Is systemic lupus erythematosus different in urban versus rural living environment? Data from the Cretan Lupus Epidemiology and Surveillance Registry.

BACKGROUND: Examining urban-rural differences can provide insights into susceptibility or modifying factors of complex diseases, yet limited data exist on systemic lupus erythematosus (SLE). OBJECTIVE: To study SLE risk, manifestations and severity in relation to urban versus rural residence. METHODOLOGY: Cross-sectional analysis of the Crete Lupus Registry. Demographics, residency history and clinical data were obtained from interviews and medical records ( N=399 patients). Patients with exclusively urban, rural or mixed urban/rural residence up to enrolment were compared. RESULTS: The risk of SLE in urban versus rural areas was 2.08 (95% confidence interval: 1.66-2.61). Compared with rural, urban residence was associated with earlier (by almost seven years) disease diagnosis - despite comparable diagnostic delay - and lower female predominance (6.8:1 versus 15:1). Rural patients had fewer years of education and lower employment rates. Smoking was more frequent among urban, whereas pesticide use was increased among rural patients. A pattern of malar rash, photosensitivity, oral ulcers and arthritis was more prevalent in rural patients. Residence was not associated with organ damage although moderate/severe disease occurred more frequently among rural-living patients (multivariable adjusted odds ratio: 2.17, p=0.011). CONCLUSION: Our data suggest that the living environment may influence the risk, gender bias and phenotype of SLE, not fully accounted for by sociodemographic factors.

Aberrant microRNA expression in tumor mycosis fungoides.

Herein, miRNA candidates relevant to mycosis fungoides were investigated to provide data on the molecular mechanisms underlying the pathogenesis of the disease. The miRNA expression profile of skin biopsies from patients with tumor stage MF (tMF) and normal donors was compared using miRNA microarrays. Overall, 154 miRNAs were found differentially expressed between tMF and the control cohort with the majority of them being up-regulated (57 %). Among the upregulated miRNAs, miR-3177, miR-514b-3p, miR-1267, and miR-1282 were exclusively detected in 70 % of tMF. Additional upregulated miRNAs included miR-34a, miR-29a, let-7a*, and miR-210, while miR-200c* was identified among the downregulated ones. Quantitative real-time polymerase chain reaction was used to further investigate the expression profiles of miR-34a and miR-29a and validated the overexpression of miR-34a. Enrichment studies revealed that the target genes of the differentially expressed miRNAs were important in several cancer-related signaling pathways. The overlapping relationship of the target genes among tMF, Sezary syndrome, and atopic dermatitis revealed several common and disease-specific genes. Collectively, our study modulated miR-34a as a candidate oncogenic molecule and miR-29a as a putative tumor suppressor highlighting their promising potential in the molecular pathogenesis of tMF.

SPNsim: A database of simulated solitary pulmonary nodule PET/CT images facilitating computer aided diagnosis.

The aim of the present work was to design and develop a database of simulated solitary pulmonary nodules (SPN) in pairs of computed tomography (CT) and positron emission tomography (PET) images, using Monte Carlo (MC) simulation methods. We have developed an SPN image modeling pipeline to feed the database entitled SPNsim. The database is web-accessible and it is contains two subsets of simulated PET/CT SPN images. The first subset is currently composed of 1000 cases containing pairs of the transaxial CT and the corresponding PET slice with various types of simulated SPNs, presented as individual records. The second subset contains pairs of the transaxial CT and the corresponding PET slice of simulated SPNs, presenting cases of graded difficulty in diagnosis. The users of the database will have the ability to set queries in order to retrieve cases with certain characteristics, as well as characterized image sets. All images are freely available and may be downloaded from the website. SPNsim provides a useful reference data set for training and evaluation of computer aided detection (CAD) and diagnosis (CADx) systems focusing on SPN.

Endoplasmic reticulum stress and mineralization inhibition mechanism by the resinous monomer HEMA.

