Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether the single ventricular hearts of these species possess any equivalent of the specialized ventricular conduction system found in higher vertebrates. Isolated hearts of adult zebrafish ( Danio rerio) and African toads ( Xenopus laevis) were stained with voltage-sensitive dye and optically mapped in spontaneous and paced rhythms followed by histological examination focusing on myocardial continuity between the atrium and the ventricle. Spread of the excitation wave through the atria was uniform with average activation times of 20 ± 2 and 50 ± 2 ms for zebrafish and Xenopus toads, respectively. After a delay of 47 ± 8 and 414 ± 16 ms, the ventricle became activated first in the apical region. Ectopic ventricular activation was propagated significantly more slowly (total ventricular activation times: 24 ± 3 vs. 14 ± 2 ms in zebrafish and 74 ± 14 vs. 35 ± 9 ms in Xenopus). Although we did not observe any histologically defined tracts of specialized conduction cells within the ventricle, there were trabecular bands with prominent polysialic acid-neural cell adhesion molecule staining forming direct myocardial continuity between the atrioventricular canal and the apex of the ventricle; i.e., the site of the epicardial breakthrough. We thus conclude that these hearts are able to achieve the apex-to-base ventricular activation pattern observed in higher vertebrates in the apparent absence of differentiated conduction fascicles, suggesting that the ventricular trabeculae serve as a functional equivalent of the His-Purkinje system.

Over the last decade, the brain's default‐mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood‐oxygen level‐dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2‐deoxy‐2‐[¹⁸F]fluoroglucose positron emission tomography (FDG‐PET), proton magnetic resonance spectroscopy (¹H‐MRS), and resting‐state functional magnetic resonance imaging (rs‐fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG‐uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal. Hum Brain Mapp 36:2027–2038, 2015. © 2015 Wiley Periodicals, Inc.

The procedure guideline for radioiodine (¹³¹I) therapy and ¹³¹I whole-body scintigraphy of differentiated thyroid cancer in paediatric patients is the counterpart to the procedure guidelines (version 3) for adult patients and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Characteristics of thyroid cancer in children are the higher aggressiveness of papillary thyroid cancer, the higher frequency of extrathyroidal extension and of disseminated pulmonary metastases as well as the high risk of local recurrences. Radioiodine therapy is generally recommended in children, the ¹³¹I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer (≤1 cm) should be considered. TSH stimulation is reached two weeks (children) or three weeks (adolescents) after withdrawal of thyroid hormones. Anti-emetic drugs are highly recommended. CT of the chest and examination of pulmonary function are clearly indicated if there is any suspicion on metastases. 3–6 months after ¹³¹I ablation, the ¹³¹I whole-body scintigraphy is highly recommended as lymph node metastases are frequently detected in paediatric patients. Follow-up care should be arranged in shorter intervals than in adults to test the compliance and to adapt dosage of thyroid hormones to the children's body weight. Reference values of fT3 are higher in children than in adults. Evidence is insufficient to describe in which constellation the TSH may be kept within the low normal level. Therefore, TSH suppression is generally recommended. Die Verfahrensanweisung zur Radioiodtherapie (RIT) und zur ¹³¹I-Ganzkörperszintigraphie beim differenzierten Schilddrüsenkarzinom im Kindes- und Jugendalter reiht sich thematisch neben die entsprechenden Verfahrensanweisungen (Version 3), die für erwachsene Patienten verfasst sind, und konkretisiert die interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft um die nuklearmedizinischen Aspekte. Besonderheiten im Kindes- und Jugendalter sind die höhere Aggressivität des papillären Schilddrüsenkarzinoms, die Häufigkeit eines organüberschreitenden Tumorwachstums und einer disseminierten pulmonalen Metastasierung sowie die hohe lokale Rezidivrate. Die TNM-Klassifikation wird aufgrund der geringen Ausdehnung der normalen kindlichen Schilddrüse der Risikostratifikation nicht gerecht. Grundsätzlich besteht auch bei Kindern die Empfehlung zur Radioiodtherapie, wobei die ¹³¹I-Aktivität gewichtsabhängig appliziert wird. Bei kleinen papillären Schilddrüsenkarzinomen (≤1 cm) ist die Indikation zu einer ablativen Radioiodtherapie eher großzügig zu stellen. Nach Hormonentzug wird die TSH-Stimulation bereits nach zwei Wochen (Kinder) bzw. drei Wochen (Jugendliche) erreicht. Antiemetika werden großzügig verordnet. Die Indikation zur CT des Thorax und zur Lungenfunktionsuntersuchung ist bei Metastasenverdacht großzügig zu stellen. Auf die diagnostische ¹³¹I-Ganzkörperszintigraphie drei bis sechs Monate nach ablativer Radioiodtherapie sollte wegen der Häufigkeit einer lymphogenen Metastasierung nicht verzichtet werden. Nachsorgeintervalle sind eher kürzer zu wählen, um eine unzureichende Compliance bei Kindern frühzeitig zu erfassen und um die Hormondosis gewichtsbezogen anzupassen. Der höhere Normbereich von fT3 für Kinder ist zu beachten. Es liegt keine ausreichende Evidenz vor, ob und wann eine nicht-suppressive Einstellung der Schilddrüsenfunktion sinnvoll ist. Daher ist die TSHSuppression grundsätzlich anzustreben.

The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It is known that defects in proteins involved in mitochondrial quality control can cause Parkinson’s disease, and there is increasing evidence linking mitochondrial dysfunction, and particularly mitochondrial DNA abnormalities, to neuronal loss in the substantia nigra. Mutations in the catalytic subunit of polymerase gamma are among the most common causes of mitochondrial disease and owing to its role in mitochondrial DNA homeostasis, polymerase gamma defects are often considered a paradigm for mitochondrial diseases generally. Yet, despite this, parkinsonism is uncommon with polymerase gamma defects. In this study, we investigated structural and functional changes in the substantia nigra of 11 patients with polymerase gamma encephalopathy. We characterized the mitochondrial DNA abnormalities and examined the respiratory chain in neurons of the substantia nigra. We also investigated nigrostriatal integrity and function using a combination of post-mortem and in vivo functional studies with dopamine transporter imaging and positron emission tomography. At the cellular level, dopaminergic nigral neurons of patients with polymerase gamma encephalopathy contained a significantly lower copy number of mitochondrial DNA (depletion) and higher levels of deletions than normal control subjects. A selective and progressive complex I deficiency was seen and this was associated with a severe and progressive loss of the dopaminergic neurons of the pars compacta. Dopamine transporter imaging and positron emission tomography showed that the degree of nigral neuronal loss and nigrostriatal depletion were severe and appeared greater even than that seen in idiopathic Parkinson’s disease. Despite this, however, none of our patients showed any signs of parkinsonism. The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism.