31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Impact of Integrated Nitrogen Management Practices on Nutrient Content and their Uptake by Transplanted Rice Crop (Oryza sativa L.)

Aim: Nitrogen is very crucial for production of rice and recently the uses of chemical fertilizers are increased for rice production, which are ruining our soils and environment. So, to evaluate the effect of integrated nitrogen management practices on nutrient content and their uptake by transplanted rice crop this study was conducted. Study Design: Randomized block design. Place and Duration of Study: One year field experiment at Research farm, School of Agriculture, Abhilashi University, Chail Chowk, Mandi, (H.P.). Methodology: The field study was conducted with eight treatments and three replications. The different treatments combinations were T1 (absolute control), T2 [100% RDN through Chemical Fertilizer (CF)], T3 (75% RDN through CF + 25% N through FYM), T4 (75% RDN through CF + 25% N through poultry manure), T5 (75% RDN through CF + 25% N through vermicompost), T6 (50% RDN through CF + 50% N through FYM), T7 (50% RDN through CF + 50% N through poultry manure), T8 (50% RDN through CF + 50% N through vermicompost). Results: The study of results revealed that the nitrogen, phosphorus and potassium content in grains and straw of rice crop showed non-significant differences with the application of nitrogen through various treatments, while the maximum contents of these nutrients were higher in treatment T2. However, the significantly highest uptake of nitrogen, phosphorus and potassium by grains and straw and total uptake of these nutrients by rice was noted in treatment T2 which was statistically (P = .05) at par with treatment T4 and T5. Whereas, the minimum content in grains and straw and uptake of these nutrients by grains and straw along with their total uptake was found under control treatment. Conclusion: This study suggests that the use of integrated nitrogen management enhances the nitrogen, phosphorus and potassium content and their uptake by rice crop

Outcomes of donation after circulatory death kidneys undergoing hypothermic machine perfusion following static cold storage: A UK population-based cohort study.

Evidence is currently lacking regarding the outcomes of kidneys undergoing hypothermic machine perfusion (HMP) in patients in the United Kingdom. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single-organ donation after circulatory death (DCD) kidneys preserved with HMP with those preserved using only static cold storage (SCS). Between 2007 and 2015, HMP was used in 19.1% (864/4,529) of kidneys. Rates of delayed graft function (DGF) were significantly lower in organs preserved with HMP than for organs preserved with SCS (34.2% vs 42.0%, P < .001), despite a slightly longer cold ischemic time (median: 14.8 vs 14.1 hours, P < .001). Multivariable analysis found the effect of preservation modality to remain significant, with HMP organs having a significantly lower rate of DGF (odds ratio 0.65, 95% confidence interval 0.53-0.80, P < .001) and significantly shorter times to DGF resolution (average: 6.1 vs 7.4 days, P = .003) than SCS organs. The patient (P = .313) and graft (P = .263) survival rates were similar in the 2 preservation groups. HMP was associated with a marginal functional benefit in 1-year creatinine values (P = .044), with adjusted averages of 1.36 mg/dL (HMP) versus 1.40 mg/dL (SCS). This study supports the use of HMP and aids decision-making over its instigation, which may improve short-term patient outcomes

Effect of Potassium on Growth, Yield, Quality and Economics of Potato (Solanum tuberosum L.)

The present investigation was carried out at Research farm of Abhilashi University, Chail Chowk, Mandi during Rabi season 2022 to evaluate the effect of potassium on growth and yield of potato. The experiment was laid down in randomized block design consisting eight treatments in which one is control and others are combination of potassium with three replications. There was significant effect found under various potassium treatments in terms of plant height, number of haulms and haulm diameter at various crop growth stages and fresh and dry weight of plants, marketable yield and harvest index and specific gravity and dry matter content of tubers. The maximum marketable tuber yield was obtained with the split application (basal + foliar spray) of potassium. The findings revealed that the growth and yield parameters were significantly influenced by different split potassium levels

In-situ Rice Residue Management Practices and Its Impact on Climate, Soil Fertility and Crop Productivity: A Review

