Triple Dose Research Articles

Immunogenicity, safety, and persistence induced by triple- and standard-strength four-dose hepatitis B vaccination regimens in hemodialysis patients: A multicenter, randomized, parallel-controlled trial in Six cities in Shanxi Province.

Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 μg) at 0-1-2-6 months (IM60×4 group). The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients.The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.

An additional intra-operative peri-articular tranexamic acid decreases the drain output but does not benefit in total blood loss conservation during bilateral Total Knee Arthroplasty: A retrospective observation

BackgroundThe preferred procedure for end-stage arthritic knees is Total Knee Arthroplasty (TKA). Hidden blood loss during and after surgery is one of the most frequent side effects of TKA. This study aims to assess the impact of an extra intraoperative dosage of local periarticular tranexamic acid (TXA) on total blood loss and drain output following bilateral TKA in comparison to conventional triple dose IV TXA. MethodsPatients who had bilateral simultaneous TKA between January 2021 and November 2022 were the subjects of a single centre based retrospective observational analysis. In group 1 and group 2, 80 knees (IV TXA with periarticular TXA) were compared to a matched paired control set of 80 knees (3 dose IV TXA). ResultsIn all, 80 patients having 160 TKAs performed were included in the study. When the two groups' total and concealed blood losses were compared, they were found to be statistically insignificant; nevertheless, first group's drain output was considerably lower than the second group due to the use of an additional dose of periarticular TXA. Comparable declines in Hb, HCT, and platelet count were observed among the two groups. The secondary goal indicated that although there was no significant difference in range of motion between the groups 72 h after surgery, group 2 had a higher rate of hospital re-admissions within 30 days compared to group 1. ConclusionThe study demonstrated that peri-articular TXA administration during bilateral simultaneous TKA resulted in no additional benefit to the total or hidden blood loss conservation, except reducing the drain amount. However, a unique finding of the current study suggests decreased chances of wound complications and lesser 30-day readmission rate among patients receiving peri-articular TXA. Present study thus advocates the use of TXA as an effective peri-articular adjunct after TKA when a negative suction drain is being used post-operatively. Level of evidenceLevel III, Retrospective comparative study.

Mosquitocidal efficacy and pharmacokinetics of single-dose ivermectin versus three-day dose regimen for malaria vector control compared with albendazole and no treatment: An open-label randomized controlled trial

ObjectivesWhen malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control. DesignWe conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was Anopheles gambiae survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment. ResultsA total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; P <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; P = 0.0.11). Albendazole had, overall, no mosquitocidal effect. ConclusionsIt is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability.

Comparative evaluation of local and downstream responses in two commercially available paclitaxel-coated balloons in healthy peripheral arteries of a swine model

ObjectiveTo investigate the local, downstream, and systemic effects of 2 different paclitaxel-coated balloons. DesignPreclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices: the test paclitaxel-coated balloon (PCB) (LuminorⓇ), a control PCB (IN.PACTⓇ), and a plain angioplasty balloon (OceanusⓇ), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis. MethodsTwenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Postprocedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects. ResultsAngioplasty was successfully carried out in all animals. Significant protocol deviations appeared in 3 arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (P = .0828), intima/media inflammation (P = .0004), transmural medial smooth muscle cell (SMC) loss (P = .0016), wall thickness loss (P = .0141), presence of fibrin in the vascular wall (P = .0054), and adventitial inflammation (P = .0080). A similar pattern was observed at the 3× dose for endothelial loss (P = .0011), intima/media inflammation (P < .0001), circumferential SMC loss (P = .0004), medial SMC replacement with proteoglycans (P = .0014), fibrin (P = .0034), and collagen content (P = .0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (P = .006). No systemic effects of toxicity were detected in any of the samples analyzed. ConclusionLuminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.

