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Worldwide, thyroid cancer accounts for some 10% of total cancer incidence, most markedly for females. Thyroid cancer radiotherapy, typically using 131I (T1/2 8.02 days; β− max energy 606 keV, branching ratio 89.9%), is widely adopted as an adjunct to surgery or to treat inoperable cancer and hyperthyroidism. With staff potentially receiving significant doses during source preparation and administration, radiation protection and safety assessment are required in ensuring practice complies with international guidelines. The present study, concerning a total of 206 patient radioiodine therapies carried out at King Faisal Specialist Hospital and Research Center over a 6-month period, seeks to evaluate patient and occupational exposures during hospitalization, measuring ambient doses and estimating radiation risk. Using calibrated survey meters, patient exposure dose-rate estimates were obtained at a distance of 30-, 100- and 300 cm from the neck region of each patient. Occupational and ambient doses were measured using calibrated thermoluminescent dosimeters. The mean and range of administered activity (AA, in MBq) for the thyroid cancer and hyperthyroidism treatment groups were 4244 ± 2021 (1669–8066), 1507.9 ± 324.1 (977.9–1836.9), respectively. The mean annual occupational doses were 1.2 mSv, that for ambient doses outside of the isolation room corridors were found to be 0.2 mSv, while ambient doses at the nursing station were below the lower limit of detection. Exposures to staff from patients being treated for thyroid cancer were less compared to hyperthyroidism patients. With a well-defined protocol, also complying with international safety requirements, occupational exposures were found to be relatively high, greater than most reported in previous studies.

Medical exposure of the general population due to radiological investigations is the foremost source of all artificial ionising radiation. Here, we focus on a particular diagnostic radiological procedure, as only limited data are published with regard to radiation measurements during urethrograpic imaging. Specifically, this work seeks to estimate patient and occupational effective doses during urethrographic procedures at three radiology hospitals. Both staff and patient X-ray exposure levels were calculated in terms of entrance surface air kerma (ESAK), obtained by means of lithium fluoride thermoluminescent dosimeters (TLD-100(LiF:Mg:Cu.P)) for 243 urethrographic examinations. Patient radiation effective doses per procedure were estimated using conversion factors obtained from the use of Public Health England computer software. In units of mGy, the median and range of ESAK per examination were found to be 10.8 (3.6-26.2), 7.0 (0.2-32.3), and 24.3 (9.0-32.0) in Hospitals A, B, and C, respectively. The overall mean and range of staff doses (in µGy) were found to be 310 (4.0-1750) per procedure. With the exception of hospital C, the present evaluations of radiation dose have been found to be similar to those of previously published research. The wide range of patient and staff doses illustrate the need for radiation dose optimisation.

Purpose:To compare tumour dose distribution, conformality, homogeneity, normal tissue avoidance, tumour control probability (TCP) and normal tissue complication probability (NTCP) using 3D conformal radiation therapy (3DCRT), 3- and 4-field intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with locally advanced rectal cancer.Materials and methods:Twenty-four patients staged T1–3N+M0 with locally advanced rectal cancer underwent neoadjuvant chemoradiation therapy. Four different radiotherapy plans were prepared for each patient: 3DCRT, 3- and 4-field IMRT and VMAT are evaluated for target distribution using CI and homogeneity index (HI), normal tissue avoidance using Dmax, V45, V40, V50 and TCP and NTCP using the Lyman–Kutcher–Burman model.Results:VMAT has better HI (HI = 1·32) and 3DCRT exhibited better conformality (CI = 1·05) than the other radiotherapy techniques. With regard to normal tissue avoidance, all radiotherapy plans met the constraints. Dmax in the 3DCRT plans was statistically significant (p = 0·04) for bladder and no significant differences in V40 and V50. In the bowel bag, no significant differences in Dmax for any radiotherapy plan and V40 was lower in 3DCRT than VMAT (p = 0·024). In the case of femoral heads, 3DCRT has a statistically significant lower dose on Dmax than 4-field IMRT (p = 0·00 « 0·05). VMAT has the biggest TCP (80·76%) than the other three radiotherapy plans. With regard to normal tissue complications, probabilities were shown to be very low, of the order of 10-14 and 10-41 for bowel bag and femoral heads respectively.Conclusions:It can be concluded that 3DCRT plan improves conformity and decreases radiation sparing in the organ at risks, but the VMAT plan exhibits better homogeneity and greater TCP.

Differentiated thyroid cancer (DTC) represents the vast majority of all thyroid cancers, with the papillary variant being the most common. According to the previous 2009 American Thyroid Association (ATA) guidelines, papillary thyroid microcarcinoma (PTMC; ≤1 cm in diameter) exhibiting cervical lymph node metastasis corresponded to an intermediate-risk group for recurrence or metastasis. However, the latest 2015 ATA guidelines advocate that a patient with PTMC is low-risk if there are ≤5 regional node micrometastases. This means that therapeutic radioactive iodine (RAI) is not required. The current study reports a rare case of a patient who underwent total thyroidectomy due to multi-nodular goiter where the pathologic specimen exhibited two PTMC foci in regional lymph nodes, but no primary cancer was identified in the thyroid despite thorough examination of the thyroid parenchyma. The etiology of such results is unknown and it was hypothesized that it may be the consequence of insufficient pathologic examination or due to the regression of a primary PTMC in the thyroid. Moreover, the risk-stratification of cases with intra-lymph node PTMC without any evidence of primary cancer in the thyroid is not considered in the ATA recommendations. The aim of the current report was to elucidate the risk-stratification of this rare occurrence and to reconsider the possible etiologies. By extrapolating the latest ATA recommendations concerning a patient with a known primary PTMC and ≤5 metastatic micro-foci (thus the only difference between cases being the absence of a primary tumor), it was concluded that the patient should be considered low-risk. As a consequence, RAI therapy should be deemed as unnecessary despite the presence of lymph node microfoci. Moreover, it was proposed that cervical lymph node PTMC with no evidence of a primary tumor in the thyroid could be the consequence of normal thyroid tissue micro-deposit progression to cancer within the lymph node, which is a rare benign entity.

