Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest-Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part II, Research Analysis.

INTRODUCTION: Much of the research impacting diagnosis, outcome, and treatment of traumatic brain injuries (TBIs) has favored time of consciousness criteria indicative of hemispheric blast focus alone. However, recent animal-based research has widely expanded the diagnostic knowledge base and potential treatment options. METHODS: Recent animal-based research findings of foramen magnum and occipital crest-focused blast injuries in laboratory rats were reviewed and compared to the Part I human case report. RESULTS: Comparing the human case report (Part I) to that of animal research studies found very similar neuropathological outcomes, many deep and delayed, and supports why non-cerebral-focused TBIs have gone unrecognized. The overpressure wave is funneled through skull openings of the foramen magnum, with the possibility of a rebound secondary contrecoup injury impacting the orbits, oral-nasal cavity, and ears resulting in additional occult axonal and white matter injury. CONCLUSIONS: Research analysis prompted by a human case report (Part I) has helped identify mechanisms that assist in recognizing and defining non-cerebral hemispheric-focused TBI injuries. Position of the head in relationship to the blast wave, the setting in which the blast occurs, and close diagnostic follow-up are critical to the recognition, diagnosis, and treatment of injuries that have otherwise gone unrecognized and unstudied in humans since the Vietnam War.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part I, Case Report.

INTRODUCTION: The diagnosis of traumatic brain injuries is typically based on hemispheric blasts resulting in degrees of unconsciousness and associated cerebral injuries. This case report describes a Vietnam War era setting in which a traumatic blast wave struck the posterior cranium in the region of the foramen magnum, occipital crest, and other skull openings (orbit, oronasal, and ear) and the unique secondary clinical signs and symptoms experienced over time. MATERIALS AND METHODS: This case report describes secondary delayed-onset clinical signs and symptoms consistent with progressive decades-long physical and functional complications. The traumatic blast resulted in brief unconsciousness, decreased vision in left eye, confusion, right sided hemotympanum, deafness, severe tinnitus, severe nasopharynx pain and difficulty swallowing, pain in right posterior and occipital area of the head, and loss of dental amalgams. Subsequent exams revealed progressive hyperacusis, sea sickness, dysdiadochokinesis, diagnosis of 9th and 10th cranial nerve traumatic schwannomas, hyperdense changes to the frontal lobe white matter, progressive tinnitus, chronic vertigo, right-sided high-frequency hearing loss, progressive oculo-gyric crisis of Tumarkin-like seizures, left-sided chronic vitreous hemorrhage, and diminished right hemisphere performance of the brain based on neurophysiological assessment. No post-traumatic stress, depression, or other emotional or psychiatric difficulties were claimed. CONCLUSION: This case report, unique to the English language scientific literature, discusses in detail the secondary signs and symptoms of a foramen magnum and occipital crest focused-associated blast injury.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused TBI of the Vietnam War and Other Conflicts: Part III, Critique of Existing TBI Criteria and Their Operational Controversies.

INTRODUCTION: In this report, we discuss the controversy of the diverse traumatic brain injury (TBI) categorization and taxonomy and the need to develop a new multidimensional and multidisciplinary categorization system that can be an aid in improved diagnostic and prognostic outcomes. Of interest, the heterogeneity of TBI marks the major obstacle to develop effective therapeutic interventions. Currently, the Glasgow Coma Scale has been utilized to guide in the prognosis and clinical management of TBI; it does not encompass the pathophysiological mechanisms leading to neurological deficits that can impede therapeutic interventions and consequently the failure of clinical trials. An unfortunate gap exists between advances in TBI research and existing U.S. Department of Defense (DoD) definitions, categorization, and management. Part I illustrates a unique posterior-focused TBI case report that does not fit any existing TBI definitions. Part II summarizes new animal-based TBI research that supports the case report as a legitimate TBI category. Part III critiques existing TBI criteria and their controversies. METHODS: Current DoD definitions and decision-making protocols based on concussion time alone are reviewed and compared to the myriad of additional TBI definitions that further illustrate the marked differences in definitions, especially in mild TBIs. RESULTS: The DoD definitions are not consistent with what academic research and science bring to the debate. With increasing world conflicts and wars, evaluators are not prepared to accept, evaluate, and properly manage those TBIs that are not associated with immediate levels of unconsciousness alone as the prime determinant of diagnosis and long-term severity. Despite comprehensive research, current understanding among decision-makers of progressive pathology of non-hemispheric TBIs remains limited, inconsistent, and confusing. CONCLUSIONS: This dilemma requires a multidisciplinary, science/medicine-led panel to actively reassess TBI criteria that take into consideration the latest research including non-cerebral hemispheric injuries. We recommend that DoD/Veterans Affairs establish a commission to regularly review the academic-related scientific evidence and incorporate these findings in a timely fashion into their operational definitions. This would guarantee that recognition, diagnosis, and follow-up of all TBIs are properly understood, managed, and documented.