Fate of emerging contaminants in the soil-plant system: a study on durum wheat irrigated with treated municipal wastewater

IntroductionEmerging contaminants in irrigation wastewater can cause bioaccumulation in crops, posing health risks to humans and other living organisms. The extent to which different emerging contaminants (ECs) are taken up by plants varies depending on the physicochemical properties of the contaminants and the type of crops grown.MethodsThis study investigated the fate of emerging contaminants (ECs), particularly pharmaceuticals, in durum wheat grown on soils irrigated with treated wastewater in southern Italy. The experiment was conducted in lysimeters irrigated with wastewater during previous crop cycles, assessing the presence and distribution of ECs in both soil and plant tissues. Three different levels of exposure to ECs were compared: freshwater irrigation (FW), wastewater treated to European average contaminant levels (TWWx1), and a triple dose of contaminants (TWWx3).ResultsThe behavior of 12 different ECs in the plant-soil complex was analyzed and found variable. Fluconazole and carbamazepine were found to have higher uptake concentrations in the plant, with accumulation observed in the plant and grain, especially in the TWWx3 treatment. However, some ECs (such as Sulfamethoxazole, Trimethoprim, Ketoprofen, Diclofenac, Metoprolol, and Naproxen) showed high uncertainties in their fate, probably due to degradation in soil and influential crop parameters.DiscussionThe results of this study contribute to the argument that the reuse of treated wastewater for irrigation, if properly monitored, can be a safe approach in agriculture and can support policymakers in developing future legislative frameworks for sustainable water management.

ОТЗЫВЧИВОСТЬ КАРТОФЕЛЯ НА УДОБРЕНИЕ НА ДЕРНОВО-ГЛЕЕВЫХ ПОЧВАХ

It was experimentally established that potato yields increased from increasing a single dose of NPK to a triple dose, which resulted in the highest yield (22.7 t/ha, which is 9.0 t/ha more than the control, or 65.7 %). The equivalent variants N2P2K2 and manure+NPK were almost equal in yield (21.0 and 21.2 t/ha). Due to liming of the soil, the yield increased by 1.7 t/ha or 12 %. The dry matter content in tubers in the fertilized variants decreased by 0.6-1.6% relative to the control, and starchy content also decreased by 0.35-2.25 % (17.3 % in the control). At the same time, the accumulation of protein increased by 0.17-0.34% and vitamin C by 0.1-3.6 mg%. The best option in terms of the amount of starch and vitamin C was manure + NPK. According to it, the payback of fertilizers was also the highest - 41.0 kg/kg a.i., in second place was N1P1K1+lime (33.5 kg/kg a.i.). With an increase in the level of fertilization, the payback of fertilizers consistently decreased from 24.3 to 16.2 kg/kg a.i. Conventionally, net income from fertilizers increased, and the profit per ruble spent decreased as the level of fertilization increased. Judging by the last indicator, the option manure + NPK was economically more profitable, for which the bioenergy coefficient was also the highest (4.48 units). In the conditions of the forest-meadow zone when cultivating potatoes, liming of acidic sod-gley soils is quite effective.

Optimizing saffron (Crocus sativus) yield and quality through nutrient inputs and timing

The study was conducted from 2016 to 2020 and involved the application of eight fertilizer treatments. These treatments included single doses of 45 g m−2 of NPK 15–15-15 applied in autumn (A), winter (W), and spring (S); double doses of 90 g m−2 split evenly in autumn-winter (AW), autumn-spring (AS), and winter-spring (WS); and a triple dose of 135 g m−2 split evenly in autumn-winter-spring (AWS). A control group (C) received no fertilizer. The triple dose treatment yielded the most effective results in terms of saffron yield parameters. The number of flowers m−2 in AWS increased from 73.0 in 2017 to 547.6 in 2020, while control exhibited a slight increase from 32.0 in 2017 to 68.1 in 2020. Double dose treatments were also effective in enhancing yield parameters compared to the control. A single dose treatment applied in spring (S) had a limited impact compared to A and W treatments. Over five years, S, A, and W treatments exhibited an average flower number of 97.9 m−2, 181.1 m−2, and 136.1 m−2 respectively. The qualitative characteristics of saffron, including color (crocin), taste (picrocrocin), and aroma (safranal), were not significantly influenced by fertilization treatments. These attributes remained within the natural limits defined by ISO-3632.

