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1.
Mol Biol Cell ; 35(8): ar114, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38985514

RESUMO

Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from patients with IPF, we generate three-dimensional hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF extracellular matrix hydrogels, IPF fibroblasts display differential contractility compared with their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared with fibroblasts seeded two-dimensionally on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell cross-talk as a possible novel therapeutic avenue.


Assuntos
Matriz Extracelular , Fibroblastos , Hidrogéis , Fibrose Pulmonar Idiopática , Pulmão , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Fibroblastos/metabolismo , Pulmão/patologia , Pulmão/metabolismo , Matriz Extracelular/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Miofibroblastos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Actinas/metabolismo , Monócitos/metabolismo
2.
Mil Med ; 189(9-10): e2192-e2199, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687599

RESUMO

INTRODUCTION: Providing resilient Damage Control Resuscitation capabilities as close to the point of injury as possible is paramount to reducing mortality and improving patient outcomes for our nation's warfighters. Emergency Fresh Whole Blood Transfusions (EFWBT) play a critical role in supporting this capability, especially in future large-scale combat operations against peer adversaries with expected large patient volumes, restrictive operating environments, and unreliable logistical supply lines. Although there are service-specific training programs for whole blood transfusion, there is currently no dedicated EFWBT training for future military medical officers. To address this gap, we developed, implemented, and evaluated a training program to enhance EFWBT proficiency in third-year military medical students at the F. Edward Hebert School of Medicine at the USU. MATERIALS AND METHODS: After reviewing both the 75th Ranger Regiment Ranger O-Low Titer program and the Marine Corps' Valkyrie program, along with the relevant Joint Trauma System Clinical Practice Guidelines, we created a streamlined and abbreviated training curriculum. The training consisted of both online preparatory materials as well as a 2-hour in-person training that included didactic and experiential learning components. Participants were 165 active duty third-year medical students at USU. Participants were assessed using a pre- and post-assessment self-reported questionnaire on their confidence in the practical application and administrative oversight requirements of an EFWBT program. Participants' performance was also assessed using a pre/post knowledge assessment consisting of 10 multiple choice questions identified as critical to understanding of the academic principles of EFWBT along with the baseline questionnaire. RESULTS: Differences in the mean scores of the pre- and post-assessment self-reported questionnaire (increased from 2.32 to 3.95) were statistically significant (P < .001). Similarly, there was a statistically significant improvement in student test scores, with the mean score increasing by approximately 3 points or 30%. There was no significant difference in student confidence assessment or test scores based on branch of service. Students who had previously deployed did not show a statistically significant difference in scores compared to students who had not previously deployed. CONCLUSIONS: Our results suggest that the implementation of streamlined EFWBT training into the undergraduate medical education of future military medical officers offers an efficient way to improve their baseline proficiency in EFWBTs. Future research is needed to assess the impact of this training on real-world applications in forward-deployed environments.


Assuntos
Transfusão de Sangue , Currículo , Militares , Humanos , Currículo/tendências , Currículo/normas , Transfusão de Sangue/métodos , Transfusão de Sangue/estatística & dados numéricos , Militares/estatística & dados numéricos , Militares/educação , Medicina Militar/métodos , Medicina Militar/educação , Inquéritos e Questionários , Região de Recursos Limitados
3.
J Spec Oper Med ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38408046

RESUMO

BACKGROUND: Blood is a highly valuable medical resource that necessitates strict guidelines to ensure the safety and well-being of the recipient. Since the onset of the war in Ukraine there has been an increased demand for training in emergency fresh whole blood transfusion (EFWBT) to improve damage control resuscitation capabilities. To meet this demand, we developed, implemented, and evaluated a training program aimed at enhancing Ukrainian EFWBT proficiency. METHODS: Eight Ukrainian healthcare professionals (UHPs), including six physicians and two medics, completed our training, derived from the Joint Trauma System Clinical Practice Guidelines, Tactical Combat Casualty Care (TCCC) Guidelines, 75th Ranger Regiment Ranger O-Low Titer (ROLO) program, and Marine Corps Valkyrie program. Participants were assessed on their confidence in the practical application and administrative oversight requirements of an EFWBT program. A cross-comparison was conducted between a larger data set of third-year medical students from the Uniformed Services University and the UHPs to determine the statistical significance of the program. RESULTS: The difference in mean scores of UHPs during preand post-training was statistically significant (p<0.001). Additionally, the average rate of improvement was greater for the UHPs compared with the third-year medical students (p=0.000065). CONCLUSION: Our study revealed that the application of an EFWBT training program for UHPs can significantly increase confidence in their ability to conduct EFWBTs on the battlefield. Further larger-scale research is needed to determine the impact of this training on performance outcomes.

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