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Background: Erythrodermic psoriasis (EP) is a potentially life-threatening disease, and there is currently no consensus regarding its optimal treatment. Biological drugs approved for Psoriasis Vulgaris treatment have been used as alternatives to traditional medications. Objective: To evaluate the clinical response and tolerability of anti- interleukin 17 (IL17) biologic drugs during a 2-year-follow-up. Methods: This was a retrospective prospective study. EP cases, defined as >75% body surface area involvement, in patients ≥18 years old treated with anti-IL17 for at least 6 consecutive months were enrolled and then followed until 104 weeks. Patient characteristics, overall clinical responses, Psoriasis Area Severity Index score changes, and adverse events were analyzed. Results: Sixteen patients met the criteria, of which 50% had achieved the Psoriasis Area Severity Index 100 response at week 12 and in 93.7% at week 24. In the prospective observation of the cohort, 87.5% were still in remission at week 52 and 81.25% at 104 weeks, without adverse events. The 3 patients in whom the treatment was interrupted lost efficacy and were switched to other therapies. Limitations: Only descriptive analysis was conducted due to the limited number of patients. Conclusions: A satisfactory long-term clinical response without adverse effects was observed in this case series, suggesting the interest of anti-IL17 in EP treatment.

Background: Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective: To provide updated and extended data on anaphylaxis in this region. Method: An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results: Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p

Purpose: The proximity or overlap of planning target volume (PTV) and organs-at-risk (OARs) poses a major challenge in stereotactic body radiation therapy (SBRT) of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality., Methods and Materials: A multiparametric specification of desired target doses (gross target volume [GTV] D50% , GTV D99% , PTV D95% , and PTV 0.5cc ) with 2 prescription doses of GTV D50% = 5 × 9.2Gy (46 Gy) and GTV D50% = 8 × 8.25 Gy (66 Gy) and OAR limits were distributed with planning computed tomography and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, replanning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion., Results: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTV D50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTV D99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTV D50% prescription was performed by 95% of planners within 2%, and GTV D99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks., Conclusions: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lignocellulolytic enzymes from a novel Myceliophthora verrucosa (5DR) strain was found to potentiate the efficacy of benchmark cellulase during saccharification of acid/alkali treated bagasse by ~ 2.24 fold, indicating it to be an important source of auxiliary enzymes. The De-novo sequencing and analysis of M. verrucosa genome (31.7 Mb) revealed to encode for 7989 putative genes, representing a wide array of CAZymes (366) with a high proportions of auxiliary activity (AA) genes (76). The LC/MS QTOF based secretome analysis of M. verrucosa showed high abundance of glycosyl hydrolases and AA proteins with cellobiose dehydrogenase (CDH) (AA8), being the most prominent auxiliary protein. A gene coding for lytic polysaccharide monooxygenase (LPMO) was expressed in Pichia pastoris and CDH produced by M. verrucosa culture on rice straw based solidified medium were purified and characterized. The mass spectrometry of LPMO catalyzed hydrolytic products of avicel showed the release of both C1/C4 oxidized products, indicating it to be type-3. The lignocellulolytic cocktail comprising of in-house cellulase produced by Aspergillus allahabadii strain spiked with LPMO & CDH exhibited enhanced and better hydrolysis of mild alkali deacetylated (MAD) and unwashed acid pretreated rice straw slurry (UWAP), when compared to Cellic CTec3 at high substrate loading rate., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This topical review focuses on Patient-Specific Quality Assurance (PSQA) approaches to stereotactic body radiation therapy (SBRT). SBRT requires stricter accuracy than standard radiation therapy due to the high dose per fraction and the limited number of fractions. The review considered various PSQA methods reported in 36 articles between 01/2010 and 07/2022 for SBRT treatment. In particular comparison among devices and devices designed for SBRT, sensitivity and resolution, verification methodology, gamma analysis were specifically considered. The review identified a list of essential data needed to reproduce the results in other clinics, highlighted the partial miss of data reported in scientific papers, and formulated recommendations for successful implementation of a PSQA protocol., (© 2023 Institute of Physics and Engineering in Medicine.)

