Spread of efflux pump overexpressing-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa by using an efflux pump inhibitor

Background: Fluoroquinolone resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression and/or target mutations. We designed this study to investigate the efflux pump mediated fluoroquinolone resistance and check the increasing effectiveness of fluoroquinolones in combination with an efflux pumps inhibitor among P. aeruginosa isolates from burn wounds infections. Materials and Methods: A total of 154 consecutive strains of P. aeruginosa were recovered from separate patients hospitalized in a burn hospital, Tehran, Iran. The isolates first were studied by disk diffusion antibiogram for 11 antibiotics and then minimum inhibitory concentration (MIC) experiments were performed to detect synergy between ciprofloxacin and the efflux pump inhibitor, carbonyl cyanide-m-chlorophenyl hydrazone (CCCP). Then to elucidate the inducing of multi drug resistance due to different efflux pumps activation in Fluoroquinolone resistant isolates, synergy experiments were also performed in random ciprofloxacin resistant isolates which have overexpressed efflux pumps phenotypically, using CCCP and selected antibiotics as markers for Beta-lactams and Aminoglycosides. The isolates were also tested by polymerase chain reaction (PCR) for the presence of the MexA, MexC and MexE, which encode the efflux pumps MexAB-OprM, MexCD-OprJ and MexEF-OprN. Results: Most of the isolates were resistant to 3 or more antibiotics tested. More than half of the ciprofloxacin resistant isolates exhibited synergy between ciprofloxacin and CCCP, indicating the efflux pump activity contributed to the ciprofloxacin resistance. Also increased susceptibility of random ciprofloxacin resistant isolates of P. aeruginosa to other selected antibiotics, in presence of CCCP, implied multidrug extrusion by different active efflux pump in fluoroquinolones resistant strains. All of Ciprofloxacin resistant isolates were positive for MexA, MexC and MexE genes simultaneously. Conclusion: In this burn hospital, where multidrug resistant P. aeruginosa isolates were prevalent, ciprofloxacin resistance and multidrug resistance due to the overexpression of fluoroquinolones mediated efflux pumps has also now emerged. Early recognition of this resistance mechanism should allow the use of alternative antibiotics and use an efflux pumps inhibitor in combination with antibiotic therapy. © 2015 by The Korean Society of Infectious Diseases

The organizational culture of Iran University of Medical Sciences from the viewpoint of faculty members

Background: It has been widely acknowledged that change and constant modification is the key to survive for any organization among their rivals. Since success in implementing changes in the organization strongly depends on the organizational culture, this study aims to assess the organizational culture in Iran University of Medical Sciences. The results of this study can be beneficial in initiating a movement towards the third - and fourth generation of universities. Methods: This study is descriptive-correlational. The Organizational Culture Assessment Instrument (OCAI) was employed to collect data. A questionnaire was sent to the faculty members via email, and the responses were collected and analyzed. Results: Out of the 982 faculty members, 189 participated (20.7) in this study. Analysis showed that the organizational culture of the university is congruent and harmonious and in the current state, it is primarily hierarchical (31) and market-oriented (28) with emphasis on stability and control in the organization. Whereas, faculty members tend to move the organizational culture of the university towards adhocracy (30) and clan culture (29). Conclusion: University administrators must strengthen the culture of innovation and creativity based on the needs of the market. This only can be achieved by supporting teamwork in their move towards desired change. © Iran University of Medical Sciences

Coordinated airborne studies in the tropics (CAST)

This is the final version of the article. It first appeared from the American Meteorological Society via http://dx.doi.org/10.1175/BAMS-D-14-00290.1Abstract The main field activities of the Coordinated Airborne Studies in the Tropics (CAST) campaign took place in the west Pacific during January–February 2014. The field campaign was based in Guam (13.5°N, 144.8°E), using the U.K. Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 atmospheric research aircraft, and was coordinated with the Airborne Tropical Tropopause Experiment (ATTREX) project with an unmanned Global Hawk and the Convective Transport of Active Species in the Tropics (CONTRAST) campaign with a Gulfstream V aircraft. Together, the three aircraft were able to make detailed measurements of atmospheric structure and composition from the ocean surface to 20 km. These measurements are providing new information about the processes influencing halogen and ozone levels in the tropical west Pacific, as well as the importance of trace-gas transport in convection for the upper troposphere and stratosphere. The FAAM aircraft made a total of 25 flights in the region between 1°S and 14°N and 130° and 155°E. It was used to sample at altitudes below 8 km, with much of the time spent in the marine boundary layer. It measured a range of chemical species and sampled extensively within the region of main inflow into the strong west Pacific convection. The CAST team also made ground-based measurements of a number of species (including daily ozonesondes) at the Atmospheric Radiation Measurement Program site on Manus Island, Papua New Guinea (2.1°S, 147.4°E). This article presents an overview of the CAST project, focusing on the design and operation of the west Pacific experiment. It additionally discusses some new developments in CAST, including flights of new instruments on board the Global Hawk in February–March 2015.CAST is funded by NERC and STFC, with grant NE/ I030054/1 (lead award), NE/J006262/1, NE/J006238/1, NE/J006181/1, NE/J006211/1, NE/J006061/1, NE/J006157/1, NE/J006203/1, NE/J00619X/1, and NE/J006173/1. N. R. P. Harris was supported by a NERC Advanced Research Fellowship (NE/G014655/1). P. I. Palmer acknowledges his Royal Society Wolfson Research Merit Award. The BAe-146-301 Atmospheric Research Aircraft is flown by Directflight Ltd and managed by the Facility for Airborne Atmospheric Measurements, which is a joint entity of the Natural Environment Research Council and the Met Office. The authors thank the staff at FAAM, Directflight and Avalon Aero who worked so hard toward the success of the aircraft deployment in Guam, especially for their untiring efforts when spending an unforeseen 9 days in Chuuk. We thank the local staff at Chuuk and Palau, as well as the authorities in the Federated States of Micronesia for their help in facilitating our research flights. Special thanks go to the personnel associated with the ARM facility at Manus, Papua New Guinea without whose help the ground-based measurements would not have been possible. Thanks to the British Atmospheric Data Centre (BADC) for hosting our data and the NCAS Atmospheric Measurement Facility for providing the radiosonde and ground-based ozone equipment. Chlorophyll-a data used in Figure 1 were extracted using the Giovanni online data system, maintained by the NASA GES DISC. We acknowledge the MODIS mission scientists and associated NASA personnel for the production of this data set. Finally we thank many individuals associated with the ATTREX and CONTRAST campaigns for their help in the logistical planning, and we would like to single out Jim Bresch for his excellent and freely provided meteorological advice

Co-ordinated Airborne Studies in the Tropics (CAST)

This is the author accepted manuscript. The final version is available from the American Meteorological Society via http://dx.doi.org/10.1175/BAMS-D-14-00290.1The Co-ordinated Airborne Studies in the Tropics (CAST) project is studying the chemical composition of the atmosphere in the Tropical Warm Pool region to improve understanding of trace gas transport in convection. The main field activities of the CAST (Co-ordinated Airborne Studies in the Tropics) campaign took place in the West Pacific in January/February 2014. The field campaign was based in Guam (13.5°N, 144.8°E) using the UK FAAM BAe-146 atmospheric research aircraft and was coordinated with the ATTREX project with the unmanned Global Hawk and the CONTRAST campaign with the Gulfstream V aircraft. Together, the three aircraft were able to make detailed measurements of atmospheric structure and composition from the ocean surface to 20 km. These measurements are providing new information about the processes influencing halogen and ozone levels in the tropical West Pacific as well as the importance of trace gas transport in convection for the upper troposphere and stratosphere. The FAAM aircraft made a total of 25 flights between 1°S-14°N and 130°-155°E. It was used to sample at altitudes below 8 km with much of the time spent in the marine boundary layer. It measured a range of chemical species, and sampled extensively within the region of main inflow into the strong West Pacific convection. The CAST team also made ground-based measurements of a number of species (including daily ozonesondes) at the Atmospheric Radiation Measurement program site on Manus Island, Papua New Guinea (2.1°S, 147.4°E). This article presents an overview of the CAST project focussing on the design and operation of the West Pacific experiment. It additionally discusses some new developments in CAST, including flights of new instruments on the Global Hawk in February/March 2015.CAST is funded by NERC and STFC, with grant NE/ I030054/1 (lead award), NE/J006262/1, NE/J006238/1, NE/J006181/1, NE/J006211/1, NE/J006061/1, NE/J006157/1, NE/J006203/1, NE/J00619X/1, and NE/J006173/1. N. R. P. Harris was supported by a NERC Advanced Research Fellowship (NE/G014655/1). P. I. Palmer acknowledges his Royal Society Wolfson Research Merit Award. The BAe-146-301 Atmospheric Research Aircraft is flown by Directflight Ltd and managed by the Facility for Airborne Atmospheric Measurements, which is a joint entity of the Natural Environment Research Council and the Met Office. The authors thank the staff at FAAM, Directflight and Avalon Aero who worked so hard toward the success of the aircraft deployment in Guam, especially for their untiring efforts when spending an unforeseen 9 days in Chuuk. We thank the local staff at Chuuk and Palau, as well as the authorities in the Federated States of Micronesia for their help in facilitating our research flights. Special thanks go to the personnel associated with the ARM facility at Manus, Papua New Guinea without whose help the ground-based measurements would not have been possible. Thanks to the British Atmospheric Data Centre (BADC) for hosting our data and the NCAS Atmospheric Measurement Facility for providing the radiosonde and ground-based ozone equipment. Chlorophyll-a data used in Figure 1 were extracted using the Giovanni online data system, maintained by the NASA GES DISC. We also acknowledge the MODIS mission scientists and associated NASA personnel for the production of this data set. Finally we thank many individual associated with the ATTREX and CONTRAST campaigns for their help in the logistical planning, and we would like to single out Jim Bresch for his excellent and freely provided meteorological advice

Potential controls of isoprene in the surface ocean

Isoprene surface ocean concentrations and vertical distribution, atmospheric mixing ratios, and calculated sea-to-air fluxes spanning approximately 125° of latitude (80°N–45°S) over the Arctic and Atlantic Oceans are reported. Oceanic isoprene concentrations were associated with a number of concurrently monitored biological variables including chlorophyll a (Chl a), photoprotective pigments, integrated primary production (intPP), and cyanobacterial cell counts, with higher isoprene concentrations relative to all respective variables found at sea surface temperatures greater than 20°C. The correlation between isoprene and the sum of photoprotective carotenoids, which is reported here for the first time, was the most consistent across all cruises. Parameterizations based on linear regression analyses of these relationships perform well for Arctic and Atlantic data, producing a better fit to observations than an existing Chl a-based parameterization. Global extrapolation of isoprene surface water concentrations using satellite-derived Chl a and intPP reproduced general trends in the in situ data and absolute values within a factor of 2 between 60% and 85%, depending on the data set and algorithm used

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis

Background: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. Methods: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18�40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. Results: Vitamin D supplementation significantly decreased pelvic pain (β � 1.12; 95 CI, �2.1, �0.09; p=.03) and total-/HDL-cholesterol ratio (β � 0.29; 95 CI, �0.57, �0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (β � 0.64 mg/L; 95 CI, �0.97, �0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (β 47.54 mmol/L; 95 CI, 19.98, 75.11; p=.001) compared with the placebo. Conclusions: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles. © 2021 Informa UK Limited, trading as Taylor & Francis Group

MicroRNA Expression and Correlation with mRNA Levels of Colorectal Cancer-Related Genes

