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Article ; Online: Low-dose X-ray radiation induces an adaptive response: A potential countermeasure to galactic cosmic radiation exposure.

Edwards, Siena / Adams, Jessica / Tchernikov, Anastasia / Edwards, John G

2024

Abstract: Space exploration involves many dangers including galactic cosmic radiation (GCR). This class of radiation includes high-energy protons and heavy ionizing ions. NASA has defined GCR as a carcinogenic risk for long-duration space missions. To date, no ... ...

Abstract	Space exploration involves many dangers including galactic cosmic radiation (GCR). This class of radiation includes high-energy protons and heavy ionizing ions. NASA has defined GCR as a carcinogenic risk for long-duration space missions. To date, no clear strategy has been developed to counter chronic GCR exposure. We hypothesize that preconditioning cells with low levels of radiation will be protective from subsequent higher radiation exposures. H9C2 cells were pretreated with 0.1 to 1.0 Gy X-rays. The challenge radiation exposure consisted of either 8 Gy X-rays or 75 cGy of GCR, using a five-ion GCRsim protocol. A cell doubling time assay was used to determine cell viability. An 8 Gy X-ray challenge alone significantly (P < 0.05) increased cell doubling time compared to the no-radiation control group. Low-dose radiation pre-treatment ameliorated the 8 Gy X-ray-induced increases in cell doubling time. A 75 cGy GCR challenge alone significantly increased cell doubling time compared to the no-radiation group. Following the 75 cGy challenge, only the 0.5 and 1.0 Gy pre-treatment ameliorated the 75 cGy-induced increases in cell doubling time. DNA damage or pathological oxidant stress will delay replicative functions and increase cell doubling time. Our results suggested that pretreatment with low-dose X-rays induced an adaptive response which offered a small but significant protection against a following higher radiation challenge. Although perhaps not a practical countermeasure, these findings may serve to offer insight into cell signalling pathways activated in response to low-dose irradiation and targeted for countermeasure development.
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1016295-1
ISSN	1469-445X ; 0958-0670
ISSN (online)	1469-445X
ISSN	0958-0670
DOI	10.1113/EP091350
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Article ; Online: Postoperative Radiation Therapy Should Not Be Used for the Therapy of Stage III-N2 NSCLC.

Faivre-Finn, Corinne / Edwards, John G / Hatton, Matthew

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2022 Volume 17, Issue 2, Page(s) 197–199

MeSH term(s)	Carcinoma, Non-Small-Cell Lung/pathology ; Humans ; Lung Neoplasms/pathology ; Neoplasm Staging ; Pneumonectomy
Language	English
Publishing date	2022-01-21
Publishing country	United States
Document type	Editorial
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2021.09.005
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Article ; Online: eComment. Further series.

Edwards, John G

Interactive cardiovascular and thoracic surgery

2016 Volume 23, Issue 2, Page(s) 319

Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2095298-3
ISSN	1569-9285 ; 1569-9293
ISSN (online)	1569-9285
ISSN	1569-9293
DOI	10.1093/icvts/ivw147
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Article ; Online: Costal margin injuries and trans-diaphragmatic intercostal hernia: Presentation, management and outcomes according to the Sheffield classification.

Byers, Jonathan L / Rao, Jagan N / Socci, Laura / Hopkinson, David N / Tenconi, Sara / Edwards, John G

The journal of trauma and acute care surgery

2023 Volume 95, Issue 6, Page(s) 839–845

Abstract: Background: Costal margin rupture (CMR) injuries are under-diagnosed and inconsistently managed, while carrying significant symptomatic burden. We hypothesized that the Sheffield Classification system of CMR injuries would relate to injury patterns and ... ...

Abstract	Background: Costal margin rupture (CMR) injuries are under-diagnosed and inconsistently managed, while carrying significant symptomatic burden. We hypothesized that the Sheffield Classification system of CMR injuries would relate to injury patterns and management options. Methods: Data were collected prospectively between 2006 and 2023 at a major trauma center in the United Kingdom. Computed tomography scans were interrogated and injuries were categorized according to the Sheffield Classification. Clinical, radiologic, management and outcome variables were assessed. Results: Fifty-four patients were included in the study. Intercostal hernia (IH) was present in 30 patients and associated with delayed presentation ( p = 0.004), expulsive mechanism of injury (i.e. such as occurs with coughing, sneezing, or retching), higher body mass index ( p < 0.001), and surgical management ( p = 0.02). There was a bimodal distribution of the level of the costal margin rupture, with IH Present and expulsive mechanism injuries occurring predominantly at the ninth costal cartilage, and IH Absent cases and other mechanisms at the seventh costal cartilage ( p < 0.001). There were correlations between the costal cartilage being thin at the site of the CMR and the presence of IH and expulsive etiology ( p < 0.001). Management was conservative in 23 and surgical in 31 cases. Extrathoracic mesh IH repairs were performed in 3, Double Layer Mesh Repairs in 8, Suture IH repairs in 5, CMR plating in 8, CMR sutures in 2, and associated Surgical Stabilization of Rib Fractures in 11 patients. There was one postoperative death. There were seven repeat surgical procedures in five patients. Conclusion: The Sheffield Classification is associated statistically with presentation, related chest wall injury patterns, and type of definitive management. Further collaborative data collection is required to determine the optimal management strategies. Level of evidence: Therapeutic/Care Management; Level III.
MeSH term(s)	Humans ; Rib Cage/surgery ; Hernia/etiology ; Hernia, Hiatal/complications ; Hernias, Diaphragmatic, Congenital/surgery ; Herniorrhaphy/methods ; Rupture/surgery
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000004068
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Article: Doxorubicin induced heart failure: Phenotype and molecular mechanisms.

Mitry, Maria A / Edwards, John G

International journal of cardiology. Heart & vasculature

2016 Volume 10, Page(s) 17–24

Abstract: Long term survival of childhood cancers is now more than 70%. Anthracyclines, including doxorubicin, are some of the most efficacious anticancer drugs available. However, its use as a chemotherapeutic agent is severely hindered by its dose-limiting ... ...

Abstract	Long term survival of childhood cancers is now more than 70%. Anthracyclines, including doxorubicin, are some of the most efficacious anticancer drugs available. However, its use as a chemotherapeutic agent is severely hindered by its dose-limiting toxicities. Most notably observed is cardiotoxicity, but other organ systems are also degraded by doxorubicin use. Despite the years of its use and the amount of information written about this drug, an understanding of its cellular mechanisms is not fully appreciated. The mechanisms by which doxorubicin induces cytotoxicity in target cancer cells have given insight about how the drug damages cardiomyocytes. The major mechanisms of doxorubicin actions are thought to be as an oxidant generator and as an inhibitor of topoisomerase 2. However, other signaling pathways are also invoked with significant consequences for the cardiomyocyte. Further the interaction between oxidant generation and topoisomerase function has only recently been appreciated and the consequences of this interaction are still not fully understood. The unfortunate consequences of doxorubicin within cardiomyocytes have promoted the search for new drugs and methods that can prevent or reverse the damage caused to the heart after treatment in cancer patients. Alternative protocols have lessened the impact on newly diagnosed cancer patients. However the years of doxorubicin use have generated a need for monitoring the onset of cardiotoxicity as well as understanding its potential long-term consequences. Although a fairly clear understanding of the short-term pathologic mechanisms of doxorubicin actions has been achieved, the long-term mechanisms of doxorubicin induced heart failure remain to be carefully delineated.
Language	English
Publishing date	2016-05-06
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2818464-6
ISSN	2352-9067
ISSN	2352-9067
DOI	10.1016/j.ijcha.2015.11.004
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Article ; Online: Elastic-Stable Chest Repair: Costal Plate Fixation for Sternotomy Nonunion.

Gooseman, Michael R / Cooper, Graham J / Edwards, John G

The Annals of thoracic surgery

2018 Volume 105, Issue 4, Page(s) e175–e176

Abstract: Sterile sternotomy nonunion is a recognized complication after median sternotomy. It is defined as sternotomy that persists after 3 months without evidence of bony healing but with healing of the overlying soft tissues. It is a morbid condition ... ...

Abstract	Sterile sternotomy nonunion is a recognized complication after median sternotomy. It is defined as sternotomy that persists after 3 months without evidence of bony healing but with healing of the overlying soft tissues. It is a morbid condition associated with pain and sternal instability. We present two challenging cases of sterile sternotomy nonunion after cardiac operations that were treated successfully with novel methods adopted from the Elastic Stable Chest Repair for complex pectus deformity repair, using transverse costal to costal external cortical plates and bicortical screws, after debridement, autologous bone grafting and double loop wire sternal approximation.
MeSH term(s)	Aged ; Bone Plates ; Bone Transplantation ; Fracture Fixation, Internal ; Fractures, Ununited/surgery ; Humans ; Male ; Ribs/surgery ; Sternotomy/adverse effects
Language	English
Publishing date	2018-03-23
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2017.10.030
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Article ; Online: The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the Classification of Residual Tumor After Resection for the Forthcoming (Ninth) Edition of the TNM Classification of Lung Cancer.

