RESUMO
BACKGROUND: Chronic stress and high workload in physicians can lead to loss of interest, emotional exhaustion and finally in burnout syndrome. This can cause serious consequences not only for the physicians personally and their own health by developing extensive health impairments, e.g. depression, suicide, substance abuse and poor self-care but also for patient care, reflected in an increase of medical errors, longer recovery times, lower care quality and consequently lower patient satisfaction. Additionally, it can also have negative effects on the healthcare system by reduced productivity, increased physician turnover and thereby higher costs. OBJECTIVE: This pilot study investigated brief interventions inspired by mindfulness-based stress reduction (MBSR) combined with short daily meditation exercises in the everyday work of anesthetists at a university hospital. Secondly, whether this program increases the development of coping mechanisms for stress and improves participants' resilience and health status. MATERIAL AND METHODS: The pilot study was designed as a monocenter prospective interventional study with four different points of measurement. Subjective and objective stress parameters were measured directly before (t0) and after (t1) the intervention as well as 3 (t2) and 6 (t3) months after end of the intervention. Measurements took place during work time and at the workplace. The intervention was based on the classical MBSR including short daily exercises and lasted for 6 weeks with sessions lasting 1- 1.5â¯h and an additional 20â¯min of daily mediation exercises. The subjective parameters were based on validated questionnaires, such as the World Health Organization (WHO) well-being index (WHO-5), resilience scale (RS-11), Maslach burnout inventory (MBI-22) and perceived stress scale (PSS-10). For objective parameters heart rate variability (HRV) was evaluated during rest and after exposure to physical exercise and hair cortisol concentrations (HCC) in a 1.5â¯cm length of a hair, which represents the equivalent of a 6-week period. RESULTS: Data from 27 subjects could be analyzed. Between t3 and t0 a significant improvement of resilience was detected as a positive personality trait measured by RS-11 with a large effect size (pâ¯= 0.013; râ¯= 0.59) as well as a significant reduction of burnout symptoms (MBI-22) also with a large effect size (pâ¯= 0.019; râ¯= 0.57). Furthermore, a significant decrease was found in well-being (WHO-5) between t2 and t0 (pâ¯= 0.003, râ¯= 0.67) and between t1 and t0 (pâ¯= 0.001, râ¯= 0.71). The objective parameters did not show any significant differences between the examinations. CONCLUSION: An MBSR-based intervention in combination with short exercises during and after work can be implemented in daily work of anesthetists at a university hospital. Furthermore, there was clear evidence that the intervention program increased resilience and reduced burnout symptoms for up to 6 months. These findings are in line with the literature that MBSR reduces risk of burnout symptoms. The decrease in well-being might be biased by a high amount of socially accepted answers at the beginning of the study (t0).
Assuntos
Serviço Hospitalar de Anestesia , Esgotamento Profissional/psicologia , Atenção Plena , Médicos/psicologia , Estresse Psicológico/psicologia , Adulto , Anestesiologistas , Feminino , Humanos , Masculino , Assistência ao Paciente , Projetos Piloto , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2). Campylobacter upsaliensis patients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7). Campylobacter fetus patients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12·5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.
Assuntos
Infecções por Campylobacter/epidemiologia , Doenças Transmitidas por Alimentos/epidemiologia , Adulto , Idoso , Infecções por Campylobacter/etiologia , Centers for Disease Control and Prevention, U.S. , Feminino , Doenças Transmitidas por Alimentos/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Viagem , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: The number of patients visiting emergency departments (ED) is steadily increasing. The cause for this rise in Germany is unclear and less examined. This study aimed to assess the reasons of walk-in patients to visit EDs by using a direct survey. METHODS: During a period of 4 weeks, 2 010 walk-in patients were anonymously surveyed in 2 major Berlin hospitals using a standardized questionnaire. Descriptive statistics were used for data analysis. RESULTS: More than 90% of patients assessed themselves as an emergency and three-quarters of patients reported pain. The majority of patients (57%) tried to contact statutory health insurance (SHI) office-based physicians in advance and 59% of patients said they would make use of ambulatory emergency facilities if they were available and well established. However, 55% of patients were unaware of the emergency service of the association of SHI physicians. CONCLUSION: The results indicate that centralized ambulatory emergency facilities should be available 24/7 at hospitals with EDs. Therefore, future planning of emergency services should integrate providers of ambulatory and inpatient sector. International experience suggests that different instruments aiming at better coordination of care, such as integrated call centers, extended ambulatory services and facilities for less urgent cases located in or nearby hospitals with EDs should also be implemented in Germany.
Assuntos
Serviço Hospitalar de Emergência , Seguro Saúde , Berlim , Alemanha , Pesquisas sobre Atenção à Saúde , Humanos , Inquéritos e Questionários , Estados UnidosRESUMO
BACKGROUND: Diagnosis-related groups (DRGs) have been used to reimburse hospitals services in Germany since 2003/04. Like any other reimbursement system, DRGs offer specific incentives for hospitals that may lead to unintended consequences for patients. In the German context, specific procedures and their documentation are suspected to be primarily performed to increase hospital revenues. Mechanical ventilation of patients and particularly the duration of ventilation, which is an important variable for the DRG-classification, are often discussed to be among these procedures. OBJECTIVES: The aim of this study was to examine incentives created by the German DRG-based payment system with regard to mechanical ventilation and to identify factors that explain the considerable increase of mechanically ventilated patients in recent years. Moreover, the assumption that hospitals perform mechanical ventilation in order to gain economic benefits was examined. MATERIAL AND METHODS: In order to gain insights on the development of the number of mechanically ventilated patients, patient-level data provided by the German Federal Statistical Office and the German Institute for the Hospital Remuneration System were analyzed. The type of performed ventilation, the total number of ventilation hours, the age distribution, mortality and the DRG distribution for mechanical ventilation were calculated, using methods of descriptive and inferential statistics. Furthermore, changes in DRG-definitions and changes in respiratory medicine were compared for the years 2005-2012. RESULTS: Since the introduction of the DRG-based payment system in Germany, the hours of ventilation and the number of mechanically ventilated patients have substantially increased, while mortality has decreased. During the same period there has been a switch to less invasive ventilation methods. The age distribution has shifted to higher age-groups. A ventilation duration determined by DRG definitions could not be found. CONCLUSION: Due to advances in respiratory medicine, new ventilation methods have been introduced that are less prone to complications. This development has simultaneously improved survival rates. There was no evidence supporting the assumption that the duration of mechanical ventilation is influenced by the time intervals relevant for DRG grouping. However, presumably operational routines such as staff availability within early and late shifts of the hospital have a significant impact on the termination of mechanical ventilation.
Assuntos
Grupos Diagnósticos Relacionados/economia , Grupos Diagnósticos Relacionados/estatística & dados numéricos , Administração Hospitalar/economia , Administração Hospitalar/estatística & dados numéricos , Pneumologia/estatística & dados numéricos , Respiração Artificial/economia , Respiração Artificial/estatística & dados numéricos , Fatores Etários , Alemanha/epidemiologia , Mortalidade Hospitalar , Humanos , Motivação , Ventilação não Invasiva , Mecanismo de Reembolso , Respiração Artificial/mortalidade , Taxa de Sobrevida , Traqueostomia/mortalidade , Traqueostomia/estatística & dados numéricosRESUMO
BACKGROUND: The number of knee arthroplasties and the prevalence of obesity are increasing exponentially. To date there have been no published reviews on utilization rates of knee arthroplasty in OECD countries. METHODS: We analysed economic, medical and population data relating to knee arthroplasty surgeries performed in OECD countries. Gross domestic product (GDP), health expenditures, obesity prevalence, knee arthroplasty utilization rates and growth in knee arthroplasty rates per 100,000 population were assessed for total population, for patients aged 65 years and over, and patients aged 64 years and younger. RESULTS: Obesity prevalence and utilization of knee arthroplasty have increased significantly in the past. The mean utilization rate of knee arthroplasty was 150 (22-235) cases per 100,000 total population in 2011. The strongest annual increase (7%) occurred in patients 64 years and under. Differences between individual countries can be explained by economic and medical patterns, with countries with higher medical expenditures and obesity prevalence having significantly higher utilization rates. Countries with lower utilization rates have significantly higher growth in utilization rates. The future demand for knee prostheses will increase x-fold by 2030, with exact rates dependant upon economic, social and medical factors. CONCLUSION: We observed a 10-fold variation in the utilization of knee arthroplasty among OECD countries. A significant and strong correlation of GDP, health expenditures and obesity prevalence with utilization of knee arthroplasty was found. Patients aged 64 years and younger show a two-fold higher growth rate in knee arthroplasty compared to the older population. This trend could result in a four-fold demand for knee arthroplasty in OECD countries by 2030.
