Effect Of Dose Research Articles

Chemical Composition, Bioactivities, and Applications of Spirulina (Limnospira platensis) in Food, Feed, and Medicine

Spirulina (Limnospira platensis) is a microalga recognised for its rich nutritional composition and diverse bioactive compounds, making it a valuable functional food, feed, and therapeutic agent. This review examines spirulina’s chemical composition, including its high levels of protein, essential fatty acids, vitamins, minerals, and bioactive compounds, such as the phycocyanin pigment, polysaccharides, and carotenoids, in food, feed, and medicine. These compounds exhibit various biological activities, including antioxidant, anti-inflammatory, immunomodulatory, antiviral, anticancer, antidiabetic and lipid-lowering effects. Spirulina’s potential to mitigate oxidative stress, enhance immune function, and inhibit tumour growth positions it as a promising candidate for preventing chronic diseases. Additionally, spirulina is gaining interest in the animal feed sector as a promotor of growth performance, improving immune responses and increasing resistance to diseases in livestock, poultry, and aquaculture. Despite its well-documented health benefits, future research is needed to optimize production/cultivation methods, improve its bioavailability, and validate its efficacy (dose–effect relationship) and safety through clinical trials and large-scale human trials. This review underscores the potential of spirulina to address global health and nutrition challenges, supporting its continued application in food, feed, and medicine.

Platelet storage failure—Metformin as causative agent

AbstractBackgroundPathogen reduction technology (PRT)‐treated apheresis platelets (APs) were returned without platelet swirl and with pH22°C < 6.2. The platelet donor was taking prescription levothyroxine and metformin plus over‐the‐counter medications and supplements. We hypothesized that either PRT or medication was causative.Study Design and MethodsOne AP from a double AP collection from this donor was PRT‐treated, the other unit untreated. Units were assessed over 7‐day storage with a standard panel of platelet assays and metabolomics using high resolution mass spectrometry. The dose effect of metformin on platelets over storage was evaluated in vitro using APs obtained from non‐medicated donors.ResultsThis donor's PRT‐ and non‐PRT treated paired units had pH values <6.2 by the end of day 2. Lactate generation rates in the PRT‐ and non‐PRT units were very high compared to previously reported values and approached that reported for anaerobic storage. Metabolomic analysis revealed impairments in a number of energy metabolic pathways between PRT‐ and non‐PRT platelets; however, this did not support a major causative role of PRT in the significant upregulation of lactic acid production. Metformin caused a dose‐dependent upregulation of glycolysis, resulting in pH decline.DiscussionWe conclude that metformin is the most likely cause for this donor's stored platelet pH failures. Metformin is commonly used to treat type 2 diabetes and is not a donor deferral medication. Further investigation is indicated into the potential impact of metformin on platelet storage characteristics, the potential implications for medication deferral, and the need for additional screening tools in the laboratory.

Clinical and Genetic Markers of Vascular Toxicity in Glioblastoma Patients: Insights from NRG Oncology RTOG-0825.

Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment. 591 Non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N=367) by occurrence of thrombosis or hypertension (grade ≥2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the clinical model as a single nucleotide polymorphism (SNP) -dose effect variable to produce the final genetic models. Thrombosis and hypertension were experienced by 62 (11%) and 59 (10%) patients, respectively. Patients who experienced hypertension displayed improved survival over those without hypertension (median overall survival: 25.72 vs 15.47 months, p=0.002). The genetic model of thrombosis included corticosteroid use (OR: 7.13, p=0.02), absolute neutrophil count (OR: 1.008, p=0.19), body surface area (OR: 18.87, p=0.0008), and the SNP-dose effect (3 variants; OR: 3.79, p<.0001). The genetic model of hypertension included bevacizumab use (OR: 0.97, p=0.95) and the SNP-dose effect (6 variants; OR: 4.44, p<.0001). In this study, germline variants were superior in predicting hypertension than clinical variables alone. Additionally, corticosteroid use was a considerable risk factor for thrombosis. Future investigations should confirm the hazard of corticosteroid use on thrombosis and the impact of bevacizumab in other malignancies after accounting for the genetic risk of hypertension.

