Search

Background/Aim: To evaluate whether whole-pelvis (WP) volumetric modulated arc therapy (VMAT) is associated with increased late toxicity compared with prostate-only (PO) VMAT in patients with localized prostate cancer. Patients and Methods: Participants comprised 384 consecutive patients treated with definitive VMAT to 78 Gy in 39 fractions from July 2011 to August 2016. Of these, 183 patients received PO-VMAT and 201 patients received initial WP-VMAT to 46.8 Gy in 26 fractions using a simultaneous integrated boost technique. Gastrointestinal (GI) and genitourinary (GU) toxicities were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. Results: Median follow-up was 49 months (range=16-88 months) in the PO-VMAT group and 52 months (range=10-85 months) in the WP-VMAT group. Frequencies of Grade 3 late GI and GU toxicities were ≤3% across both groups. No patients experienced Grade 4+ toxicity. Cumulative incidences of Grade 2+ late GI and GU toxicities were similar between PO- and WP-VMAT groups (p=0.508 and p=0.838, respectively). Five-year cumulative incidences of Grade 2+ late GI and GU toxicities were 12.2% and 6.6% for the PO-VMAT group and 12.3% and 8.9% for the WP-VMAT group, respectively. Conclusion: WP-VMAT did not increase late GI and GU toxicities. This suggests that concerns about increasing toxicity profile are insufficient reason for omitting WPRT for patients with high-risk prostate cancer.

Purpose: To evaluate whether knowledge-based volumetric modulated arc therapy plans with from a multi-institution model (broad model) are clinically useful and effective as a standardization method. Methods: A knowledge-based planning (KBP) model was trained with 561 prostate VMAT plans from five institutions with different contouring and planning policies. Five clinical plans at each institution were reoptimized with the broad and single institution model, and the dosimetric parameters and relationship between Dmean and the overlapping volume (rectum or bladder and target) were compared. Results: The differences between the broad and single institution models in the dosimetric parameters for V50, V80, V90, and Dmean were: rectum; 9.5% ± 10.3%, 3.3% ± 1.5%, 1.7% ± 1.6%, and 3.6% ± 3.6%, (p < 0.001), bladder; 8.7% ± 12.8%, 1.5% ± 2.6%, 0.7% ± 2.4%, and 2.7% ± 4.6% (p < 0.02), respectively. The differences between the broad model and clinical plans were: rectum; 2.4% ± 4.6%, 1.7% ± 1.7%, 0.7% ± 2.4%, and 1.5% ± 2.0%, (p = 0.004, 0.015, 0.112, and 0.009) bladder; 2.9% ± 5.8%, 1.6% ± 1.9%, 0.9% ± 1.7%, and 1.1% ± 4.8%, (p < 0.018), respectively. Strong correlations were observed (p < 0.001) in the relationship between Dmean and the rectal and bladder volume overlapping with the target in the broad model (R = 0.815 and 0.891, respectively). The broad model had the smallest R2 of the three plans. Conclusions: KBP with the broad model is clinically effective and applicable as a standardization method at multiple institutions.

Purpose The purpose of this study was to compare the dose–volume parameters and regression scatter plots of the iteratively improved RapidPlan (RP) models, specific knowledge‐based planning (KBP) models, in volumetric‐modulated arc therapy (VMAT) for prostate cancer over three periods. Methods A RP1 model was created from 47 clinical intensity‐modulated radiation therapy (IMRT)/VMAT plans. A RP2 model was created to exceed dosimetric goals which set as the mean values +1SD of the dose–volume parameters of RP1 (50 consecutive new clinical VMAT plans). A RP3 model was created with more strict dose constraints for organs at risks (OARs) than RP1 and RP2 models (50 consecutive anew clinical VMAT plans). Each RP model was validated against 30 validation plans (RP1, RP2, and RP3) that were not used for model configuration, and the dose–volume parameters were compared. The Cook's distances of regression scatterplots of each model were also evaluated. Results Significant differences (p

BACKGROUND/AIM We investigated the plan complexity of volumetric modulated arc therapy (VMAT) with knowledge-based plan (KBP) for oropharyngeal cancer (OPC) with a single optimization and whether it could be used clinically. MATERIALS AND METHODS KBP model was configured using 55 consecutive OPC and nasopharyngeal cancer plans. Plan complexity as a characteristic of multileaf collimator (MLC) motion and γ pass rate (2%/2 mm criterion) were compared between clinical manual plan (CMP) and KBP for other 10 plans. RESULTS Plan complexity metrics that had significant differences (p

