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Background: The importance of effective leadership for improving patient care and physician well-being is gaining increased attention in medicine. Despite this, few residency programs have formalized education on leadership in medicine. The most effective ways to train graduate medical education (GME) trainees in leadership are unclear. Methods: Our large internal medicine residency program implemented a book club to develop leadership skills in residency. Through independent reading of the selected book and resident-led small group discussions, we facilitated dialogue on the challenges of leading effectively. Results: A survey-based curricular evaluation demonstrated that 61% of respondents felt that the book club influenced their thoughts about leadership and that 66% of participants would recommend the book club to other residency programs. Lack of time was the main barrier to participation while addition of complementary media or alternative book formats were identified as possible solutions to increase engagement. Conclusions: Leadership book clubs are a practical and effective way to teach leadership during residency. More research is needed to identify the best formats for book club discussion and to develop additional tools to foster future physician leaders.
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Military physicians must often balance medical and operational priorities when providing advice to operational commanders. This case describes how a Navy Medical Corps Officer serving with a Marine Corps helicopter squadron during the initial stages of the COVID-19 pandemic helped manage risk.
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COVID-19 , Militares , Humanos , Liderança , Pandemias , SARS-CoV-2 , Estados UnidosRESUMO
Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. Injections of Y-27632 prevented and reversed the hypoxic pulmonary vasoconstrictor response. The increase in pulmonary arterial pressure in response to ventilation with a 10% O(2)-90% N(2) gas mixture was not well maintained during the period of hypoxic exposure. Treatment with the nitric oxide (NO) synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure and prevented the decline or fade in the hypoxic pulmonary vasoconstrictor response. The hypoxic pulmonary vasoconstrictor response was reversed by Y-27632 in control and in l-NAME-treated animals. The Rho kinase inhibitor attenuated increases in pulmonary arterial pressures in response to intravenous injections of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased pulmonary and systemic arterial pressures and vascular resistances in monocrotaline-treated rats. These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.
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Amidas/farmacologia , Anti-Hipertensivos/farmacologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Circulação Pulmonar/efeitos dos fármacos , Piridinas/farmacologia , Vasodilatadores/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Amidas/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática , Ativadores de Enzimas/farmacologia , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/enzimologia , Hipóxia/fisiopatologia , Injeções Intravenosas , Masculino , Monocrotalina , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/metabolismo , Guanilil Ciclase Solúvel , Fatores de Tempo , Resistência Vascular , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Quinases Associadas a rho/metabolismoRESUMO
BACKGROUND: The recently constructed river buffalo whole-genome radiation hybrid panel (BBURH5000) has already been used to generate preliminary radiation hybrid (RH) maps for several chromosomes, and buffalo-bovine comparative chromosome maps have been constructed. Here, we present the first-generation whole genome RH map (WG-RH) of the river buffalo generated from cattle-derived markers. The RH maps aligned to bovine genome sequence assembly Btau_4.0, providing valuable comparative mapping information for both species. RESULTS: A total of 3990 markers were typed on the BBURH5000 panel, of which 3072 were cattle derived SNPs. The remaining 918 were classified as cattle sequence tagged site (STS), including coding genes, ESTs, and microsatellites. Average retention frequency per chromosome was 27.3% calculated with 3093 scorable markers distributed in 43 linkage groups covering all autosomes (24) and the X chromosomes at a LOD >or= 8. The estimated total length of the WG-RH map is 36,933 cR5000. Fewer than 15% of the markers (472) could not be placed within any linkage group at a LOD score >or= 8. Linkage group order for each chromosome was determined by incorporation of markers previously assigned by FISH and by alignment with the bovine genome sequence assembly (Btau_4.0). CONCLUSION: We obtained radiation hybrid chromosome maps for the entire river buffalo genome based on cattle-derived markers. The alignments of our RH maps to the current bovine genome sequence assembly (Btau_4.0) indicate regions of possible rearrangements between the chromosomes of both species. The river buffalo represents an important agricultural species whose genetic improvement has lagged behind other species due to limited prior genomic characterization. We present the first-generation RH map which provides a more extensive resource for positional candidate cloning of genes associated with complex traits and also for large-scale physical mapping of the river buffalo genome.
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Búfalos/genética , Bovinos/genética , Genoma , Mapeamento de Híbridos Radioativos , Animais , Cromossomos de Mamíferos/genética , Etiquetas de Sequências Expressas , Marcadores Genéticos , Genômica , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O(2) gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5-10 mg/kg iv nitro-L-arginine methyl ester (L-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in L-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca(2+) channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Anestesia , Inibidores de Proteínas Quinases/farmacologia , Circulação Pulmonar/efeitos dos fármacos , Vasodilatadores/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/administração & dosagem , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Angiotensina II/farmacologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipóxia/enzimologia , Injeções Intravenosas , Isradipino/administração & dosagem , Isradipino/farmacologia , Pulmão/enzimologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Inibidores de Proteínas Quinases/administração & dosagem , Ratos , Ratos Sprague-Dawley , Resistência Vascular/efeitos dos fármacosRESUMO
The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. L-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after L-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca(++) entry blocker isradipine also decreased pulmonary and systemic arterial pressure in L-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of L-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following L-NAME treatment are mediated by Rho kinase and Ca(++) entry through L-type channels, and that responses to L-NAME can be reversed by an NO donor.
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Cálcio/metabolismo , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Artéria Pulmonar/fisiopatologia , Resistência Vascular , Vasoconstrição , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Masculino , Nitroprussiato/farmacologia , Circulação Pulmonar/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologiaRESUMO
1. Peroxynitrite (PN) is formed in biological systems from the reaction of nitric oxide (*NO) with superoxide (O2(-)*) and both exist as free radicals. By itself, PN is not a free radical, but it can generate nitrogen dioxide (*NO2) and carbonate radical (CO3(-)*) upon reaction with CO2. 2. The reaction of CO2 constitutes a major pathway for the disposition of PN produced in vivo and this is based on the rapid reaction of PN anion with CO2 and the availability of CO2 in both intra- and extracellular fluids. The free radicals *NO2 and CO3(-)*, in combination with *NO, generated from nitric oxide synthase, can bring about oxidation of critical biological targets resulting in tissue injury. However, the reactions of *NO2, CO3(-)* and *NO with carbohydrates, protein and non-protein thiols, phenols, indoles and uric acid could result in the formation of a number of nitration and nitrosation products in the vasculature. These products serve as long-acting *NO donors and, therefore, contribute to vasorelaxant properties, protective effects on the heart, inhibition of leucocyte-endothelial cell interactions and reduction of reperfusion injury. 3. Herein, we review the chemistry of PN, the observations that the effects of PN could be mediated by formation of an *NO donor-like substance and review the physiological and beneficial effects of PN.