Double Dose Research Articles

The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator DIBI in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI is a polymer with a polyvinylpyrrolidone backbone containing nine 3-hydroxy-1-(methacrylamidoethyl)-2-methyl-4(1H) pyridinone (MAHMP) residues per molecule and was given by intraperitoneal injection either as a single dose (80 mg/kg) immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24 h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Soybean Response to Seed Inoculation with Bradyrhizobium japonicum and/or Nitrogen Fertilization

Seed inoculation with symbiotic bacteria is a commonly employed practice in soybean cultivation. As a result, nodulation proceeds properly and plants self-supply atmospheric nitrogen, requiring either minimal or no additional nitrogen fertilization. The aim of the study was to investigate the response of soybeans to the application of the recommended or double dose of commercial inoculants (HiStick® Soy or TURBOSOY®) and/or mineral nitrogen fertilization compared to the untreated control. It was demonstrated that a double dose of the tested preparations had the most favorable effect on nodulation. However, the impact of weather conditions modified their effectiveness during the study years, which was especially visible in 2022. Sowing seeds without inoculation (control) resulted in the formation of sparse root nodules and consequently the lowest leaf area index (LAI) and soil plant analysis development (SPAD) measurements. In addition, the values of SPAD and LAI indices varied across the years of the study, indicating that weather conditions modified nitrogen uptake by plants. Overall, seed inoculation and/or nitrogen fertilization positively influenced the chemical composition of seeds compared to the control. The only decrease observed was in the oil content, while the double dose of HiStick® Soy preparation reduced the polyphenol content. The double dose of the tested inoculants had the most favorable impact on yield components and seed yield. However, applying inoculation at the recommended dose or in combination with nitrogen fertilization yielded similar or slightly worse results, depending on the year. Therefore, soybean seed inoculation should be recommended, although the effectiveness of the procedure will depend on various factors, including the type of inoculant, dosage, nitrogen fertilization, and weather conditions.

РОСТОВЫЕ ПРОЦЕССЫ КУКУРУЗЫ В ЗАВИСИМОСТИ ОТ УДОБРЕНИЙ НА ЧЕРНОЗЕМАХ ВЫЩЕЛОЧЕННЫХ РСО-АЛАНИЯ

In a long-term stationary field experiment that was established in 1971 on leached chernozem underlain by pebbles under conditions of field crop rotation the effect of systematic application of fertilizers for hybrid corn on plant growth processes was studied. It was found that the fertilized variants increased relative to the control: the growth of plants in height, the increase in leaf surface area, the accumulation of raw and dry biomass, increased photosynthetic potential. From the fertilized options, the calculated option N310P324K139 stood out for the better for the planned yield of 8.0 t/ha. In this variant at the end of the growing season the average height of the plant was 256 cm versus 247 cm in the control; the leaf surface area was 60056 versus 49392 m2/ha in the control; the photosynthetic potential was 3.08 million m2/ha.day versus 2.53 at the control; the amount of dry biomass is 22.5 versus 15.0 t/ha at the control. According to all indicators the double dose of N140P80K180 was in second place: respectively accordingly 255 cm, 56,808 m2/ha, 2.87 million m2/ha.day, 20.4 t/ha. Of the equivalent options a double dose of NPK had some advantage over manure+NPK (trend).

Deterministic Double Dose Vaccination Model of COVID-19 Transmission Dynamics - Optimal Control Strategies with Cost-Effectiveness Analysis

