Patient and device factors contributing to electrically-evoked stapedial reflex thresholds in cochlear implanted adults.

INTRODUCTION: Optimal cochlear implant (CI) outcomes are due to, at least in part, appropriate device programming. Objective measures, such as electrically-evoked stapedial reflex thresholds (ESRTs), can be used to more accurately set programming levels. However, underlying factors that contribute to ESRT levels are not well understood. The objective of the current study is to analyze how demographic variables of patient sex and age, along with cochlear implant electrode location, influence electrically-evoked stapedial reflex thresholds (ESRTs) in adult cochlear implant users. METHODS: A single institution retrospective review was performed. Electronic medical records, cochlear implant programming records, and clinic database of post-operative computerized tomography were reviewed to gather information regarding patient demographics, ESRTs, and electrode array metrics including medial-lateral distance and scalar location. Linear mixed models were constructed to determine how demographic variables and electrode position influence ESRTs recorded in 138 adult CI recipients. RESULTS: ESRTs were significantly affected by recipient age, with older listeners demonstrating higher ESRT levels. On average, males had higher ESRT levels when compared to females. In a subset of the study sample, ESRT levels increased with increasing medial-lateral distance, however, there was not a statistically significant effect of electrode type (lateral/straight arrays compared to perimodiolar arrays). ESRTs were not affected by scalar location. DISCUSSION/CONCLUSIONS: The results suggest that key demographic and electrode position characteristics influence the level of ESRTs in adult CI recipients. While ESRTs are widely used to assist with CI programming, underlying factors are not well understood. The significant factors of aging and sex could be due to middle ear mechanics or neural health differences, however further data are needed to better understand these associations.

Computer-based Auditory Training by New Adult Cochlear Implant Recipients Is Associated With Durable Improvements in Cochlear Implant Quality of Life.

OBJECTIVE: The process of adapting to communicate with a cochlear implant (CI) is complex. The use of auditory training after cochlear implantation may help to facilitate improvements in postoperative speech recognition and quality-of-life outcomes in new adult CI recipients. However, the effectiveness of auditory training remains uncertain and long-term effects have not been examined in a large sample of new adult CI users. As such, the objective of this study was to examine the influence of common forms of auditory training on speech recognition and CI-related quality-of-life (CI-related QOL) outcomes at 1 year after cochlear implantation. We hypothesized that patients who reported use of computer-based auditory training (CBAT) would show improved speech and CIQOL-35 Profile scores at 1 year after activation of their implant, compared with their peers. DESIGN: This study was designed as a prospective study and was undertaken at a tertiary academic CI center. Participants included 114 adults undergoing cochlear implantation for bilateral hearing loss. Patients serially self-reported use of the following types of post-CI auditory training over their first-year postactivation: (1) face-to-face training (e.g., speech-language pathologist), (2) passive home-based training (e.g., listening to audiobooks), and (3) CBAT (e.g., self-directed software). Outcomes measures for this study included change in Consonant-Nucleus-Consonant phoneme (CNCp), CNC word (CNCw), AzBio sentences in quiet, and CIQOL-35 Profile global and domain scores from pre-CI to 12-mo post-CI. RESULTS: Of 114 patients, 94 (82.5%) used one or more auditory training resources. Of these, 19.3% used face-to-face training, 67.5% passive home-based training, and 46.5% CBAT. Of 114 patients, 73 had complete CIQOL data. At 12 mo, only CBAT use was associated with significantly greater improvements in global and all domain-specific CIQOL scores ( d -range = 0.72-0.87), compared with those not using CBAT. Controlling for demographics and use of multiple training resources, CBAT remained the strongest positive predictor of CIQOL improvement, with significant associations with global score (ß = 12.019[4.127,19.9]) and all domain scores at 12-mo post-CI: communication (ß = 11.937[2.456,21.318), emotional (ß = 12.293[1.827,22.759), entertainment (ß = 17.014[5.434,28.774), environment (ß = 13.771[1.814,25.727]), listening effort (ß = 12.523[2.798,22.248]), and social (ß = 18.114[7.403,28.826]). No significant benefits were noted with use of CBAT or any other form of auditory training and speech recognition scores at 12-mo post-CI ( d -range = -0.12-0.22). CONCLUSIONS: Auditory training with CBAT was associated with improved CI-related QOL outcomes at 12-mo post-CI. Given its availability and low cost, this study provides evidence to support using CBAT to improve real-world functional abilities in new adult CI recipients.

Radiation Oncology Resident Education: Is Change Needed?

Leading successful change efforts first requires assessment of the "before change" environment and culture. At our institution, the radiation oncology (RO) residents follow a longitudinal didactic learning program consisting of weekly 1-h lectures, case conferences, and journal clubs. The resident didactic education series format has not changed since its inception over 10 years ago. We evaluated the perceptions of current residents and faculty about the effectiveness of the curriculum in its present form. Two parallel surveys were designed, one each for residents and attendings, to assess current attitudes regarding the effectiveness and need for change in the RO residency curriculum, specifically the traditional didactic lectures, the journal club sessions, and the case conferences. We also investigated perceived levels of engagement among residents and faculty, whether self-assessments would be useful to increase material retention, and how often the content of didactic lectures is updated. Surveys were distributed individually to each resident (N = 10) and attending (N = 24) either in-person or via Zoom. Following completion of the survey, respondents were informally interviewed about their perspectives on the curriculum's strengths and weaknesses. Compared to 46% of attendings, 80% of RO residents believed that the curriculum should be changed. Twenty percent of residents felt that the traditional didactic lectures were effective in preparing them to manage patients in the clinic, compared to 74% of attendings. Similarly, 10% of residents felt that the journal club sessions were effective vs. 42% of attendings. Finally, 40% of residents felt that the case conferences were effective vs. 67% of attendings. Overall, most respondents (56%) favored change in the curriculum. Our results suggest that the perceptions of the residents did not align with those of the attending physicians with respect to the effectiveness of the curriculum and the need for change. The discrepancies between resident and faculty views highlight the importance of a dedicated change management effort to mitigate this gap. Based on this project, we plan to propose recommended changes in structure to the residency program directors. Main changes would be to increase the interactive nature of the course material, incorporate more ways to increase faculty engagement, and consider self-assessment questions to promote retention. Once we get approval from the residency program leadership, we will follow Kotter's "Eight steps to transforming your organization" to ensure the highest potential for faculty to accept the expectations of a new curriculum.

Cross-species activation of hydrogen cyanide production by a promiscuous quorum-sensing receptor promotes Chromobacterium subtsugae competition in a dual-species model.

Many saprophytic bacteria have LuxR-I-type acyl-homoserine lactone (AHL) quorum-sensing systems that may be important for competing with other bacteria in complex soil communities. LuxR AHL receptors specifically interact with cognate AHLs to cause changes in expression of target genes. Some LuxR-type AHL receptors have relaxed specificity and are responsive to non-cognate AHLs. These promiscuous receptors might be used to sense and respond to AHLs produced by other bacteria by eavesdropping. We are interested in understanding the role of eavesdropping during interspecies competition. The soil saprophyte Chromobacterium subtsugae has a single AHL circuit, CviR-I, which produces and responds to N-hexanoyl-HSL (C6-HSL). The AHL receptor CviR can respond to a variety of AHLs in addition to C6-HSL. In prior studies we have utilized a coculture model with C. subtsugae and another soil saprophyte, Burkholderia thailandensis. Using this model, we previously showed that promiscuous activation of CviR by B. thailandensis AHLs provides a competitive advantage to C. subtsugae. Here, we show that B. thailandensis AHLs activate transcription of dozens of genes in C. subtsugae, including the hcnABC genes coding for production of hydrogen cyanide. We show that hydrogen cyanide production is population density-dependent and demonstrate that the cross-induction of hydrogen cyanide by B. thailandensis AHLs provides a competitive advantage to C. subtsugae. Our results provide new information on C. subtsugae quorum sensing and are the basis for future studies aimed at understanding the role of eavesdropping in interspecies competition.

Impact of auditory environments on language outcomes in children with a cochlear implant.

OBJECTIVES: To analyse the effects of auditory environments on receptive and expressive language outcomes in children with a CI. DESIGN: A single-institution retrospective review was performed. The auditory environments included Speech-Noise, Speech-Quiet, Quiet, Music, and Noise. Hearing Hour Percentage (HHP) and percent total hours were calculated for each environment. Generalised Linear Mixed Models (GLMM) analyses were used to study the effects of auditory environments on PLS Receptive and Expressive scores. STUDY SAMPLE: Thirty-nine children with CI. RESULTS: On GLMM, an increase in Quiet HHP and Quiet percent total hours were positively associated with PLS Receptive scores. Speech-Quiet, Quiet, and Music HHP were positively associated with PLS Expressive scores, with only Quiet being significant for percent total hours. In contrast, percent total hours of Speech-Noise and Noise had a significant negative association with PLS Expressive scores. CONCLUSIONS: This study suggests that more time spent in a quiet auditory environment positively influences PLS Receptive and Expressive scores and that more time listening to speech in quiet and music positively influences PLS Expressive scores. Time spent in environments recognised as Speech-Noise and Noise might negatively impact a child's expressive language outcomes with a CI. Future research is needed to better understand this association.

Evaluation of the different exposure parameters for the accurate diagnosis of peri-implantitis severity in digital panoramic radiography.

BACKGROUND: To evaluate the accuracy of the diagnosis of peri-implant bone defects' severities in digital panoramic radiographs obtained at different tube voltage and/or tube current settings. MATERIAL AND METHODS: Two different sizes of peri-implant bone defects (type 1 and type 2) were prepared after the implants were inserted into 29 bovine rib blocks. Digital panoramic radiographs were obtained at eight different tube voltage and/or tube current settings for all rib blocks. Implant images were cropped separately. The average intensity value (AIV) of cropped images were analyzed using Adobe Photoshop CC software. The Kruskal-Wallis H test was used to compare AIVs. All cropped images were evaluated using a five-point Likert scale for the likelihood of a bone defect being absent or present. The weighted kappa values were calculated to compare observer agreement and ROC analysis was performed to determine the appropriate exposure parameters. RESULTS: The lowest AIV was obtained at 72 kV/6.3 mA (92.162±16.016), and the highest AIV was obtained at 60 kV/3.2 mA (179.050±13.823). The Kruskal-Wallis H test showed significant differences in the AIVs according to the exposure parameters (p<0.001). The kappa coefficient for the inter-observer agreement was excellent (0.864, p<0.001). The AUC values for type 1 defects ranged from 0.778 and 0.860; for type 2 defects ranged from 0.920 and 0.967. The AUC value of type 1 defects was slightly better in panoramic images obtained with high kV and low mA levels (72 kV/3.2 mA), compared to others. CONCLUSIONS: In daily clinical routine, peri-implant bone defects might be evaluated by panoramic radiographs obtained with all kV and mA values tested. However, to avoid misdiagnosing and for better accuracy, panoramic radiographs obtained with high kV and low mA levels suitable for patients should be used, especially in the detection of small or initial bone defects.

A Broadly Applicable Method for Characterizing the Slope of the Electrically Evoked Compound Action Potential Amplitude Growth Function.

OBJECTIVES: Amplitudes of electrically evoked compound action potentials (eCAPs) as a function of the stimulation level constitute the eCAP amplitude growth function (AGF). The slope of the eCAP AGF (i.e., rate of growth of eCAP amplitude as a function of stimulation level), recorded from subjects with cochlear implants (CIs), has been widely used as an indicator of survival of cochlear nerve fibers. However, substantial variation in the approach used to calculate the slope of the eCAP AGF makes it difficult to compare results across studies. In this study, we developed an improved slope-fitting method by addressing the limitations of previously used approaches and ensuring its application for the estimation of the maximum slopes of the eCAP AGFs recorded in both animal models and human listeners with various etiologies. DESIGN: The new eCAP AGF fitting method was designed based on sliding window linear regression. Slopes of the eCAP AGF estimated using this new fitting method were calculated and compared with those estimated using four other fitting methods reported in the literature. These four methods were nonlinear regression with a sigmoid function, linear regression, gradient calculation, and boxcar smoothing. The comparison was based on the fitting results of 72 eCAP AGFs recorded from 18 acutely implanted guinea pigs, 46 eCAP AGFs recorded from 23 chronically implanted guinea pigs, and 2094 eCAP AGFs recorded from 200 human CI users from 4 patient populations. The effect of the choice of input units of the eCAP AGF (linear versus logarithmic) on fitting results was also evaluated. RESULTS: The slope of the eCAP AGF was significantly influenced by the slope-fitting method and by the choice of input units. Overall, slopes estimated using all five fitting methods reflected known patterns of neural survival in human patient populations and were significantly correlated with speech perception scores. However, slopes estimated using the newly developed method showed the highest correlation with spiral ganglion neuron density among all five fitting methods for animal models. In addition, this new method could reliably and accurately estimate the slope for 4 human patient populations, while the performance of the other methods was highly influenced by the morphology of the eCAP AGF. CONCLUSIONS: The novel slope-fitting method presented in this study addressed the limitations of the other methods reported in the literature and successfully characterized the slope of the eCAP AGF for various animal models and CI patient populations. This method may be useful for researchers in conducting scientific studies and for clinicians in providing clinical care for CI users.

Sexual dimorphism and biomechanical loading in occipital bone morphological variation.

We explore the contribution of biological sex and biomechanical activity from subsistence to occipital bone variation. Previous studies have used occipital bone traits to determine biological sex and identify ancestry to differing degrees of success. Biomechanical stress from variation in subsistence and gender-based divisions of labor could perhaps explain some of the noise in the signal for these grouping variables. To explore this possibility, we used metric (foramen magnum length and breadth, external occipital protuberance depth, lambda-inion length, bicondylar breadth) and nonmetric traits (general occipital form, presence of a nuchal crest, and nuchal line count). We collected original data and mined published data for our analysis using skeletal collections of Native American hunter-gatherers and horticulturalists, a historic military site, and contemporary study collections. We find that the foramen magnum area exhibits sexual dimorphism and is not influenced by subsistence, but the accuracy of sex estimation is only 71%, suggesting the chance of being correct at slightly more than two-thirds. All traits exhibited sex-based variation but only bicondylar breadth and lambda-inion metrics exhibited subsistence-based variation. Given the limited amount of variance explained by either sex or sex and subsistence, biomechanics may still play a role but not from the influence of subsistence practices in these datasets. Additional data from a wider array of skeletal samples, perhaps with known occupation, is warranted if we are to understand how occipital variation is shaped.

Clinical outcomes of patients with endometrioid epithelial ovarian cancer following surgical treatment.

BACKGROUND: Endometrioid epithelial ovarian cancer (EEOC) is rare, and its management poorly defined. We examined factors associated with 5-year progression-free survival (PFS) after surgery for EEOC. METHODS: Retrospective study: treatment and outcomes of all EEOC patients undergoing initial surgery at, or presenting to, our institution within 3 months of initial surgery, 1/2002-9/2017. RESULTS: In total, 212 patients were identified. Median follow-up, 63.9 months (range, 0.7-192); median age at diagnosis, 52 years (range, 20-88); disease stage: I, n = 145 (68%); II, n = 47 (22%); III/IV, n = 20 (9%); FIGO grade: 1, 127 (60%); 2, 66 (31%); 3, 17 (8%); unknown, 2 (1%). One hundred twenty-eight (60%) had endometriosis; 75 (35%), synchronous endometrioid endometrial cancer (80%, IA); 101 (48%), complete surgical staging; 8 (5%), positive pelvic lymph nodes (LNs); 6 (4%), positive para-aortic LNs; 176 (97%), complete gross resection; 123 (60%), postoperative chemotherapy; 56(28%), no additional treatment. Five-year PFS, 83% (95% confidence interval [CI]: 76.6%-87.8%); 5-year overall survival (OS), 92.7% (95% CI: 87.7%-95.8%). Age, stage, and surgical staging were associated with improved 5-year PFS, and younger age at diagnosis with improved 5-year OS (p < 0.001). Chemotherapy did not improve 5-year PFS in IA/IB versus observation, but improved survival in IC (hazard ratio [HR]: 1.01, 95% CI: 0.22-4.59, p = 0.99; HR: 0.17, 95% CI: 0.04-0.7, p = 0.006). CONCLUSIONS: Age, stage, and full surgical staging were associated with improved 5-year PFS. Chemotherapy showed no benefit in IA/IB disease.

