In vivo analysis of the mitochondrial protein frataxin in Drosophila melanogaster

Friedreich’s ataxia is the most common recessive ataxia in the Caucasian population. It is caused by a defect in the expression of the mitochondrial protein frataxin and leads to neurodegeneration. The main role of frataxin lies in iron-sulphur cluster biosynthesis and loss of the protein results in mitochondrial iron accumulation and diminished energy production within the cell. Although mitochondrial function is severely affected, little is known about the influence of frataxin deficiency on mitochondrial dynamics and homeostasis. In this work, I utilized previously established Drosophila melanogaster RNAi models of Friedreich’s ataxia. To unravel the effects of frataxin depletion on the mitochondrial network, I focused on glia and muscle tissue, since these RNAi lines are not very efficient in neurons. I could show that mitochondrial morphology is disturbed, in agreement with the compromised membrane potential and energy production. Through the use of autophagy markers like p62, GFP-Atg8a and the newly established mtRosella, I performed a detailed analysis of mitochondrial degradation in frataxin deficient flies. I could demonstrate that damaged mitochondria are successfully targeted for degradation via mitophagy and promoting autophagy slightly improves Friedreich’s ataxia phenotypes. To analyse potential genetic interactions between frataxin and genes involved in mitochondrial homeostasis, I carried out a forward genetic screen. This screen identified knockdown of Marf, the Drosophila homologue of Mitofusin, as a suppressor of Friedreich’s ataxia phenotypes in glia. Since Marf has been described to play a pivotal role in mitochondrial fusion, mitophagy and the interface between mitochondria and the ER, I examined how Marf silencing affects all three pathways in a frataxin deficient background. Interestingly, I could show that loss of frataxin triggers the ER stress response and identified ER stress as a key factor in the disease. Whereas mitochondrial morphology and degradation were unaffected by Marf silencing, it suppressed ER stress in frataxin-deficient cells and this was sufficient to improve locomotion, brain degeneration and lipid dyshomeostasis. Furthermore, application of the chemical TUDCA, a known attenuator of ER stress, was also able to partially rescue Friedreich’s ataxia phenotypes. These results suggest that the protection mediated by Marf knockdown is linked to its role in mitochondrial-ER contacts instead of mitochondrial fusion or degradation. Furthermore, ER stress appears to play a crucial role in the aetiology of the disease

Decision support for the capacity management of bronchoscopy devices: Optimizing the cost-efficient mix of reusable and single-use devices through mathematical modeling

BACKGROUND: Increasing costs of material resources challenge hospitals to stay profitable. Particularly in anesthesia departments and intensive care units, bronchoscopes are used for various indications. Inefficient management of single- and multiple-use systems can influence the hospitals’ material costs substantially. Using mathematical modeling, we developed a strategic decision support tool to determine the optimum mix of disposable and reusable bronchoscopy devices in the setting of an intensive care unit. METHODS: A mathematical model with the objective to minimize costs in relation to demand constraints for bronchoscopy devices was formulated. The stochastic model decides whether single-use, multi-use, or a strategically chosen mix of both device types should be used. A decision support tool was developed in which parameters for uncertain demand such as mean, standard deviation, and a reliability parameter can be inserted. Furthermore, reprocessing costs per procedure, procurement, and maintenance costs for devices can be parameterized. RESULTS: Our experiments show for which demand pattern and reliability measure, it is efficient to only use reusable or disposable devices and under which circumstances the combination of both device types is beneficial. CONCLUSIONS: To determine the optimum mix of single-use and reusable bronchoscopy devices effectively and efficiently, managers can enter their hospital-specific parameters such as demand and prices into the decision support tool

Healthcare IT Utilization and Penetration among Physicians: Novel IT Solutions in Healthcare – Use and Acceptance in Hospitals