Detterbeck, Frank C / Ostrowski, Marcin / Hoffmann, Hans / Rami-Porta, Ramón / Osarogiagbon, Ray U / Donnington, Jessica / Infante, Maurizio / Marino, Mirella / Marom, Edith M / Nakajima, Jun / Nicholson, Andrew G / van Schil, Paul / Travis, William D / Tsao, Ming S / Edwards, John G / Asamura, Hisao

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2024

Abstract: Introduction: The goal of surgical resection is to completely remove a cancer; it is useful to have a system to describe how well this was accomplished. This is captured by the residual tumor (R) classification, which is separate from the TNM ... ...

Abstract	Introduction: The goal of surgical resection is to completely remove a cancer; it is useful to have a system to describe how well this was accomplished. This is captured by the residual tumor (R) classification, which is separate from the TNM classification that describes the anatomic extent of a cancer independent of treatment. The traditional R-classification designates as R0 a complete resection, as R1 a macroscopically complete resection but with microscopic tumor at the surgical margin, and as R2 a resection that leaves gross tumor behind. For lung cancer, an additional category encompasses situations in which the presence of residual tumor is uncertain. Methods: This paper represents a comprehensive review of evidence regarding these R categories and the descriptors thereof, focusing on studies published after the year 2000 and with adjustment for potential confounders. Results: Consistent discrimination between complete, uncertain, and incomplete resection is revealed with respect to overall survival. Evidence regarding specific descriptors is generally somewhat limited and only partially consistent; nevertheless, the data suggest retaining all descriptors but with clarifications to address ambiguities. Conclusion: On the basis of this review, the R-classification for the ninth edition of stage classification of lung cancer is proposed to retain the same overall framework and descriptors, with more precise definitions of descriptors. These refinements should facilitate application and further research.
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2024.03.021
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Article: Alcoholic Cardiomyopathy: Multigenic Changes Underlie Cardiovascular Dysfunction.

Laurent, Dimitri / Edwards, John G

Journal of cardiology & clinical research

2014 Volume 2, Issue 1

Abstract: Alcoholism is the third leading cause of preventable death in the United States. Aside from promoting cardiomyopathies, chronic alcohol consumption is associated with an increased risk of dementia, the development of liver or pancreas failure, and ... ...

Abstract	Alcoholism is the third leading cause of preventable death in the United States. Aside from promoting cardiomyopathies, chronic alcohol consumption is associated with an increased risk of dementia, the development of liver or pancreas failure, and cancers of the oral cavity and pharynx. Although a J-shaped curve for all cause mortality has been identified for average alcohol consumption, irregular heavy drinking also carries significantly greater risks for cardiovascular disease. Alcohol induced cardiovascular disease has a complex multigenic etiology. There is significant variation in the initial presentation of alcoholic cardiomyopathy with diastolic dysfunction possibly being the first indication. Ethanol exposure generates toxic metabolites, primarily acetaldehyde and ROS, which activate several cell signaling systems to alter cell function across many levels. Sudden cardiac death is a known occurrence of alcoholism that may be linked to an arrhythmogenic effect of alcohol. Microscopic and molecular examination of diseased hearts has demonstrated abnormal alterations to various cellular components, including the mitochondria and myofibrils. These studies have shown not only the direct impact on myocardial contractility but also disrupted metabolism that determines the long-term survival of the myocardium. Significant variations in the response to chronic alcohol consumption may be related to unique genotypes that modify the metabolic response to ethanol. Future studies to further characterize the role of different genotypes will help indentify those genotypes are more susceptible to chronic alcohol consumption.
Language	English
Publishing date	2014-01-24
Publishing country	United States
Document type	Journal Article
ISSN	2333-6676
ISSN	2333-6676
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Article: Quantification of mitochondrial DNA (mtDNA) damage and error rates by real-time QPCR.

Edwards, John G

Mitochondrion

2008 Volume 9, Issue 1, Page(s) 31–35

Abstract: Mitochondrial dysfunction has reported in several diseases including diabetes, cancer, skeletal muscle disorders and neurodegenerative diseases such as Wolfram syndrome. Several different methods have evolved to study mtDNA damage including Southern ... ...

