A Bayesian network model to predict the role of hospital noise, annoyance, and sensitivity in quality of patient care.

BACKGROUND: Hospital noise can adversely impact nurses' health, their cognitive function and emotion and in turn, influence the quality of patient care and patient safety. Thus, the aim of this study was to predict the contributing roles of exposure to hospital noise, staff noise-sensitivity and annoyance, on the quality of patient care. METHODS: This descriptive and cross-sectional study was carried out among nurses in an Iranian hospital. To determine nurses' noise exposure level, the noise was measured in 1510 locations across the hospital in accordance with ISO 9612 standards using KIMO DB 300/2 sound level meter and analyzer. An online survey was used to collect nurses' individual data. Study questionnaires included demographics, Weinstein noise sensitivity scale, noise annoyance scale, and quality of patient care scale. Finally, to analyze the data, Bayesian Networks (BNs), as probabilistic and graphical models, were used. RESULTS: For the high noise exposure state, high noise sensitivity, and high annoyance, with the probability of 100%, the probability of delivering a desirable quality of patient care decreased by 21, 14, and 23%, respectively. Moreover, at the concurrently high noise exposure and high noise sensitivity with the probability of 100%, the desirable quality of patient care decreased by 26%. The Bayesian most influence value was related to the association of noise exposure and annoyance (0.636). Moreover, annoyance had the highest association with the physical aspect of quality of care (0.400) and sensitivity had the greatest association with the communication aspect (0.283). CONCLUSION: Annoyance induced from environmental noise and personal sensitivity affected the quality of patient care adversely. Moreover, noise and sensitivity had a separate direct adverse effect upon the quality of patient care, and their co-occurrence reduced the potential for delivering quality patient care.

The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study.

Glioblastoma tumors are resistant to radiotherapy, and the need for drugs to induce radio-sensitization in tumor cells has always been a challenge. Besides, radiotherapy using targeted radionuclide would be effective even for resistant tumors. It has been shown topoisomerase I and poly (ADP-ribose) polymerase (PARP) enzymes have critical roles in the repair process of DNA injury in cells. Therefore, the inhibition of the activity of these enzymes can halt this process and result in the accumulation of damaged DNA in cells and the induction of cell death in tumors. In the present research, the impact of beta-particles of iodine-131 in combination with Topotecan (TPT), as the inhibitor of topoisomerase I, and A-966492, as the inhibitor of the PARP enzyme on the possible increase of radio-sensitivity of glioblastoma cells was assessed. For this purpose, a human glioblastoma cell line, U87MG, was cultured in flasks coated with Poly-Hema to achieve 300 µm-diameter spheroids. Then, nontoxic concentrations of A-966492 and TPT were applied in the cell culture media. The viability of the cells treated with iodine131 in combination with A-966492 and TPT was determined by the clonogenic assay. The expression rate of gamma-H2AX, as a biomarker of DNA double-strand breaks, was analyzed using immunofluorescence microscopy to unravel the effect of TPT, A-966492 (1 µM), and radiation on the cell death induction. The combination of each TPT or A-966492 with radiation resulted in the increased rate of cell death, and the ratios of sensitizer enhancement at 50% survival (SER50) were elevated by 1.45 and 1.25, respectively. Chemo- and radio-sensitization were promoted when iodine-131 was combined with A-966492 and TPT, with the SER50 of 1.68. Also, the expression of γ-H2AX was significantly increased in cells treated with A-966492 and TPT combined with radiation. The results demonstrated that iodine-131, in combination with A-966492 and TPT, had marked effects on radio-sensitizing and can be used as a targeted radionuclide for targeting radiotherapy in combination with topoisomerase I and PARP inhibitors to enhance radiotherapy in clinics.

Magnetic Targeting of Magneto-Plasmonic Nanoparticles and Their Effects on Temperature Profile of NIR Laser Irradiated to CT26 Tumor in BALB/C Mice.

