Effective Dose Research Articles

Stereoselective Oxidation of α-Copaene, a Fire Ant Repellent Sesquiterpene from the Essential Oil of Dipterocarpus turbinatus.

Imported fire ants are significant agricultural pests. Repellents can be used to prevent foraging fire ants from entering sensitive areas, including electrical equipment, nursing homes, and hospitals. Bioassay-guided fractionation of the essential oil extracted from gurjun balsam (Dipterocarpus turbinatus) resulted in the identification of (-)-α-copaene (1) as the repellent constituent with a minimum repellent effective dose (MRED) of 15.6 μg/g against both red imported fire ants (Solenopsis invicta) and hybrid imported fire ants (Solenopsis invicta × Solenopsis richteri). Stereoselective oxidation of 1 via autoxidation and chemical methods produced (-)-5R-hydroperoxy-α-copaene (2), (+)-3S-hydroperoxycopa-4-ene (3), (-)-α-copaene oxide (4), (+)-β-copaen-4α-ol (5), copaenediol (6), and copaene ketol (7). Reduction of 2 and 3 with triphenylphosphine afforded (-)-5R-hydroxy-α-copaene (2a) and (+)-3S-hydroxycopa-4-ene (3a), respectively, which led to the structural revision of copa-3-en-2α-ol and copa-2-en-4-ol as 2a and 3, respectively. The configurational assignment of compound 4 in the literature was also clarified by the detailed analysis of 2D NMR spectroscopic data. Compounds 2-7 showed repellency with MREDs ranging from 3.9 to 15.6 μg/g against hybrid and red imported fire ants, indicating that chemical modification can enhance the repellent effect of (-)-α-copaene.

Assessing Effective Doses and Proposing DRLs for Pediatric CT Procedures in Madinah (Single Hospital), Saudi Arabia

This study aims to assess effective radiation doses (EDs) for pediatric computed tomography (CT) procedures in Madinah (single hospital), Saudi Arabia, and propose diagnostic reference levels (DRLs) for these procedures. This retrospective study collected data from 600 pediatric patients who underwent five CT procedures. The data were categorized by the type of CT procedure and the age of the patients. EDs and proposed DRLs for the pediatric CT procedures were computed. The highest EDs were found for abdominal (6.3 mSv) and head (4.8 mSv) CT procedures in pediatric patients aged <1 year. DRLs of the CTDIvol and DLP for abdominal and head CT procedures in pediatric patients aged <1 year were 4.2 mGy, 94 mGy.cm and 25 mGy, 414 mGy.cm, respectively. Chest EDs had the lowest EDs among all pediatric CT procedures, with EDs of 1.93, 1.51, 1.91, and 2.05 mSv in patients aged <1, 1 ≤ to < 5, 5 ≤ to < 10, and 10 ≤ to ≤ 15 years, respectively. It can be concluded that optimization is required for abdominal and head CT procedures in pediatric patients aged <1 year. Frequent updates on ED and DRL calculations will help monitor radiation doses and minimize radiation risks for patients undergoing these procedures.

Natural radionuclide profiles and radiological risks in soils and rocks of the Koytash-Ugam Range, Uzbekistan.