We aim to investigate the counting response variations of positron emission tomography (PET) scanners with different detector configurations in the presence of solitary pulmonary nodule (SPN). Using experimentally validated Monte Carlo simulations, the counting performance of four different scanner models with varying tumor activity, location, and patient obesity is represented using a noise equivalent count rate (NECR). NECR is a well-established quantitative metric which has positive correlation with clinically perceived image quality. The combined effect of tumor displacement and increased activity shows a linear ascending trend for NECR with slope ranges of (12.5–18.2)*10−3 (kBq/cm3)−1 for three-ring (3R) scanners and (15.3–21.5)*10−3 (kBq/cm3)−1 for four-ring (4R). The trend for the combined effect of tumor displacement and patient obesity is exponential decay with 3R configurations weakly dependent on the patient obesity if the tumor is located at the center of the field of view with exponent’s range of (6.6–33.8)*10−2cm−1. The dependence is stronger for 4R scanners (9.6–38.5)*10−2cm−1. The analysis indicates that quantitative PET data from the same SPN patient possibly examined in different time points (e.g., during staging or for the evaluation of treatment response) are affected by the different detector configurations and need to be normalized with patient weight, activity, and tumor location to reduce unwanted bias of the diagnosis. This paper provides also with a proof of concept for the ability of properly tuned simulations to provide additional insights into the counting response variability especially in tumor types where often borderline decisions have to be made regarding their characterization.

Aims and objectives To investigate the value of advanced multiparametric MR imaging biomarker analysis based on radiomic features and machine learning classification, in the non-invasive evaluation of tumor heterogeneity towards the differentiation of Low Grade vs. High Grade Gliomas. Methods and materials Forty histologically confirmed glioma patients (20 LGG and 20 HGG) who underwent a standard 3T-MRI tumor protocol with conventional (T1 pre/post-contrast, T2-FSE, T2-FLAIR) and advanced techniques (Diffusion Tensor and Perfusion Imaging, 1H-MR Spectroscopy), were included. A semi-automated segmentation technique, based on T1W-C and DTI, was used for tumor core delineation in all available parametric maps. 3D Texture analysis considered 12 Histogram, 11 Co-Occurrence Matrix (GLCM) and 5 Run Length Matrix (GLRLM) features, derived from p, q, MD, FA, T1W-C, T2W-FSE, T2W-FLAIR and raw DSCE data. Along with 1H-MRS metabolic ratios and mean rCBV values, a total of 581 attributes for each subject were obtained. A Support Vector Machine – Recursive Feature Elimination (SVM-RFE) algorithm and SVM classifier were utilized for feature selection and classification, respectively. Results Three different SVM classifiers were evaluated with consecutively SVM-RFE feature subsets. Linear SMO classifier demonstrated the highest performance for determining the optimal feature subset. Finally, 21 SVM-RFE top-ranked features were adopted, for training and testing the SMO classifier with leave-one-out cross-validation, achieving 95.5% Accuracy, 95% Sensitivity, 96% Specificity and 95.5% Area Under ROC Curve. Conclusion Results demonstrate that quantitative analysis of phenotypic characteristics, based on advanced multiparametric MR neuroimaging data and texture features, utilizing state-of-the-art radiomic analysis methods, can significantly contribute to the pre-treatment glioma grade differentiation.

Purpose Yoga is increasingly accepted to improve overall health and wellness and is considered a meaningful adjunct treatment for mental and physical health ailments associated with interpersonal violence (IV). This review provides background information about the use of yoga among individuals with IV histories and aims to inform researchers and practitioners about the available evidence on yoga's application and effectiveness. Methods Using six databases, we systematically reviewed empirical literature examining yoga among IV survivors. Criteria for study inclusion: yoga included a physical component and was the primary intervention; participants had an IV history; peer-reviewed; and participants were 17 years and older. After review, 10 articles reporting findings from seven independent samples were included. Findings Yoga demonstrated preliminary, positive implications as a complementary treatment for individuals with an IV history. Synthesizing across articles four themes emerged: (1) acceptability and feasibility, (2) enhancement of mental and physical health, (3) promotion of personal growth, and (4) facilitators and barriers to practice. Conclusions The nascent literature indicates potential benefits of integrating yoga into interventions for IV survivors to enhance physical and psychological functioning. The primary barriers to intervention were resources (e.g., access) and incompatibility with spiritual beliefs for select clients. Despite consistent barriers, preliminary findings indicate yoga has many positive implications for individuals with an IV history. Given the small evidence base and insufficient methodology, additional empirical research with diverse samples and sites, and robust designs, could improve the state of knowledge and strengthen the efficacy of this promising practice.