AIM: To investigate the expression of two endoplasmic reticulum (ER)-resident key chaperone proteins, ERdj5 and BiP, under the influence of resinous monomers and its relationship with the inhibition of mineralization caused by the monomer 2-hydroxyethyl methacrylate (HEMA). METHODOLOGY: The ERdj5 and BiP expression was studied in vitro, in primary human pulp cell cultures after treatment with three different HEMA concentrations at different time periods. Subsequently, the expression of both the odontoblast markers dentine sialoprotein (DSP) and osteonectin (OSN) was studied in human pulp cells under the same conditions. RESULTS: The ERdj5 and BiP expression was upregulated in the pulp cells. DSP and OSN were largely dispersed in the cytoplasm in control cell cultures but accumulated in a perinuclear area after exposure to HEMA. Their expression levels were not affected. CONCLUSIONS: The increased expression of ERdj5 and BiP may reflect activation of ER stress. DSP and OSN accumulation into the cells may lead to their secretion arrest and inhibition of dentine matrix formation. These events may elucidate the mechanism by which HEMA inhibits the mineralization process.

How accurate are diagnostic tools for Epstein-Barr virus (EBV) to establish causal association of an uncommon clinical condition with EBV?

UNLABELLED: Epstein-Barr virus (EBV) infection has been implicated as a possible cause of a wide range of clinical conditions in children and young adults. In uncommon clinical conditions, where clinical experience is missing, it is important to evaluate both the biological plausibility and the virological basis that substantiates their causal association with EBV. By reviewing the diagnostic procedures performed in the diagnosis of EBV infection in case reports concerning uncommon clinical conditions causally related to EBV infection in children and young adults, the aim of the present study was to discuss the limitations of the diagnostic procedure used to establish EBV diagnosis, which may cause false-positive results and compromise the reliability of such a diagnosis. We should be aware not only of the nuances of serological tests and virus detection tests for latent viruses such as EBV, but also of the risk of using them alone or in combination with molecular methods as the sole mean for establishing a causal relation between EBV infection and an uncommon clinical condition. Accurate laboratory tests for EBV detection, strict criteria for EBV infection diagnosis, and a cumulative clinical experience coupled with biological plausibility and experimental data are needed to avoid a possible coincidental association between several clinical manifestations, mainly uncommon clinical conditions, and EBV infection. KEYWORDS: Epstein-Barr virus; diagnostics; uncommon condition.

Painful vaso-occlusive crisis as a prodromal phase of acute chest syndrome. Is only one chest X-ray enough? A case report.

The predominant pathophysiological feature of homozygous sickle cell anemia (SCA) is the vaso-occlusion. Vaso-occlusion can be associated with painful crises, which are the primary reason for those patients to seek medical care. Vaso-occlusion is responsible for the acute chest syndrome (ACS) with large morbidity and mortality or more rarely (and especially in adults) for priapism and acute neurological events (strokes). A 10-year-old boy with homozygous SCA was admitted to the Pediatric Emergencies with painful vaso-occlusive crisis and fever. Initially he had normal chest X-ray but, after 24-hour-hospitalization, he developed ACS with new chest X-ray findings. He was treated with broad spectrum antibiotics, blood transfusions and bronchodilators and after a six-day treatment, he was significantly improved. The patient was discharged 13 days later with no other therapy at home. The possibility of ACS development should be still considered, even when a known patient with SCA presents a painful vaso-occlusive crisis with an initial normal chest X-ray. Therefore, repeated clinical examination is required and possible changes in the clinical status could indicate the necessity of a new radiographic examination. In this way, early ACS could be recognized and the catastrophic consequences due to this syndrome could be avoided.

Monte Carlo studies on the influence of focal spot size and intensity distribution on spatial resolution in magnification mammography.

Magnification is a special technique applied in mammography in cases where breast complaints have already been noticed, aiming to examine a specific area of the breast. Small-sized focal spots are essential in such techniques in order to reduce the resultant geometrical unsharpness. The x-ray intensity distribution of the focal spot is another crucial parameter for such a technique as it affects the mammographic resolution. In this study a Monte Carlo simulation model is utilized, in order to examine the effect of a wide range of focal spot sizes and three representative intensity distributions on spatial resolution under magnification. A thick sharp edge consisting of lead, non-transparent to x-rays was imaged under various conditions for this purpose, and the corresponding spatial resolution was calculated through the modulation transfer function (MTF). Results demonstrate that focal spots larger than 0.10 mm can mainly be used for low degrees of magnification, especially when combined with double peak Gaussian intensity distribution of the focal spot (sum of two single peak Gaussian distributions with different centers), as the resultant spatial resolution is not as high as the corresponding from smaller foci or uniform and single peak Gaussian distributions. Moreover, for the degrees of magnification usually utilized in clinical practice they do not reach the acceptable limit of 12 lp mm(-1). The replacement of the x-ray tube when the focal spot starts being destroyed is very crucial as the possible alteration of single peak Gaussian distribution to double peak Gaussian results in the degradation of spatial resolution. A focal spot of 0.10 mm or smaller, combined with single peak Gaussian intensity distribution, can be considered appropriate even for higher degrees of magnification and its use can contribute in the effort to optimize the magnification views in mammography.

