Spitz melanocytic tumours – a review

Spitz tumours comprise a spectrum of melanocytic proliferations that share a set of distinct cytological features and molecular pathways. They include benign naevi, intermediate or indeterminate tumours and rare melanomas. Spitz tumours are notorious for the difficulty of distinguishing benign neoplasms with atypical features from melanomas and the related diagnostic uncertainty. Advances in the knowledge of the molecular pathways and genomic aberrations associated with these neoplasms have permitted opportunities for a reduction in the number of uncertain diagnoses and a more objective distinction between Spitz tumours from Spitz-like neoplasms. The presence of a Spitz molecular pathway, such as Harvey rat sarcoma viral oncogene homologue (HRAS) aberrations or kinase fusions, distinguishes a bona fide Spitz neoplasm from Spitz-like naevi or melanomas with conventional driver mutations. Spitz neoplasms with benign histopathological features and, if such testing is performed, benign cytogenetic and molecular findings, are termed Spitz naevi. Spitz neoplasms with frankly malignant histopathological findings or ambiguous microscopic findings associated with genetic or genomic aberrations most in keeping with melanoma are designated as Spitz melanoma. Tumours with microscopic features and genetic/genomic aberrations in between naevi and melanomas are classified as Spitz melanocytoma.     

Cross‐sectional and longitudinal association of sports participation,media consumption and motor competence in youth

The beneficial associations of physical activity (PA) and sports with motor competence have been well documented. Similarly, high media time has been associated with poor motor competence. Limited information, however, is available on the combined effects of sport participation and media consumption on motor competence. The present study followed 213 Austrian middle‐school students (57% male; age at baseline: 10.4 ± 0.6 years) over a 4‐year period. Annual assessments included the German Motor Test 6‐18, along with self‐reported participation in club sports, time spent watching TV and using the computer. There were no interaction effects between sports participation and media time on motor competence. Club sports participation, however, was associated with higher motor competence, while there was an inverse association between media time and motor competence. Further, motor competence affected future participation in club sports while club sports had limited effects on subsequent motor development. High media time, on the other hand, impaired subsequent motor development, while effects of motor competence on media time were limited. Taken together, these results emphasize the importance of motor competence in the facilitation of sports participation during adolescence. Accordingly, a wide variety of movement experiences should be provided at young ages to promote motor development. In addition, the detrimental effects of media time on motor competence warrant that sedentary behaviors are targeted separately, particularly in youth not participating in sports.     

Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT₁ and MT₂, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT₁ and MT₂. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT₁ and MT₂ by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT₁ or MT₂. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT₂ expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.     

Antiarrhythmika im Notfall

Notfall + Rettungsmedizin -     

Primary HIV infection presenting with Kaposi sarcoma and limbic encephalitis

The development of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is often associated with neoplasia or infectious diseases as antibodies against neurons or synaptic proteins surface. A 30-year-old male patient was admitted to our department because of neurocognitive symptoms, particularly memory difficulties which had appeared a year prior and since then had been increasing. He had a medical history of smoking and hypertension. On examination, there were no focal neurological deficits. However, neuropsychological tests confirmed a lack of concentration and short-term memory impairment. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) remained unremarkable. Cerebrospinal fluid (CSF) analysis revealed a low lymphocytic pleocytosis without oligoclonal bands. Serum testing for human immunodeficiency virus (HIV) was positive with 420,000 HIV-1-RNA copies/ml. On a more detailed physical examination, a large number of purple patches were found on the entire body, which a biopsy confirmed to be Kaposi sarcoma (KS). A positive serum and CSF NMDA receptor antibody titer (serum 1:280; CSF 1:8) confirmed the diagnosis of an AIDS-associated anti-NMDA receptor encephalitis; therefore, we treated him with antiretroviral and immunosuppressive therapy. After 12 months, the KS lesions faded and the cognitive deficits improved slightly. Our case highlights that a detailed clinical examination and searching for neoplasia and/or an infection are helpful, though often neglected, tools for detecting an anti-NMDA receptor encephalitis.