Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Atlas-scale single-cell chromatin accessibility using nanowell-based combinatorial indexing.

Here we present advancements in single-cell combinatorial indexed Assay for Transposase Accessible Chromatin (sciATAC) to measure chromatin accessibility that leverage nanowell chips to achieve atlas-scale cell throughput (>105 cells) at low cost. The platform leverages the core of the sciATAC workflow where multiple indexed tagmentation reactions are performed, followed by pooling and distribution to a second set of reaction wells for polymerase chain reaction (PCR)-based indexing. In this work, we instead leverage a chip containing 5184 nanowells at the PCR stage of indexing, enabling a 52-fold improvement in scale and reduction in per-cell preparation costs. We detail three variants that balance cell throughput and depth of coverage, and apply these methods to banked mouse brain tissue, producing maps of cell types as well as neuronal subtypes that include integration with existing single-cell Assay for Transposase Accessible Chromatin (scATAC) and scRNA-seq data sets. Our optimized workflow achieves a high fraction of reads that fall within called peaks (>80%) and low cell doublet rates. The high cell coverage technique produces high unique reads per cell, while retaining high enrichment for open chromatin regions, enabling the assessment of >70,000 unique accessible loci on average for each cell profiled. When compared to current methods in the field, our technique provides similar or superior per-cell information with very low levels of cell-to-cell cross talk, and achieves this at a cost point much lower than existing assays.

Comparison of Two Place-Based Mapping Procedures on Masked Sentence Recognition as a Function of Electrode Array Angular Insertion Depth and Presence of Acoustic Low-Frequency Information: A Simulation Study.

INTRODUCTION: Cochlear implant (CI) and electric-acoustic stimulation (EAS) users may experience better performance with maps that align the electric filter frequencies to the cochlear place frequencies, known as place-based maps, than with maps that present spectrally shifted information. Individual place-based mapping procedures differ in the frequency content that is aligned to cochlear tonotopicity versus discarded or spectrally shifted. The performance benefit with different place-based maps may vary due to individual differences in angular insertion depth (AID) of the electrode array and whether functional acoustic low-frequency information is available in the implanted ear. The present study compared masked speech recognition with two types of place-based maps as a function of AID and presence of acoustic low-frequency information. METHODS: Sixty adults with normal hearing listened acutely to CI or EAS simulations of two types of place-based maps for one of three cases of electrode arrays at shallow AIDs. The strict place-based (Strict-PB) map aligned the low- and mid-frequency information to cochlear tonotopicity and discarded information below the frequency associated with the most apical electrode contact. The alternative place-based map (LFshift-PB) aligned the mid-frequency information to cochlear tonotopicity and provided more of the speech spectrum by compressing low-frequency information on the apical electrode contacts (i.e., <1 kHz). Three actual cases of a 12-channel, 24-mm electrode array were simulated by assigning the carrier frequency for an individual channel as the cochlear place frequency of the associated electrode contact. The AID and cochlear place frequency for the most apical electrode contact were 460° and 498 Hz for case 1, 389° and 728 Hz for case 2, and 335° and 987 Hz for case 3, respectively. RESULTS: Generally, better performance was observed with the Strict-PB maps for cases 1 and 2, where mismatches were 2-4 octaves for the most apical channel with the LFshift-PB map. Similar performance was observed between maps for case 3. For the CI simulations, performance with the Strict-PB map declined with decreases in AID, while performance with the LFshift-PB map remained stable across cases. For the EAS simulations, performance with the Strict-PB map remained stable across cases, while performance with the LFshift-PB map improved with decreases in AID. CONCLUSIONS: Listeners demonstrated differences with the Strict-PB versus LFshift-PB maps as a function of AID and whether acoustic low-frequency information was available (CI vs. EAS). These data support the use of the Strict-PB mapping procedure for AIDs ≥335°, though further study including time for acclimatization in CI and EAS users is warranted.

Influence of Postponed Follow-Up after Cochlear Implant Activation during the COVID-19 Pandemic on Aided Sound Field Detection and Speech Recognition.

