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1.
Am J Disaster Med ; 19(1): 45-51, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38597646

RESUMO

OBJECTIVE: Active duty military surgeons often have limited trauma surgery experience prior to deployment. Consequently, military-civilian training programs have been developed at high-volume trauma centers to evaluate and maintain proficiencies. Advanced Surgical Skills for Exposure in Trauma (ASSET) was incorporated into the predeployment curriculum at the Army Trauma Training Detachment in 2011. This is the first study to assess whether military surgeons demonstrated improved knowledge and increased confidence after taking ASSET. DESIGN: Retrospective cohort study. SETTING: Quaternary care hospital. PATIENTS AND PARTICIPANTS: Attending military surgeons who completed ASSET between July 2011 and October 2020. MAIN OUTCOME MEASURE(S): Pre- and post-course self-reported comfort level with procedures was converted from a five-point Likert scale to a percentage and compared using paired t-tests. RESULTS: In 188 military surgeons, the median time in practice was 3 (1-8) years, with specialties in general surgery (52 percent), orthopedic surgery (29 percent), trauma (7 percent), and other disciplines (12 percent). The completed self-evaluation response rate was 80 percent (n = 151). The self-reported comfort level for all body regions improved following course completion (p < 0.001): chest (27 percent), neck (23 percent), upper extremity (22 percent), lower extremity (21 percent), and abdomen/pelvis (19 percent). The overall score on the competency test improved after completion of ASSET, with averages increasing from 62 ± 18 percent pretest to 71 ± 13 percent post-test (p < 0.001). CONCLUSIONS: After taking the ASSET course, military surgeons demonstrated improved knowledge and increased confidence in the operative skills taught in the course. The ASSET course may provide sustainment of knowledge and confidence if used at regular intervals to maintain trauma skills and deployment readiness.


Assuntos
Medicina Militar , Militares , Cirurgiões , Traumatologia , Humanos , Traumatologia/educação , Estudos Retrospectivos , Competência Clínica
2.
J Trauma Acute Care Surg ; 97(2S Suppl 1): S55-S59, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38787627

RESUMO

BACKGROUND: Combat casualties receiving damage-control laparotomy at forward deployed, resource-constrained US military Role 2 (R2) surgical units require multiple evacuations, but the added risk of venous thromboembolism (VTE) in this population has not been defined. To fill this gap, we retrospectively analyzed 20 years of Department of Defense Trauma Registry data to define the VTE rate in this population. METHODS: Department of Defense Trauma Registry from 2002 to 2023 was queried for US military combat casualties requiring damage-control laparotomy at R2. All deaths were excluded in subsequent analysis. Rates of VTE were assessed, and subgroup analysis was performed on patients requiring massive transfusion. RESULTS: Department of Defense Trauma Registry (n = 288) patients were young (mean age, 25 years) and predominantly male (98%) with severe (mean Injury Severity Score, 26), mostly penetrating injury (76%) and high mortality. Venous thromboembolism rate was high: 15.8% (DVT, 10.3%; pulmonary embolism, 7.1%). In the massively transfused population, the VTE rate was even higher (26.7% vs. 10.2%, p < 0.001). CONCLUSION: This is the first report that combat casualties requiring damage-control laparotomy at R2 have such high VTE rates. Therefore, for military casualties, we propose screening ultrasound upon arrival to each subsequent capable echelon of care and low threshold for initiating thromboprophylaxis. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.


Assuntos
Laparotomia , Militares , Embolia Pulmonar , Sistema de Registros , Trombose Venosa , Humanos , Masculino , Estudos Retrospectivos , Feminino , Laparotomia/estatística & dados numéricos , Laparotomia/métodos , Adulto , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/mortalidade , Estados Unidos/epidemiologia , Militares/estatística & dados numéricos , Escala de Gravidade do Ferimento , Adulto Jovem , Ferimentos e Lesões/complicações , Ferimentos e Lesões/cirurgia , Ferimentos e Lesões/mortalidade , Medicina Militar/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos
3.
J Trauma Acute Care Surg ; 95(2S Suppl 1): S13-S18, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246291

RESUMO

OBJECTIVES: The objective of this study is to describe the United States and allied military medical response during the withdrawal from Afghanistan. BACKGROUND: The military withdrawal from Afghanistan concluded with severe hostilities resulting in numerous civilian and military casualties. The clinical care provided by coalition forces capitalized on decades of lessons learned and enabled unprecedented accomplishments. METHODS: In this retrospective, observational analysis, casualty numbers, and operative information was collected and reported from military medical assets in Kabul, Afghanistan. The continuum of medical care and the trauma system, from the point of injury back to the United States was captured and described. RESULTS: Prior to a large suicide bombing resulting in a mass casualty event, the international medical teams managed distinct 45 trauma incidents involving nearly 200 combat and non-combat civilian and military patients over the preceding 3 months. Military medical personnel treated 63 casualties from the Kabul airport suicide attack and performed 15 trauma operations. US air transport teams evacuated 37 patients within 15 hours of the attack. CONCLUSION: Lessons learned from the last 20 years of combat casualty care were successfully implemented during the culmination of the Afghanistan conflict. Ultimately, the effort, teamwork, and system adaptability exemplify not only the attitudes and character of service members who provide modern combat casualty care but also the paramount importance of the battlefield learning health care system. A continued posture to maintain military surgical preparedness in unique environments remain crucial as the US military prepares for the future.Retrospective observational analysis. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.


Assuntos
Incidentes com Feridos em Massa , Medicina Militar , Militares , Ferimentos e Lesões , Humanos , Estados Unidos , Estudos Retrospectivos , Afeganistão , Medicina Militar/métodos , Campanha Afegã de 2001-
4.
Ann Surg Open ; 3(3): e180, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37601152

RESUMO

Objectives: The research question asked to what extent do self-rated performance scores of individual surgeons correspond to assessed procedural performance abilities and to peer ratings of procedural performance during a mass casualty (MASCAL) event? Background: Self-assessment using performance rating scales is ubiquitous in surgical education as a proxy for direct measurement of competence. The validity and reliability of self-ratings as competency measures are susceptible to cognitive biases such as Dunning-Kruger effects, which describe how individuals over/underestimate their own performance compared to assessments from independent sources. The ability of surgeons to accurately self-assess their procedural performance remains undetermined. Methods: A purposive sample of military surgeons (N = 13) who collectively cared for trauma patients during a MASCAL event participated in the study. Pre-event performance assessment scores for 32 trauma procedures were compared with post-event self and peer performance ratings using F tests (P < 0.05) and effect sizes (Cohen's d). Results: There were no significant differences between peer ratings and performance assessment scores. There were significant differences between self-ratings and both peer ratings (P < 0.001) and performance assessment scores (P < 0.001). Effect sizes were very large for self to peer rating comparison (Cohen's d = 2.34) and self to performance assessment comparison (Cohen's d = 2.77). Conclusions: The outcomes demonstrate that self-ratings were significantly lower than the independently determined assessment scores for each surgeon, revealing a Dunning-Kruger effect for highly skilled individuals underestimating their abilities. These outcomes underscore the limitations of self-assessment for measuring competence.

5.
Mil Med ; 186(5-6): 571-576, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33394041

RESUMO

INTRODUCTION: In peacetime, it is challenging for Army Forward Resuscitative Surgical Teams (FRST) to maintain combat readiness as trauma represents <0.5% of military hospital admissions and not all team members have daily clinical responsibilities. Military surgeon clinical experience has been described, but no data exist for other members of the FRST. We test the hypothesis that the clinical experience of non-physician FRST members varies between active duty (AD) and Army reservists (AR). METHODS: Over a 3-year period, all FRSTs were surveyed at one civilian center. RESULTS: Six hundred and thirteen FRST soldiers were provided surveys and 609 responded (99.3%), including 499 (81.9%) non-physicians and 110 (18.1%) physicians/physician assistants. The non-physician group included 69% male with an average age of 34 ± 11 years and consisted of 224 AR (45%) and 275 AD (55%). Rank ranged from Private to Colonel with officers accounting for 41%. For AD vs. AR, combat experience was similar: 50% vs. 52% had ≥1 combat deployment, 52% vs. 60% peri-deployment patient load was trauma-related, and 31% vs. 32% had ≥40 patient contacts during most recent deployment (all P > .15). However, medical experience differed for AD and AR: 18% vs. 29% had >15 years of experience in practice and 4% vs. 17% spent >50% of their time treating critically injured patients (all P < .001). These differences persisted across all specialties, including perioperative nurses, certified registered nurse anesthetists, operating room (OR) techs, critical-care nurses, emergency room (ER) nurses, licensed practical nurse (LPN), and combat medics. CONCLUSIONS: This is the first study of clinical practice patterns in AD vs. AR, non-physician members of Army FRSTs. In concordance with previous studies of military surgeons, FRST non-physicians seem to be lacking clinical experience as well. To maintain readiness and to provide optimal care for our injured warriors, the entire FRST, not just individuals, should embed within civilian centers.