This investigation quantifies the activity concentrations of natural radionuclides (226Ra, 232Th, and 40K) in the soils and certain rocks of the Koytash-Ugam Range, Uzbekistan, and assesses their radiological risks. Gamma-spectrometric analysis of soil and rock samples revealed activity concentrations ranging from 456.2 ± 56.0 to 813.9 ± 76.0Bqkg-1 for 40K, 18.2 ± 6.3 to 70.0 ± 12.0Bqkg-1 for 226Ra, and 30.1 ± 2.9 to 57.9 ± 10Bqkg-1 for 232Th. This data indicates a heterogeneous distribution of radionuclides, informing radiation safety and health risk assessments on a global scale. The calculation of radiological hazard indices, including the alpha-index (ranging from 0.09 to 0.35), gamma-index (ranging from 0.40 to 0.73), and both internal (ranging from 0.40 to 0.54) and external (ranging from 0.36 to 0.54) hazard indices, was undertaken to ascertain potential health risks. The radium equivalent activity ranged from 108.4 to 199.3Bqkg-1, and the absorbed dose rates were 51.0-93.3 nGy h-1 indoors and 96.6-178.2 nGy h-1 outdoors. These metrics underlie the estimated annual effective dose of 536.5-988.5 × 10-3mSv y-1, highlighting the variability in radiation exposure. Additionally, the potential lifetime cancer risk was projected at 1770.4 to 3262.0 per million, with an annual gonadal dose equivalent of 361.9 to 655.5 μSv y-1, reflecting natural background radiation influence. The results underscore the importance of safe material use in construction and the necessity for routine natural radioactivity monitoring. Radon flux density (RFD) values within acceptable construction limits (26-176mBqm-2s-1) suggest the area's suitability for development, considering recommended safety guidelines. This study not only aids local environmental and public health frameworks but also enriches the international knowledge base, facilitating comparative studies for the advancement of global radiation protection standards. Through a detailed examination of radionuclide distribution in an under-researched area, our research highlights the critical need for integrated international approaches to natural radiological hazard assessment.

Biological effective dose as a predictor of local tumor control in stereotactic radiosurgery treated parasellar meningioma patients

IntroductionThe radio-surgical literature increasingly uses biological effective dose (BED) as a replacement for absorbed dose to analyze outcome of stereotactic radiosurgery (SRS). There are as yet no studies which specifically investigate the association of BED to local tumor control in para-sellar meningioma.Methodswe did a retrospective analysis of patients underwent stereotactic radiosurgery (SRS) for para-sellar meningioma during the period of 1995–2022. Demographic, clinical, SRS parameters, and outcome data were collected. The target margin BED with and without a model for sub-lethal repair was calculated, as well as a ratio of BED at the target margin to the absorbed dose at the target margin. Factors related to local control were further analyzed.ResultsThe study was comprised of 91 patients, 20 (22.0%) and 71 (78.0%) of whom were male and female, respectively. The median age was 55.0 (interquartile range Q1, Q3:47.5,65.5years). 34 (37%) patients had a resection of their meningioma prior to SRS. The median interval from SRS to last clinical follow up or progression was 89 months. 13 (14.3%) patients were found to have progression. 3-, 5- and 10-years local tumor control were 98%, 92% and 77%, respectively. In cox univariate analysis, the following factors were significant: Number of prior surgical resections (Hazard Ratio [HR] = 1.82, 95% CI = 1.08–3.05, p = 0.024), BED (HR = 0.96, 95% CI = 0.92-1.00, p = 0.03), and BED/margin (HR = 0.44, 95% CI = 0.21–0.92, p = 0.028). A BED threshold above 68 Gy was associated significantly with tumor control (P = 0.04).ConclusionBED and BED /margin absorbed dose ratio can be predictors of local control after SRS in parasellar meningioma. Optimizing the BED above 68Gy2.47 may afford better long-term tumor control.

The correlation between indoor and soil gas radon concentrations in Kiraz district, İzmir.

