3-day Intervals Research Articles

Cucumber productivity depending on the use of microbiological preparations

Relevance. In the modern production of greenhouse products, with hydroponic cultivation of crops, one of the safe ways to increase the quantity, quality of cucumber products and plant protection is the use of microbiological preparations.Methodology. The purpose of our work was to assess the effect of a complex of microbiological preparations on the productivity of cucumber hybrids in winter and spring turnover. The study was conducted in industrial greenhouses during 2021-2022. Long-fruited (Lohengrin F1) medium-fruited (Mewa F1 and Svyatogor F1) and short-fruited (Valigora F1) parthenocarpic cucumber hybrids were selected as research objects. The preparations were applied five times, at 30-day intervals throughout the entire growing period, the first application when planting plants in the production department. Measurements of economically valuable and chemical indicators were carried out weekly. Descriptive statistics and ANOVA methods were used for statistical data analysis.Results. As a result of the research, a positive stimulating effect of a complex of microbiological preparations on the accumulation of raw and dry biomass, an increase in yield and its quality in the studied cucumber hybrids was revealed. The final yield when applying microbiological preparations increased on average from 4.1 to 5.5 kg/m2 in all cucumber hybrids over the two years of study, while the yield of standard products in the total crop structure increased by 2.7% - 6.4%.

Growth, yield and anatomy of alpinia calcarata (<em>Heen Araththa</em>) as affected by irrigation frequency

Alpinia calcarata, often known as Heen Araththa, is a precious medicinal plant owing to its chemical properties in herbal treatments. The growth, yield and anatomical features related to the synthesis and accumulation of secondary metabolites of this plant are highly affected by drought stress. Therefore, this work investigated the influence of irrigation frequency on growth, yield and selected anatomical features of A. calcarata. Five levels of irrigation frequencies including daily watering (T1), 7-day (T2), 14-day (T3), 21-day (T4) and 28-day (T5) intervals were investigated in a protected plant house under controlled environmental conditions. A. calcarata rhizomes with a similar number of sprouting buds planted in common potting media (topsoil: sand: compost- 1:1:1) were arranged in Completely Randomized Design in triplicates. After three weeks of establishment, five distinct irrigation frequencies were implemented, with pots being watered daily up until that point. Growth and yield parameters (shoot height (cm), number of roots, number of shoots, number of leaves per shoot, leaf area (mm2), rhizome dry weight (g)) and the anatomical parameters (root epidermis thickness (μm), rhizome epidermis thickness (μm) and oil cell density (μm2)) were collected 10 weeks after establishment. Data were analyzed using Analysis of Variance (ANOVA) employing the SAS analysis system. Results revealed that all selected growth, yield and anatomical parameters of A. calcarata were significantly (p<0.05) affected by irrigation frequency. Significantly (p<0.05) the highest mean shoot height (20.8cm), mean number of roots (11.3), mean number of shoots (6.8), mean rhizome dry weight (9.3g) and significantly (p<0.05) higher mean leaf area (24.9mm2) and mean number of leaves per shoot (4) of A. calcarata weregiven by 14-day irrigation frequency. It was also observed that the mean root epidermis and rhizome thickness of A. calcarata gradually increased in response to escalating drought stress. In contrast, the highest oil cell density was observed under the lowest drought stress. Based on the results, it can be concluded that the most promising irrigation frequency for higher growth and yield of A. calcarata is watering with 14-day intervals. Daily watering appeared to be the most suitable treatment to enhance oil cell density associated with secondary metabolite production of A. calcarata.

Effect of Nutrient Management During the Nursery Period on the Growth, Tissue Nutrient Content, and Flowering Characteristics of Hydroponic Strawberry in 2022

The objective of a strawberry nursery is to produce numerous runners and improve the quality of the runner plants, ensuring their uniformity and health. About 80% of the strawberry nurseries in Wanju-gun, Republic of Korea, are cultivated by the growers themselves, which results in variations in the cultivation techniques. Different methods are employed to reduce the nitrogen levels to promote floral bud initiation in the later nursery stage, and these methods vary between farms. This study was conducted on the ‘Sulhyang’ cultivar (Fragaria × ananassa Dutch. cv. Sulhyang) to measure the nutrient content in runner plants obtained from eight growers using various cultivation methods, supply EC levels, nutrient solution termination times, etc., and to correlate the nutrient levels with floral bud initiation during the nursery period. Four investigations were conducted at 15-day intervals from Julian day 214 (2 August) to Julian day 259 (16 September) in 2022, focusing on nutrient management during the nursery period, runner plant growth, petiole nitrate nitrogen content (NO3-N), and soluble solid content (SSC). The NO3-N content decreased, and the SSC/NO3-N ratio increased near the transplanting period, as assessed using a rapid inorganic nutrient diagnostic device. The proportion of runner plants that had advanced to stage 3 or above in floral bud initiation was investigated using a stereomicroscope. As a result, differences in the percentage of floral bud initiation were confirmed based on the varying nutrient management among the farms. In this study, on Julian day 243 (31 August 2022), there was a strong negative correlation (r = −0.86, r2 = 0.73) between the NO3-N content in the runner plants and the percentage of floral bud initiation. These results emphasize the importance of nutrient management during the nursery period, especially for strawberry self-propagating growers, and demonstrate a strong correlation between nutrient content and floral bud initiation in strawberries.

The Effects of Carbohydrate Mouth Rinse on Psychophysiological Responses and Kinematic Profiles in Intermittent and Continuous Small-Sided Games in Adolescent Soccer Players: A Randomized, Double-Blinded, Placebo-Controlled, and Crossover Trial.

Mouth rinsing (MR) with a carbohydrate solution is one of the most popular methods athletes use to improve their game-based performance due to its acute ergogenic effect. This study aimed to evaluate the effects of the carbohydrate MR intervention on psychophysiological responses and kinematic profiles during intermittent (INT) and continuous (CON) 4-a-side small-sided soccer games (SSGs). Thirty-two adolescent soccer players (age: 16.5 ± 0.5 years) played six bouts of 4-a-side SSGs with MRINT or MRCON at 3-day intervals in a randomized, double-blinded, placebo-controlled, and crossover study design. Psychophysiological responses and kinematic profiles were continuously recorded during all games. The rating of perceived exertion (RPE), the rating scale of mental effort (RSME), and the physical enjoyment scores (PES) were also determined at the end of each game. The MRCON induced higher psychophysiological responses such as RPE, internal training load (ITL), and RSME (p ≤ 0.05, d values ranging from 0.50 to 1.04 [small to moderate effect]). Conversely, the MRINT induced higher PES (p ≤ 0.05, d values = 1.44 [large effect]) compared to MRCON. Although the MR intervention led to similar improvements in the performance of 4-a-side MRINT and MRCON, there was no significant difference between the groups. Our results suggest that the MR intervention can be used as an effective ergogenic supplement for acute game performance enhancement, regardless of the game's structure.

Newcastle Disease Virus Expressing Cap Gene of Porcine Circovirus Type 2 Confers Protection in Mice and Induced Long-Lasting Neutralizing Antibodies in Pigs.

Background/Objectives: Porcine Circovirus 2 (PCV2) infection poses significant health and economic challenges to the global swine industry. The disease in pigs leads to lymphoid depletion, resulting in immunosuppression and increased susceptibility to co-infections with other bacterial and viral pathogens. This study evaluated the efficacy of two novel recombinant Newcastle disease virus (NDV) strain R2B vectored vaccines that express the cap gene of PCV2 alone and along with the transmembrane and cytoplasmic tail (TMCT) domains of the NDV F gene. The efficacy of the vaccine candidates was studied in mouse and pig models. Methods: Six-week-old BALB/c mice were divided into five groups and immunized intramuscularly three times at 14-day intervals with various vaccine candidates, namely rNDV-R2B-PCVcap-TMCT, rNDV-R2B-PCVcap, and CircoFLEX commercial vaccine, along with controls. Following immunization and PCV2d virus challenge, multiple assays assessed the immune responses in animal trials. In the pig animal trial, pigs were divided into four groups: a control group (PBS), NDV-vectored PCVcap-TMCT group, NDV-vectored-PCVcap group, and CircoFLEX vaccine group. Pigs were immunized intramuscularly twice at 28-day intervals. Blood samples were collected at regular intervals over 70 days to evaluate the humoral and cell-mediated immune responses. Results: Both mice and pigs' trials indicated that the NDV-vectored PCV2 cap-TMCT vaccine candidate elicited superior immune responses. In mice, the rNDV-R2B-PCVcap-TMCT group showed enhanced humoral and cellular immunity, increased PCV2-specific antibody levels, higher CD4+/CD8+ ratio, elevated IFN-γ and TNF-α levels, decreased IL-10 levels, reduced viral loads, and minimal histopathological changes. In pigs, the NDV-vectored PCVcap-TMCT group demonstrated better antibody responses, cytokine profiles (IFN-γ and IL-10), and higher levels of PCV2-specific neutralizing antibodies against the PCV2a, PCV2b and PCV2d genotypes when compared to other groups. Conclusions: These findings suggest NDV-vectored PCVcap-TMCT vaccine candidate, expressing the cap gene of PCV2 along with the TMCT domain, offers a promising alternative for protecting against PCV2 infection, potentially addressing the challenges posed by emerging PCV2 strains in the swine industry.