Assuntos
Medicina Militar , Militares , Adulto , Serviço Hospitalar de Emergência , Feminino , Hospitais Militares , Humanos , Masculino , Pessoa de Meia-Idade , Ressuscitação , Estados Unidos , Adulto Jovem
6.
Mil Med ; 185(5-6): e724-e733, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32722768

RESUMO

INTRODUCTION: For trauma triage, the US Army has developed a portable heart rate complexity (HRC) monitor, which estimates cardiac autonomic input and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesize that autonomic/HPA stress associated with predeployment training in U.S. Army Forward Surgical Teams will cause changes in HRC. MATERIALS AND METHODS: A prospective observational study was conducted in 80 soldiers and 10 civilians at the U.S. Army Trauma Training Detachment. Heart rate (HR, b/min), cardiac output (CO, L/min), HR variability (HRV, ms), and HRC (Sample Entropy, unitless), were measured using a portable non-invasive hemodynamic monitor during postural changes, a mass casualty (MASCAL) situational training exercise (STX) using live tissue, a mock trauma (MT) STX using moulaged humans, and/or physical exercise. RESULTS: Baseline HR, CO, HRV, and HRC averaged 72 ± 11b/min, 5.6 ± 1.2 L/min, 48 ± 24 ms, and 1.9 ± 0.5 (unitless), respectively. Supine to sitting to standing caused minimal changes. Before the MASCAL or MT, HR and CO both increased to ~125% baseline, whereas HRV and HRC both decreased to ~75% baseline. Those values all changed an additional ~5% during the MASCAL, but an additional 10 to 30% during the MT. With physical exercise, HR and CO increased to >200% baseline, while HRV and HRC both decreased to 40 to 60% baseline; these changes were comparable to those caused by the MT. All the changes were P < 0.05. CONCLUSIONS: Various forms of HPA stress during Forward Surgical Team STXs can be objectively quantitated continuously in real time with a portable non-invasive monitor. Differences from resting baseline indicate stress anticipating an impending STX whereas differences between average and peak responses indicate the relative stress between STXs. Monitoring HRC could prove useful to field commanders to rapidly and objectively assess the readiness status of troops during STXs or repeated operational missions. In the future, health care systems and regulatory bodies will likely be held accountable for stress in their trainees and/or obliged to develop wellness options and standardize efforts to ameliorate burnout, so HRC metrics might have a role, as well.


Assuntos
Militares , Débito Cardíaco , Eletrocardiografia , Frequência Cardíaca , Humanos , Estudos Prospectivos
8.
Aerosp Med Hum Perform ; 90(12): 1009-1015, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747997

RESUMO

BACKGROUND: Portable noninvasive Heart Rate Complexity (HRC) and Compensatory Reserve Measurement (CRM) monitors have been developed to triage supine combat casualties. Neither monitor has been tested in upright individuals during physical exercise. This study tests the hypothesis that exercise evokes proportional changes in HRC and CRM.METHODS: Two instruments monitored volunteers (9 civilian and 11 soldiers) from the Army Trauma Training Department (ATTD) before, during, and following physical exercise. One recorded heart rate (HR, bpm), cardiac output (CO, L · min-1), heart rate variability (HRV, root mean square of successive differences, ms), and HRC (Sample Entropy, unitless). The other recorded HR, pulse oximetry (Spo2, %), and CRM (%).RESULTS: Baseline HR, CO, HRV, HRC, and CRM averaged 72 ± 1 bpm, 5.6 ± 1.2 L · min-1, 48 ± 24 ms, 1.9 ± 0.5, and 85 ± 10% in seated individuals. Exercise evoked peak HR and CO at > 200% of baseline, while HRC and CRM were simultaneously decreased to minimums that were ≤ 50% of baseline (all P < 0.001). HRV changes were variable and unreliable. Spo2 remained consistently above 95%. During a 60 min recovery, HR and CRM returned to baseline on parallel tracks (t1/2=11 ± 8 and 18 ± 14 min), whereas HRC recovery was slower than either CRM or HR (t1/2=40 ± 18 min, both P < 0.05).DISCUSSION: Exercise evoked qualitatively similar changes in CRM and HRC. CRM recovered incrementally faster than HRC, suggesting that vasodilation, muscle pump, and respiration compensate faster than cardiac autonomic control in young, healthy volunteers. Both HRC and CRM appear to provide reliable, objective, and noninvasive metrics of human performance in upright exercising individuals.Mulder MB, Eidelson SA, Buzzelli MD, Gross KR, Batchinsky AI, Convertino VA, Schulman CI, Namias N, Proctor KG. Exercise-induced changes in compensatory reserve and heart rate complexity. Aerosp Med Hum Perform. 2019; 90(12):1009-1015.


Assuntos
Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Adulto , Eletrocardiografia , Feminino , Hemostasia , Humanos , Masculino , Oximetria , Oxigênio/sangue , Estudos Prospectivos , Adulto Jovem
9.
Endocrinology ; 149(12): 6378-88, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18719026

RESUMO

TNF inhibits serine protease inhibitor 2.1 (Spi 2.1) and IGF-I gene expression by GH in CWSV-1 hepatocytes. The current study describes construction of a GH-inducible IGF-I promoter construct and investigates mechanisms by which TNF and nuclear factor-kappaB (NFkappaB) inhibit GH-inducible gene expression. CWSV-1 cells were transfected with GH-inducible Spi 2.1 or IGF-I promoter luciferase constructs, incubated with TNF signaling inhibitors (fumonisin B1 for sphingomyelinase and SP600125 for c-Jun N-terminal kinase), treated with or without TNF, and then stimulated with recombinant human GH. The 5- to 6-fold induction of Spi 2.1 and IGF-I promoter activity by GH was inhibited by TNF. Neither fumonisin B1 nor SP600125 prevented the inhibitory effects of TNF on GH-inducible promoter activity. Dominant-negative inhibitor-kappaBalpha (IkappaBalpha) expression vectors (IkappaBalphaS/A or IkappaBalphaTrunc), p65 and p50 expression vectors, and p65 deletion constructs were used to investigate the NFkappaB pathway. IkappaBalphaS/A and IkappaBalphaTrunc ameliorated the inhibitory effects of TNF on GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection of CWSV-1 cells with expression vectors for p65 alone or p50 and p65 together inhibited GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection with a C-terminal p65 deletion (1-450) enhanced GH-inducible promoter activity, whereas the N-terminal deletion (31-551) was inhibitory for IGF-I but not Spi 2.1. Cycloheximide did not antagonize the inhibitory effects of TNF on GH-inducible IGF-I expression. We conclude the inhibitory effects of TNF on GH-inducible promoter activity are mediated by NFkappaB, especially p65, by a mechanism that does not require protein synthesis.


Assuntos
Hormônio do Crescimento/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Ligases/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Ratos , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
10.
J Trauma ; 64(6): 1427-35; discussion 1435-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18545105

RESUMO

BACKGROUND: Hepatic expression of growth hormone (GH)-inducible genes serine protease inhibitor (Spi 2.1) and insulin-like growth factor (IGF)-I are inhibited by interleukin (IL)-1. The current study examines the role of the nuclear factor kappaB (NFkappaB) pathway and suppressor of cytokine signaling (SOCS)-3 expression as potential mechanisms for IL-1-mediated GH resistance. METHODS: CWSV-1 hepatocytes were cotransfected with Spi 2.1 or IGF-1 promoter luciferase constructs and empty pCMV4 vector or dominant negative inhibitor-kappaBalpha (IkappaBalpha)S/A construct. Cells were treated with or without IL-1 and then stimulated with or without recombinant human GH. Cell extracts were assayed for luciferase activity and protein, normalized and expressed as fold-induction. CWSV-1 cells transfected with pCMV4 or IkappaBalphaS/A were treated with or without IL-1 then SOCS-3 mRNA was measured. Finally, CWSV-1 cells were cotransfected with a SOCS-3 promoter construct with or without pCMV4 or IkappaBalphaS/A and then stimulated with or without IL-1 to investigate SOCS-3 promoter activity. RESULTS: CWSV-1 cells cotransfected with pCMV4 demonstrated a three- to fivefold induction of Spi 2.1 or IGF-1 promoter activity after GH stimulation that was almost completely inhibited by IL-1. Cotransfection with IkappaBalphaS/A increased GH-inducible Spi 2.1 and IGF-1 promoter activity, but the inhibitory effects of IL-1 on both promoters were attenuated by cotransfection with IkappaBalphaS/A. IL-1 stimulated SOCS-3 mRNA expression and promoter activity. Cotransfection with IkappaBalphaS/A increased IL-1-inducible SOCS-3 promoter activity, but not SOCS-3 mRNA or protein. CONCLUSIONS: Signaling via the NFkappaB pathway is responsible for the inhibitory effects of IL-1 on GH-inducible gene expression by a mechanism that does not seem to involve increased SOCS-3 expression.