Physiologically Important Electrolytes as Regulators of TDP-43 Aggregation and Droplet-Phase Behavior.

Intraneuronal aggregation of TDP-43 is seen in 97% of all amyotrophic lateral sclerosis cases and occurs by a poorly understood mechanism. We developed a simple in vitro model system for the study of full-length TDP-43 aggregation in solution and in protein droplets. We found that soluble, YFP-tagged full-length TDP-43 (yTDP-43) dimers can be produced by refolding in low-salt HEPES buffer; these solutions are stable for several weeks. We found that physiological electrolytes induced reversible aggregation of yTDP-43 into 10-50 nm tufted particles, without amyloid characteristics. The order of aggregation induction potency was K+ < Na+ < Mg2+ < Ca2+, which is the reverse of the Hofmeister series. The kinetics of aggregation were fit to a single-step model, and the apparent rate of aggregation was affected by yTDP-43 and NaCl concentrations. While yTDP-43 alone did not form stable liquid droplets, it partitioned into preformed Ddx4N1 droplets, showing dynamic diffusion behavior consistent with liquid-liquid phase transition, but then aggregated over time. Aggregation of yTDP-43 in droplets also occurred rapidly in response to changes in electrolyte concentrations, mirroring solution behavior. This was accompanied by changes to droplet localization and solvent exchange. Exposure to extracellular-like electrolyte conditions caused rapid aggregation at the droplet periphery. The aggregation behavior of yTDP-43 is controlled by ion-specific effects that occur at physiological concentrations, suggesting a mechanistic role for local electrolyte concentrations in TDP-43 proteinopathies.

The Essentiality of Arachidonic Acid in Infant Development.

Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence.

Novel conformation-specific monoclonal antibodies against amyloidogenic forms of transthyretin.

INTRODUCTION: Transthyretin amyloidosis (ATTR amyloidosis) is caused by the misfolding and deposition of the transthyretin (TTR) protein and results in progressive multi-organ dysfunction. TTR epitopes exposed by dissociation and misfolding are targets for immunotherapeutic antibodies. We developed and characterized antibodies that selectively bound to misfolded, non-native conformations of TTR. METHODS: Antibody clones were generated by immunizing mice with an antigenic peptide comprising a cryptotope within the TTR sequence and screened for specific binding to non-native TTR conformations, suppression of in vitro TTR fibrillogenesis, promotion of antibody-dependent phagocytic uptake of mis-folded TTR and specific immunolabeling of ATTR amyloidosis patient-derived tissue. RESULTS: Four identified monoclonal antibodies were characterized. These antibodies selectively bound the target epitope on monomeric and non-native misfolded forms of TTR and strongly suppressed TTR fibril formation in vitro. These antibodies bound fluorescently tagged aggregated TTR, targeting it for phagocytic uptake by macrophage THP-1 cells, and amyloid-positive TTR deposits in heart tissue from patients with ATTR amyloidosis, but did not bind to other types of amyloid deposits or normal tissue. CONCLUSIONS: Conformation-specific anti-TTR antibodies selectively bind amyloidogenic but not native TTR. These novel antibodies may be therapeutically useful in preventing deposition and promoting clearance of TTR amyloid and in diagnosing TTR amyloidosis.

Determining composition of micron-scale protein deposits in neurodegenerative disease by spatially targeted optical microproteomics.

