Reconstruction and analysis of circRNA-miRNA-mRNA network in the pathology of lung cancer.

BACKGROUND: The presented study aimed to gain insights into the pathogenesis of lung cancer (LC) and provide novel bio-markers for LC by building a regulatory circular (circ) RNAmicro (mi) RNAmRNA network. MATERIALS AND METHODS: High-throughput sequencing data of circRNAs, miRNAs and mRNAs related to LC originated from GEO (Gene Expression Omnibus) database, and the differential expressions of circRNAs, miRNAs and mRNAs were screened with R language Limma. The circRNA-miRNA and miRNA-mRNA pairs were used to build the ceRNA network. The functions of differential expression circRNAs were elucidated by performing the functional enrichment analysis on GO and KEGG. Furthermore, the selected LC prognostic genes were verified by tissue chips and immunohistochemistry (IHC). RESULTS: On the whole, 20 downregulated circRNAs, 55 upregulated miRNAs and 243 downregulated mRNAs were identified in LC. Lastly, a circRNA-miRNA-mRNA ceRNA network was built, which was composed of 2 circRNAs, 2 miRNAs, and 2 mRNAs. As indicated from the analysis based on public databases and IHC, the differential genes (i.e., FXYD1 and SEMA5A) in this network acted as LC prognostic factors. As confirmed by performing IHC and survival analyses, FXYD1 and SEMA5A expressions in LC were downregulated, and their expressions displayed a relationship to the overall survival (OS) of LC cases. CONCLUSIONS: This study presents novel insights into the role of circRNAs in the development of LC via the ceRNA mechanism. The identified FXYD1 and SEMA5A gene could act as novel and vital LC prognostic indicators.

Changes in the Radiation Toxicity of Human Lymphoblastic T-cell Line (Jurkat) by a Common Pesticide: Diazinon.

BACKGROUND: Diazinon is one of the most common pesticides in the world playing a similar role to radiation and it could cause DNA breaks and genetic effects. OBJECTIVE: In this study, radiosensitivity of a lymphoblastic cell line pretreated by Diazinon was investigated. MATERIAL AND METHODS: In this case-control study, the human lymphoblastic T-cell line was divided into 6 groups based on receiving radiation or/and Diazinon. After that, the DNA damage, in all of the groups, were counted by cytokinesis-block micronuclei assay using different indices. RESULTS: The mean frequency of micronuclei, nuclear bridges and nuclear buds in cell groups exposed by both Diazinon and radiation were remarkably higher than the other groups which just received radiation or Diazinon alone. The interaction between radiation and Diazinon treatment was statistically significant for NBUDS index. CONCLUSION: The results indicated that the Diazinon contamination could affect the radiosensitivity index of cancerous cells while further molecular and in-vivo studies are needed to investigate genetic and toxic effects of Diazinon on DNA and its repair system.

Combined Effect of Iodine Contrast Media, Cisplatin and External Beam Radiotherapy on Anaplastic Thyroid Cancer Cells.

INTRODUCTION: The current study investigated the combination of high Z atoms (iodine-, platinium-based drugs) with using low energy irradiation (120kvp) in Anaplastic Thyroid cancer cells. MATERIAL AND METHODS: For this purpose, eight groups were designed: control (CNT), different concentrations of Iodine contrast media (ICM), irradiation with various doses, Cis-platin (CDDP) with different concentrations, (ICM + CDDP), (ICM + RAD), (CDDP + RAD) and (ICM + CDDP + RAD). The viability was measured by MTT and Colony assay. In MTT assay, the viability of 8305c cells RAD (2 Gy)+ICM (10mg/mL) group was significantly lower than those treated with RAD or ICM alone. CDDP +ICM+RAD group significantly decreased the viability. In colony assay, cells in ICM + RAD (2 Gy) group reduced the number of colonies more significant than RAD group. The difference of colony forming ability between CDDP and CDDP + RAD (2 Gy) was significant. The difference of ICM + CDDP + RAD (2 Gy) and CDDP +RAD (2 Gy) group was significant. All data were statistically analysed using one-way analysis of variance (ANOVA) followed by Chafe's multi-comparisons tests. All data were presented as mean ± standard deviation (SD) and analysed using statistical package for social sciences (SPSS 16). Significance was considered to be p<0.05. RESULTS: In MTT assay, the viability of 8305c cells RAD (2 Gy) + ICM (10mg/mL) group was significantly lower than those treated with RAD or ICM alone. CDDP + ICM + RAD group significantly decreased the viability. In colony assay, cells in ICM + RAD (2 Gy) group reduced the number of colonies more significantly than RAD group. The difference of colony forming ability between CDDP and CDDP + RAD (2 Gy) was significant. The difference of ICM + CDDP + RAD (2 Gy) and CDDP + RAD (2 Gy) group was significant. CONCLUSION: Exposure of ATC to ICM in the presence of CDDP increases tissue X-rays absorbance by Auger electrons and photo electrons leading to more fatal effects against the tumour.