Purpose: To determine the error detection sensitivity of a commercial log file-based system (LINACWatch®, LW) for integration into clinical routine and to compare it with a measurement device (OCTAVIUS 4D, Oct4D) for IMRT and VMAT delivery QA., Materials and Methods: 76 VMAT/IMRT plans (H&N, prostate, rectum and breast) preliminarily classified according to their Modulation Complexity Score (MCS) calculated by LW, were considered. Receiver Operating Characteristic (ROC) Curves were used to establish gamma criteria for LW. 12 plans (3 for each site) were intentionally modified in order to introduce delivery errors regarding MLC, jaws, collimator, gantry and MU (for a total set of 168 incorrect plans) and irradiated on Oct4D; the corresponding log files were analysed by LW. Each incorrect plan was compared to the error-free plan using γ-index analysis for MLC, jaws and MU errors investigation and Root-Mean-Square (RMS) values for gantry and collimator errors investigation., Results: MCS ranges values were: 0.10-0.20 for H&N, 0.21-0.40 for prostate and rectum, 0.41-1.00 for breast. From ROC curves, the Gamma Passing Rate (GPR) thresholds were: 87%, 92%, 99% for H&N, prostate and rectum, and breast, respectively. The 1.5%/1.5 mm/local criteria were adopted for the γ-analysis. LW sensitivity in detecting the introduced errors was higher when compared to Oct4D: 48.5% vs 30.4% respectively., Conclusions: LW can be considered useful complement to phantom-based delivery QA of IMRT/VMAT plans. The MCS tool is effective in detecting over or under modulated plans prior to pre-treatment QA. However, rigorous and routinely machine QCs are recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study., Methods and Materials: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm 2 field sizes (FSs) (normalized to 10x10 cm 2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs., Results: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible., Conclusions: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate critical aspects and effectiveness of in vivo dosimetry (IVD) tests obtained by an electronic portal imaging device (EPID) in a multicenter and multisystem context., Materials and Methods: Eight centers with three commercial systems-SoftDiso (SD, Best Medical Italy, Chianciano, Italy), Dosimetry Check (DC, Math Resolution, LCC), and PerFRACTION (PF, Sun Nuclear Corporation, SNC, Melbourne, FL)-collected IVD results for a total of 2002 patients and 32,276 tests. Data are summarized for IVD software, radiotherapy technique, and anatomical site. Every center reported the number of patients and tests analyzed, and the percentage of tests outside of the tolerance level (OTL%). OTL% was categorized as being due to incorrect patient setup, incorrect use of immobilization devices, incorrect dose computation, anatomical variations, and unknown causes., Results: The three systems use different approaches and customized alert indices, based on local protocols. For Volumetric Modulated Arc Therapy (VMAT) treatments OTL% mean values were up to 8.9% for SD, 18.0% for DC, and 16.0% for PF. Errors due to "anatomical variations" for head and neck were up to 9.0% for SD and DC and 8.0% for PF systems, while for abdomen and pelvis/prostate treatments were up to 9%, 17.0%, and 9.0% for SD, DC, and PF, respectively. The comparison among techniques gave 3% for Stereotactic Body Radiation Therapy, 7.0% (range 4.7-8.9%) for VMAT, 10.4% (range 7.0-12.2%) for Intensity Modulated Radiation Therapy, and 13.2% (range 8.8-21.0%) for 3D Conformal Radiation Therapy., Conclusion: The results obtained with different IVD software and among centers were consistent and showed an acceptable homogeneity. EPID IVD was effective in intercepting important errors.

Tannic acid, a hydrolysable gallotannin present in plant tissues, consists of a central glucose molecule esterified with gallic acid molecules. Some microorganisms, including several Aspergillus species, can metabolize tannic acid by releasing gallic acid residues from tannic acid by secreting tannic acid specific esterases into the medium. The expression of these so-called tannases is induced by tannic acid or gallic acid. In this study, we identified a conserved transcriptional activator-repressor module involved in the regulation of predicted tannases and other genes involved in gallic acid metabolism. The transcriptional activator-repressor module regulating tannic acid utilization resembles the transcriptional activator-repressor modules regulating galacturonic acid and quinic acid utilization. Like these modules, the Zn(II) 2 Cys 6 transcriptional activator (TanR) and the putative repressor (TanX) are located adjacent to each other. Deletion of the transcriptional activator ( Δ tanR ) results in inability to grow on gallic acid and severely reduces growth on tannic acid. Deletion of the putative repressor gene ( Δ tanX ) results in the constitutive expression of tannases as well as other genes with mostly unknown function. Known microbial catabolic pathways for gallic acid utilization involve so-called ring cleavage enzymes, and two of these ring cleavage enzymes show increased expression in the Δ tanX mutant. However, deletion of these two genes, and even deletion of all 17 genes encoding potential ring cleavage enzymes, did not result in a gallic acid non-utilizing phenotype. Therefore, in A. niger gallic acid utilization involves a hitherto unknown pathway. Transcriptome analysis of the Δ tanX mutant identified several genes and gene clusters that were significantly induced compared to the parental strain. The involvement of a selection of these genes and gene clusters in gallic acid utilization was examined by constructing gene deletion mutants and testing their ability to grow on gallic acid. Only the deletion of a gene encoding an FAD-dependent monooxygenase (NRRL3&#95;04659) resulted in a strain that was unable to grow on gallic acid. Metabolomic studies showed accumulation of gallic acid in the Δ NRRL3&#95;04659 mutant suggesting that this predicted monooxygenase is involved in the first step of gallic acid metabolism and is likely responsible for oxidation of the aromatic ring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Arentshorst, Falco, Moisan, Reid, Spaapen, van Dam, Demirci, Powlowski, Punt, Tsang and Ram.)

Objectives: This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans., Methods: Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm 2 to 1 × 1 cm 2 ) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points., Results: The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC-defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms., Conclusion: The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing., Advances in Knowledge: First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.

Background and Purpose: High-dose 6‑MV radiotherapy may cause cardiac implantable electronic devices (CIEDs) to malfunction. To assess CIED malfunctions resulting from direct exposure up to 10 Gy, 100 pacemakers (PMs) and 40 implantable cardioverter-defibrillators (ICDs) were evaluated., Materials and Methods: CIEDs underwent baseline interrogation. In ICDs, antitachycardia therapies were disabled via the programmer while the detection windows were left enabled. A computed tomography (CT) scan was performed to build the corresponding treatment plan. CIEDs were "blinded" and randomized to receive single doses of either 2, 5, or, 10 Gy via a 6-MV linear accelerator (linac) in a water phantom. Twenty-two wireless telemetry-enabled CIEDs underwent a real-time session, and their function was recorded by the video camera in the bunker. The CIEDs were interrogated after exposure and once monthly for 6 months., Results: During exposure, regardless of dose, 90.9% of the CIEDs recorded electromagnetic interference, with 6 ICDs (27.3%) reporting pacing inhibition and inappropriate arrhythmia detections. After exposure, a backup reset was observed in 1 PM (0.7% overall, 1% among PMs), while 7 PMs (5% overall, 7% among PMs) reported battery issues (overall immediate malfunction rate was 5.7%). During follow-up, 4 PMs (2.9% overall; 4% among PMs) and 1 ICD (0.7% overall; 2.5% among ICDs) reported abnormal battery depletion, and 1 PM (0.7% overall; 1% among PMs) reported a backup reset (overall late malfunction rate was 4.3%)., Conclusion: Apart from transient electromagnetic interference, last-generation CIEDs withstood direct 6‑MV exposure up to 10 Gy. Permanent battery or software errors occurred immediately or later only in less recent CIEDs.

Background: COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II., Methods: The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily., Results: By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed., Conclusion: During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.

Stereotactic body radiation therapy (SBRT) has been recognized as a standard treatment option for many anatomical sites. Sophisticated radiation therapy techniques have been developed for carrying out these treatments and new quality assurance (QA) programs are therefore required to guarantee high geometrical and dosimetric accuracy. This paper focuses on recent advances on in-vivo measurements methods (IVM) for SBRT treatment. More specifically, all of the online QA methods for estimating the effective dose delivered to patients were compared. Determining the optimal IVM for performing SBRT treatments would reduce the risk of errors that could jeopardize treatment outcome. A total of 89 papers were included. The papers were subdivided into the following topics: point dosimeters (PD), transmission detectors (TD), log file analysis (LFA), electronic portal imaging device dosimetry (EPID), dose accumulation methods (DAM). The detectability capability of the main IVM detectors/devices were evaluated. All of the systems have some limitations: PD has no spatial data, EPID has limited sensitivity towards set-up errors and intra-fraction motion in some anatomical sites, TD is insensitive towards patient related errors, LFA is not an independent measure, DAMs are not always based on measures. In order to minimize errors in SBRT dose delivery, we recommend using synergic combinations of two or more of the systems described in our review: on-line tumor position and patient information should be combined with MLC position and linac output detection accuracy. In this way the effects of SBRT dose delivery errors will be reduced., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Left ventricular assist device (LVAD) is considered a standard care for patients with advanced heart failure. The aim of this work was to study in vitro the effects of direct exposure of the Jarvik 2000 LVAD to 10-MV photon beams., Methods: Jarvik 2000 pump was immersed in a siliconized box filled with deionized water. A 30 × 30 × 15 cm RW3 slabs were added forth and back to the box. A treatment plan consisting of a single direct 10 × 10 cm 2 field size beam was used to deliver 1000 MU at the center of the pump. During irradiation, the external Flow Maker controller and the lithium battery were positioned away from the beam. Pump parameter data (included voltage, current and frequency) were measured, recorded and analyzed for changes in pump function among baseline, pre-irradiation, during irradiation, post-irradiation and after 6 months. The whole session lasted 6 months. The Mann-Whitney U test was used to compare the repeated measurements. X-ray radiation attenuation was also studied., Results: The parameters investigated remained stable over the 6 months; that is, no pump stops, alarms, events, operational changes or abnormalities during the discharge rate of the connected power sources, were encountered, confirmed by the Mann-Whitney U test applied to all sessions (p > 0.1). The measured X-ray attenuation differed from the calculated one by TPS by 34%., Conclusion: The Jarvik 2000 resulted stable under direct X-ray beam of 10-MV energy. Its strong attenuation, however, can affect dose deposition in the pump in TPS, and it must be taken into account.

