Dose Group Research Articles

Researches on feeding behaviors of Nezara viridula (Linnaeus, 1758)(Hemiptera: Pentatomidae) adults in intermittent CO2 applications

In this study, the effects of 3 different doses (430, 600 and 670 ppm) of intermittent CO2 applications on the feeding behaviors of Nezara viridula L. (Hemiptera: Pentatomidae) Adults were determined. As nutritional behavior, the total nutrition duration of adult male and female individuals other than nutrients was examined. As a result of the study, no statistically significant difference was found between the total feeding times of female and male individuals of N. viridula. A statistically significant difference was found between the duration of stay on the nutrients of female and male individuals of N. viridula who received 600 ppm and 670 ppm doses of CO2. The duration of stay on the nutrients of male individuals who received 600 ppm and 670 ppm doses of CO2 was found to be significantly lower than the duration of stay on the nutrients of female individuals. The duration of stay on the nutrients of male individuals who received 670 ppm doses of CO2 was found to be significantly lower than the duration of stay on the nutrients of female individuals. No statistically significant difference was found between the CO2 dose groups of N. viridula and the total feeding times of the control group. A statistically significant difference was found between the CO2 dose groups of N. viridula and the duration of stay apart from the nutrients and the duration of stay on the nutrients of the control group. The duration of stay on the nutrients of individuals exposed to 600 and 670 ppm CO2 doses was found to be significantly lower than the duration of stay on the nutrients of individuals in the control group. In addition, the duration of stay apart from the nutrients of the individuals to whom 600 and 670 ppm CO2 doses were applied was found to be significantly higher than the duration of stay apart from the nutrients of the individuals in the control group. As a general result of this study, it was determined that as the application dose increased, the feeding behaviors of male and female individuals changed, male individuals reacted more to dose administration and remained on nutrients less than female individuals.

Study the Physiological Effects of Palm Heart Extract (PHE) on some Cardiac, Hepatic Enzymes, and Reproductive Hormones in Male Rats

Background: For a long time, researchers have extensively studied the health advantages of natural products derived from plants. Objective: The main goal of this study is to investigate the effects of palm heart extract (PHE) on the lipid profile and various parameters of the heart, liver, and reproductive system in male rabbits. Methods: The male rabbits were divided into four groups by chance; one group was given a standard diet for comparison, while the other three received a PHE supplement. The control group did not get any treatment while three groups were given medium to high doses of PHE daily for 8 weeks. Troponin and lipid profile levels were assessed for health indicators, while liver enzyme levels (ALT, AST, ALP) and total bilirubin were analyzed to evaluate liver function. Furthermore, hormone levels such as testosterone, LH (luteinizing hormone), and FSH (follicle stimulating hormone) were also observed during the entire study period. Outcomes: Lipid profile parameters, including cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), and high density lipoprotein cholesterol (HDL), were assessed before and after the intervention period. Results: The results indicated a reduction in TC and LDL levels in the treatment group compared to the control group was statistically significant (p < 0.05). Nonetheless, there were no changes observed in the levels of TG and HDL in both groups, with a p-value greater than 0.05. These results indicate that heart palm water extract might have the ability to lower lipid levels, especially in decreasing total cholesterol and LDL levels. Testosterone levels showed a small drop in the high dose group when compared to the control group, although there was no statistical significance (p > 0.05). LH levels did not significantly decrease in the medium dose group compared to the control group (p < 0.05). There were no notable variations in FSH levels among the groups (p < 0.05). In conclusion, male rabbits showed reduced troponin levels in a dose-dependent manner, indicating potential cardioprotective effects of HDP extract. The administration of HDP extract did not have any impact on liver function. Although reproductive hormone levels varied, additional research is required to understand the effects of heart palm extract on male reproductive health.

Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.

Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative. To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome. A PK/PD model was built to describe bacterial counts from 162 static in vitro time-kill curves evaluating the effect of afabicin desphosphono, the active moiety of the prodrug afabicin, against 21 Staphylococcus aureus strains. Combined with a mouse PK model, outcomes of afabicin doses of 0.011-190 mg/kg q6h against nine S. aureus strains in a murine thigh infection model were predicted, and thereafter refined by estimating PD parameters. A sigmoid Emax model, with EC50 scaled by the MIC described the afabicin desphosphono killing in vitro. This model predicted, without parameter re-estimation, the in vivo bacterial counts at 24 h within a ±1 log margin for most dosing groups. When parameters were allowed to be estimated, EC50 was 38%-45% lower in vivo, compared with in vitro, within the studied MIC range. The developed PK/PD model described the time course of afabicin activity across experimental conditions and bacterial strains. This model showed translational capacity as parameters estimated on in vitro time-kill data could well predict the in vivo outcome for a wide variety of doses in a mouse thigh infection model.

