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Article ; Online: Chr 19(A/J) modifies tumor resistance in a sex- and parent-of-origin-specific manner.

Walrath, Jessica C / Fox, Kristi / Truffer, Erika / Gregory Alvord, W / Quiñones, Octavio A / Reilly, Karlyne M

Mammalian genome : official journal of the International Mammalian Genome Society

2009 Volume 20, Issue 4, Page(s) 214–223

Abstract: Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background ... ...

Abstract	Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2, that influence resistance to PNSTs in the Nf1-/+;Trp53-/+cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a chromosome substitution strain, and further show that a modifier locus (or loci) on chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of chromosome substitution strains to study genetic modifiers.
MeSH term(s)	Animals ; Astrocytoma/genetics ; Chromosomes, Human, Pair 19/genetics ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Sheath Neoplasms/genetics ; Neurofibromatosis 1/genetics ; Sex Factors
Language	English
Publishing date	2009-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1058547-3
ISSN	1432-1777 ; 0938-8990
ISSN (online)	1432-1777
ISSN	0938-8990
DOI	10.1007/s00335-009-9179-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 3489: Show issues

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Article: Chr 19A/J modifies tumor resistance in a sex- and parent-of-origin-specific manner

Walrath, Jessica C / Fox, Kristi / Truffer, Erika / Gregory Alvord, W / Quiñones, Octavio A / Reilly, Karlyne M

Mammalian genome official journal of the International Mammalian Genome Society. 2009 Apr., v. 20, no. 4

2009

Abstract	Neurofibromatosis type 1 (NF1) is one of the most common human genetic diseases affecting the nervous system and predisposes individuals to cancer, including peripheral nerve sheath tumors (PNSTs) and astrocytomas. Modifiers in the genetic background affect the severity of the disease and we have previously mapped two modifier loci, Nstr1 and Nstr2, that influence resistance to PNSTs in the Nf1-/+;Trp53-/+cis mouse model of NF1. We report here the analysis of Nstr1 in isolation from other epistatic loci using a chromosome substitution strain, and further show that a modifier locus (or loci) on chromosome 19 influences resistance to both PNSTs and astrocytomas. This modifier locus interacts with sex, resulting in sex-specific modification of tumors. Allele variability on chromosome 19 affects both the timing and the penetrance of the growth of different tumor types associated with NF1, specifically PNSTs and astrocytoma. These results indicate that modifiers of cancer susceptibility interact and affect tumorigenesis under different genetic conditions and demonstrate the power of chromosome substitution strains to study genetic modifiers.
Keywords	alleles ; animal models ; carcinogenesis ; chromosome substitution ; disease severity ; epistasis ; genetic background ; genetic disorders ; humans ; loci ; neoplasms ; nerve tissue ; penetrance
Language	English
Dates of publication	2009-04
Size	p. 214-223.
Publisher	Springer-Verlag
Publishing place	New York
Document type	Article
ZDB-ID	1058547-3
ISSN	1432-1777 ; 0938-8990
ISSN (online)	1432-1777
ISSN	0938-8990
DOI	10.1007/s00335-009-9179-4
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Article ; Online: Interfacility Transfer Teams: A Pilot Study to Assess Viability as a Skill Sustainment Platform.

Medenbach, Andrew J / Nguyen, Alexandre / Raetz, Emily / Morrison, Theodore / Walrath, Benjamin

Military medicine

2024

Abstract: Introduction: A US Naval hospital in the remote Pacific region has developed interfacility transfer (IFT) teams staffed by active duty personnel out of necessity due to a large percentage of critically ill patients requiring IFT and a lack of local ... ...

