Oral Steroid Responsive Allergic Eruption Following COVID-19 Vaccination.

Cutaneous reactions following immunization, while rare, are a known adverse effect of many vaccinations. The precise etiology of such dermatologic manifestations and their long-term effects are largely unknown. This case study describes a 37-year-old female patient who initially presented with an edematous, pruritic facial rash that developed one day after vaccination against COVID-19, progressively worsened, and proved resistant to various forms of treatment. Following extensive workup, patch testing revealed a previously non-existent allergy to gold sodium thiosulfate. The use of metals, such as gold, in vaccine manufacturing and biotechnology may suggest the possibility of a relationship between injections and immunologic sensitization. Patch testing may be a useful adjunct in evaluating persistent cutaneous reactions following vaccination.

Outcome of cranial cruciate ligament replacement with an enhanced polyethylene terephthalate implant in the dog: A pilot clinical trial.

OBJECTIVE: To assess the 6-month outcome and survival of enhanced polyethylene terephthalate (PET) implants as a replacement for the cranial cruciate ligament (CCL) in dogs with spontaneous CCL disease (CCLD). STUDY DESIGN: Pilot, prospective case series. ANIMALS: Ten client-owned large breed dogs with unilateral spontaneous CCLD. METHODS: Dogs were evaluated before and 6 months after intra-articular placement of a PET implant with the Liverpool Osteoarthritis in Dogs questionnaire and force platform gait analysis. Arthroscopy was performed 6 months after surgery to visually assess implant integrity. RESULTS: Scores on owner questionnaires and limb asymmetry improved in all dogs that reached the 6-month time point, by 51.7% (p = .008) and 86% (p = .002), respectively. The PET implant appeared intact and functioning in two stifles, partially intact and functioning in four stifles and completely torn in three stifles. One dog had an implant infection and was removed from the study. Evidence of deterioration and tearing occurred in the midbody of the implant. CONCLUSION: Although function improved over the course of this study, only 2/10 implants appeared intact 6 months after placement. CLINICAL SIGNIFICANCE: Implant survivability prohibits further clinical investigation using this implant.

Gastrointestinal Intramural Pancreatic Pseudocysts in a Dog: A Case Report and Human Literature Review.

A 9.5 yr old Yorkshire terrier presented with chronic intermittent vomiting and lethargy of 1.5 yr duration that progressed to generalized weakness. Insulin:glucose ratio was consistent with an insulinoma. Triple-phase computed tomography revealed a mid-body pancreatic nodule. The mid-body pancreatic nodule was enucleated; histopathology was consistent with an insulinoma. Two weeks after the operation, the dog presented for anorexia and diarrhea. Abdominal ultrasound revealed a thick-walled cystic lesion along the dorsal stomach wall. An intramural gastric pseudocyst was diagnosed via exploratory laparotomy and intraoperative gastroscopy. Comparison of amylase and lipase levels of the cystic fluid with that of concurrent blood serum samples confirmed the lesion was of pancreatic pseudocyst origin. The gastric pseudocyst was omentalized. Two weeks after the operation, the dog re-presented for anorexia, regurgitation, and diarrhea. An intramural duodenal pseudocyst was identified and treated with a duodenal resection and anastomosis. The dog has remained asymptomatic and recurrence free based on serial abdominal ultrasounds 22 mo following insulinoma removal. To our knowledge, this phenomenon of pancreatic pseudocysts forming in organs other than the pancreas has not been reported in dogs. This case report and comprehensive human literature review purpose is to raise awareness of this disease process in dogs.

Cochlear Mechanisms and Otoacoustic Emission Test Performance.

OBJECTIVES: This study aims to determine the impact of controlling cochlear-source mechanism on the accuracy with which auditory status is identified using otoacoustic emissions (OAEs) in two groups of subjects with normal hearing (NH) and subjects with mild to moderate hearing loss. DESIGN: Data were collected from 212 subjects with NH and with mild to moderate hearing loss who fell into two categories based on a distortion product OAE (DPOAE) screening protocol: the uncertain-identification group (where errors were likely) and the certain-identification group (where errors were unlikely). DPOAE fine-structure patterns were recorded at intervals surrounding f2 = 1, 2 and 4 kHz (f2/f1 ratio = 1.22), with L2 = 35, 45, and 55 dB SPL (L1/L2 ratio = 10 dB). The discrete cosine transform was used to smooth fine structure, limiting the source contribution to the distortion source only. Reflection-source OAEs were also recorded using amplitude-modulated stimulus frequency OAEs (AM-SFOAE). Area under the relative operating characteristic (AROC) curve was used to quantify test accuracy when the source contribution was controlled versus the condition where both sources contribute. Additionally, failure rate, fixed at 5% for NH ears, as a function of behavioral-threshold category was evaluated. RESULTS: When data for the entire subject group were examined, reducing the reflection-source contribution to the DPOAE did not result in better test performance than the best control condition at any frequency tested. When the subjects with NH were restricted to those with confirmed fine structure, AROC analyses indicated that reducing the reflection-source contribution resulted in several small increases in the accuracy (2%-5%) with which auditory status was identified relative to the best control condition. This improvement was observed for the lowest stimulus levels (i.e., L2 = 35 or 45 dB SPL). In this subset of subjects, distortion-source DPOAEs resulted in more accurate identification of mild hearing loss for a fixed false-positive rate of 5% in NH ears at lower L2's, conditions with poor accuracy in the larger group of subjects. The impact of controlling the source contribution on the identification of moderate losses was less clear in the reduced subject group, with some conditions where the distortion-source DPOAE was more accurate than the control condition and other conditions where there was no change. There was no evidence that reflection-source AM-SFOAEs more accurately identified ears with hearing loss when compared to any of the DPOAE conditions in either the large or reduced group of subjects. CONCLUSION: While improvements in test accuracy were observed for some subjects and some conditions (e.g., mild hearing losses and low stimulus levels in the reduced subset of subjects), these results suggest that restricting cochlear source contribution by "smoothing" DPOAE fine structure is not expected to improve DPOAE test accuracy in a general population of subjects. Likewise, recording reflection-source OAEs using the AM-SFOAE technique would not be expected to more accurately identify hearing status compared to mixed- or single-source DPOAEs.

Articular cartilage lesions associated with complete lateral meniscal tears in the dog.

OBJECTIVE: To describe articular cartilage (AC) lesions associated with complete lateral meniscal tears in dogs. STUDY DESIGN: Observational series. ANIMALS: Seventeen dogs with arthroscopic evidence of a complete lateral meniscal tear and associated AC lesions. METHODS: Medical records of dogs with arthroscopic evidence of complete lateral meniscal tear and associated AC lesions between March 2006 and December 2017 were examined for arthroscopic findings. RESULTS: The cranial cruciate ligament (CrCL) was intact in 11 of 17 dogs, partially ruptured but competent in 4 of 17 dogs, and completely ruptured in 2 of 17 dogs. All dogs had grossly normal caudal cruciate ligament, medial meniscus, and AC of the medial compartment. In each dog, a complete radial tear of the caudal body of the lateral meniscus was associated with degenerative osteoarthritis (OA) of the lateral compartment of the stifle. The Outerbridge score of the lateral tibial condyle and lateral femoral condyle was 5 of 5 in 15 dogs, 3 of 5 in 1 dog, and 4 of 5 in 1 dog. CONCLUSION: Dogs with complete tears of the lateral meniscus developed degenerative OA of the lateral compartment of the stifle leading to AC loss and clinical dysfunction. CLINICAL SIGNIFICANCE: Complete lateral meniscal tears may occur as isolated injuries in dogs with a functional CrCL.

Auditory function in normal-hearing, noise-exposed human ears.

