT ON CHLORPYRIFOS POISONING IN WISTAR RATS

This study used an experimental method in the laboratory with a randomized design with five treatments and six repetitions. The parameters examined were cholinesterase (ChE), Aspartate Aminotransferase (AST), and serum Alanine Aminotransferase (ALT) of blood in the first and second treatment stages. Data were analyzed using factorial ANOVA test and LSD multiple comparison test with 95% confidence level with R software version 3.6.2. Wistar rats were given chlorpyrifos (6.75, 13.5, 27, 54) mg/kg BW/day orally once a day for 28 consecutive days, then further intervention with curcumin (27, 54, 108 and 216) mg/kg BW/day once a day for 14 consecutive days. A significant increase in ChE activity and a significant decrease in AST and ALT activity. This study shows that curcumin from Curcuma longa Linn rhizome extract provides a protective effect against chlorpyrifos poisoning in Wistar rats.

Association of Cancer Worry and Physical Activity Behaviors in Adults without Cancer

Background: Cancer worry has been conceptualized as a potential motivator to engage in cancer preventative behaviors like cancer screening, genetic testing, or smoking cessation. It is currently unknown if these findings extend to the domain of physical activity, as physical activity has been associated with decreased cancer risk. Objective: To examine if the association between cancer worry and other health behaviors will extend to physical activity in a sample of adults not diagnosed with cancer. Methods: Data are drawn from the NCI's 2017 Health Information National Trends Survey (HINTS) Iteration 5 Cycle 1 (N = 2,706) dataset, a nationally representative survey of adults in the United States. A KruskalWallis-H test was conducted to determine whether physical activity duration (i.e., daily minutes) differed between cancer worry levels with a post hoc Dunn's multiple comparison test to compare the differences between mean ranks. Results: A Kruskal-Wallis-H test showed statistically significant differences in PA duration (i.e., daily minutes) between groups that differed in their level of cancer worry. PA in minutes on a typical day was significantly lower in those who reported not at all, moderate, and extreme worry about developing cancer compared to those who reported slightly and somewhat worried. Conclusion: Contrary to our expectations, our results suggest that higher cancer worry levels are paradoxically associated with less PA. This study's results are significant in that they add to the breadth of literature linking cancer worry to health behaviors and may be used to inform future health promotion interventions.

SECONDARY SCHOOL STUDENTS’ ABILITY TO WORK WITH THE TASKS DESIGNED FOR BIOLOGY OLYMPIAD

For the possibility of using competitive tasks from the Biology Olympiad (BiO), either directly or after certain adaptations for everyday teaching tasks in the teaching process, it was aimed to determine if students could work meaningfully with them. The success of 2nd-year secondary school students (n = 113) in solutions of tasks (n = 5) designated for BiO was compared with the solutions by the regional round BiO´s participants. One-way analysis of variance and Tukey´s multiple comparison test were used for the statistical evaluation of the data. The research shows that secondary school students achieved an average success rate of 47.58 ± 12.51 % and BiO participants 62.69 ± 9.86 %. Within the results of all selected tasks, at least someone of the class of the secondary students achieved similar results in each of the tasks as BiO participants. That indicates that secondary school students were able to work meaningfully with BiO tasks which confirmed students' eligibility for work with these tasks. Keywords: biology education, Biology Olympiad, difficulty of tasks, learning tasks, science education