Background: Healthcare IT (HIT) increasingly gains public attention and clinical daily relevance. A growing number of patients and physicians increasingly relies on IT services to monitor and support well-being and recovery both in their private and professional environment. This is assumed to develop rapidly in the upcoming years. Objective: This study examines the current status of HIT, its use and penetration among physicians in hospitals and researches utilization as well as future expectations regarding HIT. Methods: Physicians in Germany, Austria and Switzerland were addressed via e-mail to answer a standardized Internet-based questionnaire consisting of 17 multiple-choice and 3 open text questions. Parameters were evaluated in 5 categories: general use, frequency, acceptance, IT needs and future expectations. Results: An overall 234 physicians (response rate 83.6%) with a median age of 45 (range 25–60) responded and filled out the entire online questionnaire. A significant correlation between parameters gender, age and level of training (resident, specialist, consultant etc.) was proven. The professional, medical employment of technology shows a strong correlation with age as well as level of training. Whereas increasing age among physicians is associated with a decreasing level of application of HIT, a higher training level is accompanied by an increasing level of professional application of IT services and tools within the healthcare context. Routine employment of HIT is regarded as a necessary and positive standard. Most users assume the importance of HIT to strongly grow in the future in comparison to current use. A clear lack of trust towards data security and storage is recognized on both patient and physician sides. Needs are currently satisfied by employing privately acquired IT in the professional setup rather than the hospitals’. Future expectations from HIT show a clear demand for interoperability and exchangeability of data. Conclusions: The results display a clear gap between demand and expectations of IT for medical purposes. The rate of use of HIT applications generally correlates with age, gender as well as role within the hospital and type of employment within the healthcare sector. The current offering does not satisfy the needs of healthcare professionals

Delay of transfer from the intensive care unit: a prospective observational analysis on economic effects of delayed in-house transfer

BACKGROUND: Intensive care unit (ICU) capacity is a scant and precious resource in hospitals. Therefore, an optimal occupancy rate as well as detailed occupation planning is of great importance. Most literature deals with admission to the ICU, while only few discuss discharge from the ICU. Specifically, a delay of transfer from the ICU can cause a shortness of beds, jeopardize urgent patient treatment and lead to a decrease in treatment quality as well as economic downsides. This study examined the incidence, costs and reasons for delayed discharge from the ICU and analyzed the influence of the department the patient was admitted to. METHODS: Over the course of 12 months, the discharges of all 1643 patients of two surgical intensive care units of a large academic medical center were analyzed. Delay in minutes and reasons were recorded and translated into financial figures. A univariate logistic regression model was developed to evaluate the impact of length of stay at the ICU, age, gender, subspecialty and specific ICU on the delay of transfer. In a next step, significant factors of the univariate logistic regression were incorporated into a multivariate regression model. RESULTS: In 326 out of 1312 patients ready for discharge (24.8%), the transfer to the floor was delayed. Time of delay for all patients added up to a total of 265,691 min in 1 year. The application of the internal cost allocation, in which 1 min corresponds to 0.75 Euro cents, led to costs of 199,268 Euros (~$240,000) for the study period. In 91.7% of the cases, the reason for the delay was the lack of an available or appropriate bed on the regular ward. Multivariate regression analysis revealed that the type of department the patient is admitted to poses a significantly influencing factor for delayed discharge from the ICU. CONCLUSION: Delay in discharge from the ICU is a common problem of economic relevance. The main reason is a lack of appropriate floor beds. Patients from certain specific departments are at a higher risk to be discharged with delay. A solution to this problem lies in the focus on the downstream units. A proper use of the scarce resources is to be pursued because of ethical as well as economic reasons in an increasingly aging population