Increased expression of specific thioredoxin family proteins; a pilot immunohistochemical study on human hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most frequent cancers worldwide, however, prognosis remains poor following its discovery. We investigate the Thioredoxin superfamily of proteins as diagnostic markers for HCC. Furthermore, we delineate possible roles of the endoplasmic reticulum member of the superfamily, ERdj5, in carcinogenesis. Using antibodies against Thioredoxin 1, Thioredoxin Reductase 1 and ERdj5, we performed immunohistochemistry on paraffin embedded liver biopsy sections from HCC patients. All three redox proteins exhibited elevated expression levels in tumor tissue compared to internal control, with ERdj5 showing a remarkable 3-fold increase. In vitro cell viability experiments using Hepatocellular Carcinoma HuH7 cells treated with ERdj5 small interfering RNA showed that ERdj5 knockdown cells exhibited less resistance to Doxorubicin (chemotherapy drug), but more resistance to Tunicamycin (Endoplasmic Stress inducer), compared to control cells. In conclusion, we introduce members of the Thioredoxin superfamily as possible immunohistochemical markers in the diagnostics of hepatocellular carcinoma and indicate a potential defensive role for ERdj5 in chemotherapeutic drug resistance.

Energy, angular and spatial distributions of primary electrons inside photoconducting materials for digital mammography: Monte Carlo simulation studies.

Materials such as a-Se, a-As(2)Se(3), GaSe, GaAs, Ge, CdTe, CdZnTe, Cd(0.8)Zn(0.2)Te, ZnTe, PbO, TlBr, PbI(2) and HgI(2) are potential candidates as photoconductors in direct detectors for digital mammography. The x-ray induced primary electrons inside a photoconductor's bulk comprise the initial signal that propagates and forms the final signal (image) on the detector's electrodes. An already developed model for a-Se has been properly extended to simulate the primary electron production in the materials mentioned. Primary electron characteristics, such as their energy, angular and spatial distributions that strongly influence the characteristics of the final image, were studied for both monoenergetic and polyenergetic x-ray spectra in the mammographic energy range. The characteristic feature in the electron energy distributions for PbI(2) and HgI(2) is the atomic deexcitation peaks, whereas for the rest of the materials their shape can also be influenced by the electrons produced from primary photons. The electrons have a small tendency to be forward ejected whereas they prefer to be ejected perpendicular (theta = pi/2) to the incident beam's axis and at two lobes around phi = 0 and phi = pi. At practical mammographic energies (15-40 keV) a-Se, a-As(2)Se(3) and Ge have the minimum azimuthal uniformity whereas CdZnTe, Cd(0.8)Zn(0.2)Te and CdTe the maximum one. The spatial distributions for a-Se, a-As(2)Se(3), GaSe, GaAs, Ge, PbO and TlBr are almost independent of the polyenergetic spectrum, while those for CdTe, CdZnTe, Cd(0.8)Zn(0.2)Te, ZnTe, PbI(2) and HgI(2) have a spectrum dependence. In the practical mammographic energy range and at this primitive stage of primary electron production, a-Se has the best inherent spatial resolution as compared to the rest of the photoconductors. PbO has the minimum bulk space in which electrons can be produced whereas CdTe has the maximum one.

Contrast-to-noise ratio in magnification mammography: a Monte Carlo study.

Magnification views are a common way to perform a secondary examination when suspicious abnormalities are found in a screening mammogram. The visibility of microcalcifications and breast lesions is restricted by the compromise between the image quality and the absorbed dose. In this study, image quality characteristics in magnification mammography were evaluated based on Monte Carlo techniques. A breast phantom was utilized, simulating a homogeneous mixture of adipose and glandular tissue in various percentages of glandularity, containing inhomogeneities of various sizes and compositions. The effect of the magnification degree, breast glandularity, tube voltage and anode/filter material combination on image quality characteristics was investigated in terms of a contrast-to-noise ratio (CNR). A performance index PI(nu) was introduced in order to study the overall performance of various anode/filter combinations under different exposure parameters. Results demonstrate that CNR is improved with the degree of magnification and degraded as the breast glandularity is increased. Degree of magnification 1.3 offers the best overall performance for most of the anode/filter combinations utilized. Under magnification conditions, the role of dose is demoted against the image quality, as magnification views are secondary, diagnostic examinations and not screening procedures oriented to non-symptomatic women. For decreased image quality weighting, some anode/filter combinations different from Mo/0.030 mmMo can be utilized as they offer a similar performance index. However, if the desired weighting for the image quality is high, the Mo/0.030 mmMo combination has the best overall performance.