Objective. The purpose of this study was to develop a new bolus (HM bolus), with tissue equivalence, transparency, reusability, and free shaping at approximately 40 °C for excellent adhesion, and to evaluate the feasibility of clinically using this bolus as an ideal bolus. Approach. We summarized the advantages and disadvantages of existing boluses. To evaluate dose characteristics, a vinyl gel sheet bolus (Gel bolus) and HM bolus placed on a water-equivalent phantom were used to obtain the percentage depth dose (PDD) of electron (6 MeV, 9 MeV) and photon (4 MV, 6 MV) beams. The average dose difference of the HM bolus and Gel bolus was calculated. The Gel bolus, a soft rubber bolus (SR bolus), and HM bolus were placed in adherence to a pelvic phantom. CT images taken after shaping and 1, 2, and 3 weeks after shaping were used to evaluate the adhesion and reproducibility using air gap and dice similarity coefficient (DSC). Main results. The average dose difference for electron beams was 0.16% ± 0.79% and photon beams was 0.06% ± 0.34%, both within 1% of the PDD results. The HM bolus showed the same build-up effect and dose characteristics as the Gel bolus. The mean air gap values for the Gel bolus, SR bolus, and HM bolus were 96.02 ± 43.77 cm3, 34.93 ± 21.44 cm3, and 4.40 ± 1.50 cm3, respectively. The mean DSC values compared to initial images for the Gel bolus, SR bolus, and HM bolus were 0.363 ± 0.035, 0.556 ± 0.042, and 0.837 ± 0.018, respectively. Excellent adhesion was observed in the CT simulation and during the treatment period. Significance. The HM bolus has unique features, such as tissue equivalence, transparency, reusability, and free shaping for excellent adhesion, and is thus an ideal bolus for use in clinical cases.

Dosimetric evaluation and variation assessment were performed with two knowledge-based planning (KBP) models created at different periods for volumetric-modulated arc therapy (VMAT) for prostate cancer at five institutes. The first and second models (F- and S-models) for KBP were created before April 2017 and April 2019, respectively. The S-model was created using feedback plans from the F-model. Dose evaluation was compared between the two models using the same two computed tomography (CT) datasets and structures. The evaluation metrics were the dose received by 95.0% and 2.0% of the planning target volume (PTV); dose-volume parameters to the rectum and bladder as V90, V80, and V50; and monitor unit (MU). Dosimetric variation was compared by exporting estimated dose-volume histograms for each model to the Model Analytics website and assessing the organ at risk volume. There were no dosimetric differences between the two models for PTV. The V50 of the rectum in the S-model had improved compared to that of the F-model (case I: 49.3 ± 15.6 and 43.5 ± 15.2 [p = 0.08]; case II: 42.5 ± 16.9 and 36.0 ± 15.6 [p = 0.138]). The differences in other parameters were within ± 1.8% between the rectum and the bladder. The MU was slightly higher in the S-model than in the F-model, and dosimetric variation was reduced to the rectum and bladder among all the institutes. The polished S-model for KBP could be used for standardization of the plan quality and sharing of KBP models in VMAT for prostate cancer.

Purpose: This study aimed to investigate the influence of cleaned-up knowledge-based treatment planning (KBP) models on the plan quality for volumetric-modulated arc therapy (VMAT) of prostate cancer. Materials and Methods: Thirty prostate cancer VMAT plans were enrolled and evaluated according to four KBP modeling methods as follows: (1) model not cleaned – trained by fifty other clinical plans (KBPORIG); (2) cases cleaned by removing plans that did not meet all clinical goals of the dosimetric parameters, derived from dose–volume histogram (DVH) (KBPC-DVH); (3) cases cleaned outside the range of ±1 standard deviation through the principal component analysis regression plots (KBPC-REG); and (4) cases cleaned using both methods (2) and (3) (KBPC-ALL). Rectal and bladder structures in the training models numbered 34 and 48 for KBPC-DVH, 37 and 33 for KBPC-REG, and 26 and 33 for KBPC-ALL, respectively. The dosimetric parameters for each model with one-time auto-optimization were compared. Results: All KBP models improved target dose coverage and conformity and provided comparable sparing of organs at risks (rectal and bladder walls). There were no significant differences in plan quality among the KBP models. Nevertheless, only the KBPC-ALL model generated no cases of >1% V78 Gy (prescribed dose) to the rectal wall, whereas the KBPORIG, KBPC-DVH, and KBPC-REG models included two, four, and three cases, respectively, which were difficult to overcome with KBP because the planning target volume (PTV) and rectum regions overlapped. Conclusions: The cleaned-up KBP model based on DVH and regression plots improved plan quality in the PTV–rectum overlap region.

The purpose of this study was to examine whether there are differences in the timed up and go (TUG) test results and physical functions due to the differences in slip recognition when performing TUG on wood flooring. The study consisted of 30 community-dwelling elderly subjects, aging over 65 years old. The differences in the perception of floor slippage before and after TUG were as follows: (1) slippery-slipped group (S-S group), (2) slippery-not slipped group (S-N group), and (3) not slippery-not slipped group (N-N group). The modified falls efficacy scale, grip strength, knee extension strength, one-leg standing time, functional reach test, Trail Making Test (TMT), two-step test were used in this study. The results showed no statistically significant difference in TUG test. However, statistically significant difference was observed in TMT between the S-S and N-N groups (p = 0.019, r = 0.51, respectively) and between the S-S and S-N groups (p = 0.003, r = 0.65, respectively). It was found that there was no statistically significant difference in TUG results due to the recognition differences of slippage. However, it was suggested that the subject who reported a history of slippage had a high attention function and could pay attention to the floor environment.

