A theoretical framework to investigate the effect of high permittivity materials in MRI using anatomy-mimicking cylinders.

PURPOSE: Recent numerical and empirical results proved that high permittivity materials (HPM) used in pads placed near the subject or directly integrated with coils can increase the SNR and reduce the specific absorption rate (SAR) in MRI. In this paper, we propose an analytical investigation of the effect on the magnetic field distribution of a layer of HPM surrounding an anatomy-mimicking cylindrical sample. METHODS: The study is based on a reformulation of the Mie scattering for cylindrical geometry, following an approach recently introduced for spherical samples. The total field in each medium is decomposed in terms of inward and outward electromagnetic waves, and the fields are expressed as series of cylindrical harmonics, whose coefficients can be interpreted as classical reflection and transmission coefficients. RESULTS: Our new formulation allows a quantitative evaluation of the effect of the HPM layer for varying permittivity and thickness, and it provides an intuitive understanding of such effect in terms of propagation and scattering of the RF field. CONCLUSION: We show how HPM can filter out the modes that only contribute to the noise or RF power deposition, resulting in higher SNR or lower SAR, respectively. Our proposed framework provides physical insight on how to properly design HPM for MRI applications.

Linguistic adaptation and psychometric evaluation of Italian version of children's sleep habits questionnaire.

BACKGROUND: The Children's Sleep Habits Questionnaire (CSHQ) is a parent-report questionnaire used to examine sleep behavior in children. Linguistic adaptation of CSHQ into several languages and/or psychometric analysis of reliability have been published. MAIN TEXT: Our aim was to translate the original 33-items CSHQ from English to Italian and to examine its reliability for use in 4-10 years-old children of Italy. After translation and back-translation procedure of the original CSHQ, the Italian CSHQ (CSHQ-IT) was administered to 69 mothers of healthy children. Reliability of CSHQ-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis obtained by asking mothers who had completed the CSHQ-IT at baseline to re-complete it after a two-week interval (measured with the Lin's Concordance Correlation Coefficient, CCC). The CSHQ-IT showed adequate internal consistency (Cronbach's alpha = 0.81 for the total scale). The total CSHQ-IT score showed a strong correlation in retests (CCC 0.87; 95% Confidence Interval, 0.80; 0.92). CONCLUSION: CSHQ-IT is a valuable tool for evaluating sleep behavior in children 4-10 years-old in Italy. Future research should be implemented to provide definitive validity of CSHQ-IT in children with sleep-disordered breathing.

Femtograms of Interferon-γ Suffice to Modulate the Behavior of Jurkat Cells: A New Light in Immunomodulation.

Since interferon-γ (IFN-γ) tunes both innate and adaptive immune systems, it was expected to enter clinical practice as an immunomodulatory drug. However, the use of IFN-γ has been limited by its dose-dependent side effects. Low-dose medicine, which is emerging as a novel strategy to treat diseases, might circumvent this restriction. Several clinical studies have proved the efficacy of therapies with a low dose of cytokines subjected to kinetic activation, while no in vitro data are available. To fill this gap, we investigated whether low concentrations, in the femtogram range, of kinetically activated IFN-γ modulate the behavior of Jurkat cells, a widely used experimental model that has importantly contributed to the present knowledge about T cell signaling. In parallel, IFN-γ in the nanogram range was used and shown to activate Signal transducer and activator of transcription (STAT)-1 and then to induce suppressor of cytokine signaling-1 (SOCS-1), which inhibits downstream signaling. When added together, femtograms of IFN-γ interfere with the transduction cascade activated by nanograms of IFN-γ by prolonging the activation of STAT-1 through the downregulation of SOCS-1. We conclude that femtograms of IFN-γ exert an immunomodulatory action in Jurkat cells.

Enhancement of the Immunostimulatory Functions of Ex Vivo-Generated Dendritic Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study.

Dendritic cells (DCs), specialized antigen-presenting cells bridging innate and adaptive immunity, play a crucial role in determining specific immune response to tumors. Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far. This pilot study compared low-dose interleukin (IL)-4 and IL-12 prepared by sequential kinetic activation (SKA) with standard doses of the same recombinant human cytokines on functional activity of ex vivo-generated monocyte-derived (Mo) DCs from colon carcinoma patients and normal subjects. MoDCs were exposed to medium alone, SKA-IL-4 (0.5 fg/ml), or SKA-IL-12 (2 fg/ml), alone or consecutively combined, in parallel with rhIL-4 (50 ng/ml) and rhIL-12 (1 ng/ml). Primary allogeneic one-way mixed lymphocyte reaction (MLR) was the end point to assess in vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and interferon-γ in MLR supernatants measured by ELISA to assay for T-helper 1-promoting MoDC phenotype. No single agent enhanced the compromised allostimulatory activity of MoDCs from colon cancer patients, unlike healthy donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential exposure to SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), displayed increased T-cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization activity, although less markedly than the effects induced by recombinant human cytokines or found in normal subjects. These results point to an immunomodulatory capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation to provide clues for the rational development of new and more effective immunotherapeutic strategies against cancer.

Low-doses of sequential-kinetic-activated interferon-γ enhance the ex vivo cytotoxicity of peripheral blood natural killer cells from patients with early-stage colorectal cancer. A preliminary study.

Natural killer (NK) cells are innate immune-system lymphocytes capable of killing tumor cells. They secrete cytokines, including interferon (IFN)-γ, which participate in shaping the initial inflammatory and downstream adaptive immune responses. Its potent immunoregulatory action means that IFN-γ might be beneficial in cases of tumor rejection, but its severe side-effects limit clinical applications. This pilot study compared low-dose IFN-γ prepared by sequential-kinetic-activation (SKA), with standard-dose recombinant (r) IFN-γ, in terms of ex-vivo cytotoxic activity of peripheral blood (PB)-NK cells from colorectal carcinoma (CRC) patients. This was tested against the NK-sensitive K562 cell line and the less-sensitive human CRC Caco-2 and HT-29 cell lines. Twenty primitive non-metastatic CRC patients, five metastatic CRC patients, and thirteen healthy donors were enrolled. PB lymphocytes (PBL) were exposed to medium alone, SKA-IFN-γ (0.25fg/ml) or rIFN-γ (1ng/ml). NK-cell cytolytic activity was examined via short-term (51)Cr-release. Pretreatment of PBL from non-metastatic patients with SKA-IFN-γ caused a significant increase in NK-cell cytotoxicity, compared to those from normal donors, although less markedly than pretreatment with rIFN-γ against all three cell lines. In contrast, PBL from metastatic CRC patients displayed significantly decreased NK-cell activity and responsiveness to both rIFN-γ and SKA-IFN-γ treatments. These results demonstrate in principle the immunomodulatory capacity of low-dose SKA-IFN-γ, and might open the door to the possibility of generating a novel, safe, and feasible approach to enhancing NK-cell antitumor activity in early-stage CRC patients.