Publications by authors named "Philipp Schulz"

24 Publications

  • Page 1 of 1

Liver stiffness and prediction of cardiac outcomes in patients with acute decompensated heart failure.

Clin Transplant 2021 Nov 24:e14545. Epub 2021 Nov 24.

Baylor Scott & White Research Institute, Baylor University Medical Center, Dallas, TX, USA.

Background: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF.

Methods: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death.

Results: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = 0.049). Moreover, the risk of composite outcome was highest in the 3rd tertile (>39.8 kPa compared to 1 and 2 combined, HR 2.83, 95% CI 1.20- 6.67, p = 0.02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = 0.01).

Conclusions: LSM may serve as a novel noninvasive tool to determine LVAD, HT or death in patients with ADHF. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ctr.14545DOI Listing
November 2021

The 'marketplace of post-conflict assistance' in Northern Uganda and beyond.

Disasters 2021 May 21. Epub 2021 May 21.

University of Bremen.

In this article, we put forward the framework of the 'marketplace of post-conflict assistance' as a conceptual, analytical and heuristic tool to better understand the holistic dynamics that take place in humanitarian and post-conflict contexts, where a variety of different actors offer various forms of services and assistance. With this conceptual framework, we seek to emphasize the relational and interactional dynamics between providers of services and intended beneficiaries in contexts where there are often a variety of different ways to conceptualize and manage problems stemming from years of armed conflict. We show this through one in-depth case study of a family who have struggled for years with mental illness/spiritual problems in the years during and after the armed conflict in Northern Uganda. By framing the post-conflict space through the marketplace metaphor, it becomes possible to gain a more holistic and dynamic understanding of the ways in which people try out different options to manage issues related to years of armed conflict and seek healing. Importantly, this framework also recognizes the agency that people exercise in doing so, and how communities and service-providers in humanitarian, developmental and post-conflict contexts relate to each other.
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http://dx.doi.org/10.1111/disa.12493DOI Listing
May 2021

A Multi-OMICs Approach Sheds Light on the Higher Yield Phenotype and Enhanced Abiotic Stress Tolerance in Tobacco Lines Expressing the Carrot β Gene.

Front Plant Sci 2021 5;12:624365. Epub 2021 Feb 5.

Max Planck Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany.

Recently, we published a set of tobacco lines expressing the (carrot) gene with accelerated development, increased carotenoid content, photosynthetic efficiency, and yield. Because of this development, expression might be of general interest in crop species as a strategy to accelerate development and increase biomass production under field conditions. However, to follow this path, a better understanding of the molecular basis of this phenotype is essential. Here, we combine OMICs (RNAseq, proteomics, and metabolomics) approaches to advance our understanding of the broader effect of expression on the tobacco transcriptome and metabolism. Upon expression, the tobacco transcriptome (~2,000 genes), proteome (~700 proteins), and metabolome (26 metabolites) showed a high number of changes in the genes involved in metabolic processes related to cell wall, lipids, glycolysis, and secondary metabolism. Gene and protein networks revealed clusters of interacting genes and proteins mainly involved in ribosome and RNA metabolism and translation. In addition, abiotic stress-related genes and proteins were mainly upregulated in the transgenic lines. This was well in line with an enhanced stress (high light, salt, and HO) tolerance response in all the transgenic lines compared with the wild type. Altogether, our results show an extended and coordinated response beyond the chloroplast (nucleus and cytosol) at the transcriptome, proteome, and metabolome levels, supporting enhanced plant growth under normal and stress conditions. This final evidence completes the set of benefits conferred by the expression of the gene, making it a very promising bioengineering tool to generate super crops.
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http://dx.doi.org/10.3389/fpls.2021.624365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893089PMC
February 2021

Predicting On-Road Driving Skills, Fitness to Drive, and Prospective Accident Risk in Older Drivers and Drivers with Mild Cognitive Impairment: The Importance of Non-Cognitive Risk Factors.

J Alzheimers Dis 2021 ;79(1):401-414

Evangelisches Klinikum Bethel (EvKB), Department of Psychiatry and Psychotherapy, Bielefeld, Germany.

Background: On-road driving behavior can be impaired in older drivers and particularly in drivers with mild cognitive impairment (MCI).

Objective: To determine whether cognitive and non-cognitive risk factors for driving safety may allow an accurate and economic prediction of on-road driving skills, fitness to drive, and prospective accident risk in healthy older drivers and drivers with MCI, we examined a representative combined sample of older drivers with and without MCI (N = 74) in an observational on-road study. In particular, we examined whether non-cognitive risk factors improve predictive accuracy provided by cognitive factors alone.

Methods: Multiple and logistic hierarchical regression analyses were utilized to predict different driving outcomes. In all regression models, we included cognitive predictors alone in a first step and added non-cognitive predictors in a second step.

Results: Results revealed that the combination of cognitive and non-cognitive risk factors significantly predicted driving skills (R2adjusted = 0.30) and fitness to drive (81.2% accuracy) as well as the number (R2adjusted = 0.21) and occurrence (88.3% accuracy) of prospective minor at-fault accidents within the next 12 months. In all analyses, the inclusion of non-cognitive risk factors led to a significant increase of explained variance in the different outcome variables.

Conclusion: Our findings suggest that a combination of the most robust cognitive and non-cognitive risk factors may allow an economic and accurate prediction of on-road driving performance and prospective accident risk in healthy older drivers and drivers with MCI. Therefore, non-cognitive risk factors appear to play an important role.
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http://dx.doi.org/10.3233/JAD-200943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902978PMC
September 2021

Assessing fitness to drive in older adults: Validation and extension of an economical screening tool.

Accid Anal Prev 2021 Jan 19;149:105874. Epub 2020 Nov 19.

Evangelisches Klinikum Bethel (EvKB), Department of Psychiatry and Psychotherapy, Research Division, Remterweg 69-71, 33617, Bielefeld, Germany; Evangelisches Klinikum Bethel (EvKB), Department of Psychiatry and Psychotherapy, Division of Geriatric Psychiatry, Bethesdaweg 12, 33617, Bielefeld, Germany; Evangelisches Klinikum Bethel (EvKB), Department of Psychiatry and Psychotherapy, Memory Clinic, Gadderbaumer Straße 33, D-33602, Bielefeld, Germany.

Objectives: Due to demographic change, the number of older drivers with impaired driving skills will increase in the next decades. The current study aimed at the validation and extension of the screening tool Safety Advice For Elderly drivers (SAFE) that allows a cost-efficient assessment of driving-related risk factors in older drivers.

Method: Seventy-four older drivers aged ≥65 years (M = 77 years) recruited from the general population were included in this prospective observational study. Receiver operating characteristic curve (ROC) and hierarchical logistic regression analyses were utilized to examine whether the SAFE and further evidence-based driving-related factors may allow the differentiation between fit and unfit older drivers assessed in standardized on-road driving assessments.

Results: ROC analyses revealed significant diagnostic accuracy of the number of SAFE risk factors in differentiating between fit and unfit older drivers (AUC = 0.71). A stepwise logistic regression model revealed that adding further evidence-based risk factors into the SAFE clearly improved diagnostic accuracy (AUC = 0.85).

Discussion: The current study shows that the risk assessed by the SAFE predicts on-road driving fitness in older adults. However, the results also suggest a need for a modification of the SAFE by the inclusion of additional evidence-based risk factors. With sensitivity and specificity scores of about 90 % and 75 %, this modified version may be more suitable for clinical use.
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http://dx.doi.org/10.1016/j.aap.2020.105874DOI Listing
January 2021

Preoperative synovial fluid culture poorly predicts the pathogen causing periprosthetic joint infection.

Infection 2021 Jun 3;49(3):427-436. Epub 2020 Nov 3.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery (CMSC), Charitéplatz 1, 10117, Berlin, Germany.

Purpose: We investigated the value of preoperative pathogen detection and evaluated its concordance with intraoperative cultures in patients with culture-positive periprosthetic joint infection (PJI).