This study aimed to clarify the inter-planner variation of plan quality in knowledge-based plans created by nine planners.Five hypofractionated prostate-only (HPO) volumetric modulated arc therapy (VMAT) plans and five whole-pelvis (WP) VMAT plans were created by each planner using a knowledge-based planning (KBP) system. Nine planners were divided into three groups of three planners each: Senior, Junior, and Beginner. Single optimization with only priority modification for all objectives was performed to stay within the dose constraints. The coefficients of variation (CVs) for dosimetric parameters were evaluated, and a plan quality metric (PQM) was used to evaluate comprehensive plan quality.Lower CVs (0.05) were observed at dosimetric parameters in the planning target volume for both HPO and WP plans, while the CVs in the rectum and bladder for WP plans (0.91) were greater than those for HPO plans (0.17). The PQM values of HPO plans for Cases1-5 (average ± standard deviation) were 41.2 ± 7.1, 40.9 ± 5.6, and 39.9 ± 4.6 in the Senior, Junior, and Beginner groups, respectively. For the WP plans, the PQM values were 51.9 ± 6.3, 47.5 ± 4.3, and 40.0 ± 6.6, respectively. The number of clinically acceptable HPO and WP plans were 13/15 and 11/15 in the Senior group, 13/15 and 10/15 plans in the Junior group, and 8/15 and 2/15 plans in the Beginner group, respectively.Inter-planner variation in the plan quality with RapidPlan remains, especially for the complicated VMAT plans, due to planners' heuristics.

Delta-5 desaturase (D5D), encoded by fatty acid desaturase 1 (Fads1), is the rate-limiting enzyme for the conversion from dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA) in the ω-6 polyunsaturated fatty acid pathway. Several AA-derived eicosanoids (e.g., prostaglandins, thromboxanes, and leukotrienes) and DGLA-derived eicosanoids are reported to promote and/or prevent atherosclerosis progression through, at least in part, its proinflammatory or anti-inflammatory effects. To elucidate the effects of D5D inhibition by a D5D inhibitor on atherosclerosis, we generated a potent, orally available and selective D5D inhibitor, 2-(2,2,3,3,3-Pentafluoropropoxy)-3-[4-(2,2,2-trifluoroethoxy) phenyl]-5,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-4,6-dione, compound-326, and examined its effects on Western-diet fed ApoE knockout (KO) mice. Oral administration of compound-326 (3-10 mg/kg per day for 15 weeks) significantly inhibited the progression of atherosclerotic lesions in the aorta without affecting plasma total cholesterol and triglyceride levels. Compound-326 significantly decreased AA levels, while it increased DGLA levels in the liver and the blood accompanied by decreases in AA-derived eicosanoid production and increases in DGLA-derived eicosanoid production from the blood cells. We conclude that compound-326 prevents the progression of atherosclerosis in Western-diet fed ApoE KO mice by modulating a profile of eicosanoid production, suggesting that D5D inhibitors can be a novel remedy for preventing atherosclerosis and subsequent cardiovascular events. SIGNIFICANCE STATEMENT: This study shows a D5D-specific and orally available potent inhibitor provided the first evidence to support the concept that D5D inhibitors will be a novel remedy for preventing the progression of atherosclerosis.

Purpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development. Methods: In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.o. for 12 weeks) significantly reduced the atherosclerotic lesion area in the aorta (24% reduction at 3 mg/kg/day). In another protocol using Paigen diet (containing 12.5% cholesterol and 5% sodium cholate), compound-326 (3 and 10 mg/kg/day, p.o. for 7 weeks) also significantly reduced the lesion area (36% reduction at 3 mg/kg/day). Results: In both protocols, Compound-326 significantly reduced the hepatic ratio of arachidonic acid to dihomo-γ-linolenic acid, blood inflammatory eicosanoid production and plasma soluble intercellular adhesion molecule 1 (sICAM-1) levels, similarly to the previous pre-treatment study. Conclusions: Compound-326 exerted anti-atherosclerotic effects in ApoE knockout mice with the two different protocols for atherosclerosis development further supporting D5D inhibition as a promising strategy in treating atherosclerosis.

Purpose The purpose of this paper was to determine the optimal imaging conditions for four-dimensional cone-beam computed tomography (4D-CBCT) using an X-ray tube and a flat-panel detector mounted on a radiotherapy device. Methods The optimal imaging conditions were examined by changing the gantry speed (GS) parameter that affected the exposure time. Exposed dose during imaging and image quality of moving phantom were compared between examined conditions. Results The weighted computed tomography dose index (CTDIW) decreased linearly with increasing GS. However, when GS was 180°/min or faster, the image quality degraded, and errors of 1 mm or more were observed regarding the size of mock tumor in the moving phantom. The accuracy of automatic image matching was within 0.1 mm when GS of 120°/min or slower was chosen. Conclusion From the results of this study, we concluded that GS of 120°/min is the optimum imaging condition. Under this imaging condition, the exposure time and CTDIW can be reduced by about 50% without compromising the accuracy of image registration, compared to the conventional GS of 70°/min. In addition, it has been clarified that there is an event that image reconstruction is not performed correctly due to the influence of phantom artifacts without depending on GS.

