Biostimulants containing amino acids in vegetable crop production

Amino acids can induce defence reactions and reduce the impact of abiotic stresses on plants, yet their impact on the yield of vegetable crops is varied. For this reason, an analysis of the published research on the effect of biostimulants containing amino acids (BCAA) on the quantity and quality of vegetable crop yield was carried out. The results of the research indicate the multidirectional effect of BCAA on vegetable plants and they also show that the use of these biostimulants may increase yield quantity and quality as well as influence biometric features and chemical composition of plants. BCAA may also affect the amount of losses caused by pests and during the storage of vegetables. However, the variability of the effects is very large and depends on many factors: composition of BCAA, time, dose, number and method of application, cultivation cycle, weather conditions, and plant species or even cultivar. Therefore, the effective use of BCAA requires further research, while their proper application in horticultural practice will require taking into account many factors.

Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval

ImportanceIncreased rates of myocarditis/pericarditis following COVID-19 mRNA vaccines have been observed. However, little data are available related to product-specific differences, which have important programmatic impacts.ObjectiveThe objective of this study was to estimate reporting rates of myocarditis/pericarditis following COVID-19 mRNA vaccine by product, age, sex, and dose number, as well inter-dose interval.DesignWe conducted a population-based cohort study using passive vaccine safety surveillance data. All individuals in Ontario, Canada who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020 and September 4, 2021 were included.SettingThis study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database.ParticipantsWe included all individuals with a reported episode of myocarditis/pericarditis following COVID-19 vaccine in the study period. We obtained information on all doses administered in the province to calculate reporting rates.ExposureReceipt of COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).Main Outcome(s) and Measure(s)Reported rate of myocarditis/pericarditis meeting level 1-3 of the Brighton Collaboration case definitions.ResultsThere were 19,740,741 doses of mRNA vaccines administered and 297 reports of myocarditis/pericarditis meeting our inclusion criteria. Among these, 69.7% occurred following the second dose of COVID-19 mRNA vaccine and 76.8% occurred in males. The median age of individuals with a reported event was 24 years. The highest reporting rate of myocarditis/pericarditis was observed in males aged 18-24 years following mRNA-1273 as the second dose; the rate in this age group was 5.1 (95% CI 1.9-15.5) times higher than the rate following BNT162b2 as the second dose. Overall reporting rates were higher when the inter-dose interval was shorter (i.e., ≤30 days) for both vaccine products. Among individuals who received mRNA-1273 for the second dose, rates were higher for those who had a heterologous as opposed to homologous vaccine schedule.Conclusions and RelevanceOur results suggest that vaccine product, inter-dose interval and vaccine schedule combinations may play a role in the risk of myocarditis/pericarditis, in addition to age and sex. Certain programmatic strategies could reduce the risk of myocarditis/pericarditis following mRNA vaccines.

Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice

Human malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.

Decision Analysis of the COVID-19 Vaccines

The entire globe is struggling with the COVID-19 pandemic since March 11, 2020. There is still a large number of infected patients and death, and there is no proven treatment for the infection yet. This has led to the race in vaccine development to protect people from COVID-19 infection. As of February 3, 2021, there were 289 experimental COVID -19 vaccines in development, 66 of which were in clinical trials with different phases, and 20 of them were in phase 3. This study aims to evaluate 15 important vaccines based on criteria such as the dose number, dosing schedule, storage advantages, efficacy, and side effect. In this evaluation, we use the fuzzy PROMETHEE approach, which is an important Multi-Criteria Decision Making (MCDM) technique. The importance level of the criteria is determined based on expert opinion. The result shows that the EpiVacCorona vaccine is the most effective vaccine to prevent COVID-19 infections based on the selected criteria and the importance level of each criterion. The result obtained may change based on individual or expert’s priorities. Due to the use of different criteria for the ranking and different weightings of the criteria, the ranking result may differ. This study also shows the strengths and weaknesses of the selected vaccines and the applicability of the MCDM technique for the evaluation of COVID -19 vaccines.

