Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type–specific RNA splicing was discovered and analyzed across tissues within an individual.

Objectives/Hypothesis To evaluate the presence of postural‐related strain and musculoskeletal discomfort, along with the level of ergonomics training and the availability of ergonomic equipment among otolaryngology surgeons. Study Design Intraoperative observations and survey study. Methods Using the Rapid Entire Body Assessment score system to identify ergonomic hazards, we conducted intraoperative observations assessing operating room personnel during different otolaryngological subspecialty procedures. Based on these findings, otolaryngology surgeons at a single academic institution in the United States were sent a survey that evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education. Results A response rate of 69% was obtained from 70 surgeons, with 72.9% of responding surgeons suffering from some level of back pain, with cervical spine pain being the most common. Interestingly, residents were equally affected when compared to more senior surgeons both in subjective survey reports and from observational risk analysis. Furthermore, 43.8% of surgeons reported suffering from the highest level of pain when standing, whereas only 12.5% experienced pain when sitting. Importantly, 10% stated that pain impacted their work. Only 24% of surgeons had any prior ergonomic training or education. Conclusions Our data suggest that pain and disability induced by poor ergonomics are widespread among the otolaryngology community and confirm that surgeons rarely receive ergonomic training in the surgical context. Additionally, intraoperative observational findings identified that the majority of observed surgeons display poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazard. These data provide guidance for future interventional studies. Level of Evidence NA Laryngoscope, 129:370–376, 2019

In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.

Objective Lack of ergonomic training and poor ergonomic habits during the operation leads to musculoskeletal pain and affects the surgeon’s life outside of work. The objective of the study was to evaluate the severity of ergonomic hazards in the surgical profession across a wide range of surgical subspecialties. We conducted intraoperative observations using Rapid Entire Body Assessment (REBA) score system to identify ergonomic hazards. Additionally, each of the ten surgical subspecialty departments were sent an optional 14 question survey which evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education. A total of 91 surgeons received intraoperative observation and were evaluated on the REBA scale with a minimum score of 0 (low ergonomic risk <3) and a maximum score of 10 (high ergonomic risk 8–10). And a total of 389 surgeons received the survey and 167 (43%) surgeons responded. Of the respondents, 69.7% reported suffering from musculoskeletal pain. Furthermore, 54.9% of the surgeons reported suffering from the highest level of pain when standing during surgery, while only 14.4% experienced pain when sitting. Importantly, 47.7% stated the pain impacted their work, while 59.5% reported pain affecting quality of life outside of work. Only 23.8% of surgeons had any prior ergonomic education. Both our subjective and objective data suggest that pain and disability induced by poor ergonomics are widespread among the surgical community and confirm that surgeons rarely receive ergonomic training. Intraoperative observational findings identified that the majority of observed surgeons displayed poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazards. This data supports the need for a comprehensive ergonomic interventional program for the surgical team and offers potential targets for future intervention.

Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.

Objective: The objective of this study is to build upon previous work validating a tablet-based software to measure cochlear duct length (CDL). Here, we do so by greatly expanding the number of cochleae (n = 166) analyzed, and examined whether computed tomography (CT) slice thickness influences reliability of CDL measurements. Study Design: Retrospective chart review study. Setting: Tertiary referral center. Patients: Eighty-three adult cochlear implant recipients were included in the study. Both cochleae were measured for each patient (n = 166). Interventions: Three raters analyzed the scans of 166 cochleae at 2 different time points. Each rater individually identified anatomical landmarks that delineated the basal turn diameter and width. These coordinates were applied to the elliptic approximation method (ECA) to estimate CDL. The effect of CT scan slice thickness on the measurements was explored. Main Outcome Measures: The primary outcome measure is the strength of the inter- and intra-rater reliability. Results: The mean CDL measured was 32.84 ± 2.03 mm, with a range of 29.03 to 38.07 mm. We observed no significant relationship between slice thickness and CDL measurement (F1,164 = 3.04; p = 0.08). The mean absolute difference in CDL estimations between raters was 1.76 ± 1.24 mm and within raters was 0.263 ± 0.200 mm. The intra-class correlation coefficient (ICC) between raters was 0.54 and ranged from 0.63 to 0.83 within raters. Conclusions: This software produces reliable measurements of CDL between and within raters, regardless of CT scan thickness.

Background Treatment of vestibular schwannomas (VS) remains controversial. Historical surgical series prioritized gross total resections (GTR); however, near total resections (NTR) and intentional subtotal resections (STR) aiming at improving cranial nerve outcomes are becoming more popular. Objective The main purpose of this article is to assess the tumor control and facial nerve outcomes in VS patients treated with STR or NTR. Methods VS patients undergoing STR or NTR at our institution between 1984 and 2016 were retrospectively reviewed. Patient demographics, extent of tumor resection, facial nerve injury, tumor recurrence, and need for Gamma Knife radiosurgery were analyzed. Facial nerve outcomes were quantified using House–Brackmann (HB) scores. Tumor regrowth was defined by the San Francisco criteria. Results Four-hundred fifty-seven VS resections were performed in a 32-year period. Sixty cases met inclusion criteria. The mean (range) follow-up duration was 30.9 (12–103) months. The STR cohort (n = 33) demonstrated regrowth in 12 patients (36.3%) at an average of 23.6 months. The NTR cohort (n = 27) did not experience tumor recurrence. Risk of tumor recurrence was positively correlated with preoperative tumor size (p = 0.002), size of residual tumor (p < 0.001), and STR (p < 0.001). Facial nerve outcomes of HB1–2 were observed in the majority of patients in both cohorts (74.1% NTR, 56% STR), though NTR was associated with a higher likelihood of facial nerve recovery (p = 0.003). Conclusion GTR remains the gold standard as long as facial nerve outcomes remain acceptable. NTR achieved superior tumor control and higher likelihood of facial nerve recovery compared with STR.

The inner ear houses the sensory epithelium responsible for vestibular and auditory function. The sensory epithelia are driven by pressure and vibration of the fluid filled structures in which they are embedded so that understanding the homeostatic mechanisms regulating fluid dynamics within these structures is critical to understanding function at the systems level. Additionally, there is a growing need for drug delivery to the inner ear for preventive and restorative treatments to the pathologies associated with hearing and balance dysfunction. We compare drug delivery to neonatal and adult inner ear by injection into the posterior semicircular canal (PSCC) or through the round window membrane (RWM). PSCC injections produced higher levels of dye delivery within the cochlea than did RWM injections. Neonatal PSCC injections produced a gradient in dye distribution; however, adult distributions were relatively uniform. RWM injections resulted in an early base to apex gradient that became more uniform over time, post injection. RWM injections lead to higher levels of dye distributions in the brain, likely demonstrating that injections can traverse the cochlea aqueduct. We hypothesize the relative position of the cochlear aqueduct between injection site and cochlea is instrumental in dictating dye distribution within the cochlea. Dye distribution is further compounded by the ability of some chemicals to cross inner ear membranes accessing the blood supply as demonstrated by the rapid distribution of gentamicin-conjugated Texas red (GTTR) throughout the body. These data allow for a direct evaluation of injection mode and age to compare strengths and weaknesses of the two approaches.