Elucidating the impact of Western diet on bone marrow cytokine signatures: understanding poor outcomes in susceptibility to infection and progression of cancer

Among other disease outcomes, obesity is associated with 1) reduction in long-lasting immune protection and 2) acquisition of cancer. Given our interest in hematopoietic stem and progenitor cell (HSPC) dynamics, we questioned if similar mechanisms in the bone marrow microenvironment contribute to obesity-induced HSPC alterations responsible for 1) decreased immune protection and 2) transformation of HSPCs in the pathogenesis of hematologic malignancies. The negative effects of obesity on immune protection are most notably established in influenza models. Influenza infection susceptibility is increased and influenza vaccine-induced immunity wains in obese individuals. Ongoing studies aim to define mechanisms for waning immunity at sites of infection. Little is understood, however, regarding how obesity affects HSPC dynamics in the bone marrow microenvironment upon immunization. We hypothesized that obesity alters the types and quantities of immune cells produced by HSPCs upon immunization. We further hypothesized that this is due to altered availability of cytokines present in the bone marrow. Similarly, we hypothesized that unique cytokine signatures in the bone marrow of obese individuals serve as a mechanism for cancer initiation and progression in those with genetic susceptibility to MDS. To test our hypotheses, we subjected applicable mouse models to low-fat or high-fat diets. In our immunization studies, results indicate that high-fat diet leads to myeloid skewing in flu-immunized mice and that cytokine trends in the bone marrow provide insight into how this occurs. In our cancer studies, MDS-susceptible mice fed a high-fat diet displayed distinct cytokine signatures when compared to those fed a low-fat diet, suggesting that this may be a mechanism by which obesity contributes to hematologic malignancy. Further understanding of the contribution of obesity-induced bone marrow cytokine signatures to poor health outcomes may inform the design of future vaccine formulations or MDS therapeutics for obese patients

Comparative Impact Of Network Adequacy Standard Strategies On Medicaid Recipient Cvd Outcomes: A Computer Simulation Modeling Study

Context: Medicaid managed care network adequacy standards vary widely across states and are not typically informed by scientific evidence. The comparative efficacy of these standards for protecting the health of the Medicaid population has not yet been comprehensively researched.Objective: The aims of this study are to construct simulation modeling methods to approach this policy problem and to determine which numeric values for network adequacy standards are most effective for producing favorable health outcomes for Medicaid recipients who develop CVD. Design and Setting: A continuous-time Markov model was used to simulate the natural history of cardiovascular disease, using a cohort that is representative of the Medicaid population over 40, under different provider appointment wait times and CVD emergency travel time delays. Input and Output Measures: Medicaid claims data from Tennessee in 2019, Social Security life expectancy data, the Centers for Disease Control and Prevention\u27s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database, and values pulled from existing literature were used to inform input parameters. Survival time, age at death, number of lifetime hospital visits, number of lifetime provider visits, time spent in recovery, time spent waiting for an appointment, lifetime healthcare costs, and lifetime healthcare costs attributable to hospitalization were collected as simulation outputs. Results: It was found that the strategy with a 45-day appointment wait time and 0-minute emergency travel time delay yielded the most favorable health outcomes for individuals with CVD: mean age at death of 83.79 (83.10, 84.47) and mean survival time of 32.08 (31.09, 33.07). When the strategies hypothesized to be the “best” (7-day wait times and no travel delay) and “worst” (90-day wait times and 90-min travel delay for emergencies) were run in comparison to one another, statistically significant differences were found for time spent in recovery, time spent waiting for an appointment, provider visit quantity, and healthcare system cost burden. Statistically significant differences were not found for life expectancy, hospital visit quantity, and costs attributable to hospitalization. Conclusion: There is not enough evidence of robustness in these results to recommend that policy decisions should be made using them; further complexities and calibration should be incorporated into the model before doing so

Enhancing the Verification-Driven Learning Model for Data Structures with Visualization

The thesis aims at teaching various data structures algorithms using the Visualization Learning tool. The main objective of the work is to provide a learning opportunity for novice computer science students to gain a broader exposure towards data structure programming. The visualization learning tool is based on the Verification-Driven Learning model developed for software engineering. The tool serves as a platform for demonstrating visualizations of various data structures algorithms. All the visualizations are designed to emphasize the important operational features of various data structures. The learning tool encourages students into learning data structures by designing Learning Cases. The Learning Cases have been carefully designed to systematically implant bugs in a properly functioning visualization. Students are assigned the task of analyzing the code and also identify the bugs through quizzing. This provides students with a challenging hands-on learning experience that complements students’ textbook knowledge. It also serves as a significant foundation for pursuing future courses in data structures

