Double Dose Research Articles

Dissipation behaviors of deltamethrin, emamectin benzoate and hexythiazox in grape under field conditions

The objective of this study was to evaluate the dissipation kinetics of deltamethrin, emamectin benzoate, and hexythiazox in grapes. The QuEChERS method was employed and validated for the precise determination of these three pesticides using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Excellent linearity was observed with regression coefficients exceeding 0.998. Notably, the limits of quantification (LOQ) were significantly lower than the maximum residue limits (MRLs) established for grapes by the European Union. The QuEChERS method l recovered 93.23% of the pesticides with an acceptable RSD of 5.35% (n = 180), demonstrating its suitability for quantifying them in grapes. Half-lives of deltamethrin, emamectin benzoate, and hexythiazox in grapes were 2.62-2.68 days, 8.15-7.30 days, and 3.24-4.01 days, respectively, for both single and double doses. Residues of all pesticides fell below the MRLs by the preharvest interval. This suggests that their application can be considered safe for grapes, ensuring both pest control and consumer safety.

Dihydrotestosterone induces arterial stiffening in female mice

BackgroundAndrogens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER.MethodsThe impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15–16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8–9/group).ResultsIn cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P < 0.0001). In control mice or mice treated with a single or double dose of DHT, a dose-dependent increase in body weight was observed (control 22 ± 2 g, single dose 24 ± 2 g, double dose 26 ± 2 g; P = 0.0002). Intracarotid stiffness measured via pulse wave velocity showed a more than two-fold increase in both DHT-treated groups (control 1.9 ± 0.3 m/s, single dose 4.3 ± 0.8 m/s, double dose 4.8 ± 1.0 m/s). This increase in arterial stiffness occurred independent of changes in blood pressure (P = 0.59). Histological analysis of aortic sections using Masson’s trichrome showed a significant decrease in collagen between the control group (24 ± 5%) and the double dose group (17 ± 3%, P = 0.007), despite no changes in aortic wall thickness or smooth muscle content. Lastly, ddPCR showed that in vivo DHT treatment decreased aortic expression of both GPER (control 20 ± 5, single dose 10.5 ± 5.6, double dose 10 ± 4 copies/ng; P = 0.001) and ERα (control 54 ± 2, single dose 24 ± 13, and double dose 23 ± 12 copies/ng; P = 0.003).ConclusionsThese findings indicate that androgen promotes arterial stiffening and cardiovascular damage in female mice and is associated with decreased estrogen receptor expression. These data are important for transgender men, women using testosterone for fitness or reduced libido, as well as patients with polycystic ovarian syndrome.

Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding

BackgroundWe aimed to develop a publicly shared computational physiologically based pharmacokinetic (PBPK) model to reliably simulate and analyze radiopharmaceutical therapies (RPTs), including probing of hot-cold ligand competitions as well as alternative injection scenarios and drug designs, towards optimal therapies.ResultsTo handle the complexity of PBPK models (over 150 differential equations), a scalable modeling notation called the “reaction graph” is introduced, enabling easy inclusion of various interactions. We refer to this as physiologically based radiopharmacokinetic (PBRPK) modeling, fine-tuned specifically for radiopharmaceuticals. As three important applications, we used our PBRPK model to (1) study the effect of competition between hot and cold species on delivered doses to tumors and organs at risk. In addition, (2) we evaluated an alternative paradigm of utilizing multi-bolus injections in RPTs instead of prevalent single injections. Finally, (3) we used PBRPK modeling to study the impact of varying albumin-binding affinities by ligands, and the implications for RPTs. We found that competition between labeled and unlabeled ligands can lead to non-linear relations between injected activity and the delivered dose to a particular organ, in the sense that doubling the injected activity does not necessarily result in a doubled dose delivered to a particular organ (a false intuition from external beam radiotherapy). In addition, we observed that fractionating injections can lead to a higher payload of dose delivery to organs, though not a differential dose delivery to the tumor. By contrast, we found out that increased albumin-binding affinities of the injected ligands can lead to such a differential effect in delivering more doses to tumors, and this can be attributed to several factors that PBRPK modeling allows us to probe.ConclusionsAdvanced computational PBRPK modeling enables simulation and analysis of a variety of intervention and drug design scenarios, towards more optimal delivery of RPTs.

Effects of applying lime and phosphogypsum in soybean and wheat nutrition

This study aimed to assess the nutritional status of soybean and wheat and the relationship with grain yield and biometric components after lime and phosphogypsum (GY) reapplication. Treatments consisted of two lime application methods, surface liming and incorporated liming, to different levels of base saturation (BS) (44, 70, and 90%), in addition to surface liming to 70% BS associated with a standard dose (70GY1) or double dose (70GY2) of GY. Treatments were applied in 2012 and reapplied in 2016. The results refer to the 2018/2019 soybean season and the 2019 wheat season. Lime + GY treatment increased leaf area, plant height, leaf dry matter, and stem dry matter in soybean but had no effect on specific leaf area (235.4 cm2 g−1), stem diameter (6.08 mm), number of pods per plant (71.7), grain number per plant (165), or thousand grain weight (117 g). Liming to 90% BS reduced leaf manganese contents in both crops and leaf iron content in soybean. GY application improved the calcium status of both crops and the sulfur status of soybean. However, 70GY2 reduced leaf magnesium contents in soybean and wheat. Soil tillage without lime reduced wheat yield by 12% compared with no-till. Soybean yield correlated positively with leaf nitrogen (0.79), leaf phosphorus (0.91), leaf area (0.62), and thousand grain weight (0.65), whereas wheat yield correlated with leaf phosphorus (0.83), calcium (0.75), and sulfur (0.74). For improved soybean and wheat performance, it is preferable to apply lime and GY to the soil surface (70GY1), permanently maintaining no-till practices.

Safety and Immunogenicity of the Convacell® Recombinant N Protein COVID-19 Vaccine.

We have developed Convacell®-a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell's® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. Convacell® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell® is safe and highly immunogenic.

Varicella-Zoster Virus Infections: Epidemiology, Diagnosis and Vaccine Safety

Varicellovirus humanalpha3 (varicella-zoster virus; VZV), a member of the Orthoherpesviridae family, is a human pathogen that is widespread worldwide and has a preventive vaccine that has been used for decades. Primary infection causes chickenpox, in which VZV remains latent in ganglionic neurons after recovery. Primary VZV infection, which is generally associated with mild infections during childhood, can lead to severe and potentially life-threatening complications in newborns, immunocompromised individuals, or the elderly. In individuals whose cellular immunity against VZV decreases with advancing age or in immunocompromised individuals, VZV may reactivate and cause zoster. VZV vaccines, developed from live virus strains weakened by serial passages, have been added to national vaccination programs for the pediatric age group as single or double doses in many countries of the world, and have contributed to a significant decrease in VZV infections and associated complications throughout the world in the post-vaccination period. Apart from pediatric vaccines, live and recombinant herpes zoster vaccines have been developed and approved for use in adults aged 50 and over. Rare complications associated with VZV vaccines, which have been used safely for decades, may also occur. The main focus of this article is VZV vaccines, and in connection with these vaccines, it is aimed to provide an overview of the history, classification, epidemiology, clinic, complications, diagnosis, and treatment of VZV infections.

Residue estimation and dietary risk assessment of fenvalerate, novaluron, and profenofos in bell pepper grown under protected and open field conditions.

Residue studies were conducted in bell pepper crops (green and yellow bell pepper) to ensure the safe use of fenvalerate, profenofos, and novaluron (under open field and protected conditions) in randomized block design (RBD) following three applications at a 10-day interval over two consecutive years, 2021 and 2022. A robust analytical method was developed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS) for the determination of pesticide residues in bell pepper samples. The half-lives for fenvalerate were 2.47-2.87 and 2.50-3.03days on bell pepper under open field conditions, whereas the corresponding values for bell pepper under protected conditions were 3.84-4.58 and 4.17-4.71days, during 2021 and 2022, respectively. Profenofos displayed half-lives of 2.03-2.65 and 2.15-2.77days in open field conditions and 3.05-3.89 and 3.16-3.78days in protected conditions during 2021 and 2022, respectively. Similarly, novaluron had half-lives of 2.87-3.49 and 3.24-3.75days under protected conditions in 2021 and 2022, respectively. The maximum residue limits (MRLs) were calculated to be 0.6mg/kg for fenvalerate, while for profenofos it was 0.7mg/kg on bell pepper under open field conditions at double doses, at the proposed pre-harvest interval (PHI) of 3days. Likewise, for bell peppers grown under protected conditions, MRLs at the PHI of 3days were determined to be 0.8mg/kg for fenvalerate, 0.3mg/kg for novaluron, and 1.5mg/kg for profenofos. A dietary risk assessment study indicated that the percentage of acute hazard index (% aHI) was significantly lower than 100, and hazard quotient (HQ) values were below 1, signifying no acute or chronic risk to consumers. These findings underscore the safety of consuming bell peppers treated with fenvalerate, profenofos, and novaluron under the protected and open field conditions.