Real-world systemic therapy treatment patterns for squamous cell carcinoma of the head and neck in Canada.

Background: In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown. Methods: Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May-July 2016 for 6-8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease). Results: Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided; 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57-68 years], and 24% were current smokers, with a mean exposure of 26.2 ± 12.7 pack-years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20-146 days). The most common second-line regimen was cetuximab monotherapy (43%); platinum-based regimens were markedly infrequent (13%). Conclusions: Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines; cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

The protective effects of melatonin on blood cell counts of rectal cancer patients following radio-chemotherapy: a randomized controlled trial.

PURPOSE: We aimed to examine the radioprotective effects of melatonin on the blood cell counts of patients with rectum cancer undergoing radiotherapy. MATERIALS AND METHODS: This double-blind placebo-controlled study was conducted on 60 rectal cancer patients who were referred to Rajaii Hospital of Babolsar, Iran. An equal number of patients were randomly assigned to the control group which received placebo and study group which received 20 mg melatonin a day as an intervention. The melatonin was administered 5 days a week for 28 days. Blood samples were taken before melatonin received on day 1 and also day 28; then, to measure the changes in blood cell counts representing our primary outcomes, the samples were analyzed by Sysmex K810i auto-analyzer. RESULTS: Our results showed that the platelet, white blood cells, lymphocyte, and neutrophil population reduction induced by radiotherapy were slighter or even insignificant in melatonin recipients compared to control. However, the difference between red blood cells in both groups was not significant. CONCLUSION: Our results are indicating that melatonin could prevent or minimize the unfavorable effects of radiotherapy on blood cell count reductions by attenuating the adverse influence of radiation, probably through stimulation of cellular antioxidant potential as previously reported in animal models. IRANIAN REGISTRY OF CLINICAL TRIALS (IRCT): Registry No. IRCT2016021626586N1.

Detection and differentiation of opportunistic viral infections potentially contributing to renal graft rejection by tetraplex-nested PCR.

The need for an intensive care protocol, sometimes weekly or biweekly, has led to a significant increase in laboratory costs for kidney recipients. In the present study, an inhouse tetraplex nested PCR assay was developed and validated for the specific detection of BKV, JCV, HCMV and EBV in clinical samples. We determined the Limit of Detection (LOD) and analytical specificity. To demonstrate the diagnostic performance of the assay, a total of 102 archival plasma samples were tested and compared with a commercial uniplex real-time PCR kits. The analytical sensitivity of the in-house tetraplex nested PCR assay was 173 copies/ml, when all four viruses were present in the specimens. These values were 79.2, 58.7, 87.6 and 96.1 copies/ml when only, BKV, JCV, HCMV and EBV respectively, were present. The cross-reactivity assays were shown no detectable signal in the tetraplex PCR results. The estimated diagnostic sensitivities were 92.6% for BKV, 92.3% for JCV and 100% for both HCMV and EBV as compared with commercial kits. Regarding the sensitivity and specificity, it seems that the developed Multiplex Nested PCR assay could be used as a reliable virusassociated renal rejection (VRR) panel in post renal transplant surveillance.

Detection and differentiation of opportunistic viral infections potentially contributing to renal graft rejection by tetraplex-nested PCR

@#The need for an intensive care protocol, sometimes weekly or biweekly, has led to a significant increase in laboratory costs for kidney recipients. In the present study, an inhouse tetraplex nested PCR assay was developed and validated for the specific detection of BKV, JCV, HCMV and EBV in clinical samples. We determined the Limit of Detection (LOD) and analytical specificity. To demonstrate the diagnostic performance of the assay, a total of 102 archival plasma samples were tested and compared with a commercial uniplex real-time PCR kits. The analytical sensitivity of the in-house tetraplex nested PCR assay was 173 copies/ml, when all four viruses were present in the specimens. These values were 79.2, 58.7, 87.6 and 96.1 copies/ml when only, BKV, JCV, HCMV and EBV respectively, were present. The cross-reactivity assays were shown no detectable signal in the tetraplex PCR results. The estimated diagnostic sensitivities were 92.6% for BKV, 92.3% for JCV and 100% for both HCMV and EBV as compared with commercial kits. Regarding the sensitivity and specificity, it seems that the developed Multiplex Nested PCR assay could be used as a reliable virusassociated renal rejection (VRR) panel in post renal transplant surveillance.