OBJECTIVES: To determine whether suprathreshold measures of auditory function, such as distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), are correlated with noise exposure history in normal-hearing human ears. Recent data from animal studies have revealed significant deafferentation of auditory nerve fibers after full recovery from temporary noise-induced hearing loss. Furthermore, these data report smaller ABR wave I amplitudes in noise-exposed animal ears when compared with non-noise-exposed control animals or prenoise exposure amplitudes in the same animal. It is unknown whether a similar phenomenon exists in the normal-hearing, noise-exposed human ear. DESIGN: Thirty normal-hearing human subjects with a range of noise exposure backgrounds (NEBs) participated in this study. NEB was quantified by the use of a noise exposure questionnaire that extensively queried loud sound exposure during the previous 12 months. DPOAEs were collected at three f2s (1, 2, and 4 kHz) over a range of L2s. DPOAE stimulus level began at 80 dB forward-pressure level and decreased in 10 dB steps. Two-channel ABRs were collected in response to click stimuli and 4 kHz tone bursts; one channel used an ipsilateral mastoid electrode and the other an ipsilateral tympanic membrane electrode. ABR stimulus level began at 90 dB nHL and was decreased in 10 dB steps. Amplitudes of waves I and V of the ABR were analyzed. RESULTS: A statistically significant relationship between ABR wave I amplitude and NEB was found for clicked-evoked ABRs recorded at a stimulus level of 90 dB nHL using a mastoid recording electrode. For this condition, ABR wave I amplitudes decreased as a function of NEB. Similar systematic trends were present for ABRs collected in response to clicks and 4 kHz tone bursts at additional suprathreshold stimulation levels (≥70 dB nHL). The relationship weakened and disappeared with decreases in stimulation level (≤60 dB nHL). Similar patterns were present for ABRs collected using a tympanic membrane electrode. However, these relationships were not statistically significant and were weaker and more variable than those collected using a mastoid electrode. In contrast to the findings for ABR wave I, wave V amplitude was not significantly related to NEB. Furthermore, there was no evidence of a systematic relationship between suprathreshold DPOAEs and NEB. CONCLUSIONS: A systematic trend of smaller ABR wave I amplitudes was found in normal-hearing human ears with greater amounts of voluntary NEB in response to suprathreshold clicks and 4 kHz tone bursts. These findings are consistent with the data from previous work completed in animals, where the reduction in suprathreshold responses was a result of deafferentation of high-threshold/low-spontaneous rate auditory nerve fibers. These data suggest that a similar mechanism might be operating in human ears after exposure to high sound levels. However, evidence of this damage is only apparent when examining suprathreshold wave I amplitude of the ABR. In contrast, suprathreshold DPOAE level was not significantly related to NEB. This was expected, given noise-induced auditory damage findings in animal ears did not extend to the outer hair cells, the generator for the DPOAE response.

Clinical Outcomes and Healthcare Resource Utilization for Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents.

INTRODUCTION: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States. PATIENTS AND METHODS: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary ESA failure by SF3B1 mutational status, per recently updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines©). RESULTS: A total of 142 patients were included with a median follow-up time of 17 months (interquartile range [IQR], 7-33). Median age at ESA initiation was 79 years (IQR, 73-85). Patients were predominantly male (54%), overweight or obese (32% and 23%, respectively), of White race (96%) and non-Hispanic ethnicity (89%). Overall, 57% patients were initially treated with darbepoetin alfa and 43% with epoetin alfa. Clinical outcomes were poor, and there was a significant burden on both the health system and individual patients treated with ESA therapies. Hematologic improvement- erythroid was only seen in 26% of 142 patients treated with ESAs, and 65% of 82 retreated patients experienced primary ESA failure. CONCLUSION: Our results indicate that primary ESA failure is largely unrecognized and that many patients should be considered for alternative treatments.

Influence of stimulus parameters on amplitude-modulated stimulus frequency otoacoustic emissions.

The present study evaluated the influence of suppressor frequency (fs) and level (Ls) on stimulus-frequency otoacoustic emissions (SFOAEs) recorded using the amplitude-modulated (AM) suppressor technique described by Neely et al. [J. Acoust. Soc. Am. 118, 2124-2127 (2005a)]. Data were collected in normal-hearing subjects, with data collection occurring in two phases. In phase 1, SFOAEs were recorded with probe frequency (fp) = 1, 2, and 4 kHz and probe levels (Lp) ranging from 0 to 60 dB sound pressure level (SPL). At each fp, Ls ranged from Ls = Lp to Ls = Lp + 30 dB. Additionally, nine relationships between fs and fp were evaluated, ranging from fs/fp = 0.80 to fs/fp = 1.16. Results indicated that for low suppressor levels, suppressors higher in frequency than fp (fs > fp) resulted in higher AM-SFOAE levels than suppressors lower in frequency than fp (fs < fp). At higher suppressor levels, suppressors both higher and lower in frequency than fp produced similar AM-SFOAE levels, and, in many cases, low-frequency suppressors produced the largest response. Recommendations for stimulus parameters that maximize AM-SFOAE level were derived from these data. In phase 2, AM-SFOAEs were recorded using these parameters for fp = 0.7-8 kHz and Lp = 20-60 dB SPL. Robust AM-SFOAE responses were recorded in this group of subjects using the parameters developed in phase 1.

