The expression of VvMYBPA1 in tobacco remodulates the phenylpropanoid pathway and diverts the synthesis of anthocyanins into condensed tannins in flowers

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus.In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects.This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task

Quantification of biventricular myocardial function using cardiac magnetic resonance feature tracking, endocardial border delineation and echocardiographic speckle tracking in patients with repaired tetralogy of fallot and healthy controls

BACKGROUND: Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function in patients with tetralogy of Fallot (ToF), but have required non-routine, tagged cardiovascular magnetic resonance (CMR) techniques. We assessed biventricular myocardial function using CMR cine-based feature tracking (FT) and compared it to speckle tracking echocardiography (STE) and to simple endocardial border delineation (EBD). In addition, the relation between parameters of myocardial deformation and clinical parameters was assessed. METHODS: Overall, 28 consecutive adult patients with repaired ToF (age 40.4 ± 13.3 years) underwent standard steady-state-free precession sequence CMR, echocardiography, and cardiopulmonary exercise testing. In addition, 25 healthy subjects served as controls. Myocardial deformation was assessed by CMR based FT (TomTec Diogenes software), CMR based EBD (using custom written software) and STE (TomTec Cardiac Performance Analysis software). RESULTS: Feature tracking was feasible in all subjects. A close agreement was found between measures of global left (LV) and right ventricular (RV) global strain. Interobserver agreement for FT and STE was similar for longitudinal LV global strain, but FT showed better inter-observer reproducibility than STE for circumferential or radial LV and longitudinal RV global strain. Reproducibility of regional strain on FT was, however, poor. The relative systolic length change of the endocardial border measured by EBD yielded similar results to FT global strain. Clinically, biventricular longitudinal strain on FT was reduced compared to controls (P < 0.0001) and was related to the number of previous cardiac operations. In addition, FT derived RV strain was related to exercise capacity and VE/VCO(2)-slope. CONCLUSIONS: Although neither the inter-study reproducibility nor accuracy of FT software were investigated, and its inter-observer reproducibility for regional strain calculation was poor, its calculations of global systolic strain showed similar or better inter-oberver reproducibility than those by STE, and could be applied across RV image regions inaccessible to echo. ‘Global strain’ calculated by EBD gave similar results to FT. Measurements made using FT related to exercise tolerance in ToF patients suggesting that the approach could have clinical relevance and deserves further study

Quantification of biventricular myocardial function using cardiac magnetic resonance feature tracking, endocardial border delineation and echocardiographic speckle tracking in patients with repaired tetralogy of fallot and healthy controls

Background: Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function in patients with tetralogy of Fallot (ToF), but have required non-routine, tagged cardiovascular magnetic resonance (CMR) techniques. We assessed biventricular myocardial function using CMR cine-based feature racking (FT) and compared it to speckle tracking echocardiography (STE) and to simple endocardial border delineation (EBD). In addition, the relation between parameters of myocardial deformation and clinical parameters was assessed. Methods: Overall, 28 consecutive adult patients with repaired ToF (age 40.4 ± 13.3 years) underwent standard steadystate- free precession sequence CMR, echocardiography, and cardiopulmonary exercise testing. In addition, 25 healthy subjects served as controls. Myocardial deformation was assessed by CMR based FT (TomTec Diogenes software), CMR based EBD (using custom written software) and STE (TomTec Cardiac Performance Analysis software). Results: Feature tracking was feasible in all subjects. A close agreement was found between measures of global left (LV) and right ventricular (RV) global strain. Interobserver agreement for FT and STE was similar for longitudinal LV global strain, but FT showed better inter-observer reproducibility than STE for circumferential or radial LV and longitudinal RV global strain. Reproducibility of regional strain on FT was, however, poor. The relative systolic length change of the endocardial border measured by EBD yielded similar results to FT global strain. Clinically, biventricular longitudinal strain on FT was reduced compared to controls (P<0.0001) and was related to the number of previous cardiac operations. In addition, FT derived RV strain was related to exercise capacity and VE/VCO2-slope. Conclusions: Although neither the inter-study reproducibility nor accuracy of FT software were investigated, and its interobserver reproducibility for regional strain calculation was poor, its calculations of global systolic strain showed similar or better inter-oberver reproducibility than those by STE, and could be applied across RV image regions inaccessible to echo. ‘Global strain’ calculated by EBD gave similar results to FT. Measurements made using FT related to exercise tolerance in ToF patients suggesting that the approach could have clinical relevance and deserves further study