All humans are exposed to radon, the primary source of natural radiation, which can harm people due to natural processes rather than human activity. Thus, it is of significant importance to determine the levels of radon in indoor, soil gas, water, and outdoors. Radon concentration (CRn) was measured in Kiraz district, İzmir, and the correlation between the indoor and soil gas CRn values was investigated. The indoor CRn values measured in 40 randomly selected dwellings in Kiraz exhibited a wide range from 19.50 ± 2.50 to 204.70 ± 8.00Bqm-3 with an average value of 61.11 ± 4.23Bqm-3. The measured indoor CRn values were compared to the reference levels in the world to help control radon in the dwellings. Indoor CRn values were lower than the ICRP reference level of 300Bqm-3 in all of the dwellings studied. Furthermore, in 34 dwellings (representing 85% of the total number of dwellings studied), indoor CRn values were lower than the WHO reference level of 100Bqm-3. Health hazard indices, namely annual effective dose (AED) and excess lifetime cancer risk (ELCR), were also calculated for each dwelling and compared with internationally acceptable levels to estimate the risk to human health. The AED values varied from 0.49 ± 0.06 to 5.16 ± 0.20mSv y-1 with an average value of 1.54 ± 0.11mSv y-1, which exceeds the world average of 1.15mSv y-1 as reported by UNSCEAR. The ELCR values ranged from 2.05 ± 0.26 × 10-3 to 21.55 ± 0.84 × 10-3 with an average value of 6.43 ± 0.44 × 10-3, exceeding the world average of 0.29 × 10-3 as reported by UNSCEAR. The soil gas CRn values measured exhibited a wide variation ranging from 129.25 ± 6.38Bqm-3 to 6172.64 ± 44.06Bqm-3 with an average value of 1291.79 ± 18.70Bqm-3. The soil gas CRn values were less than 10,000Bqm-3; hence, the research area is categorized as "low radon risk areas" according to Sweden Criteria, and so no special constructions are required in the studied area. When soil gas CRn values were compared to indoor CRn values, no linear relationship was found between the CRn values. However, a strong positive linear correlation was found between indoor and soil gas CRn values less than 200Bqm-3 and 2500Bqm-3, respectively.

Bioprospecting the Anticancer Efficacy of <i>Garcinia anomala</i> from North-East India in Ovarian Cancer Cells – An <i>In Vitro</i> Study

Background: Ovarian cancer is a type of gynaecological cancer with a worldwide prevalence affecting women aged above 50. Despite several advances made in chemotherapy and surgery, the average time of clinical exemption is approximately two years, and the 5-year survival rate is 45%. But even after survival, they have long-term side effects. So, there is an urgent need for natural anticancer drugs. In this context, Garcinia spp. is one such plant that is explored for its anticancer properties. However, the endemic species Garcinia anomala from North-East India has not been studied for anticancer efficacy. Thereby present study aimed to understand the anticancer efficacy of hexane and methanol extracts of Garcinia anomola short mamilla plant available in the North-East region of India with a major emphasis on antioxidant potential. Further, the best extract with higher antioxidant activity was used to evaluate the anticancer potential through modulation of redox status. Methods: Total phenolic content in extract samples was determined by the Folin-Ciocalteu method. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity assay was used to assess the antioxidant activities of extracts. For in vitro evaluation of the anticancer potential of the extract, ovarian teratocarcinoma PA1 cells were used as a model to study the dose-dependent effect of the extract. Various assays, such as wound healing assay and transcriptional analysis of genes, such as Bcl-2, PCNA, and TP53, were performed. For the redox parameter, DCFDA (2’,7’-Dichlorofluoroscin Diacetate) assay was used. Results: The results showed that Garcinia anomola methanol extract (EB) exhibited higher antioxidant activity in comparison to the hexane extract (EA). A cytotoxicity assay was performed to find the effective IC50. From this assay, the effective dose concentration confirmed for EA was 40 µg/mL, EB was 20 µg/mL, and the time point selected was 24 hrs. As the IC50 for EB was less than EA, EB was chosen for further assays. From the wound healing assay, the migration rate obtained was 0.967±0.041 µm/hr. The methanol extract was found to affect key cell cycle checkpoint genes at the transcript level. Conclusion: These results indicate that the anticancer potential is mediated through the modulation of antioxidant status. Thus, Garcinia anomala short mamilla extract from northeast India has good efficacy as an anticancer agent, which can be considered as a future potent drug candidate for ovarian cancer.