Purpose: The complexity of the modern Stereotactic Body Radiation Therapy (SBRT) techniques requires comprehensive quality assurance programs, to ensure the right treatment to the patient. Dosimetry of small radiation fields is a challenge especially for radiotherapy centres starting to work on this issue. The matter to be discussed here concerns the need of detailed measurement procedures and cross checks to be paired to the usual recommendations on detectors and correction factors., Materials and Methods: The presented work involved 24 Italian radiotherapy centres, with the specific purpose to minimize systematic errors in output factor measurements over different radiotherapy centres. Using the unshielded silicon diode IBA Razor, reference curves for the relative signal ratio (RSR) as a function of beam size were created for each Linac family., Results: With this study we have demonstrated consistency of small field dosimetry on all the centres involved, moreover all radiotherapy centres using Razor are allowed to compare measurements amongst each other and centres with values deviating more than 5% from the reference curve are advised to repeat their measurements. With this procedure, some critical issues were detected from two centres in RSR measurements, that, if implemented into the own treatment planning system, would induce an unwanted overdosage larger than 5%., Conclusions: The proposed approach could allow one to envision high-skilled therapy centres providing support to those featuring minor experience and could represent an important strategy for the clinical implementation of emerging technologies at high quality levels. The methodology adopted exploits crowd knowledge methods which could be applied in others areas of radiation dosimetry., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Interventional radiology is based on minimally invasive procedures that allow diagnosis and percutaneous treatment of diseases in almost all organ systems. Such procedures have many benefits, but they also contribute significantly to collective radiation dose. In this regard, effective dose (E) is a convenient quantity to estimate patients' stochastic radiation risk. However, E cannot be accurately evaluated immediately. In the present study, we aimed to estimate the E value in 15 selected interventional procedures. The estimation was based on dose area product (DAP) measurements and used case-specific conversion coefficients. The E values ranged from 3.3 to 69.9 mSv, depending on the kind of procedure. This wide range was mainly due to the broad variation in DAP values, which in turn depend on the details of how the procedures are performed. This suggests that to ensure valid comparative studies and universal reference levels, all interventional procedures should be well classified.

Purpose: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy., Patients and Methods: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/β ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan., Results: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans., Conclusion: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: The aim of the in vivo dosimetry, during the fractionated radiation therapy, is the verification of the correct dose delivery to patient. Nowadays, in vivo dosimetry procedures for photon beams are based on the use of the electronic portal imaging device and dedicated software to elaborate electronic portal imaging device images., Methods: In total, 8474 in vivo dosimetry tests were carried out for 386 patients treated with 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and volumetric modulated arc therapy techniques, using the SOFTDISO. SOFTDISO is a dedicated software that uses electronic portal imaging device images in order to (1) calculate the R index, that is, the ratio between daily reconstructed dose and the planned one at isocenter and (2) perform a γ-like analysis between the signals, S, of a reference electronic portal imaging device image and that obtained in a daily fraction. It supplies 2 indexes, the percentage γ% of points with γ < 1 and the mean γ value, γ mean . In γ-like analysis, the pass criteria for the signals agreement ΔS% and distance to agreement Δd have been selected based on the clinical experience and technology used. The adopted tolerance levels for the 3 indexes were fixed in 0.95 ≤ R ≤ 1.05, γ% ≥ 90%, and γ mean ≤ 0.5., Results: The results of R ratio, γ-like, and a visual inspection of these data reported on a monitor screen permitted to individuate 2 classes of errors (1) class 1 that included errors due to inadequate standard quality controls and (2) class 2, due to patient morphological changes. Depending on the technique and anatomical site, a maximum of 18% of tests had at least 1 index out of tolerance; once removed the causes of class-1 errors, almost all patients (except patients with 4 lung and 2 breast cancer treated with 3-dimensional conformal radiotherapy) presented mean indexes values ([Formula: see text], [Formula: see text]%, and [Formula: see text] ) within tolerance at the end of treatment course. Class-2 errors were found in some patients., Conclusions: The in vivo dosimetry procedure with SOFTDISO resulted easily implementable, able to individuate errors with a limited workload.

Small secreted proteins (SSP) have been defined as proteins containing a signal peptide and a sequence of less than 300 amino acids. In this analysis, we have compared the secretion pattern of SSPs among eight aspergilli species in the context of plant biomass degradation and have highlighted putative interesting candidates that could be involved in the degradative process or in the strategies developed by fungi to resist the associated stress that could be due to the toxicity of some aromatic compounds or reactive oxygen species released during degradation. Among these candidates, for example, some stress-related superoxide dismutases or some hydrophobic surface binding proteins (HsbA) are specifically secreted according to the species . Since these latter proteins are able to recruit lytic enzymes to the surface of hydrophobic solid materials and promote their degradation, a synergistic action of HsbA with the degradative system may be considered and need further investigations. These SSPs could have great applications in biotechnology by optimizing the efficiency of the enzymatic systems for biomass degradation., (© 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Purpose: In prostate cancer radiotherapy, the relationship between genitourinary (GU) toxicity and clinical-dosimetric parameters is debated. We report our analysis of the parameters associated with GU toxicity., Materials and Methods: Eighty-six consecutive patients treated with conformal radiotherapy for localized prostate cancer were retrospectively analyzed; the bladder was delineated both as "whole bladder" (WB: Defined in its entirety as a solid organ) and "inferior bladder" (IB: Corresponding to the distal part of the bladder). GU toxicity and dose-volume parameters were correlated using the point biserial correlation coefficient. The normal tissue complication probability (NTCP) cut-off volume model was fitted to toxicity data; univariate analysis between GU toxicity and clinical parameters was done., Results: Acute GU toxicity was correlated to doses higher than 80 Gy (P < 0.05) while late GU was correlated to doses higher than 77 Gy for WB and from 77.5 Gy for IB. The NTCP cut-off volume model identified for both WB and IB a bladder volume of 6 cc receiving a dose ≥77 Gy corresponding to a 50% probability of GU toxicity. At univariate analysis, acute GU toxicity was correlated with smoke (P < 0.001)., Conclusion: Bladder maximal doses quantified as hotspots show a correlation to GU toxicity.