Development of Macro Level Indicators of Restructuring and Workers' Health

Hauptgegenstand dieses Projektes war es, eine internationale Datenbank (insb. für Europa) von Faktoren herzustellen, die für die gesundheitlichen Auswirkungen von wirtschaftlicher Umstrukturierung und Personalabbau relevant sind. Daten von der WHO, EUROSTAT, OECD, FAO, ILO, Weltbank und der UNO wurden so zusammengeführt, dass sie die Analyse ökonomischer Faktoren, die Umstrukturierungen hervorbringen und die Gesundheit der Bevölkerungen industrialisierter Länder beeinflussen, ermöglichen. Es wurde darauf geachtet, die wichtigsten Hypothesen zu einer möglichen Relation von ökonomischer Umstrukturierung und Gesundheit in Betracht zu ziehen. Globalisierung und Umstrukturierung Brenner bestimmt die zentralen externen Faktoren, die großen Einfluss auf den Umstrukturierungsprozess haben: Globalisierung (durch internationalen Handel), technischer Wandel (als Hauptursache für Produktivitätsanstieg), politische Entscheidungen (bzgl. internationaler Konkurrenzfähigkeit, High-Tech-Investitionen, Investitionen in Bildung und Wissenschaft, Einwanderungspolitik) und Unternehmensführung (u.a. Trends in akademischen Management-Theorien bezüglich Kostenkontrolle, Profitmaximierung, sozialer Verantwortung und Investitionsentscheidungen in Kapitalgüter vs. Humankapital). Mögliche Quellen einer Gesundheitsbeeinträchtigung der Bevölkerung sind Deindustrialisierung, Personalabbau, Outsourcing, Offshoring und Standortwechsel. Geschwindigkeit des Wandels Globalisierung und die damit verbundenen Umstrukturierungen üben einen extremen Anpassungsdruck auf die betroffenen Beschäftigten, Familien und Gemeinwesen aus. Aber die Geschichte hat gezeigt, dass eine ausbleibende oder besonders langsame Umstrukturierung zu langsamen Wachstum, Inflation und instabilen Währungskursen führt. Schnelle Umstrukturierung ist in modernen, industrialisierten, vernetzten und technologisch innovativen Gesellschaften ein Teil des Lebens. Die Hypothese muss überprüft werden, dass der negative Einfluss von Umstrukturierung auf die Gesundheit der Beschäftigten proportional zur Länge des wirtschaftlichen Abschwungs verläuft. Personalabbau ist ein weiterer Aspekt des heutigen Arbeitsmarktes, der negative Auswirkungen wie höhere Arbeitsbelastung, unsicherere Arbeitsbedingungen, Gesundheitsgefahren und die Gefahr der Arbeitslosigkeit für die Weiterbeschäftigten haben kann. Andreeva et al. untersuchen diesen Hauptaspekt des Personalabbaus. Regionale Dimensionen Edenharter führt Scatterplots als ein Werkzeug zur Überwachung regionaler Entwicklung ein. Lineare Regression erzeugt die Scatterplots, die die Beziehung zwischen Lebenserwartung und zwei ökonomischen Indikatoren, Arbeitslosigkeitsrate und Einkommen, in jeder der Regionen in der Fallstudie in Deutschland anzeigen. Sozioökonomische Gesundheitsungleichheiten in der Rezession Die Untersuchung von Theodossiou geht der Frage nach, durch welche Einflusswege Rezession und ökonomische Erholung sozioökonomische Ungleichheiten und Arbeitslosigkeit verstärken, welche sich wiederum auf die physische und psychische Gesundheit auswirken. In der empirischen Literatur wird Arbeitslosigkeit als eine zentrale sozioökonomische Determinante von Gesundheit identifiziert, insbesondere bei Männern. Allerdings beeinflusst Arbeitslosigkeit nicht nur die Arbeitslosen, sondern auch ihre Partner und Kinder. Ein wichtiger politischer Rückschluss der Untersuchung ist der Langzeit- und sogar generationsübergreifende Effekt von Armut und Arbeitslosigkeit. Entsprechende Entbehrungen in der Kindheit haben langwierige Folgen für die Gesundheit der Betroffenen, die sich erst später im Erwerbsalter zeigen. Wirtschaftspolitik und gesundheitliche Ungleichheit Drakopoulos berichtet, dass infolge der Stagflation der 70er Jahre, als die Regierungen konservativer wurden, der Schwerpunkt ihrer Wirtschaftspolitik sich auf Kosten der Bekämpfung von Arbeitslosigkeit hin zur Bekämpfung der Inflation verschob. Ein positiver Einfluss wird folgenden Maßnahmen zugeschrieben: Reduzierung der Arbeitslosigkeit, höheren Ausgaben, niedrigeren Steuern und Zinsraten sowie Subventionen an Firmen, die ihre Beschäftigungsraten erhöhen. Bildungsausgaben die die Arbeitskräfte für die Bedürfnisse neuer Industrien und Bereiche mit Arbeitskräftemangel qualifizieren erhöhen das Humankapital und die Produktivität. Politische Maßnahmen zur Abschwächung der Umstrukturierungsfolgen Triomphe stellt fest, dass Umstrukturierung für Manager, Gewerkschafter und Beschäftigte eine breite Palette von Änderungen bedeutet, die mindestens einen Unternehmensbereich oder ein gesamtes Unternehmen in Form von Schließung, Personalabbau, Outsourcing, Offshoring, Leiharbeit, Zusammenlegung, Versetzungen oder anderen komplexen Reorganisationen betreffen. Doch für die betroffenen Regionen und Arbeitsämter bedeutet es vor allem Personalabbau und Fabrikschließungen.The main purpose of this project has been to construct an international database, especially for Europe, involving factors that relate to economic restructuring and job downsizing that have implications for health. Relevant data from the WHO, EUROSTAT, OECD, FAO, ILO, World Bank, and United Nations have been merged in a manner that will permit analysis of economic factors bearing on restructuring as they influence the health of industrialized country populations. In order to be certain that the relevant factors were included in the database, the investigators wanted to be confident that the major hypotheses regarding the potential relation between economic restructuring and health were