Showing papers by "University of Marburg published in 2006"
TL;DR: The results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.
Abstract: Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.
1,193 citations
Max Planck Society1, University of Marburg2, Broad Institute3, University of Toronto4, Trent University5, California State University, Long Beach6, University of British Columbia7, University of Georgia8, University of Louisville9, Utrecht University10, Saint Joseph's University11, Spanish National Research Council12, Cornell University13, CINVESTAV14, University of Kentucky15, Duke University16, University of Valencia17, Saint Louis University18, Bayer19, Exelixis20, Technische Universität München21
TL;DR: The discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi.
Abstract: Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.
1,120 citations
TL;DR: Loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia are described.
Abstract: Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.
1,112 citations
TL;DR: In vivo findings confirm that widespread microglial activation is associated with the pathological process in PD and suggest that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.
987 citations
TL;DR: In this paper, the progress so far in obtaining true quantum-optical strong coupling effects in semiconductors is reviewed and a nonlinear test for the true quantum limit is proposed.
Abstract: The recent development of techniques to produce optical semiconductor cavities of very high quality has prepared the stage for observing cavity quantum-electrodynamic effects in solid-state materials. Among the most promising systems for these studies are semiconductor quantum dots inside photonic crystal, micropillar or microdisk resonators. We review the progress so far in obtaining true quantum-optical strong-coupling effects in semiconductors. We discuss the recent results on vacuum Rabi splitting with a single quantum dot, emphasizing the differences from quantum-well systems. Finally, we propose nonlinear tests for the true quantum limit and speculate about applications in quantum information devices.
852 citations
TL;DR: The role of PPARalpha, which is highly activated in PEX5-/- mice with the absence of functional peroxisomes severe abnormalities of mitochondria in different organs are observed which resemble closely those in respiratory chain disorders associated with oxidative stress.
701 citations
TL;DR: The results demonstrate the effectiveness of the method for reliably profiling many CpG sites in parallel for the discovery of informative methylation markers and should prove useful for DNA methylation analyses in large populations.
Abstract: We have developed a high-throughput method for analyzing the methylation status of hundreds of preselected genes simultaneously and have applied it to the discovery of methylation signatures that distinguish normal from cancer tissue samples. Through an adaptation of the GoldenGate genotyping assay implemented on a BeadArray platform, the methylation state of 1536 specific CpG sites in 371 genes (one to nine CpG sites per gene) was measured in a single reaction by multiplexed genotyping of 200 ng of bisulfite-treated genomic DNA. The assay was used to obtain a quantitative measure of the methylation level at each CpG site. After validating the assay in cell lines and normal tissues, we analyzed a panel of lung cancer biopsy samples (N = 22) and identified a panel of methylation markers that distinguished lung adenocarcinomas from normal lung tissues with high specificity. These markers were validated in a second sample set (N = 24). These results demonstrate the effectiveness of the method for reliably profiling many CpG sites in parallel for the discovery of informative methylation markers. The technology should prove useful for DNA methylation analyses in large populations, with potential application to the classification and diagnosis of a broad range of cancers and other diseases.
676 citations
TL;DR: In this paper, the authors compare temporary clusters with permanent spatial clusters and other types of inter-firm interactions, and find that regular participation in temporary clusters can satisfy a firm's need to learn through interaction with suppliers, customers, peers and rivals.
Abstract: Business people and professionals come together regularly at trade fairs, exhibitions, conventions, congresses, and conferences. Here, their latest and most advanced findings, inventions and products are on display to be evaluated by customers and suppliers, as well as by peers and competitors. Participation in events like these helps firms to identify the current market frontier, take stock of relative competitive positions and form future plans. Such events exhibit many of the characteristics ascribed to permanent spatial clusters, albeit in a temporary and intensified form. These short-lived hotspots of intense knowledge exchange, network building and idea generation can thus be seen as temporary clusters. This paper compares temporary clusters with permanent clusters and other types of inter-firm interactions. If regular participation in temporary clusters can satisfy a firm's need to learn through interaction with suppliers, customers, peers and rivals, why is the phenomenon of permanent spa...
633 citations
TL;DR: The concepts and prerequisites to perform virtual ligand screening are summarized here, and explanations are sought for the enduring limitations of the technology.
609 citations
TL;DR: This Review shows that highly ordered metal-organic catalysts that might allow a rational design, synthesis, and the unequivocal structural characterization to give tailor-made catalysts have more to them than facile separation or recycling.