In this study, we propose a deterministic double dose vaccination model of COVID-19 transmission dynamics optimal control with cost-effectiveness analysis. It is imperative for decision-makers and the government to prioritize the application of preventive and control measures for COVID-19 based on efficiency and costbenefit analysis. This is pivotal in resource-constrained regions where the disease is endemic. Thus, this work is mainly devoted with the development and analysis of an optimal control for COVID-19 dynamics with five timevarying functions; first dose vaccination, second dose vaccination, personal protection, testing or screening, and treatment. The model is qualitatively analysed with the overall goal to minimize the spread of COVID-19 and the costs related to control implementation with the aid of optimal control theory. The effect of adopting each control intervention in each of the three distinct groups which are created by classifying all conceivable combinations of at least three control interventions is demonstrated through the numerical simulations of the optimality system. Using the average cost-effectiveness ratio and incremental cost-effectiveness ratio techniques, the most economical control intervention is determined for each group. The study reveals that when the resources are readily available, application of the strategy that combines optimal first dose vaccination, personal protection, screening or testing and treatment is as efficient as implementing all the five optimal control interventions simultaneously as they both avert the same number of infections. However, in resource-limited communities when joint implementation of only three interventions is possible, the strategy combining personal protection, testing or screening and treatment is strongly recommended. Out of all the intervention options being considered, this strategy is also affirmed to be the most cost-effective overall. Economic evaluation of the control intervention strategies further suggests that combination of first dose vaccination, second dose vaccination, testing or screening and treatment is the most cost-effective strategy when implementation of only four interventions is strictly allowed.

Frequency and Severity of Hypoglycemia Under Conditions of Increased Hypoglycemic Risk with Insulin Efsitora Alfa Versus Insulin Glargine Treatment in Participants with Type 2 Diabetes.

Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life. This was a single-site, open-label, two-period, fixed-sequence study in participants with type 2 diabetes (T2D) previously treated with basal insulin. The incidence, duration, and nadir glucose of hypoglycemia were assessed after treatment with efsitora versus insulin glargine (glargine) during three provocation conditions: 24-h prolonged fasting, prolonged fasting with exercise, and double dosing of study insulin. The 54 enrolled adults (BMI 21.8-39.7kg/m2, HbA1c 6.5-9.4%) achieved stable fasting glucose before undergoing provocation. Most hypoglycemic events were level 1 (≥ 54 to < 70mg/dL) and resolved spontaneously or after oral glucose. The incidences of level 1 hypoglycemia for efsitora and glargine were not significantly different: for prolonged fasting, the incidences were 44.7 vs. 42.6% and the difference in proportion was 2.1% (95% CI: - 17.2, 21.4); for prolonged fasting with exercise, the corresponding values were 65.9 vs. 50.0% and 15.9% (- 3.0, 34.8); for double dosing, the corresponding values were 68.1 vs. 61.7% and 6.4% (- 12.8, 25.6). Level 2 hypoglycemia (< 54mg/dL) was infrequent during both treatments and all provocations. No severe hypoglycemia was observed. Mean nadir glucose (range 62.8-66.3mg/dL) and hypoglycemia duration (range 76.6-115.2min) were also similar for the two treatments, depending on the provocation. Overall, weekly efsitora did not increase the incidence, duration, or severity of hypoglycemia compared to daily glargine during provocation periods in patients with T2D. ClinicalTrials.gov identifier NCT04957914.

Bifenthrin Residues in Table Grapevine: Method Optimization, Dissipation and Removal of Residues in Grapes and Grape Leaves.

The QuEChERS method was adjusted to determine bifenthrin residues in grapes and grape leaves. Extraction and cleanup procedures were optimized to decrease co-extracted materials and enhance the detection of bifenthrin. The method was validated per the European Union (EU) Guidelines criteria. Accuracy ranged from 98.8% to 93.5% for grapes and grape leaves, respectively. Precision values were 5.5 and 6.4 (RSDr) and 7.4 and 6.7 (RSDR) for grapes and grape leaves, respectively. LOQs (the lowest spiking level) were 2 and 20 µg/kg for grapes and grape leaves, respectively. Linearity as determination coefficient (R2) values were 0.9997 and 0.9964 for grapes and grape leaves, respectively, in a matrix over 1-100 µg/L range of analyte concentration. This was very close to the value in the pure solvent (0.9999), showing the efficiency of the cleanup in removing the co-extracted and co-injected materials; the matrix effect was close to zero in both sample matrices. Dissipation of bifenthrin was studied in a supervised trial conducted in a grapevine field during the summer of 2023 at the recommended dose and double the dose. Dissipation factor k values were 0.1549 and 0.1672 (recommended dose) and 0.235 and 0.208 (double dose) for grapes and grape leaves, respectively. Pre-harvest interval (PHI) was calculated for the Maximum Residue Limit (MRL) values of the EU database. Residues of bifenthrin were removed effectively from grapes using simple washing with tap water in a laboratory study. Residues reached the MRL level of 0.3 mg/kg in both washing treatments, running or soaking in tap water treatments for 5 min. Removal from leaves did not decrease residue levels to the MRL in grape leaves.