Assuntos
Artroplastia do Joelho/estatística & dados numéricos , Produto Interno Bruto , Gastos em Saúde , Obesidade/epidemiologia , Osteoartrite do Joelho/cirurgia , Idoso , Austrália/epidemiologia , Canadá/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Organização para a Cooperação e Desenvolvimento Econômico , Osteoartrite do Joelho/epidemiologia , Prevalência , República da Coreia/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Compreensão/fisiologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Idioma , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Hierarchical structures play a central role in many aspects of human cognition, prominently including both language and music. In this study we addressed hierarchy in the visual domain, using a novel paradigm based on fractal images. Fractals are self-similar patterns generated by repeating the same simple rule at multiple hierarchical levels. Our hypothesis was that the brain uses different resources for processing hierarchies depending on whether it applies a "fractal" or a "non-fractal" cognitive strategy. We analyzed the neural circuits activated by these complex hierarchical patterns in an event-related fMRI study of 40 healthy subjects. Brain activation was compared across three different tasks: a similarity task, and two hierarchical tasks in which subjects were asked to recognize the repetition of a rule operating transformations either within an existing hierarchical level, or generating new hierarchical levels. Similar hierarchical images were generated by both rules and target images were identical. We found that when processing visual hierarchies, engagement in both hierarchical tasks activated the visual dorsal stream (occipito-parietal cortex, intraparietal sulcus and dorsolateral prefrontal cortex). In addition, the level-generating task specifically activated circuits related to the integration of spatial and categorical information, and with the integration of items in contexts (posterior cingulate cortex, retrosplenial cortex, and medial, ventral and anterior regions of temporal cortex). These findings provide interesting new clues about the cognitive mechanisms involved in the generation of new hierarchical levels as required for fractals.
Assuntos
Córtex Cerebral/fisiologia , Cognição/fisiologia , Tomada de Decisões/fisiologia , Fractais , Reconhecimento Visual de Modelos/fisiologia , Reconhecimento Psicológico/fisiologia , Vias Visuais/fisiologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Rede Nervosa/fisiologia , Adulto JovemRESUMO
BACKGROUND: Hip arthroplasty and revision surgery is growing exponentially in OECD countries, but rates vary between countries. METHODS: We extracted economic data and utilization rates data about hip arthroplasty done in OECD countries between 1990 and 2011. Absolute number of implantations and compound annual growth rates were computed per 100,000 population and for patients aged 65 years old and over and for patients aged 64 years and younger. RESULTS: In the majority of OECD countries, there has been a significant increase in the utilization of total hip arthroplasty in the last 10 years, but rates vary to a great extent: In the United States, Switzerland, and Germany the utilization rate exceeds 200/100,000 population whereas in Spain and Mexico rates are 102 and 8, respectively. There is a strong correlation between gross domestic product (GDP) and health care expenditures per capita with utilization rate. Utilization rates in all age groups have continued to rise up to present day. A seven fold higher growth rate was seen in patients aged 64 years and younger as compared to older patients. CONCLUSION: We observed a 38-fold variation in the utilization of hip arthroplasty among OECD countries, correlating with GDP and health care expenditures. Over recent years, there has been an increase in the utilization rate in most countries. This was particularly evident in the younger patients. Due to increasing life expectancy and the disproportionally high use of arthroplasty in younger patients we expect an exponential increase of revision rate in the future.
