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1.
Lancet Reg Health West Pac ; 48: 101120, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38993540

RESUMEN

Background: Healthcare-associated infections (HAI) and antimicrobial use (AMU) are drivers for antimicrobial resistance, and robust data are required to inform interventions and track changes. We aimed to estimate the prevalence of HAI and AMU at Port Moresby General Hospital (PMGH), the largest hospital in Papua New Guinea. Methods: We did a point prevalence survey (PPS) on HAI and AMU at PMGH in May 2023 using the European Centre for Disease Prevention and Control (ECDC) PPS protocol. We included all critical care patients and randomly sampled half of the patients in other acute-care wards. We calculated weighted HAI and AMU prevalence estimates to account for this sampling strategy. Weighted HAI estimates were also calculated for an expanded definition that included physician diagnosis. Findings: Of 361 patients surveyed in 18 wards, the ECDC protocol identified 28 HAIs in 26 patients, resulting in a weighted HAI prevalence of 6.7% (95% CI: 4.6, 9.8). Surgical site infections (9/28, 32%) were the most common HAI. When adding physician diagnosis to the ECDC definitions, more skin and soft tissue, respiratory, and bloodstream HAIs were detected, and the weighted HAI prevalence was 12.4% (95% CI: 9.4, 16.3). The prevalence of AMU was 66.5% (95%CI: 61.3, 71.2), and 73.2% (263/359) of antibiotics were from the World Health Organization Access group. Interpretation: This is the first reported hospital PPS of HAI and AMU in Papua New Guinea. These results can be used to prioritise interventions, and as a baseline against which future point prevalence surveys can be compared. Funding: Australian Government Department of Foreign Affairs and Trade and Therapeutic Guidelines Limited Australia.

2.
J Public Health Policy ; 45(2): 283-298, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38594480

RESUMEN

Using two qualitative data sources: free-text responses to an open-ended question of an online survey and subsequent interviews and focus groups, we explored perceptions and attitudes toward COVID-19 vaccination among health professional students enrolled in Australian universities during the pandemic with data collected from October 2021 to April 2022. Students provided free-text responses to the open-ended question (n = 313) in the online survey and participated in interviews or focus groups (n = 17). Data analysis revealed three themes, including perceptions of COVID-19 seriousness and the risk of contracting the virus, information dissemination, and attitudes toward the vaccine mandate. The study identified evolving perceptions of COVID-19 seriousness among Australian health professional students and their sentiments toward the vaccine mandate. There is a need to ensure the quality of information dissemination related to the vaccine mandate. This may not only support students' uptake of mandatory vaccination but also provide a means for them to address vaccination with healthcare consumers and patients.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Investigación Cualitativa , Humanos , Australia , COVID-19/prevención & control , COVID-19/epidemiología , Masculino , Femenino , Vacunas contra la COVID-19/administración & dosificación , Adulto , Adulto Joven , SARS-CoV-2 , Actitud del Personal de Salud , Vacunación/psicología , Vacunación/estadística & datos numéricos , Estudiantes del Área de la Salud/psicología , Estudiantes del Área de la Salud/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Grupos Focales
3.
J Am Dent Assoc ; 155(6): 475-483, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38530692

RESUMEN

BACKGROUND: Tooth autotransplantation (AT) involves the surgical relocation of a tooth from 1 site in the mouth to another site within the same patient. This approach is a good option in a growing patient when dental implant placements or fixed bridges are not suitable and when preserving natural teeth is a priority. Tooth AT is a complex procedure that requires specialized skills from a multidisciplinary team with careful patient and tooth selection and treatment planning. TYPES OF STUDIES REVIEWED: The authors provided a review of the state of knowledge and research on tooth AT and presented a case scenario and barriers to adoption, with a focus on the United States. RESULTS: Success rates for tooth AT can vary depending on several factors, including the patient's overall health, specific tooth involved, skill of the dental surgeon, and postoperative care provided. Long-term outcomes of autotransplanted teeth have been cited in the literature with impressive longitudinal follow-up spanning up to 26 years. Results of several systematic reviews showed survival rates from 75% through 98%. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Adoption of tooth AT has grown over the years, owing to advancements in dental techniques, improved patient outcomes, and increased awareness among both dentists and patients. Increasing awareness and availability of tooth AT to replace missing teeth can provide a natural and functional alternative to traditional prosthetic options. Tooth AT helps preserve the alveolar bone in growing patients and can offer excellent esthetic and functional outcomes.