Sensory disruption and sensory inequities in the Anthropocene.

Anthropogenic disruptions to animal sensory ecology are as old as our species. But what about the effect on human sensory ecology? Human sensory dysfunction is increasing globally at great economic and health costs (mental, physical, and social). Contemporary sensory problems are directly tied to human behavioral changes and activity as well as anthropogenic pollution. The evolutionary sensory ecology and anthropogenic disruptions to three human senses (vision, audition, olfaction) are examined along with the economic and health costs of functionally reduced senses and demographic risk factors contributing to impairment. The primary goals of the paper are (a) to sew an evolutionary and ecological thread through clinical narratives on sensory dysfunction that highlights the impact of the built environment on the senses, and (b) to highlight structural, demographic, and environmental injustices that create sensory inequities in risk and that promote health disparities.

Underrepresentation of Phenotypic Variability of 16p13.11 Microduplication Syndrome Assessed With an Online Self-Phenotyping Tool (Phenotypr): Cohort Study.

BACKGROUND: 16p13.11 microduplication syndrome has a variable presentation and is characterized primarily by neurodevelopmental and physical phenotypes resulting from copy number variation at chromosome 16p13.11. Given its variability, there may be features that have not yet been reported. The goal of this study was to use a patient "self-phenotyping" survey to collect data directly from patients to further characterize the phenotypes of 16p13.11 microduplication syndrome. OBJECTIVE: This study aimed to (1) discover self-identified phenotypes in 16p13.11 microduplication syndrome that have been underrepresented in the scientific literature and (2) demonstrate that self-phenotyping tools are valuable sources of data for the medical and scientific communities. METHODS: As part of a large study to compare and evaluate patient self-phenotyping surveys, an online survey tool, Phenotypr, was developed for patients with rare disorders to self-report phenotypes. Participants with 16p13.11 microduplication syndrome were recruited through the Boston Children's Hospital 16p13.11 Registry. Either the caregiver, parent, or legal guardian of an affected child or the affected person (if aged 18 years or above) completed the survey. Results were securely transferred to a Research Electronic Data Capture database and aggregated for analysis. RESULTS: A total of 19 participants enrolled in the study. Notably, among the 19 participants, aggression and anxiety were mentioned by 3 (16%) and 4 (21%) participants, respectively, which is an increase over the numbers in previously published literature. Additionally, among the 19 participants, 3 (16%) had asthma and 2 (11%) had other immunological disorders, both of which have not been previously described in the syndrome. CONCLUSIONS: Several phenotypes might be underrepresented in the previous 16p13.11 microduplication literature, and new possible phenotypes have been identified. Whenever possible, patients should continue to be referenced as a source of complete phenotyping data on their condition. Self-phenotyping may lead to a better understanding of the prevalence of phenotypes in genetic disorders and may identify previously unreported phenotypes.

Utility of Neonatal Ophthalmologic Examination for Detection of Infectious Etiologies for Symmetric Intrauterine Growth Restriction.