Purpose: The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference., Methods: Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers) and by Iris(™) variable aperture collimator (4 centers). Setup conditions were: 80cm source to detector distance, and 1.5cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements., Results: Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris(™) collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications., Conclusions: Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris(™), demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective., Methods: Five CT series were sent to the participants. The dose prescription to PTV was 54Gy in 3 fractions of 18Gy. The plans were compared in terms of PTV-gEUD2 (generalized Equivalent Uniform Dose equivalent to 2Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD2 (mean lung dose equivalent to 2Gy). The data were stratified according to expertise and technology., Results: Twenty-six centers equipped with Linacs, 3DCRT (4% - 1 center), static IMRT (8% - 2 centers), VMAT (76% - 20 centers), CyberKnife (4% - 1 center), and Tomotherapy (8% - 2 centers) collaborated. Significant PTV-gEUD2 differences were observed (range: 105-161Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8±3.4Gy, 14.2±10.1%, 0.70±0.15, and 4.9±1.9. Significant correlations for PTV-gEUD2 versus PTV-HI, and MLD2 versus PTV-GI, were observed., Conclusions: The differences in terms of PTV-gEUD2 may suggest the inclusion of PTV-gEUD2 calculation for retrospective data inter-comparison., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

This study aims at optimizing treatment planning in young patients affected by lymphoma (Stage II to III) by using an inclined board (IB) that allows reducing doses to the organs at risk. We evaluated 19 young patients affected by stage I to III lymphomas, referred to our Department for consolidation radiotherapy (RT) treatment on the mediastinum. Patients underwent 2 planning computed tomography (CT) scans performed in different positions: flat standard position and inclined position. A direct comparison between the different treatment plans was carried out analyzing dosimetric parameters obtained from dose-volume histograms generated for each plan. Comparison was performed to evaluate the sparing obtained on breast and heart. Dosimetric evaluation was performed for the following organs at risk (OARs): mammary glands, lungs, and heart. A statistically significant advantage was reported for V 5 , V 20 , and V 30 for the breast when using the inclined board. A similar result was obtained for V 5 and V 10 on the heart. No advantage was observed in lung doses. The use of a simple device, such as an inclined board, allows the optimization of treatment plan, especially in young female patients, by ensuring a significant reduction of the dose delivered to breast and heart., (Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator., Methods: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors., Results: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes., Conclusions: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions., (Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Aim of the present work is to evaluate the synthetic single crystal diamond Schottky photodiode developed at the laboratories of "Tor Vergata" University in Rome in a new dosimeter configuration specifically designed for offline wireless in vivo dosimetry (IVD) applications., Methods: The new diamond based dosimeter, single crystal diamond detector (SCDD-iv), consists of a small unwired detector and a small external reading unit that can be connected to commercial electrometers for getting the detector readout after irradiation. Two nominally identical SCDD-iv dosimeter prototypes were fabricated and tested. A basic dosimetric characterization of detector performances relevant for IVD application was performed under irradiation with (60)Co and 6 MV photon beams. Preirradiation procedure, response stability, short and long term reproducibility, leakage charge, fading effect, linearity with dose, dose rate dependence, temperature dependence, and angular response were investigated., Results: The SCDD-iv is simple, with no cables linked to the patient and the readout is immediate. The range of response with dose has been tested from 1 up to 12 Gy; the reading is independent of the accumulated dose and dose rate independent in the range between about 0.5 and 5 Gy/min; its temperature dependence is within 0.5% between 25 and 38 °C, and its directional dependence is within 2% from 0° to 90°. The combined relative standard uncertainty of absorbed dose to water measurements is estimated lower than the tolerance and action level of 5%., Conclusions: The reported results indicate the proposed novel offline dosimeter based on a synthetic single crystal diamond Schottky photodiode as a promising candidate for in vivo dosimetry applications with photon beams.

The purpose of this study was to compare the dosimetric properties of small field electron beams shaped by circular Cerrobend blocks and stainless steel tubular applicators. Percentage depth dose curves, beam profiles, and output factors of small-size circular fields from 2 to 5 cm diameter, obtained either by tubular applicators and Cerrobend blocks, were measured for 6, 10, and 15 MeV electron beam energies. All measurements were performed using a PTW microDiamond 60019 premarket prototype. An overall similar behavior between the two collimating systems can be observed in terms of PDD and beam profiles. However, Cerrobend collimators produce a higher bremsstrahlung background under irradiation with high-energy electrons. In such irradiation condition, larger output factors are observed for tubular applicators. Similar dosimetric properties are observed using circular Cerrobend blocks and stainless steel tubular applicators at lower beam energies. However, Cerrobend collimators allow the delivery of specific beam shapes, conformed to the target area. On the other hand, in high-energy irradiation conditions, tubular applicators produce a lower bremsstrahlung contribution, leading to lower doses outside the target volume. In addition, the higher output factors observed at high energies for tubular applicators lead to reduced treatment times.