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

Physiologically, well known or traditional immune checkpoints (ICs), such as CTLA-4 and PD-1, are in place to promote tolerance to self-antigens and prevent generation of autoimmunity. In cancer, the ICs are effectively engaged by the tumor cells or stromal ells from the tumor microenvironment through expression of cognate ligands for the ICs present on the cell surface of CD8+ T lymphocytes. The ligation of ICs on CD8+ T lymphocytes triggers inhibitory signaling pathways, leading to quiescence or an exhaustion of CD8+ T lymphocytes. This results in failure of immunotherapy. To overcome this, several FDA-approved therapeutic antibodies are available, but the clinical outcome is quite variable due to the resistance encountered through upregulated expression of alternate ICs such as VISTA, LAG-3, TIGIT and TIM-3. This review focuses on the roles played by the traditional as well as alternate ICs and the contribution of associated signaling pathways in generating such resistance to immunotherapy. Combinatorial targeting of traditional and alternate ICs might be beneficial for immune-refractory tumors.

Monitoring biodegradation of ethene and bioremediation of chlorinated ethenes at a contaminated site using compound-specific isotope analysis (CSIA).

Chlorinated ethenes are commonly found in contaminated groundwater. Remediation strategies focus on transformation processes that will ultimately lead to nontoxic products. A major concern with these strategies is the possibility of incomplete dechlorination and accumulation of toxic daughter products (cis-1,2-dichloroethene (cDCE), vinyl chloride (VC)). Ethene mass balance can be used as a direct indicator to assess the effectiveness of dechlorination. However, the microbial processes that affect ethene are not well characterized and poor mass balance may reflect biotransformation of ethene rather than incomplete dechlorination. Microbial degradation of ethene is commonly observed in aerobic systems but fewer cases have been reported in anaerobic systems. Limited information is available on the isotope enrichment factors associated with these processes. Using compound-specific isotope analysis (CSIA) we determined the enrichment factors associated with microbial degradation of ethene in anaerobic microcosms (ε = -6.7‰ ± 0.4‰, and -4.0‰ ± 0.8‰) from cultures collected from the Twin Lakes wetland area at the Savannah River site in Georgia (United States), and in aerobic microcosms (ε = -3.0‰ ± 0.3‰) from Mycobacterium sp. strain JS60. Under anaerobic and aerobic conditions, CSIA can be used to determine whether biotransformation of ethene is occurring in addition to biodegradation of the chlorinated ethenes. Using δ(13)C values determined for ethene and for chlorinated ethenes at a contaminated field site undergoing bioremediation, this study demonstrates how CSIA of ethene can be used to reduce uncertainty and risk at a site by distinguishing between actual mass balance deficits during reductive dechlorination and apparent lack of mass balance that is related to biotransformation of ethene.

The influence of common stimulus parameters on distortion product otoacoustic emission fine structure.

OBJECTIVES: To determine whether common approaches to setting stimulus parameters influence the depth of fine structure present in the distortion product otoacoustic emission (DPOAE) response. Because the presence of fine structure has been suggested as a possible source of errors, if one of the common parametric approaches results in reduced fine-structure depth, it may be preferred over other approaches. DESIGN: DPOAE responses were recorded in a group of 21 subjects with normal hearing for 1/3-octave intervals surrounding 3 f2s (1, 2, and 4 kHz) at three L2s (30, 45, and 55 dB SPL). For each f2 and L2 combination, L1 and f2/f1 were set according to three commonly used parametric approaches. These included a simple approach, the approach recommended by Kummer et al., and the approach described by Johnson et al. These three approaches primarily differ in the recommended relationship between L1 and L2. For each parametric approach, DPOAE fine structure was evaluated by varying f2 in small steps. Differences in DPOAE level and DPOAE fine-structure depth across f2, L2, and the various stimulus parameters were evaluated using repeated-measures analysis of variance. RESULTS: As expected, significant variations in DPOAE level were observed across the three parametric approaches. For stimulus levels #45 dB SPL, the simple stimuli resulted in lower DPOAE levels than were observed for other approaches. An unexpected finding was that stimulus parameters developed by Johnson et al., which were believed to produce higher DPOAE levels than other approaches, produced the lowest DPOAE levels of the three approaches when f2 = 4 kHz. Significant differences in fine-structure depth were also observed. Greater fine-structure depth was observed with the simple parameters, although this effect was restricted to L2 # 45 dB SPL. When L2 = 55 dB SPL, all three parametric approaches resulted in equivalent fine-structure depth. A significant difference in fine-structure depth across the 3 f2s was also observed. The interval surrounding 2 kHz was associated with greater fine-structure depth than the intervals surrounding 1 and 4 kHz. CONCLUSIONS: The simple stimulus parameters resulted in more fine structure than the other parametric approaches; however, this effect was restricted to L2 # 45 dB SPL. At the moderate stimulus levels used in most clinical applications of DPOAEs (L2 = 55 dB SPL), all three approaches resulted in similar fine-structure depths. These findings suggest that manipulating stimulus parameters, particularly the L1, L2 relationship, is not an effective technique for reducing fine structure, except at the lowest stimulus levels, and that all the common parameters result in equivalent fine structure for moderate stimulus levels. These results also suggest that the stimulus parameters used in future studies of the clinical implications of fine structure may be relatively unimportant, unless stimulus levels #45 dB SPL will be evaluated.