Treatment specifics for sialadenosis of the parotid glands in patients undergoing eradication therapy

Relevance. Treating patients with comorbid pathologies of the parotid salivary glands (PSGs) and the gastrointestinal tract presents a significant clinical challenge. Sialadenosis commonly develops in acid-dependent diseases associated with H. pylori (HP) infection, often manifesting as complaints of dry mouth. This condition leads to a reduction in local immunological defense due to decreased levels of sIgA, which is predominantly sourced from parotid secretion. Gastroenterologists typically prescribe eradication therapy that includes a proton pump inhibitor (PPI), which, according to its pharmacodynamic properties, can cause drug-induced xerostomia.Material and methods. A total of 115 individuals with sialadenosis of the PSGs and HP infection, confirmed by a positive urease rapid test in parotid secretion, aged 46.42 ± 6.21 years, were examined. The participants were randomly assigned into groups based on the prescription of absorbable gingival collagen membranes and the dose of a complex immunoglobulin preparation (CIP). The groups were as follows: Group I – 35 individuals without local therapy; Group II – 40 patients receiving 30 mg CIP; Group III – 40 patients receiving 60 mg CIP. Additionally, a control group consisting of 20 healthy individuals aged 44.46 ± 4.12 years was included. Gastroenterologists prescribed a standard triple eradication regimen, which included a proton pump inhibitor (PPI) at double dosage, 1000 mg amoxicillin, and 500 mg clarithromycin, taken twice daily for 14 days. All participants underwent comprehensive dental examinations at various stages: diagnosis, day 14 of eradication, and days 21 and 28 of observation.Results. A significant increase in PSG sialometry and sIgA levels in parotid secretion was observed in patients using absorbable gingival collagen membranes and CIP in addition to standard treatment. At a CIP dose of 60 mg, a negative urease rapid test was determined in parotid secretion by day 14, while at 30 mg, this occurred by day 21, confirming the effectiveness of the therapy.Conclusion. Treating patients with PSG sialadenosis undergoing eradication therapy requires a comprehensive interdisciplinary approach. It is necessary to include absorbable gingival collagen membranes and CIP at a dose of 60 mg twice daily for 21 days.

Comparative analysis of the addition of empagliflozin versus doubling the furosemide dose in decompensated heart failure.

This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARB), as well as mineralocorticoid receptor antagonists (MRA), for heart failure with reduced ejection fraction (HFrEF) who present to the emergency department with decompensated heart failure. This study is a single-center and prospective analysis. A total of 980 decompensated heart failure (HFrEF) patients receiving optimal medical therapy (OMT) according to the 2021 European heart failure guidelines were randomized in a 2:1 ratio into the furosemide and empagliflozin treatment arms. The analysis includes patient clinical characteristics, laboratory results, and echocardiographic data. Factors influencing rehospitalization were identified through multivariate Cox regression analysis. Log-rank analysis was employed to assess factors affecting rehospitalization. The mean age of the patients was 67.9years, with 52.1% being men. There was no significant impact of demographic, clinical, or echocardiographic factors on rehospitalization at 1 month; only the effect of treatment subgroups on rehospitalization was observed (p = 0.039). Significant echocardiographic and clinical improvements were seen in both treatment arms. The empagliflozin group exhibited significant improvements in 6-min walk distance, heart rate, body weight, NT-pro BNP levels, and eGFR level compared to the furosemide group. The rate of rehospitalization in the first month was significantly lower in those receiving empagliflozin (28.7%) compared to those receiving a double dose of furosemide (40.2%) (log-rank p = 0.013). This study provides valuable insights into the management of decompensated HFrEF and demonstrates that SGLT2 inhibitors offer benefits beyond glycemic control in this patient group. The significant reduction in rehospitalization rates and improvements in echocardiographic parameters underscore the potential of SGLT2 inhibitors in reducing acute heart failure episodes.