The purpose of this work has been to dosimetrically investigate four fluoroscopically guided interventions: the percutaneous vertebroplasty (PVP), the percutaneous disc decompression (PDD), the radiofrequency medial branch neurolysis (RF) (hereafter named spine procedures), and the endovascular treatment for the critical limb ischemia (CLI). The X-ray equipment used was a Philips Integris Allura Xper FD20 imaging system provided with a dose-area product (DAP) meter. The parameters investigated were: maximum skin dose (MSD), air kerma (Ka,r), DAP, and fluoroscopy time (FT). In order to measure the maximum skin dose, we employed a system based on MOSFET detectors. Before using the system on patients, a calibration factor Fc and correction factors for energy (CkV) and field size (CFD) dependence were determined. Ka,r, DAP, and FT were extrapolated from the X-ray equipment. The analysis was carried out on 40 patients, 10 for each procedure. The average fluoroscopy time and DAP values were compared with the reference levels (RLs) proposed in literature. Finally, the correlations between MSD, FT, Ka,r, and DAP values, as well as between DAP and FT values, were studied in terms of Pearson's product-moment coefficients for spine procedures only. An Fc value of 0.20 and a very low dependence of CFD on field size were found. A third-order polynomial function was chosen for CkV. The mean values of MSD ranged from 2.3 to 10.8cGy for CLI and PVP, respectively. For these procedures, the DAP and FT values were within the proposed RL values. The statistical analysis showed little correlation between the investigated parameters. The interventional procedures investigated were found to be both safe with regard to deterministic effects and optimized for stochastic ones. In the spine procedures, the observed correlations indicated that the estimation of MSD from Ka,r or DAP was not accurate and a direct measure of MSD is therefore recommended.

High-energy electron beams generated by linear accelerators, typically in the range 6 to 20 MeV, are used in small field sizes for radiotherapy of localized superficial tumors. Unshielded silicon diodes (Si-D) are commonly considered suitable detectors for relative dose measurements in small electron fields due to their high spatial resolution. Recently, a novel synthetic single crystal diamond diode (SCDD) showed suitable properties for standard electron beams and small photon beams dosimetry. The aim of the present study is twofold: to characterize 6 to 15 MeV small electron beams shaped by using commercial tubular applicators with 2, 3, 4 and 5 cm diameter and to assess the dosimetric performance under such irradiation conditions of the novel SCDD dosimeter by comparison with commercially available dosimeters, namely a Si-D and a plane–parallel ionization chamber. Percentage depth dose curves, beam profiles and output factors (OFs) were measured. A good agreement among the dosimeters was observed in all of the performed measurements. As for the tubular applicators, two main effects were evidenced: (i) OFs larger than unity were measured for a number of field sizes and energies, with values up to about 1.3, that is an output 30% greater than that obtained at the 10 × 10 cm2 reference field; (ii) for each diameter of the tubular applicator a noticeable increase of the OF values was observed with increasing beam energy, up to about 100% in the case of the smaller applicator. This OF behavior is remarkably different from what typically observed for small blocked fields having the same size and energy as those used in this study. OFs for tubular applicators depend considerably on the field size, so interpolation is unadvisable to predict the linear accelerator output for such applicators whereas reliable high-resolution detectors, as the silicon and diamond diodes used in this work allow OF measurements with uncertainties of about 1%.

Background: To identify predictive factors of radiation-induced skin toxicity in breast cancer patients by the analysis of dosimetric and clinical factors., Methods: 339 patients treated between January 2007 and December 2010 are included in the present analysis. Whole breast irradiation was delivered with Conventional Fractionation (CF) (50 Gy, 2.0/day, 25 fractions) and moderate Hypofractionated Schedule (HS) (44 Gy, 2.75 Gy/day, 16 fractions) followed by tumour bed boost. The impact of patient clinical features, systemic treatments and, in particular, dose inhomogeneities on the occurrence of different levels of skin reaction has been retrospectively evaluated., Results: G2 and G3 acute skin toxicity were 42% and 13% in CF patients and 30% and 7.5% in HS patients respectively. The retrieval and revaluation of 200 treatment plans showed a strong correlation between areas close to the skin surface, with inhomogeneities >107% of the prescribed dose, and the desquamation areas as described in the clinical records., Conclusions: In our experience dose inhomogeneity underneath G2 - G3 skin reactions seems to be the most important predictor for acute skin damage and in these patients more complex treatment techniques should be considered to avoid skin damage. Genetic polymorphisms too have to be investigated as possible promising candidates for predicting acute skin reactions.

