A simple protocol for cultivating the bacterivorous soil nematode Caenorhabditis elegans in its natural ecology in the laboratory.

The complex interplay between an animal and its surrounding environment requires constant attentive observation in natural settings. Moreover, how ecological interactions are affected by an animal's genes is difficult to ascertain outside the laboratory. Genetic studies with the bacterivorous nematode Caenorhabditis elegans have elucidated numerous relationships between genes and functions, such as physiology, behaviors, and lifespan. However, these studies use standard laboratory culture that does not reflect C. elegans true ecology. C. elegans is found growing in nature and reproduced in large numbers in soils enriched with rotting fruit or vegetation, a source of abundant and diverse microbes that nourish the thriving populations of nematodes. We developed a simple mesocosm we call soil-fruit-natural-habitat that simulates the natural ecology of C. elegans in the laboratory. Apples were placed on autoclaved potted soils, and after a soil microbial solution was added, the mesocosm was subjected to day-night, temperature, and humidity cycling inside a growth chamber. After a period of apple-rotting, C elegans were added, and the growing worm population was observed. We determined optimal conditions for the growth of C. elegans and then performed an ecological succession experiment observing worm populations every few days. Our data showed that the mesocosm allows abundant growth and reproduction of C. elegans that resembles populations of the nematode found in rotting fruit in nature. Overall, our study presents a simple protocol that allows the cultivation of C. elegans in a natural habitat in the laboratory for a broad group of scientists to study various aspects of animal and microbial ecology.

Quantitative radiomics approach to assess acute radiation dermatitis in breast cancer patients.

PURPOSE: We applied a radiomics approach to skin surface images to objectively assess acute radiation dermatitis in patients undergoing radiotherapy for breast cancer. METHODS: A prospective cohort study of 20 patients was conducted. Skin surface images in normal, polarized, and ultraviolet (UV) modes were acquired using a skin analysis device before starting radiotherapy ('Before RT'), approximately 7 days after the first treatment ('RT D7'), on 'RT D14', and approximately 10 days after the radiotherapy ended ('After RT D10'). Eighteen types of radiomic feature ratios were calculated based on the values acquired 'Before RT'. We measured skin doses in ipsilateral breasts using optically stimulated luminescent dosimeters on the first day of radiotherapy. Clinical evaluation of acute radiation dermatitis was performed using the Radiation Therapy Oncology Group scoring criteria on 'RT D14' and 'After RT D10'. Several statistical analysis methods were used in this study to test the performance of radiomic features as indicators of radiodermatitis evaluation. RESULTS: As the skin was damaged by radiation, the energy for normal mode and sum variance for polarized and UV modes decreased significantly for ipsilateral breasts, whereas contralateral breasts exhibited a smaller decrease with statistical significance. The radiomic feature ratios at 'RT D7' had strong correlations to skin doses and those at 'RT D14' and 'after RT D10' with statistical significance. CONCLUSIONS: The energy for normal mode and sum variance for polarized and UV modes demonstrated the potential to evaluate and predict acute radiation, which assists in its appropriate management.

Novel tongue-positioning device to reduce tongue motions during radiation therapy for head and neck cancer: Geometric and dosimetric evaluation.

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue.

Predictors of Extraprostatic Extension in Patients with Prostate Cancer.

PURPOSE: To identify effective factors predicting extraprostatic extension (EPE) in patients with prostate cancer (PCa). METHODS: This retrospective cohort study recruited 898 consecutive patients with PCa treated with robot-assisted laparoscopic radical prostatectomy. The patients were divided into EPE and non-EPE groups based on the analysis of whole-mount histopathologic sections. Histopathological analysis (ISUP biopsy grade group) and magnetic resonance imaging (MRI) (PI-RADS v2.1 scores [1-5] and the Mehralivand EPE grade [0-3]) were used to assess the prediction of EPE. We also assessed the clinical usefulness of the prediction model based on decision-curve analysis. RESULTS: Of 800 included patients, 235 (29.3%) had EPE, and 565 patients (70.7%) did not (non-EPE). Multivariable logistic regression analysis showed that the biopsy ISUP grade, PI-RADS v2.1 score, and Mehralivand EPE grade were independent risk factors for EPE. In the regression assessment of the models, the best discrimination (area under the curve of 0.879) was obtained using the basic model (age, serum PSA, prostate volume at MRI, positive biopsy core, clinical T stage, and D'Amico risk group) and Mehralivand EPE grade 3. Decision-curve analysis showed that combining Mehralivand EPE grade 3 with the basic model resulted in superior net benefits for predicting EPE. CONCLUSION: Mehralivand EPE grades and PI-RADS v2.1 scores, in addition to basic clinical and demographic information, are potentially useful for predicting EPE in patients with PCa.

