Rapid progressive destruction of the cochleae in an infant due to pneumococcal meningitis.

The widespread adoption of pneumococcal conjugate vaccines has reduced the incidence of Streptococcus pneumoniae infections, but has also led to the emergence of infections due to non-vaccine serotypes. A 15-month-old girl was referred to our hospital with suspected meningitis. S. pneumoniae was isolated from her cerebrospinal fluid. She was initially treated with a combination of cefotaxime and vancomycin, followed by ampicillin and vancomycin. After 7 days, the patient's condition improved and she was transferred to the general ward; however, her mother noted signs of hearing difficulties. On the 16th day of admission, we performed an auditory brainstem response test, which suggested severe bilateral hearing impairment. This was confirmed using an auditory steady-state response test after consulting with otolaryngologists. Magnetic resonance imaging revealed fibrosis of both cochleae with labyrinthitis. The patient underwent emergency cochlear implantation at a different hospital. The S. pneumoniae isolate was later identified to be serotype 10A with a PBP2x mutation, which is not covered by the conjugate vaccine and has reduced cephalosporin susceptibility. This case was characterized by highly rapid cochlear destruction, and an earlier otolaryngologist consultation may have provided a more well-organized surgery plan. Pediatricians are urged to promptly consult with otolaryngologists for patients with similar indications.

Covalent attachment of functionalized cardiolipin on a biosensor gold surface allows repetitive measurements of anticardiolipin antibodies in serum.

Antiphospholipid antibodies (aPL) are a relevant serological indicator of antiphospholipid syndrome (APS). A solid-state surface with covalently bound ω-amine-functionalized cardiolipin was established and the binding of ß2-glycoprotein I (ß2-GPI) was investigated either by use of surface plasmon resonance (SPR) biosensor, by electrically switchable DNA interfaces (switchSENSE) and by scanning tunneling microscopy (STM). STM could clearly visualize the attachment of ß2-GPI to the cardiolipin surface. Using the switchSENSE sensor, ß2-GPI as specific ligand could be identified by increased hydrodynamic friction. The binding of anti-cardiolipin antibodies (aCL) was detected against the ω-amine-functionalized cardiolipin-modified SPR biosensor (aCL biosensor) using sera from healthy donors, APS patients and syphilis patients. Our results showed that the aCL biosensor is a much more sensitive diagnostic device for APS patients compared to previous methods. The specificity between ß2-GPI-dependent autoimmune- and ß2-GPI-independent infection-associated types of aPLs was also studied and they can be distinguished by the different binding kinetics and patterns.

Protein analysis by time-resolved measurements with an electro-switchable DNA chip.

Measurements in stationary or mobile phases are fundamental principles in protein analysis. Although the immobilization of molecules on solid supports allows for the parallel analysis of interactions, properties like size or shape are usually inferred from the molecular mobility under the influence of external forces. However, as these principles are mutually exclusive, a comprehensive characterization of proteins usually involves a multi-step workflow. Here we show how these measurement modalities can be reconciled by tethering proteins to a surface via dynamically actuated nanolevers. Short DNA strands, which are switched by alternating electric fields, are employed as capture probes to bind target proteins. By swaying the proteins over nanometre amplitudes and comparing their motional dynamics to a theoretical model, the protein diameter can be quantified with Angström accuracy. Alterations in the tertiary protein structure (folding) and conformational changes are readily detected, and even post-translational modifications are revealed by time-resolved molecular dynamics measurements.