Aim: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer., Methods: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother., Results: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue., Conclusion: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

Purpose: To investigate the dosimetric properties of synthetic single crystal diamond based Schottky diodes under irradiation with therapeutic electron beams from linear accelerators., Methods: A single crystal diamond detector was fabricated and tested under 6, 8, 10, 12, and 15 MeV electron beams. The detector performances were evaluated using three types of commercial detectors as reference dosimeters: an Advanced Markus plane parallel ionization chamber, a Semiflex cylindrical ionization chamber, and a p-type silicon detector. Preirradiation, linearity with dose, dose rate dependence, output factors, lateral field profiles, and percentage depth dose profiles were investigated and discussed., Results: During preirradiation the diamond detector signal shows a weak decrease within 0.7% with respect to the plateau value and a final signal stability of 0.1% (1σ) is observed after about 5 Gy. A good linear behavior of the detector response as a function of the delivered dose is observed with deviations below ±0.3% in the dose range from 0.02 to 10 Gy. In addition, the detector response is dose rate independent, with deviations below 0.3% in the investigated dose rate range from 0.17 to 5.45 Gy∕min. Percentage depth dose curves obtained from the diamond detector are in good agreement with the ones from the reference dosimeters. Lateral beam profile measurements show an overall good agreement among detectors, taking into account their respective geometrical features. The spatial resolution of solid state detectors is confirmed to be better than that of ionization chambers, being the one from the diamond detector comparable to that of the silicon diode. A good agreement within experimental uncertainties was also found in terms of output factor measurements between the diamond detector and reference dosimeters., Conclusions: The observed dosimetric properties indicate that the tested diamond detector is a suitable candidate for clinical electron beam dosimetry.

Purpose: During radiological interventional procedures (RIP) the skin of a patient under examination may undergo a prolonged x-ray exposure, receiving a dose as high as 5 Gy in a single session. This paper describes the use of the OneDose(TM) cable-free system based on p-type MOSFET detectors to determine the entrance skin dose (ESD) at selected points during RIP., Methods: At first, some dosimetric characteristics of the detector, such as reproducibility, linearity, and fading, have been investigated using a C-arc as a source of radiation. The reference setting (RS) was: 80 kV energy, 40 cm × 40 cm field of view (FOV), current-time product of 50 mAs and source to skin distance (SSD) of 50 cm. A calibrated PMX III solid state detector was used as the reference detector and Gafchromic(®) films have been used as an independent dosimetric system to test the entire procedure. A calibration factor for the RS and correction factors as functions of tube voltage and FOV size have been determined., Results: Reproducibility ranged from 4% at low doses (around 10 cGy as measured by the reference detector) to about 1% for high doses (around 2 Gy). The system response was found to be linear with respect to both dose measured with the PMX III and tube voltage. The fading test has shown that the maximum deviation from the optimal reading conditions (3 min after a single irradiation) was 9.1% corresponding to four irradiations in one hour read 3 min after the last exposure. The calibration factor in the RS has shown that the system response at the kV energy range is about four times larger than in the MV energy range. A fifth order and fourth order polynomial functions were found to provide correction factors for tube voltage and FOV size, respectively, in measurement settings different than the RS. ESDs measured with the system after applying the proper correction factors agreed within one standard deviation (SD) with the corresponding ESDs measured with the reference detector. The ESDs measured with Gafchromic(®) films were in agreement within one SD compared to the ESDs measured using the OneDose(TM) system, as well. The global uncertainty associated to the OneDose(TM) system established in our experiments, ranged from 7% to 10%, depending on the duration of the RIP due to fading. These values are much lower than the uncertainty commonly accepted for general diagnostic practices (20%) and of about the same size of the uncertainty recommended for practices with high risk of deterministic side effects (7%)., Conclusions: The OneDose(TM) system has shown a high sensitivity in the kV energy range and has been found capable of measuring the entrance skin dose in RIP.

Background: The OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer., Methods: An Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2)., Results: The ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session., Conclusions: The method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements.

Objectives: The aim of this study was to define a method to evaluate the total dose delivered to the rectum during the whole treatment course in six patients undergoing irradiation for prostate cancer using an offline definition of organ motion with images from a cone beam CT (CBCT) scanner available on a commercial linear accelerator., Methods: Patient set-up was verified using a volumetric three-dimensional CBCT scanner; 9-14 CBCT scans were obtained for each patient. Images were transferred to a commercial treatment planning system for offline organ motion analysis. The shape of the rectums were used to obtain a mean dose-volume histogram (), which was the average of the DVHs of the rectums as they appeared in each verification CBCT. A geometric model of an average rectum (AR) was produced using the rectal contours delineated on the CBCT scans (DVH(AR)). To check whether the first week of treatment was representative of the whole treatment course, we evaluated the DVHs related to only the first five CBCT scans ( and DVH(AR5)). Finally, the influence of a dietary protocol on the goodness of our results was considered., Results: In all six patients the original rectal DVH for the planning CT scan showed higher values than all DVHs., Conclusion: Although the application of the model to a larger set of patients is necessary to confirm this trend, reconstruction of a representative volume of the rectum throughout the entire treatment course seems feasible.