Drug repurposing in idiopathic pulmonary fibrosis filtered by a bioinformatics-derived composite score.

Idiopathic Pulmonary Fibrosis (IPF) is a rare disease of the respiratory system in which the lungs stiffen and get scarred, resulting in breathing weakness and eventually leading to death. Drug repurposing is a process that provides evidence for existing drugs that may also be effective in different diseases. In this study, we present a computational pipeline having as input a number of gene expression datasets from early and advanced stages of IPF and as output lists of repurposed drugs ranked with a novel composite score. We have devised and used a scoring formula in order to rank the repurposed drugs, consolidating the standard repurposing score with structural, functional and side effects' scores for each drug per stage of IPF. The whole pipeline involves the selection of proper gene expression datasets, data preprocessing and statistical analysis, selection of the most important genes related to the disease, analysis of biological pathways, investigation of related molecular mechanisms, identification of fibrosis-related microRNAs, drug repurposing, structural and literature-based analysis of the repurposed drugs.

Breast implant associated anaplastic large cell lymphoma: The UK experience. Recommendations on its management and implications for informed consent.

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare, Non-Hodgkin lymphoma arising in the capsule of breast implants. BIA-ALCL presents as a recurrent effusion and/or mass. Tumours exhibit CD30 expression and are negative for Anaplastic Lymphoma Kinase (ALK). We report the multi-disciplinary management of the UK series and how the stage of disease may be used to stratify treatment. METHODS: Between 2012 and 2016, 23 cases of BIA-ALCL were diagnosed in 15 regional centres throughout the UK. Data on breast implant surgeries, clinical features, treatment and follow-up were available for 18 patients. RESULTS: The mean lead-time from initial implant insertion to diagnosis was 10 years (range: 3-16). All cases were observed in patients with textured breast implants or expanders. Fifteen patients with breast implants presented with stage I disease (capsule confined), and were treated with implant removal and capsulectomy. One patient received adjuvant chest-wall radiotherapy. Three patients presented with extra-capsular masses (stage IIA). In addition to explantation, capsulectomy and excision of the mass, all patients received neo-/adjuvant chemotherapy with CHOP as first line. One patient progressed on CHOP but achieved pathological complete response (pCR) with Brentuximab Vedotin. After a mean follow-up of 23 months (range: 1-56) all patients reported here remain disease-free. DISCUSSION: BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.

Suitability of new anode materials in mammography: dose and subject contrast considerations using Monte Carlo simulation.

Mammography is the technique with the highest sensitivity and specificity, for the early detection of nonpalpable lesions associated with breast cancer. As screening mammography refers to asymptomatic women, the task of optimization between the image quality and the radiation dose is critical. A way toward optimization could be the introduction of new anode materials. A method for producing the x-ray spectra of different anode/filter combinations is proposed. The performance of several mammographic spectra, produced by both existing and theoretical anode materials, is evaluated, with respect to their dose and subject contrast characteristics, using a Monte Carlo simulation. The mammographic performance is evaluated utilizing a properly designed mathematical phantom with embedded inhomogeneities, irradiated with different spectra, based on combinations of conventional and new (Ru, Ag) anode materials, with several filters (Mo, Rh, Ru, Ag, Nb, Al). An earlier developed and validated Monte Carlo model, for deriving both image and dose characteristics in mammography, was utilized and overall performance results were derived in terms of subject contrast to dose ratio and squared subject contrast to dose ratio. Results demonstrate that soft spectra, mainly produced from Mo, Rh, and Ru anodes and filtered with k-edge filters, provide increased subject contrast for inhomogeneities of both small size, simulating microcalcifications and low density, simulating masses. The harder spectra (W and Ag anode) come short in the discrimination task but demonstrate improved performance when considering the dose delivered to the breast tissue. As far as the overall performance is concerned, new theoretical spectra demonstrate a noticeable good performance that is similar, and in some cases better compared to commonly used systems, stressing the possibility of introducing new materials in mammographic practice as a possible contribution to its optimization task. In the overall optimization task in terms of subject contrast to dose ratio, tube voltage was found to have a minor effect, while with respect to the filter material, a lesion specific performance was noticed, with Al filtered spectra showing improved characteristics in case of the inhomogeneities simulating microcalcifications, while softer k-edge filtered spectra are more suitable for the discrimination of inhomogeneities simulating masses.