Evaluating the impact of double dose vaccination on SARS-CoV-2 spread through optimal control analysis

This paper presents a new nonlinear epidemic model for the spread of SARS-CoV-2 that incorporates the effect of double dose vaccination. The model is analyzed using qualitative, stability, and sensitivity analysis techniques to investigate the impact of vaccination on the spread of the virus. We derive the basic reproduction number and perform stability analysis of the disease-free and endemic equilibrium points. The model is also subjected to sensitivity analysis to identify the most influential model parameters affecting the disease dynamics. The values of the parameters are estimated with the help of the least square curve fitting tools. Finally, the model is simulated numerically to assess the effectiveness of various control strategies, including vaccination and quarantine, in reducing the spread of the virus. Optimal control techniques are employed to determine the optimal allocation of resources for implementing control measures. Our results suggest that increasing the vaccination coverage, adherence to quarantine measures, and resource allocation are effective strategies for controlling the epidemic. The study provides valuable insights into the dynamics of the pandemic and offers guidance for policymakers in formulating effective control measures.

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.

Tamsulosin 0.8 mg daily dose in management of BPH patients with failed tamsulosin 0.4 mg monotherapy and unfit for surgical intervention

AimThis study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention.Materials and methodsBetween November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment.ResultsAll 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively.ConclusionDouble-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.

A spectrometric analysis of variedly purified cinnabar in a siddha drug- linga chendhooram.

A siddha drug, linga chendhooram was prepared from cinnabar (lingam) and Citrullus colocynthis L. The transition of heavy metals concentration throughout theprocess were analysed to comprehend the significance ofdrug preparatory methods. In addition to that the main constituent cinnabar was purified from two different methods to comparatively analyse the significance of purification methods. Atomic absorption spectrometric studies were employed to obtain the concentration of class I heavy metals (lead, arsenic, cadmium and mercury) in all five samples- raw cinnabar (R), cinnabar purified (P1 and P2) from purification method 1 and 2, linga chendhooram (D1 and D2) prepared from P1 and P2. Based on the permissible limits given by The Ayurvedic Pharmacopoeia of India, except cadmium the concentrations of all other three heavy metals were found to be above the limit in P1, P2, D1 and D2. According to the oral Permitted Daily Exposure values for elemental impurities given in ICH Q3D(R1) Guidelines, D1 was within the permissible limits for both single and double oral doses whereas D2 showed a slight increase in the concentration of lead in a single oral dose itself. The drug preparatory method showed a reduction of the heavy metals concentration and comparative analysis of the purification methods revealed a substantial reduction of heavy metals concentration in the end drug D1 when compared with D2 showing that the methods of purification and drug preparation in siddha system plays a vital role in reducing the concentrations of heavy metals accordingly.

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.

Dissipation pattern of tetraniliprole in/on green chilies

Field and lab experiments explored tetraniliprole dissipation in chili plants. A supervised trial in Devarayapuram village, Coimbatore, assessed the CO2 chili variety (December–March 2018–2019). Using the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method and ultra-high-performance liquid chromatography (UHPLC), samples were collected up to 15 d post-application. Initial tetraniliprole deposits on chili fruits, 1-h post-spray, were 0.898 and 1.271 μg g−1 at single and double doses. Over 80% dissipated within 5 d, reaching below detection limits by day 7 and 10 for single and double doses, respectively. Transformation analysis favored first-order kinetics. Tetraniliprole half-life on chili fruit was 1.49 and 1.53 d at recommended and double doses. The safe waiting period was 4.16 and 5.04 d for 60 and 120 g a.i ha−1. This study provides insights into tetraniliprole dynamics in chili plants, crucial for effective pesticide management.

Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience

ObjectivesTo report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research Design and MethodsEighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. ResultsOverall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. ConclusionsThe use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.

