Experimental in vivo fenestration of guinea pig cochlea using 2.79 Μm laser radiation

Erbium-YSGG laser systems are promising tools in ear, nose and throat (ENT) surgery. The high absorption in biological tissues, resulting in precise tissue ablation with minimal thermal tissue damage, and the possibility to guide the radiation through optical fibres make the 2.79 Μm wavelength a favourite for microsurgery. In order to simulate the fenestration of the human stapes foot plate required for prosthesis implantation when treating otosclerosis, five guinea pig cochleae were irradiated in vivo until perforation was achieved. The laser-induced temperature rise and pressure transients evoke activity in the inner hair cells that was investigated by micro-iontophoresis. Perforation of the cochlea bone (hole diameter of 350 Μm) can be performed with a few laser pulses and high precision with a thermal damage zone of<100 Μm. The bone ablation rate is 10 ± 2 Μm pulse-1 at a radiant exposure of 12 J cm-2. The functionality of the afferent inner hair cells in the guinea pig cochlea was verified before and after laser treatment using glutamate receptor agonists AMPA and NMDA. For the above selected laser parameters, the induced 15-min enhanced activity was blockable with the specific reversible AMPA and NMDA antagonists CNQX and AP-7. Micro-iontophoresis confirms the reversibility of cochlea functionality after its perforation with Er-YSGG laser pulses. A limit of radiant exposure around 12 J cm-2 is found for safe fenestration. It is demonstrated that the Er-YSGG laser is a precise and safe instrument whilst still using adequate laser parameters. On the other hand, this study demonstrates the potential of uncontrollable and unintended induced damage, resulting from vapour channel formation in the perilymph, if a high laser radiant exposure is applie

Subdermal solar energy harvesting – A new way to power autonomous electric implants

Subdermal solar harvesting has the potential to obviate the need for the periodic battery replacements as required in patients with cardiac pacemakers. The achievable power output of the subdermal solar module depends on implantation depth, optical skin properties and to an important part on solar cell characteristics. Monte Carlo simulations of light distribution in human skin were used to estimate the power output of subdermal solar cells under midday sunlight exposure in geographical mid-latitudes as a function of implantation depth and solar panel size. For the darkest skin type, the daily energy demand of a modern cardiac pacemaker (0.864 J at a power demand of 10 uW) can be provided by a 2 cm2 solar cell implanted subdermally at a depth of 3 mm when exposed to just 11 min of midday, clear sky irradiance. Our study reveals that solar harvesting with relatively small solar cells if optimized for the spectral subdermal fluence has the potential to power cardiac pacemakers in all skin types within reasonable irradiation exposure times. Solar energy harvesting is very promising to power electronic implants

Characterization of optical properties of ZnO nanoparticles for quantitative imaging of transdermal transport

Widespread applications of ZnO nanoparticles (NP) in sun-blocking cosmetic products have raised safety concerns related to their potential transdermal penetration and resultant cytotoxicity. Nonlinear optical microscopy provides means for high-contrast imaging of ZnO NPs lending in vitro and in vivo assessment of the nanoparticle uptake in skin, provided their nonlinear optical properties are characterized. We report on this characterization using ZnO NP commercial product, Zinclear, mean-sized 21 nm. Two-photon action cross-section of this bandgap material (Ebg = 3.37 eV, λbg = 370 nm) measured by two techniques yielded consistent results of ηZnOσZnO(2ph) = 6.2 ± 0.8 μGM at 795 nm, and 32 ± 6 μGM at 770 nm per unit ZnO crystal cell, with the quantum efficiency of ηZnO = (0.9 ± 0.2) %. In order to demonstrate the quantitative imaging, nonlinear optical microscopy images of the excised human skin topically treated with Zinclear were acquired and processed using σZnO(2ph) and ηZnOvalues yielding nanoparticle concentration map in skin. Accumulations of Zinclear ZnO nanoparticles were detected only on the skin surface and in skin folds reaching concentrations of 800 NPs per μm3

Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox

Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination

Deafness mutation mining using regular expression based pattern matching

<p>Abstract</p> <p>Background</p> <p>While keyword based queries of databases such as Pubmed are frequently of great utility, the ability to use regular expressions in place of a keyword can often improve the results output by such databases. Regular expressions can allow for the identification of element types that cannot be readily specified by a single keyword and can allow for different words with similar character sequences to be distinguished.</p> <p>Results</p> <p>A Perl based utility was developed to allow the use of regular expressions in Pubmed searches, thereby improving the accuracy of the searches.</p> <p>Conclusion</p> <p>This utility was then utilized to create a comprehensive listing of all DFN deafness mutations discussed in Pubmed records containing the keywords "human ear".</p

Structure of a Chaperone-Usher Pilus reveals the molecular basis of rod uncoiling

Types 1 and P pili are prototypical bacterial cell-surface appendages playing essential roles in mediating adhesion of bacteria to the urinary tract. These pili, assembled by the chaperone-usher pathway, are polymers of pilus subunits assembling into two parts: a thin, short tip fibrillum at the top, mounted on a long pilus rod. The rod adopts a helical quaternary structure and is thought to play essential roles: its formation may drive pilus extrusion by preventing backsliding of the nascent growing pilus within the secretion pore; the rod also has striking spring-like properties, being able to uncoil and recoil depending on the intensity of shear forces generated by urine flow. Here, we present an atomic model of the P pilus generated from a 3.8 Å resolution cryo-electron microscopy reconstruction. This structure provides the molecular basis for the rod’s remarkable mechanical properties and illuminates its role in pilus secretion