Monte Carlo generated conversion factors for the estimation of average glandular dose in contact and magnification mammography.

Magnification mammography is a special technique used in the cases where breast complaints are noted by a woman or when an abnormality is found in a screening mammogram. The carcinogenic risk in mammography is related to the dose deposited in the glandular tissue of the breast rather than the adipose, and average glandular dose (AGD) is the quantity taken into consideration during a mammographic examination. Direct measurement of the AGD is not feasible during clinical practice and thus, the incident air KERMA on the breast surface is used to estimate the glandular dose, with the help of proper conversion factors. Additional conversion factors adapted for magnification and tube voltage are calculated, using Monte Carlo simulation. The effect of magnification degree, tube voltage, various anode/filter material combinations and glandularity on AGD is also studied, considering partial breast irradiation. Results demonstrate that the estimation of AGD utilizing conversion factors depends on these parameters, while the omission of correction factors for magnification and tube voltage can lead to significant underestimation or overestimation of AGD. AGD was found to increase with filter material's k-absorption edge, anode material's k-emission edge, tube voltage and magnification. Decrease of the glandularity of the breast leads to higher AGD due to the increased penetrating ability of the photon beam in thick breasts with low glandularity.

Selenite and selenate inhibit human lymphocyte growth via different mechanisms.

Selenium compounds like selenite and selenate have strong inhibitory effects, particularly on mammalian tumor cell growth by unknown mechanisms. We found that the addition of sodium selenite and sodium selenate inhibited the growth of human 3B6 and BL41 lymphocytes. Selenite was more potent because 10 microM selenite produced a growth inhibitory effect similar to that of 250 microM selenate. The mechanism of action of selenite and selenate appears to be different. 3B6 and BL41 cells treated with selenite accumulated in the S-phase; however, selenate caused an accumulation of cells in G2. Selenite-mediated growth inhibition was irreversible, although the effects of selenate could be reversed. Selenite, in contrast to selenate, is efficiently reduced by the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH). At concentrations required to observe a similar effect on cell growth, the activity of thioredoxin reductase, recently shown to be a selenoprotein, increased in selenite-treated cells and decreased in selenate-treated cells. Ribonucleotide reductase activity was inhibited in an in vitro assay by selenite and selenodiglutathione but not by selenate. These results show that selenite and selenate use different mechanisms to inhibit cell growth.

Variations in Jun and Fos protein expression and AP-1 activity in cycling, resting and stimulated fibroblasts.

We have analysed the different Jun and Fos proteins as NIH3T3 fibroblasts pass from exponential growth to quiescence and during the first 24 h after their re-entry into the cell cycle following serum stimulation. We show that these proteins can be divided into 3 subgroups based on their pattern of expression. The first contains c-Jun, Jun-D and Fra-2 which are expressed at high level in cycling cells and are only mildly induced by serum. The second contains Jun-B, c-Fos, Fos-B and deltaFos-B whose levels are low in cycling cells but increase strongly and rapidly after stimulation by serum. The third group contains only Fra-1, which is absent from cycling cells and behaves as a delayed early response protein after serum stimulation. AP-1 binding activity is low both in cycling and quiescent fibroblasts but increases after stimulation by serum with kinetics matching the induction of the various Jun and Fos proteins. Antibody supershift analyses demonstrate that the composition of AP-1 binding activity reflects the relative abundance of each Jun and Fos protein. Furthermore, the state of post-translational modification varies continuously for all of the AP-1 proteins as growth conditions change. These data indicate that AP-1 activity during the G0-G1 transition is finely regulated and complex, involving changes both in protein expression and in posttranslational modification.

Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK.

