Next-Generation Sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations.

Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of variant alterations, each with unique molecular profiles. The 37 identified variants were distributed over 22 cancer-related genes (23.4%). The number of mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM samples showed mutations in at least one DNA repair gene. Our NGS study of BM of ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53, ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on these findings, pharmacological PARP inhibition could be one potential targeted therapeutic for brain metastatic ovarian cancer patients.

Research efforts to control highly pathogenic arenaviruses: a summary of the progress and gaps.

Significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several West African countries (Lassa fever virus) and in some regions of South America (Argentine and Bolivian hemorrhagic fever viruses). While this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in the clinic to date. The recent Ebola outbreak in West Africa has demonstrated very clearly that there is an urgent need to develop the prophylactic and therapeutic armamentarium against viral hemorrhagic fever viruses as part of a global preparedness for future epidemics. As it pertains to this goal, the present article summarizes the current knowledge of highly pathogenic arenaviruses and identifies opportunities for translational research.

[Observations on epidural anesthesia in cats from the anatomical viewpoint]. / Bemerkungen zur Epiduralanästhesie bei der Katze aus anatomischer Sicht.

The topographic-anatomical situation of the conus medullaris and the cauda equina in cats is shown: in about two thirds of the cases the conus medullaris at least reaches the level of the first sacral vertebra. As far as the site of the epidural injection is concerned the sacrococcygeal space or the first intercoccygeal space are proposed in order to avoid damage to the spinal cord. When seeking the site of injection it is advantageous to orientate oneself by following the sacral processus spinosi in caudal direction beginning with the lumbosacral space. In case of adipose animals the first intercoccygeal space can be palpated by moving the tail up and down. Both sites are equivalent. The volume to be injected varies between 0.3 and 0.9 ml solution per cat depending on the needs.

Fine structural and immunocytochemical studies on the eyeless aesthetes of Leptochiton algesirensis, with comparison to Leptochiton cancellatus (Mollusca, Polyplacophora).

The aesthetes of Leptochiton algesirensis (Capellini, 1859) and Leptochiton cancellatus (Sowerby, 1840) consist of six to eight microaesthetes surrounding one macroaesthete. The monocellular microaesthetes include many microtubules, neurosecretory vesicles, and unperforated, subsidiary caps. Basally they are in contact with tiny nerve processes via probably electrical synapses. Each macroaesthete consists of a perforated apical cap and various cell types: flattened peripheral cells, various types of mucous cells, and three or four monociliary sensory cells. Although lacking photoreceptors, the aesthetes of Leptochiton algesirensis combine storage-secretory and sensory functions. The latter function is confirmed by positive immunoreactions against (neuro-)tubulin and synaptophysine. The high degree of structural and functional similarity between polyplacophoran aesthetes and the analogous caeca of brachiopods is demonstrated.