The purpose of the present study is to examine the diagnostic and predictive accuracy of the thyroglobulin (Tg) to thyroid stimulating hormone (TSH) and TSH/Tg ratios in normothyroid patients with differentiated thyroid cancer (DTC). We conducted a retrospective cohort study evaluating the diagnostic accuracy of the serum Tg/TSH and TSH/Tg ratios in normothyroid patients with thyroid nodules. We also systematically searched the international literature using the Medline, Cochrane’s CENTRAL, Scopus, Clinicaltrials.gov, EMBASE, and Google Scholar databases for evidence concerning the diagnostic and predictive accuracy of these ratios. Overall, 374 patients were identified in our cohort study of whom 240 were treated for benign disease and 134 were treated for DTC. Significant differences were noted in the Tg/TSH and TSH/Tg values among cases with malignant and benign disease (P=0.020). However, the diagnostic ROC curve did not confirm these results (Tg/TSH=0.572 and TSH/Tg=0.428). After searching the international literature, we identified 8 studies. The majority of the included data reported significant differences among patients with benign/malignant disease and those with successful iodine therapy compared to those with disease relapse. However, the clinical relevance was clearer among studies that investigated the usefulness of these ratios in predicting recurrent disease. The findings of our study support that the Tg/TSH ratio increases in patients with DTC and can, thus, become useful in the future as a predictive marker of ablative 131I therapy success. However, given the significant variability of Tg its diagnostic accuracy remains to date minimal; thus, the actual cut-off value that can be used to discriminate cancer cases from benign disease has not been determined yet.

A Dzud is a climate event in the Mongolian that causes serious environmental and economic damage. Although a natural phenomenon, its effects can be exacerbated by human activities such as livestock overgrazing and inadequate fodder, resulting in mass deaths of the livestock in the spring following a severe winter. This article is based on the analysis of various Dzud events (2000, 2001, 2002, and 2010) and their specific effect on the vegetation condition by analyzing Normalized Difference Vegetation Index NDVI in the Gobi regions of Mongolia. Our evaluation methods utilize the seasonal aridity index, time series of MODIS NDVI and data from livestock statistics. Heavy snowfall is one of the limiting factors for animal productivity and socioeconomic development in Mongolia. Based on the findings, steppe areas have the highest degree of vulnerability of climate, with the potential decline of growth grassland being stronger for humid areas. When there are high snowy winters, there is a 10 to a 20-day earlier peak of NDVI values as well as an increase in vegetation growth. Additionally, grazing pressure (caused by high livestock loss) played a minor role in plant growth. We found that during the dry winter conditions of a black Dzud, low soil moisture, and high evapotranspiration, the vegetation growth phase begins later due to water deficiency, leading to a lower peak in growth. During the year 2009/2010, a white Dzud occurred in the presence of a thick snow layer, which acted as a water reservoir. The effect of livestock loss and the reduction of grazing pressure played a minor part in vegetation recovery after different types of Dzud events in Mongolia.

Most of the acute ischemic events, such as acute coronary syndromes and stroke, are attributed to vulnerable plaques. These lesions have common histological and pathophysiological features, including inflammatory cell infiltration, neo-angiogenesis, remodelling, haemorrhage predisposition, thin fibrous cap, large lipid core, and micro-calcifications. Early detection of the presence of a plaque prone to rupture could be life-saving for the patient; however, vulnerable plaques usually cause non-haemodynamically significant stenosis, and anatomical imaging techniques often underestimate, or may not even detect, these lesions. Although ultrasound techniques are currently considered as the "first-line" examinations for the diagnostic investigation and treatment monitoring in patients with atherosclerotic plaques, positron emission tomography (PET) imaging could open new horizons in the assessment of atherosclerosis, given its ability to visualize metabolic processes and provide molecular-functional evidence regarding vulnerable plaques. Moreover, modern hybrid imaging techniques, combining PET with computed tomography or magnetic resonance imaging, can evaluate simultaneously both functional and morphological parameters of the atherosclerotic plaques, and are expected to significantly expand their clinical role in the future. This review summarizes current research on the PET imaging of the vulnerable atherosclerotic plaques, outlining current and potential applications in the clinical setting.

The objective of this study is to assess the patients' effective and organ dose during theranostic applications in Kuwait. In total, eighteen adults' patients were conducted nuclear medicine procedures with 177Lu Dotatate for theranostic purpose in Kuwait Cancer control center (KCCC), Kuwait. Medium energy collimator (MEC) (208 keV Scatter 26% better than 113 keV Scatter 60%) was utilized to obtain scans in definite time intervals ranged from one to 2 h (before voiding), 6:00, 24:00, 48:00, 72:00 h. Patients, tissue and organ radiation doses were computed utilizing OLINDA/EXM Software. The average radiation effective dose (in mSv/MBq) for bladder, liver, and both kidneys (left & right), were 0.36, 0.08, 0.61 & 0.60. The range of the effective dose was from 0.55 mSv to 7.7 mSv. The acquired scans using 177Lu were delivered diagnostic findings. The patients’ effective dose is lower compared to the previous studies. Variation is attributed to the departmental protocol and administered activity. The values of the mean organ dose were comparable and lower than previously published studies. Different organs have different level of doses, which may affected by the presence of the metastatic tumors in the entire organ.

Objective Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the thyroid gland is a rare indolent malignant disease encountered in approximately 0.5% of patients with Hashimoto thyroiditis (HT). The purpose of the present systematic review was to accumulate the current evidence in the field. Study design We searched the Medline, Scopus, EMBASE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials CENTRAL databases from inception to May 2018. Statistical analysis was performed with SPSS version 22.0. Results Fourteen case series and 20 case reports were finally included in the present systematic review. Analysis of the patient data included in the published case reports suggested that the age at diagnosis of MALT lymphoma does no differ among males and females (64 [52.5-73] vs. 67 [60.5-72] years, p = 0.442). HT was detected in 60% of patients, whereas coexisting carcinoma was evident in 17% of cases. The incidence of HT and thyroid cancer was comparable among males and females (p = 0.474 and p > 0.999, respectively). Among all patients included in the present systematic review there were two disease relapses and two deaths attributed to the disease. Conclusion MALT lymphoma of the thyroid gland is a rare malignancy with an indolent course. The scarce data available in the literature preclude safe conclusions concerning the mode of treatment and follow-up of these patients. However, the combination of minimally invasive surgery and adjuvant therapy seems feasible. Moreover, an extended follow-up period is recommended.