INTRODUCTION: The objective of this study was to assess the influence of postponing the first post-activation follow-up due to the COVID-19 pandemic on the aided sound field detection thresholds and speech recognition of cochlear implant (CI) users. METHODS: A retrospective review was performed at a tertiary referral center. Two groups of adult CI recipients were evaluated: (1) patients whose first post-activation follow-up was postponed due to COVID-19 closures (postponed group; n = 10) and (2) a control group that attended recommended post-activation follow-ups prior to the COVID-19 pandemic (control group; n = 18). For both groups, electric thresholds were estimated at initial activation based on comfort levels and were measured behaviorally at subsequent post-activation follow-ups. For the control group, behavioral thresholds were measured at the 1-month follow-up. For the postponed group, behavioral thresholds were not measured until 3 months post-activation since the 1-month follow-up was postponed. The aided pure-tone average (PTA) and word recognition results were compared between groups at the 3-month follow-up and at an interim visit 2-9 weeks later. RESULTS: At the 3-month follow-up, the postponed group had significantly poorer word recognition (23 vs. 42%, p = 0.027) and aided PTA (42 vs. 37 dB HL, p = 0.041) than the control group. No significant differences were observed between 3-month data from the control group and interim data from the postponed group. CONCLUSIONS: The postponed follow-up after CI activation was associated with poorer outcomes, both in terms of speech recognition and aided audibility. However, these detrimental effects were reversed following provision of an individualized map, with behaviorally measured electric threshold and comfort levels. While adult CI recipients demonstrate an improvement in speech recognition with estimated electric thresholds, the present results suggest that behavioral mapping within the initial weeks of device use may support optimal outcomes.

Epigenetic maintenance of topological domains in the highly rearranged gibbon genome.

The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here, we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400-600 kb) TADs in human and other mammalian species. The colocalization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Last, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.

Violence Inflicted on Latina Transgender Women Living with HIV: Rates and Associated Factors by Perpetrator Type.

Many transgender individuals report violence directed against them. This study examined violence inflicted on transgender Latinas with HIV by primary partners, sexual partners and acquaintances/strangers. Logistic regression was used for analysis. 150 transgender Latinas were recruited. Rates of violence from different perpetrator types were 47-50%. For violence by primary partners, social support from cisgender people was associated with a lower likelihood of violence (AOR 0.56; CI 0.32, 0.98; p < 0.05). For violence by sexual partners, a history of childhood sexual abuse was associated with a higher likelihood of violence (AOR 2.64; CI 1.10, 6.34; p < 0.05). For violence by acquaintances/strangers, discrimination was associated with a higher likelihood of violence (AOR 2.84; CI 1.16, 6.94; p < 0.05) and social support from cisgender people with a lower likelihood (AOR 0.58; CI 0.37, 0.92; p < 0.05). Interventions are needed at individual, institutional and systemic levels to eradicate such violence.

RESUMEN: Muchas personas transgénero reportan violencia dirigida contra ellas. Este estudio examinó la violencia infligida a las mujeres transgénero latinas con VIH por sus parejas principales, parejas sexuales y conocidos/extraños. Se usó regresión logística para el análisis. 150 latinas transgénero fueron reclutadas. Las tasas de violencia de diferentes tipos de perpetradores fueron del 47­50%. Para la violencia por parte de parejas principales, el apoyo social de personas no transgénero se asoció con una menor probabilidad de violencia (AOR 0.56; CI 0.32, 0.98; p < 0.05). Para la violencia por parte de parejas sexuales, un historial de abuso sexual durante la niñez se asoció con una mayor probabilidad de violencia (AOR 2.64; CI 1.10, 6.34; p < 0.05). Para la violencia por parte de conocidos/extraños, la discriminación se asoció con una mayor probabilidad de violencia (AOR 2.84; CI 1.16, 6.94; p < 0.05) y el apoyo social de no-transgéneros con una menor probabilidad (AOR 0.58; CI 0.37, 0.92; p < 0.05). Se necesitan intervenciones a nivel individual, institucional y sistémico para erradicar dicha violencia.

Relationship Between Electrocochleography, Angular Insertion Depth, and Cochlear Implant Speech Perception Outcomes.

