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1.
N Engl J Med ; 382(5): 416-426, 2020 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-31995687

RESUMEN

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).


Asunto(s)
Lesión Renal Aguda/sangre , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Angiografía Coronaria/efectos adversos , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Anciano , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Biomarcadores/sangre , Enfermedad Crítica , Modelos Animales de Enfermedad , Femenino , Humanos , Unidades de Cuidados Intensivos , Túbulos Renales/citología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Oportunidad Relativa , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Medición de Riesgo/métodos , Activador de Plasminógeno de Tipo Uroquinasa/farmacología
2.
Front Public Health ; 10: 1009400, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311596

RESUMEN

Background: COVID-19 underscored the importance of building resilient health systems and hospitals. Nevertheless, evidence on hospital resilience is limited without consensus on the concept, its application, or measurement, with practical guidance needed for action at the facility-level. Aim: This study establishes a baseline for understanding hospital resilience, exploring its 1) conceptualization, 2) operationalization, and 3) evaluation in the empirical literature. Methods: Following Arksey and O'Malley's model, a scoping review was conducted, and a total of 38 articles were included for final extraction. Findings and discussion: In this review, hospital resilience is conceptualized by its components, capacities, and outcomes. The interdependence of six components (1) space, 2) stuff, 3) staff, 4) systems, 5) strategies, and 6) services) influences hospital resilience. Resilient hospitals must absorb, adapt, transform, and learn, utilizing all these capacities, sometimes simultaneously, through prevention, preparedness, response, and recovery, within a risk-informed and all-hazard approach. These capacities are not static but rather are dynamic and should improve continuously occur over time. Strengthening hospital resilience requires both hard and soft resilience. Hard resilience encompasses the structural (or constructive) and non-structural (infrastructural) aspects, along with agility to rearrange the space while hospital's soft resilience requires resilient staff, finance, logistics, and supply chains (stuff), strategies and systems (leadership and coordination, community engagement, along with communication, information, and learning systems). This ultimately results in hospitals maintaining their function and providing quality and continuous critical, life-saving, and essential services, amidst crises, while leaving no one behind. Strengthening hospital resilience is interlinked with improving health systems and community resilience, and ultimately contributes to advancing universal health coverage, health equity, and global health security. The nuances and divergences in conceptualization impact how hospital resilience is applied and measured. Operationalization and evaluation strategies and frameworks must factor hospitals' evolving capacities and varying risks during both routine and emergency times, especially in resource-restrained and emergency-prone settings. Conclusion: Strengthening hospital resilience requires consensus regarding its conceptualization to inform a roadmap for operationalization and evaluation and guide meaningful and effective action at facility and country level. Further qualitative and quantitative research is needed for the operationalization and evaluation of hospital resilience comprehensively and pragmatically, especially in fragile and resource-restrained contexts.


Asunto(s)
COVID-19 , Formación de Concepto , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Hospitales , Liderazgo , Comunicación
3.
Eval Health Prof ; 40(2): 127-150, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-26660346

RESUMEN

The case for a more diverse health-care workforce has never been stronger given the rapidly changing demographics of the United States and the continued underrepresentation of certain racial and ethnic groups across the health professions. To date, progress toward diversifying the health-care workforce has been and continues to be deterred by a mix of factors at the societal, institutional, and individual levels. Since the 1970s, the Federal government has invested resources in initiatives that support the training and development of the existing workforce as well increase the supply of new health professionals-particularly those from underrepresented minority groups and/or from disadvantaged backgrounds. However, limited studies have been published detailing the processes, outputs and, where available, outcomes of such investments across multiple years. This article describes how the Health Resources and Services Administration's Bureau of Health Workforce used retrospective case study methodology to evaluate processes and outputs associated with the Scholarships for Disadvantaged Students program-an over US$40 million annual Federal investment aimed at offsetting tuition costs for health professions students from disadvantaged backgrounds-over a 5-year period. Lessons learned and recommendations for strengthening the program's design and requirements are provided.