Uptake and translocation of pharmaceutically active compounds by olive tree (Olea europaea L.) irrigated with treated municipal wastewater.

The use of treated municipal wastewater (TWW) represents a relevant opportunity for irrigation of agricultural crops in semi-arid regions to counter the increasing water scarcity. Pharmaceutically active compounds (PhACs) are often detected in treated wastewater, posing a risk to humans and the environment. PhACs can accumulate in soils and translocate into different plant tissues, reaching, in some cases, edible organs and entering the food chain. This study evaluated the uptake and translocation processes of 10 PhACs by olive trees irrigated with TWW, investigating their accumulation in different plant organs. The experiment was conducted in southern Italy, in 2-year-old plants irrigated with three different types of water: freshwater (FW), TWW spiked with 10 PhACs at a concentration of 200 µg L-1 (1× TWW), and at a triple dose (3× TWW), from July to October 2021. The concentration of PhACs in soil and plant organs was assessed, collecting samples of root, stem, shoot, leaf, fruit, and kernel at 0 (T0), 50 (T1), and 107 (T2) days of irrigation. PhACs extraction from soil and plant organs was carried out using the QuEChERS method, and their concentrations were determined by high-resolution mass spectrometry coupled with liquid chromatography. Results of uptake factors (UF) showed a different behavior between compounds according to their physicochemical properties, highlighting PhACs accumulation and translocation in different plant organs (also edible part) in 1× TWW and 3× TWW compared to FW. Two PhACs, carbamazepine and fluconazole, showed interactions with the soil-plant system, translocating also in the aerial part of the plant, with a translocation factor (TF) greater than 1, which indicates high root-to-leaf translocation. Findings highlight that only few PhACs among the selected compounds can be uptaken by woody plants and accumulated in edible parts at low concentration. No effects of PhACs exposure on plant growth have been detected. Despite the attention to be paid to the few compounds that translocate into edible organs, these results are promising for adapting wastewater irrigation in crops. Increasing knowledge about PhACs behavior in woody plants can be important for developing optimized wastewater irrigation and soil management strategies to reduce PhACs accumulation and translocation in plants.

Efficacy of single-dose versus triple-doses perioperative antimicrobial prophylaxis in patients undergoing laparoscopic cholecystectomy

Introduction: Although debatable, prophylactic antibiotics may be required for patients undergoing cholecystectomy for symptomatic gallstone disease with certain associated risk factors. Our study aimed to perform a non-randomised prospective comparative trial evaluating a single-dose pre-operative antibiotic versus a triple-dose prophylactic post-operative antibiotic in patients with symptomatic uncomplicated cholelithiasis undergoing laparoscopic cholecystectomy. Methodology: This study was a non-randomised prospective comparative study in a single institution. Two hundred patients were enrolled and allocated to two groups. Group A patients were given a single dose of pre-operative prophylactic antibiotic, and Group B patients received a triple dose of prophylactic antibiotic therapy. We also studied the bacteriological profile of bile in all the patients using bile culture and antibiotic sensitivity, and we analysed their association with post-operative surgical site infection (SSI). Results: All the patients were followed up on post-operative days 7 and 30. On post-operative day 7, 2% of patients in Group A and 1% of patients in Group B were found to have SSI, and no statistically significant difference in SSI between the two groups was noted (P = 0.558). On post-operative day 30, no patient was found to have a SSI in either of the two groups. Moreover, post-operative bile culture was obtained in all the cases, and 6% of patients had a positive bile culture. However, none of them developed SSIs on post-operative day 7. Conclusion: A single-dose pre-operative antibiotic is as effective as three perioperative doses in preventing SSI in laparoscopic cholecystectomy for symptomatic, uncomplicated gallstone disease. Our study did not associate port-site SSI with a positive bile culture.