Methods: Culture-positive PJI episodes with available preoperative (synovial fluid) and intraoperative cultures (periprosthetic tissue, synovial or sonication fluid) were analyzed. The pathogen detection rate in preoperative and intraoperative cultures was compared using Fisher's exact test and their concordance was calculated.

Results: Among 167 included PJI episodes, 150 were monomicrobial with coagulase-negative staphylococci (n = 55, 37%), S. aureus (n = 34, 23%), and streptococci (n = 21, 14%) being the most common pathogens. Seventeen episodes (10%) were polymicrobial infections. The pathogen(s) grew in preoperative culture in 110 and in intraoperative cultures in 153 episodes (66% vs. 92%, p < 0.001). The pathogen detection rate was lower in preoperative compared to intraoperative cultures for low-virulent pathogens (40% vs. 94%, p < 0.001), polymicrobial infections (59% vs. 100%, p = 0.007), and in delayed and late PJI (63% vs. 94%, and 66% vs. 91%, respectively, p < 0.001). Full concordance of preoperative and intraoperative cultures was found in 87 episodes (52%). The pathogen was detected solely preoperatively in 14 episodes (8%) and solely intraoperatively in 57 cases (34%); an additional pathogen was found in 3 episodes (2%) preoperatively and in 6 episodes (4%) intraoperatively.

Conclusion: The concordance of preoperative and intraoperative cultures was poor (52%). The sole or an additional pathogen was found exclusively in intraoperative cultures in 38% of PJI episodes, hence preoperative synovial fluid cultures are considered unreliable for pathogen detection in PJI.
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http://dx.doi.org/10.1007/s15010-020-01540-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159841PMC
June 2021

Improving plant drought tolerance and growth under water limitation through combinatorial engineering of signalling networks.

Plant Biotechnol J 2021 01 26;19(1):74-86. Epub 2020 Jul 26.

Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.

Agriculture is by far the biggest water consumer on our planet, accounting for 70 per cent of all freshwater withdrawals. Climate change and a growing world population increase pressure on agriculture to use water more efficiently ('more crop per drop'). Water-use efficiency (WUE) and drought tolerance of crops are complex traits that are determined by many physiological processes whose interplay is not well understood. Here, we describe a combinatorial engineering approach to optimize signalling networks involved in the control of stress tolerance. Screening a large population of combinatorially transformed plant lines, we identified a combination of calcium-dependent protein kinase genes that confers enhanced drought stress tolerance and improved growth under water-limiting conditions. Targeted introduction of this gene combination into plants increased plant survival under drought and enhanced growth under water-limited conditions. Our work provides an efficient strategy for engineering complex signalling networks to improve plant performance under adverse environmental conditions, which does not depend on prior understanding of network function.
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http://dx.doi.org/10.1111/pbi.13441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769235PMC
January 2021

Effectiveness of inpatient versus outpatient complex treatment programs in depressive disorders: a quasi-experimental study under naturalistic conditions.

BMC Psychiatry 2019 12 2;19(1):380. Epub 2019 Dec 2.

Klinik für Psychiatrie und Psychotherapie, Evangelisches Klinikum Bethel, Remterweg 69-71, 33617, Bielefeld, Germany.

Background: Due to long waiting periods for outpatient psychotherapy and the high resource requirements of inpatient treatment, there is a need for alternative treatment programs for patients with depressive disorders. Thus, we investigated the effectiveness of the "Bielefeld Outpatient Intensive Treatment Program of Depression" (BID) in comparison with a typical inpatient treatment program by using a prospective quasi-experimental observational study. We assumed (i) that both complex programs are effective in pre-post analyses after 6 weeks and (ii) that inpatient treatment is more effective compared with the outpatient program.

Methods: Four hundred patients with depressive psychopathology - a majority with depressive episodes (ICD-10 F3X) - took part in the BID and 193 in the inpatient program. Different self- (i.e., BDI) and expert measures (i.e., MADRS) of psychopathology at baseline (t1) and 6 weeks later (t2) were applied to examine treatment effects.