Introduction: MicroRNAs (miRNAs), as a family of non-coding RNAs, have opened a new window in cancer biology and transcriptome. It has been revealed that miRNAs post-transcriptionally regulate the gene expression and involve in colorectal cancer (CRC) development and progression. Our aim was to examine the differential expression of miRNAs in a CRC and to correlate their expression levels with mRNA levels of CRC-related genes (K-ras, APC, p53). Materials and Methods: Seventy-two colorectal tumor tissues from patients with newly diagnosed CRC and 72 matched normal adjacent tissues were analyzed. Relative expression of seven CRC-related miRNAs (miR-21, miR-31, miR-20a, miR-133b, and miR-145, miR-135b and let-7g) and three CRC-related genes (K-ras, APC, p53) was detected using the SYBR Green quantitative real-time PCR technique. The correlation between gene expression levels and clinicopathological features was evaluated. Results: Our results showed a significant difference between the two groups for the expression level of miR-21, miR-31, miR-145, and miR-20a (P &lt; 0.001). Also, a significant difference between the two groups for the expression level of K-ras was found (P &lt; 0.001). Further analysis revealed an inverse significant correlation between miR-145 and K-ras (R 2 = 0.662, P &lt; 0.001), while a positive correlation was observed between miR-21 and K-ras (R 2 = 0.732, P &lt; 0.001). Conclusion: Dysregulation of miRNAs and correlation with molecular signaling pathways designated a biological role for miRNAs in various cellular mechanisms underlying CRC. On the other hand, the pattern of miRNAs expression and its correlation with transcriptional status are helpful to discovery biomarkers and design therapeutics for CRC. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

MicroRNA Expression and Correlation with mRNA Levels of Colorectal Cancer-Related Genes

Introduction: MicroRNAs (miRNAs), as a family of non-coding RNAs, have opened a new window in cancer biology and transcriptome. It has been revealed that miRNAs post-transcriptionally regulate the gene expression and involve in colorectal cancer (CRC) development and progression. Our aim was to examine the differential expression of miRNAs in a CRC and to correlate their expression levels with mRNA levels of CRC-related genes (K-ras, APC, p53). Materials and Methods: Seventy-two colorectal tumor tissues from patients with newly diagnosed CRC and 72 matched normal adjacent tissues were analyzed. Relative expression of seven CRC-related miRNAs (miR-21, miR-31, miR-20a, miR-133b, and miR-145, miR-135b and let-7g) and three CRC-related genes (K-ras, APC, p53) was detected using the SYBR Green quantitative real-time PCR technique. The correlation between gene expression levels and clinicopathological features was evaluated. Results: Our results showed a significant difference between the two groups for the expression level of miR-21, miR-31, miR-145, and miR-20a (P &lt; 0.001). Also, a significant difference between the two groups for the expression level of K-ras was found (P &lt; 0.001). Further analysis revealed an inverse significant correlation between miR-145 and K-ras (R2 = 0.662, P &lt; 0.001), while a positive correlation was observed between miR-21 and K-ras (R2 = 0.732, P &lt; 0.001). Conclusion: Dysregulation of miRNAs and correlation with molecular signaling pathways designated a biological role for miRNAs in various cellular mechanisms underlying CRC. On the other hand, the pattern of miRNAs expression and its correlation with transcriptional status are helpful to discovery biomarkers and design therapeutics for CRC. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Profiling of novel circulating microRNAs as a non-invasive biomarker in diagnosis and follow-up of high and low-grade gliomas