Cone-beam X-ray volumetric imaging in the treatment room, allows online correction of set-up errors and offline assessment of residual set-up errors and organ motion. In this study the registration algorithm of the X-ray volume imaging software (XVI, Elekta, Crawley, United Kingdom), which manages a commercial cone-beam computed tomography (CBCT)-based positioning system, has been tested using a homemade and an anthropomorphic phantom to: (1) assess its performance in detecting known translational and rotational set-up errors and (2) transfer the transformation matrix of its registrations into a commercial treatment planning system (TPS) for offline organ motion analysis. Furthermore, CBCT dose index has been measured for a particular site (prostate: 120 kV, 1028.8 mAs, approximately 640 frames) using a standard Perspex cylindrical body phantom (diameter 32 cm, length 15 cm) and a 10-cm-long pencil ionization chamber. We have found that known displacements were correctly calculated by the registration software to within 1.3 mm and 0.4°. For the anthropomorphic phantom, only translational displacements have been considered. Both studies have shown errors within the intrinsic uncertainty of our system for translational displacements (estimated as 0.87 mm) and rotational displacements (estimated as 0.22°). The resulting table translations proposed by the system to correct the displacements were also checked with portal images and found to place the isocenter of the plan on the linac isocenter within an error of 1 mm, which is the dimension of the spherical lead marker inserted at the center of the homemade phantom. The registration matrix translated into the TPS image fusion module correctly reproduced the alignment between planning CT scans and CBCT scans. Finally, measurements on the CBCT dose index indicate that CBCT acquisition delivers less dose than conventional CT scans and electronic portal imaging device portals. The registration software was found to be accurate, and its registration matrix can be easily translated into the TPS and a low dose is delivered to the patient during image acquisition. These results can help in designing imaging protocols for offline evaluations., (Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

The occurrence of substance P (SP) immunoreactivity was investigated in the adrenal gland of the lizard Podarcis sicula by ABC immunocytochemical technique: SP-immunoreactivity was present in both adrenaline and noradrenaline cells, in ganglion cells and nerve fibers in the connective capsule surrounding the gland. The involvement of substance P in the modulation of pituitary-interrenal axis was studied in vivo by intraperitoneal injections of SP. The effects were estimated by means of the morphological and morphometrical features of the tissues, as well as the plasma levels of adrenocorticotropic hormone (ACTH), corticosterone and catecholamines, adrenaline and noradrenaline. Substance P (0.07 mg/100 g body wt) decreased ACTH plasma levels and raised corticosterone release from steroidogenic tissue, that showed clear signs of stimulation. In the chromaffin tissue, the decrease in the number of noradrenaline cells, and the increase in the number of adrenaline cells, lowered numeric noradrenaline/adrenaline cell ratio. Moreover, an increase in adrenaline plasma level and a decrease in noradrenaline plasma level were found. The results suggest that (1) also in Reptiles as in other Vertebrates, SP may affect pituitary-adrenal axis activity, and (2) the chromaffin cells may be involved in the paracrine control of steroidogenic activity.

Study Design: A series of four case reports are presented. OBJECTIVE The case reports document completion of lumbar discography with gadolinium contrast followed by successful computed tomography scanning of intradiscal gadolinium., Summary of Background Data: Lumbar discography using gadolinium in cases of iodinated contrast allergy with magnetic resonance imaging used to visualize intradiscal gadolinium after the procedure has been described. To the authors' knowledge, there are no reports of gadolinium discography followed by computed tomography scanning of intradiscal gadolinium., Methods: The reported cases involved a chart review, performance of discography with gadolinium under fluoroscopic guidance, and postdiscography computed tomography scanning of the discs injected during the procedure., Results: Gadolinium was visible under fluoroscopy in all four cases. It was visualized on postdiscography computed tomography scans performed both early and late after the procedure. Normal discs retained gadolinium for a longer period than discs with annular disruption., Conclusions: Gadolinium discography is a safe, viable alternative to conventional discography in the setting of a patient with iodinated contrast allergy. Postdiscography computed tomography scans adequately visualize intradiscal gadolinium in a more timely and cost-effective manner than magnetic resonance imaging.

Cdk9 is a member of the Cdc2-like family of kinases. It binds to members of the family of cyclin T (T1, T2a and T2b) and to cyclin K. The Cdk9/cyclin T complex appears to be involved in regulating several physiological processes. In fact Cdk9 is the kinase of the P-TEFb complex, involved in basal transcription. Cdk9 has also been described as the kinase of the TAK complex, homologous to P-TEFb and involved in HIV replication. Here we show that Cdk9 interacts with gp130, the receptor of the Interleukin-6 (IL-6) family of cytokines, which includes Leukemia Inhibitory Factor (LIF), Oncostatin M (OSM), Ciliary Neurotrophic Factor (CNTF), Interleukin-11 (IL-11) and Cardiotrophin (CT-1). IL-6 is a key regulator of hematopoiesis, immunological responses and inflammation. In addition, IL-6 plays a major role in the endocrine and nervous systems. Signal transduction by gp130 is mediated by physical interaction of the cytoplasmic region of gp130 with cellular kinases and results in the transcriptional activation of cellular and viral genes. We found that Cdk9 interacts in vitro with the cytoplasmic region of gp130 and we succeded in reproducing this interaction in vivo. Cdk9 expression was found both in the nucleus and in the cytoplasm. The binding occurring between Cdk9 and gp130 increased upon IL-6 stimulation. We also observed that Cdk9 synergized with IL-6 in inducing the activation of an IL-6-responsive reporter plasmid. In summary, these results point to a previously undisclosed role for Cdk9 in signal transduction.