Development of a quasi-3D dosimeter using radiochromic plastic for patient-specific quality assurance.

BACKGROUND: Patient-specific QA verification ensures patient safety and treatment by verifying radiation delivery and dose calculations in treatment plans for errors. However, a two-dimensional (2D) dose distribution is insufficient for detecting information on the three-dimensional (3D) dose delivered to the patient. In addition, 3D radiochromic plastic dosimeters (RPDs) such as PRESAGE® represent the volume effect in which the dosimeters have different sensitivities according to the size of the dosimeters. Therefore, to solve the volume effect, a Quasi-3D dosimetry system was proposed to perform patient-specific QA using predetermined-sized and multiple RPDs. PURPOSE: For patient-specific quality assurance (QA) in radiation treatment, this study aims to assess a quasi-3D dosimetry system using an RPD. METHODS: Gamma analysis was performed to verify the agreement between the measured and estimated dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). We fabricated cylindrical RPDs and a quasi-3D dosimetry phantom. A practicability test for a pancreatic patient utilized a quasi-3D dosimetry device, an in-house RPD, and a quasi-3D phantom. The dose distribution of the VMAT design dictated the placement of nine RPDs. Moreover, a 2D diode array detector was used for 2D gamma analysis (MapCHECK2). The patient-specific QA was performed for IMRT, VMAT, and stereotactic ablative radiotherapy (SABR) in 20 prostate and head-and-neck patients. For each patient, six RPDs were positioned according to the dose distribution. VMAT SABR and IMRT/VMAT plans employed a 2%/2 mm gamma criterion, whereas IMRT/VMAT plans used a 3%/2 mm gamma criterion, a 10% threshold value, and a 90% passing rate tolerance. 3D gamma analysis was conducted using the 3D Slicer software. RESULTS: The average gamma passing rates with 2%/2 mm and 3%/3 mm criteria for relative dose distribution were 91.6% ± 1.4% and 99.4% ± 0.7% for the 3D gamma analysis using the quasi-3D dosimetry system, respectively, and 97.5% and 99.3% for 2D gamma analysis using MapCHECK2, respectively. The 3D gamma analysis for patient-specific QA of 20 patients showed passing rates of over 90% with 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. CONCLUSIONS: The quasi-3D dosimetry system was evaluated by performing patient-specific QAs with RPDs and quasi-3D phantom. The gamma indices for all RPDs showed more than 90% for 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. We verified the feasibility of a quasi-3D dosimetry system by performing the conventional patient-specific QA with the quasi-3D dosimeters.

Extension of matRad with a modified microdosimetric kinetic model for carbon ion treatment planning: Comparison with Monte Carlo calculation.

BACKGROUND: Treatment planning is essential for in silico particle therapy studies. matRad is an open-source research treatment planning system (TPS) based on the local effect model, which is a type of relative biological effectiveness (RBE) model. PURPOSE: This study aims to implement a microdosimetric kinetic model (MKM) in matRad and develop an automation algorithm for Monte Carlo (MC) dose recalculation using the TOPAS code. In addition, we provide the developed MKM extension as open-source tool for users. METHODS: Carbon beam data were generated using TOPAS MC pencil beam irradiation. We parameterized the TOPAS MC beam data with a double-Gaussian fit and modeled the integral depth doses and lateral spot profiles in the range of 100-430 MeV/u. To implement the MKM, the specific energy data table for Z = 1-6 and integrated depth-specific energy data were acquired based on the Kiefer-Chatterjee track structure and TOPAS MC simulation, respectively. Generic data were integrated into matRad, and treatment planning was performed based on these data. The optimized plan parameters were automatically converted into MC simulation input. Finally, the matRad TPS and TOPAS MC simulations were compared using the RBE-weighted dose calculation results. A comparison was made for three geometries: homogeneous water phantom, inhomogeneous phantom, and patient. RESULTS: The RBE-weighted dose (DRBE ) distribution agreed with TOPAS MC within 1.8% for all target sizes for the homogeneous phantom. For the inhomogeneous phantom, the relative difference in the range of 80% of the prescription dose in the distal fall-off region (R80) between the matRad TPS and TOPAS MC was 0.6% (1.1 mm). DRBE between the TPS and the MC was within 4.0%. In the patient case, the difference in the dose-volume histogram parameters for the target volume between the TPS and the MC was less than 2.7%. The relative difference in R80 was 0.7% (1.2 mm). CONCLUSIONS: The MKM was successfully implemented in matRad TPS, and the RBE-weighted dose was comparable to that of TOPAS MC. The MKM-implemented matRad was released as an open-source tool. Further investigations with MC simulations can be conducted using this tool, providing a good option for carbon ion research.