Assuntos
Artroplastia de Quadril/economia , Artroplastia de Quadril/estatística & dados numéricos , Custos de Cuidados de Saúde , Osteoartrite do Quadril/cirurgia , Fatores Etários , Idoso , Artroplastia de Quadril/métodos , Bases de Dados Factuais , Feminino , Prótese de Quadril/economia , Prótese de Quadril/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Organização para a Cooperação e Desenvolvimento Econômico , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/epidemiologia , Seleção de Pacientes , Prognóstico , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores Sexuais , Resultado do TratamentoRESUMO
AIM OF THE STUDY: The revenues of German hospitals are mainly determined by DRG-based payments. Therefore DRGs should appropriately explain the resource consumption of hospitals in order to avoid unintended consequences. So far little is known about the ability of German DRGs to adequately reflect the cost of a hospital stay. METHODS: Regression techniques were applied using anonymised year 2008 cost and performance data of 50,156 cases from 29 hospitals for 10 common episodes of care in order a) to analyse the impact of patient and treatment characteristics on costs and b) to test if DRG variables are better in explaining resource consumption than this set of patient variables. RESULTS: Depending on the episode of care, patient and treatment variables have a different impact on hospital costs. However, they are better in explaining resource consumption than the DRG variables for each episode of care. In addition, independent of the patient characteristics hospitals have an impact on costs which might be due to factors that are not considered by the DRG-system. CONCLUSION: The analysis shows that the German DRG system requires further research. However, to date this is limited by poor data availability. Compared to other DRG systems the German system shows a weak performance. The incorporation of some of the used variables as well as an increasing international knowledge transfer might help to further improve the German DRG system.
Assuntos
Grupos Diagnósticos Relacionados/economia , Grupos Diagnósticos Relacionados/estatística & dados numéricos , Cuidado Periódico , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/estatística & dados numéricos , Hospitalização/economia , Renda/estatística & dados numéricos , Simulação por Computador , Medicina Baseada em Evidências , Alemanha , Hospitalização/estatística & dados numéricos , Modelos Econômicos , Revisão da Utilização de Recursos de SaúdeRESUMO
BACKGROUND: Mammography screening programs (MSP) have shown that breast cancer can be detected at an earlier stage enabling less invasive treatment and leading to a better survival rate. The considerable numbers of interval breast cancer (IBC) and the additional examinations required, the majority of which turn out not to be cancer, are critically assessed. OBJECTIVE: In recent years companies and universities have used machine learning (ML) to develop powerful algorithms that demonstrate astonishing abilities to read mammograms. Can such algorithms be used to improve the quality of MSP? METHOD: The original screening mammographies of 251 cases with IBC were retrospectively analyzed using the software ProFound AI® (iCAD) and the results were compared (case score, risk score) with a control group. The relevant current literature was also studied. RESULTS: The distributions of the case scores and the risk scores were markedly shifted to higher risks compared to the control group, comparable to the results of other studies. CONCLUSION: Retrospective studies as well as our own data show that artificial intelligence (AI) could change our approach to MSP in the future in the direction of personalized screening and could enable a significant reduction in the workload of radiologists, fewer additional examinations and a reduced number of IBCs; however, the results of prospective studies are needed before implementation.
RESUMO
Magnetic properties of Au nanoparticles deposited on an archaeal S layer are reported. X-ray magnetic circular dichroism and superconducting quantum interference device magnetometries demonstrate that the particles are strongly paramagnetic, without any indication of magnetic blocking down to 16 mK. The average magnetic moment per particle is M(part)=2.36(7) µ(B). This contribution originates at the particle's Au 5d band, in which an increased number of holes with respect to the bulk value is observed. The magnetic moment per Au atom is 25 times larger than any measured in other Au nanoparticles or any other configurations up to date.
RESUMO
DRG systems were introduced across Europe based on expected transparency and efficiency gains. However, European DRG systems have not been systematically analysed so far. As a consequence little is known about the relative strengths and weaknesses of different DRG systems. The EuroDRG project closed this research and knowledge gap by systematically analysing and comparing the DRG systems of 12 countries with different health systems (Austria, the UK, Estonia, Finland, France, Germany, Ireland, The Netherlands, Poland, Portugal, Spain and Sweden).This article summarizes the results of this analysis illustrating how DRG systems across Europe differ with regard to policy goals, patient classification, data collection, price setting and actual reimbursement. Moreover, it outlines which main challenges arise within and across the different types of DRG systems. The results show that the European DRG systems are very heterogeneous. Even if the basic DRG approach of grouping similar patients remains the same across countries, the design of the main building blocks differs to a great extent.
Assuntos
Atenção à Saúde/economia , Grupos Diagnósticos Relacionados/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Mecanismo de Reembolso/economia , Europa (Continente)RESUMO
Despite there being an increasing number of installations of ultra high field MR systems (>3T) in clinical environments, no functional patient investigations have yet examined possible benefits for functional diagnostics. Here we performed presurgical localization of the primary motor hand area on 3T and 7T Siemens scanners with identical investigational procedures and comparable system specific sequence optimizations. Results from 17 patients showed significantly higher functional sensitivity of the 7T system measured via percent signal change, mean t-values, number of suprathreshold voxels and contrast to noise ratio. On the other hand, 7T data suffered from a significant increase of artifacts (ghosting, head motion). We conclude that ultra high field systems provide a clinically relevant increase of functional sensitivity for patient investigations.
Assuntos
Artefatos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/instrumentação , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiologia , Adulto JovemRESUMO
Porcine endogenous retroviruses (PERVs) represent a risk for xenotransplantation using pig cells or organs since they are integrated in the genome of all pigs and infect human cells in vitro. Recombinants between PERV-A and PERV-C have been described in pigs in vivo and found de novo integrated in the genome of somatic cells, but not in the germ line. To study whether PERV-A/C can infect and have a pathogenic effect in normal pigs, German landrace pigs were inoculated with high-titre PERV-A/C. No provirus integration was found in blood cells or in various tissues, and no antibody production was observed, indicating the absence of infection.
Assuntos
Retrovirus Endógenos/genética , Retrovirus Endógenos/patogenicidade , Recombinação Genética , Infecções por Retroviridae/veterinária , Doenças dos Suínos/virologia , Animais , Provírus/genética , Provírus/isolamento & purificação , Infecções por Retroviridae/virologia , Suínos , Doenças dos Suínos/patologia , Integração ViralRESUMO
Coronary angiography by computed tomography (CTCA) is most suitable for symptomatic patients with an intermediate likelihood to exclude a coronary stenosis as the cause of the symptoms. It would also be appropriate in a patient in whom an equivoval stress test result has led to uncertainty about the patient's further management. CTCA may occasionally be acceptable in a high risk symptomatic patient who refuses the necessary invasive coronary angiography if the results of CTCA are likely to alter patient management.The main indication for cardiac magnetic resonance imaging (CMR) is for pharmacologic stress testing. If such a test is indicated, dobutamine stress CMR is an alternative to stress echocardiography and adenosine perfusion CMR is the alternative to nuclear myocardial perfusion imaging but without radiation. Late gadolinium enhancement CMR is the current gold standard for the assessment of myocardial scars and hence is well suited to predict recovery of function in dysfunctional myocardial regions following revascularisation (viability testing).
Assuntos
Angiografia/métodos , Doença da Artéria Coronariana/diagnóstico , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Vasodilatadores , Humanos , Angiografia por Ressonância Magnética/métodosRESUMO
BACKGROUND: The renal effect of hydroxyethylstarch (HES) solutions remains controversial. We hypothesized that the use of HES with a mean molecular weight of 130 kDa would reduce renal dysfunctions in the recipients. Our study was aimed at comparing the effects of two fluid regimens (HES 130/0.4 or HES 200/0.6) used for the resuscitation of brain-dead donors on the rate of delayed graft function (DGF) and the serum creatinine levels post-transplantation. METHODS: This retrospective matched-paired study was conducted in an intensive care unit of a university hospital. Case-controls were matched at the donor patient level as follows: gender, BMI, duration of ICU stay, serum creatinine levels, vasopressor, and volume of colloids. The organ donation from 64 brain-dead donors resulted in 115 transplants. RESULTS: The renal function was similar among all donors. The characteristics of the recipients, including the cold ischaemia time, were similar. The rate of DGF was 22% in the donors treated with HES 130/0.4, compared with 33% in those treated with HES 200/0.6 (P=0.27). The serum creatinine levels at 1 month were 133 (38) micromol litre(-1) when the donors had been treated with HES 130/0.4 and 172 (83) micromol litre(-1) when they were treated with HES 200/0.6 (P=0.005). A difference was found 1 yr after transplantation [128 (36) vs147 (43) micromol litre(-1), P=0.05]. CONCLUSIONS: Using a modern, third-generation, rapidly degradable HES preparation with a low degree of substitution seems to be associated with a better effect on the renal function of recipients.
Assuntos
Morte Encefálica , Derivados de Hidroxietil Amido/análogos & derivados , Transplante de Rim/fisiologia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Creatinina/sangue , Função Retardada do Enxerto , Feminino , Humanos , Derivados de Hidroxietil Amido/uso terapêutico , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Substitutos do Plasma/uso terapêutico , Ressuscitação/métodosRESUMO
The mitochondrial heat shock protein Hsp70 (mtHsp70) is essential for driving translocation of preproteins into the matrix. Two models, trapping and pulling by mtHsp70, are discussed, but positive evidence for either model has not been found so far. We have analyzed a mutant mtHsp70, Ssc1-2, that shows a reduced interaction with the membrane anchor Tim44, but an enhanced trapping of preproteins. Unexpectedly, at a low inner membrane potential, ssc1-2 mitochondria imported loosely folded preproteins more efficiently than wild-type mitochondria. The import of a tightly folded preprotein, however, was not increased in ssc1-2 mitochondria. Thus, enhanced trapping by mtHsp70 stimulates the import of loosely folded preproteins and reduces the dependence on the import-driving activity of the membrane potential, directly demonstrating that trapping is one of the molecular mechanisms of mtHsp70 action.
Assuntos
Membrana Celular/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico , Proteínas de Membrana Transportadoras , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial , Proteínas de Saccharomyces cerevisiae , ATPases Transportadoras de Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Cisplatino/farmacologia , Reagentes de Ligações Cruzadas/farmacologia , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Proteínas Fúngicas/metabolismo , Potenciais da Membrana , Proteínas de Membrana/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Chaperonas Moleculares/metabolismo , Mutação , Testes de Precipitina , Transporte Proteico , Saccharomyces cerevisiae/metabolismo , Fatores de TempoRESUMO
The transport of preproteins into or across the mitochondrial inner membrane requires the membrane potential Deltapsi across this membrane. Two roles of Deltapsi in the import of cleavable preproteins have been described: an electrophoretic effect on the positively charged matrix-targeting sequences and the activation of the translocase subunit Tim23. We report the unexpected finding that deletion of a segment within the sorting sequence of cytochrome b(2), which is located behind the matrix-targeting sequence, strongly influenced the Deltapsi-dependence of import. The differential Deltapsi-dependence was independent of the submitochondrial destination of the preprotein and was not attributable to the requirement for mitochondrial Hsp70 or Tim23. With a series of preprotein constructs, the net charge of the sorting sequence was altered, but the Deltapsi-dependence of import was not affected. These results suggested that the sorting sequence contributed to the import driving mechanism in a manner distinct from the two known roles of Deltapsi. Indeed, a charge-neutral amino acid exchange in the hydrophobic segment of the sorting sequence generated a preprotein with an even better import, i.e. one with lower Deltapsi-dependence than the wild-type preprotein. The sorting sequence functioned early in the import pathway since it strongly influenced the efficiency of translocation of the matrix-targeting sequence across the inner membrane. These results suggest a model whereby an electrophoretic effect of Deltapsi on the matrix-targeting sequence is complemented by an import-stimulating activity of the sorting sequence.