Effect of diet combined with exercise intervention on tumor necrosis factor α in overweight or obese groups: Based on the exercise dose-response relationship

Background: Chronic low-grade systemic inflammation, often linked to obesity or being overweight, is associated with various complications and an increased risk of disease development. Tumor necrosis factor α (TNF-α) is a key inflammatory factor that significantly impacts various body functions. Objective: 1) To assess whether combined interventions are more effective than single interventions in combining diet and exercise. 2) To assess the effectiveness of exercise dose in different interventions on tumor necrosis factor (TNF-α) levels in obese or overweight patients. Methods: A thorough search was conducted across four electronic databases of randomized controlled trials that focus on exercise or dietary interventions for patients with obesity or overweight. This comprehensive review encompasses data collected up to August 2024. Two independent researchers conducted a thorough evaluation of the literature's quality. Network and dose-response analyses were performed using random effects models to examine the impact of diverse interventions on TNF-α. Results: A total of 19 randomized controlled trials with 1479 patients with obesity or overweight were included. The meta-analysis showed that the hypocaloric diet combined with aerobic training (HDAT) possessed the highest ranking (SMD= -1.00,95%CI -1.51 to -0.49), followed by the hypocaloric diet (HD) (SMD= -0.40,95%CI -0.89 to 0.09), hypocaloric diet combined with resistance training (HDRT) (SMD= -0.48,95%CI- 1.43 to 0.48), and aerobic training combined with resistance training (ART) (SMD= -0.18,95%CI -0.92 to 0.57). Additionally, a notable improvement in TNF-α levels was observed in individuals adhering to a hypocaloric diet in conjunction with exercise when the cumulative exercise volume reached 150 metabolic equivalent of task minutes per week. Conclusion: Based on the GRADE rating guidelines, moderate-quality research evidence indicates that a hypocaloric diet combined with aerobic training (HDAT) is the most effective intervention for enhancing tumor TNF-α levels in individuals with obesity or overweight. Additionally, the dose-response relationship was observed between the total exercise dose and TNF-α levels. Future research should investigate the specific effects of various aerobic exercise modalities on TNF-α levels in obese or overweight patients to develop a more personalized approach to exercise prescription.

Effect of different durations of preoperative computerised cognitive training on postoperative delirium in older patients undergoing cardiac surgery: a study protocol for a prospective, randomised controlled trial

IntroductionPostoperative delirium (POD) is a common neurological complication after surgery among older patients, characterised by acute disturbances in consciousness, attention and cognition, usually occurring within 24–72 hours after surgery. POD...

Radiation adaptive response: the biophysical phenomenon and its theoretical description.

The radiation adaptive response (or radioadaptation) effect is a biophysical and radiobiological phenomenon responsible for, e.g. the enhancement of repair processes, cell cycle and apoptosis regulation or enhancement of antioxidant production in cells/organisms irradiated by low doses and low dose-rates of ionising radiation. This phenomenon, however, is not always present, which creates many problems both for experimenters and theoreticians. Here we propose a comprehensive and complete theoretical model of radioadaptation grounded in mathematical concept of dose- and time-related probability function of the adaptive response appearance. This can be used in the context of two special cases of the adaptive response: the Raper-Yonezawa (priming dose) effect or constant low-dose-rate irradiation (e.g. for high natural background). This complete theoretical approach is supported by Monte Carlo simulations and real-experimental data used for model calibration and validation.