Climate and water contacts are among the most important risk factors of human schistosomiasis transmission. This study aimed to determine—through direct field observations—the influence of air temperature on the frequencies of children´s water contacts with respect to human schistosomiasis transmission risk in the Sourou Valley, located in the North-western part of Burkina Faso. The objectives of the study were: (i) to study the air temperature at which children have the sensation of heat and start looking for water as a means for natural cooling; and (ii) to study whether high frequencies of swimming or bathing may lead to a higher risks of schistosomiasis transmission. To do so, swimming or bathing were observed during two different periods: a cold one from 3rd January to 2nd February 2011 and a hot one from 3rd April to 3rd May 2011 in Toma-Ile, a village totally surrounded by water. The results showed that daily mean air temperatures never exceeded 30 °C during the coldest period, while they were above this value during the hottest period. In total, swimming activities were observed 11/31 days during the coldest period and 31/31 during the hottest period. Bathing of children below the age of 5 years occurred on 55/62 days. 25 °C was the day mean air temperature from which children felt hot and began playing in water. The hourly occurrence of swimming and bathing showed peaks at 2 PM. This coincides with the diurnal maximum of infective cercariae present in the same water. Thus, in order to freshen up during hot periods of the day, children used to look for freshwater and thus expose themselves to a high schistosomiasis transmission risk.

BACKGROUND Lutetium-based scintillators with high-performance electronics introduced time-of-flight (TOF) reconstruction in the clinical setting. Let G' be the total signal to noise ratio gain in a reconstructed image using the TOF kernel compared with conventional reconstruction modes. G' is then the product of G1 gain arising from the reconstruction process itself and (n-1) other gain factors (G2, G3, … Gn) arising from the inherent properties of the detector. METHODS We calculated G2 and G3 gains resulting from the optimization of the coincidence and energy window width for prompts and singles, respectively. Both quantitative and image-based validated Monte Carlo models of Lu2SiO5 (LSO) TOF-permitting and Bi4Ge3O12 (BGO) TOF-nonpermitting detectors were used for the calculations. RESULTS G2 and G3 values were 1.05 and 1.08 for the BGO detector and G3 was 1.07 for the LSO. A value of almost unity for G2 of the LSO detector indicated a nonsignificant optimization by altering the energy window setting. G' was found to be ∼1.4 times higher for the TOF-permitting detector after reconstruction and optimization of the coincidence and energy windows. CONCLUSION The method described could potentially predict image noise variations by altering detector acquisition parameters. It could also further contribute toward a long-lasting debate related to cost-efficiency issues of TOF scanners versus the non-TOF ones. Some vendors re-engage nowadays to non-TOF product line designs in an effort to reduce crystal costs. Therefore, exploring the limits of image quality gain by altering the parameters of these detectors remains a topical issue.

During the preparation of radioisotopes, during their administration and during patient imaging nuclear medicine personnel are routinely exposed to ionising radiation. With radiation risks increasing with dose, safety assessment is required in seeking to ensure practice complies with international guidelines and dose limits. A particular aim herein is to measure staff exposures during certain molecular imaging procedures including through use of positron emission tomography with computed tomography (PET/CT) and single photon emission computed tomography (SPECT) procedures. Over a one-year period occupational doses were monitored for 30 nuclear medicine personnel at King Faisal Specialist Hospital and Research Center (KFSH&RC) in Riyadh. Dose equivalent values were measured in terms of Hp (10) (deep dose) and Hp (0.07) (skin dose), extremity doses also being measured via ring dosimeters. The measurements were made using calibrated thermoluminescent dosimeters, type LiF:Mg, Ti (TLD-100). In mSv, the respective mean annual dose and range for Hp (10), Hp (0.07) and extremities were 3.05 ± 2.1 (0.23–0.91), 3.15 ± 2.2 (0.1–9.1) and 28.25 (0.1–298.0). In all cases, extremity dose values were well below the annual dose limit (500 mSv). Nevertheless, with personnel doses varying significantly, careful assessment of working conditions is recommended in efforts to ensure occupational exposures remain below annual dose limits.

Over the years, MR systems have evolved from imaging modalities to advanced computational systems producing a variety of numerical parameters that can be used for the noninvasive preoperative assessment of breast pathology. Furthermore, the combination with state-of-the-art image analysis methods provides a plethora of quantifiable imaging features, termed radiomics that increases diagnostic accuracy towards individualized therapy planning. More importantly, radiomics can now be complemented by the emerging deep learning techniques for further process automation and correlation with other clinical data which facilitate the monitoring of treatment response, as well as the prediction of patient’s outcome, by means of unravelling of the complex underlying pathophysiological mechanisms which are reflected in tissue phenotype. The scope of this review is to provide applications and limitations of radiomics towards the development of clinical decision support systems for breast cancer diagnosis and prognosis.