Asunto(s)
Diente , Trasplante Autólogo , Humanos , Diente/trasplante , Femenino
4.
J Dent Educ ; 87(12): 1718-1724, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37740716

RESUMEN

INTRODUCTION: As part of curriculum innovation, the University of North Carolina (UNC) Adams School of Dentistry identified core entrustable professional activities (EPAs) that graduates must demonstrate for practice readiness. This paper describes the development of the UNC EPAs and the perceptions of the general dentistry faculty. METHODS: Upon establishing a blueprint of knowledge, skills, and attitudes of UNC graduates, using a distributed leadership approach, faculty teams developed EPAs focused on the patient care process. The American Dental Education Association Compendium of Clinical Competency Assessments and Commission on Dental Accreditation Standards informed the team's work. Perceptions of the assessment framework were examined using a questionnaire completed by 13 general dentistry faculty considering the importance, accuracy, and agreement of each EPA, associated domains of competence, and encounter management on a 6-point rating scale. RESULTS: Distributed leadership was a useful strategy in EPA development to disperse decision-making and build ownership. Through multiple iterations, four EPAs (assessment, plan of care, collaborative care, and provision of care) with associated sub-EPAs emerged. EPAs included a description, required knowledge and skills, and rubrics for assessment. The general dentistry faculty reported a high level of importance, accuracy, and agreement with EPAs, domains of competence, and encounter management. DISCUSSION: EPAs provide a standardized manner to describe the comprehensive work dentists perform, shifting away from individual competencies. The UNC EPAs provide the foundation for longitudinal measures of competence preparing graduates for independent practice. With limited EPAs frameworks available in dentistry, we aim to inform the development and implementation of EPAs across dental education.


Asunto(s)
Educación Basada en Competencias , Internado y Residencia , Humanos , Evaluación Educacional , Curriculum , Competencia Clínica , Odontología
5.
J Dent Educ ; 87(9): 1279-1283, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37401448

RESUMEN

Curriculum transformation is a guiding principle and driving force to continued institutional growth and innovation in oral health education. The transformation process starts from the need and desire for change to achieve the strategic goals of curriculum invocation. The design and implementation process must follow a systematic approach to ensure the oral health curricula are meeting the demands of preparing learners for their future careers and are in line with the institutional strategic goals and processes. The process of curriculum transformation needs to be carefully crafted and implemented to include all constituents and have clear and measurable outcomes to define its path and results. The University of North Carolina at Chapel Hill Adams School of Dentistry is undergoing the journey of oral health curriculum innovation and transformation. The goal of this paper is to describe the change management process using Kotter's organizational model that may apply to other schools aiming to innovate dental curricula.


Asunto(s)
Gestión del Cambio , Curriculum , Educación en Odontología/métodos , Modelos Educacionales , Instituciones Académicas
6.
J Public Health Policy ; 44(3): 400-414, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37330562

RESUMEN

Using a cross-sectional online survey we investigated knowledge, attitudes, and risk perception about COVID-19 vaccination and identified factors influencing vaccine uptake among Australian health professional students from October 2021 to January 2022. We analysed data from 1114 health professional students from 17 Australian universities. Most participants were enrolled in nursing programs (n = 958, 86.8%), and 91.6% (n = 858) of the participants received COVID-19 vaccination. Approximately 27% believed COVID-19 was no more serious than seasonal influenza and that they had a low risk of acquiring COVID-19. Nearly 20% disagreed that COVID-19 vaccines in Australia were safe and perceived they were at higher-risk of acquiring COVID infection than the general population. Higher-risk perception viewing vaccination as their professional responsibility, and vaccine mandate strongly predicted vaccination behaviour. Participants consider COVID-19 information from health professionals, government websites, and World Health Organization as the most trusted information sources. The findings highlight that healthcare decision-makers and university administrators need to monitor students' hesitancy with vaccination to improve students' promotion of the vaccination to the general population.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Estudios Transversales , Australia/epidemiología , Estudiantes , Vacunación
7.
Infect Dis Health ; 28(2): 75-80, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36182544