Fabrication of tannic acid/poly(N-vinylpyrrolidone) layer-by-layer coating on Mg-based metallic glass for nerve tissue regeneration application.

For improving recovery rates and functional outcomes in large nerve defects, a nerve guide conduit, in addition to topographic, physical and chemical cues should provide contact guidance and adequate mechanical support for cell migration and axon outgrowth. Among biomaterials, magnesium (Mg) metal has potential to support nerve regeneration owing to its electrical conductivity, biodegradation and ability to be formed into wires, filaments and ribbons. However, rapid degradation of magnesium can pose a challenge. Mg-based metallic glasses with desirable features including favorable biocompatibility, proper biodegradation and good mechanical properties are a good alternative to crystalline Mg alloys. This study investigates the biocorrosion and biocompatibility of Mg-Zn-Ca metallic glass ribbon with Mg70Zn26Ca4 composition. For controlling biocorrosion, layer-by-layer coating of tannic acid/ poly(N-vinylpyrrolidone) was applied on Mg70Zn26Ca4 ribbon and characterized by SEM and FTIR. Immersion and potentiodynamic polarization test results indicated that coating significantly improved the corrosion resistance of Mg70Zn26Ca4. Schwann cells were selected for the cytocompatibility evaluation of samples due to their key role in peripheral nerve regeneration and ability to repair spinal cord injuries. The MTT assay and cell morphology results showed good biocompatibility for Mg70Zn26Ca4 metallic glass as a promising candidate for nerve regeneration and implantable nervous prosthetic devices.

Modeling the economic outcomes of immuno-oncology drugs: alternative model frameworks to capture clinical outcomes.

BACKGROUND: Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. MATERIALS AND METHODS: This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy. Two variants of the PSM and a Markov model were populated with data from one clinical trial in metastatic melanoma patients. Short-term modeled outcomes were benchmarked to the clinical trial data and a lifetime model horizon provided estimates of life years and quality adjusted life years (QALYs). RESULTS: The PSM-based models produced short-term outcomes closely matching the trial outcomes. Adding health states generated increased QALYs while providing a more granular representation of outcomes for decision making. The Markov model gave the greatest level of detail on outcomes but gave short-term results which diverged from those of the trial (overstating year 1 progression-free survival by around 60%). CONCLUSION: Increased sophistication in the representation of disease dynamics in economic models is desirable when attempting to model treatment response in I-O. However, the assumptions underlying different model structures and the availability of data for health state mapping may be important limiting factors.

Oral Administration of Vitamin C, Cimetidine and Famotidine on Micronuclei Induced by Low Dose Radiation in Mouse Bone Marrow Cells.

BACKGROUND: In many studies, chemicals and natural materials were tested to reduce the harmful effects of radiation. It is known that Famotidine and vitamin C reduce DNA damage. OBJECTIVE: The aim of this study was to evaluate the radioprotective effect of vitamin C, Cimetidine and Famotidine on gamma-radiation-induced damage on mouse bone marrow. METHODS: Six-to-seven week male NMRI mice (28 g ±3) were randomly divided into fourteen groups: control, 2Gy irradiation, six group drugs without irradition (Famotidine, Cimetidine, vitaminC, Fam-Cim, Fam-Vit, Cim-Vit), six groups received drugs and 2Gy radiation with a 60Co |γ|-ray source at room temperature 22 ± 2 °C. The mice were killed 48 hours after irradiation by cervical dislocation. Slides were prepared from bone marrow cells and stained in May-Granwald and Giemsa. Finally, the cells were counted with microscope, frequencies of polychromatic erythrocyte (PCE), normochoromatic erythrocyte (NCE) and their micronuclated cell were recorded. PCE / PCE + NCE were calculated. RESULTS: There were significant differences of MNPCE/1000PCE, MNNCE/1000NCE and PCE/PCE+NCE among different groups with similar radiation doses (p≤0.01). Moreover, there were significant differences of MNPCE/1000PCE and PCE/PCE+NCE among different doses of radiation (p≤0.01). While considering MNNCE/1000NCE, there were no significant differences among silimar groups with radiation dose (p˃0.05). CONCLUSION: Oral administration of Famotidine, vitamin C and Cimetidine demonstrate reliable and similar radioprotective effects. Additionally, the protective effect of single use of these drugs was similar to the combination form. Thus, the oral use of combination, 48 hours after irradiation cannot induce more radioprotective effect.

Evaluation of Radiation Exposure to Staff and Environment Dose from [18F]-FDG in PET/CT and Cyclotron Center using Thermoluminescent Dosimetry.

BACKGROUND: PET/CT imaging using [18F]-FDG is utilized in clinical oncology for tumor detecting, staging and responding to therapy procedures. Essential consideration must be taken for radiation staff due to high gamma radiation in PET/CT and cyclotron center. The aim of this study was to assess the staff exposure regarding whole body and organ dose and to evaluate environment dose in PET/CT and cyclotron center. MATERIALS AND METHODS: 80 patients participated in this study. Thermoluminescence, electronic personal dosimeter and Geiger-Muller dosimeter were also utilized for measurement purpose. RESULTS: The mean annual equivalent organ dose for scanning operator with regard to lens of eyes, thyroid, breast and finger according to mean±SD value, were 0.262±0.044, 0.256±0.046, 0.257±0.040 and 0.316±0.118, respectively. The maximum and minimum estimated annual whole body doses were observed for injector and the chemist group with values of (3.98±0.021) mSv/yr and (1.64±0.014) mSv/yr, respectively. The observed dose rates were 5.67 µSv/h in uptake room at the distance of 0.5 meter from the patient whereas the value 4.94 and 3.08 µSv/h were recorded close to patient's head in PET/CT room and 3.5 meter from the reception desk. CONCLUSION: In this study, the injector staff and scanning operator received the first high level and second high level of radiation. This study confirmed that low levels of radiation dose were received by all radiation staff during PET/CT procedure using 18F-FDG due to efficient shielding and using trained radiation staff in PET/CT and cyclotron center of Masih Daneshvari hospital.

Radioprotective Effects of Sulfur-containing Mineral Water of Ramsar Hot Spring with High Natural Background Radiation on Mouse Bone Marrow Cells.

BACKGROUND: We intend to study the inhibitory effect of sulfur compound in Ramsar hot spring mineral on tumor-genesis ability of high natural background radiation. OBJECTIVE: The radioprotective effect of sulfur compounds was previously shown on radiation-induced chromosomal aberration, micronuclei in mouse bone marrow cells and human peripheral lymphocyte. Ramsar is known for having the highest level of natural background radiation on Earth. This study was performed to show the radioprotective effect of sulfur-containing Ramsar mineral water on mouse bone marrow cells. METHOD: Mice were fed three types of water (drinking water, Ramsar radioactive water containing sulfur and Ramsar radioactive water whose sulfur was removed). Ten days after feeding, mice were irradiated by gamma rays (0, 2 and 4 Gy). 48 and 72 hours after irradiating, mice were killed and femurs were removed. Frequency of micronuclei was determined in bone marrow erythrocytes. RESULTS: A significant reduction was shown in the rate of micronuclei polychromatic erythrocyte in sulfur-containing hot spring water compared to sulfur-free water in hot spring mineral water. Gamma irradiation induced significant increases in micronuclei polychromatic erythrocyte (MNPCE) and decreases in polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte ratio (PCEs/PCEs+NCEs) (P < 0.001) in sulfur-containing hot spring water compared to sulfur-free hot spring mineral water. Also, apparently there was a significant difference between drinking water and sulfur-containing hot spring water in micronuclei polychromatic erythrocyte and polychromatic erythrocyte/polychromatic erythrocyte+ normochromatic erythrocyte ratio. CONCLUSION: The results indicate that sulfur-containing mineral water could result in a significant reduction in radiation-induced micronuclei representing the radioprotective effect of sulfur compounds.

Local-Reference Patient Dose Evaluation in Conventional Radiography Examinations in Mazandaran, Iran.

