An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is ...functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.
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Swallowing impairment (dysphagia) has been associated with COPD and may contribute to exacerbations of this chronic and progressive disease. Further, risk of mortality increases with concomitant ...presence of cachexia in the COPD population. The purpose of this prospective study was to depict oropharyngeal swallowing physiology in underweight patients with stable but advanced-stage COPD.
Ten underweight patients with stable but advanced COPD underwent a modified barium swallow study. Analysis of oropharyngeal swallowing function was completed using the standardized Modified Barium Swallow Impairment Profile and the Penetration-Aspiration Scale. Scores from the Dysphagia Handicap Index and 10-item Eating Assessment Tool were collected to assess patient perception of swallowing difficulty. Findings were compared to age- and sex-matched healthy controls.
Significantly higher MBSImP oral total scores (
=0.007) were observed in COPD patients compared to matched controls, but no difference was observed in pharyngeal total scores (
=0.105). Patients with COPD had significantly higher maximum PAS scores compared with controls (
=0.030). There was no significant difference in EAT-10 or DHI scores between patients with COPD and controls (
=0.41 and
=0.08, respectively).
Underweight patients with severe but stable COPD present with dysphagia that may not be recognized by the patient. Further investigation is needed to elucidate the interaction between the respiratory-swallowing systems, how muscular weakness may contribute to swallowing impairment, and responsiveness to swallowing treatment.
Purpose
The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the ...residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques.
Methods
A total of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12 patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface (“SGRT shift”) during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose–volume histogram (DVH) metrics. A global plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques.
Results
Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases.
Conclusion
The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.
Purpose
To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold – DIBH treatment) with different predefined beam gating thresholds and to evaluate ...their impact on motion management and DIBH stability.
Methods
An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface (“SGRT shift”). Beam gating tolerances were 5 mm/4 mm for the SGRT shifts and 5 mm/3 mm for the gating window amplitude for breast tangential and breast + lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated.
Results
Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values < 1 mm). The distribution of the percentage of beam on time with SGRT shift > 3 mm, > 4 mm, or > 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample.
Conclusion
Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted.
Infection by group B streptococcus (GBS) is an important cause of bacterial disease in neonates, pregnant women, and nonpregnant adults. Whereas serotypes Ia, Ib, II, in, and V are most commonly ...associated with colonization and disease in the United States, strains of other serotypes have been isolated from patients in Japan. By use of an inhibition ELISA, the serotypes of 73 vaginal colonizing GBS strains isolated from healthy pregnant Japanese women were investigated. Twenty-six (35.6%) were type VIII, 18 (24.7%) were type VI, and the remaining 29 were distributed among more traditional serotypes. Strains were also tested by immunoblot for the presence of GBS surface proteins. Fifty-three (72.6%) of the 73 strains expressed one or more laddering GBS proteins. These data show that type VI and VIII GBS strains are common vaginal isolates in pregnant Japanese women and that one or more laddering proteins are present in most GBS strains.
Group B streptococcus (GBS) pili may enhance colonization and infection by mediating bacterial adhesion to host cells, invasion across endothelial and epithelial barriers, and resistance to bacterial ...ingestion and killing by host phagocytes. However, it remains unclear how pilus expression is regulated and how modulation of pilus production affects GBS interactions with the human host. We investigated the regulation and function of pilus island 1 (PI-1) pili in GBS strain 2603. We found that PI-1 gene expression was controlled by the CsrRS two-component system, by Ape1, an AraC-type regulator encoded by a divergently transcribed gene immediately upstream of PI-1, and by environmental pH. The response regulator CsrR repressed expression of Ape1, which is an activator of PI-1 gene expression. In addition, CsrR repressed PI-1 gene expression directly, independent of its regulation of Ape1. In vitro assays demonstrated specific binding of both CsrR and Ape1 to chromosomal DNA sequences upstream of PI-1. Pilus gene expression was activated by acidic pH, and this effect was independent of CsrRS and Ape1. Unexpectedly, characterization of PI-1 deletion mutants revealed that PI-1 pili do not mediate adhesion of strain 2603 to A549 respiratory epithelial cells, ME180 cervical cells, or VK2 vaginal cells in vitro. PI-1 pili reduced internalization and intracellular killing of GBS by human monocyte-derived macrophages, by approximately 50%, but did not influence complement-mediated opsonophagocytic killing by human neutrophils. These findings shed new light on the complex nature of pilus regulation and function in modulating GBS interactions with the human host.
The spectral energy distribution (SED) of galaxies is a complex function of the star formation history and geometrical arrangement of stars and gas in galaxies. The computation of the radiative ...transfer of stellar radiation through the dust distribution is time-consuming. This aspect becomes unacceptable in particular when dealing with the predictions by semi-analytical galaxy formation models populating cosmological volumes, to be then compared with multi-wavelength surveys. Mainly for this aim, we have implemented an artificial neural network (ANN) algorithm into the spectro-photometric and radiative transfer code grasil in order to compute the SED of galaxies in a short computing time. This allows to avoid the adoption of empirical templates that may have nothing to do with the mock galaxies output by models. The ANN has been implemented to compute the dust emission spectrum (the bottleneck of the computation), and separately for the star-forming molecular clouds (MC) and the diffuse dust (due to their different properties and dependencies). We have defined the input neurons effectively determining their emission, which means this implementation has a general applicability and is not linked to a particular galaxy formation model. We have trained the net for the disc and spherical geometries, and tested its performance to reproduce the SED of disc and starburst galaxies, as well as for a semi-analytical model for spheroidal galaxies. We have checked that for this model both the SEDs and the galaxy counts in the Herschel bands obtained with the ANN approximation are almost superimposed to the same quantities obtained with the full grasil. We conclude that this method appears robust and advantageous, and will present the application to a more complex SAM in another paper.
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