RESUMEN

BACKGROUND: To describe and analyse the infection prevention and control (IPC) curricula within Public Health degrees across Australian and New Zealand Universities and identify foundational IPC knowledge deficits. METHODS: A cross-sectional study of public health and related programs across tertiary education institutions within Australia and New Zealand was conducted to comprehensively illustrate the current inclusion of IPC core and elective courses and identify areas of IPC content deficit. RESULTS: Australian (n = 32) and New Zealand (n = 9) universities were audited, consisting of 217 public health/public health related degrees within Australia and 45 within New Zealand. Within Australia 41% of public health degrees and 49% in New Zealand did not offer any IPC content as core or elective subjects. CONCLUSIONS: Public health tertiary education in Australia and New Zealand is lacking in equipping and imbedding IPC skills and knowledge in public health graduates. This highlights the need for a framework guiding mandatory IPC content within Australian and New Zealand public health programs.


Asunto(s)
Salud Pública , Humanos , Universidades , Nueva Zelanda , Estudios Transversales , Australia
8.
Artículo en Inglés | MEDLINE | ID: mdl-36483332

RESUMEN

The updated vancomycin guideline for treatment of serious methicillin-resistant Staphylococcus aureus infections prompted institutions to convert from trough to area-under-the-curve monitoring. The physician perception of the transition, coupled with that of pharmacists, was measured by pre- and postimplementation surveys. Both groups believed safety would be increased without efficacy changes.

9.
Open Forum Infect Dis ; 9(7): ofac287, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35866101

RESUMEN

Mycobacterium chimaera, a member of the Mycobacterium avium complex, can cause infections in individuals after open heart surgery due to contaminated heater-cooler units. The diagnosis can be challenging, as the incubation period can be quite variable, and symptoms are nonspecific. In addition to aggressive surgical management, combination pharmacologic therapy is the cornerstone of therapy, which should consist of a macrolide, a rifamycin, ethambutol, and amikacin. Multiple second-line agents may be utilized in the setting of intolerances or toxicities. In vitro susceptibility of these agents is similar to activity against other species in the Mycobacterium avium complex. Drug-drug interactions are frequently encountered, as many individuals have chronic medical comorbidities and are prescribed medications that interact with the first-line agents used to treat M. chimaera. Recognition of these drug-drug interactions and appropriate management are essential for optimizing treatment outcomes.

10.
Australas Emerg Care ; 25(4): 361-366, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35688783

RESUMEN

OBJECTIVE: To investigate the prevalence of intravenous and interosseous device insertion in the prehospital setting by prehospital clinicians, and the characteristics of patients receiving these devices as reported to the United States of America National Emergency Medical Services Information System. METHODS: A retrospective analysis of the United States of America National Emergency Medical Services Information System public release dataset for the 2016 calendar year. RESULTS: A total of 20,454,975 events involving 40,438,959 procedures were analysed. One or more peripheral intravenous catheters were inserted during 27.4 % of events, and one or more intraosseous devices in 0.4 % of events. Insertion was completed with one attempt in 71.6 % of peripheral intravenous catheter insertions and 86.9 % of intraosseous devices insertions. Insertion was successful for 74.7 % of peripheral intravenous catheter insertions and 85.4 % of intraosseous device insertions. High rates of peripheral intravenous catheter insertion were found with: being female (51.6 %), aged 40-90 years (80.2 %), having a cardiac rhythm disturbance (70.3 %), having a primary symptom of change in responsiveness (58.7 %), or when there was initiation of chest compressions (50.4 %). There were high rates of intraosseous device insertion if the patient was male (57.8 %), aged 40-90 years (77.2 %), experienced a cardiac arrest (29.2 %), had chest compressions initiated (33.6 %), or died (16.4 %). Scene time was longest for events with intraosseous devices inserted (19.7 min, IQR 13.2-28.6) but transport time shortest (9.0 min, IQR 5.0-15.0). CONCLUSIONS: The distribution of patient factors and the insertion of peripheral intravenous catheters and intraosseous devices is described at a national level for the first time. The results provide prehospital clinicians and Emergency Medical Services rigorous data to compare, and possibly improve, practice.