OBJECTIVE: To determine the utility of ophthalmologic examination as part of evaluation for infection in infants with intrauterine growth restriction (IUGR). STUDY DESIGN: This is a single-institution retrospective chart review of neonates diagnosed with symmetric IUGR or small for gestational age (SGA) who underwent complete ophthalmologic consultation to assess for intraocular findings suggestive of congenital infection. Data collected included other factors that may cause IUGR, findings of general and ophthalmologic examinations, and results of investigation for intrauterine infection. Cost minimization analysis was also performed. RESULTS: One hundred neonates met the study's inclusion criteria (IUGR, n = 24; SGA, n = 45; IUGR and SGA, n = 31). The mean gestational age at birth was 34.6 ± 3.0 weeks, and the mean birth weight was 1691 ± 530 g; 74% had an identifiable risk factor for IUGR and 84 patients underwent investigation for intrauterine infection. Two of the 73 patients who had urine culture for cytomegalovirus (CMV) were positive (1 of whom had systemic signs of severe congenital infection without eye involvement, the other who had no clinical signs of congenital CMV); evaluations for infection were negative otherwise. No patients had any ophthalmologic signs of congenital infection. CONCLUSIONS: Current literature suggests that routine evaluation of neonates with isolated IUGR for congenital infection may be low-yield and not cost-effective. Our study found that routine ophthalmologic evaluation in newborns with symmetric IUGR who have no systemic signs of intrauterine infection is of little value.

Minimally invasive surgery versus laparotomy for radical hysterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: To compare oncologic and perioperative outcomes in patients who underwent minimally invasive surgery (MIS) compared to laparotomy for newly diagnosed early-stage cervical carcinoma. METHODS: We retrospectively identified patients who underwent radical hysterectomy for stage IA1 with lymphovascular invasion (LVI), IA2, or IB1 cervical carcinoma at our institution from 1/2007-12/2017. Clinicopathologic characteristics and surgical and oncologic survival outcomes were compared using appropriate statistical testing. Multivariable Cox regression analysis was used to control for potential confounders. RESULTS: We identified 196 evaluable cases-117 MIS (106 robotic [90.6%]) and 79 laparotomy cases. Cohorts had similar age, BMI, substage, histologic subtype, clinical and pathologic tumor size, positive margins, and presence of LVI. The MIS group had more cases with no residual tumor in the hysterectomy (24.8% vs. 10.1%, P = 0.01). The laparotomy group had more cases with positive nodes (29.1% vs. 17.1%, P = 0.046) and more patients who received adjuvant therapy (53.2% vs. 33.3%, P = 0.006). Median follow-up was ~4 years. Five-year disease-free survival (DFS) rates were 87.0% in the MIS group and 86.6% in the laparotomy group (P = 0.92); 5-year disease-specific survival (DSS) rates were 96.5% and 93.9%, respectively (P = 0.93); and 5-year overall survival (OS) rates were 96.5% and 87.4%, respectively (P = 0.15). MIS was not associated with DFS, DSS, or OS on multivariable regression analysis. The rate of postoperative complications was significantly lower in the MIS cohort (11.1% vs. 20.3%; P = 0.04). CONCLUSIONS: MIS radical hysterectomy for cervical carcinoma did not confer worse oncologic outcomes in our single-center and concurrent series of patients with early-stage cervical carcinoma.

Field-testing olfactory ability to understand human olfactory ecology.

OBJECTIVES: We know little about human olfactory ability in natural settings because current knowledge derives from lab-based studies using nonrepresentative samples of convenience. The primary objective was to use a validated lab tool, the five-item odor identification test, to assess variation in olfactory ability in different environments. METHODS: Using the five-item test, we conducted two repeated measures experiments that assessed participant ability to correctly identify an odor source in different odor environments. We also examined consistency in odor labelling due to documented potential bias from idiosyncrasies in odor terms. RESULTS: We found no variation in olfactory ability due to environment, but this may be due to methodological biases. First, subjective bias results from idiosyncratic differences in participant labelling and researcher coding of answer correctness. Second, better ability to learn odors may provide an advantage to women. Third, reducing positive female learning bias by analyzing consistency in response (regardless of correct odor source identification) results in no sex differences but fails to assess the functional aspect of olfactory ability (naming the correct odor source). Fourth, functional olfactory ability is significantly better in women, especially in food-rich odor environments. CONCLUSIONS: Environment was not a significant factor in olfactory ability in this study but that result may be confounded by methodological biases. We do not recommend odor identification as a field tool. Functional olfactory ability exhibits a sex-based pattern but consistency in recognizing the same odor does not. Food-rich odors may enhance olfactory ability in females. We discuss evolutionary and ecological implications of superior female functional olfactory ability relative to food foraging activity.