Abstract	Mitochondrial dysfunction has reported in several diseases including diabetes, cancer, skeletal muscle disorders and neurodegenerative diseases such as Wolfram syndrome. Several different methods have evolved to study mtDNA damage including Southern blotting, 8-oxoG damage, or a comprehensive scanning of the mitochondrial genome by RFLP or TTGE analyses. However these approaches require large amounts of DNA or are labor intensive. The use of polymerase amplification of long DNA products (LRPCR) has been described by several groups and more recently summarized by Van Houten's group. The underlying basis use of DNA polymerases capable of generating long DNA products and the rationale is that any lesion (strand breaks, base modifications, apurinic sites) will stop a thermostable DNA polymerase. In this method, band density of the PCR product is quantified either by Southern blotting or binding of a fluorescent dye. Although the latter approach still has some limited use in the study gene expression, it is semi-quantitative and realtime PCR analysis has largely supplanted it. Direct application of real-time PCR to LRPCR has been made difficult because of low processivity and polymerization rates of the DNA polymerases used and SYBR green inhibition of DNA amplification. We have modified the LRPCR protocol to use the commercially available PfuUltra() II Fusion HS DNA Polymerase for real-time determination of mitochondrial DNA amplification as a means to simplify and improve of the accuracy for quantification of mtDNA damage.
MeSH term(s)	8-Hydroxy-2'-Deoxyguanosine ; Cell Line, Tumor ; DNA/chemistry ; DNA Damage ; DNA Primers/chemistry ; DNA Repair ; DNA, Mitochondrial/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/pharmacology ; Fluorescent Dyes/pharmacology ; Humans ; Mitochondria/metabolism ; Polymerase Chain Reaction/methods ; Polymorphism, Restriction Fragment Length ; Reproducibility of Results ; Ultraviolet Rays
Chemical Substances	DNA Primers ; DNA, Mitochondrial ; Fluorescent Dyes ; 8-Hydroxy-2'-Deoxyguanosine (88847-89-6) ; DNA (9007-49-2) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Deoxyguanosine (G9481N71RO)
Language	English
Publishing date	2008-12-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2008.11.004
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Article ; Online: Testing the clinical validity of the Bemelman Rib Fracture Management Guideline.

Dorman, Jessica R / Clarke, Peter T M / Simpson, Rosalind B / Edwards, John G

Interactive cardiovascular and thoracic surgery

2020 Volume 30, Issue 4, Page(s) 597–599

Abstract: Whilst surgical stabilization of rib fractures (SSRF) results in better outcomes, selection algorithms are lacking. We aimed to validate the Rib Fracture Management Guideline proposed by Bemelman. From a cohort of 792 patients with multiple rib fractures, ...

Abstract	Whilst surgical stabilization of rib fractures (SSRF) results in better outcomes, selection algorithms are lacking. We aimed to validate the Rib Fracture Management Guideline proposed by Bemelman. From a cohort of 792 patients with multiple rib fractures, 2 sequential cohorts were selected: 48 patients who underwent SSRF and 48 patients who managed conservatively. Admission computed tomography scans and records were reviewed by an investigator blinded to the SSRF outcome. Adherence to the Bemelman guideline, revised to take account of consensus rib fracture definitions, was tested. Fifty-seven patients had multiple rib fractures only, and 39 patients also had a flail segment. Thirty-nine patients with flail segment underwent SSRF, and 18 patients were managed conservatively. Of the patients that the guideline predicted should have received surgery, 87% did. Of those that it predicted should not receive SSRF, 98% did not. The guideline displayed a sensitivity (95% confidence interval) and specificity for predicting the fixation of 0.98 (0.89-0.9995) and 0.83 (0.70-0.93), respectively. The positive and negative predictive values for surgical fixation were 0.87 (0.76-0.92) and 0.98 (0.85-0.99), respectively. The Bemelman guideline was thus a good predictor of SSRF in retrospective cohort but should be used in conjunction with clinical judgement. Further validation is indicated in a prospective study.
MeSH term(s)	Adult ; Female ; Fracture Fixation, Internal/methods ; Humans ; Male ; Middle Aged ; Practice Guidelines as Topic ; Prospective Studies ; Rib Fractures/diagnosis ; Rib Fractures/surgery ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2095298-3
ISSN	1569-9285 ; 1569-9293
ISSN (online)	1569-9285
ISSN	1569-9293
DOI	10.1093/icvts/ivz317
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