The Effectiveness of Intrauterine Treatment with Momordica charantia L. on Some Hormone Parameters in Repeat Breeder Cattle

Background: Repeated breeding is a substantial problem in dairy cattle affecting reproductive efficiency. The goal of the current study was to see how intrauterine treatment of phytotherapeutic plant extract affected some hormonal indicators and conception rates in dairy cattle with fertility issues. Methods: In the study, 40 repeat breeder (RB) cattle were randomly divided into two groups. Forty ml (0.25 g/mL) Momordica charantia L. (MC) extract was administered intrauterine to cattle in group I (n=20) and 40 ml of pure olive oil was administered intrauterine to cattle in group II (n=20) at a time. The control group, group III (n=20), was composed of healthy heifers. Endometrial smear samples were taken from all RB cattle for cytological examination before the treatment and all were stained with Giemsa. Estradiol (E2), progesterone (P4) and insulin-like growth factor (IGF-1) levels were assessed by collecting blood samples starting from intrauterine treatment on days 0, 7 and 14. After the last blood sample was collected, the estrus cycles of all cattle were synchronized through a double dose of PGF2α administration at 14-day intervals. GnRH was administered with single insemination at the 60th hour following the second PGF2α treatment. Result: Subclinical endometritis was determined in 82.5% (33/40) of RB cattle. Pregnancy rates in group I, group II and group III were determined as 55%, 35% and 35%.respectively.(P greater than 0.05). There was no significant difference in E2 values according to time and between groups. For P4, there were also no significant differences between three time-dependent measurements, but there was a difference in the 7th and 14th days of the groups (P less than 0.01). For IGF-1, significant differences were found between the three time-dependent measurements of the groups (P less than 0.001). In conclusion, it was observed that the MC extract treatment, especially in RB with SCE, can improve the pregnancy rate by positively affecting the increase in IGF-1 which is a key element of the extremely complex endocrine system.

Uroprotective and pain-relieving effect of dietary supplementation with micronized palmitoyl-glucosamine and hesperidin in a chronic model of cyclophosphamide-induced cystitis.

Feline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations. The current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug. Higher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson's trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine. PGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.

Effect of doubled dose administration of foot-and-mouth disease vaccine against heterologous virus infection in cattle.

Vaccination is a feasible approach for controlling foot-and-mouth disease (FMD). In FMD-free countries, vaccines are stored as a precautionary measure to control potential outbreaks. However, the challenge lies in pre-stocking optimal vaccines against the newly emerging strains. This study examined the potency of pre-stocked vaccines administered at elevated doses during emergencies. We vaccinated the cows with either a single or double trivalent vaccine dose containing two serotype O and one serotype A strains. Subsequently, vaccinated and unvaccinated cows were exposed to virulent strains of serotype O (O/JPN/2010; topotype Southeast Asia/Mya-98 lineage) or A (A/IRN/2016; topotype ASIA/G-VII lineage), which were genetically and antigenically distinct from the vaccine strains. Following challenge infections, all cows that received a single dose vaccination exhibited vesicular lesions with excreted viruses in the oral and nasal discharges. However, a substantial reduction was observed in the total clinical scores and virus titers in the sera and nasal discharges compared to those in the unvaccinated group. Cows receiving a doubled dose vaccination were completely protected from infection with O/JPN/2010 or demonstrated a significant decrease in viral shedding and clinical scores against A/IRN/2016. To note, vesicular lesions harbor significant amounts of viruses; thus, by mitigating their formation, viral transmission can be impeded, thereby slowing viral spread in the field. Furthermore, increasing the vaccine dose induced higher neutralizing antibody titers against heterologous strains. These findings suggest an alternative strategy for the effective management of future epidemics using pre-stocked vaccines.

Reduction of egg reappearance period of cyathostomins in naturally infected horses after increasing doses of ivermectin in Brazil: a grim picture for sustainable parasite control.

Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. A systematic review and network meta-analysis. Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. The study protocol was registered with INPLASY (registration number INPLASY2023120053).