Spatially targeted optical microproteomics (STOMP) is a novel proteomics technique for interrogating micron-scale regions of interest (ROIs) in mammalian tissue, with no requirement for genetic manipulation. Methanol or formalin-fixed specimens are stained with fluorescent dyes or antibodies to visualize ROIs, then soaked in solutions containing the photo-tag: 4-benzoylbenzyl-glycyl-hexahistidine. Confocal imaging along with two photon excitation are used to covalently couple photo-tags to all proteins within each ROI, to a resolution of 0.67 µm in the xy-plane and 1.48 µm axially. After tissue solubilization, photo-tagged proteins are isolated and identified by mass spectrometry. As a test case, we examined amyloid plaques in an Alzheimer's disease (AD) mouse model and a post-mortem AD case, confirming known plaque constituents and discovering new ones. STOMP can be applied to various biological samples including cell lines, primary cell cultures, ex vivo specimens, biopsy samples, and fixed post-mortem tissue.

Efficacy and safety of arachidonic acid for treatment of school-age children in Schistosoma mansoni high-endemicity regions.

Arachidonic acid (ARA), an omega-6 fatty acid, is a potent schistosomicide that displayed significant and safe therapeutic effects in Schistosoma mansoni-infected schoolchildren in S. mansoni low-prevalence regions. We here report on ARA efficacy and safety in treatment of schoolchildren in S. mansoni high-endemicity areas of Kafr El Sheikh, Egypt. The study was registered with ClinicalTrials.gov (NCT02144389). In total, 268 schoolchildren with light, moderate, or heavy S. mansoni infection were assigned to three study arms of 87, 91, and 90 children and received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA, respectively. The children were examined before and after treatment for stool parasite egg counts and blood biochemical, hematological, and immunological parameters. ARA, like PZQ, induced moderate cure rates (50% and 60%, respectively) in schoolchildren with light infection and modest cure rates (21% and 20%, respectively) in schoolchildren with high infection. PZQ and ARA combined elicited 83% and 78% cure rates in children with light and heavy infection, respectively. Biochemical and immunological profiles were either unchanged or ameliorated after ARA therapy. Combination of PZQ and ARA might be useful for treatment of children with schistosomiasis in high-endemicity regions.

Efficacy and safety of arachidonic acid for treatment of Schistosoma mansoni-infected children in Menoufiya, Egypt.

Arachidonic acid (ARA), an omega-6 fatty acid, kills juvenile and adult schistosomes in vitro and displays highly significant and safe therapeutic effects in mice and hamsters infected with Schistosoma mansoni or S. haematobium. This study aims to examine the efficacy and safety of ARA in treatment of school-age children infected with S. mansoni. In total, 66 S. mansoni-infected schoolchildren (20-23 children/study arm) received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA. The children were examined before and after treatment for worm egg counts in stool and blood biochemical and immunological parameters. ARA proved to be as efficacious as PZQ in treatment of schoolchildren with low infection intensity (78% and 85% cure rates, respectively). For moderate-intensity infection, the ARA and PZQ combination led to 100% cure rate. Biochemical, hematological, and immunological parameters were either unchanged or ameliorated after ARA therapy.

Coarse-Grained Molecular Models of Water: A Review.

Coarse-grained (CG) models have proven to be very effective tools in the study of phenomena or systems that involve large time- and length-scales. By decreasing the degrees of freedom in the system and using softer interactions than seen in atomistic models, larger timesteps can be used and much longer simulation times can be studied. CG simulations are widely used to study systems of biological importance that are beyond the reach of atomistic simulation, necessitating a computationally efficient and accurate CG model for water. In this review, we discuss the methods used for developing CG water models and the relative advantages and disadvantages of the resulting models. In general, CG water models differ with regards to how many waters each CG group or bead represents, whether analytical or tabular potentials have been used to describe the interactions, and how the model incorporates electrostatic interactions. Finally, how the models are parameterized depends on their application, so, while some are fitted to experimental properties such as surface tension and density, others are fitted to radial distribution functions extracted from atomistic simulations.

Analyzing complicated protein folding kinetics rapidly by analytical Laplace inversion using a Tikhonov regularization variant.

