Combined effects of salicylic acid and furosemide and noise on hearing

<p>Abstract</p> <p>Background</p> <p>A major cause of the hearing loss following exposure to intense noise involves release of free radicals resulting from the elevated metabolism. The free radicals induce damage to several of the components of the cochlear amplifier including the outer hair cells and indirectly to the transduction currents. Salicylic acid induces a reversible hearing loss since it binds to the motor protein prestin in the outer hair cells, reducing electromotility. Furosemide also induces a reversible hearing loss since it reduces the endocochlear potential which is a major component of the cochlear transduction currents. On the other hand, each of these drugs also provides protection from a noise induced hearing loss if they are injected just before a noise exposure, probably as a result of the decreased metabolism induced in their presence, with release of lower levels of free radicals. In this study, both drugs were administered in order to assess whether their protective effects would be additive.</p> <p>Methods</p> <p>The study was conducted on normal hearing albino mice of the Sabra strain. They were injected with either salicylic acid alone (N = 11), or furosemide alone (N = 14), or both together (N = 14), or with saline control (N = 11) and exposed to broad band noise for 3.5 hours. An additional group of 9 mice was injected with both salicylic acid and furosemide, but not exposed to noise. The degree of the resulting hearing loss was assessed by recording thresholds of the auditory nerve brainstem evoked responses to broad band clicks before the injections and noise, and 7, 14 and 21 days after.</p> <p>Results</p> <p>The noise induced hearing loss in the mice injected with salicylic acid alone or furosemide alone was smaller than in those injected with saline, i.e. these drugs provided protection, as in previous studies in this laboratory. There was no threshold elevation after two weeks in the mice injected with both drugs without noise exposure, i.e. the effects of the two drugs given together was reversible. On the other hand, there was a significant hearing loss (i.e. threshold elevation) in the group which received both drugs and was also exposed to noise, with mean threshold elevations of 38.8 ± 19.0 dB and 28.3 ± 11.7 dB 7 days after noise exposure.</p> <p>Conclusions</p> <p>This result is very surprising, if not paradoxical. Drugs which provide protection from a noise induced hearing loss when administered alone, not only do not provide protection when given together, but also induce a greater hearing loss when accompanied by noise. This observation may be related to the finding that the depression of the endocochlear potential normally caused by furosemide is reduced in the presence of salicylic acid, so that the protection usually provided by furosemide is not present when it is administered together with salicylic acid. Thus it seems that each drug may interfere with the protective action of the other when coupled with noise.</p

PAMAM Dendrimer as Quantized Building Blocks for Biomedical Applications.

Heterogeneity, whether from polydispersity within the polymeric scaffold or due to a broad distribution of covalently conjugated products, is a remaining challenge in theranostics. Chapter 1 of this thesis presents the challenges conjugate heterogeneity introduces to synthesis, characterization, and application of multivalent conjugates. A brief review of recent literature approaches to address sample heterogeneity is also provided. Chapter 2 highlights the heterogeneity of the scaffold of interest, poly(amidoamine) dendrimer. It was found that the mass range of commercial polymer was ~1.4-115 kDa, and that skeletal defects in the dendrimer structure occur at a rate of 8-15%. Methods to isolate dendrimer monomers with decreased polydispersity are introduced. Chapter 3 of this thesis presents the first application of these monomers as soft superatoms for the assembly of new, precise nanostructures. New chromatography strategies to obtain ligand-dendrimer conjugates with precise ratios are introduced, and these conjugates are employed as building blocks for novel megamers. In Chapter 4, dendrimers with precise numbers of ring-strain promoted click ligands are clicked to folic acid-azide derivatives to synthesize dendrimer-folic acid conjugates with narrow ligand-to-dendrimer ratio distributions. These materials are evaluated for binding to a folate binding protein, and the results used to interpret the mechanism of increased binding of these conjugates compared to free folic acid. Mathematical models were developed to differentiate between three proposed mechanisms, and it was determined that the observed increase in avidity is due to nonspecific interactions between the polymer scaffold and protein, which are initiated by a specific interaction between folic acid and the protein. Chapter 5 examines the impact of scaffold size, ligand-to-scaffold linking systems, and conjugate valency on the activity of dendrimer-methotrexate conjugates. The larger mass and diameter of dimer impurities contributed significantly to observed activity of these and previous conjugates. The weaker methotrexate-folate binding protein interaction was not strong enough to key the nonspecific interactions until higher valencies in larger conjugates. The final chapter provides conclusions as to how this thesis impacts the current field of multivalent conjugates for targeted drug delivery, and gives some insight to where the field must continue to grow.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107121/1/mavd_1.pd

Results of the minimally invasive coronary artery bypass grafting angiographic patency study

ObjectiveMinimally invasive coronary artery bypass grafting is safe and widely applicable, and may be associated with fewer transfusions and infections, and better recovery than standard coronary artery bypass grafting. However, graft patency rates remain unknown. The Minimally Invasive Coronary Artery Bypass Grafting Patency Study prospectively evaluated angiographic graft patency 6 months after minimally invasive coronary artery bypass grafting.MethodsIn this dual-center study, 91 patients were prospectively enrolled to undergo minimally invasive coronary artery bypass grafting via a 4- to 7-cm left thoracotomy approach. The left internal thoracic artery, the ascending aorta for proximal anastomoses, and all coronary targets were directly accessed without endoscopic or robotic assistance. The study primary outcome was graft patency at 6 months, using 64-slice computed tomography angiography. Secondary outcomes included conversions to sternotomy and major adverse cardiovascular events (Clinical Trial Registration Unique identifier: NCT01334866).ResultsThe mean age of patients was 64 ± 8 years, the mean ejection fraction was 51% ± 11%, and there were 10 female patients (11%) in the study. Surgeries were performed entirely off-pump in 68 patients (76%). Complete revascularization was achieved in all patients, and the median number of grafts was 3. There was no perioperative mortality, no conversion to sternotomy, and 2 reopenings for bleeding. Transfusion occurred in 24 patients (26%). The median length of hospital stay was 4 days, and all patients were followed to 6 months, with no mortality or major adverse cardiovascular events. Six-month computed tomography angiographic graft patency was 92% for all grafts and 100% for left internal thoracic artery grafts.ConclusionsMinimally invasive coronary artery bypass grafting is safe, feasible, and associated with excellent outcomes and graft patency at 6 months post-surgery