Asunto(s)
Diversidad Cultural , Becas/organización & administración , Financiación Gubernamental/organización & administración , Personal de Salud/educación , Grupos Minoritarios/educación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Socioeconómicos , Estados Unidos , Adulto Joven
4.
Public Health Rep ; 129 Suppl 2: 51-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24385665

RESUMEN

The Health Resources and Services Administration maintains a strong emphasis on increasing the diversity of the health-care workforce through its grant programs. Increasing the diversity of the workforce is important for reducing health disparities in the population caused by socioeconomic, geographic, and race/ethnicity factors because evidence suggests that minority health professionals are more likely to serve in areas with a high proportion of underrepresented racial and ethnic minority groups. The data show success in increasing the diversity of enrollees in five nursing programs.


Asunto(s)
Diversidad Cultural , Fuerza Laboral en Salud/estadística & datos numéricos , United States Health Resources and Services Administration/organización & administración , Femenino , Humanos , Masculino , Grupos Minoritarios/estadística & datos numéricos , Enfermería/estadística & datos numéricos , Dinámica Poblacional/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Estados Unidos/epidemiología , Poblaciones Vulnerables/estadística & datos numéricos
5.
Int J Food Microbiol ; 151(2): 216-22, 2011 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-21924789

RESUMEN

Escherichia coli O157:H7 has been associated in multiple outbreaks linked to the consumption of whole produce and fresh-cut leafy vegetables. However, plant-based foods had not been traditionally recognized as a host for enteric pathogens until the elevated incidence of produce-related outbreaks became apparent. The survival dynamics of two cocktails of generic E. coli (environmental water, plant and soil isolates) and E. coli O157:H7 within the phyllosphere of Mizuna, Red Chard and Tatsoi during their production, harvest, minimal processing, packaging and storage over two greenhouse production cycles were studied. Genotyping of applied generic E. coli strains to evaluate their comparative survival and relative abundance in the phyllosphere by REP-PCR is also reported. The Mizuna, Red Chard and Tatsoi shoots were grown under standard greenhouse conditions and fertility management. Both E. coli cocktails were spray-inoculated separately and determined to result in an initial mean population density of log 4.2 CFU/cm². Leaves were harvested as mini-greens approximating commercial maturity, minimally processed in a model washing system treated with 3 mg/L of ClO2 and stored for 7 days at 5 °C. Rapid decline of generic E. coli and E. coli O157:H7 populations was observed for all plant types regardless of the leaf age at the time of inoculation and the irrigation type across both seasonal growth cycle trials. The decline rate of the surviving populations for the fall season was slower than for the summer season. The minimal processing with 3 mg/L of ClO2 was not sufficient to fully disinfect the inoculated leaves prior to packaging and refrigerated storage. Viable populations of E. coli and E. coli O157:H7 were confirmed throughout storage, including the final time point at the end of acceptable visual leaf quality. In this study, the ability of low populations of E. coli to survive during production and postharvest operations in selected mini-greens has been demonstrated. However, further field-based trials are needed to expand understanding of the post-contamination fate of enteric bacterial pathogens on leafy vegetables. In summary, this research work provides baseline data upon which to develop food safety preventive control guidance during the production and minimal processing of these crops.


Asunto(s)
Escherichia coli O157/crecimiento & desarrollo , Escherichia coli/crecimiento & desarrollo , Contaminación de Alimentos/análisis , Lactuca/microbiología , Recuento de Colonia Microbiana , Escherichia coli/genética , Escherichia coli O157/genética , Manipulación de Alimentos , Genotipo , Viabilidad Microbiana , Hojas de la Planta/microbiología
6.
Acta Cir Bras ; 25(1): 28-33, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20126884

RESUMEN

PURPOSE: To verify the effect of highly concentrated platelet-rich plasma (hPRP) in the pathways of bone repair using non-critical defects in the calvaria of rabbits. METHODS: The hPRP was produced from collected venous blood of 21 rabbits. Four non-critical defects of 8 mm in diameter were created on the calvaria of each animal. The defects were all treated differently: autogenous particled bone (APB, group 1), autogenous particled bone associated with hPRP (APB + hPRP, group 2), isolated hPRP (group 3), and blood clot (control, group 4). Animals were submitted to euthanasia on the 2nd, 4th and 6th week postoperatively. Histological and histomorphometric analysis were carried through. RESULTS: After two weeks, groups 1 and 2 were in more advanced stage of repair than 3 and 4. At this period, comparing the groups 1 and 2, no significant differences were found between both, which also happened between the groups 3 and 4. However, after four and six weeks, the group 1 showed a more advanced stage of repair among all the other studied groups, while group 2 was in more advanced signs of bone repair than groups 3 and 4. Comparing groups 3 and 4, after four and six weeks, the least advanced stage of bone repair was found to be within group 3. CONCLUSION: The use of a highly concentrated PRP was considered prejudicial to the repair of non-critical defects in the calvaria of rabbits, either in the association of autogenous particled bone, when compared to autogenous particled bone alone, or in its isolated form, when compared to blood clot (control).


Asunto(s)
Regeneración Ósea/fisiología , Plasma Rico en Plaquetas , Cráneo/lesiones , Animales , Femenino , Modelos Animales , Conejos , Distribución Aleatoria , Cráneo/metabolismo
8.
Acta cir. bras ; 25(1): 28-33, jan.-fev. 2010. ilus, tab
Artículo en Inglés | LILACS | ID: lil-537118

RESUMEN

PURPOSE: To verify the effect of highly concentrated platelet-rich plasma (hPRP) in the pathways of bone repair using non-critical defects in the calvaria of rabbits. METHODS: The hPRP was produced from collected venous blood of 21 rabbits. Four non-critical defects of 8 mm in diameter were created on the calvaria of each animal. The defects were all treated differently: autogenous particled bone (APB, group 1), autogenous particled bone associated with hPRP (APB + hPRP, group 2), isolated hPRP (group 3), and blood clot (control, group 4). Animals were submitted to euthanasia on the 2nd, 4th and 6th week postoperatively. Histological and histomorphometric analysis were carried through. RESULTS: After two weeks, groups 1 and 2 were in more advanced stage of repair than 3 and 4. At this period, comparing the groups 1 and 2, no significant differences were found between both, which also happened between the groups 3 and 4. However, after four and six weeks, the group 1 showed a more advanced stage of repair among all the other studied groups, while group 2 was in more advanced signs of bone repair than groups 3 and 4. Comparing groups 3 and 4, after four and six weeks, the least advanced stage of bone repair was found to be within group 3. CONCLUSION: The use of a highly concentrated PRP was considered prejudicial to the repair of non-critical defects in the calvaria of rabbits, either in the association of autogenous particled bone, when compared to autogenous particled bone alone, or in its isolated form, when compared to blood clot (control).


OBJETIVO: Verificar os efeitos do plasma rico em plaquetas altamente concentrado (hPRP) sobre o reparo ósseo, utilizando defeitos não críticos na calvária de coelhos. MÉTODOS: O concentrado de plaquetas foi produzido a partir de sangue venoso coletado de 21 coelhos. Quatro defeitos não críticos de 8 mm de diâmetro foram criados na calvária de cada animal. Os defeitos foram tratados de modo distinto: osso autógeno particulado (grupo 1), osso autógeno particulado associado com hPRP (grupo 2), hPRP de modo isolado (grupo 3) e coágulo sangüineo (controle, grupo 4). Os animais foram mortos na 2º, 4º e 6º semanas do pós-operatório. Análises histológicas e histomorfométricas foram realizadas. RESULTADOS: Em duas semanas, os grupos 1 e 2 estavam num estado de reparação mais adiantado que os grupos 3 e 4. Neste período, quando comparados os grupos 1 e 2, não foram observadas diferenças estatísticamente significativas, o mesmo acontecendo quando a comparação foi entre os grupos 3 e 4. Após quatro e seis semanas, contudo, o grupo1 mostrou um estágio mais avançado de reparo, isto quando comparado com todos os outros grupos estudados, enquanto o grupo 2 apresentou sinais mais avançados de reparo que os grupos 3 e 4. Comparando os grupos 3 e 4, após 4 e 6 semanas, um estágio menos avançado do reparo ósseo foi observado no grupo 3. CONCLUSÃO: O uso do plasma rico em plaquetas altamente concentrado foi considerado prejudicial ao reparo de defeitos não críticos na calvária de coelhos, tanto quando em associação com enxerto ósseo autógeno em partículas (quando comparado com enxerto ósseo em partículas de forma isolada) quanto em sua forma isolada (quando comparado com o coágulo sangüíneo-controle).


Asunto(s)
Animales , Femenino , Conejos , Regeneración Ósea/fisiología , Plasma Rico en Plaquetas , Cráneo/lesiones , Modelos Animales , Distribución Aleatoria , Cráneo/metabolismo
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