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Objective@#: The optic nerve sheath diameter (ONSD)/eyeball transverse diameter (ETD) ratio is a more reliable marker of intracranial pressure than the ONSD alone. We aimed to investigate the predictive value of the ONSD/ETD ratio (OER) for neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). @*Methods@#: Adult patients with aSAH who visited the emergency department of a tertiary hospital connected to a South Korean university between January 2015 and December 2021 were included. Data on patient characteristics and brain computed tomography scan findings, including the ONSD and ETD, were collected using a predefined protocol. According to the neurological outcome at hospital discharge, the patients were divided into the unfavorable neurological outcome (UNO; cerebral performance category [CPC] score 3–5) and the favorable neurological outcome (FNO; CPC score 1–2) groups. The primary outcome was the association between the OER and neurological outcomes in patients with aSAH. @*Results@#: A total of 171 patients were included in the study, of whom 118 patients (69%) had UNO. Neither the ONSD (p=0.075) nor ETD (p=0.403) showed significant differences between the two groups. However, the OER was significantly higher in the UNO group in the univariate analysis (p=0.045). The area under the receiver operating characteristic curve of the OER for predicting UNO was 0.603 (p=0.031). There was no independent relationship between the OER and UNO in the multivariate logistic regression analysis (adjusted odds ratio, 0.010; p=0.576). @*Conclusion@#: The OER was significantly higher in patients with UNO than in those with FNO, and the OER was more reliable than the ONSD alone. However, the OER had limited utility in predicting UNO in patients with aSAH.
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Purpose@#This study aims to examine the performance of early warning scoring systems regarding adverse events of unanticipated clinical deterioration in complementary and alternative medicine hospitals. @*Methods@#A medical record review of 500 patients from 5-year patient data in two traditional Korean medicine hospitals was conducted. Unanticipated clinical deterioration events included unexpected in-hospital mortality, cardiac arrest, and unplanned transfers to acute-care conventional medicine hospitals. Scores of the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and National Early Warning Score 2 (NEWS2) were calculated. Their performance was evaluated by calculating areas under the receiver-operating characteristic curve for the event occurrence. Multiple logistic regression analyses were performed to determine the factors associated with event occurrence. @*Results@#The incidence of unanticipated clinical deterioration events was 1.1% (225/21101). The area under the curve of MEWS, NEWS, and NEWS2 was .68, .72, and .72 at 24 hours before the events, respectively. NEWS and NEWS2, with almost the same performance, were superior to MEWS (p = .009). After adjusting for other variables, patients at low-medium risk (OR = 3.28; 95% CI = 1.02–10.55) and those at medium and high risk (OR = 25.03; 95% CI = 2.78–225.46) on NEWS2 scores were more likely to experience unanticipated clinical deterioration than those at low risk. Other factors associated with the event occurrence included frailty risk scores, clinical worry scores, primary medical diagnosis, prescribed medicine administration, acupuncture treatment, and clinical department. @*Conclusions@#The three early warning scores demonstrated moderate-to-fair performance for clinical deterioration events. NEWS2 can be used for early identification of patients at high risk of deterioration in complementary and alternative medicine hospitals. Additionally, patient, care, and system factors need to be considered to improve patient safety.
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Purpose@#Dedicated breast CT is an emerging volumetric X-ray imaging modality for diagnosis that does not require any painful breast compression. To improve the detection rate of weakly enhanced lesions, an adaptive image rescaling (AIR) technique was proposed. @*Materials and Methods@#Two disks containing five identical holes and five holes of different diameters were scanned using 60/100 kVp to obtain single-energy CT (SECT), dual-energy CT (DECT), and AIR images. A piece of pork was also scanned as a subclinical trial. The image quality was evaluated using image contrast and contrast-to-noise ratio (CNR). The difference of imaging performances was confirmed using student’s t test. @*Results@#Total mean image contrast of AIR (0.70) reached 74.5% of that of DECT (0.94) and was higher than that of SECT (0.22) by 318.2%. Total mean CNR of AIR (5.08) was 35.5% of that of SECT (14.30) and was higher than that of DECT (2.28) by 222.8%. A similar trend was observed in the subclinical study. @*Conclusion@#The results demonstrated superior image contrast of AIR over SECT, and its higher overall image quality compared to DECT with half the exposure. Therefore, AIR seems to have the potential to improve the detectability of lesions with dedicated breast CT.
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Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.