Purpose European legislation concerning the protection of workers from exposure to Electromagnetic Fields (EMF) was recently (26.6.2013) completed by Directive 2013/35/EU. This Directive is a specific one of the framework Directive 89/391/EEC and part of the overall legislation for Occupational Health and Safety (OHS). Magnetic Resonance Imaging (MRI) systems have played a key role, both in the postponement of the former 2004/40 EMF Directive and in the formation of the latest limits adopted by the new Directive. On the other hand, MRI systems are associated with the exposure of personnel to EMF of various frequencies and modulations, arousing peculiar safety issues. Therefore, we will try to acquire the highly important knowledge of the exact occupational exposure levels, in all working scenarios and practices. Methods Different MRI systems (1.5 and 3 T) have been chosen for a variety of measurements in order to assess occupational exposure compared to the limits (ALs) of the Directive and to the main OHS principles. Gradient function of MRI systems results in low frequency exposure, while high frequency exposure comes from the application of the RF excitation frequency. Results In most of the cases the RMS and peak value measurements do not exceed the corresponding ALs, apart from a few specific hot spots, manageable through OHS principles. Discussion Complete occupational exposure results can form the basis for dealing with multiple exposures present in MRI systems. Peculiar RF harmonic components, of no safety concern, were detected. Their origin is under examination.

Even though the Selenga is the main tributary to Lake Baikal in Russia, the largest part of the Selenga River basin is located in Mongolia. It covers a region that is highly diverse, ranging from almost virgin mountain zones to densely urbanized areas and mining zones. These contrasts have a strong impact on rivers and their ecosystems. Based on two sampling campaigns (summer 2014, spring 2015), we investigated the longitudinal water quality pattern along the Selenga and its tributaries in Mongolia. While headwater regions typically had a very good water quality status, wastewater from urban areas and impacts from mining were found to be main pollution sources in the tributaries. The highest nutrient concentrations in the catchment were found in Tuul River, and severely elevated concentrations of trace elements (As, Cd, Cu, Cr, Fe, Mn, Ni, Pb, Zn), nutrients (NH4+, NO2-, NO3-, PO43-), and selected major ions (SO42-) were found in main tributaries of Selenga River. Moreover, trace element concentrations during spring 2015 (a time when many mines had not yet started operation) were markedly lower than in summer 2014, indicating that the additional metal loads measured in summer 2014 were related to mining activities. Nevertheless, all taken water samples in 2014 and 2015 from the main channel of the Mongolian Selenga River complied with the Mongolian standard (MNS 1998) for the investigated parameters.

Background Hmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction. Methods We investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO activity was inhibited. Adiposity, signaling proteins, fasting glucose and oxygen consumption were determined and compared to adipocyte cultures with depressed levels of both HO-1/HO-2. Results Adipo-HO-1-/- female mice exhibited increased adipocyte size, and decreases in the mitochondrial fusion to fission ratio, PGC1, and SIRT3. Importantly, ablation of HO-1 in adipose tissue resulted in fat acquiring many properties of visceral fat such as decreases in thermogenic genes including pAMPK and PRDM16. Deletion of HO-1 in mouse adipose tissue led to complete metabolic dysfunction, an increase in white adipose tissue, a reduction of beige fat and associated increases in FAS, aP2 and hyperglycemia. Mechanistically, genetic deletion of HO-1 in adipose tissues decreased the mitochondrial fusion to fission ratio; disrupted the activity of the PGC1 transcriptional axis and thermogenic genes both in vitro and in vivo. Conclusion Ablation of adipose tissue-HO-1 abridged PGC1 expression promoted mitochondrial dysfunction and contributed to an increase of pro-inflammatory visceral fat and abrogated beige-cell like phenotype.

The advent of PET instrumentation signaled the beginning of a new perspective in nuclear medicine diagnostic imaging. PET systems rely on several corrections that must be applied in order to establish accurate and reliable quantification. The inherent properties of PET detector architecture and the crystals themselves are sources of different types of systematic and random errors with subsequent count rate variability that should be accounted for. Normalization is the correction dealing with these errors. In this work, the reasons resulting in this variability are explored and the different normalization approaches are described. Special focus is paid to component-based normalization, with an attempt to describe the discrete factors and discuss the underlying mechanisms of their contribution to sensitivity variations of the lines of response.

Background: Obesity and diabetes are independently associated with the development of cardiac events that occur in db mice that are linked to a decrease in heme oxygenase-1 (HO-1) and epoxyeicosatrienoics (EETs). An increase in HO-1 and EET levels is associated with a decrease of ROS, adiposity and increased mitochondrial function in several animal models. The roles and inter-relationship of HO-1, EET, and PGC-1α in cardiomyopathy pathogenesis has not been investigated. Methods: Obese (db) mice 5 wks of age were allowed to acclimate for 17 wks, and then divided into 3 groups. A) Control, B) EET-A in drinking water, and C) EET-A and lentiviral (Ln) PGC-1α Sh, which decreased PGC1α by 40-60 %. Echocardiography was performed at 5 and 34 wks, serum and heart tissue were harvested to measure signaling and mitochondrial fusion proteins. Results: Group A) developed hyperglycemia, insulin resistance, and LV dysfunction. These changes were associated with decreases in PGC-1α, HO-1, MnSOD, and mitochondrial fusion associated proteins; Mfn 1/2 and OPA-1: Group B), received EET-A, and displayed normal levels of glucose, adipose adiponectin (p Conclusion: An EET-A agonist ameliorates adiposity, BP elevation, mitochondrial function and cardiomyopathy as a result of increased levels of PGC1α and HO-1-expression. Suppression of PGC1α by Ln PGC1α (Sh) worsened insulin resistance suggesting targeting mitochondrial fusion/fission may be a promising therapy for diabetes and heart disease.

Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P

Background/Objectives. Obesity and metabolic syndrome and associated adiposity are a systemic condition characterized by increased mitochondrial dysfunction, inflammation, and inhibition of antioxidant genes, HO-1, and EETs levels. We postulate that EETs attenuate adiposity by stimulating mitochondrial function and induction of HO-1 via activation of PGC-1αin adipose and hepatic tissue.Methods. Cultured murine adipocytes and mice fed a high fat (HF) diet were used to assess the functional relationship among EETs, PGC-1α, HO-1, and mitochondrial signaling using an EET-agonist (EET-A) and PGC-1α-deficient cells and mice using lentiviral PGC-1α(sh).Results. EET-A is a potent inducer of PGC-1α, HO-1, mitochondrial biogenesis (cytochrome oxidase subunits 1 and 4 and SIRT3), fusion proteins (Mfn1/2and OPA1) and fission proteins (DRP1 and FIS1) (p<0.05), fasting glucose, BW, and blood pressure. These beneficial effects were prevented by administration of lenti-PGC-1α(sh). EET-A administration prevented HF diet induced mitochondrial and dysfunction in adipose tissue and restored VO2effects that were abrogated in PGC-1α-deficient mice.Conclusion. EET is identified as an upstream positive regulator of PGC-1αthat leads to increased HO-1, decreased BW and fasting blood glucose and increased insulin receptor phosphorylation, that is, increased insulin sensitivity and mitochondrial integrity, and possible use of EET-agonist for treatment of obesity and metabolic syndrome.

We examined the hypothesis that adipocyte dysfunction in mice fed a high-fat (HF) diet can be prevented by lentiviral-mediated and adipocyte specific-targeting delivery of the human heme oxygenase-1 (aP2-HO-1). A bolus intracardial injection of aP2-HO-1 resulted in expression of human HO-1 for up to 9.5 months. Transduction of aP2-HO-1 increased human HO-1 expression in fat tissues without affecting murine HO-1. In mice fed a HF diet, aP2-HO-1 transduction attenuated the increases in body weight, blood glucose, blood pressure, and inflammatory cytokines, as well as the content of both visceral and subcutaneous fat. Transduction of aP2-HO-1 increased the numbers of adipocytes of small cell size ( P P P P

Purpose. To evaluate the diagnostic value of 3T1H-MRS in grading cerebral gliomas using short and long echo times.Methods. 1H-MRS was performed on 71 patients with untreated cerebral gliomas. Metabolite ratios of NAA/Cr, Cho/Cr, Cho/NAA, and mI/Cr were calculated for short and long TE and compared between low and high grade gliomas. Lipids were qualitatively evaluated. ROC analysis was performed to obtain the cut-off values for the metabolic ratios presenting statistical difference between the two glioma grades.Results. Intratumoral Cho/Cr at both TEs and long TE Cho/NAA were significantly different between low and high grade gliomas. Peritumoral NAA/Cr of both TEs, as well as long TE Cho/Cr and Cho/NAA ratios, significantly differentiated the two tumor grades. Diagnostic sensitivity of peritumoral short TE NAA/Cr proved to be superior over the other metabolic ratios, whereas intratumoral short TE Cho/Cr reached the highest levels of specificity and accuracy. Overall, short TE 1H-MRS reached higher total sensitivity in predicting glioma grade, over long TE.Conclusion. An advantage was found in using short TE over long TE 1H-MRS in the discrimination of low versus high grade gliomas. Moreover, the results suggested that the peritumoral area of gliomas may be more valuable in predicting glioma grade than using only the intratumoral area.

HO-1 and EETs are functionally linked and their interactions influence body weight, insulin sensitivity, and serum levels of inflammatory cytokines in metabolic syndrome phenotype of HO-2 null mice. The HO-2 isozyme is essential for regulating physiological levels of ROS. Recent studies have suggested a potential role of EET in modifying adipocyte differentiation through up-regulation of HO-1-adiponectin-AkT signaling in human mesenchymal stem cells (MSCs). Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo.Four-month-old HO-2 null (HO-2(-/-)) and B6/129SF2/J (WT) mice were divided into three groups (four mice/group): WT, HO-2(-/-), and HO-2(-/-) +CoPP. Adipogenesis was performed on purified MSC-derived adipocytes cultured in adipogenic differentiation media and an EET-agonist was added every 3 days.HO-2 depletion of MSC adipocytes resulted in increased adipogenesis (p0.01) and increased levels of inflammatory cytokines including (TNF)-alpha (p0.05), (MCP)-1 (p0.05), and (IL-1)-beta (p0.05). These results were accompanied by decreases in HO-1 (p0.05) and subsequently EET and HO activity (p0.05). Up-regulation of HO-1 resulted in decreased MSC-derived adipocyte differentiation, decreased production of TNF-alpha and MCP-1 and increased levels of adiponectin (p0.05). Cyp2J5 (p0.05), HO-1 (p0.05), and adiponectin mRNA levels (p0.05) were also decreased in visceral adipose tissue isolated from HO-2 null compared to WT mice. EET agonist stimulation of MSC adipocytes derived from HO-2 null mice yielded similar results.Increased levels of EET and HO-1 are essential for protection against the adverse effects of adipocyte hypertrophy and the ensuing metabolic syndrome. These results offer a portal into therapeutic approaches for the prevention of the metabolic syndrome.

Barium studies investigations (barium swallow, barium meal and barium enema) are the basic routine radiological examination, where barium sulphate suspension is introduced to enhance image contrast of gastrointestinal tracts. The aim of this study was to quantify the patients' radiation doses during barium studies and to estimate the organ equivalent dose and effective dose with those procedures. A total of 33 investigations of barium studies were measured by using thermoluminescence dosemeters. The result showed that the patient entrance surface doses were 12.6 ± 10, 44.5 ± 49 and 35.7 ± 50 mGy for barium swallow, barium meal, follow through and enema, respectively. Effective doses were 0.2, 0.35 and 1.4 mSv per procedure for barium swallow, meal and enema respectively. Radiation doses were comparable with the previous studies. A written protocol for each procedure will reduce the inter-operator variations and will help to reduce unnecessary exposure.