Mycotoxin Challenge in Dairy Cows: Assessment of the Efficacy of an Anti-Mycotoxin Agent by Adopting an In Vitro Rumen Simulation Method

To protect ruminants from the harmful effects of mycotoxins, anti-mycotoxin agents can be added to the dietary ration, thus guaranteeing animal health and production. Therefore, the objective of this study was to evaluate the in vitro ruminal initial sequestration (weak binding) and subsequent desorption (strong binding) of an anti-mycotoxin agent based on a mixture of adsorbing material, turmeric and milk thistle extracts and yeast-based components to adsorb or bio-convert aflatoxins (AF), fumonisins B1 and B2 (FB), trichothecene deoxynivalenol (DON), T-2 and HT-2 toxins, and zearalenone (ZEN). Two doses were tested: Dose 1 simulated 30 mg/cow/d, while Dose 2 simulated 90 mg/cow/d of the anti-mycotoxin agent. Each treatment involved three analytical replicates at each of three incubation times (1, 4, and 24 h post-incubation), with two independent experimental runs providing experimental replicates. Analytical methods, including UHPLC-HRMS and multivariate analyses, were used to both quantify mycotoxin concentrations and reveal dose-dependent reductions, with statistical validations indicating significant changes in mycotoxin levels across both dose and time. The results indicated that the anti-mycotoxin agent was able to highly bind AFB1, T2, and HT-2 toxins since its concentration was always under the limit of detection (&lt;1 ppb). Regarding ZEN (weak binding mean: 94.6%; strong binding mean: 62.4%) and FBs (weak binding mean: 58.7%; strong binding mean: 32.3%), orthogonal contrasts indicated that the anti-mycotoxin agent was able to effectively bind these toxins using Dose 1 (p &lt; 0.05). This finding suggests that Dose 1 may be sufficient to achieve the targeted effect and that a further increase does not significantly improve the outcome. Regarding DON, a strong linear relationship was observed between dose and adsorption. However, the complex interactions between the mycotoxin, the ruminal environment, and the anti-mycotoxin agent made it difficult to establish a clear dose–effect relationship (p &gt; 0.10). UHPLC-HRMS analysis identified over 1500 mass features in rumen samples, which were further analyzed to assess the effects of the anti-mycotoxin agent. Hierarchical clustering analysis (HCA) revealed significant changes in the untargeted metabolomic profiles of samples treated with mycotoxins compared to control samples, particularly after 24 h with the anti-mycotoxin treatments. Clear differences were noted between strong binding and weak binding samples. Further analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted distinct metabolomic profiles, with stronger predictive ability in the strong binding group (Q2 cumulative value of 0.57) compared to the weak binding group (0.30). The analysis identified 44 discriminant compounds in the strong binding model and 16 in the weak binding model. Seven compounds were common to both groups, while silibinin, known for its antioxidant and anti-inflammatory properties, was found among the unique compounds in the weak binding group. Overall, the findings suggest that both doses of the anti-mycotoxin agent significantly influenced the chemical profiles in the rumen, particularly enhancing the binding of mycotoxins, thereby supporting the role of phytogenic extracts in mitigating mycotoxin effects.

Effect of molar dose on the in vivo tissue biodistribution profile of FAP-targeted radioligand therapeutics.

177Lu-OncoFAP-23 is a novel FAP-targeted radioligand therapeutic (RLT) with high and prolonged tumor residence time and promising preclinical efficacy. In this work, we investigated the correlation between the injected molar dose and the in vivo tumor-to-organ ratios and tumor-targeting performance of 177Lu-OncoFAP-23. We evaluated the quantitative biodistribution profile of 177Lu-OncoFAP-23 at different molar doses (i.e., 3 to 2250nmol/kg) in tumor-bearing mice by means of ex vivo gamma counting, we included 177Lu-OncoFAP and 177Lu-BiOncoFAP as experimental controls. The biodistribution profile of 177Lu-OncoFAP-23 strongly depends on the molar dose injected. Molar doses below 30nmol/kg result in unwanted uptake of the compound in healthy organs, while doses higher than 725nmol/kg determined a reduced tumor uptake due to receptor saturation. We identified an optimal molar dose ranging from 90 to 250nmol/kg, characterized by elevated tumor uptake and adequate tumor-to-organ ratios. 177Lu-OncoFAP-23 presents a favorable in vivo biodistribution profile at molar doses ranging from 90 to 250nmol/kg in tumor-bearing mice. Our results guide the design of the first-in-human Phase I clinical trial with this novel FAP-targeted radioligand therapeutic.

