Elevated Doses Research Articles

Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.

Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As2O3) in the mouse striatal region. Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 and 8mg/kg bw) alone and along with CUR (100mg/kg bw) orally for 45days.Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations. Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8mg/kg bw) and curcumin (100mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 and 8mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment. Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

ОЦІНКА ПОТОЧНОГО СТАНУ РАДІАЦІЙНОГО ЗАБРУДНЕННЯ ТЕРИТОРІЇ МАЙДАНЧИКУ УРАНОВОЇ СПАДЩИНИ КОЛИШНЬОГО ВО «ПХЗ»

The article summarizes the results of long-term radioecological monitoring of the environment radioactive state within the former 'Prydniprovsk chemical plant' and adjacent territories at the preparatory stage life cycle of uranium legacy site. Data analysis have been determined the background activity levels of natural radionuclides (in particular 238U, 226Ra, 230Th, 210Pb, 210Po) in soils, underground and surface waters, air (fall density and volume activity), exhalation of 222Rn from the soil surface and its volume activity. The results of the determined dynamics and trends in the formation of pollution of environmental elements, which form the main factors of exposure of workers and the population, are presented. Areas with elevated dose rate (≥0.5 μSv·h-1) occupy more than 30% of the entire legacy site territory. In the soil activity may be 10 to 1000 times higher than background (30-50 Bq·kg-1) and can exceed 1000 times the exemption level. In aerosols 238U and 226Ra activitis exceeding the background (0.1 µBq·m-2·s-1, 11.5 µBq·m3) by 100-200 times only during periods of earthworks, under normal conditions they are up to 1.5-2.0 times. The monthly average activity 222Rn in the air of open space are 4-5 times higher of the background (median 200±68 Bq∙m-3), in some areas they can exceed by up to 50 times. In the buildings premises on the site 222Rn can exceed the reference level (250 Bq∙m-3) by 1-5 times, and in individual basements by up to 100 times. The data analysis proves that main ways of exposure of workers are external gamma radiation, the inhalation exposure routes from aerosol pollution and the spread of OA 222Rn in the air can be significant only for workers work at the legacy site and do not pose a threat to the city's population. Radiation assessment contamination of underground and surface water showed in present conditions aquatic pathways cannot form any significant contributions to the radiation exposure dose of the public. The obtained results and data analysis of monitoring observations were used to substantiate the measures of the remediation strategy legacy site.

First-in-human study of dosimetry, safety and efficacy for [177Lu]Lu-P15-073: a novel bisphosphonate-based radioligand therapy (RLT) agent for bone metastases.

Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [177Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases. Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [177Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [99mTc]Tc-MDP bone scans. Serial planar whole-body scans monitored biodistribution over a 14-day period. Dosimetry was assessed for major organs and tumor lesions, while safety was evaluated through blood biomarkers and pain scores. Serial planar whole-body scans demonstrated rapid and substantial accumulation of [177Lu]Lu-P15-073 in bone metastases, with minimal uptake in blood and other organs. The absorbed dose in the critical organ, red marrow, was measured at (0.034 ± 0.010 mSv/MBq), with a notably low normalized effective dose (0.013 ± 0.005 mSv/MBq) compared to other 177Lu-labeled bisphosphonates. Persistent high uptake in bone metastases was observed, resulting in elevated tumor doses (median 3.12Gy/GBq). Patients exhibited favorable tolerance to [177Lu]Lu-P15-073 therapy, with no new instances of side effects. Additionally, 87.5% (7/8) of patients experienced a significant reduction in pain scale (numerical rating scale, NRS, from 5.1 ± 2.3 to 3.0 ± 1.8). The tumor-background ratio (TBRmean) of [99mTc]Tc-MDP correlated significantly with [177Lu]Lu-P15-073 uptake (P < 0.01), indicating its potential for prediction of absorbed dose. This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [177Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [177Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.