Biventricular myocardial strain analysis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) using cardiovascular magnetic resonance feature tracking

BACKGROUND: Fibrofatty degeneration of myocardium in ARVC is associated with wall motion abnormalities. The aim of this study was to examine whether Cardiovascular Magnetic Resonance (CMR) based strain analysis using feature tracking (FT) can serve as a quantifiable measure to confirm global and regional ventricular dysfunction in ARVC patients and support the early detection of ARVC. METHODS: We enrolled 20 patients with ARVC, 30 with borderline ARVC and 22 subjects with a positive family history but no clinical signs of a manifest ARVC. 10 healthy volunteers (HV) served as controls. 15 ARVC patients received genotyping for Plakophilin-2 mutation (PKP-2), of which 7 were found to be positive. Cine MR datasets of all subjects were assessed for myocardial strain using FT (TomTec Diogenes Software). Global strain and strain rate in radial, circumferential and longitudinal mode were assessed for the right and left ventricle. In addition strain analysis at a segmental level was performed for the right ventricular free wall. RESULTS: RV global longitudinal strain rates in ARVC (−0.68 ± 0.36 sec(−1)) and borderline ARVC (−0.85 ± 0.36 sec(−1)) were significantly reduced in comparison with HV (−1.38 ± 0.52 sec(−1), p ≤ 0.05). Furthermore, in ARVC patients RV global circumferential strain and strain rates at the basal level were significantly reduced compared with HV (strain: −5.1 ± 2.7 vs. -9.2 ± 3.6%; strain rate: −0.31 ± 0.13 sec(−1) vs. -0.61 ± 0.21 sec(−1)). Even for patients with ARVC or borderline ARVC and normal RV ejection fraction (n=30) global longitudinal strain rate proved to be significantly reduced compared with HV (−0.9 ± 0.3 vs. -1.4 ± 0.5 sec(−1); p < 0.005). In ARVC patients with PKP-2 mutation there was a clear trend towards a more pronounced impairment in RV global longitudinal strain rate. On ROC analysis RV global longitudinal strain rate and circumferential strain rate at the basal level proved to be the best discriminators between ARVC patients and HV (AUC: 0.9 and 0.92, respectively). CONCLUSION: CMR based strain analysis using FT is an objective and useful measure for quantification of wall motion abnormalities in ARVC. It allows differentiation between manifest or borderline ARVC and HV, even if ejection fraction is still normal

Mobility in a Globalised World

The term mobility has different meanings in the following academic disciplines. In economics, mobility is the ability of an individual or a group to improve their economic status in relation to income and wealth within their lifetime or between generations. In information systems and computer science, mobility is used for the concept of mobile computing, in which a computer is transported by a person during normal use. Logistics creates, by the design of logistics networks, the infrastructure for the mobility of people and goods. Electric mobility is one of today’s solutions from engineering perspective to reduce the need of energy resources and environmental impact. Moreover, for urban planning, mobility is the crunch question about how to optimize the different needs for mobility and how to link different transportation systems. The conference “Mobility in a Globalised World” took place in Iserlohn, Germany, on September 14th – 15th, 2011. The aim of this conference was to provide an interdisciplinary forum for the exchange of ideas among practitioners, researchers, and government officials regarding the different modes of mobility in a globalised world, focusing on both domestic and international issues. The proceedings at hand document the results of the presentations and ensuing discussions at the conference

Nowa metoda pomiaru odkształcenia mięśnia sercowego na podstawie techniki śledzenia cech obrazów ruchomych CMR. Porównanie z echokardiograficzną metodą śledzenia markerów akustycznych u zdrowych ochotników i u chorych z przerostem lewej komory