Effect of Mexel®432 on DNA Damage in Haliotis Discus Hannai and Mesocentrotus Nudus

Mexel®432 is a surfactant-like substance that is a biosuppressant against marine fouling organisms. Therefore, to study the toxic effect of Mexel®432 on marine organisms, the wrinkled abalone and echinococcus was exposed to concentrations of 0.175 mg·L-1, 0.350 mg·L-1, 0.700 mg·L-1, 0.275 mg·L-1, 0.550 mg∙L−1, 1.100 mg·L-1 Mexel®432 solution, and single-cell gel electrophoresis (comet experiment) was used to detect different exposure times (0, 10, 20 d) DNA damage effect of digestive gland cells and echinococcus pallidae intestinal cells in wrinkled disc abalone, and tail DNA content, tail length, tail distance, and Olive tail distance were used as evaluation indexes. The results showed that different concentrations of Mexel®432 could cause DNA disintegration and tailing in digestive gland cells and intestinal cells in a short period of time (10 d), and with the increase of Mexel®432 concentration and the extension of exposure time, DNA deformation was obvious, the fragmentation increased, and the degree of damage was aggravated. When the concentration of Mexel®432 reaches 0.350 mg·L-1, it produces certain genotoxicity to the digestive gland cells of wrinkled abalone, and when the concentration of Mexel®432 reaches 1.1000 mg·L-1, it also has certain genotoxicity to the intestinal cells of Mesocentrotus nudus. The experimental results showed that Mexel®432 had a significant dose effect relationship on DNA damage in the cells of two biological tissues.

The effect of caffeine dose on caffeine and paraxanthine changes in serum and saliva and CYP1A2 enzyme activity in athletes: a randomized placebo-controlled crossover trial.

Although caffeine (CAF) supplementation has been shown to improve exercise performance, its dose-dependent effect on CAF metabolism has not been sufficiently investigated. The aim of this study was to evaluate the effects of 3, 6 and 9mg of CAF/kgBM on changes of CAF and paraxanthine (PRX) in the serum and saliva at four time-points. In a randomized, double-blind, placebo-controlled crossover design, acute pre-exercise supplementation in 26 moderately-trained athletes, participating in high-intensity functional training (HIFT), was examined. The study protocol involved CAF/PRX biochemical analyses of serum and saliva with respect to CYP1A2 polymorphism and CYP1A2 enzyme activity. Despite significant differences between the serum and saliva levels of CAF and PRX, there was no difference in the PRX/CAF ratio. The interaction effect of dose and time-points for PRX concentration was revealed. The main effects of dose were observed for CAF and the PRX/CAF ratio. The main effect of time-points was registered only for serum CAF. Dose- and time-dependent effect of CAF supplementation on CAF and PRX in the serum and saliva of athletes was confirmed, but there was no effect of the CAF dose on CYP1A2 enzyme activity, nor was there an interaction of CYP1A2 with enzyme inducibility. The CAF/PRX correlation indicated the possibility of interchangeable use of serum and/or saliva analyses in exercise studies. This trial was registered prospectively at ClinicalTrials.gov (NCT03822663, registration date: 30/01/2019).

Pain Control and Opioid Consumption in Patients Undergoing Total Hip or Knee Arthroplasty Receiving a Preoperative Low Dose of Gabapentin

Background: Meta-analyses and randomized controlled trials were inconclusive regarding the role of gabapentinoids in patients undergoing joint arthroplasties. The aim of the present study was to investigate the effect of a preoperative low dose of gabapentin in patients undergoing total hip (THA) and knee arthroplasties (TKA). Methods: A retrospective observational study was conducted on 135 patients undergoing THA and TKA at the National Orthopedic Hospital Cappagh, Dublin, from July to December 2022. The primary outcome was the assessment of numerical rating scores (NRS) for postoperative pain at various time intervals. Results: During the observation period, 55 patients received a preoperative dose of gabapentin, while 80 patients did not. Statistically significant differences in numerical rating scores (NRS) were found at 6 (3 vs. 0, p &lt; 0.001), 12 (4 vs. 2, p &lt; 0.001), 18 (4 vs. 3, p &lt; 0.001), and 24 h (4 vs. 3, p = 0.010) after surgery, in favor of the group receiving gabapentin. A reduction in opioid consumption, measured as morphine equivalents, was also noted in the gabapentin group (40 vs. 30 mg, p = 0.040). Conclusions: A low preoperative dose of gabapentin was associated with reduced postoperative pain and opioid consumption in patients undergoing TKA and THA, without impacting hospital stay. Prospectively designed trials are encouraged to assess the safety and effect on pain control of a preoperative low dose of gabapentin.

Dosing of Bacterial Phytase (EC 3.1.3.26) in Laying Hens’ Diets

Despite the acknowledged advancements in the utilization of phytase dosing, limited research has been conducted on commercial laying hens. To assess the effectiveness of doses of exogenous phytase, a total of 320 laying hens aged between 44 and 64 weeks were utilized. These hens were divided into five treatments, which were then distributed using a completely randomized design with eight replicates, each containing eight birds. The treatments consisted of phytase supplementation levels of 0, 500, 1000, 1500, and 3000 FTU/kg. Quadratic regression equations were utilized to determine the maximum and minimum values for the levels of phytase supplementation. A significant difference was observed in the levels of phytase supplementation, where a quadratic model was fitted to various variables including egg weight (g), egg mass (g/bird/day), feed conversion per egg mass (g/g), yolk concentration (%), albumen concentration (%), shell thickness (μm), shell strength (kgf), specific gravity, and yolk color. Further, an increased supplementation improved the digestive tract of the hens, thereby providing a better villus–crypt ratio. Considering the advantageous effects of phytase dosing, it is recommended to supplement corn and soybean meal-based diets with 1500 FTU/kg of bacterial phytase for laying hens during the 44- to 64-week production period.

Multi-strain modeling of influenza vaccine effectiveness in older adults and its dependence on antigenic distance

Influenza vaccine effectiveness (VE) varies seasonally due to host, virus and vaccine characteristics. To investigate how antigenic matching and dosage impact VE, we developed a mechanistic knowledge-based mathematical model. Immunization with a split vaccine is modeled for exposure to A/H1N1 or A/H3N2 virus strains. The model accounts for cross-reactivity of immune cells elicited during previous immunizations with new antigens. We simulated vaccine effectiveness (sVE) of high dose (HD) versus standard dose (SD) vaccines in the older population, from 2011 to 2022. We find that sVE is highly dependent on antigenic matching and that higher dosage improves immunogenicity, activation and memory formation of immune cells. In alignment with clinical observations, the HD vaccine performs better than the SD vaccine in all simulations, supporting the use of the HD vaccine in the older population. This model could be adapted to predict the impact of alternative virus strain selection on clinical outcomes in future influenza seasons.

Comparison of total ionizing dose effects in SiC MOSFETs with double trench versus asymmetric trench

Comparison of total ionizing dose effects in SiC MOSFETs with double trench versus asymmetric trench

A pooled analysis of the efficacy of sertraline in women, with a focus on those of childbearing age