Around two-thirds of all food contributes in India is produced in the Indo-Gangetic Plains (IGP), where rice and wheat are the two main crops. In India, rice is grown on the largest percentage of land (32%) followed by wheat (23%). Reusing rice residues has an impact on the soil's characteristics and crop yield. Rice residues are significant natural resources. With a total yield of 10 to 12 t/ha, a rice-wheat sequence depletes the soil of more than 300 kg N, 30 kg P, and 300 kg K per ha. Residue burning results in nutrient losses of 100% C, 90% N, 60% S, and 25% each of P and K. Air pollution has a negative impact on health, including respiratory conditions, eye and skin irritation, and other conditions. An analysis has been done based on the stated research findings from various researchers. It is necessary to study and update the technology in order to prevent residues from burning in the rice and wheat cropping system. A good alternative for their management is to in-situ incorporate rice wastes with microbial consortia in wheat crops. Increased yield, water productivity, and profitability can be achieved by incorporating microbial consortia, while Phaleris minor weed is reduced, further enhancements to soil quality. Because rice residues are a substantial source of plant nutrients, applying them continuously will improve fertiliser management and reduce air pollution

Recipient Outcomes From Nondirected Live Kidney Donors: A UK-based Cohort Study

Background. Increasing numbers of patients with end-stage renal failure are receiving kidneys from nondirected kidney donors (NKDs), also known as altruistic donors. Transplant outcomes for recipients of such kidneys are largely inferred from studies on specified kidney donors (SKDs), which may be inaccurate due to differences in donor, recipient and transplant specific factors. We report the outcomes for recipients of NKD in the United Kingdom. Methods. Outcomes for 6861 patients receiving a living donor kidney transplant between January 2007 and December 2014 were analyzed using both the National Health Service Blood and Transplant and the UK Renal Registry datasets. Graft and patient outcomes were compared for patients receiving NKD and SKD organs using univariable and multivariable analyses. Results. There was significant discordance between the NKD and SKD donors and recipients. These included increased donor age (median, 58 years vs 47 years; P < 0.001) and higher rates of hemodialysis and previous transplants in the NKD group (both P < 0.001). Despite such markers of increased risk among both donors and recipients of NKD kidneys, there was no difference in graft survival on univariable (hazard ratio, 1.20; 95% confidence interval, 0.77-1.86; P = 0.419) or multivariable analysis (hazard ratio, 1.13; 95% confidence interval, 0.65-1.95; P = 0.665). Conclusions. Despite some markers of transplant complexity, nondirected kidney donor organs are an excellent source of organs for transplantation

Brief initial and end-ischemic O2 supply via bubble and perfusate surface oxygenation during standard HMP demonstrated to be simple yet effective for improving early recovery of renal function in an ischemia-reperfusion porcine autotransplant model.

Background Static cold storage (SCS) and hypothermic machine perfusion (HMP) are today the gold standard for kidney preservation. The aim of this study was to determine the ideal start time and least complicated method for adding oxygen during HMP to improve early graft function in a porcine kidney ischemia-reperfusion autotransplant model. Methods The left kidney of ±40 kg Landrace pig was exposed to 30 minutes of warm ischemia by vascular clamping and randomized after ex vivo cold flush. The LifePort Kidney Transporter® modified to include an external oxygenator was used in the following study groups: 1) 22h oxygenated HMP (HMPO (FiO 90%), n=8), 2) 2h HMPO2+20h HMP(n=6), and 3) 20h HMP + 2h HMPO (n=5). The LifePort kidney Transporter without external oxygenator but direct perfusate oxygenation via bubble and perfusate surface (FiO =95%) oxygenation was used in a 4th study group, 22h standard HMP including 30min at start and 1h end-ischemic O uploading (HMPO uploading). SCS and standard HMP (no active oxygen supply) for 22h served as control groups. Results The perfusate pO at the start and the end of HMP is shown in Figure 1 according to the study group. Graft recovery measured by serum creatine levels was superior in the 22h HMPO , the 2h HMPO +20h HMP and the HMPO2uploading groups compared with 22h SCS (p<0.0001), standard 22h HMP (p<0.0001) and 20h HMP+2hHMPO (p=0.0288) (Figure 2). Conclusion Our data suggest that during cold perfusion continuous oxygenation might not be required. Brief O uploading via bubble and perfusate surface oxygenation was shown to be as effective as continuous oxygenation via an external oxygenator to obtain supraphysiological pO and similar superior early graft function compared with standard HMP or SCS alone. Such simple but effective oxygenation method might easily get adopted in the clinic since it would hardly complicate handling or logistics during organ sharing