Expanding the dose window of step-etched space-modulated JTE for ultrahigh voltage 4H-SiC devices

A step-etched space-modulated junction termination extension (SE-SM-JTE) is proposed for ultrahigh voltage (≥10 kV) 4H-SiC devices in this work. The proposed structure creates a stepped effective JTE dose profile by introducing the step etching into space-modulated JTE (SM-JTE), which shows great merits in the compromises of the JTE dose window, termination efficiency, termination area, and the complexity of the fabrication process. According to the TCAD simulation results, the SE-SM-JTE with a length of 300 μm (3 times the drift layer thickness) obtains a wide implantation dose window of ±47 % above 12 kV, achieving a wide tolerance to JTE dose and surface fixed charge. The maximum breakdown voltage (BV) of the proposed SE-SM-JTE is 13.8 kV, exhibiting a termination efficiency of 92 %. Moreover, the proposed JTE structure requires only a single ion implantation and subsequent two etchings, which facilitates the fabrication feasibility in ultrahigh voltage 4H-SiC devices.

Practical guidance on the assessment of radiation risks for diagnostic radiological examinations.

Patient doses cannot be limited; instead, radiological examinations should be justified and optimized to ensure the necessary diagnostic or therapeutic effect with the lowest patient dose achievable. Assessment of the radiation risks from patient exposure is important part of the justification process. Hence, medical staff within the framework of their professional activities should possess necessary information on the data on radiation risk from different types of radiological procedures. An approach has been developed that allows considering age and gender dependences of the risk coefficients of radiogenic cancer and the age and gender distribution of patients for various radiological examinations to assess the individual radiation risk for patient and collective risk for population from medical exposure. The approach is based on a new expanded use of the effective dose concept proposed in ICRP Publication 147 and demonstrated using the medical exposure in the Russian Federation as the example. For 30 radiological examinations that compose about 80% of the collective dose from medical exposure of the public in the Russian Federation radiation risk was assessed based on calculated age and gender specific risk coefficients per unit effective dose. For the rest of the examinations a simplified approach was used to assess the risk, which was based on using an age and gender specific risk coefficient determined for one of 4 anatomical regions (head, neck, chest and abdomen) or for uniform irradiation of the whole body. The proposed approach allows significantly improving the assessment of the radiation risk while continuing to use the effective dose as a dosimetric quantity within the framework of the state program in the Russian Federation. As a result the collective risk from medical examinations in the Russian Federation in 2022 was lower by the factor of 3 compared to the previous assessment based on the effective dose with the nominal risk coefficient.

Investigation of the in-vitro lethal effect of spilanthol on demodex and finding the most effective dose.

Demodex species are associated with many dermatological diseases, so an acaricidal agent that is effective against them and safe for skin applications may benefit many diseases. This study aims to investigate the anti-demodex potential of spilanthol, a product obtained from the Spilanthes Acmella plant, by determining the minimal effective dose for the first time in the literature. Demodex mites were obtained from 70 patients with standard superficial skin biopsy. Spilanthol extract was used at 1%, 2%, 3%, 4%, and 5%. Standard immersion oil was used for the negative control, and permethrin 5% was used for the positive control group. The dependent variable is the survival time of the mite. Comparisons with the negative control group, the anti-demodex effect demonstrated itself in all groups, creating a statistically significant difference (p < 0.001). The positive control group, had 3%, 4%, and 5% spilanthol rates which were very similar to the results with 5% permethrin (p > 0.05). Higher concentrations than 3% did not make any additional contribution to survival times. This is the first attempt to show the dose-dependent acaricidal effect of spilanthol on demodex mites. Even the 3% dose shows similar results to 5% permethrin, and no additional effect increase was observed at higher doses. Therefore, in vivo, studies may be planned with a 3% spilanthol dose for further studies.

Calculation of Effective Dose of Phenylephrine Bolus for Treatment of Post–Spinal Hypotension in Preeclamptic Patients Undergoing Caesarean Section—A Nonrandomized Controlled Trial

Calculation of Effective Dose of Phenylephrine Bolus for Treatment of Post–Spinal Hypotension in Preeclamptic Patients Undergoing Caesarean Section—A Nonrandomized Controlled Trial

"Ultralow-dose" CT Without Sedation in Pediatric Patients With Neuromuscular Scoliosis.