Radiotherapy is an important treatment modality against cancer resulting in apoptosis and inhibition of cell growth. Survivin is an important cancer biomarker conferring to tumour cells increased survival potential by inhibiting apoptosis. In the present study, we investigated the implication of breast cancer cells features, as hormone receptors and p53 status, in the radio-resistance of breast cancer cells and in the regulation of survivin’s expression by nuclear factor (NF)-κB and c-myc. Six breast cancer cell lines Michigan Cancer Foundation (MCF-7), MCF-7/Human Epidermal Growth Factor Receptor (HER)2, M. D. Anderson – Metastatic Breast (MDA-MB-231), SK-BR-3, BT-474 and Human Breast Lactating (HBL-100) were irradiated and cell viability as well as cell cycle distribution were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Survivin mRNA and protein levels were evaluated by real time PCR and Western blot analysis. Survivin and HER2 gene knockdown was performed with siRNA technology and investigation of transcription factors binding to survivin and c-myc gene promoters was assessed by chromatin immunoprecipitation. Student’s t-test and F-statistics were used for statistical evaluation. Our results demonstrated that only HER2+ breast cancer cells up-regulated survivin upon irradiation, whereas HER2 knockdown in HER2+ cells led to survivin’s down-regulation. Survivin and especially HER2 knockdown abolished the observed G2/M cell cycle checkpoint and reduced the radio-resistance of HER2 overexpressing breast cancer cells. Additionally, HER2 was found to regulate survivin’s expression through NF-κB and c-myc transcription factors. This study revealed the significance of HER2 in the radio-resistance of HER2+ breast cancer cells through induction of transcription factors NF-κB and c-myc, leading to activation of survivin, a downstream target oncogene preventing apoptosis.

Purpose Preoperative differentiation between low and high grade gliomas is critical for adapting appropriate treatment strategies. However biopsy based diagnosis presents limitations in assessing tumor diffusive and solid growth patterns, respectively, due to the potential subsampling of tumor region as well as the associated patient risk. The purpose of this study is to investigate the value of imaging biomarker analysis in terms of a 3D texture analysis of T1 pre/post-contrast, T2, and DTI maps in the evaluation of tumor heterogeneity towards glioma grading. Methods In this study a semi-automated segmentation technique, based on T1 pre/post-contrast, T2, and DTI parametric maps, is used for the identification of the tumor core and peritumoral edema regions from 3 Tesla MR Data. 3D Texture analysis was performed on 10 low grade and 10 high grade glioma patients, considering several 3D Histogram, Gray Level Co-Occurrence Matrices (GLCM) and Gray Level Run Length Matrices (GLRLM) derived features. Results Initial evaluation of the proposed method is performed in terms of textural features statistical significant differences between the two tumor groups, with the prospect of implementing an advance classification scheme for identifying more complex correlations. The preliminary results suggest that 3D Texture Analysis findings might be utilized as a surrogate biomarker for the global non-invasive assessment of glioma grading. Conclusions Results demonstrate the potential role of Texture Analysis of 3D tumor imaging appearance in structural MRI, for pre-treatment gliomas grade differentiation.

The study investigates the vulnerability of vegetation over Africa to El-Nino Southern Oscillation (ENSO) events using the moving window statistical correlation analysis technique. The correlation analysis was done between Normalized Difference Vegetation Index (NDVI) data from Advanced Very High Resolution Radiometer (AVHRR) and an ENSO index, namely Multivariate ENSO Index (MEI). The study develops a new monitoring approach (ENSO vulnerability assessment system) to quantify the relationships between monthly maximum NDVI anomalies and their month-to-month correlations with the ENSO indices for the vegetative land areas of Africa. The data used in this study was for the period 1982–2006. The new monitoring approach was used in the assessment of the long-time vegetation sensitivity to the ENSO warm events that occurred during the study period. A map of Africa indicating the vegetation vulnerability to ENSO is produced. Different areas of vegetation vulnerability are identified within the main vegetation cover classes. For the African vegetative land, 16% of the total area was characterized by moderate vulnerability of vegetation to El-Nino, whereas 1.18% showed high vulnerability. Results suggest that the vulnerability of vegetative land surfaces across Africa to climate extremes, such as ENSO depends considerably on the vegetation type. In particular, results show that areas of equatorial rainforest are more resistant to drought stress than the wooded and non-wooded vegetation categories.

The Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of diagnostic reference dose levels (DRLs). The aims of this study are to perform measurements of the entrance surface dose (ESD) during diagnostic digital subtraction angiography (DSA) of the renal and carotid arteries using thermoluminescence dosemeters (TLDs), extraction of local DRLs, and calculation of the effective dose. Dose measurement for the staff was also performed. Dose measurements were performed on 48 participating patients. The mean effective dose was calculated to be 15.9 mSv and 8.9 mSv, for the renal and carotid DSA, respectively. The effective dose of the radiologist was calculated to be 0.022 mSv and 0.023 mSv per procedure for renal and carotid DSA respectively, when wearing a protective apron and using a movable ceiling mounted shield. Radiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and on the difficulties in conducting the procedures. The lack of DRLs for the specific examinations lead the research team to choose the DRL for DSA of the renal arteries to be 169 mGy for ESD at the pelvic region and for DSA of the carotid arteries to be 313 mGy for ESD at the region of the aortic arc.