Influence of Gamma irradiation on shape memory polymer nano-composite for satellite deployment mechanism

This research investigates the impact of gamma irradiation on epoxy-MWCNT nanocomposites for satellite deployment mechanisms. Nanocomposites, enhanced with surfactants, were meticulously prepared and subjected to controlled gamma irradiation (250–1000 kGy) utilizing the Cobalt-60 facility Industrial Mega Gamma-1 at NCRRT in Egypt. Surface tension measurements explored surfactant effects on epoxy-MWCNT composites in acetone. Acetone reduced tension from 26.7 to be 24.2 (mN/m). Surfactants (Tween 80, SDS) effectively lowered tension (24.4 mN/m), while surfactant-free systems had higher tension (25.1 mN/m). Cationic surfactant (CTAB) slightly increased tension (25.4 mN/m) but aided MWCNT dispersion. Nonionic and anionic surfactants showed superior dispersing power, aligning with MWCNTs and enhancing dispersion. Thermogravimetric analysis (TGA) unveiled alterations in the thermal stability of epoxy-MWCNT nanocomposites induced by radiation, particularly evident at elevated doses (500 and 1000 kGy). Notably, surfactant-modified specimens exhibited discernible effects on various thermal stability parameters. DMA analysis revealed radiation-induced changes in viscoelastic properties. Unirradiated epoxy exhibited a Tg of 58 °C, while 250 kGy irradiation enhanced crosslinking (Tg: 64 °C). Higher doses (500 kGy, 1000 kGy) caused marginal Tg changes. Surfactant-modified samples showed varied effects, with Tween 80 emphasizing its role in phase separation. Results highlighted radiation’s influence on stiffness and energy dissipation. Shape memory behavior indicated increased recovery time with higher doses, except at 250 kGy. Epoxy-MWCNT exhibited a stable recovery time, suggesting a MWCNT stabilizing effect. Fixation rates consistently reached 100%, indicating improved shape recovery influenced by MWCNTs and surfactants. This study provides insights into optimizing nanocomposites for satellite deployment applications.

PSIV-19 The use of microencapsulated zinc oxide improves the growth performance and intestinal health of newly weaned piglets

Abstract The application of microencapsulation technology to protect zinc may support inclusion of reduced levels with similar benefits to elevated doses of free zinc oxide. This study aimed to compare the effects of different doses of a microencapsulated ZnO (Zinco-Plus S) and free ZnO in nursery diets on growth performance and intestinal health of pigs. A total of 480 newly weaned piglets [26 d of age, initial body weight (BW) = 7.39 kg] were randomly assigned to one of four dietary treatments for 35d. Treatments were as follow: free ZnO (3,000, 1,500, and 0 ppm at phase 1, 2, and 3, respectively) or one of three doses of the microencapsulated ZnO (400, 600, and 800 ppm) maintained consistently across all 3 nursery phases (total amount of zinc in diets were within limits allowed by Canadian regulation). Each dietary treatment had 10 replicates, with 12 pigs/pen, gender balanced. All treatments had protease (Jefo Protease; 125 g/t), xylanase (Belfeed Xylanase; 100 g/t) and protected organic acids and essential oils (Porcinat+; 2 kg/t in phase 1 and 2, 1 kg/t in phase 3). Body weight, BW gain and feed intake were measured to determine feed conversion. At the end of phase 1, fecal sample was collected (pooled of 4 samples/pen) to determine zinc excretion. At the end of phase 2, blood serum was collected (1 pig/pen) to measure calprotectin and diamine oxidase concentrations and, ileal tissue was collected (1 pig/pen) to measure expression of zonular occludens (ZO) -1. Data were submitted to ANOVA and Fisher test with significance set at P &amp;lt; 0.05. There was no difference (P &amp;gt; 0.05) in final BW of pigs across all treatments. Nonetheless, piglets receiving 800 ppm of the microencapsulated ZnO had improved (P &amp;lt; 0.05) feed conversion ratio compared with pigs fed diet containing free ZnO. There was no difference (P &amp;gt; 0.05) in serum concentrations of calprotectin and diamine oxidase across all treatments, indicating improved intestinal health regardless of the form of ZnO. Piglets supplemented with microencapsulated ZnO at 800 ppm had an increased (P &amp;lt; 0.05) intestinal expression of ZO-1 in comparison with piglets receiving free ZnO, indicating better intestinal integrity. Fecal zinc concentrations were reduced (P &amp;lt; 0.05) by 75 % with the inclusion of microencapsulated ZnO compared with free ZnO. Piglets supplemented with microencapsulated ZnO at 800 ppm improved (P &amp;lt; 0.05) feed cost per kg BW gain by 10.7 % when compared with free ZnO. These findings show that supplementing lower levels of zinc in nursery diets via microencapsulation technology improves growth performance and supports intestinal health at levels comparable with increased free ZnO supplementation. Moreover, the utilization of microencapsulated zinc oxide has the additional advantage of minimizing environmental impact through the reduction of zinc wastage.