Investigation of Geographic and Macrolevel Variations in LGBTQ Patient Experiences: Longitudinal Social Media Analysis.

BACKGROUND: Discrimination in the health care system contributes to worse health outcomes among lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients. OBJECTIVE: The aim of this study is to examine disparities in patient experience among LGBTQ persons using social media data. METHODS: We collected patient experience data from Twitter from February 2013 to February 2017 in the United States. We compared the sentiment of patient experience tweets between Twitter users who self-identified as LGBTQ and non-LGBTQ. The effect of state-level partisan identity on patient experience sentiment and differences between LGBTQ users and non-LGBTQ users were analyzed. RESULTS: We observed lower (more negative) patient experience sentiment among 13,689 LGBTQ users compared to 1,362,395 non-LGBTQ users. Increasing state-level liberal political identification was associated with higher patient experience sentiment among all users but had stronger effects for LGBTQ users. CONCLUSIONS: Our findings highlight that social media data can yield insights about patient experience for LGBTQ persons and suggest that a state-level sociopolitical environment influences patient experience for this group. Efforts are needed to reduce disparities in patient care for LGBTQ persons while taking into context the effect of the political climate on these inequities.

How electrically evoked compound action potentials in chronically implanted guinea pigs relate to auditory nerve health and electrode impedance.

This study examined how multiple measures based on the electrically evoked compound action potential (ECAP) amplitude-growth functions (AGFs) were related to estimates of neural [spiral ganglion neuron (SGN) density and cell size] and electrode impedance measures in 34 specific pathogen free pigmented guinea pigs that were chronically implanted (4.9-15.4 months) with a cochlear implant electrode array. Two interphase gaps (IPGs) were used for the biphasic pulses and the effect of the IPG on each ECAP measure was measured ("IPG effect"). When using a stimulus with a constant IPG, SGN density was related to the across-subject variance in ECAP AGF linear slope, peak amplitude, and N1 latency. The SGN density values also help to explain a significant proportion of variance in the IPG effect for AGF linear slope and peak amplitude measures. Regression modeling revealed that SGN density was the primary dependent variable contributing to across-subject variance for ECAP measures; SGN cell size did not significantly improve the fitting of the model. Results showed that simple impedance measures were weakly related to most ECAP measures but did not typically improve the fit of the regression model.

Body Composition Is Associated With Physical Performance in Individuals With Knee Osteoarthritis.

BACKGROUND/OBJECTIVE: The purpose of this cross-sectional study was to determine associations between body composition, self-reported function, and physical performance after accounting for body mass index (BMI) in individuals with knee osteoarthritis. METHODS: Percent fat and lean mass were evaluated using dual energy x-ray absorptiometry. Self-reported function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function subscale) and physical performance (20-m walk, chair stand, and stair climb) were collected on 46 adults (30% male; BMI, 29.6 ± 3.8 kg/m) with radiographically defined knee osteoarthritis (Kellgren-Lawrence grades 2-4). Linear regressions determined the unique association between WOMAC and physical performance explained individually by percent fat and lean mass ([INCREMENT]R) after accounting for BMI. RESULTS: Lower percent fat mass significantly associated with better physical performance after accounting for BMI (20-m walk: [INCREMENT]R = 0.10, p = 0.03; chair stand: [INCREMENT]R = 0.16, p = 0.01; stair climb: [INCREMENT]R = 0.11, p = 0.03). Higher percent lean mass significantly associated with better chair stand ([INCREMENT]R = 0.09, p = 0.04) but not 20-m walk or stair climb ([INCREMENT]R range, 0.04-0.07, p > 0.05). After accounting for BMI, neither percent fat nor lean mass associated with WOMAC. Body mass index did not significantly associate with WOMAC or physical performance. CONCLUSIONS: Lower percent fat and higher percent lean mass associated with better physical performance after accounting for BMI. Body composition and BMI may be used together in the future to more comprehensively understand the association between obesity and disability.

