A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim-and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH 2 ), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH 2 . We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments.-Babino, D., Perkins, B. D., Kindermann, A., Oberhauser, V., von Lintig, J. The role of 11-cisretinyl esters in vertebrate cone vision. FASEB J. 29, 216-226 (2015). www.fasebj.org
The HiGHmed consortium aims to create a shared information governance framework to integrate clinical routine data. One challenge is the replacement of unstructured reporting (e.g. doctoral letters) with structured reporting in clinical routine. The Heidelberg cardiology department evaluates dynamic PDF forms for structured data reporting of heart failure (HF) patients. In this use case, we aim to identify potential caveats or shortcomings in data processing at an early stage. We employed data mining strategies to detect patterns related to incomplete or false data, which we found to be present among all data types. We then discuss the characteristics of the baseline patient cohort in Heidelberg to find out about specific peculiarities and potential biases, which may be site-specific. Briefly, our patient population is predominantly male (67%), NYHA I & II are the most common severity classes, NYHA IV is missing entirely. Most patients have a dilated cardiomyopathy (DCM) or coronary heart disease (CHD) diagnosed as their cause of HF. Finally, we also analyzed how comorbidities and risk factors relate to specific disease entities of heart failure patients. Family anamnesis was more frequent among cardiomyopathy patients than among CHD patients, who show a more dominating presence of dyslipidemia instead. Generally, the most dominant risk factor was arterial hypertension, while at the other end of the scale alcoholism appears to be underreported.
Introduction Cardiomyopathies (CMPs) are leading causes of heart failure (HF) and sudden cardiac death (SCD). Comparative data of the multiple cardiomyopathy forms are largely missing. The TranslatiOnal Registry for CardiomyopatHies (TORCH) is the largest prospective multicentre CMP registry world-wide. Enrolled patients are comprehensively phenotyped by clinical examinations, state-of-the-art imaging, and molecular investigations. In this study, we present the baseline and 1-year follow-up data. Methods TORCH is a national, prospective, multicentre registry within the German Centre for Cardiovascular Research (DZHK) and includes 2300 patients with non-ischemic (primary and secondary) CMP from 20 centres. The minimum follow up was one year. The DZHK-wide harmonization of datasets and SOPs ensure a high level of data quality and comparability across different CMP forms. Results Dilated cardiomyopathy (DCM) has the highest prevalence with 64% of all enrolled patients, followed by hypertrophic cardiomyopathy (HCM) with 16%. At baseline, patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) were treated more often with ICD implantation and showed high rates of adequate ICD therapies (65.8%, p<0.05 and 47.8%, p<0.05, respectively). The prevalence of stroke or transient ischemic attack (TIA) was in multivariate analysis significantly higher (p<0.05) in left ventricular non-compaction cardiomyopathy (LVNC, 14.9%), while atrial fibrillation was lower than in other cardiomyopathy forms. Patients with amyloidosis had the worst outcome (HR: 6; 95% CI: 2.5–14.5, P<0.05) with annual mortality of >15% and 12% receiving heart transplantation. In DCM, reverse remodelling with improvement of functional parameters and biomarkers was more often observed in idiopathic and inflammatory cases compared to familial ones. HCM patients had the most favourable outcome. Conclusion and outlook TORCH is the largest prospective study focusing on CMPs. We provided for the first time prospectively the clinical data of patients with diverse cardiomyopathies with outcome. Furthermore, comparing the different CMP forms on the clinical and molecular level will be an important step to enable translational research projects. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research (DZHK)
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