Redox Concomitant Formation Method for Fabrication of Cu(I)-MOF/Polymer Composites with Antifouling Properties.

Marine biofouling, which is one of the technical challenges hindering the growth of the marine economy, has been controlled using cuprous oxide (Cu2O) nanoparticles due to the exceptional antifouling properties of Cu(I) ions. However, Cu2O nanoparticles have encountered bottlenecks due to explosive releases of Cu+ ions, high toxicity at elevated doses, and long-term instability. Here, we present a novel method called Redox Concomitant Formation (RCF) for fabricating a hierarchical Cu(I) metal-organic framework polypyrrole (Cu(I)-MOF/PPy) composite. This method enables in-situ phase transition via successive redox reactions that change the chemical valence state and coordination mode of Cu(II)-MOF, resulting in a new structure of Cu(I)-MOF while creating a PPy layer surrounded by the hierarchical structure. Owing to the steady release of Cu+ ions from the Cu(I) sites and photothermal properties of PPy, Cu(I)-MOF/PPy exhibits superior and broad-spectrum resistance to marine bacteria, algae, and surface-adhered biofilms in complex biological environments, as well as long-term stability, resulting in 100% eradication efficiency under solar-driven heating. Mechanistic insights into successive structural redox reactions and formation using the RCF method are provided in detail, enabling the fabrication of novel MOFs with the desired composition and structure for a wide range of potential applications.

Redox Concomitant Formation Method for Fabrication of Cu(I)−MOF/Polymer Composites with Antifouling Properties

AbstractMarine biofouling, which is one of the technical challenges hindering the growth of the marine economy, has been controlled using cuprous oxide (Cu2O) nanoparticles due to the exceptional antifouling properties of Cu(I) ions. However, Cu2O nanoparticles have encountered bottlenecks due to explosive releases of Cu+ ions, high toxicity at elevated doses, and long‐term instability. Here, we present a novel method called Redox Concomitant Formation (RCF) for fabricating a hierarchical Cu(I) metal–organic framework polypyrrole (Cu(I)−MOF/PPy) composite. This method enables in situ phase transition via successive redox reactions that change the chemical valence state and coordination mode of Cu(II)−MOF, resulting in a new structure of Cu(I)−MOF while creating a PPy layer surrounded by the hierarchical structure. Owing to the steady release of Cu+ ions from the Cu(I) sites and photothermal properties of PPy, Cu(I)−MOF/PPy exhibits superior and broad‐spectrum resistance to marine bacteria, algae, and surface‐adhered biofilms in complex biological environments, as well as long‐term stability, resulting in 100 % eradication efficiency under solar‐driven heating. Mechanistic insights into successive structural redox reactions and formation using the RCF method are provided in detail, enabling the fabrication of novel MOFs with the desired composition and structure for a wide range of potential applications.