Assuntos
Matriz Extracelular/metabolismo , L-Lactato Desidrogenase/metabolismo , Potenciais da Membrana/fisiologia , Proteínas de Membrana Transportadoras , Mitocôndrias/metabolismo , Sinais Direcionadores de Proteínas , Proteínas de Saccharomyces cerevisiae , Sequência de Aminoácidos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Precursores Enzimáticos/genética , Precursores Enzimáticos/metabolismo , Proteínas de Choque Térmico HSP70/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase (Citocromo) , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Dados de Sequência Molecular , Mutação , Transporte Proteico/efeitos dos fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Tetra-Hidrofolato Desidrogenase/efeitos dos fármacos , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo , Leveduras/efeitos dos fármacos , Leveduras/genética , Leveduras/metabolismoRESUMO
BACKGROUND: Obtaining consent from relatives is essential for cornea donation. When a face-to-face interview is not possible, telephone contact is used to obtain donation consent. We tried to evaluate the role of experience on the acceptance rate using this method. METHODS: This was a prospective study conducted over a 22-month period. Two nonmedical coordinators were evaluated. Telephone contact was conducted using a standardized procedure. We recorded for each coordinator the number of telephone contacts and the acceptance rate. RESULTS: Among 455 families contacted, the mean acceptance rate was 60%. Initial acceptance rate was below 30% for both coordinators, showing dramatic improvement with experience (acceptance rate >70% after 100 contacts). CONCLUSIONS: Telephone contact is an efficient method to obtain cornea donation consent. However, as with other new methods, a training period is necessary to increase effectiveness.
Assuntos
Transplante de Córnea/ética , Consentimento Livre e Esclarecido , Telefone , Doadores de Tecidos , Atitude Frente a Saúde , HumanosRESUMO
PURPOSE: To evaluate the impact of procedures developed to increase cornea donation in a general hospital. Comparative study before and after intervention. Since february 2002 all cases of intra-hospital death were considered by the hospital coordinator. A written selection protocol for potential donors was adopted and telephone interviews to obtain family consent were conducted using a standardized procedure. METHODS: The number of deaths in the institution, deaths considered by the hospital coordinator, clinical contraindications to harvesting, potential donors, face-to-face interview and telephone contact with families, the donation acceptance rate during telephone and face-to-face interviews, and the number of donors and corneas actually collected were recorded before and after intervention. The data were analyzed during two consecutive periods: Period 1, february 2001 to january 2002 (before protocol), and period 2, february 2002 to january 2003 (after protocol). RESULTS: The number of deaths in the institution was similar for the two periods. The increase in deaths considered by the hospital coordinator and the decrease in contraindications resulted from increasing the pool of potential donors from 188 to 401 (p < 0.001). The number of telephone interviews increased from 33 to 274. The rate of family consent given during face-to-face interviews was similar, 61% versus 72% (p = 0.1), but acceptance during telephone interviews increased from 15% to 60% (p < 0.001) and 138 corneas were collected in period 1 and 443 in period 2. The rate of cornea donors increased from 6% to 20% of the hospital's deaths. CONCLUSION: The consideration of all hospital deaths, the use of a written protocol of contraindications for cornea donation and the wide use of telephone interviews to obtain family consent led to a dramatic increase in cornea donation.