Results: Treatment effects were high in separate analyses of both groups with Cohen's d ranging from 1.10 to 1.76., while ANOVA comparative analyses did not reveal any significant differences between both treatment settings nor did a set of independent covariates analyzed here. Response rates of BDI (p = .002) and MADRS (p = .001) were higher in the outpatient group. Results indicate BID not to be inferior compared to an inpatient program, although diverging pathways to treatment, higher rates of clinical recurrent depressive disorders and severe episodes as well as lower rates of employment and partnership in the inpatient treatment group have to be considered.

Conclusion: Outpatient intensive treatment programs may represent a solution for patients needing more than a treatment session once per week but less than a complex inpatient or day clinic program.
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http://dx.doi.org/10.1186/s12888-019-2371-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889566PMC
December 2019

Symbol Comprehension in Patients With Alzheimer Disease Dementia, Mild Cognitive Impairment, and Major Depressive Disorder.

Alzheimer Dis Assoc Disord 2020 Jan-Mar;34(1):85-93

Department of Psychiatry and Psychotherapy, Research Division.

Introduction: Previous research suggests that specific symbol features attenuate symbol comprehension deficits in seniors suffering from Alzheimer disease dementia (ADD). However, it remains unclear whether these findings also apply to other disorders associated with cognitive dysfunctions.

Methods: Ninety healthy controls, 30 patients with major depressive disorder (MDD), 35 patients with mild cognitive impairment (MCI), and 55 patients with ADD performed a Symbol Processing Task with 4 different symbol categories. Nonparametric between×within subjects analyses were conducted to examine the impact of different symbol categories on performance accuracy in all experimental groups.

Results: Analyses revealed a higher symbol comprehension accuracy in healthy seniors than in MDD, MCI, and ADD patients, with the lowest accuracy rates shown by ADD patients. Although the type of symbol hardly affected performance accuracy in healthy seniors and MDD patients, different symbol categories influenced the performance of MCI and ADD patients significantly.

Conclusions: Our findings indicate that symbols with distracting features impede symbol comprehension in ADD and MCI. Symbols with visual cues, by contrast, facilitate symbol comprehension in ADD and may even be advantageous over standardized symbols used in public life.
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http://dx.doi.org/10.1097/WAD.0000000000000347DOI Listing
November 2020

Avoidance Behavior Is an Independent Indicator of Poorer On-road Driving Skills in Older Adults.

J Gerontol B Psychol Sci Soc Sci 2020 11;75(10):2152-2161

Research Division, Department of Psychiatry and Psychotherapy, Evangelisches Klinikum Bethel (EvKB), Bielefeld, Germany.

Objectives: The aim of the current work was to investigate the relationship between avoidance of specific driving situations and on-road driving skills in older drivers considering factors found to be related to both avoidance behavior and driving skills.

Method: Seventy-two older drivers (M = 76 years) from the general population were included in this study. Self-reported avoidance behavior, driving practice, perceived driving difficulties, driving-related cognitive functions, as well as medical conditions were assessed within two sessions. Standardized on-road assessments served for assessing on-road driving skills in a third session.

Results: Self-reported avoidance behavior was associated with reduced driving skills (r = -.41), and this relationship remained significant beyond the influence of cognitive skills, self-reported health, driving practice, and perceived driving difficulties. Specifically, avoidance of driving in bad weather, poor visibility and complicated parking was found to be associated with reduced driving skills.

Discussion: This study suggest that avoidance behavior is an independent indicator of impaired driving skills in older drivers. Our results argue against the assumption that avoidance behavior may be a reasonable strategy for safe traffic participation. Longitudinal studies are urgently needed to get more evidence on safety aspects of avoidance behavior.
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http://dx.doi.org/10.1093/geronb/gbz063DOI Listing
November 2020

How is childhood emotional abuse related to major depression in adulthood? The role of personality and emotion acceptance.

Child Abuse Negl 2017 Oct 5;72:98-109. Epub 2017 Aug 5.