Optimizing phosphorus fertilization for two commonly grown ground covers: creeping jenny and periwinkle

Growing nursery plants in containers usually requires the addition of fertilizer to achieve optimal growth. However, misconceptions among growers often lead them to apply quantities of fertilizers exceeding the recommended dose, resulting in nutrient runoff and increased production costs. Reducing fertilizer application is beneficial to have healthy plants and environment as well as to save on fertilizer costs. In this study, we wanted to determine the minimal level of phosphorus (P) required to grow bedding plants i.e. Lysimachia nummularia ‘creeping jenny’ (moneywort) and Vinca minor ‘Bowles’ (periwinkle) in nursery. The plants were grown within a greenhouse in a mixture of peat moss, vermiculite, and rice hulls (3:1:1 v/v) substrates and subjected to various P treatments. The treatments included single dose of 1, 3, or 6 mg/L of P, double doses of 3 or 6 mg/L of P, or a control that received 6 mg/L of P at each irrigation. The results indicated that single dose of 6 mg/L of P had similar fresh weight compared to control in both taxa. Reducing P application further to a single dose of 1 and 3 mg/L reduced fresh weight and leaf area in both groundcovers however did not reduce their stem length or physiological parameters such as Soil Plant Analysis Development (SPAD) and normalized difference vegetation index (NDVI). Phosphorus concentration in the plant tissue at maturity was lower in all treatments than control for both the taxa. During the study period, control plants received 26 times the dose of P compared to plants receiving 6 mg/L of P once. Therefore, this study outlines the possibility of reducing P fertilizer application while growing these groundcovers in nurseries for sale.

Safety and effectiveness of single- versus double-dose of seasonal influenza vaccine in kidney transplant recipients: a randomized clinical trial

Introduction. Influenza virus poses significant risks to immunocompromised individuals such as those who have received organ transplants and are undergoing immunosuppressive treatment to prevent transplant rejection. Therefore, annual influenza vaccination is recommended for these individuals. This study aimed to comparison of safety and effectiveness of single- versus double-dose of seasonal influenza vaccine in kidney transplant recipients. Materials and methods. This randomized clinical trial involved 50 kidney transplant recipients at Imam Khomeini Hospital. Participants were randomly assigned to two groups: those receiving a single dose (standard dose) and those receiving a double dose of the seasonal flu vaccine. Serum samples were collected before and 4 weeks after vaccination to measure influenza AB-related antibodies. Sixteen patients were excluded from the study. The trial focused on evaluating the vaccine safety and immunogenicity, as well as documenting any local and systemic side effects following vaccination. Results. The results indicated no significant difference in gender, age, and type of immunosuppressive drug used between the single- and double-dose groups (p 0.05). No significant difference in post-vaccination adverse effects, such as injection site pain (p = 0.21) between the two groups. The seroconversion rates (change from IgG 9 IU/µL to IgG 11 IU/µL) for IgG Influenza A were 12.5% (n = 2) in the single-dose group and 26.7% (n = 4) in the double-dose group, and for IgG Influenza B, they were 11.8% (n = 2) and 21.4% (n = 3), respectively. Conclusion. A double dose of the influenza vaccine slightly enhanced the immune response in kidney transplant patients without causing any adverse side effects.

Dissipation, processing factors and dietary risk assessment of the bioinsecticide abamectin in herbal plants belonging to Lamiaceae family from open field to herbal tea infusion

Abamectin, the mixture of avermectin B1a and B1b, is widely used as a bioinsecticide and is an alternative to chemical pest control from insects. To our knowledge, its behaviour is not fully recognized, especially in herbs. Thus, the objective of this study was to investigate the environmental fate of abamectin in herbal plants belonging to the Lamiaceae family, its dissipation in open field studies laboratory processing treatments and dietary risk assessment. Three medicinally and culinary important species of herbs: Melissa officinalis L., Mentha × piperita L. and Salvia L. were treated with single and double dose than recommended on the label during their cultivation (BBCH 11–29). Residues were monitored using the QuEChERS method followed by the LC-MS/MS. The dissipation pattern of the sum of avermectin B1a and B1b and their persistence were observed 14 d after spraying. Abamectin decline was very rapid in plants and followed the first-order kinetics model. The half-life (t1/2) was in the range of 0.96–1.08 d (single dose) and 0.93–1.02 d (double dose). The pre-harvest intervals (decrease to the level of 0.01 mg kg−1) were 7.29–7.92 d at single and 7.99–8.64 d at double dose application. Herbal infusion preparation in previously washed and dried mint, lemon balm and sage leaves was the key processing step in the removal of abamectin residues. The reduction of initial deposits after single dose treatment was noted up to 65% (PF = 0.35–0.67) and up to 79% after double dose application (PF = 0.21–0.72) in herbal tea. Acute risk assessment of children and adults for the highest residues in EFSA PRIMo model at single and double dose expressed as hazard quotients (HQ) were <1, indicating no risk to humans via consumption of the herbal products. The data provide a better understanding of abamectin behaviour in herbal plants and can help assure herbs' safety for consumers.