Incidence and severity of systemic allergic reactions (SAR) reported with chemotherapeutic drugs.

e18802 Background: SAR, a known adverse event of cancer therapy has variable severity. Despite the availability of many approved grading tools, there is still a lack of a globally applicable grading system. To address this, World Allergy Organization (WAO) created a uniform 5-grade classification system which was modified recently to be applicable for all SAR’s. This study aims to understand the incidence and severity of chemotherapy induced SAR and overall response rate (ORR) of rechallenged drugs in a tertiary cancer center. Methods: A retrospective single centered analysis of 103 patients with chemotherapy induced SAR was carried out. Patients were stratified based on age, gender, drugs given, dose number and severity of reaction. We used Modified WAO Grading System for assessing the severity. Descriptive statistics was applied to decipher the data. ORR is defined as the proportion of patients who have a partial or complete response to rechallenged drugs using RECIST Criteria for solid tumors and Lugano Classification for lymphoma. Results: Among 103 patients who reported SAR, 63.1% were female and 64.1% patients were less than 60 years of age. Among the 22 drugs, median dose number was high for Oxaliplatin (6) and Carboplatin (5). SAR was more observed with Paclitaxel (20.39%), Carboplatin (17.48%) and Rituximab (13.59%). However, carboplatin and rituximab had more incidence of grade 1 SAR(25.92% and 29.63% respectively). Grade 1 SAR (39.80%) were reported the highest followed by grade 3 (29.13%), grade 5 (13.59%), grade 2 (11.65%), and grade 4 (5.83%). Cetuximab precipitated the most grade 5 reactions (33.33%). Among patients exhibiting SAR with Paclitaxel, 42.86% were switched to alternatives, Nab-paclitaxel (28.57%) being preferred the most. Carboplatin was changed to cisplatin in 16.66% patients and Nanosomal docetaxel lipid suspension replaced docetaxel in 42.86% patients who reported SAR with carboplatin and docetaxel respectively. Rituximab was rechallenged the most (11.65%) off which one patient had reaction. ORR was observed to be 62.5% and 50% among rechallenged Paclitaxel and Rituximab respectively. The incidence of SAR is depicted in the below table. Conclusions: The study inferred that most SAR reactions occurred with Paclitaxel and Carboplatin. Oxaliplatin and Carboplatin presented with delayed SAR. Grade 1 and grade 3 reaction were relatively more. Cetuximab reported the most grade 5 reactions. ORR of rechallenged drugs should be monitored in further larger studies.[Table: see text]

MO304COMPLEMENT INHIBITION FOR REFRACTORY GLOMERULONEPHRITIS IN SYSTEMIC VASCULITIS

Background and Aims Systemic vasculitis(SV) is a life-threatening disease and, in some cases, refractory to intensive multi-immunosuppressant drugs. Complement hyperactivation has gained interest in the pathogenesis of the SV. We report the efficacy of the short course of C5-inhibitor (eculizumab) in refractory cases of lupus nephritis (r-LN) and refractory ANCA-associated glomerulonephritis (r-AGN). Method In this retrospective study, eight consecutive patients were assessed (r-LN:n=3 and r-AGN:n=5). All patients were previously treated with three or more drugs included: corticosteroids (n=8), mycophenolate (n=8), rituximab (n=7), immunoglobulins (n=5), therapeutic plasma exchange (n=4), cyclophosphamide (n=1), and belimumab (n=1). Eculizumab was considered for use in off-label indication in patients with progressive renal deterioration (worsening creatinine, protein-to-creatinine ratio) or developing a high-risk lethal complication after the induction immunosuppressive therapy. The histologic lesson observed were: a) r-LN: Type VI (n=1), Type V(n=1), and type IV(n=1), and b) r-AGN: sclerotic (n=3), and malignant hypertension+/-thrombotic microangiopathy (n=1), in one patient who developed pulmonary hemorrhage no renal biopsy was performed. Results Mean age (SD): 51(17)years. Median (p25-p75) of follow-up: 19(12-28) months. Overall, 2(25%) of the patients needed chronic renal replacement therapy (one r-AGN patient who required urgent haemodialysis at presentation and one r-LN within 12 months after the onset eculizumab). During the follow-up the eGFR(mean(95%CI) changed from 28(16-40) to 30(20-41)mil/min/1.73m2(P = 0.51) and the median(p25-p75) protein-to-creatinine ratio decreased from 2.3(1.5-6.4) to 0.6(0.3-1.7) mg/mg(P= 0.028). The mean eculizumab cycle dose number was 5(95%CI:3-6), four patients required two cycles. Overall, the mean eculizumab dosage required was 7162 mg (95%CI: 2969-11355). No major side effects were recorded. Conclusion The coadyuvant complement inhibition with eculizumab stabilized renal function and decreased proteinuria in six out of the eight previously refractory patients and represents a promising tool in treating lupus and ANCA vasculitis nephritis.