Highlights • Acoustic streaming velocity in aluminum melt and water was measured through Karman vortex frequency measurement. • The velocity of acoustic streaming is independent of amplitude of horn tip oscillation both in water and aluminum melt. • The velocity of acoustic streaming in aluminum melt is approximately the same as that in water., It is well known that ultrasonic cavitation causes a steady flow termed acoustic streaming. In the present study, the velocity of acoustic streaming in water and molten aluminum is measured. The method is based on the measurement of oscillation frequency of Karman vortices around a cylinder immersed into liquid. For the case of acoustic streaming in molten metal, such measurements were performed for the first time. Four types of experiments were conducted in the present study: (1) Particle Image Velocimetry (PIV) measurement in a water bath to measure the acoustic streaming velocity visually, (2) frequency measurement of Karman vortices generated around a cylinder in water, and (3) in aluminum melt, and (4) cavitation intensity measurements in molten aluminum. Based on the measurement results (1) and (2), the Strouhal number for acoustic streaming was determined. Then, using the same Strouhal number and measuring oscillation frequency of Karman vortices in aluminum melt, the acoustic streaming velocity was measured. The velocity of acoustic streaming was found to be independent of amplitude of sonotrode tip oscillation both in water and aluminum melt. This can be explained by the effect of acoustic shielding and liquid density.

Sphingomyelin synthase 2 (SMS2) has attracted attention as a drug target for the treatment of various cardiovascular and metabolic diseases. The modification of a high throughput screening hit, 2-quinolone 10, enhanced SMS2 inhibition at nanomolar concentrations with good selectivity against SMS1. To improve the pharmaceutical properties such as passive membrane permeability and aqueous solubility, adjustment of lipophilicity was attempted and 1,8-naphthyridin-2-one 37 was identified as a potent and selective SMS2 inhibitor. A significant reduction in hepatic sphingomyelin levels following repeated treatment in mice suggested that compound 37 could be an effective in vivo tool for clarifying the role of SMS2 enzyme and developing the treatment for SMS2-related diseases.

Adequate matching methods are critical for accurate volumetric-modulated arc therapy (VMAT). We investigated the dosimetric differences in the target and organs at risk (OARs) between bone matching and target matching in patients with prostate cancer treated with VMAT. The relationship between the dosimetric differences and interfractional motion of the prostate was also evaluated. Forty patients with prostate cancer classified as intermediate risk were enrolled in a study to assess the differences in dosimetry between two matching methods. These patients were treated with VMAT and prescribed dose was 78 Gy. The dose distribution was calculated using cone-beam computed tomography (CBCT) for this study. We selected clinical target volume (CTV) as the target, and the rectum and bladder as the OARs. The Dmean, D98, D95, and D2 to the target and V10-V70 to the OARs were calculated as different dose from target matching value minus bone matching value. Multiple regression analysis was used to evaluate the effect of interfractional motion of the prostate on the differences in dose. The CTV D95 values differed by -0.22 ± 1.01 Gy (mean ± standard deviation). Rectum and bladder V70 values differed by 4.6% ± 7.2% and -2.6% ± 7.2%, respectively. There was a correlation between interfractional motion of the prostate and the dose differences to OARs (R2 = 0.73 - 0.94). The dose differences to OARs also varied depending on the direction of the prostate’s motion. We found that bone matching resulted in an increased rectal dose and high risk of decreasing dose to the CTV.

BACKGROUND AND PURPOSE Neonicotinoid insecticides interact with the orthosteric site formed at subunit interfaces of insect nicotinic ACh (nACh) receptors. However, their interactions with the orthosteric sites at α-non α and α-α subunit interfaces remain poorly understood. The aim of this study was to elucidate the mechanism of neonicotinoid actions using the Drosophila Dα1-chicken β2 hybrid nACh receptor. EXPERIMENTAL APPROACH Computer models of the (Dα1)3 (β2)2 nACh receptor in complex with imidacloprid and thiacloprid were generated. Amino acids in the Dα1 subunit were mutated to corresponding amino acids in the human α4 subunit to examine their effects on the agonist actions of neonicotinoids on (Dα1)3 (β2)2 and (Dα1)2 (β2)3 nACh receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology. KEY RESULTS The (Dα1)3 (β2)2 nACh receptor models indicated that amino acids in loops D, E and G probably determine the effects of neonicotinoids. The amino acid mutations tested had minimal effects on the EC50 for ACh. However, the R57S mutation in loop G, although having minimal effect on imidacloprid's actions, reduced the affinity of thiacloprid for the (Dα1)3 (β2)2 nACh receptor, while scarcely affecting thiacloprid's action on the (Dα1)2 (β2)3 nACh receptor. Both the K140T and the combined R57S;K140T mutations reduced neonicotinoid efficacy but only for the (Dα1)3 (β2)2 nACh receptor. Combining the E78K mutation with the R57S;K140T mutations resulted in a selective reduction of thiacloprid's affinity for the (Dα1)3 (β2)2 nACh receptor. CONCLUSIONS AND IMPLICATIONS These findings suggest that a triangle of residues from loops D, E and G contribute to the selective actions of neonicotinoids on insect-vertebrate hybrid nACh receptors. LINKED ARTICLES This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

Diamond-like-carbon (DLC) films are promising as coating materials. Ion plating, an excellent method in terms of adhesiveness, step coverage, and deposition rate, can form not only pure metal films but also oxide films, nitride films, and carbonized films. In this study, which aimed to form a DLC film with good adhesiveness and a diamond crystal structure, a DLC film, with a SiC interlayer formed by ion plating with introduction of tetramethylsilane (TMS), was formed. It was experimentally revealed that as the interlayer thickness increases, the crystal structure in the DLC film becomes more diamond rich, and the adhesiveness of the DLC film and substrate is thereby improved.