Background The Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of reference dose levels (DRLs). Purpose To perform measurements of the dose delivered during diagnostic angiography of the lower limbs using thermoluminescence dosimeters (TLDs), extraction of DRLs and estimation of the effective dose and radiation risk for this particular examination. Methods Dose measurement was performed on 30 patients by using TLD sachets attached in 5 different positions not only on the patient, but also to the radiologist. All the appropriate factors were recorded. Measurement of the ESD was performed after each examination. Results The mean entrance skin dose (ESD) was calculated to be 70.8, 67.7, 24.3, 18.4, 9.7 mGy at the level of aorta bifurcation, pelvis, femur, knees, and at feet, respectively. The average effective dose is 9.8 mSv with the radiation risks for fatal cancer to be 5.4 × 10−4. The effective dose of the radiologist was calculated to be 0.023 mSv per procedure. Conclusion Radiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and the difficulties in conducting procedures. The main reason for the increased patient dose, compared to other studies, is the number of frames rather than the duration of fluoroscopy. For DSA of the lower limbs, the DRL was chosen to be an entrance skin dose of 96.4 mGy in the pelvic region. The dose to the radiologist is negligible.

Blood vessel formation requires the integrated regulation of endothelial cell proliferation and branching morphogenesis, but how this coordinated regulation is achieved is not well understood. Flt-1 (vascular endothelial growth factor [VEGF] receptor 1) is a high affinity VEGF-A receptor whose loss leads to vessel overgrowth and dysmorphogenesis. We examined the ability of Flt-1 isoform transgenes to rescue the vascular development of embryonic stem cell–derived flt-1−/− mutant vessels. Endothelial proliferation was equivalently rescued by both soluble (sFlt-1) and membrane-tethered (mFlt-1) isoforms, but only sFlt-1 rescued vessel branching. Flk-1 Tyr-1173 phosphorylation was increased in flt-1−/− mutant vessels and partially rescued by the Flt-1 isoform transgenes. sFlt-1–rescued vessels exhibited more heterogeneous levels of pFlk than did mFlt-1–rescued vessels, and reporter gene expression from the flt-1 locus was also heterogeneous in developing vessels. Our data support a model whereby sFlt-1 protein is more efficient than mFlt-1 at amplifying initial expression differences, and these amplified differences set up local discontinuities in VEGF-A ligand availability that are important for proper vessel branching.

The aims of the present study were to assess whether sustained HO-1 expression could moderate or prevent diabetes in an animal model of the disease and, if so, to examine the possible mechanisms involved. Our results showed that HO-1 expression and HO activity were upregulated in the pancreas of non-obese diabetic (NOD) mice by the weekly administration of cobalt protoporphyrin (CoPP). Blood glucose levels in CoPPtreated mice decreased to normal, but continuously increased in untreated controls. Beta-cell numbers were preserved in the islets of CoPP-treated mice, whereas no beta cells were found in untreated diabetic mice. The number of CD11c(+) dendritic cells was significantly decreased in the pancreas of CoPP-treated NOD mice, but this effect was reversed by the inhibition of HO activity. Increased levels of HO-1 produced a new pancreatic phenotype, as reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and decreases in O(2)- and 3-NT levels. These novel findings provide a link between the increase in HO-1 activity, with its concurrent enhanced production of carbon monoxide (CO) and bilirubin, a decrease in infiltrated CD11c(+) dendritic cells and an increase in anti-apoptotic proteins, including RSK and BcL-xL, in the interdiction of the diabetic state.

Heme oxygenase-1 (HO-1) is crucial in regulating oxidative injury. The present study was designed to assess whether HO-1 upregulation by cobalt protoporphyrin IX (CoPP) moderates or prevents the diabetic state in non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes (T1D). HO-1 expression and HO activity were upregulated in the pancreas by the intermittent administration of CoPP. This was associated with decreases in blood glucose and pancreatic O2-, but increased pAKT and BcL-XL and cell survival. A considerable number of beta cells were preserved in the islets of CoPP-treated NOD mice, while none were found in untreated diabetic mice. The number of CD11c+ dendritic cells was decreased in the pancreas of CoPP-treated NOD mice (p < 0.05). These novel findings provide a link between the increase in HO-1 and a decrease in infiltrated CD11c+ dendritic cells, and suggest that induction of HO-1 activity can be used to enhance cell survival and moderate the diabetic state in T1D.

This work aims to evaluate the predictive strength of the relative seriality, parallel and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis (RP), in a group of patients following lung cancer radiotherapy and also to examine their correlation with pulmonary function tests (PFTs). The study was based on 47 patients who received radiation therapy for stage III non-small-cell lung cancer. For each patient, lung dose volume histograms (DVHs) and the clinical treatment outcome were available. Clinical symptoms, radiological findings and pulmonary function tests incorporated in a post-treatment follow-up period of 18 months were used to assess the manifestation of radiation induced complications. Thirteen of the 47 patients were scored as having radiation induced pneumonitis, with RTOG criteria grade 3 and 28 of the 47 with RTOG criteria grade 2. Using this material, different methods of estimating the likelihood of radiation effects were evaluated, by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Lungs were evaluated as a paired organ as well as individual lungs. Of the NTCP models examined in the overall group considering the dose distribution in the ipsilateral lung, all models were able to predict radiation induced pneumonitis only in the case of grade 2 radiation pneumonitis score, with the LKB model giving the best results (chi2-test: probability of agreement between the observed and predicted results Pchi(chi2)=0.524 using the 0.05 significance level). The NTCP modelling considering lungs as a paired organ did not give statistically acceptable results. In the case of lung cancer radiotherapy, the application of different published radiobiological parameters alters the NTCP results, but not excessively as in the case of breast cancer radiotherapy. In this relatively small group of lung cancer patients, no positive statistical correlation could be established between the incidence of radiation pneumonitis as estimated by NTCP models and the pulmonary function test evaluation. However, the use of PFTs as markers or predictors for the incidence or severity of radiation induced pneumonitis must be investigated further.