Abstract: Limited natural resources and an increasing demand for enantiomerically pure compounds render catalysis and especially heterogeneous asymmetric catalysis a key technology. The field has rapidly advanced from the initial use of chiral biopolymers, such as silk, as a support for metal catalysts to the modern research areas. Mesoporous supports, noncovalent immobilization, metal-organic catalysts, chiral modifiers: many areas are rapidly evolving. This Review shows that these catalysts have more to them than facile separation or recycling. Better activities and selectivities can be obtained than with the homogeneous catalyst and novel, efficient reaction mechanisms can be employed. Especially fascinating is the outlook for highly ordered metal-organic catalysts that might allow a rational design, synthesis, and the unequivocal structural characterization to give tailor-made catalysts.
573 citations
University of Michigan1, University of Cologne2, Harvard University3, Medical University of Vienna4, University of Marburg5, Hacettepe University6, Rabin Medical Center7, Tel Aviv University8, University of Freiburg9, Technische Universität München10, Dokuz Eylül University11, Charité12, Hannover Medical School13, State University of New York Upstate Medical University14, University of Rochester15
TL;DR: These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotsic syndrome.
Abstract: Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome.
TL;DR: Plaque assay under Avicel-containing overlay media is easier, faster and more sensitive than assays under agar- and methylcellulose overlays and seems particularly suitable for high-throughput virus titrations, serological studies and experiments on viral drug sensitivity.
Abstract: Plaque assays in cell culture monolayers under solid or semisolid overlay media are commonly used for quantification of viruses and antiviral substances. To overcome the pitfalls of known overlays, we tested suspensions of microcrystalline cellulose Avicel RC/CL™ as overlay media in the plaque and plaque-inhibition assay of influenza viruses. Significantly larger plaques were formed under Avicel-containing media, as compared to agar and methylcellulose (MC) overlay media. The plaque size increased with decreasing Avicel concentration, but even very diluted Avicel overlays (0.3%) ensured formation of localized plaques. Due to their low viscosity, Avicel overlays were easier to use than methylcellulose overlays, especially in the 96-well culture plates. Furthermore, Avicel overlay could be applied without prior removal of the virus inoculum thus facilitating the assay and reducing chances of cross-contamination. Using neuraminidase inhibitor oseltamivir carboxylate, we demonstrated applicability of the Avicel-based plaque reduction assay for testing of antiviral substances. Plaque assay under Avicel-containing overlay media is easier, faster and more sensitive than assays under agar- and methylcellulose overlays. The assay can be readily performed in a 96-well plate format and seems particularly suitable for high-throughput virus titrations, serological studies and experiments on viral drug sensitivity. It may also facilitate work with highly pathogenic agents performed under hampered conditions of bio-safety labs.
TL;DR: A critical review of 88 studies on the assessment of insight and its impact on symptoms and functioning finds a positive cross-sectional and longitudinal relationship between insight and depression, but the underlying processes need further clarification.
Abstract: Between 50 and 80% of the patients diagnosed with schizophrenia have been shown to be partially or totally lacking insight into the presence of their mental disorder. Although a causal chain connecting poor insight with poor treatment adherence and thus with poorer outcome and functioning is straight forward, numerous studies investigating correlates and long-term impact of insight have provided differing results. In addition, higher levels of insight in schizophrenia have been associated with depression and hopelessness, but the causal direction of the relationship is unclear and the data are inconclusive. The current study provides a critical review of 88 studies on the assessment of insight and its impact on symptoms and functioning. Studies published by June 2006 were selected using a keyword search for English peer-reviewed articles in the databases PsycINFO and MEDLINE. The majority of studies support the assumption that insight is associated with adherence during treatment phase, but the association with long-term adherence remains unclear. Insight correlates with better long-term functioning, but this might be explained by its association with symptoms. There is a positive cross-sectional and longitudinal relationship between insight and depression, but the underlying processes need further clarification. In the concluding discussion, the problems relating to definition and study designs are considered responsible for many of the inconclusive findings. Suggestions for further research are derived.
TL;DR: The cloned two human type II transmembrane serine proteases with known airway localization, TMPRSS2 and HAT, are suggested to be candidates for proteolytic activation of influenza viruses in vivo.
Abstract: Host cell proteases that cleave the hemagglutinin (HA) of influenza viruses in the human respiratory tract are still not identified. Here we cloned two human type II transmembrane serine proteases with known airway localization, TMPRSS2 and HAT, into mammalian expression vector. Cotransfection of mammalian cells with plasmids encoding HA and either protease resulted in HA cleavage in situ. Transient expression of either protease in MDCK cells enabled multicycle replication of influenza viruses in these cells in the absence of exogenous trypsin. These data suggest that TMPRSS2 and HAT are candidates for proteolytic activation of influenza viruses in vivo.
TL;DR: In the development of modern nation states, the state has not only been the guarantor of civil rights, e.g. the right to own property, to enter into private contracts, and to engage in market activity, but also provided political participation rights, the right of the citizen to take part in the processes that determine public rules and issues of public concern as discussed by the authors.
Abstract: Economic activities require the existence of rules and their enforcement as preconditions that the market cannot generate itself. Property rights, and contractual rights and obligations, are minimal prerequisites for modern societies that are provided and enforced by the state. Without such prerequisites, the market cannot flourish. The state thus determines regulations and delineates the sphere of private freedom, within which individual citizens and private institutions are entitled to conclude contracts with one another, to which the system of property and contractual rights compels obedience. In the development of modern nation states, the state has not only been the guarantor of civil rights, e. g. the right to own property, to enter into private contracts, and to engage in market activity. In its role as a democratic constitutional state, it has also been the guarantor of political participation rights, the right of the citizen to take part in the processes that determine public rules and issues of public concern. Finally, in its role as a welfare state, it has provided social rights for citizens, such as the right to education, to health care, and to other forms of welfare (Marshall 1965). The combination of state-guaranteed civil, political, and social rights has provided legitimacy, solidarity, and welfare to modern society, thereby contributing to peaceful, stable communities of anonymous individuals (Habermas 2001). Following Matten and Crane (Matten/Crane 2005) we refer to this triad of rights as citizenship rights.
TL;DR: In this article, the effects of mild law in the provision of public goods by comparing it to severe law (deterrent sanctions) and no law are investigated, and the results show that exogenously imposing mild law does not achieve compliance, but compliance is much improved if mild law is endogenously chosen, i.e. self-imposed.
Abstract: Law backed by non-deterrent sanctions (mild law) has been hypothesized to achieve compliance because of norm activation. We experimentally investigate the effects of mild law in the provision of public goods by comparing it to severe law (deterrent sanctions) and no law. The results show that exogenously imposing mild law does not achieve compliance, but compliance is much improved if mild law is endogenously chosen, i.e. self-imposed. We show that voting for mild law induces expectations of cooperation, and that people tend to comply with the law if they expect many others to do so.
TL;DR: A survey of geographical knowledge spillovers and regional growth can be found in this article, where Doring et al. provide a survey of theoretical and empirical findings highlighting the question of how geographically limited knowledge diffusion can help to explain clusters of regions with persistently different levels of growth.
Abstract: Doring T. and Schnellenbach J. (2006) What do we know about geographical knowledge spillovers and regional growth?: a survey of the literature, Regional Studies 40, 375–395. Modern (endogenous) growth theory tells us that knowledge is crucial for the sustained growth of high-income economies. Against this background, the paper provides a survey of theoretical and empirical findings highlighting the question of how geographically limited knowledge diffusion can help to explain clusters of regions with persistently different levels of growth. It discusses this topic in two steps. First, the theoretical concept of knowledge spillovers is outlined by discussing the different types of knowledge, the spatial dimension of knowledge spillovers, and the geographical mechanisms and structural conditions of knowledge diffusion. Second, it analyses the empirical evidence concerning the theoretical propositions. Doring T. and Schnellenbach J. (2006) What do we know about geographical knowledge spillovers and regional ...
TL;DR: A neurocognitive model of online comprehension that accounts for cross-linguistic unity and diversity in the processing of core constituents (verbs and arguments) and can derive the appearance of similar neurophysiological and neuroanatomical processing correlates in seemingly disparate structures in different languages.
Abstract: Real-time language comprehension is a principal cognitive ability and thereby relates to central properties of the human cognitive architecture. Yet how do the presumably universal cognitive and neural substrates of language processing relate to the astounding diversity of human languages (over 5,000)? The authors present a neurocognitive model of online comprehension, the extended argument dependency model (eADM), that accounts for cross-linguistic unity and diversity in the processing of core constituents (verbs and arguments). The eADM postulates that core constituent processing proceeds in three hierarchically organized phases: (1) constituent structure building without relational interpretation, (2) argument role assignment via a restricted set of cross-linguistically motivated information types (e.g., case, animacy), and (3) completion of argument interpretation using information from further domains (e.g., discourse context, plausibility). This basic architecture is assumed to be universal, with cross-linguistic variation deriving primarily from the information types applied in Phase 2 of comprehension. This conception can derive the appearance of similar neurophysiological and neuroanatomical processing correlates in seemingly disparate structures in different languages and, conversely, of cross-linguistic differences in the processing of similar sentence structures.
TL;DR: In this article, the authors show that an increase in the percentage of ethnic minority members affords the majority greater opportunity for intergroup contact and thus reduces the majority's prejudice, which supports threat theory.
Abstract: Research on the relationship between the percentage of an ethnic minority population in a geographically defined area and majority members' prejudice typically reveals a positive covariation. This result supports threat theory. Recent studies, however, have demonstrated significant exceptions. Based on intergroup contact theory, the present study demonstrates with a German probability sample that an increase in the percentage of ethnic minority members affords the majority greater opportunity for intergroup contact and thus reduces the majority's prejudice. These results also falsify frequent political claims that an increase in the minority population above a particular threshold necessarily worsens intergroup relations. The data are discussed in the context of the divergence of our results from those of other studies. Whether threat or contact effects occur may depend on an array of moderators that require further testing.
TL;DR: In this article, the authors investigated the relationship between organizational identification and organizational Citizenship Behaviour (e.g., helping colleagues, making innovative suggestions) using ten samples across different occupational groups and countries.
Abstract: The current study investigates the relationship between Organizational Identification and Organizational Citizenship Behaviour (e.g. helping colleagues, making innovative suggestions). We replicate earlier findings of such a relationship between those behaviours and organizational identification using ten samples across different occupational groups and countries in Study 1. Study 2 investigates the relationship in a longitudinal approach. Study 3 looks into this relationship on a group-level analysis while Study 4 extends our findings by linking identification to customer perceptions and financial performance, mediated by OCBs (Organizational Citizenship Behaviours).
TL;DR: In this paper, a many-body theory based on an equation-of-motion approach for the interacting electron, hole, photon, and phonon system is reviewed, and the infinite hierarchy of coupled equations for the relevant correlation functions is systematically truncated using a cluster-expansion scheme.
TL;DR: Only complete resection was associated with prolonged survival in recurrent ovarian cancer and the identified criteria panel will be verified in a prospective trial evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent Ovarian cancer.
Abstract: The role of cytoreductive surgery in relapsed ovarian cancer is not clearly defined. Therefore, patient selection remains arbitrary and depends on the center’s preference rather than on established selection criteria. The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in recurrent OVARian cancer (DESKTOP OVAR) trial was undertaken to form a hypothesis for a panel of criteria for selecting patients who might benefit from surgery in relapsed ovarian cancer. The DESKTOP trial was an exploratory study based on data from a retrospective analysis of hospital records. Twenty-five member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee (AGO OC) and AGO-OVAR boards collected data on their patients with cytoreductive surgery for relapsed invasive epithelial ovarian cancer performed in 2000–2003. Two hundred and sixty-seven patients were included. Complete resection was associated with significantly longer survival compared with surgery leaving any postoperative residuals [median 45.2 vs. 19.7 months; hazard ratio (HR) 3.71; 95% confidence interval (CI) 2.27–6.05; P 0; P 500 ml (P < .001). A combination of PS, early FIGO stage initially or no residual tumor after first surgery, and absence of ascites could predict complete resection in 79% of patients. Only complete resection was associated with prolonged survival in recurrent ovarian cancer. The identified criteria panel will be verified in a prospective trial (AGO-DESKTOP II) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent ovarian cancer.
TL;DR: Researchers have described three distinct assembly systems in eukaryotes that are involved in the maturation of cellular Fe/S proteins, including the ISC-the iron-sulfur cluster assembly machinery that was inherited from a similar system of eubacteria in evolution.
Abstract: Iron-sulfur (Fe/S) clusters require a complex set of proteins to become assembled and incorporated into apoproteins in a living cell. Researchers have described three distinct assembly systems in eukaryotes that are involved in the maturation of cellular Fe/S proteins. Mitochondria are central for biogenesis. They contain the ISC-the iron-sulfur cluster assembly machinery that was inherited from a similar system of eubacteria in evolution and is involved in biogenesis of all cellular Fe/S proteins. The basic principle of mitochondrial (and bacterial) Fe/S protein maturation is the synthesis of the Fe/S cluster on a scaffold protein before the cluster is transferred to apoproteins. Biogenesis of cytosolic and nuclear Fe/S proteins is facilitated by the cytosolic iron-sulfur protein assembly (CIA) apparatus. This process requires the participation of mitochondria that export a still unknown component via the ISC export machinery, including an ABC transporter.
TL;DR: Both the chain length and graft density of PEG were found to strongly influence siRNA condensation and stability and hence affect the knockdown efficiency of PEI-PEG/siRNA polyplexes.
TL;DR: It is found that the surface of the edge of chaos coincides with the stable manifold of a periodic orbit, whereas at higher Reynolds numbers it is the stable set of a higher-dimensional chaotic object.
Abstract: We study the transition between laminar and turbulent states in a Galerkin representation of a parallel shear flow, where a stable laminar flow and a transient turbulent flow state coexist. The regions of initial conditions where the lifetimes show strong fluctuations and a sensitive dependence on initial conditions are separated from the ones with a smooth variation of lifetimes by an object in phase space which we call the ``edge of chaos.'' We describe techniques to identify and follow the edge, and our results indicate that the edge is a surface. For low Reynolds numbers we find that the surface coincides with the stable manifold of a periodic orbit, whereas at higher Reynolds numbers it is the stable set of a higher-dimensional chaotic object.
TL;DR: Experimental data and numerical calculations covering more than two decades of lifetimes are presented, showing that the lifetime does not in fact diverge but rather increases exponentially with the Reynolds number, implying that turbulence in pipes is only a transient event, and that the turbulent and laminar states remain dynamically connected, suggesting avenues for turbulence control.
Abstract: Generally, the motion of fluids is smooth and laminar at low speeds but becomes highly disordered and turbulent as the velocity increases. The transition from laminar to turbulent flow can involve a sequence of instabilities in which the system realizes progressively more complicated states, or it can occur suddenly. Once the transition has taken place, it is generally assumed that, under steady conditions, the turbulent state will persist indefinitely. The flow of a fluid down a straight pipe provides a ubiquitous example of a shear flow undergoing a sudden transition from laminar to turbulent motion. Extensive calculations and experimental studies have shown that, at relatively low flow rates, turbulence in pipes is transient, and is characterized by an exponential distribution of lifetimes. They also suggest that for Reynolds numbers exceeding a critical value the lifetime diverges (that is, becomes infinitely large), marking a change from transient to persistent turbulence. Here we present experimental data and numerical calculations covering more than two decades of lifetimes, showing that the lifetime does not in fact diverge but rather increases exponentially with the Reynolds number. This implies that turbulence in pipes is only a transient event (contrary to the commonly accepted view), and that the turbulent and laminar states remain dynamically connected, suggesting avenues for turbulence control.
TL;DR: To provide evidence‐based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature, a list of therapeutic interventions is provided, including classification of evidence and ratings of efficacy.
Abstract: The aim of the study was to provide evidence-based recommendations for the management of early (uncomplicated) Parkinson's disease (PD), based on a review of the literature. Uncomplicated PD refers to patients suffering from the classical motor syndrome of PD only, without treatment-induced motor complications and without neuropsychiatric or autonomic problems. MEDLINE, Cochrane Library and International Network of Agencies for Health Technology Assessment (INAHTA) database literature searches were conducted. National guidelines were requested from all European Federation of Neurological Societies (EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I of the guidelines deals with prevention of disease progression, symptomatic treatment of motor features (parkinsonism), and prevention of motor and neuropsychiatric complications of therapy. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (good practice point) is made.
TL;DR: The majority of patients with epilepsy maintain seizure control during pregnancy, and the apparently higher risk of seizures among women treated with ox carbazepine and the more frequent increases in drug load in the oxcarbazepines and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes.
Abstract: Objective: To analyze seizure control and treatment in pregnant women with epilepsy. Methods: Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Results: Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5; 1.7 to 3.9) and polytherapy (OR: 9.0; 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4; 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8; 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6; 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8; 2.1 to 6.9) or oxcarbazepine (OR: 3.7; 1.1 to 12.9). Conclusions: The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.