taken into account. Thus, the more specific aims of the project were to identify the literatures and hypotheses that bear on these issues. These literatures are reviewed below. Globalisation and Restructuring: Indicators Brenner identifies the principal external factors that are thought to have a major influence on the restructuring process. These include globalization (via international trade), technological change (i.e. the principal source of productivity growth), government policies (involving international competitiveness, high technology investments, investments in science and education, immigration policies) and management style (including the trends in academic managerial theories as to cost control, profit maximization, social responsibility, investment in capital goods versus human capital etc). Potential sources of harm to the health of the population include: deindustrialization, downsizing, outsourcing, offshoring and delocalization. Rate of Change We know that globalization, and associated restructuring, places extreme pressure on adaptation of affected workers, families and communities. But, history has shown that lack of restructuring or restructuring at very slow speed leads to slow growth, inflation and exchange rate instability. Rapid restructuring is a fact of life for modern, industrialised, highly interconnected, technologically innovative societies. A hypothesis that needs testing is the belief that negative impacts of restructuring on workers‘ health are proportional to the length of the economic downturn. Downsizing is another aspect of today‘s labour market which can introduce negative changes for those who remain employed, such as heavier workload, unsafe working conditions, physical hazards, and job insecurity. Andreeva and colleagues review these main effects of downsizing. Regional Dimension Edenharter introduces scatter-plots as a tool to monitor regional development over time. Linear regression generated the scatter-plots indicating the relationship between life expectancy and two economic indicators, unemployment rate and income, in each of the regions in the case study of Germany. Socioeconomic Inequalities of Health in Recessions The review by Theodossiou suggests mechanisms, or pathways, for how recession and economic upheaval foster socioeconomic inequalities and unemployment, which, in turn, impact on physical and mental health. The review of the empirical literature identifies unemployment as a key socioeconomic determinant of health, particularly for men. However, unemployment does not only affect unemployed individuals but also their spouses and children. A main policy implication of this review of evidence is the long term and even intergenerational effect of poverty and unemployment. Childhood deprivation due to poverty and unemployment of their parents have long lasting detrimental effects on the health of individuals that are visible at later ages of working life. Economic Policy and Health Inequalities Drakopoulos recounts that, following the stagflation of the 1970’s, as governments became more conservative, the emphasis of their economic policies shifted towards eliminating inflation at the expense of unemployment. What particular economic policies have a beneficial impact on health? These include policies targeted to reducing unemployment, including increased government spending, lowered taxation and low interest rates as well as employment subsidies to firms in order to maintain/increase employment levels. Education and training funds directed toward capacity building of the workforce to fill new industries and address critical shortages improves human capital and also increases productivity. Policies Mitigating Consequences of Restructuring Triomphe indicates that for managers, trade unions and employees, restructuring refers to a wide panel of changes, affecting at least a whole organizational sector or an entire company in the forms of closure, downsizing, job losses, outsourcing, off-shoring, sub-contracting, merging, delocalization, internal job mobility or other complex internal reorganizations. But, it means mostly downsizing, closing factories and dismissals for employment services and territories

Brain dysfunction in chronic pain patients assessed by resting-state electroencephalography

Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity, and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4-8 Hz) and gamma (>60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. Although substantial challenges concerning the reproducibility of the findings and the accuracy, specificity, and validity of potential electroencephalography-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for noninvasive brain stimulation and/or neurofeedback approaches

Die Komitologie nach dem Vertrag von Lissabon: Verschiebung der Einflussmöglichkeiten zugunsten der EU-Kommission?

Durch den Vertrag von Lissabon hat sich das institutionelle Gleichgewicht von EU-Kommission, Ministerrat und Europaparlament grundlegend verändert. Betroffen von den weit reichenden Reformen ist auch das sog. Komitologieverfahren, in dem die EU-Kommission Durchführungsbestimmungen für EU-Rechtsakte erlässt. Das Komitologieverfahren ist durch Ausschüsse geprägt, die mit Experten aus den Mitgliedstaaten besetzt sind und die von der Kommission beim Erlass von Durchführungsrechtsakten beteiligt werden müssen. Der Beitrag untersucht, welche Änderungen das Komitologieverfahren durch den Vertrag von Lissabon erfahren hat und wie sich diese Änderungen auf die Machtverteilung zwischen Kommission, Rat und Parlament auswirken