BACKGROUND: Photothermal therapy (PTT) is a promising method in the field of cancer hyperthermia. In this method, interaction between laser light and photosensitizer material, such as plasmonic nanoparticles, leads into a localized heating. Recent efforts in the area of PTT aim to exploit targeting strategies for preferential accumulation of plasmonic nanoparticles within the tumor. OBJECTIVE: To investigate the impact of magneto-plasmonic (Au@Fe2O3) nanoparticles on temperature profile of CT26 tumor, bearing mice were irradiated by NIR laser. MATERIAL AND METHODS: In this in vivo study, Au@Fe2O3 NPs were injected intraperitoneally to Balb/c mice bearing CT26 colorectal tumor. Immediately after injection, a magnet (magnetic field strength of 0.4 Tesla) was placed on the tumor site for 6 hours in order to concentrate nanoparticles inside the tumor. In the next step, the tumors were exposed with NIR laser source (808 nm; 2 W/cm2; 5 min). RESULTS: Tumor temperature without magnetic targeting increased ~7 ± 0.9 °C after NIR irradiation, whereas the tumors in magnetic targeted group experienced a temperature rise of ~12 ± 1.4 °C. CONCLUSION: It is concluded that Au@Fe2O3 nanoparticle is a good candidate for therapeutic nanostructure in cancer photothermal therapy.

Cytogenetic damage from hyperthermia,6 MV X-rays, and topotecan in glioblastoma spheroids, simultaneously, and separately.

PURPOSE: Glioblastoma multiform (GBM) is one of the most common brain tumors. Surgery, radiation therapy, hyperthermia, and chemotherapy are the most common treatments for brain tumors such as GBM. This study investigated the cytogenetic damage caused by hyperthermia, radiation (6 MV-X-rays), and topotecan in glioma spheroids, simultaneously and separately. MATERIALS AND METHODS: Human glioblastoma cell line was cultured to form spheroids 350 µm in diameter that were arranged in eight groups and coded as follows: control, T: topotecan, H: hyperthermia, T + H: topotecan + hypertermia, X 1-10: X-ray with 1-10 fraction irradiation, H + X (1-10): hypertermia + X-ray with 1-10 fraction irradiation, T + X (1-10): topotecan + X-ray with 1-10 fraction irradiation, and H + T + X (1-10): hypertermia + topotecan + X-ray with 1-10 fraction irradiation. DNA damage was then evaluated using clonogenic assay. RESULTS: The effect of combined treatment with X + H + T was greater than the sum of the effects in other groups. In H + T + X group, failure to form colonies was observed in the seventh session. CONCLUSION: Use of X + H + T combination therapy significantly increased cell death and possibly improved the treatment. This suggests that the synergistic effect of different therapeutic methods increased cell death in glioblastoma tumor cells and reduced the necessary dose of radiation in the treatment of tumor in radiation therapy.

The combination of A-966492 and Topotecan for effective radiosensitization on glioblastoma spheroids.