Harnessing Nature's Defence: The Antimicrobial Efficacy of Pasteurised Cattle Milk-Derived Extracellular Vesicles on Staphylococcus aureus ATCC 25923.

Increasing antimicrobial resistance (AMR) challenges conventional antibiotics, prompting the search for alternatives. Extracellular vesicles (EVs) from pasteurised cattle milk offer promise, due to their unique properties. This study investigates their efficacy against five pathogenic bacteria, including Staphylococcus aureus ATCC 25923, aiming to combat AMR and to develop new therapies. EVs were characterised and tested using various methods. Co-culture experiments with S. aureus showed significant growth inhibition, with colony-forming units decreasing from 2.4 × 105 CFU/mL (single dose) to 7.4 × 104 CFU/mL (triple doses) after 12 h. Milk EVs extended lag time (6 to 9 h) and increased generation time (2.8 to 4.8 h) dose-dependently, compared to controls. In conclusion, milk EVs exhibit dose-dependent inhibition against S. aureus, prolonging lag and generation times. Despite limitations, this suggests their potential in addressing AMR.

Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis

BackgroundKnee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months.MethodsThis is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period.ResultsThere was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection.ConclusionThis study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.

Cotyledon-Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast-Enhanced MRI.

Recently, dynamic contrast-enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions. To measure cotyledon-specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury. Prospective animal model. Placental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 μg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165). 3 T, T1-weighted spoiled gradient echo sequence (product sequence, DISCO). Source images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP-1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals. Wilcoxon rank sum test, significance level P < 0.05. No motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute-1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel-treated (single dose) animal and both Tisseelx3 (triple dose) animals. This study demonstrates the feasibility of cotyledon-specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol-enhanced DCE MRI. NA TECHNICAL EFFICACY: Stage 2.

Effects of the active botanical blend "WKUP GT" on attention and cognitive functions after lunch in healthy volunteers.

"WKUP GT", a low caffeine beverage consisting of carob, Guarana, Green Tea and Elderberry extracts was studied on attention and cognitive functions post-lunch in a pilot randomized double blind placebo controlled trial. Thirty healthy volunteers were included in a crossover design trial, presenting five beverages randomly assigned to the following groups: placebo, "WKUP GT" (single, double or triple doses), or "caffeine" as an active control. Hemodynamic measurements were assessed as safety outcomes. The Cambridge Neuropsychological Test Automated Battery (CANTAB), was used to evaluate the patients when beverages were consumed 30 and 120min after lunch (respectively Delta30 and Delta120 considering baseline). Drinking "caffeine" or "WKUP GT" after lunch, showed significant improvement (p<0.05) in rapid visual information processing compared to placebo (Delta120 of "caffeine", "WKUP" single and double). In addition, improvement in Multitasking Test (Delta30 for "WKUP" double, and Delta120 for "caffeine" and "WKUP" triple compared to placebo) was observed. "WKUP" triple also showed significant improvement for "memory" when compared to placebo (Delta120). Compared to "caffeine", WKUP GT did not increase systolic blood pressure. "WKUP GT" showed improvements for attention, memory, psychomotor and executive function tasks after lunch without increase in pulse rate.

Impact of blood meals taken on ivermectin-treated livestock on survival and egg production of the malaria vector Anopheles coluzzii under laboratory conditions.

Treatment of livestock with endectocides such as ivermectin is viewed as a complementary vector control approach to address residual transmission of malaria. However, efficacy of this treatment may vary between animal species. Hence, our purpose was to investigate the effects of ivermectin treatments of common livestock species on life history traits of the opportunistic malaria vector Anopheles coluzzii. Sheep, goats and pigs were treated using injectable veterinary ivermectin formulation at the species-specific doses (recommended dose for all species and high dose in pig). Mosquito batches were exposed to treated and control (not injected) animals at different days after treatment. Daily mosquito mortality was recorded and fecundity assessed through the count of gravid females and the number of eggs they developed. The recommended dose of ivermectin induced a significant decrease in mosquito survival for up to 7 days after injection (DAI), with a decrease of 89.7%, 66.7%, and 48.4% in treated pigs, goats and sheep, respectively, compared to control animals. In treated pigs, the triple therapeutic dose decreased mosquito survival of 68.97% relatively to controls up to 14 DAI. The average number in gravid females Anopheles that survived after feeding on treated animals were reduced when blood-meals were taken on sheep (2.57% and 42.03% at 2 and 7 DAI), or on goats (decrease of the 28.28% and 73.64% respectively at 2 and 7 DAI). This study shows that ivermectin treatments to animals negatively impacts An. coluzzii life history traits and could reduce vector densities in areas where livestock live near humans. However, due to short-term efficacy of single dose treatments, repeated treatments and potentially increased dosages would be required to span the transmission season. The use of long-acting ivermectin formulations is discussed as a mean for extending efficacy while remaining cost effective.

Insufficient anti-spike RBD IgA responses after triple vaccination with intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2

ObjectivesThis study aims to examine whether the parenterally administered mRNA-based COVID-19 vaccines can induce sufficient mucosal-type IgA responses to prevent SARS-CoV-2 transmission. MethodsWe examined the longitudinal kinetics of SARS-CoV-2 spike RBD-specific IgA and IgG responses in sera of Japanese healthcare workers (HCWs) after receiving two doses and the third dose of BNT162b2 mRNA vaccines. During the prospective cohort study, Omicron breakthrough infections occurred in 62 participants among 370 HCWs who had received triple doses of the vaccine. Pre-breakthrough sera of infected HCWs and non-infected HCWs were examined for the levels of anti-RBD IgA and IgG titers. ResultsThe seropositivity of anti-RBD IgA at 1 M after the second vaccine (2D-1M) and after the third dose (3D-1M) was 65.4% and 87.4%, respectively, and wanes quickly. The boosting effect on anti-RBD Ab titers following breakthrough infections was more notable for anti-RBD IgA than for IgG. There were partial cause-relationships between the lower anti-RBD IgA or IgG at pre-breakthrough sera and the breakthrough infection. ConclusionsParenterally administered COVID-19 vaccines do not generate sufficient mucosal-type IgA responses despite strong systemic IgG responses to SARS-CoV-2. These results demonstrate the necessity and importance of reevaluating vaccine design and scheduling to efficiently increase oral or respiratory mucosal immunity against SARS-CoV-2.

Yield and energy efficiency in winter wheat agrocenosis under different fertilization systems in the conditions of the northern part of the Forest-Steppe

The influence of different types of fertilizers on the yield and energy efficiency of winter wheat cultivation was evaluated. It was found that the highest productivity was obtained under the organic-mineral fertilizer system, which involves the combined use of 12 t/ha of cattle bedding manure and mineral fertilizers in a dose of N100Р60К100, applied against the background of two-time fertilization with complex chelated fertilizers at a dose of 2 l/ha, where the yield was 5.67 t/ha, and when applying a double mineral dose (N100Р60К100) and a triple dose (N150Р90К150) – 5.76 and 6.00 t/ha respectively, which in terms of yield growth was lower than the NIR05 values. The combined use of litter manure and mineral fertilizers resulted in a synergistic effect, as winter wheat grain yields were 15–20 % lower when mineral and organic fertilizers were applied separately than when they were applied together. Increasing NPK doses by 1.5 times to N150P90K150 compared to N100P60K100 did not compensate for the lack of manure. Under the organic fertilizer system, the grain yield was the highest when OMBF was applied at a dose of 2 t/ha against a background of pea straw 3 t/ha, which amounted to 5.18 t/ha with an increase of 41 %, compared to the control (straw). The highest levels of energy efficiency were determined for the application of organic-mineral fertilizer of the organic brand in doses of 1 and 2 t/ha (5.4 and 5.3) and OMBF brand 4-4-4 in a dose of 1 t/ha (5.2). Under the organic-mineral system of fertilizing application of N50P30K50 and N100P60K100 at the background of 12 t/ha of manure established the index of energy efficiency at the level of 3.4 and 3.7 units, respectively. Application of cattle manure at a dose of 12 t/ha did not provide a significant difference in crop energy, compared to the variant 6 t/ ha – 75755 and 73305 MJ/ha respectively, but due to increased energy inputs in production and application of more manure Kee was 3.9 and 4.6 respectively. Key words: cattle manure, fertilizers, OMBF, yield, mineral fertilizers, by-products, fertilizer system, energy efficiency.

Productivity and grain quality of winter wheat varieties depending on the fractional nitrogen top dressings and seeding rates

The study was carried out in the Kostroma region on soddy-podzolic soils with an average degree of cultivation in 2019–2022, with three repetitions of a field trial. The purpose of the study was to estimate the effect of different doses of nitrogen top dressings applied at critical phases of plant development on productivity and grain quality of winter wheat at seeding rates of 2, 4, and 6 million germinating kernels per hectare. There have been studied 5 winter wheat varieties of domestic breeding, such as ‘Moskovskaya 39’ (a standard variety), ‘Moskovskaya 40’, ‘Moskovskaya 56’, ‘Nemchinovskaya 57’ and ‘Nemchinovskaya 85’. The used agrotechnology corresponds to the zonal one in the Kostroma region. As a result of the study there has been identified a productivity variation from 2.9 to 3.7 t/ha depending on a variety. The largest productivity was formed by the variety ‘Moskovskaya 56’ with the use of a triple dose of nitrogen at a seeding rate of 6 million germinating kernels per hectare, which significantly exceeded the control variant on 0.5 t/ha. There has been estimated an influence of doses of nitrogen top dressings on technological parameters and flour properties of winter wheat grain. There has been found that the high content of crude protein (17.44–19.41 %), gluten (28.16–35.80 %) and hardiness (65.9–74.6 %) was demonstrated by the variety ‘Moskovskaya 40’. There has been also established a large hardiness of the variety ‘Nemchinovskaya 57’ (62.5–75.0 %). The largest 1000-grain weight (42.0–45.2 g) has been found in the variety ‘Moskovskaya 56’. Through three years of the study, there has been proved a stable response of the studied varieties to the improvement of productivity and n qualitative indicators as a result of the use of doses of nitrogen top dressings for winter wheat crops.

Evaluating probiotic efficacy on weight loss in adults with overweight through a double-blind, placebo-controlled randomized trial

The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month double-blinded, randomized, placebo-controlled trial, followed by a 3-month open phase, was conducted at Karolinska Institutet, Sweden. The probiotic compound AB001 was tested at two doses (single and double) and compared with placebo during the blinded phase, and at triple dose during the open phase. Eighty-one volunteers, 18–45 years old, with overweight were included. The primary outcome was change in weight. Secondary outcomes were changes in; BMI, waist circumference, blood pressure, blood lipids, glucose metabolism, liver enzymes, vitamin levels, and bowel habits. After 3 months (n = 81), no difference in weight, BMI, waist circumference, blood pressure, or biomarkers were observed between the groups. Forty-five individuals continued with triple dose. The group with initial single dose decreased 0.93 ± 4.73 kg (p = 0.34), and the group with double dose initially decreased 1.93 ± 3.70 kg (p = 0.027). Reported changes in bowel habits and gastro-intestinal problems were similar for all doses. The results indicate that a long-term use of at least double dose AB001 may be more beneficial for weight loss than lower doses. However, in the double blinded phase, no differences between groups were found. The probiotic compound AB001 was well tolerated and can safely be used up to double dose for 90 days followed by triple dose for 90 days.Trial registration: Clinicaltrial.gov NCT04897698, registered on 21 May 2021.