Protocol for a prospective, longitudinal cohort study on the incidence of dementia after the onset of delirium in patients with mild cognitive impairment: MDDCohort (Mild Cognitive Impairment Delirium Dementia)

BackgroundMild cognitive impairment (MCI) is a major risk factor for delirium. Few studies with mid- to long-term follow-up periods have examined delirium, MCI, and the conversion of MCI to dementia. This prospective, longitudinal cohort study aims to assess the incidence of dementia after delirium onset in patients with MCI and to develop an artificial intelligence algorithm for predicting the conversion of MCI to dementia.MethodsA 30-day evaluation for delirium will be performed for adults aged ≥ 65 years diagnosed with MCI who score 18–23 on the Korean Mini-Mental State Exam. Individuals exhibiting delirium at least once will be classified into the delirium group and the remainder into the non-delirium group. Over 3 years, patients will undergo follow-ups for survival and conversion to dementia at 30-day intervals to analyze risk factors for delirium and clinical outcomes. Differences between the two groups will be analyzed using the chi-square and independent t-tests. Kaplan-Meier survival and Cox proportional hazard regression will be used to assess the effects on 30-day, 60-day, 12-month, 24-month, and 36-month mortality, whereas linear regression will be used to assess the length of stay at long-term care facilities and medical costs.DiscussionThe results will emphasize the importance of preventing delirium in MCI patients, and preventive interventions can be strengthened.Trial RegistrationNCT05113446 (ClinicalTrials.gov). Registered 9 November 2021 - Retrospectively registered.

EXOSOMES FROM CYCLIC MICE MODULATE LIVER TRANSCRIPTOME IN ESTROUPAUSE MICE INDEPENDENT OF AGE.

Exosomes are extracellular vesicles secreted by cells that contain microRNAs (miRNAs). These miRNAs can induce changes in gene expression and function of recipient cells. In different cells exosome content can change with age and physiological state affecting tissues function and health. Therefore, the aim of this study was to characterize the miRNA content and role of exosomes from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age VCD-treated mice were divided in control group (VCD) and exosome treated group (VCD+EXO), which received 10 injections at 3-day intervals of exosomes extracted from serum of cyclic female mice (CTL). Exosome injection in estropausal mice had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum exosomes of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD+EXO compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by exosome treatment, indicating that exosomes from cyclic mice can reverse changes promoted by estropause in liver. Cyp4a12a expression which is male-specific was increased in VCD females and not reversed by exosome treatment. Our findings indicate that miRNAs content in exosomes is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with exosomes from cyclic mice can partially reverse changes in liver transcriptome.

Fluctuations in Prejudice Do Not Track Fluctuations in Ordinary Contact in Three 5-Wave “Shortitudinal” Studies Examining Daily, Weekly, or Monthly Intervals

Intergroup contact is regarded as one of the most effective ways to reduce prejudice. However, recent longitudinal studies using contemporary statistical techniques (e.g., random intercept cross-lagged panel models [RI-CLPMs]) have failed to find evidence of within-person changes in prejudice following contact fluctuations. We propose that past time-lags may have been too long to capture change and conducted three studies with shorter time-lags of single days, weeks, or months. We also considered effects of positive versus negative contact frequency. We consistently found that people who are less prejudiced have more contact (i.e., between-person effects); however, fluctuations in naturally occurring contact were not followed by corresponding within-person changes in prejudice, suggesting shorter-term contact fluctuations are detached from prejudice. With abundant support for contact in the field, we argue that prejudice may be impacted by major contact events, or through gradually acquired cumulative experiences, but effects are not apparent when examining “thin-slices” of time.

Dynamic Thiol-Disulfide Homeostasis Post-COVID-19 Depends on Age, Gender, and Symptom Severity.

It has been indicated that the thiol-disulfide homeostasis plays a role in the pathogenesis of COVID-19 infection. We assessed the impact on the thiol-disulfide homeostasis at 15-day intervals until 60 days, implicated in the pathogenesis of COVID-19, and its clinical relevance in disease progression. In this study, 43 COVID-19 patients (18 females and 25 males) were categorized based on symptom severity, age group, and body mass index. Serum samples were collected on days 15, 30, 45, and 60 after COVID-19 diagnosis. Thiol and disulfide parameters were measured in the collected serum samples using spectrophotometric methods. Serum thiol levels were higher in females and disulfide levels in males (p<0.05). Disulfide levels increased in those older on 15-day post-symptom onset (p<0.05). Serum native thiol levels were higher in patients with moderate and severe symptom severity (p<0.05) than in those with mild severity. The symptoms of chest pain, shortness of breath, loss of taste, and loss of appetite were negatively correlated with thiol levels (p<0.05). This study suggested critical findings of higher disulfide levels in older age and men, even in the weeks after disease onset. This discovery is significant as it could pave the way for interventions to repair thiol-disulfide homeostasis, potentially transforming the treatment of this group. Moreover, native thiols can point to disease severity even weeks after the onset of symptoms.