Abstract	Introduction: A US Naval hospital in the remote Pacific region has developed interfacility transfer (IFT) teams staffed by active duty personnel out of necessity due to a large percentage of critically ill patients requiring IFT and a lack of local resources. The IFT program underwent significant improvements in training and quality assurance in 2017. We sought to assess patient safety when transport was performed by our locally sourced and trained IFT teams. En route care (ERC) is a recognized critical capability gap in the US Navy requiring clinicians with current knowledge and skills to maintain competency. IFT programs may be a viable skill sustainment program for ERC clinicians. Materials and methods: A database was created as part of the quality assurance program to collate information on patient demographics, level of care provided, reason for transport, and interventions provided by the transporting team. A retrospective review of these data was conducted with emphasis on the appropriateness of patient management and skill sustainment for active duty personnel. The project was deemed institutional review board exempt. Results: Of the 1,193 patient care reports reviewed, interventions were required in 128 (10.7%) of patients and 58 (4.9%) required ventilator management. Medical deterioration occurred during 22 (1.8%) of the transports, with 20 (90.9%) of the deterioration episodes managed appropriately. No patient harm occurred. Conclusions: IFT teams with local training were able to safely transport critically ill patients with no adverse outcomes, defined as direct harm to the patients as a result of transport. Patient care during transports included routine interventions, ventilator management, and troubleshooting of patient deteriorations. Our data further suggest IFT programs may be a viable skill sustainment platform for ERC clinicians.
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usae093
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Article ; Online: Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures.

Khair, Shanawaj / Walrath, Travis M / Curtis, Brenda J / Orlicky, David J / McMahan, Rachel H / Kovacs, Elizabeth J

Burns : journal of the International Society for Burn Injuries

2023 Volume 49, Issue 8, Page(s) 1935–1943

Abstract: Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. ... ...

Abstract	Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation. Specifically, intoxicated burned mice had worsened pulmonary responses, including increased leukocyte infiltration and heightened levels of CXCL1 and IL-6. Herein, we examined whether a single binge ethanol exposure before scald burn injury yields similar pulmonary responses. C57BL/6 male mice were given ethanol (1.2 g/kg) 30 min before a 15 % total body surface area burn. These mice were compared to a second cohort given episodic ethanol binge for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. 24 h after burn, histopathological examination of lungs were performed. In addition, survival, and levels of infiltrating leukocytes, CXCL1, and IL-6 were quantified. Episodic and single ethanol exposure before burn decreased survival compared to burn only mice and sham vehicle mice, respectively (p < 0.05). However, no difference in survival was observed between burned mice with single and episodic ethanol binge. Examination of H&E-stained lung sections revealed that regardless of ethanol binge frequency, intoxication prior to burn worsened pulmonary inflammation, evidenced by elevated granulocyte accumulation and congestion, relative to burned mice without any ethanol exposure. Levels of infiltrating granulocyte in the lungs were significantly higher in burned mice with both episodic and single ethanol intoxication, compared to burn injury only (p < 0.05). In addition, there was no difference in the granulocyte count between single and ethanol binge mice with burn injury. Neutrophil chemoattractant CXCL1 levels in the lung were similarly increased following single and episodic ethanol exposure prior to burn compared to burn alone (22-fold and 26-fold respectively, p < 0.05). Lastly, we assessed pulmonary IL-6, which revealed that irrespective of frequency, ethanol exposure combined with burn injury raised pro-inflammatory cytokine IL-6 in the lungs relative to burn mice. Again, we did not find any difference in the amount of IL-6 in lungs of burned mice with single and episodic ethanol intoxication. Taken altogether, these data demonstrate that both single and episodic exposure to ethanol prior to burn injury similarly worsens pulmonary inflammation. These results suggest that ethanol-induced exacerbation of the pulmonary responses to burn injury is due to presence of ethanol at the time of injury rather than longer-term effects of ethanol exposure.
MeSH term(s)	Male ; Humans ; Animals ; Mice ; Ethanol ; Alcoholic Intoxication/complications ; Interleukin-6 ; Burns/complications ; Burns/pathology ; Mice, Inbred C57BL ; Pneumonia/complications
Chemical Substances	Ethanol (3K9958V90M) ; Interleukin-6
Language	English
Publishing date	2023-07-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	197308-3
ISSN	1879-1409 ; 0305-4179
ISSN (online)	1879-1409
ISSN	0305-4179
DOI	10.1016/j.burns.2023.07.008
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Zs.A 1250: Show issues

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Article: Aging, Cutaneous Burn Injury and Multi-Organ Complications: The Role of the Gut.