The impact of Codonopsis Pilosulae and Astragalus Membranaceus extract on growth performance, immunity function, antioxidant capacity and intestinal development of weaned piglets.

The objective of this study was to examine the impact of Codonopsis pilosula and Astragalus membranaceus extract (CA) on the growth performance, diarrhea rate, immune function, antioxidant capacity, gut microbiota, and short-chain fatty acids (SCFAs) in weaned piglets. A total of forty-eight 31-day-old weaned piglets, were divided into four groups randomly based on the treatment type: control group (CON), low dose group (LCA, 0.5% CA), medium dose group (MCA, 1.0% CA), and high dose group (HCA, 1.5% CA), and were fed for a duration of 28 days. On the morning of the 1st and 29th day, the piglets were assessed by weighing them on an empty stomach, recording their daily feed intake and diarrhea rate. CA increased the average daily weight gain and reduced F/G without significant differences, and the diarrhea rate was reduced in the LCA and MCA groups. Furthermore, the levels of T-AOC, SOD, GSH-Px, and MDA were increased. The levels of T-AOC in the LCA group and the MCA group, SOD in the MCA group, and GSH-Px in the HCA group were significantly higher compared with the CON group (p < 0.05). Additionally, CA significantly increased IgM, IgG, and IgA levels (p < 0.05). The results of gut microbiota analysis showed that the bacterial population and diversity of faeces were changed with the addition of CA to basal diets. CA increased the abundance of the beneficial bacterial Firmicutes and Lactobacillus. Additionally, Compared with the CON group, CA significantly increased the SCFAs content of weaned piglets (p < 0.05). CA can alleviate oxidative stress, improve immunity and antioxidant capacity, increase the abundance of beneficial bacteria, and the content of SCFAs for improving the intestinal barrier of piglets, thus promoting growth and reducing diarrhea rate in weaned piglets.

Real-Time Fluorescence Monitoring System for Optimal Light Dosage in Cancer Photoimmunotherapy.

Background/Objectives: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued. Methods: Mice were subcutaneously transplanted with A431 xenografts and categorized into control, clinical dose (cylindrical irradiation at 100 J/cm², frontal irradiation at 50 J/cm²), and evaluation groups. The rate of tumor IR700 fluorescence intensity decay to reach predefined rates (-0.05%/s or -0.2%/s) until the cessation of light irradiation was calculated using a real-time fluorescence imaging system. Results: The evaluation group exhibited antitumor effects comparable to those of the clinical dose group at a low irradiation dose. Similar results were observed across tumor sizes and irradiation methods. Conclusions: In conclusion, the optimal antitumor effect of NIR-PIT is achieved when the fluorescence decay rate reaches a plateau, indicating the potential to determine the appropriate dose for PIT using a real-time fluorescence monitoring system.

Research on ameliorating pulmonary fibrosis in silicosis mice of Cordyceps cicadae polysaccharides

Objective: A mouse silicosis model was constructed by injecting silicon dioxide (SiO(2)) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods: In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO(2) suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results: The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased (P<0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue (P<0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased (P<0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue (P<0.05) . Conclusion: The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO(2) particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Studies on the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue

Purpose To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels. Material and methods Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined. Results Compared with the control group, the histopathological scores, the positive area of senescence-associated-β-galactosidase (SA-β-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice. Conclusions The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.