European Committee on Antimicrobial Susceptibility Testing-Recommended Rapid Antimicrobial Susceptibility Testing of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus From Positive Blood Culture Bottles.

Background: Early diagnosis and treatment are important for a good prognosis of bloodstream infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends rapid antimicrobial susceptibility testing (RAST) based on the disk diffusion methodology for 4, 6, and 8 hours of incubation. We evaluated EUCAST-RAST of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus from positive blood culture bottles. Methods: Twenty strains of E. coli, K. pneumoniae, and S. aureus were tested using EUCAST-RAST. Ten antimicrobial agents against E. coli and K. pneumoniae and four agents against S. aureus were tested. The diameter of the inhibition zone (mm) was compared with the minimal inhibitory concentration (µg/mL) obtained using the Sensititre AST system (TREK Diagnostic Systems, East Grinstead, UK). Results: For E. coli, the percentage of total categorical agreement (CA) was 69.5% at 4 hours, and 87% at 8 hours. For K. pneumoniae, the total CA was 89% at 4 hours, and 95.5% at 6 hours. For S. aureus, the total CA was 100% after 4 hours. Discrepancies were observed mainly for E. coli with ß-lactam antimicrobial agents, and the numbers of errors decreased over time. Conclusions: EUCAST-RAST for K. pneumoniae and S. aureus met the United States Food and Drug Administration criteria at 6 and 4 hours, respectively, whereas that for E. coli did not meet the criteria for up to 8 hours. RAST can shorten the turn-around testing time by more than one day; therefore, if applied accurately according to laboratory conditions, antimicrobial agent results can be reported faster.

How to grow an oscillators' network with enhanced synchronization.

We study a way to set the natural frequency of a newly added oscillator in a growing network to enhance synchronization. Population growth is one of the typical features of many oscillator systems for which synchronization is required to perform their functions properly. Despite this significance, little has been known about synchronization in growing systems. We suggest effective growing schemes to enhance synchronization as the network grows under a predetermined rule. Specifically, we find that a method based on a link-wise order parameter outperforms that based on the conventional global order parameter. With simple solvable examples, we verify that the results coincide with intuitive expectations. The numerical results demonstrate that the approximate optimal values from the suggested method show a larger synchronization enhancement in comparison with other naïve strategies. The results also show that our proposed approach outperforms others over a wide range of coupling strengths.

Autodisplay of streptococcal protein G for construction of an orientation-controlled immunoaffinity layer.

An immunoaffinity layer with orientation-controlled antibodies was constructed to express streptococcal protein G in Escherichia coli cells using autodisplay technology. The sequence of protein G, a specific IgG-binding protein, was inserted into the autodisplay vector using recombinant technology and the constructed plasmid vector was transformed into E. coli cells. Protein G was confirmed to be autodisplayed with a high density of 2 × 105 copies per cell by SDS-PAGE analysis, and its IgG-binding affinity was confirmed by fluorescence microscopy. Autodisplayed protein G showed higher affinity than the IgG-binding Z-domain for goat IgG. Immunoassays based on E. coli cells were established to detect horseradish peroxidase (HRP) and C-reactive protein (CRP). Protein G autodisplaying E. coli cells were utilized as a solid support and immunoassays showed improved sensitivity by orientation control of autodisplayed protein G. The outer membrane (OM) of protein G autodisplaying E. coli was isolated and layered to construct an immunoaffinity layer. The OM was coated on a microplate to perform the immunoassays, which showed limits of detection of 5 and 0.2 ng mL-1 for HRP and CRP, respectively. An OM layer with autodisplayed protein G was applied as the immunoaffinity layer of a surface plasmon resonance (SPR) biosensor. After CRP detection, the SPR responses showed good linearity, with an R2 value of 0.99. The immunoaffinity layer with orientation control by autodisplayed protein G was confirmed to be applicable in immunoassays and immunosensors to improve sensitivity.