Subject(s)
Amino Acids , Binding Sites , Calcium , Cytosol , Glutamic Acid , Myocytes, Smooth Muscle , Permeability , Polyamines , Receptors, Muscarinic , Spermine , Transient Receptor Potential ChannelsABSTRACT
Purpose@#To evaluate and compare the feasibilities of magnetic resonance (MR) image-based planning using synthetic computed tomography (sCT) versus CT (pCT)-based planning in helical tomotherapy for prostate cancer. @*Materials and Methods@#A retrospective evaluation was performed in 16 patients with prostate cancer who had been treated with helical tomotherapy. MR images were acquired using a dedicated therapy sequence; sCT images were generated using magnetic resonance for calculating attenuation (MRCAT). The three-dimensional dose distribution according to sCT was recalculated using a previously optimized plan and was compared with the doses calculated using pCT. @*Results@#The mean planning target volume doses calculated by sCT and pCT differed by 0.65% ± 1.11% (p = 0.03). Three-dimensional gamma analysis at a 2%/2 mm dose difference/distance to agreement yielded a pass rate of 0.976 (range, 0.658 to 0.986). @*Conclusion@#The dose distribution results obtained using tomotherapy from MR-only simulations were in good agreement with the dose distribution results from simulation CT, with mean dose differences of less than 1% for target volume and normal organs in patients with prostate cancer.
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KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
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KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.
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The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or GTPγS. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.
Subject(s)
Humans , Calcium , Carbachol , Hydrogen-Ion Concentration , Ion Channels , Kidney , Mass Screening , Mutagenesis, Site-Directed , Mutant Proteins , Protein Kinase C , Receptors, MuscarinicABSTRACT
Radiotherapy for the treatment of cancer in companion animals is currently administered by using megavoltage X-ray machines. Because these machines are expensive, most animal hospitals do not perform radiotherapy. This study evaluated the ability of relatively inexpensive kilovoltage X-ray machines to treat companion animals. A simulation study based on a commercial treatment-planning system was performed for tumors of the brain (non-infectious meningoencephalitis), nasal cavity (malignant nasal tumors), forefoot (malignant muscular tumors), and abdomen (malignant intestinal tumors). The results of kilovoltage (300 kV and 450 kV) and megavoltage (6 MV) X-ray beams were compared. Whereas the 300 kV and 6 MV X-ray beams provided optimal radiation dose homogeneity and conformity, respectively, for brain tumors, the 6 MV X-rays provided optimal homogeneity and radiation conformity for nasal cavity, forefoot, and abdominal tumors. Although megavoltage X-ray beams provided better radiation dose distribution in most treated animals, the differences between megavoltage and kilovoltage X-ray beams were relatively small. The similar therapeutic effects of the kilovoltage and 6 MV X-ray beams suggest that kilovoltage X-ray beams may be effective alternatives to megavoltage X-ray beams in treating cancers in companion animals.
Subject(s)
Animals , Humans , Abdomen , Brain , Brain Neoplasms , Friends , Hospitals, Animal , Nasal Cavity , Pets , Radiotherapy , Therapeutic UsesABSTRACT
OBJECTIVES: With the increased use of computed tomography (CT) in clinics, dose reduction is the most important feature people seek when considering new CT techniques or applications. We developed an intensity-weighted region-of-interest (IWROI) imaging method in an exact half-fan geometry to reduce the imaging radiation dose to patients in cone-beam CT (CBCT) for image-guided radiation therapy (IGRT). While dose reduction is highly desirable, preserving the high-quality images of the ROI is also important for target localization in IGRT. METHODS: An intensity-weighting (IW) filter made of copper was mounted in place of a bowtie filter on the X-ray tube unit of an on-board imager (OBI) system such that the filter can substantially reduce radiation exposure to the outer ROI. In addition to mounting the IW filter, the lead-blade collimation of the OBI was adjusted to produce an exact half-fan scanning geometry for a further reduction of the radiation dose. The chord-based rebinned backprojection-filtration (BPF) algorithm in circular CBCT was implemented for image reconstruction, and a humanoid pelvis phantom was used for the IWROI imaging experiment. RESULTS: The IWROI image of the phantom was successfully reconstructed after beam-quality correction, and it was registered to the reference image within an acceptable level of tolerance. Dosimetric measurements revealed that the dose is reduced by approximately 61% in the inner ROI and by 73% in the outer ROI compared to the conventional bowtie filter-based half-fan scan. CONCLUSIONS: The IWROI method substantially reduces the imaging radiation dose and provides reconstructed images with an acceptable level of quality for patient setup and target localization. The proposed half-fan-based IWROI imaging technique can add a valuable option to CBCT in IGRT applications.
Subject(s)
Humans , Cone-Beam Computed Tomography , Copper , Image Processing, Computer-Assisted , Methods , Pelvis , Radiation Exposure , Radiotherapy, Image-GuidedABSTRACT
PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.
