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1.
Gynecol Oncol Rep ; 55: 101499, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39308902

ABSTRACT

Climate change is a complex, global issue that is impacting human health in various ways, with healthcare being a significant contributor to carbon emissions in the United States. This review discusses the environmental impact of important aspects of gynecologic oncology care, including surgery, anesthesia care, radiology, chemotherapy, and radiation oncology. Operating room energy and material use is highlighted, with a focus on the environmental impact of robotic surgery. The contribution of certain anesthetic gases in increasing greenhouse gas emissions is addressed. Additionally, the environmental impacts of radiologic imaging, chemotherapy, and radiation oncology are also discussed. Despite the complexity of climate change, there are multiple strategies on the individual and institutional level that can help mitigate the environmental impact of gynecologic oncology care. Individual efforts include practicing red bag stewardship, limiting single use-supplies, decreasing the use of potentially deleterious anesthetics, and supporting research into alternative dosing for chemotherapy and radiation which requires less patient travel. Institutional strategies include investing in efficient HVAC systems, utilizing reusable and reprocessed materials and devices, and purchasing renewable energy sources. Both individuals and institutions can advocate with industry and government at all levels for practices and policies that support lower carbon emissions. By recognizing our role in reducing carbon emissions, we can work towards improving the well-being of our patients and the larger community.

2.
Cureus ; 16(6): e63076, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39055446

ABSTRACT

The morphological variations in roots and root canals vary greatly in multi-rooted teeth making it a challenge for accurate diagnosis and effective endodontic therapy. In addition to using technology appropriately, this article highlights how important it is to have a complete understanding of root canal morphology. With the assistance of cone-beam computed tomography (CBCT) images and a dental operating microscope (DOM), successful endodontic treatment was performed on a single-rooted maxillary first molar with Vertucci's type II canal configuration. CBCT and DOM proved to be valuable tools for the effective diagnosis and management of this atypical morphology.

3.
Abdom Radiol (NY) ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954003

ABSTRACT

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management.

4.
Abdom Radiol (NY) ; 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39066812

ABSTRACT

Penile MRI is a vital yet underutilized diagnostic tool that provides detailed information crucial for managing various penile pathologies. Due to its infrequent use, many radiology trainees lack confidence in interpreting these exams. This article reviews the anatomy, key technical considerations, and interpretive pearls for penile trauma, Peyronie's disease, priapism, penile neoplasms, prosthesis evaluation, and a few miscellaneous conditions. Through illustrative case examples, this review aims to enhance the understanding and proficiency of radiologists in performing and interpreting penile MRI in these clinical scenarios.

5.
Protein Sci ; 33(3): e4912, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38358254

ABSTRACT

Outer membrane proteins perform essential functions in uptake and secretion processes in bacteria. MspA is an octameric channel protein in the outer membrane of Mycobacterium smegmatis and is structurally distinct from any other known outer membrane protein. MspA is the founding member of a family with more than 3000 homologs and is one of the most widely used proteins in nanotechnological applications due to its advantageous pore structure and extraordinary stability. While a conserved C-terminal signal sequence is essential for folding and protein assembly in the outer membrane of Gram-negative bacteria, the molecular determinants of these processes are unknown for MspA. In this study, we show that mutation and deletion of methionine 183 in the highly conserved C-terminus of MspA and mutation of the conserved tryptophan 40 lead to a complete loss of protein in heat extracts of M. smegmatis. Swapping these residues partially restores the heat stability of MspA indicating that methionine 183 and tryptophan 40 form a conserved sulfur-π electron interaction, which stabilizes the MspA monomer. Flow cytometry showed that all MspA mutants are surface-accessible demonstrating that oligomerization and membrane integration in M. smegmatis are not affected. Thus, the conserved C-terminus of MspA is essential for its thermal stability, but it is not required for protein assembly in its native membrane, indicating that this process is mediated by a mechanism distinct from that in Gram-negative bacteria. These findings will benefit the rational design of MspA-like pores to tailor their properties in current and future applications.