OBJECTIVES: Electrocochleography (ECochG), obtained before the insertion of a cochlear implant (CI) array, provides a measure of residual cochlear function that accounts for a substantial portion of variability in postoperative speech perception outcomes in adults. It is postulated that subsequent surgical factors represent independent sources of variance in outcomes. Prior work has demonstrated a positive correlation between angular insertion depth (AID) of straight arrays and speech perception under the CI-alone condition, with an inverse relationship observed for precurved arrays. The purpose of the present study was to determine the combined effects of ECochG, AID, and array design on speech perception outcomes. DESIGN: Participants were 50 postlingually deafened adult CI recipients who received one of three straight arrays (MED-EL Flex24, MED-EL Flex28, and MED-EL Standard) and two precurved arrays (Cochlear Contour Advance and Advanced Bionics HiFocus Mid-Scala). Residual cochlear function was determined by the intraoperative ECochG total response (TR) measured before array insertion, which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies across the speech spectrum. The AID was then determined with postoperative imaging. Multiple linear regression was used to predict consonant-nucleus-consonant (CNC) word recognition in the CI-alone condition at 6 months postactivation based on AID, TR, and array design. RESULTS: Forty-one participants received a straight array and nine received a precurved array. The AID of the most apical electrode contact ranged from 341° to 696°. The TR measured by ECochG accounted for 43% of variance in speech perception outcomes (p < 0.001). A regression model predicting CNC word scores with the TR tended to underestimate the performance for precurved arrays and deeply inserted straight arrays, and to overestimate the performance for straight arrays with shallower insertions. When combined in a multivariate linear regression, the TR, AID, and array design accounted for 72% of variability in speech perception outcomes (p < 0.001). CONCLUSIONS: A model of speech perception outcomes that incorporates TR, AID, and array design represents an improvement over a model based on TR alone. The success of this model shows that peripheral factors including cochlear health and electrode placement may play a predominant role in speech perception with CIs.

An Annotated Draft Genome for the Andean Bear, Tremarctos ornatus.

The Andean bear is the only extant member of the Tremarctine subfamily and the only extant ursid species to inhabit South America. Here, we present an annotated de novo assembly of a nuclear genome from a captive-born female Andean bear, Mischief, generated using a combination of short and long DNA and RNA reads. Our final assembly has a length of 2.23 Gb, and a scaffold N50 of 21.12 Mb, contig N50 of 23.5 kb, and BUSCO score of 88%. The Andean bear genome will be a useful resource for exploring the complex phylogenetic history of extinct and extant bear species and for future population genetics studies of Andean bears.

Improved genome assembly of American alligator genome reveals conserved architecture of estrogen signaling.

The American alligator, Alligator mississippiensis, like all crocodilians, has temperature-dependent sex determination, in which the sex of an embryo is determined by the incubation temperature of the egg during a critical period of development. The lack of genetic differences between male and female alligators leaves open the question of how the genes responsible for sex determination and differentiation are regulated. Insight into this question comes from the fact that exposing an embryo incubated at male-producing temperature to estrogen causes it to develop ovaries. Because estrogen response elements are known to regulate genes over long distances, a contiguous genome assembly is crucial for predicting and understanding their impact. We present an improved assembly of the American alligator genome, scaffolded with in vitro proximity ligation (Chicago) data. We use this assembly to scaffold two other crocodilian genomes based on synteny. We perform RNA sequencing of tissues from American alligator embryos to find genes that are differentially expressed between embryos incubated at male- versus female-producing temperature. Finally, we use the improved contiguity of our assembly along with the current model of CTCF-mediated chromatin looping to predict regions of the genome likely to contain estrogen-responsive genes. We find that these regions are significantly enriched for genes with female-biased expression in developing gonads after the critical period during which sex is determined by incubation temperature. We thus conclude that estrogen signaling is a major driver of female-biased gene expression in the post-temperature sensitive period gonads.

Frequency-to-Place Mismatch: Characterizing Variability and the Influence on Speech Perception Outcomes in Cochlear Implant Recipients.