Subject(s)
Humans , Cyclotrons , Helium , Korea , Metallurgy , Particle Accelerators , Patient Positioning , Proton Therapy , Protons , Radiation Oncology , Respiratory System , SeoulABSTRACT
The funding acknowledgment in this article was partially omitted as published.
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PURPOSE: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. MATERIALS AND METHODS: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. RESULTS: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and Pinnacle3 script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the pre-existing database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, Pinnacle3 v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. CONCLUSION: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.
Subject(s)
Humans , Incidence , Lung Neoplasms , Medical Records , Radiation Pneumonitis , Retrospective StudiesABSTRACT
Depth of prostate volume from the skin can vary due to intra-fractional and inter-fractional movements, which may result in dose reduction to the target volume. Therefore we evaluated the feasibility of automated depth determination-based adaptive proton therapy to minimize the effect of inter-fractional movements of the prostate. Based on the center of mass method, using three fiducial gold markers in the prostate target volume, we determined the differences between the planning and treatment stages in prostate target location. Thirty-eight images from 10 patients were used to assess the automated depth determination method, which was also compared with manually determined depth values. The mean differences in prostate target location for the left to right (LR) and superior to inferior (SI) directions were 0.9 mm and 2.3 mm, respectively, while the maximum discrepancies in location in individual patients were 3.3 mm and 7.2 mm, respectively. In the bilateral beam configuration, the difference in the LR direction represents the target depth changes from 0.7 mm to 3.3 mm in this study. We found that 42.1%, 26.3% and 2.6% of thirty-eight inspections showed greater than 1 mm, 2 mm and 3 mm depth differences, respectively, between the planning and treatment stages. Adaptive planning based on automated depth determination may be a solution for inter-fractional movements of the prostate in proton therapy since small depth changes of the target can significantly reduce target dose during proton treatment of prostate cancer patients.
Subject(s)
Humans , Prostate , Prostatic Neoplasms , Proton Therapy , Protons , SkinABSTRACT
Depth of prostate volume from the skin can vary due to intra-fractional and inter-fractional movements, which may result in dose reduction to the target volume. Therefore we evaluated the feasibility of automated depth determination-based adaptive proton therapy to minimize the effect of inter-fractional movements of the prostate. Based on the center of mass method, using three fiducial gold markers in the prostate target volume, we determined the differences between the planning and treatment stages in prostate target location. Thirty-eight images from 10 patients were used to assess the automated depth determination method, which was also compared with manually determined depth values. The mean differences in prostate target location for the left to right (LR) and superior to inferior (SI) directions were 0.9 mm and 2.3 mm, respectively, while the maximum discrepancies in location in individual patients were 3.3 mm and 7.2 mm, respectively. In the bilateral beam configuration, the difference in the LR direction represents the target depth changes from 0.7 mm to 3.3 mm in this study. We found that 42.1%, 26.3% and 2.6% of thirty-eight inspections showed greater than 1 mm, 2 mm and 3 mm depth differences, respectively, between the planning and treatment stages. Adaptive planning based on automated depth determination may be a solution for inter-fractional movements of the prostate in proton therapy since small depth changes of the target can significantly reduce target dose during proton treatment of prostate cancer patients.
Subject(s)
Humans , Prostate , Prostatic Neoplasms , Proton Therapy , Protons , SkinABSTRACT
TomoTherapy has a merit to treat cancer with Intensity modulated radiation and combines precise 3-D imaging from computerized tomography (CT scanning) with highly targeted radiation beams and rotating beamlets. In this paper, we comparing the dose distribution between TomoTherapy and linear accelerator based intensity modulated radiotherapy (IMRT) for 10 Head & Neck patients using TomoTherapy which is newly installed and operated at National Cancer Center since Sept. 2006. Furthermore, we estimate how the homogeneity and Normal Tissue Complication Probability (NTCP) are changed by motion of target. Inverse planning was carried out using CadPlan planning system (CadPlan R.6.4.7, Varian Medical System Inc. 3100 Hansen Way, Palo Alto, CA 94304-1129, USA). For each patient, an inverse IMRT plan was also made using TomoTherapy Hi-Art System (Hi-Art2_2_4 2.2.4.15, TomoTherapy Incorporated, 1240 Deming Way, Madson, WI 53717-1954, USA) and using the same targets and optimization goals. All TomoTherapy plans compared favorably with the IMRT plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Our results suggest that TomoTherapy is able to reduce the normal tissue complication probability (NTCP) further, keeping a similar target dose homogeneity.