Children with neuromuscular scoliosis undergoing scoliosis surgery face substantial rates of complications. To mitigate surgical risks such as blood loss in pediatric patients with neuromuscular scoliosis, this study focuses on enabling instrumentation planning for their abnormal vertebral and pelvic anatomy and osteopenia. This study assessed the feasibility of an "ultralow-dose" CT (ULD CT) protocol without sedation in pediatric patients with neuromuscular scoliosis who often have comorbid movement disorders. Our prospective quality improvement study aims: (1) to determine if ULD CT without sedation is feasible in this patient group; (2) to quantify the radiation dose from ULD CT and compare it with preoperative spine radiographs (XR); and (3) to assess if ULD CT allows accurate anatomical assessment and intraoperative navigation given the prevalence of movement disorders. Children with neuromuscular scoliosis underwent spine XR and ULD CT scans. Chart reviews assessed disease etiology and comorbidities. Radiation dose was quantified through Monte-Carlo simulations giving dose indices and effective dose, with statistical analysis done using a paired student's t-test (α=0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation. Fourteen patients (5 males, 9 females, average age 14±3y) participated. One patient needed sedation due to autism spectrum disorder and global developmental delay. The radiation dose for spine XR was 0.5±0.2mSv, and ULD CT was 0.6±0.1mSv. There was no statistically significant difference in radiation doses between methods. All ULD CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2 Alar-Iliac screw orientation, and intraoperative navigation. ULD CT without sedation is feasible for children with neuromuscular scoliosis. Radiation doses were comparable to standard radiographs. ULD CT provided accurate anatomical assessments and supported intraoperative navigation, proving beneficial despite movement disorders in these patients. Level 2-Development of diagnostic criteria on basis of consecutive patients (with universally applied reference widely accepted standard).

Evaluation of ocular and systemic endpoints after radiation of posterior uveal melanoma – A systematic review and meta-analysis

BackgroundDue to the large number of radiotherapeutic options for treatment of posterior uveal melanoma (UM), advantages of each option regarding important clinical endpoints have yet to be determined. Therefore, objective of this systematic review was to analyze the numerous pro- and retrospective cohort studies focusing on the efficacy of different radiotherapeutic options for UM in adults, considering local tumor control, overall survival, visual acuity, eye preservation, metastasis, radiation side effects and dose rates. MethodsThe Review was performed based on the Cochrane Handbook of Systematic Reviews. The PubMed database was searched for studies published from January 1st, 2000, up to December 31st, 2021. Research, study selection and critical appraisal was performed by two reviewers. The risk of bias assessment was performed through the revised Cochrane risk of bias tools RoB 2 and ROBINS-I. A meta-analysis of proportions was performed using R (R version 4.1.3, library: meta, procedure: metaprop). This systematic review was registered with Prospero (ID CRD42022311758). ResultsOf 4886 studies identified in the database, a total of 20 studies with 4979 participants were included in the qualitative synthesis. Through critical appraisal with ROBINS-I and RoB 2, studies received a ‘moderate’, ‘serious’ or ‘some concerns’ overall risk of bias. Heterogeneity analysis allowed for meta-analysis of proportion of 3 outcome-therapy combinations: local tumor control with I-125 Brachytherapy (proportion: 0.94, CI 95 %: 0.91–0.98), local tumor control with proton therapy (proportion: 0.96, CI 95 %: 0.92–1.00) and eye preservation with I-125 brachytherapy (proportion: 0.91, CI 95 %: 0.88–0.93). This shows local tumor control to be at 94 % with I-125 brachytherapy and at 96 % with proton therapy, as well as an eye preservation rate of 91 % with I-125 brachytherapy. DiscussionThe evaluation of outcomes of radiotherapy in UM is limited because of missing data on radiation doses as well as great heterogeneity of study protocols. Radiation therapy outcomes are so far not comparable. Therefore, we recommend for upcoming studies on this topic to provide the biological effective dose (BED) or the equivalent dose in 2 Gy fractions (EQD2) per eye structure, thereby enabling a comparison of outcomes of different forms of radiation therapy.