Assuntos
Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Interleucina-1/farmacologia , NF-kappa B/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Fator de Crescimento Insulin-Like I/genética , Interleucina-1/metabolismo , NF-kappa B/efeitos dos fármacos , Probabilidade , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Mensageiro/análise , Sensibilidade e Especificidade , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética
11.
Mil Med ; 178(5): 507-10, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23756008

RESUMO

The Altitude Performance Test is a measure designed to assess an individual's degree of acclimatization to reduce the risk of acute mountain sickness during high-altitude activities. The aim of this study was to investigate the hypothesis that test results will improve in pre-acclimatized soldiers after several days of further acclimatization. The Altitude Performance Test consists of an uphill run at high altitude. The event is timed and performed with continuous oxygen saturation (SpO2) monitoring. The individual's time and lowest SpO2 measurement are recorded. This test was performed on the first day of arriving at 11,060 ft, and after 9 days at the same location. The 37 male soldiers were all pre-acclimatized before arrival. The sleeping altitude remained constant at 11,060 ft, and the daytime altitudes increased up to a maximum of 15,775 ft. Test results improved significantly after a further 9 days of acclimatization (time, -11 s; SpO2, +5%-points; p ≤ 0.001). This is remarkable because all soldiers were pre-acclimatized and showed only minor acute mountain sickness symptoms during the entire stay. This indicates that the acclimatization process is not finished after amelioration of altitude symptoms. The demonstrated improvement in physical performance could prove very important, particularly during military missions performed at high altitude.


Assuntos
Aclimatação/fisiologia , Adaptação Fisiológica/fisiologia , Doença da Altitude/fisiopatologia , Altitude , Militares , Montanhismo/fisiologia , Adulto , Doença da Altitude/diagnóstico , Doença da Altitude/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Adulto Jovem
12.
Am J Physiol Gastrointest Liver Physiol ; 292(6): G1793-803, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17395896

RESUMO

During systemic inflammation, the liver becomes unresponsive to growth hormone (GH), resulting in decreased plasma insulin-like growth factor-I (IGF-I) with concomitant reductions in lean body mass. Transgenic mice that overexpress IL-6 also demonstrate impaired growth and decreased IGF-I. To determine whether IL-6 directly inhibits GH-inducible gene expression, CWSV-1 hepatocytes were incubated with IL-6 (10 ng/ml), then stimulated with recombinant human GH (500 ng/ml, 18 h). The increase in IGF-I and serine protease inhibitor 2.1 (Spi 2.1) mRNA in GH-treated cells was inhibited by treatment with IL-6 for 24 h. To investigate potential mechanisms, we examined the effects of IL-6 on GH receptor (GHR) expression and GH signaling via the JAK/signal transducer and activator of transcription (STAT) and MAP kinase pathways. Incubation of cells with IL-6 (10 ng/ml, 24 h) had no effect on GHR abundance or signaling proteins JAK2, STAT5b, and ERK1/2. Although GH transiently increased (2- to 5-fold) the tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2, IL-6 did not alter these phosphorylation events. However, nuclear protein from IL-6-treated cells demonstrated reduced STAT5 DNA binding (by EMSA) at 15 min (-20%) and 60 min (-43%) after GH stimulation. To determine whether IL-6 inhibits GH-inducible promoter activity, CWSV-1 cells were transfected with Spi 2.1 or prolactin receptor promoter luciferase vectors, incubated with or without IL-6, then stimulated with GH. The induction of both Spi 2.1 (7.5-fold) and prolactin receptor (4-fold) promoter activity by GH was inhibited by IL-6. In summary, IL-6 mediates hepatic GH resistance by a time-dependent inhibition of GH-inducible promoter activity that is associated with reductions in STAT5 DNA binding.


Assuntos
Hepatócitos/metabolismo , Hormônio do Crescimento Humano/metabolismo , Interleucina-6/metabolismo , Transdução de Sinais , Transcrição Gênica , Animais , Linhagem Celular , Cromatina/metabolismo , Genes Reporter , Hepatócitos/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/farmacologia , Luciferases , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Ratos , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos , Transfecção
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