BACKGROUND: The most efficient application of ionizing radiation is serving medical purposes and using this radiation has caused people to learn that artificial sources of radiation exposure among these resources can be of highest exposure rate. OBIECTIVE: The present study is aimed at initially establishing a baseline for local-reference dose level in Mazandaran, Iran in 12 projections of the most conventional x-ray examination. METHODS: In this study, 13 public hospitals in Mazandaran province were selected for review and required data collected for ten adult patients with mean weight of 70±10kg in each projection. Then, information of each center was separately analyzed. Next, in order to measure x-ray output tube, the dosimeter RTI model Barracuda calibrated has been applied for measuring air karma within energy rage of 40-150kvp. ESAK and ESD parameters, usually used for monitoring DRL in conventional radiography, were calculated. RESULTS: Mean ESDs in this study has been obtained to 1.47±0.98 for skull (PA/AP), 1.01±0.79 for skull (LAT), 0.67±0.38 for cervical spine (AP), 0.79±0.37 for cervical (LAT), 0.49±0.38 for chest (PA/AP), 1.06±0.44 for chest (LAT), 2.15±0.73 for thoracic spine (AP), 3±0.87 for thoracic spine (LAT), 2.81 ±0.82 for lumbar spine (AP), 4.28±0.78 for lumbar (LAT), 2.07±1.17 for abdomen and 1.90±0.99 for pelvis, respectively. The ESDs calculated for chest examination in both projections, PA and LAT are more than values recommended by the UK (2000), Brazil and Slovenia. CONCLUSION: The present study has determined wide variations in radiation dose of x-ray examinations among hospitals in Mazandaran, Iran. In order to reduce skin dose, an optimization procedure should be considered. Application of a reference dose (DRL) could be a practical method for this purpose. The role of optimization of radiography parameters for reducing patient dose is a significant issue. Through optimizing parameters, it would be possible to preserve image quality while reduction of patient dose.

Cost-effectiveness of daclatasvir plus sofosbuvir-based regimen for treatment of hepatitis C virus genotype 3 infection in Canada.

OBJECTIVE: New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV + SOF) and sofosbuvir plus ribavirin (SOF + RBV), from a Canadian health-system perspective. METHODS: A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0-F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis. RESULTS: In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV + SOF (12.37) and SOF + RBV (12.48) compared to that of pINF + RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV + SOF ($170,371) and SOF + RBV ($194,776) vs pINF + RBV regimen ($90,905). Compared to pINF + RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV + SOF and SOF + RBV, respectively. In treatment-experienced patients, DCV + SOF regimen dominated the SOF + RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV + SOF regimen was cost saving in treatment-experienced patients. CONCLUSION: Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.

Dose Assessment in Computed Tomography Examination and Establishment of Local Diagnostic Reference Levels in Mazandaran, Iran.

BACKGROUND: Medical X-rays are the largest man-made source of public exposure to ionizing radiation. While the benefits of Computed Tomography (CT) are well known in accurate diagnosis, those benefits are not risk-free. CT is a device with higher patient dose in comparison with other conventional radiation procedures. OBJECTIVE: This study is aimed at evaluating radiation dose to patients from Computed Tomography (CT) examination in Mazandaran hospitals and defining diagnostic reference level (DRL). METHODS: Patient-related data on CT protocol for four common CT examinations including brain, sinus, chest and abdomen & pelvic were collected. In each center, Computed Tomography Dose Index (CTDI) measurements were performed using pencil ionization chamber and CT dosimetry phantom according to AAPM report No. 96 for those techniques. Then, Weighted Computed Tomography Dose Index (CTDIW), Volume Computed Tomography Dose Index (CTDI vol) and Dose Length Product (DLP) were calculated. RESULTS: The CTDIw for brain, sinus, chest and abdomen & pelvic ranged (15.6-73), (3.8-25. 8), (4.5-16.3) and (7-16.3), respectively. Values of DLP had a range of (197.4-981), (41.8-184), (131-342.3) and (283.6-486) for brain, sinus, chest and abdomen & pelvic, respectively. The 3rd quartile of CTDIW, derived from dose distribution for each examination is the proposed quantity for DRL. The DRLs of brain, sinus, chest and abdomen & pelvic are measured 59.5, 17, 7.8 and 11 mGy, respectively. CONCLUSION: Results of this study demonstrated large scales of dose for the same examination among different centers. For all examinations, our values were lower than international reference doses.

Breast dosimetry in transverse and longitudinal field MRI-Linac radiotherapy systems.

PURPOSE: In the framework of developing the integration of a MRI-Linac system, configurations of MRI-Linac units were simulated in order to improve the dose distribution in tangential breast radiotherapy using transverse and longitudinal magnetic field geometries of Lorentz force for both medial and lateral tangential fields. METHODS: In this work, the geant4 Monte Carlo (MC) code was utilized to compare dose distributions in breast radiotherapy for Linac-MR systems in the transverse and longitudinal geometries within humanoid phantoms across a range of magnetic field strengths of 0.5 and 1.5 T. The dose increment due to scattering from the coils was investigated for both geometries as well. Computed tomography images of two patients were used for MC simulations. One patient had intact breast while the other was mastectomized. In the simulations, planning and methods of chest wall irradiation were similar to the actual clinical planning. RESULTS: In a longitudinal geometry, the magnetic field is shown to restrict the lateral spread of secondary electrons to the lung, heart, and contralateral organs, which reduced the mean dose of the ipsilateral lung and heart by means of 17.2% and 6% at 1.5 T, respectively. The transverse configuration exhibits a significant increase in tissue interface effects, which increased dose buildup in the entrance regions of the lateral and medial tangent beams to the planning target volume (PTV) and improved dose homogeneity within the PTV. The improved relative average homogeneity index for two patients to the PTV at magnetic field strength of 1.5 T with respect to no magnetic field case evaluated was 11.79% and 34.45% in the LRBP and TRBP geometries, respectively. In both geometries, the simulations show significant mean dose reductions in the contralateral breast and chest wall skin, respectively, by a mean of 16.6% and 24.9% at 0.5 T and 17.2% and 28.1% at 1.5 T in the transverse geometry, and 10.56% and 14.6% at 0.5 T and 11.3% and 16.3% at 1.5 T in the longitudinal geometry. Considering the scattered photons which reflected from the coils, the average relative dose of each voxel is slightly increased by 0.53% and 0.32% in the LRBP and TRBP geometries, respectively. CONCLUSIONS: Orienting the B0 magnetic field parallel to the photon beam axis, LRBP geometry, tends to restrict the radial spread of secondary electrons which resulted in dose reduction to the lung. Dosimetry issues observed in both Linac-MR geometries, such as changes to the lateral dose distribution, significantly exhibited dose reduction in the contralateral organs on a representative breast plan. Further, the results show sharper edge dose volume histogram curves at 1.5 T for both geometries, especially in the LRBP configuration.

Improvement of dose distribution in breast radiotherapy using a reversible transverse magnetic field Linac-MR unit.

PURPOSE: To investigate the improvement in dose distribution in tangential breast radiotherapy using a reversible transverse magnetic field that maintains the same direction of Lorentz force between two fields. The investigation has a potential application in future Linac-MR units. METHODS: Computed tomography images of four patients and magnetic fields of 0.25-1.5 Tesla (T) were used for Monte Carlo simulation. Two patients had intact breast while the other two had mastectomy. Simulations of planning and chest wall irradiation were similar to the actual clinical process. The direction of superior-inferior magnetic field for the medial treatment beam was reversed for the lateral beam. RESULTS: For the ipsilateral lung and heart mean doses were reduced by a mean (range) of 45.8% (27.6%-58.6%) and 26.0% (20.2%-38.9%), respectively, depending on various treatment plan setups. The mean V20 for ipsilateral lung was reduced by 55.0% (43.6%-77.3%). In addition acceptable results were shown after simulation of 0.25 T magnetic field demonstrated in dose-volume reductions of the heart, ipsilateral lung, and noninvolved skin. CONCLUSIONS: Applying a reversible magnetic field during breast radiotherapy, not only reduces the dose to the lung and heart but also produces a sharp drop dose volume histogram for planning target volume, because of bending of the path of secondary charged particles toward the chest wall by the Lorentz force. The simulations have shown that use of the magnetic field at 1.5 T is not feasible for clinical applications due to the increase of ipsilateral chest wall skin dose in comparison to the conventional planning while 0.25 T is suitable for all patients due to dose reduction to the chest wall skin.

The survey of diastolic function changes in end-stage renal disease patients before and 3 and 6 months after kidney transplantation.

