Surgical planning tool for robotically assisted hearing aid implantation

PURPOSE : For the facilitation of minimally invasive robotically performed direct cochlea access (DCA) procedure, a surgical planning tool which enables the surgeon to define landmarks for patient-to-image registration, identify the necessary anatomical structures and define a safe DCA trajectory using patient image data (typically computed tomography (CT) or cone beam CT) is required. To this end, a dedicated end-to-end software planning system for the planning of DCA procedures that addresses current deficiencies has been developed. METHODS :    Efficient and robust anatomical segmentation is achieved through the implementation of semiautomatic algorithms; high-accuracy patient-to-image registration is achieved via an automated model-based fiducial detection algorithm and functionality for the interactive definition of a safe drilling trajectory based on case-specific drill positioning uncertainty calculations was developed. RESULTS :    The accuracy and safety of the presented software tool were validated during the conduction of eight DCA procedures performed on cadaver heads. The plan for each ear was completed in less than 20 min, and no damage to vital structures occurred during the procedures. The integrated fiducial detection functionality enabled final positioning accuracies of [Formula: see text] mm. CONCLUSIONS :    Results of this study demonstrated that the proposed software system could aid in the safe planning of a DCA tunnel within an acceptable time.

3CAPS – a structural AP-site analogue as a tool to investigate DNA base excision repair

Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP-sites. With its 3′-phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase β but repaired only by strand displacement as the 5′-deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases.