Discrimination between FRET and non-FRET quenching in a photochromic CdSe quantum dot/dithienylethene dye system

A photochromic Förster resonance energy transfer (FRET) system was employed to disentangle the fluorescence quenching mechanisms in quantum dot/photochromic dye hybrids. In the off-state of the dye the main quenching mechanism is FRET whereas the moderate quenching in the on-state is due to non-FRET pathways opened up upon assembly

Bodenzustand nach Erstellung einer Photovoltaik-Freiflächenanlage in Südniedersachsen

Vorgestellt werden die Ergebnisse einer Untersuchung nach Errichtung einer Photovoltaik-Freiflächenanlage (PVF) auf einer 20 ha großen, vormaligen Ackerfläche in Südniedersachsen. Nach Abschluss der Bauarbeiten (2010) wurden 4 Bodenprofile aufgenommen und eine Reihe von bodenphysikalischen Labor- und Feldmethoden angewandt, u.a. zur Ermittlung der Bodenverdichtung. Im Ergebnis lassen sich die Veränderungen des Bodenzustands unterteilen in baubedingte und betriebsbedingte Störungen und Schädigungen. Baubedingte Folgen sind Flächenversiegelung, stellenweise extrem starke Bodenverdichtungen sowie stark veränderter Profilaufbau infolge Nivellierung der Fläche (teils über 40 cm abgeschoben). Als Anlage- bzw. betriebsbedingte Veränderungen ist insbesondere die Teilversiegelung der Fläche durch die Bedeckung mit den Modulen zu nennen. Folgen sind kleinräumig stark variierende Bodenfeuchte- und Infiltrationsverhältnisse sowie dauerhafte Beschattung / Austrocknung der überdeckten Bereiche. Als Schlussfolgerung bleibt festzuhalten, dass der Einsatz einer Bodenkundlichen Baubegleitung geholfen hätte, präventive Maßnahmen zu ergreifen und damit eine Schadensminderung hauptsächlich bei den baubedingten Bodenschadverdichtungen, damit die Errichtung einer Anlage zur umweltfreundlichen Energiegewinnung auch in einer umweltschonenden Bauweise erfolgt wäre

Direct intramyocardial plasmid vascular endothelial growth factor-A165gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: The Euroinject One trial

ObjectivesIn the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A165) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.BackgroundEvidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.MethodsEighty “no-option” patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A165(n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on 99mTc sestamibi/tetrofosmin single-photon emission computed tomography.ResultsNo differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 ± 3% and 44 ± 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A165-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.ConclusionsThe VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: a meta-analysis

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy

Quantitative aortography for assessment of aortic regurgitation in the era of percutaneous aortic valve replacement

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries

Paravalvular Aortic Regurgitation Severity Assessed by Quantitative Aortography: ACURATE neo2 versus ACURATE neo Transcatheter Aortic Valve Implantation

The new-generation ACURATE neo2 system was commercially released in September 2020. In this study, we sought to compare the aortic regurgitation (AR) severity of the ACURATE neo2 versus the ACURATE neo transcatheter heart valve, using quantitative videodensitometric angiography (qAR). This is a retrospective, Corelab analysis of final post-transcatheter aortic valve implantation (TAVI) aortograms of patients treated with the ACURATE neo2 and ACURATE neo systems. The ACURATE neo2 cohort comprised consecutive patients treated between September 2020 and January 2021 at two centers. The ACURATE neo cohort included consecutive patients treated before September 2020. Our primary objective was to compare AR severity on qAR following TAVI with ACURATE neo2 and ACURATE neo. Out of 401 aortograms, 228 (56.9%) were analyzable, with 120 in the ACURATE neo2 cohort, and 108 in the ACURATE neo cohort. The mean AR fraction was 4.4 ± 4.8% in the neo2 cohort, and 9.9 ± 8.2% in the neo cohort (p < 0.001). Furthermore, moderate or severe AR (qAR > 17%) was detected in 2 aortograms (1.7%) in the neo2 cohort and 15 aortograms (13.9%) in the neo cohort (p < 0.001). Quantitative aortography shows a lower rate of moderate or severe paravalvular AR in what is the first European experience of the new-generation, self-expanding ACURATE neo2 when compared to the first-generation ACURATE neo. Moreover, aortographic data need to be correlated and compared to Core Laboratory-adjudicated 30-day echocardiographic data