Objective: Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system (CNS). Despite the progress in therapeutic strategies such as surgical techniques, radiotherapy, chemotherapy, and targeted therapy, prognosis and therapeutically convenient monitoring tools in patients with GBM has not improved significantly up to now.Therefore, exosomal miRNAs as novel non-invasive biomarkers having high sensitivity and specificity are required to improve diagnosis and to develop new targeted therapy strategies for GBM patients. The aim of the present study was to investigate a novel miRNA signature as a predictive biomarker for diagnosis and measurement of response to therapeutic interventions in plasma of GBM patients versus traumatic brain injury and diffuse low-grade astrocytoma (LGA) patients. Patients and methods: Plasma exosomal-microRNAs were isolated from GBM (n = 25), LGA (n = 25), and head trauma patients (n = 15) as non-glioma control from March 2017 to June 2018 in Department of Neurosurgery at Rasoul-e-Akram Hospital. Through a bioinformatics analysis, we used Miranda, TargetScan, mirBase, DIANA-microT-CDS, and KEGG database as well as microarray data analysis from GEO for microRNA candidates. Finally, miR-210, miR-185, miR-5194, and miR-449 were selected among those miRNAs because they were recorded to target the maximum number of genes in EGFR and c-MET signaling pathways. Then, exosomal microRNAs were extracted from plasma of patients and quantitated by locked nucleic acid real-time PCR in GBM, LGA, and trauma patients. Results: This result is the first report on the role of circulating miR-185, miR-449, and miR-5194 in GBM compared to LGA and trauma. The plasma expression of miR-210 as an oncogenic miR was upregulated in GBM and LGA groups (P < 0.0001). Otherwise, miR-185, miR-5194, and miR-449 were significantly downregulated (P � 0.05) in GBM and LGA compared to trauma patients. There was no significant downregulation in the expression of miR-185 between GBM and LGA, while the expression of miR-5194 (P � 0.05) and miR-449 (P � 0.05) was significantly decreased in GBM patients compared with LGA. Conclusions: These results indicate that the levels of miR-210, miR-449, and miR-5194 are a promising diagnostic and prognostic biomarker positively correlated with histopathological grade and invasiveness of GBM. These findings imply that circulating microRNA can be potentially used as novel biomarkers for glioma that might be beneficial in clinical management of glioma patients. © 2019 Elsevier B.V

MicroRNA Expression Levels and Histopathological Features of Colorectal Cancer

Introduction: Non-coding RNAs have opened a new window in cancer biology. MicroRNAs (miRNAs), as a family of non-coding RNAs, play an important role in the gene regulation. The aberrant expression of these small molecules has been documented to involve in colorectal cancer (CRC) pathogenesis. This study aimed to examine the expression of miRNAs in CRC and to correlate their expression levels with histological markers (Ki-67 and CD34). Materials and Methods: Tumor tissues and matched normal adjacent tissues were collected from 36 patients with newly diagnosed CRC. Immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. A polyadenylation SYBER Green quantitative real-time PCR technique was used to quantify the expression of a panel of five CRC-related miRNAs (hsa-miR-21, 31, 20a, 133b, and 145). Histopathological (H) scores and miRNA expression levels were correlated with clinicopathological features including the degree of differentiation, staging, and lymphovascular invasion. Results: Our results showed the significant difference between the two groups for the expression level of hsa-miR-21, hsa-miR-31, hsa-miR-145, and miR-20a (P < 0.001), but not for hsa-miR-133b (P = 0.57). Further analysis revealed an inverse significant correlation between hsa-miR-145 and Ki-67 (r = � 0.942, P < 0.001). While a positive correlation was observed between hsa-miR-21 and Ki-67 (r = 0.920, P < 0.001), and hsa-miR-21 and CD34 (r = 0.981, P < 0.001). Also, a positive correlation between hsa-miR-31 and Ki-67 (r = 0.913, P < 0.001), hsa-miR-31 and CD34 (r = 0.798, P < 0.05), hsa-miR-20a and Ki-67 (r = 0.871, P < 0.001), and hsa-miR-20a and CD34 (r = 0.890, P < 0.001) was found. Conclusion: Dysregulation of miRNAs and correlation with molecular histopathology indicate a biological role for miRNAs in various cellular processes including cell proliferation and angiogenesis in CRC development. On the other hand, the pattern of miRNA expression and its correlation with histological markers are potentially valuable to apply as diagnostic biomarkers for CRC. © 2018, Springer Science+Business Media, LLC, part of Springer Nature