IntroductionGender- and age-specific research on medications is essential for personalizing treatment plans, optimizing dosing, minimizing adverse effects and improving outcomes. Women are twice as likely to be diagnosed with major depressive disorder (MDD), and it is commonly reported during their reproductive years. This post-hoc pooled analysis evaluated the efficacy of sertraline (one of the most studied medications in women) in women of reproductive age (18–44 years).MethodsData was pooled from nine clinical trials of sertraline that included 1832 subjects with MDD. The analysis set included 1097 women, 651 of those were of reproductive age. Sertraline was compared with placebo for changes in total HAM-D17 and CGI scores measured over time through MMRM analysis. The change from baseline to the end of study (-week 8) was assessed using ANCOVA.ResultsThe changes from baseline in total HAM-D17 and CGI scores were significantly higher for sertraline than for placebo at the end of 8 weeks for all women (LS Mean difference, 95% CI: -1.81(-3.01,-0.62), P = 0.0029; -0.38(-0.55,-0.20), P < 0.0001, respectively). For women of reproductive age these changes (LS Mean difference, 95% CI: -2.08(-3.52,-0.64), P = 0.0047; -0.44(-0.66,-0.22), P < 0.0001, respectively), were significant from week 2 (HAM-D17) and week 1 (CGI) till the end of study.LimitationsOnly sertraline and placebo arms were included in the analysis. The dosing varied between studies, and the effect of dose was not addressed.ConclusionsSertraline is an effective option for treatment of MDD in women, including those in the childbearing age.

Supramolecular solvents: a gateway to all-in-one extractions in chemical exposomics.

The characterization of the human chemical exposome through daily estimated intakes or biomonitoring has become paramount to understand the causal pathways leading to common diseases. The paradigm shift that hastaken place in looking at health has moved research from the classical biomedical model based on "one exposure, one disease" to a more comprehensive approach based on multiple chemicals and low dose effects. For this purpose, untargeted and/or suspect analysis of chemicals based on liquid chromatography and high-resolution mass spectrometry (LC-HRMS) has been proposed as the most relevant strategy for sequencing the exposome. A key aspect in this respect is the development of unbiased sample preparation methods that efficiently concentrate the wide range of untargeted/suspected chemicals while minimizing interference from sample matrices. Here, we aim to critically discuss the potential of tailored supramolecular solvents (SUPRAS) for achieving all-in-one extractions in chemical exposomics, as analternative to overcome the limitations of the current sample treatment strategies, on the basis of their intrinsic properties and the applications reported so far.

Design of a New Catalyst, Manganese(III) Complex, for the Oxidative Degradation of Azo Dye Molecules in Water Using Hydrogen Peroxide.

In the current work, chloro(meso-tetrakis(phenyl)porphyrin) manganese(III) [Mn(TPP)Cl] was synthesized following two steps: the preparation of meso-tetraphenylporphyrin (H⁠2TPP) and the insertion of manganese into the free porphyrin H2TPP. The compounds were characterized using SEM, FT-IR, UV, TGA/DTA, and XRD analyses. Manganese(III) meso-porphyrins exhibited hyper-type electronic spectra with a half-vacant metal orbital with symmetry, such as [dπ:dxz and dyz]. The thermal behavior of [Mn(TPP)(Cl)] changed (three-step degradation process) compared to the initial H2TPP (one-step degradation process), confirming the insertion of manganese into the core of the free porphyrin H2TPP. Furthermore, [Mn(TPP)Cl] was used to degrade calmagite (an azo dye) using H2O2 as an oxidant. The effects of dye concentration, reaction time, H2O2 dose, and temperature were investigated. The azo dye solution was completely degraded in the presence of [Mn(TPP)(Cl)]/H2O2 at pH = 6, temperature = 20 °C, C0 = 30 mg/L, and H2O2 = 40 mL/L. The computed low activation energy (Ea = 10.55 Kj/mol) demonstrated the efficiency of the proposed catalytic system for the azo dye degradation. Overall, based on the synthesis process and the excellent catalytic results, the prepared [Mn(TPP)Cl] could be used as an effective catalyst for the treatment of calmagite-contaminated effluents.