Determination of the center of mass in a heterogeneous population of dogs.

The center of mass (CoM) is the location in a body where mass distribution is balanced. It has a fundamental role in balance and motion which has been poorly described in the dog. The objective of this study was to estimate the variance of the center of mass (CoM) in a heterogeneous population of client-owned dogs and to describe the relationship between CoM, subject morphometrics and an inertial measurement unit (IMU) box positioned ventrally on a neck collar. A single force platform and a reaction board were used to determine CoM in the transverse, sagittal and dorsal planes in thirty-one healthy adult dogs. A series of morphometric measurements were acquired with each dog standing, including distances relative to an IMU box positioned ventrally on a neck collar. Mean transverse plane CoM was 48% the distance from ischium to the IMU box, near the xiphoid process. Mean sagittal place CoM was 59% the width of the chest on the left side. Mean dorsal plane CoM was 41% the distance from the most dorsal to the most ventral aspect of the body. Dog length was the primary variable required to maximize the relationship between three-dimensional CoM and identifiable variables measured. A CoM based normalization procedure should be considered to normalize mass or motion based outcome measure output (e.g., ground reaction forces, vector acceleration) in a heterogeneous population of dogs. Future research will be needed to determine if CoM-based normalization procedures reduce variance in outcome measures affected by subject morphometrics.

Gender, bottom-line mentality, and workplace mistreatment: The roles of gender norm violation and team gender composition.

Although gender has been identified as an important antecedent in workplace mistreatment research, empirical research has shown mixed results. Drawing on role congruity theory, we propose an interactive effect of gender and bottom-line mentality on being the target of mistreatment. Across two field studies, our results showed that whereas women experienced more mistreatment when they had higher levels of bottom-line mentality, men experienced more mistreatment when they had lower levels of bottom-line mentality. In another field study, using round-robin survey data, we found that team gender composition influenced the degree to which the adoption of a bottom-line mentality by female team members was perceived to be a gender norm violation, which subsequently predicted their likelihood of being mistreated. Specifically, women who had higher (vs. lower) levels of bottom-line mentality were more likely to be perceived to violate gender norms in teams with a lower proportion of women, and in turn, perceived gender norm violation was positively associated with being mistreated. We discuss theoretical and practical implications of our findings and directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sustenance for Success: Connections between Community College Students and Food Insecurity.

To assess the connections between student success and food insecurity of community college students the authors present the results of three studies conducted between fall 2017 and spring 2020. Using a cross-sectional design and the intercept method, 858 participants completed the Household Food Security Survey Module. The three hypotheses for the studies were: there is a relationship between food insecurity and (a) GPA, (b) concentration, and (c) energy levels. Food insecurity levels for the participants varied-Monroe, 99%; Spaid and Gillett-Karam, 52%; and Liburd, 30%. Liburd found a significant relationship for all three hypotheses. Monroe's 2020 findings that 99% of her sample was food insecure presents challenges for addressing unmet needs for African American/Black students. Spaid and Gillett-Karam's 2018 findings showed that minority women with Pell Grants had food insecurity levels three times higher than other groups. Traditional student support services should include supplemental services for food-insecure student populations.