Radiotherapy is one of the modalities in the treatment of glioblastoma patients, but glioma tumors are resistant to radiation and also chemotherapy drugs. Thus, researchers are investigating drugs which have radiosensitization capabilities in order to improve radiotherapy. PARP enzymes and topoisomerase I enzymes have a critical role in repairing DNA damage in tumor cells. Thus, inhibiting activity of these enzymes helps stop DNA damage repair and increase DSB lethal damages. In the current study, we investigated the combination of TPT as a topoisomerase I inhibitor, and A-966492 as a novel PARP inhibitor for further radiosensitization. U87MG cells (a human glioblastoma cell line) were cultured in Poly-Hema coated flasks to reach 300 µm-diameter spheroids. Treatments were accomplished by using non-toxic concentrations of A-966492 and Topotecan. The surviving fraction of treated cells was determined by clonogenic assay after treatment with drugs and 6 MV X-ray. The γ-H2AX expression was measured by an immunofluorescence staining method to examine the influence of A-966492, TPT and radiation on the induction of double stranded DNA breaks. Treatments using the A-966492 drug were conducted in concentration of 1 µM. Combining A-966492 and TPT with radiation yielded enhanced cell killing, as demonstrated by a sensitizer enhancement ratio at 50% survival (SER50) 1.39 and 1.16 respectively. Radio- and chemo-sensitization was further enhanced when A-966492 was combined with both X-ray and TPT, with SER50 of 1.53. Also γ-H2AX expression was higher in the group treated with a combination of drugs and radiation. A-966492 is an effective PARP inhibitor and has significant radio-sensitivity on U87MG spheroids. By accumulating cells in the S phase and by inhibiting the DNA damage repair, TPT enhanced radio-sensitivity. A-966492 combined with TPT as a topoisomerase I inhibitor had additive radio-sensitizing effects. As a result, applying PARP and topoisomerase I inhibitors can be a suitable strategy for improving radiotherapy in clinics.

Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer.

Because of their great scientific and technological potentials, iron oxide nanoparticles (IONPs) have been the focus of extensive investigations in biomedicine over the past decade. Additionally, the surface plasmon resonance effect of gold nanoparticles (AuNPs) makes them a good candidate for photothermal therapy applications. The unique properties of both IONPs (magnetic) and AuNPs (surface plasmon resonance) may lead to the development of a multi-modal nanoplatform to be used as a magnetic resonance imaging (MRI) contrast agent and as a nanoheater for photothermal therapy. Herein, core-shell gold-coated IONPs (Au@IONPs) were synthesized and investigated as an MRI contrast agent and as a light-responsive agent for cancer photothermal therapy.The synthesized Au@IONPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. The transverse relaxivity (r 2) of the Au@IONPs was measured using a 3-T clinical MRI scanner. Through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of the Au@IONs was examined on a KB cell line, derived from the epidermal carcinoma of a human mouth. Moreover, the photothermal effects of Au@IONPs in the presence of a laser beam (λ = 808 nm; 6.3 W/cm2; 5 min) were studied.The results show that the Au@IONPs are spherical with a hydrodynamic size of 33 nm. A transverse relaxivity of 95 mM-1 S-1 was measured for the synthesized Au@IONPs. It is evident from the MTT results that no significant cytotoxicity in KB cells occurs with Au@IONPs. Additionally, no significant cell damage induced by the laser is observed. Following the photothermal treatment using Au@IONPs, approximately 70% cell death is achieved. It is found that cell lethality depended strongly on incubation period and the Au@IONP concentration.The data highlight the potential of Au@IONPs as a dual-function MRI contrast agent and photosensitizer for cancer photothermal therapy.

Synergistic Effects of Arsenic Trioxide and Radiation: Triggering the Intrinsic Pathway of Apoptosis

Background: Arsenic trioxide (ATO) has been reported as an effective anti-cancer and a US Food and Drug Administration (FDA) approved drug for treatment of some cancers. The aim of this study was to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation (IR) in vitro in the glioblastoma multiforme (GBM) cell line, U87MG. Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and the expression analysis of Bax, Bcl-2, and caspase-3 genes, respectively. All treatments were performed on 100-µm diameter spheroids. Results: Results showed a significant reduction in the survival of the cells in all treated groups. As expected, cell survival was much less in combination treatment than treatment with only ATO. Moreover, combination therapy made Bax and caspase-3 up-regulated and Bcl-2 down-regulated. Conclusion: ATO and radiation had a synergistic apoptotic effect on GBM cells by up-regulation of caspase-3 and alteration of the Bax-Bcl-2 balance; therefore, ATO may act as a potential anti-cancer agent against GBM cells through triggering the mitochondrial pathway of apoptosis.

Hyperthermia: How Can It Be Used?