Stochastic and Deterministic Models for Rubella Dynamics with Two Doses of Vaccination and Vertical Transmission

Rubella is a highly contagious viral disease that can be transmitted through contact with infected people or objects. If a pregnant woman is infected with rubella, the virus can be transmitted to the fetus, which can cause birth defects. To prevent rubella, children need to receive the MMR vaccine twice. In this study, we developed a deterministic and stochastic mathematical model to investigate the dynamics of rubella infection, considering vertical transmission and environmental factors. The model divides the population into five groups: susceptible, first vaccinated, protected, infected, and recovered. From the perspective of the qualitative behavior of the model, the model is bound to an invariant domain, and all solutions within the compartment are positive. We analyzed the equilibrium point of the model and its stability, and we determined the basic reproductive number using the next‐generation matrix. The basic reproductive number for the stochastic model is smaller than that for the deterministic model due to randomness. By comparing the two models in terms of the basic reproductive number, extending the deterministic model to a stochastic model can provide more realistic information about the disease, predict its dynamic propagation, and give suggestions for control mechanisms. Numerical simulations and sensitivity analyses were performed to study the influence of fundamental parameters, and the simulation results were displayed graphically using the MATLAB computer software. Parameter values were obtained from published papers, some of which were assumed. The simulation results show that the stochastic curve is not as smooth as the deterministic curve due to the randomness of the rubella. The consideration of the double vaccination dose and white noise intensity plays an important role in predicting disease status and minimizing and eradicating rubella. Therefore, reducing vertical infection and transmission rates and increasing vaccination and recovery rates will help to prevent and control the spread of rubella.

Distribuição de fertilizantes granulados em dosadores montados com helicoidal simples e duplo

ABSTRACT: The high dependence of agriculture on fertilizers demands an improvement in the processes involved, with the purpose of environmental and economic sustainability. The objective was to compare the performance of helical dosing mechanisms with two formulations of granulated NPK fertilizers at three operating speeds. During the experiment, we used an electronic and automated bench to evaluate the performance of the single helical and double helical dosing mechanisms, in a completely randomized design. This bench measured the overflow of the two formulations of granulated NPK fertilizers (04-14-08 and 04-30-10) under different angular velocities (1.11; 1.94; and 2.77 m s-1). On the tests, we collected flow data and submitted them to descriptive statistics, frequency histograms, and statistical process control. The single helical feeder, as the speed increased, exhibited greater homogeneity of granulated NPK fertilizer deposition, with 611 flaws ha-1 compared to 3763 flaws ha-1 in the double screw. Although, the speeds of 7.0 and 10.0 km h-1 generated an increase in the flow of both granular fertilizers, as expected, the 04-30-10 fertilizer obtained the most uniform distribution at the lowest speed.

Single Versus Double Dose Tamsulosin for Patients with Moderate or Severe Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: Prospective Randomized Study

Single Versus Double Dose Tamsulosin for Patients with Moderate or Severe Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: Prospective Randomized Study

Is less more? Intravenous immunoglobulin for pediatric immune thrombocytopenia.

Treatment of pediatric immune thrombocytopenia (ITP) is guided by the risk of bleeding. Intravenous immunoglobulin (IVIg) is one of the first-line therapy options for new-onset pediatric ITP. However, the exact optimal dose of IVIg has not been determined. This retrospective cohort study included all hospitalized children with newly diagnosed ITP receiving IVIg as first-line therapy during 2010-2020. We compared the safety and efficacy of two common IVIg dose regimens, 1 and 2 g/kg. Outcomes were short and long-term treatment responses and adverse events to the different doses. A total of 168 children were included in our cohort. Eighty-two children were treated with 1 g/kg of IVIg and 86 with 2 g/kg. There was no difference in sustained response (platelet count > 20 × 109, > 14 days) between the groups (74.3% vs 76.7%, respectively, p = 0.72) and maximal platelet counts following treatment (p = 0.44). No difference was found regarding the percentage of chronic ITP between the two groups (24.4% in the 1 g/kg group as compared to 17.4% in the 2 g/kg group; p = 0.34). Logistic regression analysis demonstrated there was no effect of the IVIg dose on treatment failure and development of chronic ITP. As anticipated, 47.7% of adverse events were in the 2 g/kg group and 32.9% in the 1 g/kg group, with borderline statistical significance (p = 0.06). The initial treatment of newly diagnosed pediatric ITP using a 1 g/kg IVIg regimen may give comparable results to the double dose of 2 g/kg in attaining a prolonged safe hemostatic threshold, without impacting the incidence of chronic disease.

The crop yield of spring wheat under conditions of the Aridized climate

Due to the global warming, massive aridization is observed in the Transbaikal territory, including Buryatia, as a result, agriculture is forced to function under conditions of a strict limit of atmospheric and soil moisture. In spring and early summer, the potential evaporation here is 3-5 times higher than the amount of rainfalls, which leads to crop shortages and to a harvest failure. Thus, it is necessary to use irrigation reclamation for the effective management of agricultural production in this territory. This work researches the manifestation of soil drought in alluvial meadow soil. The study of the effect of various doses of mineral fertilizers and maintenance of soil moisture at the lowest moisture level at 70% LMC and 80% LMC showed that maximum yield and minimum water consumption coefficient are provided by maintaining soil moisture above 80% LMC and fertilization with a doubled dose of nitrogen.

The double shared epitope: Its impact on clinical features and ultrasound findings in rheumatoid arthritis.

The link between the HLA-DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome-wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on RA and explore its clinical associations, including the response to abatacept. We evaluated RA patients treated with csDMARDs or abatacept for HLA-DRB1 typing, clinical characteristics at baseline, and disease activity and ultrasound findings over 12 months. Patients with the double SE (n = 12) had significantly higher anti-citrullinated protein antibody (ACPA) titers, higher total grayscale (GS) score, and power Doppler (PD) score at baseline than patients without the double SE. Patients with the double SE exhibited reduced rates of SDAI remission and pronounced improvements in multiple disease activity between baseline and 12 months, including SDAI, CDAI, total GS score, and total PD score. When focusing on abatacept-treated patients, the decreases in SDAI, CDAI, and total PD score between baseline and 12 months were significantly larger in patients with the double SE. Patients with the double SE exhibited distinct characteristics, increased disease activity, and improved response to abatacept treatment.

Characterisation of reproductive tract microbiome and immune biomarkers for bovine genital campylobacteriosis in vaccinated and unvaccinated heifers.

Bovine genital campylobacteriosis (BGC) is a globally important venereal disease of cattle caused by Campylobacter fetus subspecies venerealis. Diagnosis of BGC is highly challenging due to the lack of accurate diagnostic tests. To characterise the biomarkers for C. fetus venerealis infection, a total of twelve cycling heifers were selected and categorised as vaccinated (n = 6) with Vibrovax® (Zoetis™) and unvaccinated (n = 6). All heifers were oestrous synchronised with a double dose of prostaglandin (PGF2α) 11 days apart and when in oestrous intravaginally challenged with 2.7 x 109 CFU live C. fetus venerealis. DNA extracted from vaginal mucus samples was screened using a C. fetus qPCR and 16S rRNA was characterised using Illumina sequencing (V5-V8 region). Relative abundances of serum proteins were calculated using sequential window acquisition of all theoretical fragment ion spectra coupled to tandem mass spectrometry (SWATH-MS) for all heifers at three timepoints: pre-challenge, post-challenge and post-recovery. In 16S rRNA sequencing of vaginal mucus, Campylobacter spp. appeared two days following challenge in unvaccinated compared to 14 days in vaccinated animals, consistent with the qPCR results. Increased relative abundances of Firmicutes and Campylobacterota were identified after C. fetus venerealis challenge and were associated with C. fetus venerealis in vaccinated and unvaccinated heifers. Greater relative abundance of Streptococcus spp. was observed during oestrous rather than dioestrous. In both vaccinated and unvaccinated heifers, Acinetobacter spp. increased after challenge with higher abundance of Corynebacterium spp. in the vaccinated group. A total of 130 unique proteins were identified in SWATH analysis of the serum samples, and the number of differentially abundant proteins found was higher in the vaccinated group after recovery from infection compared to pre-and post-challenge (adjusted P < 0.05 and Log2FC > 0.2). Coglutinin, clusterin, HP homologs, vitamin D binding protein and fetuin B were identified as potential biomarkers for C. fetus venerealis infection and need further study to validate their efficiency as immune biomarkers for BGC.

Mathematical Analysis of Covid-19 with Double Dose Vaccination and Treatment

A compartmental model of covid-19 with double dose vaccine based on a system of non-linear ordinary differential equations is formulated and theoretically analyzed. The model is divided into eight compartmental classes, namely, susceptible (S), first dose vaccinated ( second dose vaccinated exposed (E), asymptomatic (A), symptomatic (I), hospitalized (H), and recovery (R). There are several kinds of approval vaccines, and each has a different efficacy and mechanism of action for reducing the outbreak of epidemic. Fortunately, there is a mathematical precise scale can be used as an indicator to determine whether the disease will be eradicated or persisted in the population, that is a basic reproduction number The next generation method (NGM) is used to compute , before vaccination, and after two doses were taken. Comparison the results shows -clearly- the positive effect of the intrinsic efficacy of vaccine on reducing , and hence on eradication the epidemic.