Vessel wall-embedded dendritic cells induce T-cell autoreactivity and initiate vascular inflammation.

Human medium-sized and large arteries are targeted by inflammation with innate and adaptive immune responses occurring within the unique microspace of the vessel wall. How 3D spatial arrangements influence immune recognition and cellular response thresholds and which cell populations sense immunoactivating ligands and function as antigen-presenting cells are incompletely understood. To mimic the 3D context of human arteries, bioartificial arteries were engineered from collagen type I matrix, human vascular smooth muscle cells (VSMCs), and human endothelial cells and populated with cells implicated in antigen presentation and T-cell stimulation, including monocytes, macrophages, and myeloid dendritic cells (DCs). Responsiveness of wall-embedded antigen-presenting cells was probed with the Toll-like receptor ligand lipopolysaccharide, and inflammation was initiated by adding autologous CD4(+) T cells. DCs colonized the outermost VSMC layer, recapitulating their positioning at the media-adventitia border of normal arteries. Wall-embedded DCs responded to the microbial product lipopolysaccharide by entering the maturation program and upregulating the costimulatory ligand CD86. Activated DCs effectively stimulated autologous CD4 T cells, which produced the proinflammatory cytokine interferon-gamma and infiltrated deeply into the VSMC layer, causing matrix damage. Lipopolysaccharide-triggered macrophages were significantly less efficacious in recruiting T cells and promoting T-cell stimulation. CD14(+) monocytes, even when preactivated, failed to support initial steps of vascular wall inflammation. Innate immune cells, including monocytes, macrophages, and DCs, display differential functions in the vessel wall. DCs are superior in sensing pathogen-derived motifs and are highly efficient in breaking T-cell tolerance, guiding T cells toward proinflammatory and tissue-invasive behavior.

Clinical test performance of distortion-product otoacoustic emissions using new stimulus conditions.

OBJECTIVES: To determine whether new stimulus parameters, which have been shown to produce large distortion-product otoacoustic emission (DPOAE) levels in a group of normal-hearing listeners (Neely et al. 2005; Johnson et al. 2006), result in more accurate identification of auditory status and more accurate predictions of behavioral threshold than traditional stimulus conditions. DESIGN: DPOAE input/output (I/O) functions for eight f2 frequencies ranging from 0.7 to 8 kHz were recorded from 96 ears with normal hearing and 226 ears with sensorineural hearing losses ranging from mild to profound. The primary-level differences and primary-frequency ratios were set according to the stimulus relations developed by Johnson et al. (2006). The accuracy of the dichotomous decision task (area under the relative operating characteristic curve [AROC]) for these new stimulus conditions was evaluated as a function of L2 and was compared with previous reports in the literature where traditional stimuli were used (Stover et al. 1996). Here, traditional stimuli are defined as L1 = L2 + 10 and f2/f1 = 1.22 for all L2 and f2 values. In addition to I/O functions, DPgrams with L2 = 55-dB sound pressure level (SPL) and f2 ranging from 0.7 to 8 kHz were recorded for each subject using the traditional stimuli. This provided a direct within-subject comparison of AROC for moderate-level stimuli when the new and traditional stimuli were used. Finally, the accuracy with which DPOAE thresholds predicted behavioral thresholds was evaluated in relation to previous reports in the literature for two definitions of DPOAE threshold, one where the entire I/O function was used to make the prediction and a second where the lowest L2 producing a signal to noise ratio > or =3 dB was used. RESULTS: There was no evidence that the new stimuli improved the accuracy with which auditory status was identified from DPOAE responses. With both the new and traditional stimuli, moderate stimulus levels (L2 = 40- to 55-dB SPL) resulted in the most accurate identification of auditory status. When L2 = 55-dB SPL, the new stimuli produced AROC values that were equivalent to those observed with traditional stimuli. The new stimuli resulted in more accurate prediction of behavioral threshold for several f2 values when using the entire I/O function, although the effect was small. Furthermore, using the entire I/O function to predict behavioral threshold results in more accurate predictions of behavioral threshold than using the signal to noise ratio definition, although this approach can be applied to a smaller percentage of ears. CONCLUSIONS: The new stimuli that had been shown previously to produce large DPOAE levels in normal-hearing listeners (Neely et al. 2005; Johnson et al. 2006) do not result in more accurate identification of auditory status and have only a small positive effect on the prediction of behavioral threshold.