A recombinant pseudorabies virus surface - displaying the classical swine fever E2 protein induces specific antibodies rapidly

Pseudorabies virus (PRV) and classical swine fever virus (CSFV) are both economically important pathogens threatening the pig industry in many countries. The triple-gene-deleted variant of PRV, herein referred to as rPRVTJ-delgE/gI/TK, has exhibited pronounced efficacy and safety profiles. This underscores its viability as a prospective vaccine vector. However, the generation of specific anti-E2 antibodies necessitates elevated immunization doses and extended durations when the extracellular domain of the E2 protein of CSFV is secreted via the recombinant rPRVTJ-delgE/gI/TK vector. To enhance the presentation of exogenous antigens by antigen-presenting cells (APCs), we engineered the E2 protein expressed on the surface of PRV particles in this study. The recombinant virus expressing the E2 protein with a heterogonous transmembrane domain was generated in the backbone of rPRVTJ-delgE/gI/TK and designated as rPRVTJ-UL44-E2. The E2 gene was fused to the 3′ terminus of the UL44 gene utilizing P2A, a self-cleaving peptide sequence. The electron microscopy showed that the E2 protein was anchored on the surface of the viral particles of rPRVTJ-delgE/gI/TK-E2. The insertion of the E2 gene did not alter the native biological characteristics of the viral vector. Rabbits immunized with 107 median tissue culture infective doses (TCID50) of rPRVTJ-UL44-E2 exhibited a rapid seroconversion to anti-E2 specific antibodies within 7 days post-immunization (dpi). All the rabbits immunized with the rPRVTJ-UL44-E2 had generated antibodies specific to E2 prior to the administration of the booster immunization. However, the immunized rabbits were not protected from the CSFV C-strain challenge. Nevertheless, this strategy has notably achieved rapid induction of E2-specific non-neutralizing antibodies. These findings provide insights that the design of rPRVTJ-UL44-E2 requires optimization, thereby indicating a promising avenue for augmenting vaccine-induced immune responses.

Interaction between antidepressant drug trazodone with double-stranded DNA: Multi-spectroscopic and computational analysis

Trazodone (TZD) is an antidepressant drug used to treat major depressive and sleeping disorders. Elevated doses of trazodone are associated with central nervous system depression, which manifests as nausea, drowsiness, confusion, vertigo, exhaustion, etc. To develop a clinically viable active pharmaceutical compound with minimal adverse effects, it is imperative to possess a comprehensive knowledge of the drug's action mechanism on DNA. Hence, we investigate the mode of interaction between trazodone and DNA utilizing various spectroscopic and computational techniques. Studies using UV–vis titration showed that the DNA and trazodone have an effective interaction. The magnitude of the Stern-Volmer constant (KSV) has been calculated to be 5.84 × 106 M−1 by the Lehrer equation from a steady-state fluorescence study. UV–vis absorption, DNA melting, dye displacement, and circular dichroism studies suggested that trazodone binds with DNA in minor grooves. Molecular docking and molecular dynamic simulation demonstrated that the TZD-DNA system was stable, and the mode of binding was minor groove. Furthermore, ionic strength investigation demonstrates that DNA and trazodone do not have a substantial electrostatic binding interaction.

P-699 High levels of total FSH during COS is detrimental to oocyte development in good responders: results from a three-year retrospective, multicenter study

Abstract Study question Are elevated doses of follicle stimulating hormone (FSH) detrimental to oocyte maturation and the efficacy of ovarian stimulation in good responders? Summary answer Elevated FSH levels reduce the number of oocytes collected from good responders. Patients receiving lower total FSH doses had optimal and higher maturation rates. What is known already There is an inverse relationship between the dose of exogeneous follicle stimulating hormone (FSH) and the number of oocytes retrieved. This relationship is independent of patient age or health and implies that excessive FSH doses administered during artificial reproductive technologies (ART) may be detrimental to oocyte maturation. Study design, size, duration This three-year retrospective, multicenter study included 1,075 oocyte donor cycles performed in three IVF clinics between January 2020 and December 2023 with at least a six-month interval between each cycle. Donors were all considered good responders and divided according to the total dose of FSH received per cycle (n = 289 cycles with &amp;lt;1,700 IU FSH; 400 cycles with 1,700 to 2,900 IU FSH; and 386 cycles with &amp;gt;2,900 IU FSH). Participants/materials, setting, methods The mean oocyte donor age was between 26.13 and 27.45 years old. The mean BMI for all three groups was 21. The association between the total FSH dose and serum anti-Müllerian hormone (AMH) level, follicle-to-oocyte index (FOI), number of oocytes retrieved, and oocyte maturation was assessed using the Student’s t-test (parametric) or Mann-Whitney-U test (non-parametric). Main results and the role of chance There were no significant differences in the mean serum AMH levels (5.31 vs. 5.27 vs. 5.13 ng/mL, respectively) and FOI (81.1 vs. 80.2 vs. 81.5, respectively) of patients who received different total doses of FSH. However, the number of oocytes retrieved from each group was inversely related to the total dose of FSH received (24.4 vs. 22.9 vs. 21.01 oocytes, respectively; p &amp;lt; 0.05) Limitations, reasons for caution Full characterization of the oocytes and their developmental potential was outside the scope of this retrospective study. Wider implications of the findings Gaining a better understanding of the complex interplay of gonadotropins throughout folliculogenesis can help optimize ovarian stimulation protocols to maximize the number of mature and developmentally competent oocytes recovered for clinical use. Trial registration number non applicable