McMahan, Rachel H / Boe, Devin M / Walrath, Travis M / Idrovo, Juan-Pablo / Kovacs, Elizabeth J

Advances in geriatric medicine and research

2022 Volume 4, Issue 2

Abstract: Advanced age escalates post-burn complications and older burn patients, and even those with relatively minor burns, have worse clinical outcomes after injury. While the mechanism(s) responsible for the compounding effects of age and burn injury have not ... ...

Abstract	Advanced age escalates post-burn complications and older burn patients, and even those with relatively minor burns, have worse clinical outcomes after injury. While the mechanism(s) responsible for the compounding effects of age and burn injury have not been defined, in this viewpoint, we highlight the emerging data suggesting that age-mediated impairment of gut barrier integrity and dysbiosis of the fecal microbiome in older subjects may play a role in the heightened multi-organ responses seen in older patients. Studies aimed at exploring the contribution of intestinal dysfunction in age-related exacerbations of post-burn inflammatory responses could highlight novel therapeutic interventions that can be used to treat victims of burns and other traumatic injuries.
Language	English
Publishing date	2022-06-28
Publishing country	England
Document type	Journal Article
DOI	10.20900/agmr20220004
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Article ; Online: Cutaneous burn injury induces neuroinflammation and reactive astrocyte activation in the hippocampus of aged mice.

Walrath, Travis / McMahan, Rachel H / Idrovo, Juan-Pablo / Quillinan, Nidia / Kovacs, Elizabeth J

Experimental gerontology

2022 Volume 169, Page(s) 111975

Abstract: Background: By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro- ... ...

Abstract	Background: By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury. Reduced levels of phosphorylated cyclic-AMP response binding element (pCREB), caused by elevated systemic pro-inflammatory cytokines, could lead to cognitive decline and memory impairment. Methods: To examine the effects of remote injury on neuroinflammation in advanced age, young and aged mice were subjected to a 15 % total body surface area scald burn or sham injury, and euthanized after 24 h. Expression of ccl2 and tnfa were measured by qPCR in the whole brain and HPC. Astrocyte activation was measured by immunofluorescence within the HPC. pCREB was measured by immunohistochemistry in the dentate gyrus. Results: We saw an 80-fold increase in ccl2 and a 30-fold elevation in tnfa after injury in the whole brain of aged mice compared to young groups and aged sham mice (p < 0.05 and p < 0.05, respectively). Additionally, there was a 30-fold increase in ccl2 within isolated HPC of aged injured mice when compared to sham injured animals (p < 0.05). When investigating specific HPC regions, immunofluorescence staining showed a >20 % rise in glial fibrillary acidic protein (GFAP) positive astrocytes within the cornu ammonis 3 (CA3) of aged injured mice when compared to all other groups (p < 0.05). Lastly, we observed a >20 % decrease in pCREB staining by immunohistochemistry in the dentate gyrus of aged mice compared to young regardless of injury (p < 0.05). Conclusions: These novel data suggest that remote injury in aged, but not young, mice is associated with neuroinflammation and astrocyte activation within the HPC. These factors, paired with an age related reduction in pCREB, could help explain the increased cognitive decline seen in burn patients of advanced age. To our knowledge, we are the first group to examine the impact of advanced age combined with burn injury on inflammation and astrocyte activation within the brain.
MeSH term(s)	Animals ; Mice ; Astrocytes/metabolism ; Burns/complications ; Burns/metabolism ; Hippocampus/metabolism ; Neuroinflammatory Diseases ; Age Factors
Language	English
Publishing date	2022-10-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	390992-x
ISSN	1873-6815 ; 0531-5565
ISSN (online)	1873-6815
ISSN	0531-5565
DOI	10.1016/j.exger.2022.111975
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Zs.A 579: Show issues

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Article ; Online: Geographic Distribution and Neuropathology of Elaeophora schneideri in Moose (Alces alces shirasi) in Idaho, USA.

Haake, Christine J E / Taylor, Kyle R / Weyand, Logan K / Van Beek, Eric T / Eckstrand, Chrissy D / Williams, Laura B A / Dauwalter, Stacey / Walrath, Nicole L / Miyasaki, Hollie M / Roberts, Shane B / Hurley, Mark A / Rachlow, Janet L

Journal of wildlife diseases

2024

Abstract: Elaeophorosis, infection by the filarial worm Elaeophora schneideri, is a parasitic disease of wild ungulates in North America; however, our understanding of the relevance of E. schneideri to moose (Alces alces) morbidity and mortality is incomplete. ... ...

Abstract	Elaeophorosis, infection by the filarial worm Elaeophora schneideri, is a parasitic disease of wild ungulates in North America; however, our understanding of the relevance of E. schneideri to moose (Alces alces) morbidity and mortality is incomplete. Between March 2020 and July 2022, necropsy and histopathology were performed on 61 Shiras moose (Alces alces shirasi) in Idaho, US. Among the 41 adults (greater than 1 yr old), 21 moose were from northern Idaho, and 20 were from southeastern Idaho. Elaeophorosis was diagnosed in 24% (10 of 41). All 10 infected moose were from southeastern Idaho; none of the 21 moose from northern Idaho were infected. No juvenile moose (nine from northern and 11 from southeastern Idaho) were infected. Microfilariae were detected histologically in 9 of 10 infected moose, most consistently in brain tissue associated with lesions indicative of ischemic injury to the neuroparenchyma attributed to occlusion of arterioles and capillaries by microfilariae or fibrin thrombi, including edema, necrosis, and glial nodules. Microfilariae found in other tissues of the head, including the eye, tongue, and pinnae of some animals, as well as in lung, heart, liver, and kidney, typically were associated with inflammation. Three of the 10 infected moose had cropped ears attributed to elaeophorosis, and four exhibited abnormal behavior, which may have been due to neuropathology associated with E. schneideri microfilariae in the brain.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	410709-3
ISSN	1943-3700 ; 0090-3558
ISSN (online)	1943-3700
ISSN	0090-3558
DOI	10.7589/JWD-D-23-00112
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Zs.B 1441: Show issues

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Article: Salpingectomy for ovarian cancer prevention: Video education for the surgeon.

MacArthur, Emily / Long Roche, Kara / Sakran, Joseph / Patel, Sunil H / Najjar, Peter / Lu, Karen H / Gornet, Megan / Frost, Anja S / Walrath, Meghan / Bauer, Tom / Oh, Gyyong / Stone, Rebecca

Gynecologic oncology reports

2024 Volume 53, Page(s) 101368

Abstract: Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer ...

Abstract	Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on the knowledge mobilization of a standard surgical approach for surgeons (Hanley et al., 2017, Morelli et al., 2013). Resources for accomplishing this knowledge mobilization activity are needed. We therefore aim to create a peer-reviewed, publicly available surgical instructional video that facilitates standardization of the practice of salpingectomy for the purpose of OC prevention. Content creation was generated by a team of surgeon stakeholders, medical illustrators, instructional designers, and health education specialists. Expert gynecologic surgeons were filmed performing salpingectomy in order to build a video library. Accurate illustration and editing of live video footage was executed to support surgeons in visualizing key anatomic landmarks to ensure safe and complete fallopian tube excision. Review of eligibility criteria, fundamentals of preoperative counseling, and strategic and technical points were prioritized. This endeavor is strictly educational, with no commercial benefit. Publicly available, peer-reviewed surgical education tools will help us collaborate to safely and equitably expand OS within and beyond the current scope of surgical practice.
Language	English
Publishing date	2024-03-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2818505-5
ISSN	2352-5789
ISSN	2352-5789
DOI	10.1016/j.gore.2024.101368
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Article: Rapid Ketamine Infusion at an Analgesic Dose Resulting in Transient Hypotension and Bradycardia in the Emergency Department.

Emerling, Alec D / Fisher, Jason / Walrath, Benjamin / Drew, Brendon

Journal of special operations medicine : a peer reviewed journal for SOF medical professionals

2020 Volume 20, Issue 1, Page(s) 31–33

Abstract: Ketamine's favorable hemodynamic and safety profile is motivating increasing use in the prehospital environment. Despite these advantages, certain side effects require advanced planning and training. We present a case of rapid intravenous administration ... ...

Abstract	Ketamine's favorable hemodynamic and safety profile is motivating increasing use in the prehospital environment. Despite these advantages, certain side effects require advanced planning and training. We present a case of rapid intravenous administration of ketamine causing bradycardia and hypotension. A 46-year-old man presented to the emergency department for an exacerbation of chronic shoulder pain. Given the chronicity of the pain and multiple failed treatment attempts, ketamine at an analgesic dose was used. Despite the local protocol directing administration over several minutes, it was pushed rapidly, resulting in malaise, nausea, pallor, bradycardia, and hypotension. The patient returned to his baseline without intervention. This and other known side effects of ketamine, such as behavioral disturbances, altered sense of reality, and elevated heart rate and blood pressure, are well documented in the literature. With this report, the authors aim to raise awareness of transient bradycardia and hypotension associated with the rapid administration of ketamine at an analgesic dose.
MeSH term(s)	Analgesics/administration & dosage ; Analgesics/adverse effects ; Bradycardia/chemically induced ; Emergency Service, Hospital ; Humans ; Hypotension/chemically induced ; Infusions, Intravenous ; Ketamine/administration & dosage ; Ketamine/adverse effects ; Male ; Middle Aged
Chemical Substances	Analgesics ; Ketamine (690G0D6V8H)
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Case Reports
ZDB-ID	3006517-3
ISSN	1553-9768
ISSN	1553-9768
DOI	10.55460/N455-UKW4
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Zs.A 7196: Show issues

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Article ; Online: Transition From Military Prehospital Medicine to Civilian EMS.

Westcott, Sally / Walrath, Benjamin / Miller, Jeremy / Trumbull, Melissa / Manifold, Craig

Military medicine

2020 Volume 185, Issue 9-10, Page(s) e1803–e1809

Abstract: Introduction: Currently, there is a disconnection between veteran military medics and the civilian Emergency Medical Services (EMS) workforce. This project aimed to characterize the rate of civilian certification among military medics, both active duty ... ...

Abstract	Introduction: Currently, there is a disconnection between veteran military medics and the civilian Emergency Medical Services (EMS) workforce. This project aimed to characterize the rate of civilian certification among military medics, both active duty and retired, and identify perceived barriers to continuing a career in EMS after military separation. Materials and methods: The National Association of Emergency Medical Technicians (EMTs) administered a 21-question online survey to participants. Individuals were recruited through the National Association of EMTs membership communications, Military Relations Committee members, and social media. All responses were anonymous and no identifiable information was collected. Survey questions were compiled and reported as a percentage of respondents. Free-text responses were categorized based on broad themes identified by the authors and are reported as a percentage of respondents. Results: Results included 456 veteran and active duty respondents, of whom 304 (70.7%) had prehospital experience while in the military and 250 (58.1%) had emergency department experience. Over 60% of respondents participated in combat-related duty with 37% having at least 18 months of overseas deployment. Civilian EMT certification was held by 164 (36.7%) survey participants and 170 held paramedic certification (38.1%), while 65 (14.6%) held no EMS certification. There were 119 (28.1%) respondents who stated that they did not plan to work in civilian EMS. Top selected reasons for not pursuing civilian EMS careers included: pursuing a medical career that was not prehospital (28.5%), pay disparity (18.1%), and no interest in civilian prehospital medicine (16.4%). Write in responses indicated general frustration with maintaining certification and a desire for advanced certification (AEMT, paramedic) to be supplied by the military prior to transitioning to a civilian workforce as many respondents felt their military-endowed skills and experiences were better aligned with these advanced EMS licenses. Conclusion: The majority of survey respondents held an EMS certification of some kind and suggests that recent efforts to supply military medics with civilian certifications have been largely successful. However, there is still a large portion that remains noncertified or expresses disinterest with entering the civilian workforce. Generally, many of those certified feel their military scope of practice exceeded civilian EMT certification and requested AEMT or paramedic licensure opportunities while still active duty military.
MeSH term(s)	Allied Health Personnel ; Emergency Medical Services ; Emergency Medical Technicians ; Humans ; Military Personnel
Language	English
Publishing date	2020-06-04
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usaa099
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