Kinetic experiments provide much information about protein folding mechanisms. Time-resolved signals are often best described by expressions with many exponential terms, but this hinders the extraction of rate constants by nonlinear least squares (NLS) fitting. Numerical inverse Laplace transformation, which converts a time-resolved dataset into a spectrum of amplitudes as a function of rate constant, allows easy estimation of the rate constants, amplitudes, and number of processes underlying the data. Here, we present a Tikhonov regularization-based method that converts a dataset into a rate spectrum, subject to regularization constraints, without requiring an iterative search of parameter space. This allows more rapid generation of rate spectra as well as analysis of datasets too noisy to process by existing iterative search algorithms. This method's simplicity also permits highly objective, largely automatic analysis with minimal human guidance. We show that this regularization method reproduces results previously obtained by NLS fitting and that it is effective for analyzing datasets too complex for traditional fitting methods. This method's reliability and speed, as well as its potential for objective, model-free analysis, make it extremely useful as a first step in analysis of complicated noisy datasets and an excellent guide for subsequent NLS analysis.

Multiphoton ANS fluorescence microscopy as an in vivo sensor for protein misfolding stress.

The inability of cells to maintain protein folding homeostasis is implicated in the development of neurodegenerative diseases, malignant transformation, and aging. We find that multiphoton fluorescence imaging of 1-anilinonaphthalene-8-sulfonate (ANS) can be used to assess cellular responses to protein misfolding stresses. ANS is relatively nontoxic and enters live cells and cells or tissues fixed in formalin. In an animal model of Alzheimer's disease, ANS fluorescence imaging of brain tissue sections reveals the binding of ANS to fibrillar deposits of amyloid peptide (Aß) in amyloid plaques and in cerebrovascular amyloid. ANS imaging also highlights non-amyloid deposits of glial fibrillary acidic protein in brain tumors. Cultured cells under normal growth conditions possess a number of ANS-binding structures. High levels of ANS fluorescence are associated with the endoplasmic reticulum (ER), Golgi, and lysosomes-regions of protein folding and degradation. Nuclei are virtually devoid of ANS binding sites. Additional ANS binding is triggered by hyperthermia, thermal lesioning, proteasome inhibition, and induction of ER stress. We also use multiphoton imaging of ANS binding to follow the in vivo recovery of cells from protein-damaging insults over time. We find that ANS fluorescence tracks with the binding of the molecular chaperone Hsp70 in compartments where Hsp70 is present. ANS highlights the sensitivity of specific cellular targets, including the nucleus and particularly the nucleolus, to thermal stress and proteasome inhibition. Multiphoton imaging of ANS binding should be a useful probe for monitoring protein misfolding stress in cells.

Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury.

BACKGROUND: Although various strategies for prevention of brain disease have been implemented, no substance has been found to be advantageous for prophylaxis against brain injury. OBJECTIVE: While previous work in our laboratory and others have shown positive effects using the omega-3 fatty acid docosahexaenoic acid (DHA) in post-injury treatment following traumatic and ischemic insults, we wished to test its effects when given prior to injury. We have attempted to measure anatomical, cellular, and behavioral outcomes with a prophylactic administration of DHA. METHODS: Five groups of 16 adult male Sprague-Dawley rats were subjected to an impact acceleration traumatic brain after having received a prior administration of DHA in doses of 3, 12, and 40 mg/kg for 30 days prior. Serum fatty acid levels were determined from isolated plasma phospholipids at baseline and at the end of 30 days supplementation. Following sacrifice 1 week after injury, brainstem white matter tracts underwent fluorescent immunohistochemical processing for labeling of beta amyloid precursor protein (APP), an anatomical marker of brain injury, as well as measurements of CD68 and caspase-3 levels, and water maze testing was used for behavioral assessment. RESULTS: Dietary supplementation with DHA resulted in increased serum DHA levels proportionate with the escalating dosage. Immunohistochemical analysis revealed significantly (P < .05) decreased numbers of APP levels in all groups of animals receiving pre-injury supplementation with DHA of 4, 12, and 40 mg/kg at 13955, 4186, and 2827 axons per mm³, respectively, vs 37442 in unsupplemented animals, as measured by stereological methodology. Using a selective measuring technique, only the highest dosage group, 40 mg/kg showed significantly (P < .05) decreased numbers of APP positive axons, at 1.15 axons per high power field vs 6.78 in unsupplemented animals. CD-68, caspase-3, and water maze testing all were significantly (P < .05) improved in the high dose group. CONCLUSION: Dietary supplementation with DHA increases serum levels and, if given prior to traumatic brain injury, reduces the injury response, as measured by axonal injury counts, markers for cellular injury and apoptosis, and memory assessment by water maze testing. This uniform response was seen for the highest dosage group, 40 mg/kg given over 30 days prior to injury, but when measured by stereological counting methodology there was a positive response to anatomical injury across low to high doses of DHA. The potential for DHA to provide prophylactic benefit to the brain against traumatic injury appears promising and requires further investigation.