Lack of detectable sex differences in the mitochondrial function of Caenorhabditis elegans

BackgroundSex differences in mitochondrial function have been reported in multiple tissue and cell types. Additionally, sex-variable responses to stressors including environmental pollutants and drugs that cause mitochondrial toxicity have been observed. The mechanisms that establish these differences are thought to include hormonal modulation, epigenetic regulation, double dosing of X-linked genes, and the maternal inheritance of mtDNA. Understanding the drivers of sex differences in mitochondrial function and being able to model them in vitro is important for identifying toxic compounds with sex-variable effects. Additionally, understanding how sex differences in mitochondrial function compare across species may permit insight into the drivers of these differences, which is important for basic biology research. This study explored whether Caenorhabditis elegans, a model organism commonly used to study stress biology and toxicology, exhibits sex differences in mitochondrial function and toxicant susceptibility. To assess sex differences in mitochondrial function, we utilized four male enriched populations (N2 wild-type male enriched, fog-2(q71), him-5(e1490), and him-8(e1498)). We performed whole worm respirometry and determined whole worm ATP levels and mtDNA copy number. To probe whether sex differences manifest only after stress and inform the growing use of C. elegans as a mitochondrial health and toxicologic model, we also assessed susceptibility to a classic mitochondrial toxicant, rotenone.ResultsWe detected few to no large differences in mitochondrial function between C. elegans sexes. Though we saw no sex differences in vulnerability to rotenone, we did observe sex differences in the uptake of this lipophilic compound, which may be of interest to those utilizing C. elegans as a model organism for toxicologic studies. Additionally, we observed altered non-mitochondrial respiration in two him strains, which may be of interest to other researchers utilizing these strains.ConclusionsBasal mitochondrial parameters in male and hermaphrodite C. elegans are similar, at least at the whole-organism level, as is toxicity associated with a mitochondrial Complex I inhibitor, rotenone. Our data highlights the limitation of using C. elegans as a model to study sex-variable mitochondrial function and toxicological responses.

Residues determination, risk assessment, and dissipation behavior of myclobutanil formulation on apple.

This study aimed to investigate the dissipation pattern, risk assessment, and waiting period of myclobutanil on apple fruit (Malus domestica Borkh.) under temperate conditions in Kashmir, India. The study involved the application of myclobutanil 10 WP at a single recommended dosage (125 g a.i.ha-1) and double dosage (250 g a.i.ha-1) on Red Velox apple trees, 2 months before harvest. GC equipped with an electron capture detector was used to analyze myclobutanil residues in fruit samples. The study revealed that myclobutanil, at both recommended and double recommended doses, dissipated rapidly and became nondetectable after 55 and 60 days, respectively. The waiting period for myclobutanil application was determined to be 12.41 days for the single dose and 25.58 days for the double dose, respectively. These waiting periods were based on the maximum residue limit of 0.6 ppm as prescribed by the Codex Alimentarius Commission, Food Safety and Standards Authority of India, and European Commission. The study concludes that myclobutanil 10 WP is safe for consumers at both recommended and double recommended doses when applied 2 months before harvest. Risk assessment, considering the average daily apple consumption in India and theoretical maximum residue contributions (TMRCs), indicates negligible health hazards even at double the recommended dosage. The calculated TMRC values at Day 0 were significantly below the maximum permissible intake. For average and maximum myclobutanil residues at single and double doses, the TMRC values were found to be 0.0069 and 0.0070 mg day-1 person-1 and 0.0105 and 0.0106 mg day-1 person-1, respectively. These results indicate that myclobutanil, when used according to recommended dosages and waiting periods, poses minimal health risks to consumers. The study emphasizes the importance of prudent fungicide use to minimize fungicide residues on fruits, thereby ensuring their safety for consumption.