Synthesis and Activity of T-Cell Tumor-Directing MegaMolecules.

This paper describes the synthesis, characterization, and functional activity of 26 MegaMolecule-based bispecific antibody mimics for T-cell redirection toward HER2+ cancer cells. The work reports functional bispecific MegaMolecules that bind both receptor targets, and recruit and activate T-cells resulting in lysis of the target tumor cells. Changing the orientation of linkage between Fabs against either HER2 or CD3ε results in an approximately 150-fold range in potency. Increasing scaffold valency from Fab dimers up to tetramers improves the potency of the antibody mimics up to 5-fold, but with diminishing returns in effective dose beyond trimeric formats. Antibody mimics that present either one or two Fabs against either receptor target allows for initial engagement of one cell type over the other. Finally, the antibody mimics significantly reduce HER2+ tumor volumes in a humanized xenograft model of breast cancer.

Palmitoylethanolamide as a Supplement: The Importance of Dose-Dependent Effects for Improving Nervous Tissue Health in an In Vitro Model.

Palmitoylethanolamide (PEA) is a highly lipophilic molecule with low solubility, making absorption difficult. Recent techniques like micronisation, ultra-micronisation and combining PEA with solvents have improved their bioavailability and stability. Our study analysed particle size differences and absorption kinetics using specific solvents (PEAΩ and PEA DynoΩ) over time (0.5 h-6 h) in a dose-dependent manner (200 mg-1800 mg). The results showed that PEAΩ and PEA DynoΩ achieved 82-63% absorption at 3 h, compared to 30-60% for micronised, ultra-micronised PEA and a commercial product, highlighting the optimal dose range of 300 mg-600 mg. In addition, a 3D model of the peripheral nerve was utilised to explain the efficacy after gut passage and support the most effective dose (300 mg or 600 mg) achieved at the gut level. PEAΩ and PEA DynoΩ, which are associated with better intestinal bioavailability compared to PEA-micronised, PEA ultra-micronised and a commercial product, have allowed not only a reduction in the inflammatory context but also an improvement of peripheral nerve well-being by increasing specific markers like MPZ (26-36% vs. 8-15%), p75 (25-32% vs. 13-16%) and NRG1 (22-29.5% vs. 11-14%). These results highlight the potential of advanced PEA formulations to overcome solubility challenges and maintain in vitro efficacy, modulating peripheral nerve well-being.

Assessment of contamination level of radon (222Rn) in drinking water around Tulsishyam geothermal area and Savarkundla fault in Saurashtra, India.

This study aimed to estimate radon concentrations in groundwater and surface water to evaluate radon (222Rn) contamination in drinking water within the Amreli region of Saurashtra, Gujarat, India. Water samples from 84 sites, covering about 3000km2, were analyzed using the RAD7 device from Durridge Instruments. Samples were collected in 250ml radon-tight bottles. Radon concentrations ranged from 0.1 to 13.6Bq/L, averaging 4.52Bq/L. At three sites (P9, P29, P35), radon levels exceeded the USEPA limit of 11.1Bq/L. P9 and P29 are near the Tulsishyam geothermal area, while P35 is close to the Savarkundla fault. Geothermal fluids in Tulsishyam may facilitate radon migration, and swarm-type earthquakes near Savarkundla could also contribute to radon migration. Concurrently, physicochemical parameters like Potential of Hydrogen (pH) and Total Dissolved Solid (TDS) were measured, with no significant correlation found between radon levels and these parameters. Samples were taken from tube wells with depths ranging from 105 to 750 feet, averaging 359 feet. A strong and significant correlation (0.83) was observed between radon concentration and water depth. Health risks from radon exposure were assessed by estimating annual effective dose rates for different age groups through ingestion and inhalation. In some instances, the annual effective dose rate surpassed the WHO-recommended value of 100µSv/year. However, in most instances, the presence of radon in the water does not indicate a significant radiological risk.

