Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.

The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-α) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-γ) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-α -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-γ, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-γ and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; Pc, 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease

Investigation of suitable biopsy markers for grating-based phase contrast mammography

Phase-contrast mammography is a rising technology where, in addition to X-ray absorption, images show phase and dark-field contrast. Although the use of biopsy markers constitutes a fundamental task in breast examinations, there has not been any investigation concerning appropriate clips for this technology. We studied the suitability of three markers (Tumark, Somatex Medical Technologies; Hydromark, Mammotome; and Mammostar, Mammotome) for this modality on a laboratory source setup using a chicken breast phantom. The first two clips appeared to be innocuous, whereas Mammostar showed the potential that the non-metallic portion only could be used as a marker for this technique

Breast-density assessment with hand-held ultrasound: A novel biomarker to assess breast cancer risk and to tailor screening?

OBJECTIVES To assess feasibility and diagnostic accuracy of a novel hand-held ultrasound (US) method for breast density assessment that measures the speed of sound (SoS), in comparison to the ACR mammographic (MG) categories. METHODS ACR-MG density (a=fatty to d=extremely dense) and SoS-US were assessed in the retromamillary, inner and outer segments of 106 women by two radiographers. A conventional US system was used for SoS-US. A reflector served as timing reference for US signals transmitted through the breasts. Four blinded readers assessed average SoS (m/s), ΔSoS (segment-variation SoS; m/s) and the ACR-MG density. The highest SoS and ΔSoS values of the three segments were used for MG-ACR whole breast comparison. RESULTS SoS-US breasts were examined in <2 min. Mean SoS values of densities a-d were 1,421 m/s (SD 14), 1,432 m/s (SD 17), 1,448 m/s (SD 20) and 1,500 m/s (SD 31), with significant differences between all groups (p<0.001). The SoS-US comfort scores and inter-reader agreement were significantly better than those for MG (1.05 vs. 2.05 and 0.982 vs. 0.774; respectively). A strong segment correlation between SoS and ACR-MG breast density was evident (r=0.622, p=<0.001) and increased for full breast classification (r=0.746, p=<0.001). SoS-US allowed diagnosis of dense breasts (ACR c and d) with sensitivity 86.2 %, specificity 85.2 % and AUC 0.887. CONCLUSIONS Using hand-held SoS-US, radiographers measured breast density without discomfort, readers evaluated measurements with high inter-reader agreement, and SoS-US correlated significantly with ACR-MG breast-density categories. KEY POINTS • The novel speed-of-sound ultrasound correlated significantly with mammographic ACR breast density categories. • Radiographers measured breast density without women discomfort or radiation. • SoS-US can be implemented on a standard US machine. • SoS-US shows potential for a quantifiable, cost-effective assessment of breast density

Breast Density Assessment in Young Women with Ultrasound based on Speed of Sound: Influence of the Menstrual Cycle

To investigate changes in breast density (BD) during the menstrual cycle in young women in comparison to inter-breast and -segment changes as well as reproducibility of a novel Speed-of-Sound (SoS) Ultrasound (US) method.SoS-US uses a conventional US system with a reflector and a software add-on to quantify SoS in the retro-mammillary, inner and outer segments of both breasts. Twenty healthy women (18-40 years) with regular menstrual cycles were scanned twice with two weeks in-between. Three of these were additionally measured twice per week for 25 days. Average SoS (m/s) and ΔSoS (segment-variation SoS; m/s) were measured. Variations between follicular and luteal phases and changes over the four-week period were assessed. Inter-examiner and inter-reader agreements were also evaluated. Variances between cycle phases, examiners and readers were compared.No significant SoS difference was observed between follicular and luteal phases for the twenty women (P = .126), and between all different days for the three more frequently measured women (P = .892). Inter-reader (ICC = 0.999) and inter-examiner (ICC = 0.990) agreements were high. The SoS variance due to menstrual variations was not significantly larger than the inter-examiner uncertainty (P = .461). Inter-reader variations were significantly smaller than menstrual and examiner variations (P < .001).SoS-US showed high inter-examiner and inter-reader reproducibility. The alterations during the menstrual cycles were not significantly larger than the confidence interval of measurements

Microbubbles as a contrast agent in grating interferometry mammography: an ex vivo proof-of-mechanism study

Grating interferometry mammography (GIM) is an experimental breast imaging method at the edge of being clinically implemented. Besides attenuation, GIM can measure the refraction and scattering of x-rays resulting in differential phase contrast (DPC) and dark-field (DF) images. In this exploratory study, we assessed the feasibility of using microbubbles as a contrast agent in GIM. Two millilitres of microbubbles and iodine were respectively injected into ex vivo breast phantoms, consisting of fresh chicken breasts. Native and postcontrast images were acquired with a clinically compatible GIM setup, operated at 38 kVp, 14-s acquisition time, and with a dose of 1.3 mGy. The visibility of the contrast agents was analysed in a side-by-side comparison by three radiologists. The contrast-to-noise-ratio (CNR) was calculated for each contrast agent. We found that both contrast agents were judged to be visible by the readers. The mean CNR was 3.1 ± 1.9 for microbubbles in DF and 24.2 ± 6.5 for iodine in attenuation. In conclusion, this is a first proof-of-mechanism study that microbubbles could be used as a contrast agent in clinically compatible GIM, due to their scattering properties, which implies the potential use of a contrast agent with a high safety profile in x-ray-based breast imaging.ISSN:2509-928

Criticality of the biological and physical stimuli array inducing resident cardiac stem cell determination

The replacement of injured cardiac contractile cells with stem cell-derived functionally efficient cardiomyocytes has been envisaged as the resolutive treatment for degenerative heart diseases. Nevertheless, many technical issues concerning the optimal procedures to differentiate and engraft stem cells remain to be answered before heart cell therapy could be routinely used in clinical practice. So far, most studies have been focused on evaluating the differentiative potential of different growth factors without considering that only the synergistic cooperation of biochemical, topographic, chemical and physical factors could induce stem cells to adopt the desired phenotype. The present study demonstrates that the differentiation of cardiac progenitor cells to cardiomyocytes does not occur when cells are challenged with soluble growth factors alone, but requires strictly controlled procedures for the isolation of a progenitor cell population and the artifactual recreation of a microenvironment critically featured by a fine-tuned combination of specific biological and physical factors. Indeed, the scaffold geometry and stiffness are crucial in enhancing growth factor differentiative effects on progenitor cells. The exploitation of this concept could be essential in setting up suitable procedures to fabricate functionally efficient engineered tissue

Towards clinical grating-interferometry mammography.

Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography