Dihydrophenazine: a multifunctional new weapon that kills multidrug-resistant Acinetobacter baumannii and restores carbapenem and oxidative stress susceptibilities.

AIMS: The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority. METHODS AND RESULTS: An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics. CONCLUSIONS: This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.

Hematological consequences of polyethylene microplastics toxicity in male rats: Oxidative stress, genetic, and epigenetic links.

Microplastics (MPs) pollution is a newly emerging environmental issue. MPs can accumulate within animals and humans, which can pose a serious health threat. Petroleum-based polyethylene (PE) is one of the most popular plastics. Accordingly, its exposure rates have steadily increased over the years. This study aimed to analyze the effects of PE-MPs on the hematological system of albino rats and the epigenetic effect. Five groups of adult male eight-weeks-old rats received either distilled water, corn oil, 3.75 mg/kg PE-MPs, 15 mg/kg PE-MPs, or 60 mg/kg of PE-MPs, daily by oral gavage for 35 days. PE-MPs significantly increased the body weights of the rats and lipid peroxidation, with concomitant reduction of superoxide dismutase activity and depletion of reduced glutathione, thus adversely affecting oxidants/antioxidants balance. Moreover, PE-MPs increased the % of abnormal RBCs, irregular cells, tear drop cells, Schistocyte cells, and folded cells. The genotoxic effects on DNA were evident by increased DNA damage, confirmed by the comet assay, in addition to increased DNA methylation. The effects of PE-MPs have been shown to be dose correlated. In conclusion, this study provides evidence of dose-related PE-MPs-induced hematological, genotoxic, and epigenetic effects in mammals, and thus emphasizes the potentially hazardous health effects of environmental PE-MPs.

Dosimetric evaluation study of IMRT and VMAT techniques for prostate cancer based on different multileaf collimator designs.

The hypofractionated radiotherapy modality was established to reduce treatment durations and enhance therapeutic efficiency, as compared to conventional fractionation treatment. However, this modality is challenging because of rigid dosimetric constraints. This study aimed to assess the impact of multi-leaf collimator (MLC) widths (10 mm and 5 mm) on plan quality during the treatment of prostate cancer. Additionally, this study aimed to investigate the impact of the MLC mode of energy on the Agility flattening filter (FF), MLC Agility-free flattening filter (FFF), and MLCi2 for patients receiving hypofractionated radiotherapy. Two radiotherapy techniques; Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), were used in this research. In the present study, computed tomography simulations of ten patients (six plans per patient) with localized prostate adenocarcinoma were analyzed. Various dosimetric parameters were assessed, including monitor units, treatment delivery times, conformity, and homogeneity indices. To evaluate the plan quality, dose-volume histograms (DVHs) were estimated for each technique. The results demonstrated that the determined dosimetric parameters of planning target volume (PTV)p (such as D mean, conformity, and homogeneity index) showed greater improvement with MLC Agility FF and MLC Agility FFF than with MLCi2. Additionally, the treatment delivery time was reduced in the MLC Agility FF (by 31%) and MLC Agility FFF (by 10.8%) groups compared to the MLCi2 group. It is concluded that for both the VMAT and IMRT techniques, the smaller width (5 mm) MLCs revealed better planning target volume coverage, improved the dosimetric parameters for PTV, reduced the treatment time, and met the constraints for OARs. It is therefore recommended to use 5 mm MLCs for hypofractionated prostate cancer treatment due to better target coverage and better protection of OARs.

Swallowing sparing intensity modulated radiotherapy versus standard parotid sparing intensity-modulated radiotherapy for treatment of head and neck cancer: a randomized clinical trial.

BACKGROUND: Dysphagia is a distressing symptom during and after radiotherapy treatment in head and neck cancer (HNC) patients. The objective of this prospective study was to investigate whether swallowing sparing intensity modulated radiotherapy (SW-IMRT) reduces the occurrence of swallowing dysfunction compared to the standard IMRT (ST-IMRT). METHODS: We randomized, planned, and treated patients with HNC who needed whole neck irradiation using the simultaneous integrated boost (SIB) IMRT technique. Doses of 70, 60, and 54 Gy (over 33 daily fractions) were prescribed to the primary tumor, high-risk and low-risk regions, respectively. The postoperative cases received 60 and 54 Gy (over 30 daily fractions) to the high-risk planning target volume (PTV) and low-risk PTV. We contoured organs at risk related to swallowing dysfunction (SWOARs) in all cases. In the ST-IMRT group, parotids only were spared. In the SW-IMRT group, parotids and SWOARs outside the high-risk PTV were spared. Assessment of dysphagia included clinical and instrumental evaluation. RESULTS: One hundred forty-six patients ended their radiotherapy treatment. Dose distribution showed comparable PTV coverage and no difference in parotid glands sparing between the two groups. SWOARs dose reduction with SW-IMRT differs according to tumor location and its overlap with SWOARs. Using different assessment methods, SW-IMRT was associated with a lower occurrence of dysphagia up to one year after treatment. There was no difference between the two groups regarding acute dysphagia (p = 0.262), overall survival (p = 0.811), and disease-free survival (p = 0.876). CONCLUSION: SW-IMRT is significantly better than ST-IMRT regarding a physician-rated and objective assessment of swallowing dysfunction at short- and long-term post-treatment follow-up.

Palliative spleen irradiation: can we standardize its technique?

PURPOSE: To explore the pattern of practice of palliative splenic irradiation (PSI) at the National Cancer Institute (NCI), Cairo University. PATIENTS AND METHODS: The medical records of patients referred for PSI during the time period from 1990 to 2005 were retrospectively reviewed. We compared the three most common planning techniques (two parallel opposing, single direct field, anterior and lateral fields). RESULTS: Eighteen patients who received PSI were identified. Thirteen patients were diagnosed as CML and 5 as CLL. The mean age of the patients was 44 (+/-16) years and the majority were men (60%). Spleen enlargement was documented in all cases. The single direct anterior field was the most commonly used technique. The dose per fraction ranged from 25 cGy to 100 cGy. The total dose ranged from 125 cGy to 1200 cGy and the median was 200 cGy (mean 327 cGy). There was no significant difference between CML and CLL patients regarding the dose level. Three out of 5 CLL patients and only one out of 13 CML patients received re-irradiation. All patients showed subjective improvement regarding pain and swelling. There was a significant increase in the hemoglobin level and a significant decrease in the WBC count. The single direct field shows variations in the dose from 56 to 102%; however, it is the simplest and the best regarding the dose to the surrounding normal tissues especially the kidney and the liver. CONCLUSION: PSI has a significant palliative benefit. Although the most widely accepted technique is the 2 parallel opposing anterior-posterior fields, single anterior field is also considered as a suitable option. Higher doses are needed for CLL patients compared to CML patients.