Communications Biophysics

Contains reports on five research projects.National Institutes of Health (Grant 5 PO1 GM14940-03)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NGL 22-009-304

Automated Performance Assessment in Transoesophageal Echocardiography with Convolutional Neural Networks

Transoesophageal echocardiography (TEE) is a valuable diagnostic and monitoring imaging modality. Proper image acquisition is essential for diagnosis, yet current assessment techniques are solely based on manual expert review. This paper presents a supervised deep learning framework for automatically evaluating and grading the quality of TEE images. To obtain the necessary dataset, 38 participants of varied experience performed TEE exams with a high-fidelity virtual reality (VR) platform. Two Convolutional Neural Network (CNN) architectures, AlexNet and VGG, structured to perform regression, were finetuned and validated on manually graded images from three evaluators. Two different scoring strategies, a criteria-based percentage and an overall general impression, were used. The developed CNN models estimate the average score with a root mean square accuracy ranging between 84% − 93%, indicating the ability to replicate expert valuation. Proposed strategies for automated TEE assessment can have a significant impact on the training process of new TEE operators, providing direct feedback and facilitating the development of the necessary dexterous skills

Optical bench development for LISA

For observation of gravitational waves at frequencies between 30 μHz and 1 Hz, the LISA mission will be implemented in a triangular constellation of three identical spacecraft, which are mutually linked by laser interferometry in an active transponder scheme over a 5 million kilometer arm length. On the end point of each laser link, remote and local beam metrology with respect to inertial proof masses inside the spacecraft is realized by the LISA Optical Bench. It implements further- more various ancillary functions such as point-ahead correction, acquisition sensing, transmit beam conditioning, and laser redundancy switching. A comprehensive design of the Optical Bench has been developed, which includes all of the above mentioned functions and at the same time ensures manufacturability on the basis of hydroxide catalysis bonding, an ultrastable integration technology already perfected in the context of LISA's technology demonstrator mission LISA Pathfinder. Essential elements of this design have been validated by dedicated pre-investigations. These include the demonstration of polarizing heterodyne interferometry at the required Picometer and Nanoradian performance levels, the investigation of potential non-reciprocal noise sources in the so-called backlink fiber, as well as the development of a laser redundancy switch breadboard

Variability of black carbon mass concentrations, sub-micrometer particle number concentrations and size distributions: results of the German Ultrafine Aerosol Network ranging from city street to High Alpine locations

This work reports the first statistical analysis of multi-annual data on tropospheric aerosols from the German Ultrafine Aerosol Network (GUAN). Compared to other networks worldwide, GUAN with 17 measurement locations has the most sites equipped with particle number size distribution (PNSD) and equivalent black carbon (eBC) instruments and the most site categories in Germany ranging from city street/roadside to High Alpine. As we know, the variations of eBC and particle number concentration (PNC) are influenced by several factors such as source, transformation, transport and deposition. The dominant controlling factor for different pollutant parameters might be varied, leading to the different spatio-temporal variations among the measured parameters. Currently, a study of spatio-temporal variations of PNSD and eBC considering the influences of both site categories and spatial scale is still missing. Based on the multi-site dataset of GUAN, the goal of this study is to investigate how pollutant parameters may interfere with spatial characteristics and site categories

Fitting model of ABR age dependency in a clinical population of normal hearing children

The purpose of this study was to present a simple and powerful fitting model that describes age-dependent changes of auditory brainstem responses (ABR) in a clinical population of normal hearing children. A total of 175 children (younger than 200 weeks postconceptional age) were referred for audiologic assessment with normal ABR results. ABR parameters of normal hearing children between 2003 and 2008 were included. The results of the right ears recorded at 90 dB nHL were analyzed. A simple and accurate fitting model was formulated based on these data. A very similar age-dependent effect was found for peaks III and V, and I–III and I–V intervals; latencies decrease as postconceptional age increases. It shows that the total age-dependent effect will be completed after 1.5–2 years. The age-dependent effect can be modeled by a relatively simple and accurate exponential function. This fitting model can be easily implemented to analyze ABR results of infants in daily clinical practice. We speculate about the underlying physiological processes

Feel it in my bones: Composing multimodal experience through tissue conduction

We outline here the feasibility of coherently utilising tissue conduction for spatial audio and tactile input. Tissue conduction display-specific compositional concerns are discussed; it is hypothesised that the qualia available through this medium substantively differ from those for conventional artificial means of appealing to auditory spatial perception. The implications include that spatial music experienced in this manner constitutes a new kind of experience, and that the ground rules of composition are yet to be established. We refer to results from listening experiences with one hundred listeners in an unstructured attribute elicitation exercise, where prominent themes such as “strange”, “weird”, “positive”, “spatial” and “vibrations” emerged. We speculate on future directions aimed at taking maximal advantage of the principle of multimodal perception to broaden the informational bandwidth of the display system. Some implications for composition for hearing-impaired are elucidated.n/