We developed a novel low‐radiation‐absorbent lok‐bar (HM‐bar) that is used to secure the immobilizers to the couch. The aim of this study was to investigate the X‐ray scattering and absorption properties of the HM‐bar in computed tomography (CT) simulation and radiotherapy dose delivery using the Varian Exact™ lok‐bar (VL‐bar) as a benchmark. CT images were obtained with or without lok‐bar, and then each image was visually evaluated for artifacts. The attenuation rates for each lok‐bar were measured using a farmer‐type ionization chamber (PTW30013) and the I'mRT phantom (IBA Dosimetry GmbH). Measurement points were between gantry angles of 110 and 180°. The treatment apparatus was a NovalisTx (Brainlab AG); X‐ray energies were set at 6 MV and 10 MV. In the presence of each lok‐bar, the radiation dose was measured in accordance with 10 volumetric modulated arc therapy–stereotactic body radiation therapy (VMAT‐SBRT) plans for lung cancer. Artifacts were seldom observed in the CT scans of the HM‐bar. The attenuation rate of each lok‐bar was higher when the X‐ray energy was set at 6 MV than at 10 MV. The highest attenuation rate in the VL‐bar was observed at a gantry angle of 112°; the rates were 22.4% at 6 MV and 19.3% at 10 MV. Similarly, the highest attenuation rate for the HM‐bar was also observed at a gantry angle of 112°; the rates were 12.2% and 10.1% at 6 MV and 10 MV, respectively. When the VL‐bar was evaluated, the isocenter dose of the VMAT‐SBRT plans was attenuated by 2.6% as a maximum case. In the case of the HM‐bar, the maximum attenuation was 1.4%. In the measurements of each VMAT‐SBRT plan, the difference of the dose attenuation rate between the VL‐bar and HM‐bar was approximately 1%. The HM‐bar could be used to minimize the occurrence of artifacts and provide good images in CT scans regarding radiotherapy planning and dose calculation. It can be used for patient therapy at hospitals to provide accurate dose delivery because of its low X‐ray scattering and absorption characteristics.

Electron grid therapy is expected to be a valid treatment for bulky superficial tumors. It is difficult, however, to fit irradiation fields to bulky superficial tumor shapes for conventional electron grid therapy with a cerrobend grid collimator. In this study, we investigated whether a grid collimator using tungsten functional paper (TFP), with its radiation shielding ability, could be used for electron grid therapy. Dose distributions were measured using 9 MeV electron grid beams from a cerrobend grid collimator. For the simulation study, the same grid irradiation fields were shaped using a TFP grid collimator (thicknesses of 0.15, 0.3, 0.6, 0.9, and 1.2 cm) by laying them on a phantom. We then determined the dose distributions using Monte Carlo calculations and compared the cerrobend and TFP electron grid beams regarding dose distributions, including the depths of the maximum dose (d max), 90% dose (d 90), and 80% dose (d 80), and the ratios of the doses in the areas with and without shielding (valley to peak ratios). The equivalent dosimetric thickness was obtained with the TFP grid collimator that was equivalent to the dose distribution of the cerrobend grid collimator. For the cerrobend electron grid beams, the d max, d 90, and d 80 were 1.0, 2.1, and 2.5 cm, respectively, and the valley to peak ratios at those depths were 0.48, 0.66, and 0.73, respectively. The equivalent dosimetric thickness of TFP was 0.52 cm. The d max, d 90, and d 80 for the 0.52 cm thick TFP electron grid beams were 1.1, 1.9, and 2.3 cm, respectively, and the valley to peak ratios at those depths were 0.49, 0.63, and 0.71, respectively. The TFP grid collimator flexibly delivered excellent dose distributions by simply attaching it to the patient's skin. It could thus be used for electron grid therapy instead of the cerrobend grid collimator.

Delta-5 desaturase (D5D), encoded by fatty acid desaturase 1 (

Aim To evaluate the success of a patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA) practice for prostate cancer patients across multiple institutions using a questionnaire survey. Background The IMRT QA practice involves different methods of dose distribution verification and analysis at different institutions. Materials and Methods Two full-arc volumetric modulated arc therapy (VMAT) plan and 7 fixed-gantry IMRT plan with DMLC were used for patient specific QA across 22 institutions. The same computed tomography image and structure set were used for all plans. Each institution recalculated the dose distribution with fixed monitor units and without any modification. Single-point dose measurement with a cylindrical ionization chamber and dose distribution verification with a multi-detector or radiochromic film were performed, according to the QA process at each institution. Results Twenty-two institutions performed the patient-specific IMRT QA verifications. With a single-point dose measurement at the isocenter, the average difference between the calculated and measured doses was 0.5 ± 1.9%. For the comparison of dose distributions, 18 institutions used a two or three-dimensional array detector, while the others used Gafchromic film. In the γ test with dose difference/distance-to-agreement criteria of 3%−3 mm and 2%−2 mm with a 30% dose threshold, the median gamma pass rates were 99.3% (range: 41.7%–100.0%) and 96.4% (range: 29.4%–100.0%), respectively. Conclusion This survey was an informative trial to understand the verification status of patient-specific IMRT QA measurements for prostate cancer. In most institutions, the point dose measurement and dose distribution differences met the desired criteria.

The purpose of this study was to determine appropriate beam arrangement for volumetric-modulated arc therapy (VMAT)-based stereotactic body radiation therapy (SBRT) in the treatment of patients with centrally located lung tumors. Fifteen consecutive patients with centrally located lung tumors treated at our institution were enrolled. For each patient, three VMAT plans were generated using two coplanar partial arcs (CP VMAT), two non-coplanar partial arcs (NCP VMAT), and one coplanar full arc (Full VMAT). All plans were designed to deliver 70 Gy in 10 fractions. Target coverage and sparing of organs at risk (OARs) were compared across techniques. PTV coverage was almost identical for all approaches. The whole lung V 10Gy was significantly lower with CP VMAT plans than with NCP VMAT plans, whereas no significant differences in the mean lung dose, V 5Gy , V 20Gy or V 40Gy were observed. Full VMAT increased mean contralateral lung V 5Gy by 12.57% and 9.15% when compared with NCP VMAT and CP VMAT, respectively. Although NCP VMAT plans best achieved the dose–volume constraints for mediastinal OARs, the absolute differences in dose were small when compared with CP VMAT. These results suggest that partial-arc VMAT may be preferable to minimize unnecessary exposure to the contralateral lung, and use of NCP VMAT should be considered when the dose–volume constraints are not achieved by CP VMAT.

Background This study clarified the mechanical performance of volumetric modulated arc therapy (VMAT) plans for prostate cancer generated with a commercial knowledge-based treatment planning (KBP) and whether KBP system could be applied clinically without any major problems with mechanical performance. Methods Thirty consecutive prostate cancer patients who underwent VMAT using extant clinical plans were evaluated. The mechanical performance and dosimetric accuracy of the single optimized KBPs, which were trained with other 51 clinical plans, were compared with the clinical plans. The mechanical performance metrics were mean field area (MFA), mean asymmetry distance (MAD), cross-axis score (CAS), closed leaf score (CLS), small aperture score (SAS), leaf travel (LT), modulation complexity score (MCSv), and monitor unit (MU). The γ passing rates were evaluated with ArcCheck and EBT3 film. Results The mean mechanical performance metrics (clinical plan vs. KBP) were as follows: 18.28 cm2 vs. 17.25 cm2 (MFA), 21.08 mm vs. 20.47 mm (MAD), 0.54 vs. 0.55 (CAS), 0.040 vs. 0.051 (CLS), 0.20 vs. 0.23 (SAS5mm), 458.5 mm vs. 418.8 mm (LT), 0.27 vs. 0.27 (MCSv), and 618.2 vs. 622.1 (MU), respectively. Significant differences were observed for CLS and LT. The average γ passing rates (clinical plan vs. KBP) were as follows: 99.0% vs. 99.1% (3%/3 mm) and 92.4% vs. 92.5% (2%/2 mm) with ArcCHeck, and 99.5% vs. 99.4% (3%/3 mm) and 95.2% vs. 95.4% (2%/2 mm) with EBT3 film, respectively. Conclusions The KBP used lower multileaf collimator (MLC) travel and more closed or small MLC apertures than the clinical plan. The KBP system of VMAT for the prostate cancer was acceptable for clinical use without any major problems.

Background/aim Patient immobilization systems are used to establish a reproducible patient position relative to the couch. In this study, the impact of conventional lok-bars for CT-simulation (CIVCO-bar) and treatment (iBEAM-bar) were compared with a novel lok-bar (mHM-bar) in tomotherapy. Materials and methods Verification was obtained as follows: i. artifacts in CT images; ii. dose attenuation rate of lok-bar, compared to without lok-bar; and iii. dose differences between the calculated and measured absorbed doses. Results With the CIVCO-bar, there were obvious metal artifacts, while there were nearly no artifacts with the mHM-bar. The mean dose attenuation rates with the mHM-bar and iBEAM-bar were 1.31% and 2.28%, and the mean dose difference was 1.55% and 1.66% for mHM-bar and iBEAM-bar. Conclusion Using the mHM-bar reduced artifacts on the CT image and improved dose attenuation are obtained. The lok-bar needs to be inserted as a structure set in treatment planning with tomotherapy.

The discovery and optimization of Δ-5 desaturase (D5D) inhibitors are described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a pharmacophore model constructed from the common features of several hit compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one 5h as a novel lead showing potent in vitro activity. Subsequent optimization focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a derivative with improved metabolic stability. Moreover, adding a substituent into the upper phenyl moiety further enhanced the intrinsic activity, which led to the discovery of 5-[(4S,5S)-5-(4fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-dicarbonitrile (4S,5S)-5n, endowed with excellent D5D binding affinity, cellular activity, and high oral bioavailability in a mouse. It exhibited robust in vivo hepatic arachidonic acid/dihomo-γ-linolenic acid ratio reduction (a target engagement marker) in an atherosclerosis mouse model. Finally, an asymmetric synthetic procedure for this compound was established.