Examining the impact of the COVID-19 pandemic on hospital-associated Clostridioides difficile infection.

To evaluate the impact of changes in the size and characteristics of the hospitalized patient population during the COVID-19 pandemic on the incidence of hospital-associated Clostridioides difficile infection (HA-CDI). Interrupted time-series analysis. A 576-bed academic medical center in Portland, Oregon. We established March 23, 2020 as our pandemic onset and included 24 pre-pandemic and 24 pandemic-era 30-day intervals. We built an autoregressive segmented regression model to evaluate immediate and gradual changes in HA-CDI rate during the pandemic while controlling for changes in known CDI risk factors. We observed 4.5 HA-CDI cases per 10,000 patient-days in the two years prior to the pandemic and 4.7 cases per 10,000 patient-days in the first two years of the pandemic. According to our adjusted segmented regression model, there were neither significant changes in HA-CDI rate at the onset of the pandemic (level-change coefficient = 0.70, P-value = 0.57) nor overtime during the pandemic (slope-change coefficient = 0.003, P-value = 0.97). We observed significant increases in frequency and intensity of antibiotic use, time at risk, comorbidities, and patient age before and after the pandemic onset. Frequency of C. difficile testing did not significantly change during the pandemic (P= 0.72). Despite large increases in several CDI risk factors, we did not observe the expected corresponding changes in HA-CDI rate during the first two years of the COVID-19 pandemic. We hypothesize that infection prevention measures responding to COVID-19 played a role in CDI prevention.

A 50-year-old question: Can imidocarb chemoprophylaxis ensure seroconversion for babesiosis in cattle under field conditions?

Bovine babesiosis, caused by Babesia bovis or Babesia bigemina, is a major tick-borne disease affecting livestock. In regions with limited vaccine availability, imidocarb is widely used as a chemoprophylactic drug. Although it is assumed that chemoprophylaxis allows for the development of immunity shortly after treatment, the extent of seroconversion during the imidocarb administration protocol remains largely unexplored, with most investigations emphasizing symptom prevention. This research endeavors to verify the seroconversion rate (humoral immunity) of cattle undergoing imidocarb chemoprophylaxis while exposed to tick vectors in field conditions. Fifteen tick-naïve heifers were used, with twelve receiving imidocarb (experimental group) on day 0 of the experiment, and the remaining three serving as controls. On day one of the study, all animals were introduced into a tick-infested pasture. Subsequently, at 28-day intervals (days 28, 56, 84, 112, 140, and 168), the experimental group received imidocarb treatments (1.2 mg/Kg). The detection of antibodies against B. bovis and B. bigemina was performed using commercial ELISA kits. Throughout the study, all animals were exposed to natural infestation by Rhipicephalus microplus ticks. By the 56th day, after two imidocarb doses, 25 % of the experimental group had seroconverted for B. bovis, and 41 % for B. bigemina. By the 84th day, 66 % were seropositive for B. bovis and B. bigemina. By the 112th day, 75 % were seropositive for B. bovis. Notably, one heifer (8 %) failed to seroconvert for either species, while 41 % remained seropositive for only one Babesia species. These findings underscore certain limitations of the chemoprophylaxis protocol for bovine babesiosis. While the majority of treated cattle become seropositive for at least one Babesia species after four successive treatments, exposure to the parasite while receiving imidocarb chemoprophylaxis does not guarantee seroconversion for all treated animals.

Thumbtack needle at front-mu points for abnormal behavior in children with autism spectrum disorders

To compare the clinical effect of thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training in the treatment of autism spectrum disorders (ASD). A total of 40 children with ASD were randomly divided into a combination group (20 cases, 3 cases dropped out) and a conventional rehabilitation group (20 cases, 3 cases dropped out). Conventional rehabilitation training i.e. language-cognition training and comprehensive education training was adopted in the conventional rehabilitation group, once a day, 5 days a week. On the basis of the treatment in the conventional rehabilitation group, thumbtack needle was applied at Zhongwan (CV 12), bilateral Tianshu (ST 25) and Guanyuan (CV 4) in the combination group, the needles were retained for 3 days each time, 3-day interval was taken between each treatment, for 5 times per month. One-month treatment was as one course and a total of 3 courses were required in both groups, with 10-day break between each course. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), TCM spleen-stomach symptoms and Achenbach child behavior checklist (CBCL) were observed, and the serum ratio of glutamate and gamma-aminobutyric acid (Glu/GABA) was measured. After treatment, the scores of ABC, CARS and CBCL were decreased compared with those before treatment (P<0.05, P<0.01) in both groups, the TCM spleen-stomach symptoms score was decreased compared with that before treatment (P<0.05) in the combination group; the changes in the scores of ABC, CARS, TCM spleen-stomach symptoms and CBCL, as well as the serum Glu/GABA in the combination group were lager than those in the conventional rehabilitation group (P<0.05, P<0.01). Both thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training can effectively treat ASD, the combination treatment has superior effect on improving the abnormal behavior, spleen-stomach symptoms and balance of nerve impulse and inhibition.

The Short Questionnaire to Assess Health-Enhancing Physical Activity in Syrian Adults’ Populations

Background: To date, no studies have evaluated the reliability and/or validity of methods for measuring physical activity (PA) in free-living conditions within the Syrian population.Methods: This study compared estimates of PA and sedentary behavior (SB) obtained from the ActiGraph WGT3X-TB (AG) accelerometer and the Short Questionnaire to Assess Health Enhancing Physical Activity (SQUASH). Forty-five adults (13 men and 32 women, mean age 36.9 ±8.3 years) completed the SQUASH twice, with a 45-day interval between administrations. Time spent in low, moderate, vigorous, and moderate-vigorous PA (MVPA) was calculated using the SQUASH and AG accelerometer data. Reliability was assessed by calculating the Spearman correlation coefficient between the PA items scores. Bland-Altman analysis was also performed. The validity of the SQUASH was determined using the AG accelerometer as the reference method.Results: PA levels were systematically higher when measured by the SQUASH compared to the AG accelerometer. The Spearman’s correlation coefficient for the overall SQUASH reproducibility was 0.64. The Spearman’s correlation coefficient between the calculated total activity score from the SQUASH and the AG accelerometer was 0.31, indicating moderate reliability and validity of the SQUASH.Conclusion: Given its simplicity, brevity, ease of use, and low cost, the SQUASH appears to be a suitable method for monitoring PA in Syrian adults. Further strengthening of the validity scores may be possible by providing more detailed information on the types of activities included in the questionnaire.

6459 A Novel Long-Acting GH Receptor Antagonist Optimizing Therapeutic Efficacy and Duration

Abstract Disclosure: C. Ku: None. C. Kang: None. J. Oh: None. E. Wang: None. H. Song: None. K. Park: None. B. Kim: None. K. Kim: None. S. You: None. S. Park: None. E. Lee: None. Background: Forty to sixty percent of acromegalic patients undergo medical treatment, utilizing somatostatin analogues, dopamine agonists, and GH receptor (GHR) antagonists. The GHR antagonist, pegvisomant exhibits the most robust efficacy in reducing IGF-1 levels in acromegalic patients. However, pegvisomant faces several clinical limitations, such as poor compliance due to the necessity of daily injections. This study aimed to develop a novel, long-acting fusion GHR antagonist with optimized therapeutic efficacy and duration. Method: Twelve mutant proteins with alterations in the C-terminal and N-terminal regions of GHR were generated to confirm the GHR binding affinity and inhibitory potency compared with pegvisomant, which was evaluated with STAT5b luciferase reporter assay. Several carriers were engineered into selected mutant GHRs to increase the therapeutic duration. For in vivo experiments, single or repetitive injection of GHR antagonists were applied to acromegalic mouse model (somatotroph specific Aip knock out (sAIPKO) mice). Pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated in New Zealand White (NZW) rabbits. Result: Four out of the 12 GHR mutants exhibited higher affinity and stronger inhibitory potency toward human GHR when compared to pegvisomant. Specifically, three GHR mutants significantly reduced serum IGF-1 levels in sAIPKO mice following daily injections of 20 mg/kg for 7 days (52.3±6.0 to 5.9±1.3, 50.3±3.5 to 32.3±2.3, and 49.8±3.7 to 13.9±4.3 ng/mL; all p &amp;lt; 0.05). Among them, S4020N exhibited the lowest EC50 value for GHR binding affinity in in vitro analysis containing human GHR (0.594 nM) and mouse GHR (0.891 nM). Following fusion with each long-acting carrier, S4020N with the Fc carrier protein (ALT-B5) demonstrated the highest binding affinity and the strongest inhibitory potency toward human GHR, surpassing pegvisomant by 14 and 25 times, respectively. Administration of ALT-B5 (80 mg/kg) and pegvisomant (24 mg/kg) at a 3-day interval revealed the superior efficacy of ALT-B5 over pegvisomant (1879±219.4 vs. 3800±355.9 ng*hr/mL IGF-1 AUC for 5 days in ALT-B5 and pegvisomant, respectively; p &amp;lt; 0.01). In PK/PD studies, ALT-B5 was administered at doses of 3 mg/kg and 10 mg/kg in NZW rabbits, and PK/PD parameters were compared with the same molar concentration of pegvisomant. ALT-B5 exhibited the longest therapeutic duration and the highest efficacy compared to pegvisomant. Conclusion: ALT-B5 exhibited the longest duration and highest effectiveness in lowering IGF-1 levels. ALT-B5 emerges as a potential novel therapeutic option for acromegaly. Presentation: 6/1/2024

Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial

MERS-CoV is a respiratory pathogen with a case-fatality rate of 36%, and for which no vaccines are currently licensed. MVA-MERS-S is a candidate vaccine based on recombinant modified vaccinia virus Ankara (MVA). In this study, the safety, immunogenicity, and optimal dose schedule of MVA-MERS-S was assessed in individuals with previous exposure to SARS-CoV-2 infections and vaccines. We conducted a multicentre, double-blind, randomised controlled phase 1b clinical trial at two university medical centres in Germany and the Netherlands. Healthy volunteers aged 18-55 years were assigned by computer randomisation to receive three intramuscular injections of 107 or 108 plaque-forming units (PFU) of MVA-MERS-S, with two treatment groups each of either 28-day or 56-day intervals between the initial two doses, and one control arm that received only placebo, at a ratio of 2:2:2:2:1. The third dose was given after 224 days. The sponsor, clinical and laboratory staff, and participants were masked to both vaccine dose and dosing interval. The primary outcome was safety, assessed in the all participants who had received at least one injection; daily solicited vaccine reactions were recorded after each dose for 7 days, unsolicited adverse events for 28 days, and serious adverse events throughout the study. The secondary outcome was humoral immunogenicity, measured with vaccine-induced geometric mean antibody concentrations and seroconversion rates, analysed in all participants who received at least three allocated treatments. This study is registered at ClinicalTrials.gov (NCT04119440) and is completed. Between 26 July, 2021, and 3 March, 2022, 244 volunteers were screened, 177 of whom were eligible and 140 were randomly assigned either to the 28-day 107 PFU group (n=32), 56-day 107 PFU group (n=31), 28-day 108 PFU group (n=31), 56-day 108 PFU group (n=30), or placebo group (n=16). In total, 178 doses were administered of 107 PFU of MVA-MERS-S, 174 of 108 PFU, and 164 doses of placebo, and 139 participants received at least one injection. 73 (53%) were female and 66 (48%) were male. No serious vaccine-related adverse events occurred. Solicited local reactions were mild in 288 (93%, 95% CI 90-96) of 309 reports and consisted primarily of pain or tenderness. Pain or tenderness (of any severity) occurred after 69 (39%, 32-46) of 178 107 PFU injections, 138 (79%; 73-85) of 174 108 PFU injections, and 18 (11%; 7-11) of 164 placebo injections. Of 595 reported solicited systemic reactions, 479 (81%, 77-83) were graded as mild. Systemic reactions of any grade occurred after 77 (43%; 36-51) 107 PFU injections, 102 (59%; 51-66) 108 PFU injections, and 67 (41%; 34-49) of 164 placebo injections. At 28 days after the second dose, MERS-CoV neutralising antibodies were highest for participants assigned to 56-day 108 PFU, with geometric mean ratios of 7·2 (95% CI 3·9-13·3) for the 56-day 108 PFU group versus the 28-day 108 PFU group (p<0·0001), 3·9 (2·1-7·2) for the 56-day 108 PFU group versus the 56-day 107 PFU group (p=0·0031), and 5·4 (2·9-10·0) for the 56-day 108 PFU group versus the 28-day 107 PFU group (p=0·0003). MVA-MERS-S was safe and immunogenic in individuals with previous and concurrent SARS-CoV-2 exposure. The second vaccination with the 108 PFU dose of MVA-MERS-S elicited a stronger humoral immune response when administered 56 days after the first dose than a 28-day interval. Further studies are needed to verify these findings in groups at risk for MERS-CoV exposure, and at risk of severe disease, including older individuals and those with relevant comorbidities. Coalition for Epidemic Preparedness Innovations, the German Centre for Infection Research, and the German Research Foundation.

"Before medically advised" hospital discharge and the risk of subsequent drug overdose: A case-crossover analysis.