Subject(s)
Mycobacterium , Tryptophan , Tryptophan/metabolism , Porins/chemistry , Porins/genetics , Porins/metabolism , Mycobacterium smegmatis/genetics , Mycobacterium smegmatis/metabolism , Methionine/metabolism
6.
Ann Surg Oncol ; 31(2): 1252-1263, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38006531

ABSTRACT

BACKGROUND: Discontinuation of the Codman 3000 pump in 2018 left no Food and Drug Administration (FDA)-approved hepatic artery infusion (HAI) device for unresectable colorectal liver metastases (uCLM) and intrahepatic cholangiocarcinoma (uIHC). Historically, HAI has been performed at academic medical centers in large metropolitan areas, which are often inaccessible to rural patients. Consequently, feasibility of dissemination of HAI to rural populations is unknown. PATIENTS AND METHODS: Under an FDA investigational device exemption, we opened the only HAI program in Kentucky and enrolled patients with uCLM and uIHC in a phase I clinical trial. The trial examined the safety of the hybrid Codman catheter/Medtronic SynchroMed II pump (hCMP) combination, defined as successful completion of one cycle of HAI chemotherapy. Rural feasibility was assessed by number of missed pump fills appointments. RESULTS: A total of 21 patients (n = 17 uCLM, n = 4 uIHC) underwent hCMP implantation before accrual was stopped early owing to FDA approval of the Intera 3000 pump. 20/21 (95%) patients met the primary safety endpoint. Serious adverse events (AEs) included a grade 5 coronavirus disease 2019 (COVID-19) infection (n = 1) and a grade 3 catheter erosion into the bowel (n = 1). Biliary sclerosis developed in two patients (9.5%). Median distance to infusion center was 47.6 miles (2-138 miles), and 62% were from Appalachia, yet there were no missed pump fill appointments. The 2-year overall survival was 82.4% (uCLM) and 50% (uIHC). CONCLUSIONS: The hCMP device had an acceptable safety profile. Despite the complexity of starting a new HAI program, early results showed feasibility for HAI delivery in a rural catchment area and comparable outcomes to larger urban-based HAI centers.


Subject(s)
Bile Duct Neoplasms , Colorectal Neoplasms , Liver Neoplasms , Vascular Access Devices , Humans , Colorectal Neoplasms/pathology , Hepatic Artery/pathology , Feasibility Studies , Antineoplastic Combined Chemotherapy Protocols , Liver Neoplasms/secondary , Infusions, Intra-Arterial , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/etiology
8.
MethodsX ; 11: 102344, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37711139

ABSTRACT

Bacterial populations in the in vitro laboratory cultures, environment, and patients contain metabolically different subpopulations that respond differently to stress agents, including antibiotics, and emerge as stress tolerant or resistant strains. To contain the emergence of such strains, it is important to study the features of the metabolic status and response of the subpopulations to stress agents. For this purpose, an efficient method is required for the fractionation and isolation of the subpopulations from the cultures. Here we describe in detail the manual setting up of a simple, easy-to-do, reproducibly robust Percoll discontinuous density gradient centrifugation for the fractionation of subpopulations of short-sized cells (SCs) and normal/long-sized cells (NCs) from Mycobacterium smegmatis and Mycobacterium tuberculosis cultures, which we had reported earlier. About 90-98% enrichment was obtained respectively for SCs and NCs for M. smegmatis and 69-67% enrichment was obtained respectively for the SCs and NCs for M. tuberculosis.•The Percoll discontinuous density gradient centrifugation helps the fractionation and isolation of mycobacterial subpopulations that differ in density.•The method offers a consistently reproducible high enrichment of the subpopulations of SCs and NCs from the in vitro cultures of M. smegmatis and M. tuberculosis.•Our earlier reports on the consistency in the differential response of the subpopulations, enriched using the method, to oxidative, nitrite, and antibiotic stress proves its validity.