Efficacy and Mechanisms of Antioxidant Compounds and Combinations Thereof against Cisplatin-Induced Hearing Loss in a Rat Model.

Cisplatin is an election chemotherapeutic agent used for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. Here, we show evidence that a cocktail of vitamins A, C, and E along with Mg++ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in rats. The addition of 500 mg N-acetylcysteine (NAC), which, administered individually, also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation results in functional degradation of ACEMg otoprotection. Mg++ administered alone, as MgSO4, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection is also greatly degraded. Increasing the dose of NAC to 1000 mg also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet-to-be-defined "antioxidation threshold", results in unrecoverable redox imbalance with loss of otoprotectant activity.

Enhancing Micropropagation of Adenophora liliifolia: Insights from PGRs, Natural Extracts, and pH Optimization.

The endangered plant species Adenophora liliifolia faces threats to its survival in the wild, necessitating the development of effective micropropagation techniques for potential reintroduction efforts. This study demonstrates that Adenophora liliifolia effectively reproduces on MS synthetic medium with diverse plant growth regulators (PGR) and natural extracts, facilitating swift micropropagation for potential future reintroduction endeavors. It highlights the substantial impact of PGR composition and natural extracts on the growth and development of A. liliifolia. The ideal growth medium for A. liliifolia was determined to be ½ MS with specific treatments. Additionally, incorporating silver nitrate (AgNO3) at 5 mg L-1 into the medium led to enhanced root formation and shoot length, albeit excessive concentrations adversely affected root development. Varying concentrations of NAA significantly affected different plant growth parameters, with the 0.1 mg L-1 treatment yielding comparable plant height to the control. Moreover, 50 mL L-1 of coconut water bolstered root formation, while 200 mL L-1 increased shoot formation during in vitro propagation. However, elevated doses of coconut water (CW) impeded root development but stimulated shoot growth. Experiments measuring chlorophyll a + b and carotenoid content indicated higher concentrations in the control group than differing levels of applied coconut water. Optimizing pH levels from 6.8-7 to 7.8-8.0 notably enhanced plant height and root formation, with significant carotenoid accumulation observed at pH 6.8-7. Soil samples from A. liliifolia's natural habitat exhibited a pH of 6.65. Ultimately, the refined in vitro propagation protocol effectively propagated A. liliifolia, representing a pioneering effort and setting the stage for future restoration initiatives and conservation endeavors.

The Impact of Cholecystectomy in Patients with Post-Bariatric Surgery Hypoglycemia