Cochlear sources and otoacoustic emissions.

Current understanding suggests that there are two different mechanisms by which otoacoustic emissions (OAEs) are generated in the cochlea. These mechanisms include a nonlinear-distortion mechanism and a coherent-reflection mechanism. Distortion product OAEs (DPOAEs) are believed to include contributions from both mechanisms, while stimulus frequency OAEs (SFOAES), at least at low and moderate levels, are believed to be generated primarily by the coherent-reflection mechanism. In the case of DPOAEs, the interaction of the two mechanisms produces a series of alternating peaks and valleys in the response level when recorded in small frequency increments. This pattern of peaks and valleys typically is referred to as fine structure. There has been much speculation that the interaction of the two mechanisms and the resulting fine structure limits the clinical test performance of DPOAEs. There are few data to address this speculation. Here, we review the literature that describes the cochlear source mechanisms and their potential relationship to clinical applications. We then present results for preliminary data collected in a group of 10 normal-hearing subjects where we explore the influence of common approaches to setting DPOAE stimulus parameters on the resulting fine structure. These preliminary results suggest that, at the moderate stimulus levels used in clinical applications, each of the different stimulus parameters results in a similar amount of fine structure and, therefore, fine structure cannot be eliminated through manipulation of stimulus parameters. We also review the results of some preliminary efforts to identify stimulus parameters that can be used to record SFOAEs (OAEs generated by the reflection mechanism). The potential clinical applications of SFOAEs have received little attention in the literature. By identifying stimulus parameters producing robust responses in normal-hearing ears, it may be possible to more fully evaluate clinical applications of SFOAEs.

Distortion-product otoacoustic emission input/output characteristics in normal-hearing and hearing-impaired human ears.

Distortion-product otoacoustic emission (DPOAE) input/output (I/O) functions were measured in 322 ears of 176 subjects at as many as 8 f(2) frequencies per ear for a total of 1779 I/O functions. The f(2) frequencies ranged from 0.7 to 8 kHz in half-octave steps. Behavioral thresholds (BTs) at the f(2) frequencies ranged from -5 to 60 dB hearing loss (HL). Both linear-pressure and nonlinear, two-slope functions were fitted to the data. The two-slope function describes I/O compression as output-controlled self-suppression. Most I/O functions (96%) were better fitted by the two-slope method. DPOAE thresholds based on each method were used to predict BTs. Compared to estimates based on linear-pressure functions, individual BTs predicted from DPOAE thresholds based on the two-slope model had lower residual error and accounted for more variance. Another advantage of the two-slope method is that it provides an estimate of response growth rate (RGR) that is not tied to threshold. At all frequencies, the median low-level RGR (across I/O functions of the same f(2) and BT) usually increased as BT increased, while high-level compression decreased. The observed characteristics of DPOAE I/O functions are consistent with the loss of cochlear compression that is typically associated with mild-to-moderate HL.

Endothelial connexin 37, connexin 40, and connexin 43 respond uniquely to substrate and shear stress.

Endothelial connexins have been linked to atherosclerosis and hypertension; however, little is know about their sensitivity to stimuli and individual functions. This study investigates the responses of endothelial connexin 37, connexin 40, and connexin 43 (Cx37, Cx40, and Cx43) to shear stress and substrate. Human endothelial cells were seeded on adsorbed collagen or a collagen gel containing smooth muscle cells and exposed to static or laminar shear stress. Connexin mRNA, protein, and gap junction communication were examined. Endothelial monolayers were treated with connexin-specific short interfering RNA (siRNA) and evaluated for communication, proliferation, and morphology under static and shear stress. Results show differential responses of Cx37, Cx40, and Cx43 to substrate and shear stress with reduced communication after shear exposure. RNA interference of individual connexins resulted in expression change of nontarget connexins, which suggests linked expression. Gap junction communication under static conditions is reduced following Cx43 siRNA treatment. Endothelial cells are more elongated with RNA interference (RNAi) targeting Cx40. In conclusion, endothelial connexins demonstrated novel sensitivity to mechanical environment and substrate. Individual isotypes show differential responses and RNAi knockdown provides new insight into connexin function and potential roles in the vasculature.