Green Synthesis, Biological Evaluation of Newer Benzothiazole Derivatives

Benzothiazole is one of the most important heterocyclic compound, weak base, having varied biological activities and still of great scientific interest now a days. They are widely found in bioorganic and medicinal chemistry with application in drug discovery. In the present study some novel benzothiazole derivatives were synthesized under green synthesis by microwave irradiation method by using Phenyliodoniumbis-trifluoroacetate (PIFA) in ethanol according to the scheme. All the synthesized benzothiazole derivatives have been characterized by using elemental analysis, FT-IR, 1HNMR, 13C NMR spectroscopy and further supported by mass spectroscopy. Purity of all the compounds has been checked on thin layer chromatographic plate and HPLC technique. All the synthesized compounds were evaluated for antimicrobial activity by estimating the minimum inhibitory concentration (MIC) by adopting serial dilution technique and analgesic activity was examined by using the hot-plate method. All the compounds exhibited moderate to significant antimicrobial and analgesic activities

Synthesis, Characterization and Screening of Novel 5,6-Dihydroacridine Derivatives as Potent Antidiabetic and Antioxidant Agent

Acridine is an important nucleus in heterocyclic compounds which posses a wide spectrum of pharmacological activities. In this present work 10-Chloro-5,6-dihydro-12-phenylpyrimido[4,5-a]acridin-2-amine derivatives (PD-1 to PD-5) and 2-Amino-10-chloro-1,4,5,6-tetrahydro-12-phenylbenzo-[1,7] phenanthroline derivatives (PD-6 to PD-10) were synthesized from (E)-2-Benzylidene-7-chloro-3,4-dihydro-9-phenylacridin-1(2H)-one with guanidine carbonate and malononitrile. All the synthesized compounds have been characterized by using elemental analysis, FT-IR, 1H NMR, 13C NMR spectroscopy and further supported by mass spectroscopy. Purity of all the compounds has been checked on thin layer chromatographic plate and HPLC technique. All the synthesized compounds were tested for in vitro anti-diabetic and anti-oxidant activities. These compounds can be further exploited to get the potent lead compounds. The detailed synthesis and the anti-diabetic and anti-oxidant screening of the new compounds are reported

DEVELOPMENT AND VALIDATION OF A STABILITY-INDICATING RP-HPLC METHOD FOR THE ESTIMATION OF METFORMIN, SAXAGLIPTIN, AND DAPAGLIFLOZIN

Objective: A new combination of Metformin, Saxagliptin, and Dapagliflozinfixed-dose combination of antidiabetic medication is being used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Methods: Chromatography was carried out using Kromasil C18 250×4.6, 5.0 mm column with a flow rate of 1.0 ml/min. The mobile phase comprised of pH 4.8 0.01 N Potassium dihydrogen phosphate buffer and Acetonitrile in the ratio of 65:35 is used. The developed method has been validated for various parameters such as precision, accuracy, linearity, robustness, limit of detection (LOD), limit of quantification (LOQ), and solution stability. The stability-indicating capability of the method was established by forced degradation studies under stress conditions such as acid, base, peroxide, UV, thermal, and humidity. Results: The retention times of Metformin, Saxagliptin, and Dapagliflozin were found to be 2.294, 2.869, and 3.887 min, respectively. The method was specific and linear (R2>0.999) for MET, SXG, and DGF. The LOD and LOQ were found to be 13.85 μg/ml and 41.95 μg/ml for MET, 0.06 μg/ml and 0.19 μg/ml for SXG and 0.19 μg/ml and 0.57 μg/ml for DGF, respectively. The mean % recovery obtained was found to be 100.21% for MET, 99.83% for SXG, and 99.97% for DGF, respectively. Conclusion: Hence, the chromatographic method developed was said to be rapid, simple, specific, sensitive, precise, accurate, robust, and reliable that can be effectively applied for routine analysis in research institutions, quality control departments in industries