INTRODUCTION: Left ventricular diastolic dysfunction, which is prevalent in end-stage renal disease, predicts morbidity and mortality among affected patients. The aim of this study was to evaluate diastolic function changes in end-stage renal disease patients before as well as 3 and 6 months after kidney transplantation. METHODS AND MATERIALS: This longitudinal study from November 2008 to November 2009, enrolled 27 consecutive kidney transplant patients. Systolic and diastolic blood pressures and echocardiograghic parameters such as ejection fraction, left ventricular mass, and diastolic functions were measured before, as well as 3 and 6 months after transplantation. Data were analyzed by repeated-measure analysis of variance and Friedman tests using SPSS version 18. RESULTS: The mean patients age was 39.47 ± 12.27 years with 55.6% males. The mean systolic and diastolic blood pressure and left ventricular mass decreased significantly in the first 3 (125.44 ± 11.35, 78.51 ± 6.32, 141.94 ± 3.32) and 6 months (121.48 ± 10.63, 72.96 ± 4.21, 138.25 ± 3.12) after renal transplantation compared to the values before the procedure (136.77 ± 14.09, 81.92 ± 9.01, 158.30 ± 3.58 respectively; P < .05). The left ventricular ejection fraction increased significantly at 3 (63.00 ± 6.49) and 6 months (66.11 ± 5.87) compared with preoperative (62.48 ± 5.74; P < .05). Step mean diastolic function also decreased significantly at 3 (1.94) and 6 months (1.81) compared with before transplantation (2.24; P < .05). CONCLUSION: According to our findings, transplantation can correct ejection fraction and systolic and diastolic blood pressure and lead to regression of left ventricular hypertrophy. Diastolic function was improved after transplantation.

Estimating the contribution of selected risk factors in attributable burden to stroke in iran.

BACKGROUND: Knowledge of the magnitude of avoidable burden by risk factors is needed for health policy, priority setting, and preventing stroke. The aim of this study was to estimate the contribution of selected risk factors including hypertension, overweight, obesity, tobacco use, and physical inactivity to the attributable burden of stroke in Iran. METHODS: The World Health Organization Comparative Risk Assessment (CRA) methodology was employed to calculate the Potential Impact Fraction (PIF) and percentage of avoidable burden of stroke, which attributed to its risk factors among Iranian adults in 2009. Prevalence of risk factors was obtained from the 5(th) STEPS survey of chronic disease risk factors which conducted in 2009. PIF was estimated on both theoretical minimum and feasible minimum risk. A simulation procedure incorporating sources of uncertainty was used to estimate the uncertainties for the attributable burden. RESULTS: About 15.7% (95% uncertainty intervals: 5.8- 23.5) of attributable Disability Adjusted Life Years (DALYs) to stroke in adult males and 15.8% (95% uncertainty intervals: 5.8- 23.5) in adult females are avoidable after changing the current prevalence (16.0% and 16.1% for males and females, respectively) of hypertension to 10% in both sexes. CONCLUSION: This work highlighted the important role of hypertension and overweight. Accordingly, policy makers are advised to consider these risk factors once implementing interventional program in Iran.

Application of lag-time into exposure definitions to control for protopathic bias.

PURPOSE: To control for protopathic bias, some studies have incorporated the concept of lag-time into their exposure definition (time period before the index date that was not considered in assessing exposure). The objective of this study was to introduce a procedure to identify the best lag-time to be applied in studies where control for protopathic bias is required. METHODS: We used data from a case-control study carried out to assess the association between exposure to proton pump inhibitors (PPIs) and risk of gastric cancer, using RAMQ databases. Exposure was defined as the number of defined daily doses of PPIs dispensed during the 5-year period prior to the index date (divided into four quartiles). Thirty-one different lag-times were applied (0-30 months) based on 1-month intervals. Logistic regression was used to estimate the matched odds ratio (OR) for each lag-time. The change point in the ln(ORs) was identified by applying a two-compartmental model and a segmented regression model. RESULTS: A trend of decreasing ORs was found with the application of an increasing lag-time. As an illustration, the ORs for the 1st quartile of defined daily doses, when applying the 31 different lag-times, ranged between 3.52 when applying a 0 lag-time and 0.97 when applying a 30 months lag-time. Applying the two methods for the different lag-times showed that the ORs stabilized at around 6 months. CONCLUSION: For the purpose of controlling for protopathic bias in pharmacoepidemiological studies, we have provided a method to assess the most appropriate lag-time that should be applied for the assessment of drug exposure.