Evaluation of Antiviral Activity of Ivermectin against Infectious Bovine Rhinotracheitis Virus in Rabbit Model.

Infectious bovine rhinotracheitis (IBR) caused by bovine herpes virus 1 (BoHV-1) can lead to enormous economic losses in the cattle industry. Vaccine immunization is preferentially used to decrease its transmission speed and resultant clinical signs, rather than to completely stop viral infection. Therefore, a drug effective in treating IBR is urgently needed. Our previous work demonstrated that ivermectin significantly inhibited viral replication in a cell infection model. This study aimed to investigate its antiviral effects in vivo by using a rabbit infection model. The viral inhibition assay was first used to confirm that ivermectin at low concentrations (6-25 nM) could reduce viral titers (TCID50) significantly (p < 0.001) at 24 h post-infection. In rabbits, ivermectin was administrated with one to three doses, based on the recommended anti-parasite treatment dosage (0.2 mg/kg bodyweight) through subcutaneous injection at different days post-infection in the treated IBRV infection groups, while non-treated infection group was used as the control. The infected rabbits showed hyperthermia and other clinical signs, but the number of high-fever rabbits in the ivermectin treatment groups was significantly lower than that in the non-treated infection group. Furthermore, in ivermectin treatment groups, the cumulative clinical scores correlated negatively with drug doses and positively with delay of administration time post-infection. The overall nasal shedding time in ivermectin-treated groups was two days shorter than the non-treated challenge group. At the same time point, the titer of neutralizing antibodies in the treatment group with triple doses was higher than the other two-dose groups, but the difference between the treatment groups decreased with the delay of drug administration. Correspondingly, the serious extent of lung lesions was negatively related to the dosage, but positively related to the delay of drug administration. The qPCR with tissue homogenates showed that the virus was present in both the lung tissues and trigeminals of the infected rabbits. In conclusion, ivermectin treatment had therapeutic effect by decreasing clinical signs and viral shedding, but could not stop virus proliferation in lung tissues and trigeminals.

The change in agrochemical parameters of light gray forest soil from the level of mineral nutrition against the background of the aftereffect of liming in the conditions of the Nizhny Novgorod region

Relevance. The modern level of agricultural production is inconceivable without the use of chemicals: lime, mineral fertilizers. Liming acidic soils with the introduction of mineral fertilizers are important methods of complex land reclamation. Excessive acidity of the medium is one of the main reasons for low productivity of agricultural crops.Methods. The research was carried out in a long-term stationary experiment in the Nizhny Novgorod region on light gray forest soil. The influence of various doses of mineral fertilizers on the background of lime aftereffect on the productivity of the crop rotation link and changes in the acidity and degree of saturation of the soil bases were studied. The experience was based on a two-factor scheme.Results. The article says that by 2022, the aftereffects of various studied lime doses do not affect changes in the level of productivity of fodder crops of the crop rotation link: vicа-oats (vicоoats) + clover — clover 1 g. p. — clover 2 g. p. — clover 3 g. р. The total productivity is 19.6–20.8 t/ha by the factor of lime application in 1978. The greatest productivity of the studied crop rotation link is provided by triple doses of mineral fertilizers (24.4 t/ha by the standard), double and single doses provide the level of productivity of the crop rotation link in 20.0–20.1 t/ha by the standard, the cultivation of forage crops according to the natural agrophone provides a productivity level of 17.2 t/ha k. е.The applied lime doses, when laying the experiment, by 2022 do not affect the changes in agrochemical (exchange, hydrolytic density and the degree of saturation of the soil with bases) indicators in the twenty-centimeter soil layers. The use of triple and double doses of mineral fertilizers contributes to acidifying the soil compared to options without the use of mineral fertilizers and single doses.