Hyperthermia (HT) is a method used to treat tumors by increasing the temperature of the cells. The treatment can be applied in combination with other verified cancer treatments using several different procedures. We sought to present an overview of the different HT tumor treatment, recent advances in the field, and combinational treatment sequences and outcomes. We used a computer-aided search to identify articles that contained the keywords hyperthermia, cancer treatment, chemotherapy, radiotherapy, nanoparticle, and cisplatin. There are three types of HT treatment, which each need the use of applicators that are in contact with or in the proximity of the patient for the purpose of heating. Heating can be achieved using different types of energy (including microwaves, radio waves, and ultrasound). However, the source of energy will depend on the cancer type and location. The temperature used will also vary. HT is rarely used alone, and can be combined with other cancer treatments. When used in combination with other treatments, improved survival rates have been observed. However, despite in vitro and in vivo studies that support the use of concurrent hypothermia treatments, contradictory results suggest there is a need for more studies to identify other hidden effects of HT.

Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan.

OBJECTIVE: To explore the cumulative genotoxic damage to glioblastoma (GBM) cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy, 22 Gy) with or without, 2- methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay. MATERIALS AND METHODS: The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided into five groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the following three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/ TPT. One specimen was used as the irradiated only sample (R). The last group was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study. RESULTS: R/TPT treated group had more DNA damage [double strand break (DSB)/single strand break (SSB)] compared with the untreated group (P<0.05). Moreover the R/ TPT group treated with 2ME2 followed by IUDR had maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/ß ratio based on biologically effective dose (BED) formulae. CONCLUSION: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPT- treated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB) and impairment of DNA repair machinery, more cell death will occur. This in turn may improve the treatment of GBM.

DNA damage of glioblastoma multiform cells induced by Beta radiation of iodine-131 in the presence or absence of topotecan: a picogreen and colonogenic assay.

OBJECTIVE: Glioblastoma multiforme (GBM), one of the most common and aggressive malignant brain tumors, is highly resistant to radiotherapy. Numerous approaches have been pursued to find new radiosensitizers. We used a picogreen and colonogenic assay to appraise the DNA damage and cell death in a spheroid culture of GBM cells caused by iodine-131 (I-131) beta radiation in the presence of topotecan (TPT). MATERIALS AND METHODS: U87MG cells were cultured as spheroids with approximate diameters of 300 µm. Cells were treated with beta radiation of I-131 (at a dose of 2 Gy) and/ or TPT (1 µg/ml for 2 hours). The numbers of cells that survived were compared with untreated cells using a colonogenic assay. In addition, we evaluated possible DNA damages by the picogreen method. The relation between DNA damage and cell death was assessed in the experimental study of groups. RESULTS: The findings showed that survival fraction (SF) in the I-131+TPT group (39%) was considerably less than the I-131 group (58.92%; p<0.05). The number of single strand breaks (SSB) and double strand breaks (DSB), in the DNA of U87MG cells treated with beta radiation of I-131 and TPT (I-131+TPT) significantly increased compared to cells treated with only I-131 or TPT (p<0.05). The amount of SSB repair was more than DSB repair (p<0.05). The relationship between cell death and DNA damage was close (r≥0.6) and significant (p<0.05) in the irradiated and treated groups. Also the maximum rate of DNA repair occurred 24 hours after the treatments. A significant difference was not observed on other days of the restoration. CONCLUSION: The findings in the present study indicated that TPT can sensitize U87MG cells to radiation and increase DNA damages. Potentially, TPT can cause an increase in damage from DSB and SSB by its inhibitory effects on topoisomerase enzyme and the cell cycle. The increased complex damages following the use of a genotoxic agent and beta I-131 radiation, causes a significant increase the cell death because of the difficult repair process. By assessing the relationship between DNA damage and cell death, the picogreen method can be useful in predicting colonogenic assay. Consequently, it is suggested that co-treatment with I-131 beta radiation and TPT can improve GBM treatment.