A Case of Myopericarditis and the HPV vaccine

Introduction: Human Papillomavirus (HPV) is the underlying etiology of numerous cancers and genital warts in both males and females. Vaccines were developed against HPV to prevent transmission and arrest development of cancers caused by the virus. Gardasil 9â is the newest vaccine, covering 9 serotypes of HPV and is recommended by the CDC for both males and females over 9 years of age in a series of vaccinations. Myopericarditis (including myocarditis and pericarditis) is not reported as an adverse reaction in the Gardasil 9â package insert. Case Report A healthy 18-year-old male with no significant past medical or social history received dose number 3 of HPV vaccine at his physician’s office. Within 24 hours, he developed chills and a fever (normal HPV reactions) and then recovered without sequelae within 48 hours. Three days later, he developed crushing chest pain, with arm tingling and jaw pain. He was triaged directly to the emergency room where he had troponins of greater than 11000 and T wave inversions on his EKG. Other diagnostic tests and labs showed normal heart anatomy and no early coronary artery disease. He was diagnosed with myopericarditis by cardiology. He was treated and recovered fully within 3 months. Discussion Using the WHO tool for adverse vaccine reactions, this case has a consistent causal relationship with vaccination. This is the eleventh case of myopericarditis reported to the Vaccine Adverse Effects Reporting system for the HPV vaccine. Conclusion Although rare, myopericarditis should be considered as a possible adverse effect from the human papillomavirus vaccine.

147 Simplification of the follicle-stimulating hormone protocol for superovulation of the first follicular wave in sheep

The objective of the present study was to evaluate the effect of length of the FSH superstimulatory treatment on ovarian response and embryo production in sheep. Poll Dorset ewes (n=63) 3.2±0.2 years old weighing 58.5±1.5kg and with a body condition score of 2.7±0.1 (0=emaciated; 5=obese) were used during the transition from the breeding to the non-breeding season. All ewes received an ovarian superstimulatory treatment during the first follicular wave (Day 0 protocol). On Day −9 all ewes received a 0.3-g progesterone intravaginal device (CIDR, Zoetis) for 6 days. On Day −3, the CIDR was removed and all ewes were administered 125μg of cloprostenol sodium intramuscularly (IM) (PGF, estroPLAN, Parnell) and 200IU of equine chorionic gonadotrophin (eCG)+100IU of human chorionic gonadotrophin (hCG) IM (P.G. 600, Merck). Thirty-six hours after CIDR removal (Day −1.5) ewes were administered 100μg of gonadorelin acetate IM (gonadotrophin-releasing hormone, GnRH; Gonabreed, Parnell). Superstimulatory treatments were initiated on Day 0 (84 h after CIDR removal) with a total of 240mg of NIH-FSH-P1 (12 mL, Folltropin, Vetoquinol), and a new CIDR was used from the first to the last FSH dose (6-dose=3 days; 8-dose=4 days). Ewes were randomised to receive the total dose of FSH distributed in eight decreasing doses (8-dose group, n=33) or six decreasing doses (6-dose group, n=30) twice daily 12h apart. Two doses of PGF were administered with the last two doses of FSH, and GnRH was administered 12h after the last FSH administration. Intrauterine AI with fresh semen was performed by laparoscopy 16h after GnRH administration. Ovarian response was determined by laparoscopy 6 days after AI and ova/embryos were collected surgically in ewes with >2 corpora lutea (CL). Data were analysed using generalized linear mixed models (SAS 9.4; SAS Institute Inc.) and presented as mean±s.e.m. in Table 1. The percentage of responding donors (>2 CL) was 93.3% (28/30) and 78.8% (26/33; P=0.5) for the 6-dose and 8-dose groups, respectively. The number of CL tended (P=0.06) to be lesser in ewes in the 6-dose than the 8-dose group. However, no differences (P>0.10) were found in total ova/embryo, fertilized ova, transferable embryos, or freezable embryos. In conclusion, despite a tendency for a greater ovarian response in ewes treated with 8 doses of FSH, embryo yield did not appear to differ after either 6 or 8 doses of FSH administered during the first follicular wave in sheep. Table 1. Ovulatory response and embryo production in responding ewes (>2 corpora lutea) superstimulated with either 6 or 8 doses of FSH during the first follicular wave Outcome Treatment P-value 6-dose 8-dose Number of ewes 28 26 Corpora lutea (n) 14.2±1.7 20.3±2.8 0.06 Total ova/embryos (n) 9.0±1.3 10.9±1.8 0.38 Fertilized ova (n) 8.1±1.4 10.2±1.9 0.34 Fertilized ova (% per ewe) 89.0±5.0 81.7±7.0 0.40 Degenerate embryos 1.3±0.4 2.0±0.8 0.89 Transferable embryos (Grade 1–3) 6.8±1.2 8.2±1.8 0.52 Transferable embryos (% per ewe) 85.7±4.4 75.4±8.4 0.46 Freezable embryos (Grade 1–2) 6.6±1.1 8.2±1.8 0.43 Freezable embryos (% per ewe) 80.5±5.6 75.4±8.4 0.61

Investigating Gut Microbial Taxa and Asparaginase Related Genes in Children Showing Different Direction of Change in Serum Asparaginase Activity Levels during Pegasparaginase Treatment for Acute Lymphoblastic Leukemia

Background: L-asparaginase (ASNase) converts Asn to Asp and at sustained high levels depletes circulating Asn, leading to leukemic cell death. This dependency has led to the use of ASNase (in a peglyated form, PEGASNase) as an important therapy in the treatment of acute lymphoblastic leukemia (ALL) and has improved survival in patients with ALL. ASNase treatment efficacy relies on significant depletion of circulating Asn for sustained periods of time. Therapeutic monitoring is therefore critical to ensure sufficient levels of ASNase activity to maintain Asn depletion. Serum ASNase activity is monitored as a proxy for Asn levels, having an inverse relationship to Asn. The predictors of serum levels of ASNase activity are not clear however with variation in levels within the same patient between doses. The gut microbiome plays a role in human health and disease, producing metabolites that could impact ASNase therapy. To date, the role of the gut microbiome community in impacting serum ASNase activity levels has not been investigated. Methods: We investigated 12 paediatric ALL patients for which serum ASNase levels were measured (7 days post treatment) for two consecutive doses of PEGASNase and a stool sample was collected between these two doses (17 samples). Change in serum ASNase activity was determined by examining the difference in consecutive serum ASNase levels. Activity was considered to have decreased when change was negative (serum ASNase levels declined from previous measurement). Gut microbial community composition of the stool samples was determined from a portion of the 16S rRNA gene. In addition whole shotgun metagenome sequencing was used to investigate the relationship between microbial ASNase and ASNS genes and changes in serum ASNase levels during treatment. We utilized a Bayesian model to examine the microbial community structure in serum ASNase decreasing (SD) vs increasing (SI) samples. We used Mann-Whitney U test to examine differences in counts of bacterial ASNase and ASNS genes in SD and SI groups. Finally we investigated counts of bacterial ASNase and ASNS genes along with age, gender, disease risk, dose number, serum ASNase level at previous dose and time between stool sample and dose at predicting change in serum ASNase activity levels using regression models after applying lasso reduction. Results: Patients in this study were 50% male and had an average age of 5 years ranging from 1 month to 14.6 years. Among samples examined 35% had decreased serum activity compared to measurements from the previous dose. We identified differing assemblages of microbial taxa prior to PEGASNase treatment. The SD community was predominated by Escherichia prior to treatment while Bacteroides and Streptococcus predominated in the SI community (Fig 1). We found that counts of microbial ASNS were significantly (p=0.003) negatively correlated with change in serum ASNase activity levels (Fig 2), however neither bacterial ASNase gene (ansA or ansB) was significant. Including covariates and applying model reduction we find that ASNS (p=0.0005), dose number (p= 0.001), age at diagnosis (p= 0.001), serum ASNase levels at previous dose (p= 0.008), and counts of ansA (p=0.04) predict change in serum ASNase levels (adjusted R2=0.826, p= 0.0002). Only dose-number was positively correlated with change in serum ASNase level. Conclusions: We found differences in the microbial community prior to PEGASNase treatment possibly suggesting that modifying the microbiome (decreasing contribution of Escherichia) prior to treatment could result in increased serum ASNase activity. This data also suggests that increased amounts of bacterial ASNS genes present may be associated with a decrease in serum ASNase activity. Future work should focus on a larger and more diverse set of samples in order to further investigate SD and SI community-level properties and the role of covariates (e.g., age and dose number), and further exam the interplay between serum ASNase activity, and bacterial ASNS. Disclosures No relevant conflicts of interest to declare.