OBJECTIVES: The spatial position of a cochlear implant (CI) electrode array affects the spectral cues provided to the recipient. Differences in cochlear size and array length lead to substantial variability in angular insertion depth (AID) across and within array types. For CI-alone users, the variability in AID results in varying degrees of frequency-to-place mismatch between the default electric frequency filters and cochlear place of stimulation. For electric-acoustic stimulation (EAS) users, default electric frequency filters also vary as a function of residual acoustic hearing in the implanted ear. The present study aimed to (1) investigate variability in AID associated with lateral wall arrays, (2) determine the subsequent frequency-to-place mismatch for CI-alone and EAS users mapped with default frequency filters, and (3) examine the relationship between early speech perception for CI-alone users and two aspects of electrode position: frequency-to-place mismatch and angular separation between neighboring contacts, a metric associated with spectral selectivity at the periphery. DESIGN: One hundred one adult CI recipients (111 ears) with MED-EL Flex24 (24 mm), Flex28 (28 mm), and FlexSOFT/Standard (31.5 mm) arrays underwent postoperative computed tomography to determine AID. A subsequent comparison was made between AID, predicted spiral ganglion place frequencies, and the default frequency filters for CI-alone (n = 84) and EAS users (n = 27). For CI-alone users with complete insertions who listened with maps fit with the default frequency filters (n = 48), frequency-to-place mismatch was quantified at 1500 Hz and angular separation between neighboring contacts was determined for electrodes in the 1 to 2 kHz region. Multiple linear regression was used to examine how frequency-to-place mismatch and angular separation of contacts influence consonant-nucleus-consonant (CNC) scores through 6 months postactivation. RESULTS: For CI recipients with complete insertions (n = 106, 95.5%), the AID (mean ± standard deviation) of the most apical contact was 428° ± 34.3° for Flex24 (n = 11), 558° ± 65.4° for Flex28 (n = 48), and 636° ± 42.9° for FlexSOFT/Standard (n = 47) arrays. For CI-alone users, default frequency filters aligned closely with the spiral ganglion map for deeply inserted lateral wall arrays. For EAS users, default frequency filters produced a range of mismatches; absolute deviations of ≤ 6 semitones occurred in only 37% of cases. Participants with shallow insertions and minimal or no residual hearing experienced the greatest mismatch. For CI-alone users, both smaller frequency-to-place mismatch and greater angular separation between contacts were associated with better CNC scores during the initial 6 months of device use. CONCLUSIONS: There is significant variability in frequency-to-place mismatch among CI-alone and EAS users with default frequency filters, even between individuals implanted with the same array. When using default frequency filters, mismatch can be minimized with longer lateral wall arrays and insertion depths that meet the edge frequency associated with residual hearing for CI-alone and EAS users, respectively. Smaller degrees of frequency-to-place mismatch and decreased peripheral masking due to more widely spaced contacts may independently support better speech perception with longer lateral wall arrays in CI-alone users.

Chromosome-scale shotgun assembly using an in vitro method for long-range linkage.

Long-range and highly accurate de novo assembly from short-read data is one of the most pressing challenges in genomics. Recently, it has been shown that read pairs generated by proximity ligation of DNA in chromatin of living tissue can address this problem, dramatically increasing the scaffold contiguity of assemblies. Here, we describe a simpler approach ("Chicago") based on in vitro reconstituted chromatin. We generated two Chicago data sets with human DNA and developed a statistical model and a new software pipeline ("HiRise") that can identify poor quality joins and produce accurate, long-range sequence scaffolds. We used these to construct a highly accurate de novo assembly and scaffolding of a human genome with scaffold N50 of 20 Mbp. We also demonstrated the utility of Chicago for improving existing assemblies by reassembling and scaffolding the genome of the American alligator. With a single library and one lane of Illumina HiSeq sequencing, we increased the scaffold N50 of the American alligator from 508 kbp to 10 Mbp.

The use of PRP injections in the management of knee osteoarthritis.

Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented.

Effects of match play and training on circulating S100B concentration in professional rugby players.