Asunto(s)
Cateterismo Periférico , Servicios Médicos de Urgencia , Servicios Médicos de Urgencia/métodos , Femenino , Humanos , Sistemas de Información , Infusiones Intraóseas , Masculino , Estudios Retrospectivos , Estados Unidos
11.
Australas Emerg Care ; 25(4): 302-307, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35272963

RESUMEN

OBJECTIVE: To overcome the lack of larger, population-based studies reporting the prevalence of insertion of PIVCs and IO devices, and to describe the patient-related and service-related characteristics of these devices, inserted by paramedics, in an Australian state ambulance service. METHODS: A retrospective analysis of the electronic Ambulance Report Form (medical record) and Computer Aided Dispatch system from the 1st July 2016 until 30th June 2017. RESULTS: 709,217 events were analysed. Of these, 20.4% involved at least one successful PIVC insertion and 0.07% involved at least one successful IO device insertion; most of the time on first attempt (89% and 86.4% respectively). Most PIVCs were inserted into the right antecubital fossa or dorsum of the right hand while IO devices were inserted into the proximal tibia. Of male patients, 21.4% received PIVCs while 19.5% of female patients received PIVCs. Very low numbers of both male and female patients received IOs (0.1%). Medical, non-traumatic presentations were the most common presentation and received the most insertions of both devices, followed by trauma presentations. Advanced Care Paramedics inserted 84.0% of PIVCs while Critical Care Paramedics inserted 94.4% of IO devices. Time treating and transporting patients generally increased with number of attempts at vascular access undertaken. CONCLUSIONS: Queensland paramedic practices relating to insertion of PIVCs, and IO devices appears consistent with documented practice internationally. Further study is required to determine whether the antecubital fossa and dorsum of the hand insertions are clinically necessary in this population as areas of flexion and distal extremities are generally to be avoided for PIVC insertion.


Asunto(s)
Ambulancias , Infusiones Intraóseas , Australia , Catéteres , Femenino , Humanos , Masculino , Estudios Retrospectivos
12.
Prehosp Disaster Med ; 36(3): 321-337, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33618789

RESUMEN

BACKGROUND: Infectious disease emergencies are increasingly becoming part of the health care delivery landscape, having implications to not only individuals and the public, but also on those expected to respond to these emergencies. Health care workers (HCWs) are perhaps the most important asset in an infectious disease emergency, yet these individuals have their own barriers and facilitators to them being willing or able to respond. AIM: The purpose of this review was to identify factors affecting HCW willingness to respond (WTR) to duty during infectious disease outbreaks and/or bioterrorist events. METHODS: An integrative literature review methodology was utilized to conduct a structured search of the literature including CINAHL, Medline, Embase, and PubMed databases using key terms and phrases. PRISMA guidelines were used to report the search outcomes and all eligible literature was screened with those included in the final review collated and appraised using a quality assessment tool. RESULTS: A total of 149 papers were identified from the database search. Forty papers were relevant following screening, which highlighted facilitators of WTR to include: availability of personal protective equipment (PPE)/vaccine, level of training, professional ethics, family and personal safety, and worker support systems. A number of barriers were reported to prevent WTR for HCWs, such as: concern and perceived risk, interpersonal factors, job-level factors, and outbreak characteristics. CONCLUSIONS: By comprehensively identifying the facilitators and barriers to HCWs' WTR during infectious disease outbreaks and/or bioterrorist events, strategies can be identified and implemented to improve WTR and thus improve HCW and public safety.