Efflux Pumps in Chromobacterium Species Increase Antibiotic Resistance and Promote Survival in a Coculture Competition Model.

Members of the Chromobacterium genus include opportunistic but often-fatal pathogens and soil saprophytes with highly versatile metabolic capabilities. In previous studies of Chromobacterium subtsugae (formerly C. violaceum) strain CV017, we identified a resistance nodulation division (RND)-family efflux pump (CdeAB-OprM) that confers resistance to several antibiotics, including the bactobolin antibiotic produced by the soil saprophyte Burkholderia thailandensis Here, we show the cdeAB-oprM genes increase C. subtsugae survival in a laboratory competition model with B. thailandensis We also demonstrate that adding sublethal bactobolin concentrations to the coculture increases C. subtsugae survival, but this effect is not through CdeAB-OprM. Instead, the increased survival requires a second, previously unreported pump we call CseAB-OprN. We show that in cells exposed to sublethal bactobolin concentrations, the cseAB-oprN genes are transcriptionally induced, and this corresponds to an increase in bactobolin resistance. Induction of this pump is highly specific and sensitive to bactobolin, while CdeAB-OprM appears to have a broader range of antibiotic recognition. We examine the distribution of cseAB-oprN and cdeAB-oprM gene clusters in members of the Chromobacterium genus and find the cseAB-oprN genes are limited to the nonpathogenic C. subtsugae strains, whereas the cdeAB-oprM genes are more widely distributed among members of the Chromobacterium genus. Our results provide new information on the antibiotic resistance mechanisms of Chromobacterium species and highlight the importance of efflux pumps for saprophytic bacteria existing in multispecies communities.IMPORTANCE Antibiotic efflux pumps are best known for increasing antibiotic resistance of pathogens; however, the role of these pumps in saprophytes is much less well defined. This study describes two predicted efflux pump gene clusters in the Chromobacterium genus, which is comprised of both nonpathogenic saprophytes and species that cause highly fatal human infections. One of the predicted efflux pump clusters is present in every member of the Chromobacterium genus and increases resistance to a broad range of antibiotics. The other gene cluster has more narrow antibiotic specificity and is found only in Chromobacterium subtsugae, a subset of entirely nonpathogenic species. We demonstrate the role of both pumps in increasing antibiotic resistance and demonstrate the importance of efflux-dependent resistance induction for C. subtsugae survival in a dual-species competition model. These results have implications for managing antibiotic-resistant Chromobacterium infections and for understanding the evolution of efflux pumps outside the host.

Can the Red Reflex Test Detect Unequal Refractive Error?

OBJECTIVE: To determine the accuracy of the red reflex test in the detection of anisometropia. STUDY DESIGN: This prospective, single-masked study enrolled new patients younger than the age of 18 years who had not undergone pharmacologic pupillary dilation. A fellow who was masked to all clinical information illuminated both eyes with a direct ophthalmoscope in a darkened room from a distance of 1 m, assessing whether the red reflex between the 2 eyes was symmetric or asymmetric. The patient was then dilated, and cylcoplegic refraction was performed by an attending pediatric ophthalmologist. Exclusion criteria included the presence of strabismus, anisocoria, previous intraocular surgery, media opacity, leukocoria, or nystagmus. Sensitivity was compared with a null hypothesized value of 50% using a 1-sided binomial test. RESULTS: Ninety-two patients with a mean age of 7.3 years (range 3 months to 16 years) were enrolled. With spherical anisometropia greater than or equal to 0.125 diopters, the sensitivity of the red reflex test was 90.6% and the specificity was 58.3%. With cylindrical anisometropia greater than or equal to 0.25 diopters, the sensitivity of the red reflex test was 81.3% and the specificity was 70%. Anisometropia greater than 1.5 diopters in spherical equivalent (4 patients, range -10.625 to -2.625) or cylinder (3 patients, range 1.75-2.25) was accurately detected by red reflex testing in each case. CONCLUSIONS: The red reflex test can be an accurate screening tool to detect anisometropia when performed by an ophthalmologist.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.