OBJECTIVES: Examine the effects of match play and a season of training on serum S100B concentration in male professional rugby players. To assess the influence of contact play, values were compared with age- and fitness-matched athletes not involved in a contact sport. METHODS: Over a 2-year period, blood samples were collected from 38 players in pre-season, end of season, and post-matches (within 2 h). A control group of rowers (n = 15) was assessed pre- and post-training. RESULTS: S100B concentration changed significantly over a season (χ2(2) = 17.636, p < 0.0005); post-match values were significantly increased from baseline (early season: Z = -3.670, p < 0.0005; late season: Z = -3.408, p = 0.001). There were no significant differences in S100B concentrations between pre-seasons (Z = -1.601, p = 0.109), or between end of season and subsequent pre-season (Z = -0.330, p = 0.741). While comparable at baseline, samples taken from rugby players post-match were significantly increased compared with samples taken from rowers post-exercise (U = 47.0, p < 0.0005). CONCLUSION: Exercise has a significant effect on circulating S100B in elite male athletes, with levels following rugby matches significantly higher than following non-contact sport. This elevation in S100B is temporary, with a return to baseline values after periods without play.

Cochleostomy and facial recess packing alter cochlear implant electrode location in a human cochlea model.

PURPOSE: Determine the effect of cochleostomy and facial recess packing on cochlear implant electrode distance from the modiolus. MATERIALS AND METHODS: Two otolaryngology residents (PGY5 and PGY6) and one attending ear surgeon performed electrode insertions on a human cochlea model using perimodiolar (Cochlear® Slim Modiolar 532™, CI532) and lateral wall electrodes (Cochlear® Slim Straight 522™, CI522) via a cochleostomy. Packing material was simulated using cotton and placed in the cochleostomy and facial recess under the following conditions: 1) inferior to the electrode, 2) superior, 3) both inferior and superior, and 4) no packing. Distance of the electrode from the modiolus at the proximal, middle, and distal basal turn of the cochlea were measured by photomicrograph analysis. RESULTS: Packing superior to the CI532 resulted in a significant decrease in distance from the modiolus at the middle and distal basal turn compared to the inferior condition, with the largest effect in the middle basal turn (0.25 mm vs. 1.92 mm, respectively, p < 0.001). For the CI522, packing superior similarly resulted in decreased distance to the modiolus when compared to the inferior packing condition at the middle and distal basal turn regions, with the largest effect in the middle basal turn (1.25 mm vs. 1.75 mm, respectively, p = 0.002). CONCLUSIONS: Packing of the cochleostomy site and facial recess has a significant effect on electrode distance from the modiolus in the middle and distal basal turn using a model of a human cochlea. Effects were more pronounced when using the perimodiolar (CI532) electrode.

Cochlear implantation for single-sided deafness and tinnitus suppression.

OBJECTIVE: To quantify the potential effectiveness of cochlear implantation for tinnitus suppression in patients with single-sided deafness using the Tinnitus Handicap Inventory. METHODS: The study included 12 patients with unilateral tinnitus who were undergoing cochlear implantation for single-sided deafness. The Tinnitus Handicap Inventory was administered at the patient's cochlear implant candidacy evaluation appointment prior to implantation and every cochlear implant follow-up appointment, except activation, following implantation. Patient demographics and speech recognition scores were also retrospectively recorded using the electronic medical record. RESULTS: A significant reduction was found when comparing Tinnitus Handicap Inventory score preoperatively (61.2±27.5) to the Tinnitus Handicap Inventory score after three months of cochlear implant use (24.6±28.2, p=0.004) and the Tinnitus Handicap Inventory score beyond 6months of CI use (13.3±18.9, p=0.008). Further, 45% of patients reported total tinnitus suppression. Mean CNC word recognition score improved from 2.9% (SD 9.4) pre-operatively to 40.8% (SD 31.7) by 6months post-activation, which was significantly improved from pre-operative scores (p=0.008). CONCLUSION: The present data is in agreement with previously published studies that have shown an improvement in tinnitus following cochlear implantation for the large majority of patients with single-sided deafness.

Improving resident familiarity with the translabyrinthine approach to the internal auditory canal.