Asunto(s)
Personal de Salud , Equipo de Protección Personal , Actitud del Personal de Salud , Bioterrorismo , Brotes de Enfermedades/prevención & control , Humanos
13.
BMJ Open ; 8(4): e020838, 2018 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-29678988

RESUMEN

OBJECTIVES: The Medical Protection Society (MPS) is a leading protection organisation for healthcare professionals worldwide. In the UK and Ireland, a small minority of MPS members experience significantly more medicolegal cases than their peers and are invited to participate in a risk education (RE) remediation process. To understand more about this educational intervention, we sought to explore participating doctors' views of their experiences of this process and identify self-reported performance improvements and what elements of the intervention could be improved. DESIGN: Qualitative semistructured telephone interviews with a convenience sample of doctors with significantly more medicolegal cases than their peers identified by MPS. SETTING: UK and Ireland MPS members. PARTICIPANTS: A convenience sample of 20 general medical practitioners and hospital specialists from a total of 79 who completed the RE process (25.3% response rate), with a particular focus on the Member Risk Review programme, between November 2013 and October 2015. RESULTS: 19 participants were male and 16 were based in general medical (office) practice. Three key themes were generated: personal and professional impacts and actions (eg, member has taken action to reduce clinical workload); comprehension and validity of RE interventions (eg, risks were related to wider patient management); and feedback and proposals (eg, the supportive nature of the educational interventions should be clear from the start). A number of recommendations were made by participants to improve the RE process and enhance the educational experience. CONCLUSIONS: The RE process was largely valued by participants with many reporting that participation led to some positive professional behaviour changes and improvements in practice processes and personal well-being.


Asunto(s)
Educación Profesional , Responsabilidad Legal , Mala Praxis/legislación & jurisprudencia , Médicos/legislación & jurisprudencia , Gestión de Riesgos , Educación Médica , Femenino , Personal de Salud , Humanos , Irlanda , Masculino , Investigación Cualitativa , Riesgo , Reino Unido
14.
Australas Emerg Nurs J ; 19(3): 149-52, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27133874

RESUMEN

BACKGROUND: Emergency department (ED) presentations have increased significantly domestically and internationally. Swift identification and implementation of transmission based precautions (TBP) for patients known or suspected of having an epidemiologically important pathogen is important. ED staff, particularly triage nurses, are pivotal in detecting and preventing infection, including healthcare associated infections (HAI). METHODS: MEDLINE, CINAHL, PubMed and Ovid were searched for articles published between 2004 and 2015 using key search terms: infection control/prevention and emergency department(s), triage, and transmission based precautions and emergency department(s), and triage, to identify common themes for discussion. Systematic review/meta-analysis was not in the scope of this exploration. FINDINGS: Themes were identified relating to HAI and ED practices and grouped into: assisted detection of conditions for which TBP is required, ED and TBP, mass-causality event/bioterrorism/pandemic/epidemic, infection control not TBP and multi-resistant organisms not TBP. The literature is heavily influenced by worldwide epidemic/pandemics and bioterrorist risks resulting in increased awareness of the importance of swift identification of syndromes that require TBP, but only in these situations. CONCLUSION: Implementation of appropriate TBP, changing triage practices, training and measures to assist decision-making could assist in preventing HAI in the ED context. A systematic quantitative review of the literature is recommended to guide practice change research.


Asunto(s)
Infección Hospitalaria/prevención & control , Control de Infecciones/métodos , Infección Hospitalaria/enfermería , Infección Hospitalaria/transmisión , Enfermería de Urgencia/métodos , Servicio de Urgencia en Hospital , Humanos , Práctica Profesional , Triaje/métodos
15.
Nurse Educ Pract ; 14(1): 12-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23880300

RESUMEN

The use of simulation as a teaching strategy in undergraduate nursing education is gaining increasing credibility and popularity. This article describes a study undertaken to evaluate first-year undergraduate nursing students' level of satisfaction with a new model of teaching clinical skills using unfolding case studies in a high-fidelity simulated clinical setting. The design incorporated a case study design conducted over 4 × 6 h simulation sessions. Participants included 47 first year Bachelor of Nursing Science students, three academic staff and two standardised patients. Findings from the study provide qualitative and quantitative evidence to support a high fidelity simulated model of teaching clinical skills development for first year undergraduate nursing students. High positive scores in all sections of the student survey provide quantitative evidence of student's satisfaction with all elements of the teaching model and qualitative data from interviews supporting this claim. Additionally, analysis of interview data provides qualitative evidence to support the value of the learning experience for students and academics, and students desire to participate more frequently in simulation sessions.


Asunto(s)
Bachillerato en Enfermería/métodos , Simulación de Paciente , Aprendizaje Basado en Problemas/métodos , Estudiantes de Enfermería/psicología , Comportamiento del Consumidor , Curriculum , Bachillerato en Enfermería/normas , Humanos , Entrevistas como Asunto , Modelos Educacionales , Aprendizaje Basado en Problemas/tendencias , Investigación Cualitativa , Enseñanza/métodos , Enseñanza/tendencias
16.
Prehosp Disaster Med ; 28(3): 272-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23534527

RESUMEN

INTRODUCTION: Tropical cyclone (TC) Yasi, thought to be the largest and most severe cyclone to cross the Queensland coast since 1918, made landfall on the southern tropical coast near Mission Beach and continued to track westward across Northern Queensland on February 3, 2011. The warning and response model (WRM) suggests that situational factors, personal characteristics, and social contextual variables influence the degree of threat perceived and protective actions taken. Aim The aim of this study was to examine preparation for this impending natural disaster by residents of the affected regions, and to identify the residents' resource losses and symptoms of psychological distress following TC Yasi. METHODS: A cross-sectional survey was conducted 6-12 months after the cyclone using an adapted tool designed to measure preparedness, loss and psychosocial distress. Four hundred and thirty-three responses were received. Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS). Categorical characteristics were described using sample size and percentages. RESULTS: Almost all respondents perceived the cyclone warning as serious or very serious, and more than a third started preparing for the cyclone at least three days before it reached landfall. Overall, 115 (26.7%) respondents reported moderate and 59 (13.7%) reported major property damage; 72 (17.1%) reported a moderate and 49 (11.6%) reported a major change in their feeling of whether they have control over their life; 55 (13.1%) reported a major change in their motivation of getting things done; and 33 (7.9%) reported a major change in their perception of feeling valuable to others. Overall, 142 (34.1%) documented at least one of five symptoms of acute distress. CONCLUSION: The findings document the experiences of Australians who have lived through tropical cyclone Yasi. The results support the WRM theory which proposes that people with previous experience take threatened disasters seriously.


Asunto(s)
Tormentas Ciclónicas , Planificación en Desastres , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Actitud , Estudios Transversales , Tormentas Ciclónicas/historia , Femenino , Historia del Siglo XXI , Humanos , Masculino , Persona de Mediana Edad , Queensland , Estrés Psicológico , Adulto Joven
17.
Physiol Rev ; 91(3): 1023-70, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21742795

RESUMEN

One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses.


Asunto(s)
Miocardio/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Señalización del Calcio/fisiología , Cardiomiopatías/fisiopatología , Supervivencia Celular/fisiología , Activación Enzimática , Humanos , MicroARNs/metabolismo , Mitocondrias/enzimología , Contracción Miocárdica/fisiología , Neovascularización Fisiológica/fisiología , Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Caracteres Sexuales , Transducción de Señal/fisiología
18.
Proc Natl Acad Sci U S A ; 108(15): 6145-50, 2011 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-21444791

RESUMEN

Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control of cell proliferation and stress responses. Our group previously demonstrated induction of the nucleolar protein nucleostemin (NS) in response to cardiac pathological insult. NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective properties. The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event associated with stress response in cardiac cells. Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosomal RNA synthesis occurs in both neonatal rat cardiomyocytes (NRCM) and cardiac progenitor cells (CPC) upon exposure to doxorubicin or actinomycin D. Silencing of NS significantly increases cell death resulting from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death. Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultured cardiomyocytes challenged with doxorubicin. The presence of altered nucleolar structures resulting from myocardial infarction in mice supports the model of nucleolar stress as a general response to pathological injury. Collectively, these findings serve as the initial description of myocardial nucleolar stress and establish the postulate that nucleoli acts as sensors of stress, regulating the cellular response to pathological insults.