A comprehensive investigation of total ionizing dose effects on bulk FinFETs through TCAD simulation

This study investigates the total-ionizing-dose (TID) effect on bulk FinFETs under ON-state irradiation bias, aiming to analyze the cause and physical mechanism of irradiation enhancement effects. Utilizing technology computer-aided design (TCAD), for the first time, we find that parasitic transistors located at the apex of the shallow trench isolation (STI) oxide significantly contribute to the subthreshold degradation of the device, leading to a notable increase in off-state leakage current. Furthermore, under identical irradiation bias conditions, narrower-fin and shorter-channel devices exhibit a more pronounced increase in off-state leakage current. This escalation is attributed to an increased amount of trapped charge in the STI oxide and the elevated electrostatic potential of the punch-through stop (PTS) layer, respectively. Additionally, higher drain voltage reduces the threshold voltage of the STI parasitic transistors, resulting in an increased off-state current as drain voltage rises. In summary, investigating the TID effect of bulk FinFETs under ON-bias is crucial, as it can provide theoretical support for reinforcing nanostructured devices against irradiation-induced degradation.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Effects of dose, dietary nutrient composition, and supplementation period on the efficacy of methane mitigation strategies in dairy cows: A meta-analysis

The objective of this meta-analysis was to quantify the potential of CH4-mitigating strategies in dairy cattle when accounting for the effects of treatment dose, dietary nutrient composition, and supplementation period. Data from 218 studies with dairy cattle published between 1963 to 2022 were reviewed. Individual CH4 mitigation strategies selected for the analysis were algae (Asparagopsis spp.), 3-nitrooxypropanol, nitrate, lipids, plant secondary compounds, and direct-fed microbials (DFM). Response variables evaluated were daily CH4 emission (g/d), CH4 yield (g CH4/kg DMI), and CH4 intensity (g CH4/kg milk yield [MY] and ECM). Relative mean difference between treatment and control means reported in the studies were calculated and used in the statistical analysis. Robust variance estimation method was used to analyze the effects of CH4 mitigation strategies. Dose, forage-to-concentrate ratio (F:C), dietary concentrations of CP, ether extract (EE), NDF, ADF, and starch, and supplementation period were used as continuous explanatory variables. Data for algae supplementation were limited and responses to studied species were contrasting but, overall, Asparagopsis spp. effectively decreased daily CH4 emission, CH4 yield, and CH4 intensities by 29.8 ± 4.6%, 23.0 ± 5.3%, 34.0 ± 4.3%, and 22.6 ± 7.3%, respectively. Supplementation of 3-nitrooxypropanol decreased daily CH4 emission, yield, and intensity (per kg MY and ECM) by 28.2 ± 3.6%, 28.7 ± 2.8%, 29.2 ± 3.1%, and 31.8 ± 2.8%, respectively, compared with control. Decreasing dietary fiber (i.e., F:C, NDF, and ADF), whereas increasing dietary starch concentration increased the efficacy of 3-nitrooxypropanol at mitigating enteric CH4 emission. Nitrate supplementation decreased CH4 emission, yield, and intensity (per kg ECM) by 18.5% ± 1.9%, 17.6 ± 1.6%, and 13.0 ± 0.2%, respectively, compared with control. Efficacy of nitrate at mitigating enteric CH4 yield and CH4 intensity was positively associated with dose, and efficacy of nitrate at mitigating CH4 yield was positively associated with dietary starch concentration. Lipid supplementation decreased CH4 emission, yield, and intensities by up to 14.8 ± 2.3%, respectively, compared with control. Efficacy of lipids supplementation was positively associated with dietary EE, starch, and supplementation period, but negatively associated with dietary ADF concentration. Free oil supplementation tended to increase lipid efficacy by 31% at decreasing CH4 emission, compared with control. Condensed tannins and plant-derived bioactive compounds decreased CH4 yield by 11.3 ± 2.9% and 5.7 ± 2.5%, respectively, but oregano did not affect enteric CH4 emission metrics in the current meta-analysis. Direct-fed microbials were not effective in mitigating enteric CH4 emission variables. Data were limited to determine the effects of dietary nutrients and duration of supplementation on efficacy of Asparagopsis spp., plant secondary compounds and DFM. Overall, supplementation of the diet with Asparagopsis spp., 3-nitrooxypropanol, nitrate, and lipids were the most effective strategies for decreasing enteric CH4 emission in dairy cattle. Variability in the efficacy of most CH4 mitigation strategies can be partially explained by differences in treatment dose, dietary nutrient composition, and supplementation period.