OBJECTIVE: To increase otolaryngology resident experience with drilling and dissection of the internal auditory canal (IAC) via a translabyrinthine approach. STUDY DESIGN: Pilot study involving temporal bone education and drilling with completion of pre- and post-drilling surveys. METHODS: Participants observed an educational presentation on IAC anatomy and drilling, followed by manipulation of IAC nerves using a prosected cadaveric temporal bone. Participants then drilled the IAC and identified nerves using temporal bones with previously drilled mastoidectomies and labyrinthectomies. Pre- and post-drilling 5-point Likert-based surveys were completed. RESULTS: 7 participants were included in this study ranging in experience from PGY1 through PGY 5. The median number of times the IAC had been drilled previously was 0. Participants reported statistically significantly improved familiarity with the translabyrinthine approach after the session with median scores increasing from 2 to 3 (p=0.02), and a near-significant increase in familiarity with IAC anatomy with median scores increasing from 3 to 4 (p=0.06). Prior to the session, 71% of participants either disagreed or strongly disagreed that they had an idea of what the procedure would be like in a real operating room, whereas after the session 0% reported disagreement. 100% of participants were very satisfied with the overall experience. CONCLUSIONS: An educational session and temporal bone drilling experience using prosected bones significantly increased the reported familiarity with the translabyrinthine approach. Experiences such as this may enhance resident exposure to advanced lateral skull base approaches in a safe environment, and increase comprehension of the complex anatomic relationships of the IAC.

The Relation between Obesity and Hospital Length of Stay after Elective Lateral Skull Base Surgery: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program.

PURPOSE: Length of stay is a marker of quality and efficiency of health care delivery. The objective of this study was to identify preoperative, intraoperative, and postoperative variables that impact length of stay after lateral skull base surgery. Methods/Procedures: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases from 2009-2012 were analyzed, and patients undergoing elective lateral skull base surgery for benign lesions of cranial nerves were identified. The primary outcome measure of interest was length of hospital stay. Protracted length of stay was defined as ≥75th percentile of length of stay for all patients. The impact of demographic factors, intraoperative variables, and postoperative complications on length of stay was assessed. RESULTS: In total, 252 patients were included. Almost half of the patients (41.2%) were classified as obese (body mass index ≥30). Patients who were obese had significantly longer lengths of stay (5.6 ± 3.9 days) when compared to patients who were not obese (4.6 ± 3.4 days, p = 0.006). Multivariate regression analysis demonstrated that operative time, reoperation within 30 days of initial surgery, and obesity were independent predictors for protracted length of stay. CONCLUSION: National multi-institutional data from the ACS-NSQIP suggest that operative time, reoperation, and obesity are predictors of longer hospital stays after lateral skull base approaches for benign cranial nerve neoplasms.

Calcium Hydroxylapatite Injection for Persistent Velopharyngeal Insufficiency after Sphincter Pharyngoplasty.

BACKGROUND: The role of calcium hydroxylapatite injection pharyngoplasty after failed sphincter pharyngoplasty surgery has not previously been described. We report our technique of injecting calcium hydroxylapatite into the pharyngoplasty site to add bulk to specific areas of the velopharyngeal port. METHODS: A retrospective review of children undergoing calcium hydroxylapatite injection pharyngoplasty for persistent velopharyngeal insufficiency after sphincter pharyngoplasty was performed. Our surgical technique is described. Outcome measures included postoperative perceptual assessment of resonance, improvement in phoneme-specific nasometry scores, and rate of revision surgery. RESULTS: Fourteen patients were included in the study. Improvement in hypernasality on perceptual assessment was noted in the majority of children (85.7%). The rate of achievement of normal resonance on perceptual analysis was 35.7%. A significant decrease in nasometry scores was noted for the following phonemes: /pa/, /sa/, /sha/, and /pi/. There were no intraoperative complications or immediate postoperative complications associated with calcium hydroxylapatite injection. CONCLUSIONS: Our early experience suggests that calcium hydroxylapatite injection after failed sphincter pharyngoplasty is a safe, minimally invasive technique with favorable short-term results.