BackgroundMetabolic surgery is the foremost treatment for obesity and its associated medical conditions. Nonetheless, post-bariatric hypoglycemia (PBH) emerges as a prevalent complication. PBH pathophysiology implicates heightened insulin and glucagon-like peptide 1 (GLP-1) levels, with bile acids (BA) contributing to GLP-1 release. A plausible association exists between cholecystectomy and PBH, which is attributed to alterations in BA metabolism and ensuing hormonal responses. The objective of this retrospective cohort study was to evaluate the impact of cholecystectomy on PBH pharmacological treatment, diagnostic timelines and metabolic parameters.Materials and methodsPatients diagnosed with PBH after bariatric surgery were evaluated based on their history of cholecystectomy. Demographic, anthropometric and clinical data were collected. Mixed meal tolerance tests (MMTT) results were compiled to assess metabolic responses.ResultsOf the 131 patients with PBH included in the study, 29 had prior cholecystectomy. The time to PBH diagnosis was similar across groups. Patients with prior cholecystectomy required higher doses of acarbose (p = 0.046), compared to those without prior cholecystectomy. Additionally, MMTT revealed higher insulin (t = 60 min: p = 0.010 and t = 90 min: p = 0.034) and c-peptide levels (t = 60 min: p = 0.008) and greater glycemic variability in patients with prior cholecystectomy (p = 0.049), highlighting the impact of cholecystectomy on glucose metabolism.ConclusionOur study offers novel insights into PBH pharmacotherapy, indicating that PBH patients with a history of cholecystectomy require elevated doses of acarbose for symptom control than PBH patients without such surgical history. Furthermore, our findings underscore the pivotal role of hyperinsulinism in PBH aetiology, emphasizing the significance of the BA-GLP-1-insulin axis.Graphical

#1496 High levels of sclerostin promote bone resorption and changes and mineral metabolism

Abstract Background and Aims The physiological function of sclerostin (SOST) remains unknown. It is known that SOST is produced in osteocytes and functions as an inhibitor of the Wnt/β-catenin pathway. Similarly, it is well-established that low levels of SOST lead to bone alterations affecting cortical bone, resulting in osteopetrosis and reduced calciuria. High levels of SOST are associated with osteoporosis. In this study, we aimed to investigate the impact of three elevated doses of SOST on cortical, trabecular, and subchondral bone, as well as its relationship with other parameters of mineral metabolism. Method Bone histomorphometry, mCT, immunohistochemistry, and analysis of mineral metabolism parameters revealed that high doses of SOST over a 14-day period led to a reduction in trabecular bone volume due to a significant increase in bone resorption through the direct activation of osteoclastogenesis. Results Bone resorption, as measured by TRAP activity, was higher in trabecular, cortical, and subchondral bone. Similarly, high doses of SOST increased the number of hypertrophic chondrocytes, consequently expanding the growth plate area. Cortically, positive TRAP staining was observed, suggesting osteocytic osteolysis and trabecularization of cortical bone. The increased bone resorption resulted in a substantial rise in urinary excretion of phosphorus and calcium, accompanied by elevated levels of FGF23 and a significant decrease in PTH. Conclusion The findings suggest that elevated levels of SOST promote bone resorption through the activation of osteoclasts and the generation of osteocytic osteolysis. The increase in calcium and phosphorus levels led to changes in mineral metabolism, indicating a close relationship between SOST and other mineral metabolism parameters.

Phenomena observed in electron EBRT using a pulse-by-pulse radioluminescence dosimetry system with cloud-based analytics

The pulse-by-pulse characteristics of electron beams from a clinical linear accelerator (linac) at high dose rates are crucial for ensuring precise dose delivery in radiation therapy. In this research, we employ a radioluminescence scintillator made from Ge-doped silica optical fiber to analyse electron beams at standard therapy dose rates 600 cGy/min with energy of 15 MeV. The scintillator is combined with a photomultiplier tube (PMT) and a photon-counting setup to achieve microsecond (μs) gating times, providing high temporal resolution. For sub-microsecond (sub-μs) temporal resolution, we utilize a multi-pixel photon counter and a rapid digital oscilloscope. Our study examines the peak time and the time it takes for pulses to return to baseline, uncovering the effects of afterglow at elevated dose rates and its potential implications for dosimetry precision. Our results indicate that monitor chambers, which have lower temporal resolution than the radioluminescence system outlined in this study, may struggle to accurately track high-rate dose delivery, emphasizing the necessity for advanced monitoring methods in FLASH radiotherapy. The dosimetric data was further analysed for deeper analytics on a cloud-based system. The dosimetric data underwent advanced analysis on a cloud-based platform, employing a prototype analytics software system comprised of Dosi-Client and Dosi-Cloud Backend components for real-time data acquisition and processing. This innovative approach revealed significant insights into radiation dosimetry, including the detection of anomalies through a reconstruction convolutional autoencoder, enhancing the precision and reliability of dosimetric measurements.