Phospholipid hydroperoxide glutathione peroxidase (Gpx4) is highly regulated in male turkey poults and can be used to determine dietary selenium requirements.

The dietary selenium recommendation for turkeys of 0.2 microg Se/g is higher than for many other species. Liver glutathione peroxidase-1 (Gpx1) activity levels determined using hydrogen peroxide (H(2)O(2)) in previous studies suggest that 0.2 microg Se/g may still be too low and that some of this Gpx1 activity might be due to phospholipid hydroperoxide Gpx (Gpx4). Thus we separated Gpx1 from Gpx4 by chromatography, demonstrated that 47% of the H(2)O(2) activity in Se-adequate turkey liver was due to Gpx4, and determined a factor for calculation of each activity. Day-old male poults were fed an Se-deficient torula diet (0.007 microg Se/g) supplemented with graded levels of Se (0-0.5 microg Se/g) for 27 days. Final body weights indicated a minimum Se requirement for growth of 0.05 microg Se/g. The liver had the highest Gpx4 activity in Se-adequate poults, and Gpx4 activity in Se-deficient liver decreased to 5% of Se-adequate levels, with an Se requirement of 0.29 microg Se/g. Liver Gpx1, gizzard Gpx1 and gizzard Gpx4 activities also had Se requirements of 0.28-0.30 microg Se/g, collectively yielding an Se requirement of 0.3 microg Se/g, which is three times higher than the requirements found in comparable rodent studies. We also sequenced partial cDNA clones for turkey Gpx1 (GQ502186) and Gpx4 (GQ502187), and found >60% identity with rodents and humans and >90% identity with chickens. Ribonuclease protection analysis showed that Gpx4 mRNA levels decrease substantially in Se-deficient turkey liver, unlike in rodents. These underlying differences in selenoprotein molecular biology may explain the elevated dietary Se requirements of turkeys.

On the investigation of coarse-grained models for water: balancing computational efficiency and the retention of structural properties.

Developing accurate models of water for use in computer simulations is important for the study of many chemical and biological systems, including lipid bilayer self-assembly. The large temporal and spatial scales needed to study such self-assembly have led to the development and application of coarse-grained models for the lipid-lipid, lipid-solvent, and solvent-solvent interactions. Unfortunately, popular center-of-mass-based coarse-graining techniques are limited to modeling water with one water per be ad. In this work, we have utilized the K-means algorithm to determine the optimal clustering of waters to allow the mapping of multiple waters to single coarse-grained beads. Through the study of a simple mixture between water and an amphiphilic solute (1-pentanol), we find a four-water bead model has the optimal balance between computational efficiency and accurate solvation and structural properties when compared to water models ranging from one to nine waters per bead. The four-water model was subsequently utilized in studies of the solvation of hexadecanoic acid and the structure, as measured via radial distribution functions, for the hydrophobic tails and the bulk water phase were found to agree well with experimental data and their atomistic target.

Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats.

The nutritional influence of zinc on markers of bone extracellular matrix resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15 or 30 microg Zn/g diet for 24 days. Femur zinc increased substantially as zinc increased from 5 to 15 microg/g diet and modestly between 15 and 30 microg/g (P<.05). By morphological assessment, trabecular bone increased steadily as dietary zinc increased to 30 microg/g. Increasing dietary zinc tended to decrease Zip2 expression nonsignificantly and elevated the relative expression of metallothionen-I at 15 but not 30 microg Zn/g diet. Femur osteoclastic resorption potential, indicated by matrix metalloproteinases (MMP-2 and MMP-9) and carbonic anhydrase-2 activities decreased with increasing dietary zinc. In contrast to indicators of extracellular matrix resorption, femur tartrate-resistant acid and alkaline phosphatase activities increased fourfold as dietary zinc increased from 2.5 to 30 microg Zn/g. Likewise, 15 or 30 microg Zn/g diet resulted in maximum relative expression of osteocalcin, without influencing expression of core-binding factor alpha-1, collagen Type 1 alpha-1, or nuclear factor of activated T cells c1. In conclusion, increased trabecular bone with additional zinc suggests that previous requirement estimates of 15 microg Zn/g diet may not meet nutritional needs for optimal bone development. Overall, the up-regulation of extracellular matrix modeling indexes and concomitant decrease in resorption activities as dietary zinc increased from 2.5 to 30 microg/g provide evidence of one or more physiological roles for zinc in modulating the balance between bone formation and resorption.

Iron absorption by healthy women is not associated with either serum or urinary prohepcidin.

BACKGROUND: Although hepcidin is proposed as a regulator of iron absorption, this has not been assessed in humans. OBJECTIVE: Our objective was to assess the relation between serum or urinary prohepcidin and iron absorption in healthy premenopausal women. DESIGN: The subjects were 28 healthy women aged 22-51 y with normal hemoglobin concentrations (120-152 g/L). Absorption of 0.5 mg Fe with 0.2 microCi 59Fe tracer, both as FeSO4, was measured by whole-body scintillation counting 13 d after oral administration. Fasting blood and urine samples were collected the day of and 16 wk after the absorption measurement. Serum and urinary prohepcidin concentrations were measured by an enzyme-linked immunosorbent assay by using an antibody against amino acid residues 28-47 of the proregion. RESULTS: Mean (+/-SD) iron absorption was 36 +/- 19% (range: 4-81%), and serum ferritin (geometric x) was 27 microg/L (range: 4-122 microg/L), as commonly observed in healthy premenopausal women. Serum prohepcidin was 196 microg/L (range: 99-376 microg/L) and, in contrast with urinary prohepcidin, was relatively consistent for the women between 0 and 16 wk. Serum prohepcidin correlated directly with serum ferritin (R2 = 0.28, P < 0.01) but was unrelated to 59Fe absorption, in contrast to serum ferritin (R2 = 0.33, P < 0.01). CONCLUSIONS: Serum prohepcidin concentrations were relatively stable within subjects and correlated with serum ferritin. However, unlike serum ferritin, neither serum nor urinary prohepcidin concentrations were related to iron absorption in healthy women.

Reversible peripheral vestibulopathy: the treatment of superior canal dehiscence.

OBJECTIVE: Superior canal dehiscence (SCD) is a recently described disorder that results from absence of bone over the superior semicircular canal. We have reviewed 30 cases of SCD found at our institution and report their presentation, workup, and response to therapy. STUDY DESIGN: Retrospective chart review of all patients diagnosed with SCD from 1999 to 2004 at the University of Utah. RESULTS: Thirty patients were identified with SCD. Patients presented with chronic disequilibrium (63%), Tullio's phenomenon (41%), pressure evoked vertigo (44%), hearing loss (30%), and pulsatile tinnitus (7%). ENG performed early in our series revealed abnormal nystagmus with sound presentation, Valsalva, or tympanogram; however, history and CT examination alone was used to identify this condition in most of our patients. Twenty-seven of the 30 patients had some symptoms related to SCD; the other 3 were found to have incidental SCD on CT examination. Of these patients, 14 had severe enough symptoms to warrant operative intervention. All, but one had resolution of their symptoms after completion of intervention. CONCLUSIONS: Superior canal dehiscence is a highly treatable form of vestibulopathy once recognized. When patients present with typical symptoms, workup with CT is reliable and accurate. Surgical intervention results in reversal of symptoms in most cases with low morbidity. EBM RATING: C-4.

Basic anatomy and physiology of olfaction and taste.

The chemical senses of taste and smell are important to survival and quality of life. Both senses rely on the binding of odorant molecules to receptors located on the receptor cells. Olfaction and gustation have complex systems of coding, but they display differing methods for coding the receptor stimulus. Both have numerous central projections that allow for the perception and interpretation of these important sensory inputs.