The influence of natural antioxidants on the quality and storage capacity of semi-finished horse meat products

The article is devoted to the influence of natural antioxidants on the quality parameters of meat semi-finished products from horse meat and the microbiological stability of the product during its storage. In solving the set tasks, the standard, generally accepted methods of research were used. Statistical processing of the obtained results and assessment of data reliability were carried out by statistical methods using Microsoft Excel and Statistica (version 12.0). A new antioxidant of natural origin, dihydroquercetin, has been proposed and tested. Effective doses of its application have been established: 0.05 - 0.075% for raw horse fat and 0.075% for semi-finished meat products from horse meat produced with its addition. It has been shown that the administration of dihydroquercetin (Dx) together with ascorbic acid (AA) and tocopherol (Tp) is 10-30% more effective. The effect of dihydroquercetin on the indicators of oxidative spoilage in the technological process, from the production of horse meat to finished products using the latter, has been studied. The organoleptic parameters (appearance, odour, colour) of the control sample and the sample with 0.025% Dx by fat weight corresponded in their characteristics to the experimental samples with 0.05%, 0.075% and 0.1% by 45 days of storage. The introduction of dihydroquercetin, ascorbic acid, and tocopherol also makes it possible to slow down the microbiological spoilage of the semi-finished products that have been obtained during storage.

A new era of high-resolution CT diagnostics of the lung: improved image quality, detailed morphology, and reduced radiation dose with high-resolution photon-counting CT of the lungs compared to high-resolution energy-integrated CT.

High-resolution computed tomography (HRCT) is dependent on detailed morphology in diagnostic assessment of interstitial lung diseases. Photon-counting CT (PCCT) enables improved resolution while reducing radiation. To compare if the image quality, detailed morphology, and radiation dose in HRCT of the lung improves with PCCT compared to energy-integrated CT (EICT). HRCT with PCCT in patients with body mass index (BMI) from normal to obese, previously examined with different EICT were included. They were evaluated in a five-step scale for image quality according to Quality Criteria for CT (Diagnostic Requirement of the ImPACT group-European standardization). In addition, ground-glass opacities, bronchiectasis, emphysema, nodules, and subpleural detailed morphology (≤1 cm from the pleural border) were evaluated by three independent thoracic and/or pediatric radiologists. Visual grading characteristics (VGC) were used for comparison of image quality and detailed morphology and Fleiss kappa for intra-observer variability. Dose-length product (DLP) and CT dose index-volume (CTDIvol) were collected to calculate effective radiation dose. HRCT with PCCT in 52 women and 48 men (mean age=67.2 ± 13.6 years; age range=27-87 years; BMI=26.9 kg/m2; range=18.6-45 kg/m2) previously examined with EICT (mean age=65.3 ± 13.6 years; age range=27-85 years; BMI=27 kg/m2; range=18.9-45 kg/m2) were included. There were significant differences in image quality for all entities in favor of PCCT. The radiation dose was reduced with PCCT by 47% in all, particularly pronounced in obese with 48.5%. Image quality, detailed morphology, and radiation dose, particularly in obese patients, were significantly improved in HRCT with PCCT compared to conventional EICT. The new technique enables visualization of subpleural structures.

Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor.