9.
Clin Imaging ; 100: 7-9, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37120923

ABSTRACT

The Kissing ovaries sign is a radiological sign seen in women with deep pelvic endometriosis. It refers to abutment of the ovaries within the cul-de-sac. The term kissing ovaries was first described by Ghezzi et al. (2005) and has been since used widely. When seen on imaging it indicates moderate to severe endometriosis with the ovaries tethered within abnormal pelvic soft tissue, which may warrant surgical management.


Subject(s)
Endometriosis , Ovary , Female , Humans , Ovary/diagnostic imaging , Endometriosis/diagnostic imaging , Douglas' Pouch/surgery , Pelvis
10.
Abdom Radiol (NY) ; 48(4): 1237-1245, 2023 04.
Article in English | MEDLINE | ID: mdl-36809560

ABSTRACT

PURPOSE: The authors sought to test if there was a difference in key pelvic floor measurements obtained during MR defecography at-rest, i.e., H-line, M-line and anorectal angle (ARA), before and after rectal gel administration. The authors also sought to determine if any observed differences would affect the interpretation of the defecography studies. METHODS: Institutional Review Board approval was obtained. An abdominal fellow retrospectively reviewed the images of all patients who underwent MRI defecography at our institution from January 2018 through June 2021. The H-line, M-line and ARA values were remeasured on T2-weighted sagittal images, with and without rectal gel for each patient. RESULTS: One hundred and eleven (111) studies were included in the analysis. 18% (N = 20) of patients satisfied the criterion for pelvic floor widening before gel administration based on H-line measurement. This increased to 27% (N = 30) after rectal gel (p = 0.08). 14.4% (N = 16) met the M-line measurement criterion for pelvic floor descent before gel administration. This increased to 38.7% after rectal gel (N = 43) (p < 0.001). 67.6% (N = 75) demonstrated an abnormal ARA prior to administration of rectal gel. This decreased to 58.6% (N = 65) after rectal gel administration (p = 0.07). The overall reporting discrepancies incurred by the presence or absence of rectal gel were 16.2%, 29.7% and 23.4% for H-line, M-line and ARA, respectively. CONCLUSION: The instillation of gel during MR defecography can cause significant changes to the observed pelvic floor measurements at-rest. This in turn can influence the interpretation of defecography studies.


Subject(s)
Defecography , Pelvic Floor , Humans , Defecography/methods , Retrospective Studies , Pelvic Floor/diagnostic imaging , Magnetic Resonance Imaging/methods
11.
Br J Soc Psychol ; 62(1): 393-413, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35751463

ABSTRACT

Social psychological research on collective victimhood has often focused on comparisons between the ingroup's and outgroups' collective victimization (i.e. comparative victim beliefs such as competitive victimhood or inclusive victim beliefs). This qualitative study examines how people in different contexts of collective victimization and its aftermath make sense of items commonly used to assess comparative victim beliefs, and how they extend or challenge these constructs and their underlying assumptions. We used thematic analysis to analyse eight focus group discussions among four minority groups in the United States with historical or more recent experiences of collective victimization (Armenian Americans, Burundian refugees, Jewish Americans and Nepali-speaking Bhutanese refugees). Findings extend commonly assessed comparative victim beliefs and reveal participants' critical perspectives on these constructs. The findings also highlight the dialectical structure of collective victim beliefs: Participants not only endorsed but also rejected comparative victim beliefs, and relatedly described both ingroup power and outgroup power in the context of their group's victimization. These findings extend existing social psychological literature on comparative victim beliefs and intergroup relations.


Subject(s)
Crime Victims , Group Processes , Humans , United States , Bhutan , Social Identification , Jews/psychology , Crime Victims/psychology
12.
Abdom Radiol (NY) ; 48(1): 136-150, 2023 01.
Article in English | MEDLINE | ID: mdl-36063181

ABSTRACT

Primary sclerosing cholangitis is a rare chronic inflammatory disease affecting the bile ducts, which can eventually result in bile duct strictures, cholestasis and cirrhosis. Patients are often asymptomatic but may present with clinical features of cholestasis. Imaging plays an important role in the diagnosis and management. This review covers the pathophysiology, clinical features, imaging findings as well as methods of surveillance and post-transplant appearance.


Subject(s)
Cholangitis, Sclerosing , Cholestasis , Humans , Cholangitis, Sclerosing/diagnostic imaging , Cholangitis, Sclerosing/pathology , Bile Ducts/pathology , Cholestasis/diagnostic imaging , Cholestasis/pathology , Liver Cirrhosis/pathology , Radiologists
13.
Abdom Radiol (NY) ; 48(1): 166-185, 2023 01.
Article in English | MEDLINE | ID: mdl-36289069

ABSTRACT

Liver transplantation is a potentially curative treatment for patients with acute liver failure, end-stage liver disease, and primary hepatic malignancy. Despite tremendous advancements in surgical techniques and immunosuppressive management, there remains a high rate of post-transplant complications, with one of the main complications being biliary complications. In addition to anastomotic leak and stricture, numerous additional biliary complications are encountered, including ischemic cholangiopathy due to the sole arterial supply of the bile ducts, recurrence of primary biliary disease, infections, biliary obstruction from stones, cast, or hemobilia, and less commonly cystic duct remnant mucocele, vanishing duct syndrome, duct discrepancy and kinking, post-transplant lymphoproliferative disorder, retained stent, and ampullary dysfunction. This article presents an overview of biliary anatomy and surgical techniques in liver transplantation, followed by a detailed review of post-transplant biliary complications with their corresponding imaging findings on multiple modalities with emphasis on magnetic resonance imaging and MR cholangiopancreatography.


Subject(s)
Biliary Tract , Cholestasis , Liver Transplantation , Postoperative Complications , Humans , Bile Ducts/pathology , Biliary Tract/blood supply , Biliary Tract/diagnostic imaging , Cholestasis/surgery , Liver , Liver Transplantation/adverse effects , Postoperative Complications/pathology , Cholangiopancreatography, Magnetic Resonance
14.
Bioinformation ; 19(13): 1312-1317, 2023.
Article in English | MEDLINE | ID: mdl-38415039

ABSTRACT

Evaluation and comparison of natural products like triphala, eucalyptus and carvacol with conventional root canal irrigant such as sodium hypochlorite (NaOCL) and Chlorhexidine against persistent root canal pathogens like E. faecalis is of interest. Samples were taken both before irrigation as well as after irrigation. CFU was counted after the plates had been incubated overnight at temperature of 37°C overnight. The herbal products showed antibacterial effectiveness against persistent root canal pathogens like E. faecalis. The antibacterial effectiveness was high in NaOCL, chlorhexidine and eucalyptus extract.

15.
Front Microbiol ; 13: 920117, 2022.
Article in English | MEDLINE | ID: mdl-36338044

ABSTRACT

Bacteria regulate FtsZ protein levels through transcriptional and translational mechanisms for proper cell division. A cis-antisense RNA, StfZ, produced from the ftsA-ftsZ intergenic region, was proposed to regulate FtsZ level in Escherichia coli. However, its structural identity remained unknown. In this study, we determined the complete sequence of StfZ and identified the isoforms and its promoters. We find that under native physiological conditions, StfZ is expressed at a 1:6 ratio of StfZ:ftsZ mRNA at all growth phases from three promoters as three isoforms of 366, 474, and 552 nt RNAs. Overexpression of StfZ reduces FtsZ protein level, increases cell length, and blocks cell division without affecting the ftsZ mRNA stability. We did not find differential expression of StfZ under the stress conditions of heat shock, cold shock, or oxidative stress, or at any growth phase. These data indicated that the cis-encoded StfZ antisense RNA to ftsZ mRNA may be involved in the fine tuning of ftsZ mRNA levels available for translation as per the growth-phase-specific requirement at all phases of growth and cell division.

16.
Int J Mycobacteriol ; 11(3): 273-286, 2022.
Article in English | MEDLINE | ID: mdl-36260446

ABSTRACT

Background: We recently reported the de novo emergence of unusually high numbers of antibiotic resisters from the in vitro cultures of Mycobacterium tuberculosis and Mycobacterium smegmatis surviving in the presence of minimum bactericidal concentration (MBC) of antituberculosis antibiotics. The resisters emerged due to multiple asymmetric divisions of elongated mother cells containing multiple nucleoids and multiple septae. We had earlier found a minor subpopulation of short-sized cells (SCs) and a major subpopulation of normal-sized cells (NCs) (10% and 90%, respectively, of the whole population), with significant difference in antibiotic susceptibility and resister generation frequency, in the in vitro cultures of M. tuberculosis, M. smegmatis, and Mycobacterium xenopi, as well as in pulmonary tuberculosis patients' sputum. However, the mechanisms of growth and division promoting the emergence of antibiotic resisters from these subpopulations remained unknown. Therefore, here, we took up the first-time study to find out the mechanism of growth and division by which antibiotic resisters emerge from the antibiotic-surviving population of the two subpopulations of M. smegmatis. Methods: M. smegmatis SCs and NCs were fractionated from mid-log phase cultures using Percoll gradient centrifugation; their purity was checked and exposed to 10×, 2×, and 0.4× MBC of rifampicin for 120 h. The colony-forming units (CFUs) were determined on rifampicin-free plates for the total population and on rifampicin-containing plates for scoring rifampicin resisters. The phenotype and the morphology of the cells at various stages of the exposure were determined using transmission electron microscopy. The dynamic growth and division mechanisms of the cells to emerge as rifampicin resisters were monitored using live-cell time-lapse imaging. The rifampicin resisters were sequenced for mutations in the rifampicin resistance determining region of rpoB gene. Statistical significance was calculated using two-tailed paired t-test, with *P ≤ 0.05 and **P ≤ 0.01. Results: Multinucleated and multiseptated elongated cells emerged from their respective antibiotic-surviving populations. They produced a large number of sibling-daughter cells through multiple asymmetric divisions in short durations, showing abnormally high spurts in CFUs of antibiotic resisters. The CFUs were several-fold higher than that expected from the mass-doubling time of the subpopulations. Despite this commonality, the subpopulations showed specific differences in their response to different multiples of their respective MBC of rifampicin. Conclusions: Mycobacterial subpopulations come out of rifampicin stress by undergoing multiple nucleoid replications, multiple septation for nucleoid segregation, and acquisition of antibiotic target-specific mutations, followed by multiple asymmetric divisions to generate unusually a large number of rifampicin resisters. Because we had earlier shown that SCs and NCs are present in the pulmonary tuberculosis patients' sputum, the present findings have clinical relevance on the mechanism of emergence of antibiotic-resistant strains from mycobacterial subpopulations.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Humans , Rifampin/pharmacology , Anti-Bacterial Agents/pharmacology , Mycobacterium tuberculosis/genetics , Mycobacterium smegmatis/genetics
17.
Curr Res Microb Sci ; 3: 100142, 2022.
Article in English | MEDLINE | ID: mdl-35909599

ABSTRACT

The physiological role of mono-ADP-ribosyl transferase (Arr) of Mycobacterium smegmatis, which inactivates rifampicin, remains unclear. An earlier study reported increased expression of arr during oxidative stress and DNA damage. This suggested a role for Arr in the oxidative status of the cell and its associated effect on DNA damage. Since reactive oxygen species (ROS) influence oxidative status, we investigated whether Arr affected ROS levels in M. smegmatis. Significantly elevated levels of superoxide and hydroxyl radical were found in the mid-log phase (MLP) cultures of the arr knockout strain (arr-KO) as compared those in the wild-type strain (WT). Complementation of arr-KO with expression from genomically integrated arr under its native promoter restored the levels of ROS equivalent to that in WT. Due to the inherently high ROS levels in the actively growing arr-KO, rifampicin resisters with rpoB mutations could be selected at 0 hr of exposure itself against rifampicin, unlike in the WT where the resisters emerged at 12th hr of rifampicin exposure. Microarray analysis of the actively growing cultures of arr-KO revealed significantly high levels of expression of genes from succinate dehydrogenase I and NADH dehydrogenase I operons, which would have contributed to the increased superoxide levels. In parallel, expression of specific DNA repair genes was significantly decreased, favouring retention of the mutations inflicted by the ROS. Expression of several metabolic pathway genes also was significantly altered. These observations revealed that Arr was required for maintaining a gene expression profile that would provide optimum levels of ROS and DNA repair system in the actively growing M. smegmatis.