Comparison of residual dose rates from MARS and DORIAN simulations with experimental data from the SINBAD database

This benchmarking study aims to compare residual dose rate predictions from the MARS and DORIAN codes with experimental measurements taken from samples irradiated at CERN's CERF facility. The research evaluates the residual dose rates of these samples over varied cooling intervals. Additionally, it delves into the influence of parameter choices, such as specific physics processes and energy thresholds, on the production and transport of particles and their effects on simulation outcomes. While both MARS and DORIAN largely align with experimental findings, discrepancies were observed in the copper sample. This prompted an in-depth examination of the elevated dose rates from MARS.

Germicidal lamps using UV-C radiation may pose health safety issues: a biomolecular analysis of their effects on apoptosis and senescence.

The battle against the COVID-19 pandemic has spurred a heightened state of vigilance in global healthcare, leading to the proliferation of diverse sanitization methods. Among these approaches, germicidal lamps utilizing ultraviolet (UV) rays, particularly UV-C (wavelength ranging from 280 to 100 nm), have gained prominence for domestic use. These light-emitting diode (LED) lamps are designed to sanitize the air, objects, and surfaces. However, the prevailing concern is that these UV lamps are often introduced into the market without adequate accompanying information to ensure their safe utilization. Importantly, exposure to absorbed UV light can potentially trigger adverse biological responses, encompassing cell death and senescence. Our research encompassed a series of investigations aimed at comprehending the biological repercussions of UV-C radiation exposure from readily available domestic lamps. Our focus centered on epithelial retinal cells, keratinocytes, and fibroblasts, components of the skin and ocular targets frequently exposed to UV irradiation. Our findings underscore the potential harm associated with even brief exposure to UV, leading to irreversible and detrimental alterations in both skin cells and retinal cells of the eye. Notably, epithelial retinal cells exhibited heightened sensitivity, marked by substantial apoptosis. In contrast, keratinocytes demonstrated resilience to apoptosis even at elevated UV doses, though they were prone to senescence. Meanwhile, fibroblasts displayed a gradual amplification of both senescence and apoptosis as radiation doses escalated. In summary, despite the potential benefits offered by UV-C in deactivating pathogens like SARS-CoV-2, it remains evident that the concurrent risks posed by UV-C to human health cannot be ignored.

Spatial Distribution of Gamma Dose Rates and Radioactivity Levels in Some Parts of Iju Community in Ado-Odo Ota, Ogun State

This study investigates the background dose rates and radiological risk exposure to Iju community in Ado-Odo Ota. Using a hand-held calibrated gamma detector (RS-125 Gamma-Spec), the study area’s outdoor gamma dose rates and radionuclide activity concentrations of 40K, 238-U, and 32-Th were measured in situ. The results showed differing activities of the primordial radionuclides (40-K, 238-U, and 232-Th) with average values lying within the recommended limits, with the exception of 40K, which geologically can be caused by regional subsidence while on marine transgression. Based on statistical analysis, the correlation results verified that 40K, 238-U, and 232-Th were the primary causes of the elevated outdoor dose rates at Iju community. The International Commission on Radiological Protection (ICRP) specified allowable limits for radiation exposure, and the estimated mean hazard indices for the increased lifetime cancer risk in the research area exceeded these limitations. In order to ensure sufficient radiation protection, the research area needs attention right away.

MANAGEMENT OF DIABETES INSIPIDUS AFTER SUBLABIAL TRANSSPHENOIDAL HYPOPHYSECTOMY SURGERY

MANAGEMENT OF DIABETES INSIPIDUS AFTER SUBLABIAL TRANSSPHENOIDAL HYPOPHYSECTOMY SURGERY

Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.