Evangelisches Klinikum Bethel (EvKB), Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Bethesdaweg 12, D-33617 Bielefeld, Germany; Faculty of Psychology, Department of Applied Psychology, Health, Development, Enhancement, and Intervention, University of Vienna, Liebiggasse 5, 1010 Vienna, Austria. Electronic address:

Accumulated evidence provides support that childhood emotional abuse (CEA) is related to adult major depressive disorder (MDD) outcomes. However, the psychological mechanisms of this relation are still not well understood. Changes in personality and emotion regulation are indicated to play a mediating role what should be examined in this paper. A sample of 123 MDD inpatients was examined in a prospective observational study with two times of measurement. Patients provided data on childhood trauma history, personality disorder (PD) traits and emotion acceptance. Self- and expert-ratings of depressive symptoms were assessed at baseline and at the end of treatment. Treatment duration as an objective indicator of treatment outcome was additionally considered. Partial correlation analyses revealed associations between CEA and self-ratings of MDD symptom severity and symptom improvement independent of sexual and physical abuse. Expert-ratings of depression and treatment duration were not related to CEA. Mediation analyses revealed that particularly the factors borderline psychopathology as well as acceptance of pleasant emotions mediated the association of CEA and self-rated MDD symptoms. Passive-aggressive PD traits mediated the link between CEA and a lower self-rated symptom improvement. CEA affect specific personality traits and acceptance of emotions. This association may play a critical role for self-reported depressive symptoms with implications for prevention, psychoeducation, and treatment of MDD.
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http://dx.doi.org/10.1016/j.chiabu.2017.07.022DOI Listing
October 2017

Ca coordination controls sonic hedgehog structure and its Scube2-regulated release.

J Cell Sci 2017 Oct 4;130(19):3261-3271. Epub 2017 Aug 4.

Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, D-48149 Münster, Germany

Proteolytic processing of cell-surface-bound ligands, called shedding, is a fundamental system to control cell-cell signaling. Yet, our understanding of how shedding is regulated is still incomplete. One way to increase the processing of dual-lipidated membrane-associated Sonic hedgehog (Shh) is to increase the density of substrate and sheddase. This releases and also activates Shh by the removal of lipidated inhibitory N-terminal peptides from Shh receptor binding sites. Shh release and activation is enhanced by Scube2 [signal sequence, cubulin (CUB) domain, epidermal growth factor (EGF)-like protein 2], raising the question of how this is achieved. Here, we show that Scube2 EGF domains are responsible for specific proteolysis of the inhibitory Shh N-terminus, and that CUB domains complete the process by reversing steric masking of this peptide. Steric masking, in turn, depends on Ca occupancy of Shh ectodomains, unveiling a new mode of shedding regulation at the substrate level. Importantly, Scube2 uncouples processing of Shh peptides from their lipid-mediated juxtamembrane positioning, and thereby explains the long-standing conundrum that N-terminally unlipidated Shh shows patterning activity in Scube2-expressing vertebrates, but not in invertebrates that lack Scube orthologs.
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http://dx.doi.org/10.1242/jcs.205872DOI Listing
October 2017

Do self-reports provide valid information about driving fitness in seniors?

Int J Geriatr Psychiatry 2017 02;32(2):231-232

Evangelisches Krankenhaus Bielefeld (EvKB), Department of Psychiatry and Psychotherapy Bethel, Research Division, Bielefeld, Germany.

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http://dx.doi.org/10.1002/gps.4612DOI Listing
February 2017

Advice for Elderly Drivers in a German Memory Clinic: A Case Report on Medical, Ethical and Legal Consequences.

Geriatrics (Basel) 2016 Mar 19;1(1). Epub 2016 Mar 19.

Division of Geriatric Psychiatry, Department of Psychiatry and Psychotherapy Bethel, Evangelisches Krankenhaus Bielefeld, Bethesdaweg 12, D-33617 Bielefeld, Germany.

We report on a 75-year-old female who consulted our Memory Clinic because of subjective memory complaints that she first recognized three months previously. Next to the standard detailed patient history, neuropsychological assessment, psychopathological status, the patient's driving history played an important role in the diagnostic process. In this case report, we illustrate the diagnostic process starting with the first consultation, including a short neuropsychological examination and communicating its results, reporting on further work-up (detailed neuropsychological assessment, MRI scan and cerebrospinal fluid (CSF) analysis) up to the final consultation, including advice for the patient. We will focus on several medical, ethical and legal difficulties that may occur when consulting elderly drivers with initial cognitive decline.
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http://dx.doi.org/10.3390/geriatrics1010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371184PMC
March 2016

Preliminary Validation of a Questionnaire Covering Risk Factors for Impaired Driving Skills in Elderly Patients.

Geriatrics (Basel) 2016 Jan 8;1(1). Epub 2016 Jan 8.

Evangelisches Krankenhaus Bielefeld, Department of Psychiatry and Psychotherapy Bethel, Research Division, Remterweg 69-71, D-33617 Bielefeld, Germany.

Due to rather unspecific statutory regulations in Germany, particularly for patients with neurodegenerative disorders, many seniors still drive despite severe driving-related cognitive deficits. An accurate assessment of driving fitness requires immense financial, personnel and temporal resources which go beyond daily clinical routines. In cooperation with a working group from Switzerland, we therefore developed the questionnaire (SAFE), an economic instrument covering different risk factors for driving safety. The main aim of the current work was a first validation of the SAFE. Twenty-two driving seniors performed the Corporal A, a test battery permitted by law to assess driving-related cognitive functions. Based upon the Corporal results and the percentile rank 16 criterion, participants were divided into cognitively impaired and unimpaired drivers. Moreover, participants were assessed using the SAFE and an extensive neuropsychological test battery. The results revealed high sensitivity and specifity scores for the SAFE suggesting that the SAFE may be a valuable and economical instrument to quantify and document individual risk factors for driving safety and to differentiate between impaired and unimpaired drivers. Notably, the results must be replicated in future studies including a larger sample, different clinical subgroups, and a practical driving lesson.
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http://dx.doi.org/10.3390/geriatrics1010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371095PMC
January 2016

"A bend in time": Shaping the sheath facilitates left atrial appendage closure.

Catheter Cardiovasc Interv 2015 Nov 23;86(5):E224-8. Epub 2015 May 23.

CardioVascular Center Frankfurt, Frankfurt, Germany.

Objectives: The purpose of this study is to determine feasibility, safety, and effectiveness of the "shape-the-sheath" method in left atrial appendage closure.

Background: LAA occlusion is often a difficult procedure, due to not just the learning curve but also the three-dimensional variable nature of the left atrial appendage. Multiple sheaths have been created for various takeoffs. The purpose of this article is to show the feasibility of the "shape-the-sheath" method in left atrial appendage closure.

Methods: Ten consecutive patients undergoing LAA occlusion without the "shape-the-sheath" method were compared to 10 consecutive patients undergoing LAA occlusion with the "shape-the-sheath" method using the Amplatzer Cardiac Plug (ACP) system and the Amplatzer TorqVue 45×45 sheath.

Results: The "shape-the-sheath" method resulted in significant decreases in fluoroscopy time (7.2±3.0 min vs. 13.7±6.7 min, P<0.05), number of partial recaptures (0% vs. 50%, P<0.05), with a trend toward decrease in the number of complete recaptures (0 vs. 40%, P=0.09) compared to conventional sheath use.

Conclusions: Shaping-the-sheath is a simple, elegant way to help conform delivery systems to better access the LAA and ensure stable position. Further experience with this procedure optimization step is warranted.
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http://dx.doi.org/10.1002/ccd.25996DOI Listing
November 2015

Use of EchoNavigator, a novel echocardiography-fluoroscopy overlay system, for transseptal puncture and left atrial appendage occlusion.

J Interv Cardiol 2015 Apr 13;28(2):215-7. Epub 2015 Feb 13.

CardioVascular Center Frankfurt, Frankfurt, Germany.

Structural heart disease requires a coordinated effort to join echocardiographic and fluoroscopic data. Various methods have been used, including echocardiography, CT, and MRI. We report on the use of EchoNavigator (Philips Inc., Amsterdam, Netherlands), a novel echocardiographic-fluoroscopic fusion system. This new system allows real-time integration and marking of important structures that track on fluoroscopy even with movement of the C-arm. In this article, we describe potential uses for this system in respect to transseptal puncture and left atrial appendage closure.
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http://dx.doi.org/10.1111/joic.12170DOI Listing
April 2015

Poly(ADP-ribose)polymerase activity controls plant growth by promoting leaf cell number.

PLoS One 2014 28;9(2):e90322. Epub 2014 Feb 28.

Bayer CropScience NV, Innovation Center, Zwijnaarde, Belgium.

A changing global environment, rising population and increasing demand for biofuels are challenging agriculture and creating a need for technologies to increase biomass production. Here we demonstrate that the inhibition of poly (ADP-ribose) polymerase activity is a promising technology to achieve this under non-stress conditions. Furthermore, we investigate the basis of this growth enhancement via leaf series and kinematic cell analysis as well as single leaf transcriptomics and plant metabolomics under non-stress conditions. These data indicate a regulatory function of PARP within cell growth and potentially development. PARP inhibition enhances growth of Arabidopsis thaliana by enhancing the cell number. Time course single leaf transcriptomics shows that PARP inhibition regulates a small subset of genes which are related to growth promotion, cell cycle and the control of metabolism. This is supported by metabolite analysis showing overall changes in primary and particularly secondary metabolism. Taken together the results indicate a versatile function of PARP beyond its previously reported roles in controlling plant stress tolerance and thus can be a useful target for enhancing biomass production.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090322PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938684PMC
October 2014

Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells.

J Cell Sci 2014 Apr 12;127(Pt 8):1726-37. Epub 2014 Feb 12.

The Institute for Physiological Chemistry and Pathobiochemistry, Westfälische Wilhelms Universität Münster, Waldeyerstrasse 15, D-48149 Münster, Germany.

All morphogens of the Hedgehog (Hh) family are synthesized as dual-lipidated proteins, which results in their firm attachment to the surface of the cell in which they were produced. Thus, Hh release into the extracellular space requires accessory protein activities. We suggested previously that the proteolytic removal of N- and C-terminal lipidated peptides (shedding) could be one such activity. More recently, the secreted glycoprotein Scube2 (signal peptide, cubulin domain, epidermal-growth-factor-like protein 2) was also implicated in the release of Shh from the cell membrane. This activity strictly depended on the CUB domains of Scube2, which derive their name from the complement serine proteases and from bone morphogenetic protein-1/tolloid metalloproteinases (C1r/C1s, Uegf and Bmp1). CUB domains function as regulators of proteolytic activity in these proteins. This suggested that sheddases and Scube2 might cooperate in Shh release. Here, we confirm that sheddases and Scube2 act cooperatively to increase the pool of soluble bioactive Shh, and that Scube2-dependent morphogen release is unequivocally linked to the proteolytic processing of lipidated Shh termini, resulting in truncated soluble Shh. Thus, Scube2 proteins act as protease enhancers in this setting, revealing newly identified Scube2 functions in Hh signaling regulation.
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http://dx.doi.org/10.1242/jcs.137695DOI Listing
April 2014

A phenomics approach to the analysis of the influence of glutathione on leaf area and abiotic stress tolerance in Arabidopsis thaliana.

Front Plant Sci 2013 5;4:416. Epub 2013 Nov 5.

Centre of Plant Sciences, Faculty of Biology, University of Leeds Leeds, UK.

Reduced glutathione (GSH) is an abundant low molecular weight plant thiol. It fulfills multiple functions in plant biology, many of which remain poorly characterized. A phenomics approach was therefore used to investigate the effects of glutathione homeostasis on growth and stress tolerance in Arabidopsis thaliana. Rosette leaf area was compared in mutants that are either defective in GSH synthesis (cad2, pad2, and rax1) or the export of γ-glutamylcysteine and GSH from the chloroplast (clt) and in wild-type plants under standard growth conditions and following exposure to a range of abiotic stress treatments, including oxidative stress, water stress, and high salt. In the absence of stress, the GSH synthesis mutants had a significantly lower leaf area than the wild type. Conversely, the clt mutant has a greater leaf area and a significantly reduced lateral root density than the wild type. These findings demonstrate that cellular glutathione homeostasis exerts an influence on root architecture and on rosette area. An impaired capacity to synthesize GSH or a specific depletion of the cytosolic GSH pool did not adversely affect leaf area in plants exposed to short-term abiotic stress. However, the negative effects of long-term exposure to oxidative stress and high salt on leaf area were less marked in the GSH synthesis mutants than the wild type. These findings demonstrate the importance of cellular glutathione homeostasis in the regulation of plant growth under optimal and stress conditions.
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http://dx.doi.org/10.3389/fpls.2013.00416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817356PMC
November 2013

Calcium-dependent protein kinases: hubs in plant stress signaling and development.

Plant Physiol 2013 Oct 6;163(2):523-30. Epub 2013 Sep 6.

Department of Plant Biochemistry, Dahlem Center of Plant Sciences, Freie Universität Berlin, 14195 Berlin, Germany.

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http://dx.doi.org/10.1104/pp.113.222539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793034PMC
October 2013

Chemical PARP inhibition enhances growth of Arabidopsis and reduces anthocyanin accumulation and the activation of stress protective mechanisms.

PLoS One 2012 25;7(5):e37287. Epub 2012 May 25.

Bayer CropScience NV, Gent, Belgium.

Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through the addition of ADP-ribose polymers, yet its role in modulating plant development and stress responses is only poorly understood. The experiments presented here address some of the gaps in our understanding of its role in stress tolerance and thereby provide new insights into tolerance mechanisms and growth. Using a combination of chemical and genetic approaches, this study characterized phenotypes associated with PARP inhibition at the physiological level. Molecular analyses including gene expression analysis, measurement of primary metabolites and redox metabolites were used to understand the underlying processes. The analysis revealed that PARP inhibition represses anthocyanin and ascorbate accumulation under stress conditions. The reduction in defense is correlated with enhanced biomass production. Even in unstressed conditions protective genes and molecules are repressed by PARP inhibition. The reduced anthocyanin production was shown to be based on the repression of transcription of key regulatory and biosynthesis genes. PARP is a key factor for understanding growth and stress responses of plants. PARP inhibition allows plants to reduce protection such as anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high energy levels likely enabling the observed enhancement of biomass production under stress, opening interesting perspectives for increasing crop productivity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360695PMC
December 2012

Purinergic receptor-mediated Ca signaling in the olfactory bulb and the neurogenic area of the lateral ventricles.

Purinergic Signal 2010 Dec 1;6(4):429-45. Epub 2010 Dec 1.

Like in other vertebrates, the anterior part of the telencephalon of amphibians mainly consists of the olfactory bulb (OB), but different from higher vertebrates, the lateral telencephalic ventricles of larval Xenopus laevis expand deep into the anterior telencephalon. The neurogenic periventricular zone (PVZ) of the lateral ventricles generates new OB neurons throughout the animal's lifetime. We investigated the ultrastructural organization of the PVZ and found that within a time period of 24 h, 42.54 ± 6.65% of all PVZ cells were actively proliferating. Functional purinergic receptors are widespread in the central nervous system and their activation has been associated with many critical physiological processes, including the regulation of cell proliferation. In the present study we identified and characterized the purinergic system of the OB and the PVZ. ATP and 2MeSATP induced strong [Ca(2+)](i) increases in cells of both regions, which could be attenuated by purinergic antagonists. However, a more thorough pharmacological investigation revealed clear differences between the two brain regions. Cells of the OB almost exclusively express ionotropic P2X purinergic receptor subtypes, whereas PVZ cells express both ionotropic P2X and metabotropic P1 and P2Y receptor subtypes. The P2X receptors expressed in the OB are evidently not involved in the immediate processing of olfactory information.
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http://dx.doi.org/10.1007/s11302-010-9207-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033506PMC
December 2010
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