Patient-initiated or "before medically advised" (BMA) hospital discharge is more common among people who use drugs. Transitions of care can be destabilizing and might increase the risk of subsequent illicit drug overdose. This study sought to evaluate whether BMA discharge is associated with an increased risk of subsequent drug overdose (primary objective) and whether physician-advised discharge is associated with an increased risk of subsequent drug overdose (secondary objective). We performed a case-crossover analysis of population-based linked administrative health data for individuals experiencing an overdose between 2016 and 2019 in British Columbia, Canada. Using conditional logistic regression, we compared the likelihood of hospital discharge in the 28 days before overdose (the "pre-overdose interval") to the likelihood of hospital discharge in two self-matched 28-day control intervals ending 26 and 52 weeks before overdose. Over the 3.5-year study interval, 235 of 27,584 (0.9%) pre-overdose intervals and 189 of 55,168 (0.3%) control intervals included a BMA discharge, suggesting that BMA discharge was associated with a twofold increase in the risk of subsequent drug overdose (adjusted odds ratio [aOR], 2.08; 95% confidence interval [95% CI], 1.68-2.58; p < 0.001). Physician-advised hospital discharge was also a risk factor for subsequent overdose, occurring in 1350 of 27,584 (4.9%) pre-overdose intervals and 1625 of 55,168 (2.9%) control intervals (aOR, 1.39; 95% CI, 1.27-1.52; p < .001). Both BMA and physician-advised hospital discharge are independently associated with transient increases in the risk of subsequent illicit drug overdose. Better in-hospital treatment of substance use disorder and novel means of post-discharge outreach should be deployed to reduce this risk.

Fulvic and Salicylic Acids Improve Morpho-Physio-Biochemical Attributes, Yield and Fruit Quality of Two Mango Cultivars Exposed to Dual Salinity and Heat Stress Conditions

Abstract Purpose The present research’s main objective was to explore the potential stimulative effect of fulvic acid (FA) as a soil conditioner and salicylic acid (SA) as foliar spraying on morpho-physio-biochemical attributes, fruit yield, and quality of ‘Sediek’ and ‘Ewais’ mango cultivars (cvs.) grown under saline calcareous soil and heat stress conditions Methods Eight treatments, namely, 200 (FA200) and 400 (FA400) g FA tree−1 as a soil addition, 200 (SA200) or 400 (SA400) mg SA L−1 as foliar spraying, and their bilateral combinations (e.g., FA200 + SA200, FA200 + SA400, FA400 + SA200, and FA400 + SA400) compared to untreated control on morpho-physio-biochemical attributes, yield, and fruit quality of ‘Sediek’ and ‘Ewais’ mango cvs. grown under saline calcareous soil and heat stress conditions were assessed. These treatments were carried out using a split-plot arrangement in a randomized complete block design replicated three times during the 2022 and 2023 seasons. Results Cultivar Sediek had higher SPAD value, leaf proline and phenolic content, leaf area, fruit weight, yield and vitamin C than Ewais which had higher tree water status and shoot length. Saline calcareous and heat-stressed mango trees without FA or/and SA treatment had a significant decline in their water status, photosynthetic traits, biochemical responses that adversely affected growth and yield and fruit quality. However, soil FA addition and foliar SA spraying alone or in combination at any application level attenuated the negative effects of saline calcareous and heat-stress conditions via enhancing the morpho-physio-biochemical attributes, positively reflecting in tree growth, yield, and fruit quality. FA treatment alone improved tree water status (membrane stability index; MSI and relative water content; RWC), photosynthetic traits (SPAD value and maximum photochemical efficiency; Fv/Fm), leaf area, fruit weight, fruit yield, and fruit vitamin C (fruit vit.C), while SA treatment alone enhanced leaf proline and phenolic content, shoot length, and fruit total soluble solids (fruit TSS) compared to the non-FA or SA-treated control. Moreover, co-application of FA400 and SA400 effectively alleviated the harmful impacts of dual stress of heat and salinity on mango trees by improving MSI, RWC, SPAD value, Fv/Fm, proline and phenolic content, fruit weight, fruit yield, fruit TSS, fruit vit.C by 19.7, 26.1, 46.7, 18.7, 101.7, 390.7, 42.7, 6.8, 22.6, 69.6% (averages of the two seasons), respectively, compared to the non-FA or SA-treated trees. Conclusion It is recommended to add 400 g FA tree−1 to soil integrated with 400 mg SA L−1 foliar spraying four times at 30-day intervals for improving water status and photosynthetic traits, proline and phenolic accumulation, thereby growth, yield, and fruit quality of mango trees exposed to dual stress of heat and salinity under arid conditions.

Flexural behaviour and post-cracking performance of polypropylene fibre-reinforced waste cardboard blended concrete

The requalification of recycled materials has become of significance owing to a global shift towards net zero emissions and the severe environmental impact of misused recyclable waste. Cardboard and polypropylene have evolved into significant waste products, and the purpose of the study was to focus on the repurposing of both waste materials in determining the structural behaviour of an eco-efficient fibre-reinforced waste concrete. The study extended upon the findings of a precursor study in the development of an eco-efficient fibre-reinforced waste concrete mix. Finely processed municipally collected waste cardboard and recycled polypropylene macro-fibres were incorporated into a concrete mix design for which an experimental program was realised. To achieve this, uniaxial compressive strength, modulus of rupture, modulus of elasticity, and indirect tensile strength of the waste and reference mixtures were determined for 7- and 28-day intervals. Crack mouth open displacement testing was achieved to assess the post-cracking response, and retaining wall beams were prepared and loaded to determine the efficacy of the concrete mixture for low load-bearing structures. Mechanical and post-cracking properties of the hybrid waste concrete underscored excellent performance in comparison to other waste fibre-reinforced concrete mixtures, and superior to those blended with similar kraft fibre volume fractions. Moreover, the structural performance of beams cast from the hybrid mixture closely matched those of the reference mixture, emphasising the viability of the mixture and the role waste materials have in the construction and building industry.

Assessment of ChatGPT's Compliance with ESC-Acute Coronary Syndrome Management Guidelines at 30-Day Intervals.

Background: Despite ongoing advancements in healthcare, acute coronary syndromes (ACS) remain a leading cause of morbidity and mortality. The 2023 European Society of Cardiology (ESC) guidelines have introduced significant improvements in ACS management. Concurrently, artificial intelligence (AI), particularly models like ChatGPT, is showing promise in supporting clinical decision-making and education. Methods: This study evaluates the performance of ChatGPT-v4 in adhering to ESC guidelines for ACS management over a 30-day interval. Based on ESC guidelines, a dataset of 100 questions was used to assess ChatGPT's accuracy and consistency. The questions were divided into binary (true/false) and multiple-choice formats. The AI's responses were initially evaluated and then re-evaluated after 30 days, using accuracy and consistency as primary metrics. Results: ChatGPT's accuracy in answering ACS-related binary and multiple-choice questions was evaluated at baseline and after 30 days. For binary questions, accuracy was 84% initially and 86% after 30 days, with no significant change (p = 0.564). Cohen's Kappa was 0.94, indicating excellent agreement. Multiple-choice question accuracy was 80% initially, improving to 84% after 30 days, also without significant change (p = 0.527). Cohen's Kappa was 0.93, reflecting similarly high consistency. These results suggest stable AI performance with minor fluctuations. Conclusions: Despite variations in performance on binary and multiple-choice questions, ChatGPT shows significant promise as a clinical support tool in ACS management. However, it is crucial to consider limitations such as fluctuations and hallucinations, which could lead to severe issues in clinical applications.

Association between automatic milking system parameters and intramammary infections in dairy cows at dry-off

IntroductionThe current global concern over increasing antimicrobial resistance among animal and human pathogens has motivated efforts to reduce antimicrobial drug use in food animals and its impact on antimicrobial resistance. One such strategy is to use selective dry cow therapy (SDCT) in dairy cows, which involves treating only cows with intramammary infection (IMI) at dry-off. However, efficient methods are needed to identify cows with IMI at dry-off to implement SDCT. Automatic Milking Systems (AMS) data may help farmers identify cows with IMI when individual Somatic Cell Count (SCC) is not routinely tested. This study assessed the correlation between cow-level and quarter-level AMS parameters and IMI at dry-off.Methods &amp;amp; ResultsA total of 733 udder quarters (comprising both Primiparous [PRIM] and Multiparous [MULT] cows) were sampled and categorized for IMI based on bacterial growth and SCC. Data were aggregated both daily and into 7-day and 15-day intervals preceding dry-off. The quarter-level prevalence of bacterial growth at dry-off was 24.28% overall. When stratified by parity, logistic regression analysis at 15 days to dry-off revealed that the average difference in mastitis detection index (MDi) in PRIM, MDi, and standard deviation milk flow rate in MULT were associated with increased odds of IMI at dry-off. Similarly, data from 7 days to dry-off revealed that average peak milk flow rate in PRIM, and MDi in MULT were associated with increased odds of IMI at dry-off. However, an increase in average milk yield was associated with decreased odds of IMI.Discussion &amp;amp; ConclusionOur findings underscore the significance of MDi, milk flow rate, peak milk flow rate, and milk yield in predicting IMI at dry-off. Notably, stronger associations were observed with data collected 7 days preceding dry-off. Further research is warranted to refine and validate algorithms amalgamating these variables for precise IMI prediction in cows at dry-off.