It is important to improve the magnitude of dose variation that is caused by the interplay effect. The aim of this study was to investigate the impact of the number of breaths (NBs) to the dose variation for VMAT‐SBRT to lung cancer. Data on respiratory motion and multileaf collimator (MLC) sequence were collected from the cases of 30 patients who underwent radiotherapy with VMAT‐SBRT for lung cancer. The NBs in the total irradiation time with VMAT and the maximum craniocaudal amplitude of the target were calculated. The MLC sequence complexity was evaluated using the modulation complexity score for VMAT (MCSv). Static and dynamic measurements were performed using a cylindrical respiratory motion phantom and a micro ionization chamber. The 1 standard deviation which were obtained from 10 dynamic measurements for each patient were defined as dose variation caused by the interplay effect. The dose distributions were also verified with radiochromic film to detect undesired hot and cold dose spot. Dose measurements were also performed with different NBs in the same plan for 16 patients in 30 patients. The correlations between dose variations and parameters assessed for each treatment plan including NBs, MCSv, the MCSv/amplitude quotient (TMMCSv), and the MCSv/amplitude quotient × NBs product (IVS) were evaluated. Dose variation was decreased with increasing NBs, and NBs of >40 times maintained the dose variation within 3% in 15 cases. The correlation between dose variation and IVS which were considered NBs was shown stronger (R 2 = 0.43, P 40 times during irradiation of two partial arcs VMAT (i.e., NBs = 16 breaths per minute) may be suitable for VMAT‐SBRT for lung cancer.

Purpose This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. Methods We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D 95% , and D 2% to planning target volume (PTV), mean dose, V 50Gy , V 70Gy , V 75Gy , and V 78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity. Results RP and CMO values for PTV D 95% , PTV D 2% , HI, and CN were significantly similar ( p 50Gy , and V 70Gy to rectum were superior or comparable to CMO values; RP V 75Gy and V 78Gy were higher than in CMO plans ( p 78Gy ) were lower than in CMO plans ( p p p Conclusions RP plans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planner’s skill and knowledge.

BACKGROUND AND PURPOSE: Neonicotinoid insecticides interact with the orthosteric site formed at subunit interfaces of insect nicotinic ACh (nACh) receptors. However, their interactions with the orthosteric sites at α–non α and α–α subunit interfaces remain poorly understood. The aim of this study was to elucidate the mechanism of neonicotinoid actions using the Drosophila Dα1‐chicken β2 hybrid nACh receptor. EXPERIMENTAL APPROACH: Computer models of the (Dα1)(3)(β2)(2) nACh receptor in complex with imidacloprid and thiacloprid were generated. Amino acids in the Dα1 subunit were mutated to corresponding amino acids in the human α4 subunit to examine their effects on the agonist actions of neonicotinoids on (Dα1)(3)(β2)(2) and (Dα1)(2)(β2)(3) nACh receptors expressed in Xenopus laevis oocytes using voltage‐clamp electrophysiology. KEY RESULTS: The (Dα1)(3)(β2)(2) nACh receptor models indicated that amino acids in loops D, E and G probably determine the effects of neonicotinoids. The amino acid mutations tested had minimal effects on the EC(50) for ACh. However, the R57S mutation in loop G, although having minimal effect on imidacloprid's actions, reduced the affinity of thiacloprid for the (Dα1)(3)(β2)(2) nACh receptor, while scarcely affecting thiacloprid's action on the (Dα1)(2)(β2)(3) nACh receptor. Both the K140T and the combined R57S;K140T mutations reduced neonicotinoid efficacy but only for the (Dα1)(3)(β2)(2) nACh receptor. Combining the E78K mutation with the R57S;K140T mutations resulted in a selective reduction of thiacloprid's affinity for the (Dα1)(3)(β2)(2) nACh receptor. CONCLUSIONS AND IMPLICATIONS: These findings suggest that a triangle of residues from loops D, E and G contribute to the selective actions of neonicotinoids on insect‐vertebrate hybrid nACh receptors. LINKED ARTICLES: This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc

A microcapsule diffuser of the transparent type is proposed to reduce the speckle noise generated on a laser display. This diffuser has a microcapsule that is secured between two transparent electrodes. The microcapsule contains light diffusion particles that are electrically charged. Because the particles in the microcapsules are moved by the electric field, the proposed device reduces speckle noise. This paper reports the results of one study of the device reliability.

Various noninvasive imaging methods have been developed to evaluate atherosclerotic plaques. Among them, 18F-FDG PET and MR imaging with ultrasmall superparamagnetic iron oxide particles (USPIO) have been used to quantify plaque inflammation. Both methods are based on the efficient uptake of FDG and USPIO by macrophages in atherosclerotic lesions. Differently polarized macrophages have been reported to have different characteristics that are involved in the pathologic development of atherosclerosis. M1 polarized macrophages are considered the more proatherogenic phenotype than M2 polarized macrophages. However, little is known regarding the association between macrophage polarization and FDG or USPIO accumulation. In this study, we investigated intracellular FDG and USPIO accumulation in M1 and M2 polarized macrophages. Methods: THP-1 macrophages were differentiated into M1 and M2 polarized macrophages. Under optimal glucose conditions, we investigated the 3H-labeled FDG uptake in M1 and M2 polarized macrophages. We then investigated intracellular USPIO uptake by M1 and M2 macrophages. Results: We found that M1 polarization, compared with M2 polarization, results in increased intracellular accumulation of FDG. To elucidate the mechanism by which FDG was preferentially accumulated in M1 macrophages, we examined messenger RNA expressions of glucose transporters (GLUTs) and hexokinases, which have pivotal roles in glucose uptake, and glucose-6-phosphatase (G6Pase), which catalyzes the reverse reaction of hexokinase. In M1 macrophages, GLUT-1, GLUT-3, hexokinase 1, and hexokinase 2 were upregulated and G6Pase was downregulated. In contrast to FDG, M1 polarization resulted in decreased intracellular accumulation of USPIO. We found that scavenger receptor A and CD11b, which are involved in USPIO binding and uptake, were significantly downregulated by M1 polarization. Conclusion: Compared with M2, proatherogenic M1 macrophages preferentially accumulated FDG but not USPIO, suggesting that FDG PET is a useful method for the detection of proinflammatory M1 macrophages.

Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

This study investigated the associations between the intensity of mobile phone use and health-related lifestyle. For 275 university students, we evaluated health-related lifestyle using the Health Practice Index (HPI; Hagihara & Morimoto, 1991; Kusaka, Kondou, & Morimoto, 1992) and analyzed responses to a questionnaire (MPDQ; Toda, Monden, Kubo, & Morimoto, 2004) designed, with a self-rating scale, to gauge mobile phone dependence. For males, there was a significant relationship between smoking habits and mobile phone dependence. We also found that male respondents with low HPI scores were significantly higher for mobile phone dependence. These findings suggest that, particularly for males, the intensity of mobile phone use may be related to healthy lifestyle.

Conditions to remove contaminations adsorbed on a surface in wet cleaning processes have to be perfectly controlled. Megasonic excitation of ozonized water removes hydrocarbon contamination from silicon surfaces. When ozonized water was excited by megasonics at a frequency of about 1 MHz, OH radicals were produced in the cleaning solution. As a result, we have shown that hydrocarbons on the wafer surface were oxidized by OH radicals, leading to hydrocarbon-free Si surfaces.

The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC50 was 1.0 μm in SD rats. 2.1 μm in NZ white rabbits, and 0.3 μm in WHHL rabbits. With human SMC, the value was 0.02 μm in the presence of 10% FCS and 0.2 μm with a mixture of growth factors. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg−1 day−1. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P

A spin battery concept is applied for the dynamical generation of pure spin current and spin transport in p-type silicon (p-Si). Ferromagnetic resonance and effective s-d coupling in Ni(80)Fe(20) results in spin accumulation at the Ni(80)Fe(20)/p-Si interface, inducing spin injection and the generation of spin current in the p-Si. The pure spin current is converted to a charge current by the inverse spin Hall effect of Pd evaporated onto the p-Si. This approach demonstrates the generation and transport of pure spin current in p-Si at room temperature.

The effects of a new endothelin receptor antagonist, TAK-044, (cyclo[ d -α-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl] l -alanyl- l -α-aspartyl- d -2-(2-thienyl)glycyl- l -leucyl- d -tryptophyl]d salt, on ischemic and post-ischemic myocardial dysfunction (stunned myocardium) were studied in anesthetized open-chest dogs. A short (15 min) occlusion of the left anterior descending coronary artery followed by 5-h reperfusion significantly reduced myocardial segment shortening during and after the ischemic period in the ischemic region. Regional myocardial blood flow was also decreased significantly 10 min after the occlusion, whereas it returned almost completely to its pre-ischemic value 5 h after reperfusion. TAK-044 (3 mg/kg,i.v.) administered 10 min before occlusion significantly improved the reduced myocardial segment shortening in the ischemic region during and after occlusion. Cardiovascular hemodynamics and regional myocardial blood flow in a TAK-044-treated group were identical to those in the control group. These results indicate that endogenous endothelin contributes to the cause of ischemic and post-ischemic myocardial dysfunction without changing either hemodynamics or regional myocardial blood flow.

Protective effects of a new endothelin (ET) receptor antagonist, TAK-044, were studied in a model of acute renal failure (ARF) in rats. ARF was induced by clamping the left renal pedicle for 45 minutes with contralateral nephrectomy and subsequent reperfusion of the left kidney. Plasma creatinine concentration (Pcr) increased to 2.28mg/dl 24 hours after reperfusion of the ischemic kidney. Intravenous administration of TAK-044 (1–10mg/kg) prior to renal occlusion dose-dependently but partially attenuated the increase in Pcr and the morphological damages of the kidney. ET-1 and ET-3 increased perfusion pressure in isolated kidney preparations with similar potency, indicating that the renal vasoconstriction evoked by these ET isomers is mainly via ETB receptors, and TAK-044 (10nM) shifted the ET-1 dose-response curve to the right by a factor about 10. In a rat renal membrane fraction, ET-1 showed competitive inhibition of specific [125I]ET-1 binding with an IC50 value of 0.34nM and a Hill slope of 1.10. ET-3 did so with a higher IC50 value (3.3nM) and a lower Hill slope (0.56), suggesting that rat kidney contains both ETA and another receptor subtype, probably ETB. TAK-044 inhibited ET-1 binding with an IC50 value of 6.6nM and a Hill slope of 0.41. Plasma concentrations of immunoreactive TAK-044 were maintained over 7nM for 8 hours following i.v. injection of 10mg/kg TAK-044. These results suggest that endogenous ET is involved in the pathogenesis of post-ischemic ARF, at least, in part and that TAK-044 provided protective effects against ARF by blocking ET receptors, possibly both ETA and ETB receptors in renal vasculature and parenchymal cells.