JNK/SAPKs are identified as new members of the MAPK family; they phosphorylate c-Jun protein in response to several cellular stimuli including ultraviolet irradiation, TNF and osmotic shock. We have identified a protein kinase, MUK, as an activator of the JNK-pathway, whose kinase domain shows significant homology to MAPKKK-related proteins such as c-Raf and MEKK. The over-expression of MUK or MEK kinase (MEKK) in NIH3T3 or COS1 cells results in the activation of JNK1 and the accumulation of a hyper-phosphorylated form of c-Jun. While MEKK also activates the ERK pathway, MUK is a rather selective activator of the JNK pathway. On the other hand, c-Raf activates the JNK pathway only slightly despite its remarkable ability to activate the ERK pathway. Even though we originally identified MUK as a MAPKKK-related protein kinase, a greater similarity to mixed lineage kinase (MLK) is found not only in the catalytic domain but also in the 'leucine-zipper'-like motifs located at the C-terminal side of the catalytic domain. The structural divergence between MUK and MEKK reveals the multiplicity of signaling pathways that activate JNK/SAPKs.

cDNA cloning, expression and chromosomal localization of the mouse mitochondrial thioredoxin reductase gene(1).

Cytosolic thioredoxin (Trx) and thioredoxin reductase (TrxR) comprise a ubiquitous system that uses the reducing power of NADPH to act as a general disulfide reductase system as well as a potent antioxidant system. Human and rat mitochondria contain a complete thioredoxin system different from the one present in the cytosol. The mitochondrial system is involved in the oxidative stress protection through a mitochondrial thioredoxin-dependent peroxidase. We report here the cDNA cloning and chromosomal localization of the mouse mitochondrial thioredoxin reductase gene (TrxR2). The mouse TrxR2 cDNA encodes for a putative protein of 527 amino acid residues with a calculated molecular mass of 57 kDa, that displays high homology with the human and rat counterparts. The N-terminus of the protein displays typical features of a mitochondrial targeting sequence with absence of acidic residues and abundance of basic residues. Mouse TrxR2 also contains a stop codon in frame at the C-terminus of the protein, necessary for the incorporation of selenocysteine that is required for enzymatic activity. The typical stem-loop structure (SECIS element) that drives the incorporation of selenocysteine is identified in the 3'-UTR. Northern analysis of the mouse TrxR2 mRNA shows a similar pattern of expression with the human homologue, with higher expression in liver, heart and kidney. Finally, we have assigned the mouse TrxR2 gene to chromosome 16 mapping at 11.2 cM from the centromer and linked to the catechol-o-methyltransferase (comt) gene.

Monte Carlo simulation of primary electron production inside an a-selenium detector for x-ray mammography: physics.

Selenium is among the materials under investigation that may form effective detectors and provide a major contribution to digital mammography. Till the final image formation, there is an intervention of the x-ray photons transformation to primary electrons and their subsequent ionizing drift towards the electrodes that collect them. The characteristics of the generated primary electrons inside a-Se material such as their angular, spatial and energy distribution affect the characteristics of the final image. A Monte Carlo based model has been developed that simulates the x-ray irradiation of an a-Se detector plate, including primary photon interactions (photoelectric absorption, coherent and incoherent scattering), as well as secondary ones, such as fluorescence (Kalpha, Kbeta) and emission of Auger electrons. The angular, spatial and energy distributions for the generated primary electrons inside a-Se have been produced for various mammographic x-ray spectra and their usefulness in designing and optimizing a detector made of a-Se for digital mammography is discussed.

DOSIS: a Monte Carlo simulation program for dose related studies in mammography.

Dosimetric studies in mammography are addressed by means of a Monte Carlo simulation program. The core of this program (DOSIS: dosimetry simulation studies) is a simulation model developed using FORTRAN 90, enriched with a graphical user interface developed in MS Visual Basic. User defined mammographic technique parameters affecting breast dose are imported to the simulation model and the produced results are provided by means of both absolute (surface dose, exposure at detector plane) and relative quantities (percentage depth dose, isodose curves). The program functionality has been demonstrated in the evaluation of various mammographic examination techniques. Specifically, the influence of tube voltage and filtration on the surface dose and the exposure at detector plane has been studied utilizing a water phantom. Increase of tube voltage from 25 to 30 kVp for a Mo/Mo system resulted in a 42% decrease of the surface dose for a thick breast (6 cm), without changing the exposure at the detector plane. Use of 1.02 mm Al filter for a W anode system operating at 30 kVp resulted in a 19.1% decrease of the surface dose delivered to a 5 cm water equivalent breast. Overall, W/Al systems appear to have improved dosimetric performance, resulting up to a 65% decrease of surface dose compared to Mo/Mo systems, for identical exposures at the detector plane and breast thicknesses.