Background: Left ventricular longitudinal strain (LV-LS) and strain rate (SR) are sensitive markers of early systolic dysfunction.Aim: To evaluate the feasibility of a novel, cardiac magnetic resonance (CMR) based method known as feature tracking (FT) for the assessment of strain and SR, and to compare the CMR based results to those obtained on standard transthoracic echocardiography (TTE) in healthy volunteers and in patients with left ventricular hypertrophy cardiomyopathy (HCM).Methods: Overall, 20 healthy volunteers (ten male, mean age 24 ± 3 years) and 20 consecutive patients with HCM (12 male, mean age 47 ± 19 years) were included. Longitudinal and circumferential strain and SR of the left ventricle were measured on CMR at 1.5 Tesla and TTE and interobserver variability was assessed.Results: FT measurements were feasible in all subjects. A good agreement between global LV-LS measured on CMR (controls: 20.8 ± 3.0; HCM: 17.6 ± 3.8) and TTE (controls: 19.4 ± 2.1; HCM: 16.6 ± 2.9) was found, while the agreement was worse for circumferential strain and all SR measurements. For the left and right ventricles, interobserver reproducibility was higher for strain measurements compared to SR. Coefficients of variation were lowest for LV-LS (13.2%) by CMR.Conclusions: FT analysis is a novel CMR based method for the analysis of myocardial strain and SR that is simple and correlates well with the echocardiographic measurements. Since CMR is unaffected by inadequate acoustic windows, FT may represent an attractive alternative to echocardiography in assessing the increasingly important parameters of myocardial deformation.Wstęp: Odkształcenie podłużne lewej komory (LV-LS) i prędkość odkształcenia (SR) są czułymi wskaźnikami wczesnej dysfunkcji skurczowej.Cel: Celem niniejszej pracy były: ocena nowej metody pomiaru odkształcenia mięśnia sercowego na podstawie techniki śledzenia cech (FT, feature tracking) obrazów ruchomych rezonansu magnetycznego serca (CMR) oraz porównanie wyników uzyskanych w CMR do rezultatów standardowej przezklatkowej echokardiografii (TTE) przeprowadzonej u zdrowych ochotników i u chorych z kardiomiopatią przerostową (HCM).Metody: Do badania włączono 20 zdrowych ochotników (10 mężczyzn, średnia wieku 24 ± 3 lata) i 20 kolejnych pacjentów z HCM (12 mężczyzn, średnia wieku 47 ± 19 lat). Odkształcenie podłużne i okrężne oraz SR lewej komory zmierzono w CMR przy natężeniu pola magnetycznego 1,5 tesli. Oceniono również TTE i zmienność zależną od obserwatora.Wyniki: Pomiar FT był możliwy u wszystkich badanych. Stwierdzono dużą zgodność między całkowitym LV-LS mierzonym przy użyciu CMR (grupa kontrolna: 20,8 ± 3,0; HCM: 17,6 ± 3,8) i za pomocą TTE (grupa kontrolna: 19,4 ± 2,1; HCM:16,6 ± 2,9), natomiast pomiary odkształcenia okrężnego i wszystkie pomiary SR charakteryzowały się mniejszą zgodnością. Powtarzalność wyników dotyczących lewej i prawej komory uzyskiwanych przez różnych obserwatorów była większa w przypadku pomiarów odkształceń w porównaniu z SR. Najniższe współczynniki zmienności stwierdzono w przypadku pomiarów LV-LS (13,2%) metodą CMR.Wnioski: Analiza FT, będącego nową metodą oceny odkształceń mięśnia sercowego oraz SR opartą na badaniu CMR, jest prosta i dobrze koreluje z pomiarami echokardiograficznymi. Ze względu na to, że na CMR nie ma wpływu niewłaściwe okno akustyczne, FT może być atrakcyjną alternatywą dla badania echokardiograficznego w ocenie bardzo ważnych parametrów deformacji miokardium

Past and current cause-specific mortality in Eisenmenger syndrome

Aims Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015. Methods and results This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 +/- 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P <0.001). Conclusion The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly neede

Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome:A Multicenter Study

Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients. In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters. We studied 1098 patients (median age, 34.4 years; range, 16.1-84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4-5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24-1.59; P <0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02-2.39; P=0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43-0.65; P <0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32-0.88; P=0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59-3.66; P <0.001) remained significant predictors of death. There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this populatio