Myocardial gene therapy and gene expression in angina pectoris

Background Angiogenesis does not fully counteract myocardial ischemia in stable angina pectoris. Refractory angina pectoris, with remaining symptoms despite medication and no possibility for bypass surgery or angioplasty, is rather common. Angiogenic gene therapy is a novel treatment strategy for these patients. Methods and results In study I, six patients with refractory angina received intramyocardial injections of 0.25-1 mg plasmid encoding Vascular Endothelial Growth Factor (phVEGF-A165) via thoracotomy. The peak systolic velocity improved in all six patients but perioperative myocardial infarction occurred in two patients. Study II was a double-blind randomised controlled trial of the same plasmid or placebo plasmid (0.5 mg), delivered via a percutaneous catheter system in 80 patients with refractory angina. Reversible perfusion defects and wall motion improved in the phVEGF-A165-treated area compared to placebo. Nitroglycerin use tended to decrease with active treatment while symptom class and exercise capacity showed no effect beyond placebo. Five catheter-related adverse events occurred but no adverse effects were related to the plasmid. In study III, the prognosis of refractory angina was assessed in all 225 patients screened for study II. The mortality was 10.6% at three years. The baseline screening angiogram found revascularisation options in 10% of patients, although previous examinations had ruled out such possibilities. After twelve months, 36% of the trial patients had improved by at least two symptom classes and 37% had increased their exercise time by at least 60 seconds, with no difference between placebo and active groups. In study IV-V, the gene expression pattern in a reversibly ischemic myocardial area was compared to a normal area in eight patients with stable angina pectoris. Real-time polymerase chain reaction showed increased expression of ANP and BNP but not of VEGF and VEGF receptor 1 and 2 in reversibly ischemic myocardium. In microarray measurements, 15 additional known angiogenesis stimulators lacked differential expression. Instead, we found increased expression of several other genes with potential angiogenic, angiogenesis inhibiting, anti-apoptotic and muscle-related function but with yet unknown role in the myocardium. Conclusions Intramyocardial phVEGF-A165 is safe and increases myocardial perfusion in patients with stable angina pectoris. The effect on symptoms should be tested in a larger trial. Patients with refractory angina pectoris have a rather low mortality and symptomatic improvement is common. Overexpressing VEGF (or other angiogenic factors) seems a rational strategy, as most angiogenesis stimulators not are overexpressed in ischemic myocardium in stable angina. The ischemia-related overexpression of ANP, BNP and other genes with a probable anti-angiogenic function might be a limiting factor in angiogenesis

Beteiligung von Kindern und Jugendlichen in Niedersachsen

In der von der niedersächsischen Kinder- und Jugendkommission beauftragten Sekundäranalyse bestehender Datenquellen über die Beteiligung von Kindern und Jugendlichen in Niedersachsen wurde auf der Grundlage eines systematischen Review der surveybasierten Kinder- und Jugendforschung danach gefragt, wie sich Kinder und Jugendliche in Niedersachsen beteiligen bzw. beteiligt werden. Als Hintergrundfolie der Recherche wurde das Drei-P-Modell der Kinderrechtskonvention der Vereinten Nationen angesetzt. Die Sekundäranalyse macht deutlich, dass entsprechend nutzbare Daten für Niedersachsen nur in begrenztem Umfang vorliegen sowie insgesamt momentan keine systematische, indikatorengestützte und flächendeckende Beobachtung der Beteiligung junger Menschen in Niedersachsen (und darüber hinaus in Deutschland) stattfindet. Ergänzend zeigt die Publikation anhand einer Literaturreview und einer Befragung der Mitglieder der Kinder- und Jugendkommission auf, welche Beteiligungsmöglichkeiten und -projekte bereits vorhanden sind und wo Bedarfe gesehen werden, um das Recht auf Beteiligung von Kindern und Jugendlichen in Niedersachsen flächendeckend umzusetzen