Green Synthesis, Biological Evaluation of Novel Benzoxazole Derivatives

Benzoxazole is one of the most important heterocyclic compound, having varied biological activities and still of great scientific interest now a days. They are widely found in bioorganic and medicinal chemistry with application in drug discovery. In the present study some novel benzoxazole derivatives were synthesized under green synthesis by microwave irradiation method by using Phenyliodoniumbis-trifluoroacetate (PIFA) in ethanol according to the scheme. All the synthesized benzoxazole derivatives have been characterized by using elemental analysis, FT-IR, 1HNMR, 13C NMR spectroscopy and further supported by Mass spectroscopy. Purity of all the compounds has been checked on thin layer chromatographic plate and HPLC technique. All the synthesized compounds were evaluated for antimicrobial activity by estimating the minimum inhibitory concentration (MIC) by adopting serial dilution technique and analgesic activity was examined by using the hot-plate method. All the compounds exhibited moderate to significant antimicrobial and analgesic activitie

Review of Autonomous Underwater Vehicles

The exploration of ocean space requires underwater vehicles (UV) such as submarines, autonomous underwater vehicles (AUV), manned underwater vehicles, remotely operated vehicles (ROV) and ship towed instrumentation packages. Of these, AUVs dominate the exploration of deep oceans. The list of applications where UVs can be employed include long-term deployments where they would serve as platforms for spatiotemporal samplings of physical characteristics (e.g., temperature, depth, conductivity, current) of the water column; use of multiple vehicles for mapping out an evolving phenomenon such as hydrothermal vents, tsunamis, etc., rapidly; transiting long distances to a site for making observations as part of a response team; search and mapping of seabed minerals; underwater warfare using submarines; and mine hunting, pipe laying, and inspection and maintenance of offshore structures

Green Synthesis & Biological Evaluation of Novel Benzimidazole Derivatives as Antianxiety Agents

Benzimidazole is one of the most important heterocyclic compound, having varied biological activities and still of great scientific interest now a days. They are widely found in bioorganic and medicinal chemistry with application in drug discovery. In the present study some novel benzimidazole derivatives were synthesized under green synthesis by solvent free conditions by using catalytic amount of silica supported sodium hydrogen sulphate according to the scheme. All the synthesized benzimidazole derivatives have been characterized by using elemental analysis, FT-IR, 1HNMR, 13C NMR spectroscopy and further supported by Mass spectroscopy. Purity of all the compounds has been checked on thin layer chromatographic plate and HPLC technique. All the synthesized compounds were tested for their anti anxiety and neurotoxicity activities by elevated plus maze test in mice. Test compounds and diazepam was administered intraperitoneally in antianxiety study at dose of 2 mg/kg. Compounds BZ-6 & BZ-7 showed highest antianxiety activity compared to diazepam and did not show neurotoxicity in rotarod test. All the compounds exhibited moderate to significant antianxiety activity

Sodium selenate treatment using a combination of seed priming and foliar spray alleviates salinity stress in rice

Soil salinity is one of the important abiotic stress factors that affect rice productivity and quality. Research with several dicotyledonous plants indicated that the detrimental effects associated with salinity stress can (partly) be overcome by the external application of antioxidative substances. For instance, sodium selenate (Na2SeO4) significantly improved the growth and productivity of several crops under various abiotic stress conditions. At present there is no report describing the impact of Na2SeO4 on salinity stressed cereals such as rice. Rice cultivation is threatened by increasing salinity stress, and in future this problem will further be aggravated by global warming and sea level rise, impacting coastal areas. The current study reports on the effect of Na2SeO4 in alleviating salinity stress in rice plants. The optimal concentration of Na2SeO4 and the most efficient mode of selenium application were investigated. Selenium, sodium, and potassium contents in leaves were determined. Antioxidant enzyme activities as well as proline, hydrogen peroxide (H2O2), and malondialdehyde (MDA) concentrations were analyzed. In addition, the transcript levels for OsNHX1, an important Na+/H+ antiporter, were quantified. Treatment of 2-week-old rice plants under 150 mM NaCl stress with 6 mg l(-1) Na2SeO4 improved the total biomass. A significantly higher biomass was observed for the plants that received Na2SeO4 by a combination of seed priming and foliar spray compared to the individual treatments. The Na2SeO4 application enhanced the activity of antioxidant enzymes (SOD, APX, CAT, and GSH-Px), increased the proline content, and reduced H2O2 and MDA concentrations in plants under NaCl stress. These biochemical changes were accompanied by increased transcript levels for OsNHX1 resulting in a higher K+/Na+ ratio in the rice plants under NaCl stress. The results suggest that Na2SeO4 treatment alleviates the adverse effect of salinity on rice plant growth through enhancing the antioxidant defense system and increase of OsNHX1 transcript levels