18.
Curr Res Microb Sci ; 3: 100148, 2022.
Article in English | MEDLINE | ID: mdl-35909613

ABSTRACT

Exposure to antibiotics most often generates oxidative stress in bacteria. Oxidative stress survival mechanisms would facilitate the evolution of antibiotic resistance. As part of an effort to understand oxidative stress survival mechanisms in mycobacteria, here we show that the minor subpopulation (SCs; short-sized cells constituting 10% of the population) of Mycobacterium smegmatis significantly increased the survival of its major kin subpopulation (NCs; normal/long-sized cells constituting 90% of the population) in the mid-log-phase (MLP) cultures against the oxidative stress induced by rifampicin and exogenously added H2O2 (positive control). We had earlier shown that the SCs in the MLP cultures inherently and naturally release significantly high levels of H2O2 into the medium. Addition of the SCs' culture supernatant, unlike the supernatant of the dimethylthiourea (H2O2 scavenger) exposed SCs, enhanced the survival of NCs. It indicated that NCs' survival required the H2O2 present in the SCs' supernatant. This H2O2 transcriptionally induced high levels of catalase-peroxidase (KatG) in the NCs. The naturally high KatG levels in the NCs significantly neutralised the endogenous H2O2 formed upon exposure to rifampicin or H2O2, thereby enhancing the survival of NCs against oxidative stress. The absence of such enhanced survival in the furA-katG and katG knockout (KO) mutants of NCs in the presence of wild-type SCs, confirmed the requirement of the H2O2 present in the SCs' supernatant and NCs' KatG for enhanced oxidative stress survival. The presence of SCs:NCs at 1:9 in the pulmonary tuberculosis patients' sputum alludes to the clinical significance of the finding.

19.
Int J Mycobacteriol ; 11(2): 150-158, 2022.
Article in English | MEDLINE | ID: mdl-35775547

ABSTRACT

Background: The antibiotic-exposed bacteria often contain the reactive oxygen species (ROS), hydroxyl radical, which inflicts genome-wide mutations, causing the de novo formation of antibiotic-resistant strains. Hydroxyl radical is generated by Fenton reaction of Fe (II) with the ROS, H2O2, which, in turn, is formed by the dismutation of the ROS, superoxide. Therefore, for the emergence of bacterial strains genetically resistant to antibiotics, increased levels of superoxide, H2O2, hydroxyl radical, and Fe (II) should be present in the antibiotic-exposed bacteria. Here, we verified this premise by finding out whether the in vitro cultures of M. smegmatis, exposed to MBC of moxifloxacin for a prolonged duration, contain significantly high levels of superoxide, H2O2, hydroxyl radical, and Fe (II). Methods: Biological triplicate cultures of M. smegmatis, were exposed to MBC of moxifloxacin for 84 h. The colony-forming units (CFUs) of the cultures were determined on moxifloxacin-free and moxifloxacin-containing plates for the entire 84 h at a regular interval of 6 h. The cultures were analyzed at specific time points of killing phase (KP), antibiotic-surviving phase (ASP), and regrowth phase (RGP) for the presence of superoxide, H2O2, hydroxyl radical, and Fe (II) using the ROS- and Fe (II)-detecting fluorescence probes. The experimental cultures were grown in the presence of ROS and Fe (II) quenchers also and determined the levels of fluorescence corresponding to the ROS- and Fe (II)-specific probes. This was performed to establish the specificity of detection of ROS and Fe (II). Biological triplicate cultures, unexposed to moxifloxacin but cultured for 84 h, were used as the control for the measurement of ROS and Fe (II) levels. The CFUs of the cultures were determined on moxifloxacin-free and moxifloxacin-containing plates for the entire 84 h at regular intervals of 6 h. Flow cytometry analyses were performed for the detection and quantitation of the levels of fluorescence of the ROS-and Fe (II)-specific probes. The experimental cultures were grown in the presence of thiourea and bipyridyl as the ROS and Fe (II) quenchers, respectively, for the determination of the levels of fluorescence corresponding to the ROS- and Fe (II)-specific probes. Paired t-test was used to calculate statistical significance (n = 3). Results: The moxifloxacin-exposed cultures, but not the cultures unexposed to moxifloxacin, showed a triphasic response with a KP, ASP, and RGP. The cells in the late KP and ASP contained significantly elevated levels of superoxide, H2O2, hydroxyl radical, and Fe (II). Thus, high levels of the ROS and Fe (II) were found in the small population (in the ASP) of M. smegmatis cells that survived the moxifloxacin-mediated killing. From this moxifloxacin-surviving population (in the ASP), moxifloxacin-resistant genetic resisters emerged de novo at high frequency, regrew, divided, and populated the cultures. The levels of these ROS, Fe (II), and the high moxifloxacin resister generation frequency were quenched in the cultures grown in the presence of the respective ROS and Fe (II) quenchers. The cultures unexposed to moxifloxacin did not show any of these responses, indicating that the whole response was specific to antibiotic exposure. Conclusions: Significantly high levels of superoxide, H2O2, hydroxyl radical, and Fe (II) were generated in the M. smegmatis cultures exposed to moxifloxacin for a prolonged duration. It promoted the de novo emergence of genetic resisters to moxifloxacin at high frequency.


Subject(s)
Hydroxyl Radical , Superoxides , Anti-Bacterial Agents/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Moxifloxacin/pharmacology , Mycobacterium smegmatis , Reactive Oxygen Species
20.
Phys Med Biol ; 67(14)2022 07 08.
Article in English | MEDLINE | ID: mdl-35709707

ABSTRACT

Objective.While simulated low-dose CT images and phantom studies cannot fully approximate subjective and objective effects of deep learning (DL) denoising on image quality, live animal models may afford this assessment. This study is to investigate the potential of DL in CT dose reduction on image quality compared to iterative reconstruction (IR).Approach.The upper abdomen of a live 4 year old sheep was scanned on a CT scanner at different exposure levels. Images were reconstructed using FBP and ADMIRE with 5 strengths. A modularized DL network with 5 modules was used for image reconstruction via progressive denoising. Radiomic features were extracted from a region over the liver. Concordance correlation coefficient (CCC) was applied to quantify agreement between any two sets of radiomic features. Coefficient of variation was calculated to measure variation in a radiomic feature series. Structural similarity index (SSIM) was used to measure the similarity between any two images. Diagnostic quality, low-contrast detectability, and image texture were qualitatively evaluated by two radiologists. Pearson correlation coefficient was computed across all dose-reconstruction/denoising combinations.Results.A total of 66 image sets, with 405 radiomic features extracted from each, are analyzed. IR and DL can improve diagnostic quality and low-contrast detectability and similarly modulate image texture features. In terms of SSIM, DL has higher potential in preserving image structure. There is strong correlation between SSIM and radiologists' evaluations for diagnostic quality (0.559) and low-contrast detectability (0.635) but moderate correlation for texture (0.313). There is moderate correlation between CCC of radiomic features and radiologists' evaluation for diagnostic quality (0.397), low-contrast detectability (0.417), and texture (0.326), implying that improvement of image features may not relate to improvement of diagnostic quality.Conclusion.DL shows potential to further reduce radiation dose while preserving structural similarity, while IR is favored by radiologists and more predictably alters radiomic features.


Subject(s)
Deep Learning , Radiographic Image Interpretation, Computer-Assisted , Abdomen/diagnostic imaging , Algorithms , Animals , Drug Tapering , Phantoms, Imaging , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted/methods , Sheep , Tomography, X-Ray Computed/methods
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