Asunto(s)
Proteínas Portadoras/metabolismo , Nucléolo Celular/metabolismo , Miocardio/metabolismo , Proteínas Nucleares/metabolismo , Estrés Fisiológico , Animales , Aorta/metabolismo , Aorta/patología , Apoptosis , Nucléolo Celular/patología , Células Cultivadas , Constricción Patológica/metabolismo , Constricción Patológica/patología , Proteínas de Unión al GTP , Humanos , Ratones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Nucleofosmina , ARN Ribosómico/biosíntesis , Proteínas de Unión al ARN , Ratas
19.
Eur Heart J ; 32(17): 2179-88, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21228009

RESUMEN

AIMS: The cascade of events leading to compromised mitochondrial integrity in response to stress is mediated by various combinatorial interactions of pro- and anti-apoptotic molecules. Nur77, an immediate early gene that encodes a nuclear orphan receptor, translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis in cancer cells in response to various pro-apoptotic treatments. However, the role of Nur77 in the cardiac setting is still unclear. The objective of this study is to determine the physiological relevance and pathophysiological importance of Nur77 in cardiomyocytes. METHODS AND RESULTS: Myocardial Nur77 is upregulated following cardiomyopathic injury and, while expressed in the postnatal myocardium, declines in level within weeks after birth. Nur77 is localized predominantly in cardiomyocyte nuclei under normal conditions where it is not apoptotic, but translocates to mitochondria in response to oxidative stress both in vitro and in vivo. Mitochondrial localization of Nur77 induces cytochrome c release and typical morphological features of apoptosis, including chromatin condensation and DNA fragmentation. Knockdown of Nur77 rescued hydrogen peroxide-induced cardiomyocyte apoptosis. CONCLUSION: Translocation of Nur77 from the nucleus to the mitochondria in cardiomyocytes results in the loss of mitochondrial integrity and subsequent apoptosis in response to ischaemia/reperfusion injury. Our findings identify Nur77 as a novel mediator of cardiomyocyte apoptosis and warrants further investigation of mitochondrial Nur77 translocation as a mechanism to control cell death in the treatment of ischaemic heart diseases.


Asunto(s)
Apoptosis/fisiología , Mitocondrias Cardíacas/fisiología , Isquemia Miocárdica/patología , Miocitos Cardíacos/patología , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/fisiología , Animales , Constricción , Femenino , Masculino , Ratones , Daño por Reperfusión Miocárdica/patología , Ratas , Ratas Sprague-Dawley , Transfección , Regulación hacia Arriba
20.
Circ Res ; 106(7): 1265-74, 2010 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-20203306

RESUMEN

RATIONALE: Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity. OBJECTIVE: The purpose of this study is to demonstrate that the cardioprotective kinase Pim-1 acts to inhibit cell death by preserving mitochondrial integrity in cardiomyocytes. METHODS AND RESULTS: A combination of biochemical, molecular, and microscopic analyses demonstrate beneficial effects of Pim-1 on mitochondrial integrity. Pim-1 protein level increases in the mitochondrial fraction with a corresponding decrease in the cytosolic fraction of myocardial lysates from hearts subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Cardiac-specific overexpression of Pim-1 results in higher levels of antiapoptotic Bcl-X(L) and Bcl-2 compared to samples from normal hearts. In response to oxidative stress challenge, Pim-1 preserves the inner mitochondrial membrane potential. Ultrastructure of the mitochondria is maintained by Pim-1 activity, which prevents swelling induced by calcium overload. Finally, mitochondria isolated from hearts created with cardiac-specific overexpression of Pim-1 show inhibition of cytochrome c release triggered by a truncated form of proapoptotic Bid. CONCLUSION: Cardioprotective action of Pim-1 kinase includes preservation of mitochondrial integrity during cardiomyopathic challenge conditions, thereby raising the potential for Pim-1 kinase activation as a therapeutic interventional approach to inhibit cell death by antagonizing proapoptotic Bcl-2 family members that regulate the intrinsic apoptotic pathway.


Asunto(s)
Apoptosis , Mitocondrias Cardíacas/enzimología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/enzimología , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Animales , Animales Recién Nacidos , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Supervivencia Celular , Células Cultivadas , Citocromos c/metabolismo , Modelos Animales de Enfermedad , Humanos , Potencial de la Membrana Mitocondrial , Ratones , Ratones Transgénicos , Mitocondrias Cardíacas/ultraestructura , Dilatación Mitocondrial , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/ultraestructura , Estrés Oxidativo , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/genética , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/metabolismo , Factores de Tiempo , Transfección , Proteína bcl-X/metabolismo
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