Influencing factors of occupational health of clinical nuclear medical staff

Objective: To analyze the characteristics and its influencing factors of occupational injury among clinical nuclear medicine staff, and to put forward suggestions for formulating relevant radiation protection intervention measures. Methods: In March 2022, a study was conducted involving 12 medical institutions engaged in nuclear medicine in Gansu Province. The occupational health examination data of 1451 clinical nuclear medicine staff were analyzed. The study subjects were divided into two groups based on the median annual effective dose of external exposure in 2022: Group A (annual effective dose ≤0.2 mSv, n=927) and group B (annual effective dose >0.2 mSv, n=524). The effects of annual effective dose, age, seniority, gender and occupational category on occupational health of clinical nuclear medicine staff were analyzed. Classification variables between groups were compared with Pearson χ(2) test. Multivariate logistic regression was used to analyze the influencing factors of the abnormal results. Results: The abnormal rates of white blood cell count (WBC), red blood cell count (RBC) and hemoglobin (HGB) in female clinical nuclear medical staff were higher than those in males, and the differences were statistically significant (P<0.001). The abnormal rates of WBC and HGB in clinical nuclear medicine staff of different occupational categories were statistically significant (P<0.05). The abnormal rates of RBC and HGB of clinical nuclear medicine staff in annual effective dose group B were higher than those in group A, and the differences were statistically significant (P<0.05). Multivariate logistic regression results showed that the abnormal risks of RBC in annual effective dose group B was 2.465 times of that in group A, the abnormal risks of RBC, WBC and HGB in females were 9.354, 2.939 and 6.760 times of those in males, respectively. The abnormal risk of WBC in the radiotherapy group was 2.334 times of that in general radiotherapy group. The abnormal risk of lens in nuclear medicine group was 2.459 times of that in general radiotherapy group. The abnormal risk of ECG and lens in ≥35 years old age group were 1.814 times and 1.969 times of those in <35 years old age group, respectively. The abnormal risk of lens of the ≥10 working years group was 1.899 times of that in the <10 working years group. The risk of lymphocyte micronucleus abnormality in the interventional group was 1.481 times of that in the general radiotherapy group, the risk of lymphocyte micronucleus abnormality in females was 2.215 times of that in males. The risk of lymphocyte micronucleus abnormality and lymphocyte chromosome aberration in ≥35 years old age group were 2.552 and 2.266 times of those in <35 years old age group, respectively. The risk of lymphocyte micronucleus abnormality in the group with≥10 working years was 1.443 times of that in<10 working years group (P<0.05) . Conclusion: Long-term low-dose ionizing radiation has a certain effect on the lens and genetic indexes of clinical nuclear medicine staff.

Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease

BackgroundColony-stimulating factor 1 receptor (CSF1R)–dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.MethodsIn this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%.ResultsA total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group.ConclusionsTargeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.)

Which dose of calcium dobesilate is more effective and safe in chronic venous insufficiency? Multicenter retrospective clinical trial

Objectives This study aimed to evaluate the effectiveness and safety of different dosages of calcium dobesilate in the management of Chronic Venous Insufficiency (CVI) among patients in CEAP classes C3–C4. Methods A comprehensive multicenter retrospective analysis was conducted, including patients aged 18-70 with CEAP class C3–C4 CVI. Participants were divided into two groups: one receiving 500 mg of calcium dobesilate twice daily and the other 1000 mg twice daily. Patient progress was monitored using the Global Index Score, CIVIC-20 Score, and precise measurements of ankle and calf circumferences over a 12-month period. Results The higher dosage group (1000 mg twice daily) showed significant improvements in both symptom relief and edema reduction. Ankle circumference reduced notably at 6 months, while calf circumference and overall quality of life, measured by the Global Index Score, showed significant improvement by 12 months compared to the lower dosage group. Conclusions Higher doses of calcium dobesilate markedly enhance the management of CVI symptoms and reduce edema more effectively than lower doses, particularly in patients with advanced CVI. These findings support the use of higher dosages for optimal treatment, though further research is needed to fully evaluate long-term safety.

Pengaruh Bulai pada Perubahan Indeks Kadar Klorofil, Serapan Fosforus dan Boron pada Jagung Manis

Maize production and quality are affected by infection with plant pathogens. One of the maize's essential and main diseases is downy mildew caused by Peronosclerospora spp. Downy mildew is a limiting factor in increasing production and can reduce production by 80-100%. It is because the affected plant cannot produce cobs. Pathogens obtain nutrients from the host cell, which can kill the cell and damage the surrounding tissues, resulting in visible downy mildew symptoms. Boron (B) plays a role in forming phloem, increasing the fruit's number, weight, bunch weight, and diameter. The primary function of B at the molecular level is the cross-linking of pectin in the plant cell wall. Ramnogalacturonan II (RG II) is a pectic polysaccharide that contributes to the mechanical strength and properties of the primary wall cross-linked by borate diesters. Phosphorus (P) controls the downsides in the greenhouse and field conditions. This study aims to measure changes in chlorophyll index, P and B uptakes in downy mildew affected plants. The field experiment used a group randomized design with six natural phosphate (FA) application treatments and four groups of borax doses as replicates. The results showed that the downy mildew decreased the chlorophyll index of the leaves at different levels of attack. The results of P concentration according to the position of healthy plant leaves were significantly different due to P treatment. In contrast to concentration B, there is no real difference. P and B uptake results in downy mildew-infested plants showed a significant difference only in P uptake in leaves with 1 FA treatment. Keywords: boron, downy mildew, maize, phosphate

Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into five groups (n=120 each): negative control; positive control (3mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats

The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N′,N′-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.

Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography - a prospective single-center study.

Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies. Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography. Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch's t-tests. No biomarker exhibited a dose-dependent response following radiation (γH2AX: R2 = 0.0012, P = 0.86; MMP: R2 = 0.016, P = 0.53; mtDNA: R2 = 0.10, P = 0.11; ROS: R2 = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65). Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation.

Randomized dose-response trial of n-3 fatty acids in hormone receptor negative breast cancer survivors- impact on breast adipose oxylipin and DNA methylation patterns.

Increasing evidence suggests the unique susceptibility of estrogen receptor and progesterone receptor negative (ERPR-) breast cancer to dietary fat amount and type. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may modulate breast adipose fatty acid profiles and downstream bioactive metabolites to counteract pro-inflammatory, pro-carcinogenic signaling in the mammary microenvironment. To determine effects of ~1 to 5 g/d EPA+DHA over 12 months on breast adipose fatty acid and oxylipin profiles in women with ERPR(-) breast cancer, a high-risk molecular subtype. We conducted a 12-month randomized controlled, double-blind clinical trial of ~5g/d vs ~1g/d DHA+EPA supplementation in women within 5 years of completing standard therapy for ERPR(-) breast cancer Stages 0-III. Blood and breast adipose tissue specimens were collected every 3 months for biomarker analyses including fatty acids by gas chromatography, oxylipins by LC-MS/MS, and DNA methylation by reduced-representation bisulfite sequencing (RRBS). A total of 51 participants completed the 12-month intervention. Study treatments were generally well-tolerated. While both doses increased n-3 PUFAs from baseline in breast adipose, erythrocytes, and plasma, the 5g/d supplement was more potent (n =51, p <0.001). The 5g/d dose also reduced plasma triglycerides from baseline (p =0.008). Breast adipose oxylipins at 0, 6, and 12 months showed dose-dependent increases in unesterified and esterified DHA and EPA metabolites (n =28). Distinct DNA methylation patterns in adipose tissue after 12 months were identified, with effects unique to the 5g/d dose group (n =17). Over the course of 1 year, EPA+DHA dose-dependently increased concentrations of these fatty acids and their derivative oxylipin metabolites, producing differential DNA methylation profiles of gene promoters involved in metabolism-related pathways critical to ERPR(-) breast cancer development and progression. These data provide evidence of both metabolic and epigenetic effects of n-3 PUFAs in breast adipose tissue, elucidating novel mechanisms of action for high-dose EPA+DHA-mediated prevention of ERPR(-) breast cancer.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents

BackgroundExtending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose.MethodsWe quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches.ResultsWe estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21–27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose.ConclusionsImplementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Personalized selection of unequal sub-arc collimator angles in VMAT for multiple brain metastases

PurposeInvestigating the effects of unequal sub-arc personalized collimator angle selection on the quality of Volumetric Modulated Arc Therapy (VMAT) plans for treating multiple brain metastases. MethodsThis study included 21 patients, each with 2–4 target volumes of multiple brain metastases. Two stereotactic radiotherapy (SRT) approaches were utilized: sub-arc collimator VMAT (SAC-VMAT) and fixed collimator VMAT (FC-VMAT). In the SAC-VMAT group, multi-leaf collimators (MLC) shaped the target area, dividing the full arc into four unequal sub-arcs under the beam's eye view (BEV). Each sub-arc had an appropriate collimator angle selected to mitigate ‘island blocking problems'. Conversely, the FC-VMAT group used a fixed collimator angle of 15° or 345°. A comparative analysis of the dosimetric parameters of the target volumes and normal tissues, along with the monitor units (MU), was conducted between the two groups. ResultsThe mean dose and dose-volume to normal brain tissue (2–26 Gy, with a step of 2 Gy) were significantly lower in the SAC-VMAT group (P < 0.01). There was no statistical difference between the two groups in dose to the target volumes, conformity index (CI), homogeneity index (HI), and other normal tissues (P > 0.05). Compared with the FA-VMAT group, the SAC-VMAT group significantly reduced the gradient index (GI) (4.5 ± 0.59 vs 5.2 ± 0.75, P < 0.001) and MU (1774.33 ± 181.77 vs 2001.0 ± 344.86, P < 0.001). Notably, with an increase in the number of PTV, the SAC-VMAT group demonstrated more significant improvements in the dose-volume of normal brain tissue, GI, and MU. ConclusionsIn this study, personalized selection of the unequal sub-arc collimator angle ensured the prescribed dose to the PTV, CI, and HI, while significantly reducing the GI, MU, and the dose to normal brain tissue in the VMAT plan for multi-target brain metastases in the cohort of cases with 2–4 target volumes. Particularly as the number of targets increase, the advantages of this method become more pronounced.

Outcome and incidence of hypothyroidism in low-dose radioactive iodine treatment for hyperthyroidism

ObjectiveThe study aimed to analyze the outcome of low-dose radioactive iodine (RAI) treatment for hyperthyroidism, disclose whether age and gender influence the outcome and determine the incidence and onset time of hypothyroidism following low-dose RAI. Material and methodsA total of 158 patients who received doses less than 370 Mbq RAI were enrolled in the study. Treatment outcome and incidence of hypothyroidism were compared between different gender (45 male vs.113 female), age (77 patients ≥45 years old vs. 81 patients <45 years old) and dose (39 patients receiving higher doses RAI vs. 119 receiving lower dose with a cutoff of 222 MBq) groups. Treatment outcomes were categorized into post-treatment hypothyroidism, treatment failure (persistent hyperthyroidism), and euthyroidism. In those becoming hypothyroid, time to develop hypothyroidism was calculated for cumulative incidences over time. ResultsOut of 158 patients, 47 (29.7%) developed hypothyroidism, 101 (63.9%) had treatment failure, and 10 (6.3%) remained euthyroid after treatment. Response rates (33.6% vs. 43.5%, p = 0.260) and hypothyroidism incidences (26.9% vs. 38.5%, p = 0.170) did not differ significantly between lower and higher dose groups, neither between lower and higher age groups (p = 0.69 in response rates and p = 0.75 in hypothyroidism incidence). Females exhibited higher response rates (42.5% vs. 20.0%, p = 0.008) and hypothyroidism incidence (46.3% vs. 13.3%, p = 0.004) compared to males. Hypothyroidism onset occurred at a mean of 24.0 ± 29.2 months, and the cumulative incidences over time were 47% and 60% in six and twelve months, respectively. ConclusionsLow-dose RAI has a low response rate for treating hyperthyroidism. Although there may be a lower incidence of hypothyroidism following low-dose RAI compared to high-dose RAI, hypothyroidism may occur early after treatment. Besides, females have higher response rates but more incidence of hypothyroidism. The balance between the risks and benefits of using low-dose RAI should be taken into deliberate consideration.

Assessment of Mannitol-Induced Chronic Blood-Brain Barrier Dysfunction In Vivo Using Magnetic Resonance.

The blood-brain barrier (BBB) is essential for protection and plays a crucial role in chronic neurological disorders like small-vessel disease and Alzheimer's disease. Its complexity poses significant challenges for effective diagnostics and treatments, highlighting the need for novel animal models and comprehensive BBB dysfunction studies. This study investigates chronic BBB dysfunction induction using osmotic disruption via mannitol in healthy adult male Sprague Dawley rats over 12 weeks. Group 1 received 1 bolus/week (2.0 g/kg), Group 2 received 3 boluses/week (1.5 g/kg), and Group 3 received 3 boluses/week (2.5 g/kg). BBB dysfunction was assessed using gadolinium (Gd) infusion and MRI to evaluate location, severity, evolution, and persistence. MR spectroscopy (MRS) examined the brain metabolism changes due to intravenous mannitol, with T2-weighted MRI assessing brain lesions. Biomarkers of neuroinflammation were analyzed in the highest mannitol dose group. Our data show chronic BBB dysfunction primarily in the cortex, hippocampus, and striatum, but not in the corpus callosum of rats under periodic mannitol dosing in groups 1 and 2. MRS identified a distinctive metabolite signature, including changes in alanine, choline, and N-acetyl aspartate in the striatum of Group 1. No significant differences were found in the serum levels of all pro- and anti-inflammatory cytokines analyzed in the high-dose Group 3. This study underscores the feasibility and implications of using osmotic disruption to model chronic BBB dysfunction, offering insights for future neuroprotection and therapeutic strategies research.

In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats.

Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating-related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased Esr2 expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased Kiss1 transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.