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria.

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

Near-maximum rib dose is the most relevant risk factor for ipsilateral spontaneous rib fracture: a dosimetric analysis of breast cancer patients after radiotherapy.

PURPOSE: Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. METHODS: We retrospectively reviewed 2204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). RESULTS: Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6 months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. CONCLUSION: Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.

Performance evaluation of a visual guidance patient-controlled respiratory gating system for respiratory-gated magnetic-resonance image-guided radiation therapy.

The performance of a visual guidance patient-controlled (VG-PC) respiratory gating system for magnetic-resonance (MR) image-guided radiation therapy (MR-IGRT) was evaluated through a clinical trial of patients with either lung or liver cancer. Patients can voluntarily control their respiration utilizing the VG-PC respiratory gating system. The system enables patients to view near-real-time cine planar MR images projected inside the bore of MR-IGRT systems or an external screen. Twenty patients who had received stereotactic ablative radiotherapy (SABR) for lung or liver cancer were prospectively selected for this study. Before the first treatment, comprehensive instruction on the VG-PC respiratory gating system was provided to the patients. Respiratory-gated MR-IGRT was performed for each patient with it in the first fraction and then without it in the second fraction. For both the fractions, the total treatment time, beam-off time owing to the respiratory gating, and number of beam-off events were analyzed. The average total treatment time, beam-off time, and number of beam-off events with the system were 1507.3 s, 679.5 s, and 185, respectively, and those without the system were 2023.7 s (p < 0.001), 1195.0 s (p < 0.001), and 380 times (p < 0.001), respectively. The VG-PC respiratory gating system improved treatment efficiency through a reduction in the beam-off time, the number of beam-off events, and consequently the total treatment time when performing respiratory-gated MR-IGRT for lung and liver SABR.

Scanning methodology for contact lens-type ocular in vivo dosimeter (CLOD) dosimetry applying a silicone material.

PURPOSE: Contact lens-type ocular in vivo dosimeters (CLODs) were recently developed as the first in vivo dosimeter that can be worn directly on the eye to measure the dose delivered to the lens during radiotherapy. However, it has an inherent uncertainty because of its curved shape. Newton's ring effect inevitably occurs because the spacing between the glass window and the active layer is not constant. Furthermore, it involves a large uncertainty because the objective of the CLOD with such morphological characteristics is to measure the dose delivered to an out-of-field lens. In this study, we aimed to investigate the effects of various compensating materials on the sensitivity, accuracy, and uniformity of analysis using a curved CLOD. We developed a new scanning methodology that involves applying a compensating material to reduce the uncertainty caused by the air gap. METHODS: Four compensating materials-Dragon Skin™ 10 (DS), a transparent silicon material, SORTA-Clear™ 40 (SC), optical grease (OG), and air (no compensating material)-were used in this study. The CLOD was scanned in the reflective mode and transmission mode using each compensating material. We then examined the sensitivity, accuracy, and scan uniformity to evaluate the scanning methodology using compensating materials. RESULTS: The increase in sensitivity was the highest for OG compared to that for air in the reflective mode. On average, the sensitivity in the reflective mode was higher than that in the transmission mode by a factor of 2.5 for each dose. Among the four compensating materials, OG had the smallest uncertainty. Therefore, the best scan uniformity was achieved when OG was used. CONCLUSIONS: Scanning methodology was proposed in which a compensating material is applied for a curved lens-type dosimeter. Our results show that OG is the most suitable compensating material to obtain the best accuracy of dose analysis. Following this methodology, the scan uncertainty of curved dosimeters significantly decreased.

Development of an anthropomorphic multimodality pelvic phantom for quantitative evaluation of a deep-learning-based synthetic computed tomography generation technique.

PURPOSE: The objective of this study was to fabricate an anthropomorphic multimodality pelvic phantom to evaluate a deep-learning-based synthetic computed tomography (CT) algorithm for magnetic resonance (MR)-only radiotherapy. METHODS: Polyurethane-based and silicone-based materials with various silicone oil concentrations were scanned using 0.35 T MR and CT scanner to determine the tissue surrogate. Five tissue surrogates were determined by comparing the organ intensity with patient CT and MR images. Patient-specific organ modeling for three-dimensional printing was performed by manually delineating the structures of interest. The phantom was finally fabricated by casting materials for each structure. For the quantitative evaluation, the mean and standard deviations were measured within the regions of interest on the MR, simulation CT (CTsim ), and synthetic CT (CTsyn ) images. Intensity-modulated radiation therapy plans were generated to assess the impact of different electron density assignments on plan quality using CTsim and CTsyn . The dose calculation accuracy was investigated in terms of gamma analysis and dose-volume histogram parameters. RESULTS: For the prostate site, the mean MR intensities for the patient and phantom were 78.1 ± 13.8 and 86.5 ± 19.3, respectively. The mean intensity of the synthetic image was 30.9 Hounsfield unit (HU), which was comparable to that of the real CT phantom image. The original and synthetic CT intensities of the fat tissue in the phantom were -105.8 ± 4.9 HU and -107.8 ± 7.8 HU, respectively. For the target volume, the difference in D95% was 0.32 Gy using CTsyn with respect to CTsim values. The V65Gy values for the bladder in the plans using CTsim and CTsyn were 0.31% and 0.15%, respectively. CONCLUSION: This work demonstrated that the anthropomorphic phantom was physiologically and geometrically similar to the patient organs and was employed to quantitatively evaluate the deep-learning-based synthetic CT algorithm.

3D star shot analysis using MAGAT gel dosimeter for integrated imaging and radiation isocenter verification of MR-Linac system.

PURPOSE: This study aims to investigate a star shot analysis using a three-dimensional (3D) gel dosimeter for the imaging and radiation isocenter verification of a magnetic resonance linear accelerator (MR-Linac). METHODS: A mixture of methacrylic acid, gelatin, and tetrakis (hydroxymethyl) phosphonium chloride, called MAGAT gel, was fabricated. One MAGAT gel for each Linac and MR-Linac was irradiated under six gantry angles. A 6 MV photon beam of Linac and a 6 MV flattening filter free beam of MR-Linac were delivered to two MAGAT gels and EBT3 films. MR images were acquired by MR-Linac with a clinical sequence (i.e., TrueFISP). The 3D star shot analysis for seven consecutive slices of the MR images with TrueFISP was performed. The 2D star shot analysis for the central plane of the gel was compared to the results from the EBT3 films. The radius of isocircle (ICr ) and the distance between the center of the circle and the center marked on the image (ICd ) were evaluated. RESULTS: For MR-Linac with MAGAT gel measurements, ICd at the central plane was 0.46 mm for TrueFISP. Compared to EBT3 film measurements, the differences in ICd and ICr for both Linac and MR-Linac were within 0.11 and 0.13 mm, respectively. For the 3D analysis, seven consecutive slices of TrueFISP images were analyzed and the maximum radii of isocircles (ICr_max ) were 0.18 mm for Linac and 0.73 mm for MR-Linac. The tilting angles of radiation axis were 0.31° for Linac and 0.10° for MR-Linac. CONCLUSION: The accuracy of 3D star shot analysis using MAGAT gel was comparable to that of EBT3 film, having a capability for integrated analysis for imaging isocenter and radiation isocenter. 3D star shot analysis using MAGAT gel can provide 3D information of radiation isocenter, suggesting a quantitative extent of gantry-tilting.

Amelioration of cancer cachexia with preemptive administration of tumor necrosis factor-α blocker.

Cancer cachexia is syndrome accompanying weight reduction, fat loss, muscle atrophy in patients with advanced cancer. Since tumor necrosis factor-α (TNF-α) played pivotal role in cancer cachexia, we hypothesized preemptive administration of TNF-α antibody might mitigate cancer cachexia. Detailed molecular mechanisms targeting muscle atrophy, cachexic inflammation, and catabolic catastrophe were explored whether TNF-α antibody can antagonize these cachexic mechanisms. Stimulated with preliminary finding human antibody, infliximab or adalimumab, significantly inhibited TNF-α as well as their signals relevant to cachexia in mice, preemptive administration of 1.5 mg/kg adalimumab was done in C-26-induced cancer cachexia. Adalimumab significantly mitigated cancer cachexia manifested with significantly lesser weight loss, leg muscle preservation, and higher survival compared to cachexia control (p<0.05). Significant ameliorating action of muscle atrophy were accompanied significant decreases of muscle-specific UPS like atrogin-1/MuRF-1, Pax-7, PCG-1α, and Mfn-2 after adalimumab (p<0.01) and significantly attenuated lipolysis with inhibition of ATGL HSL, and MMPs. Cachexic factors including IL-6 expression, serum IL-6, gp130, IL-6R, JAK2, and STAT3 were significantly inhibited with adalimumab (p<0.01). Genes implicated in cachexic inflammation like NF-κB, c-Jun/c-Fos, and MAPKs were significantly repressed, while mTOR/AKT was significantly increased adalimumab (p<0.05). Conclusively, preemptive administration of adalimumab can be tried in high risk to cancer cachexia.

Quantitative evaluation of radiodermatitis following whole-breast radiotherapy with various color space models: A feasibility study.

PURPOSE: We analyzed skin images with various color space models to objectively assess radiodermatitis severity in patients receiving whole-breast radiotherapy. METHODS: Twenty female patients diagnosed with breast cancer were enrolled prospectively. All patients received whole-breast radiotherapy without boost irradiation. Skin images for both irradiated and unirradiated breasts were recorded in red-green-blue (RGB) color space using a mobile skin analysis device. For longitudinal analysis, the images were acquired before radiotherapy (RTbefore), approximately 7 days after the first fraction of radiotherapy (RT7days), RT14days, and approximately 10 days after radiotherapy completion (RTafter). Four color space models (RGB, hue-saturation-value (HSV), L*a*b*, and YCbCr models) were employed to calculate twelve color space parameters for each skin image. Skin dose measurements for irradiated breasts were performed using nanoDot optically stimulated luminescent dosimeters on the first fraction of radiotherapy. Subsequently, acute radiation dermatitis in each patient was assessed according to the Radiation Therapy Oncology Group scoring criteria at both RT14days and RTafter. Finally, several statistical analysis methods were applied to investigate the performance of the color space parameters to objectively assess the radiodermatitis. RESULTS: Owing to radiation-induced skin damage, R value of RGB model as well as S and V values of the HSV model for irradiated breasts increased significantly, while those for unirradiated breasts showed smaller increases. These parameters showed the longitudinal changes in color space parameters within each group and between groups over time with statistical significance. Strong correlations of the parameters for irradiated breasts at RT7days with skin doses and those at RTafter were observed with statistical significance. CONCLUSION: The R value of RGB model as well as the S and V values of HSV model showed relatively better performance in evaluating the acute radiation dermatitis. These color space parameters could therefore serve as useful tools to assess radiodermatitis severity in a dose-dependent manner.

Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats.

BACKGROUND: Previous studies have shown that vagus nerve stimulation (VNS) can attenuate inflammatory responses in peripheral tissues and also improve some neurological disorders and cognitive function in the brain. However, it is not clear how VNS is involved in neuropathological processes in brain tissues. Here, we investigated the regulatory effects of VNS on the production of proinflammatory cytokines in the hippocampus of an animal model of continuous stress (CS). METHODS: CS was induced by placing rats in cages immersed with water, and acute or chronic electrical stimulation was applied to the cervical vagus nerve of CS animals. Protein levels in the gastric and hippocampal tissues were measured by western blotting and protein signals analyzed by immunofluorescence staining. von Frey test and forced swimming test were performed to assess pain sensitivity and depressive-like behavior in rats, respectively. RESULTS: Levels of TNF-α, IL-1ß, and IL-6 in the gastric and hippocampal tissues were significantly increased in CS animals compared to the untreated control and downregulated by acute VNS (aVNS). Iba-1-labeled microglial cells in the hippocampus of CS animals revealed morphological features of activated inflammatory cells and then changed to a normal shape by VNS. VNS elevated hippocampal expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in CS animals, and pharmacological blockade of α7 nAChR increased the production of TNF-α, IL-1ß, and IL-6, thus suppressing cholinergic anti-inflammatory activity that was mediated by VNS. Chronic VNS (cVNS) down-regulated the hippocampal production of active form of caspase 3 and 5-HT1A receptors and also decreased levels of TNF-α, IL-1ß, and IL-6 in the gastric and hippocampal tissues of CS animals. Pain sensitivity and depressive-like behavior, which were increased by CS, were improved by cVNS. CONCLUSIONS: Our data suggest that VNS may be involved in modulating pathophysiological processes caused by CS in the brain.

Traumatic iliac vein rupture managed using a bare-metal stent.

Iliac vein rupture resulting from blunt trauma is rare but can be fatal and challenging to diagnose despite thorough clinical investigation and image workup. Here, we present a case of traumatic iliac vein rupture managed by emergent endovascular repair using a bare-metal stent. Low pressure traumatic venous rupture is different from arterial rupture, and a bare-metal stent can be a sufficient tool to control bleeding.