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/β = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20Gy (in 27%), 20-30Gy (24%), 30-40Gy (36%) and ≥ 40Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

The Role of Nitric Oxide in the Proconvulsant Effect of Paraxanthine During the Intravenous Pentylenetetrazole Seizure Threshold Test in Mice

Background: Paraxanthine is the major metabolite of caffeine in humans. There is no definitive proof that paraxanthine affects seizures. Nitric oxide (NO) contributes to the central effects of paraxanthine. Objectives: In this study, we examined the effect of acute paraxanthine administration on the pentylenetetrazole (PTZ)-induced seizure threshold, focusing on the NO-cyclic guanosine monophosphate (cGMP) signaling pathway. Methods: Naval Medical Research Institute (NMRI) male mice (25 - 30 g) received paraxanthine (5, 10, 50, and 100 mg/kg) alone. L-arginine [a substrate for NO synthase (NOS)] (50 mg/kg) or L-NAME [a non-selective NOS inhibitor] (5 mg/kg) was administered alone or as pretreatment before the ineffective or effective doses of paraxanthine, respectively. The intravenous PTZ seizure threshold test was used to determine the thresholds for the onset of myoclonic twitch (MCT), generalized clonus (GNC), and forelimb tonus (FLT). Nitric oxide metabolites (NOx) were measured using the Griess method. Results: Paraxanthine administered at doses of 10 and 50 mg/kg significantly reduced the threshold for FLT (P &lt; 0.05 for both). At a dose of 100 mg/kg, paraxanthine significantly reduced the thresholds for the onset of MCT (P &lt; 0.001), GNC (P &lt; 0.01), and FLT (P &lt; 0.001). L-arginine (50 mg/kg), either alone or as pretreatment before paraxanthine (5 mg/kg), did not significantly change the seizure threshold. L-NAME (5 mg/kg) alone had no effect, but L-NAME pretreatment before paraxanthine (100 mg/kg) significantly increased the thresholds for the onset of MCT (P &lt; 0.001), GNC (P &lt; 0.001), and FLT (P &lt; 0.001). Only paraxanthine at a dose of 100 mg/kg significantly increased NOx levels in brain tissues (P &lt; 0.05). Pretreatment with L-arginine further increased the NOx level (P &lt; 0.001), whereas pretreatment with L-NAME decreased it (P &lt; 0.001) compared to the paraxanthine groups. Conclusions: Our results show that paraxanthine has a proconvulsant effect. The results of L-arginine or L-NAME pretreatment before paraxanthine support the possible interaction of the NO-cGMP pathway in the proconvulsant effect of paraxanthine.

Oral Pyronaridine Tetraphosphate Reduces Tissue Presence of Parasites in a Mouse Model of Chagas Disease.

The eukaryotic parasite Trypanosoma cruzi (T. cruzi) is responsible for Chagas disease, which results in heart failure in patients. The disease is more common in Latin America, and is an emerging infection with The Centers for Disease Control estimating that greater than 300,000 people are currently infected in the United States. This disease has also spread from South and Central America, where it is endemic to many other countries, including Australia, Japan, and Spain. Current therapy for Chagas disease is inadequate due to limited efficacy in the indeterminate and chronic phases of the disease, in addition to the adverse effects from nifurtimox and benznidazole, which are nitro-containing drugs used for therapy. There is a clear need for new therapies for the Chagas disease. Using a computational machine learning approach, we have previously shown that the antimalarial pyronaridine tetraphosphate is active against T. cruzi Brazil-luc in vitro against parasites infecting a myoblast cell line and is also active in vivo in an acute mouse model of Chagas disease when dosed i.p. We now further evaluated oral pyronaridine as a monotherapy to determine the minimum effective dose to treat acute and chronic models of Chagas disease. Our results for T. cruzi Brazil-luc demonstrated daily oral dosing with pyronaridine from 150 to 600 mg/kg resulted in statistically significant inhibition in the 7 day acute mouse model. Combination therapy with daily dosing of benznidazole and pyronaridine in the acute infection model demonstrated that 300 mg/kg pyronaridine could return statistically significant antiparasitic activity to a subtherapetic 10 mg/kg benznidazole. In contrast, pyronaridine as monotherapy or combined with benznidazole lacked efficacy in the chronic mouse model, whereas 100 mg/kg benznidazole alone demonstrated undetectable parasites in the heart of mice. Pyronaridine requires further assessment in other chronic models to identify if it can be used beyond the acute stage of T. cruzi infection.