Transcriptional profiling of retinal astrocytes identifies a specific marker and points to functional specialization.

Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the "classical" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.

Prevalence and burden of migraine in the United States: A systematic review.

BACKGROUND: This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability. METHODS: We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut-scores. RESULTS: Of the 1609 identified records, 26 publications from 11 US population-based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate-to-severe MIDAS disability (Grades III-IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men. CONCLUSION: The prevalence of migraine in the United States has remained stable over the past three decades while migraine-related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation.

Guinea Pig Round Window Membrane Explantation for Ex Vivo Studies.

Efficient and minimally invasive drug delivery to the inner ear is a significant challenge. The round window membrane (RWM), being one of the few entry points to the inner ear, has become a vital focus of investigation. However, due to the complexities of isolating the RWM, our understanding of its pharmacokinetics remains limited. The RWM comprises three distinct layers: the outer epithelium, the middle connective tissue layer, and the inner epithelial layer, each potentially possessing unique delivery properties. Current models for investigating transport across the RWM utilize in vivo animal models or ex vivo RWM models which rely on cell cultures or membrane fragments. Guinea pigs serve as a validated preclinical model for the investigation of drug pharmacokinetics within the inner ear and are an important animal model for the translational development of delivery vehicles to the cochlea. In this study, we describe an approach for explantation of a guinea pig RWM with surrounding cochlear bone for benchtop drug delivery experiments. This method allows for preservation of native RWM architecture and may provide a more realistic representation of barriers to transport than current benchtop models.

A Benchtop Round Window Model for Studying Magnetic Nanoparticle Transport to the Inner Ear.

INTRODUCTION: The round window membrane (RWM) presents a significant barrier to the local application of therapeutics to the inner ear. We demonstrate a benchtop preclinical RWM model and evaluate superparamagnetic iron oxide nanoparticles (SPIONs) as vehicles for magnetically assisted drug delivery. METHODS: Guinea pig RWM explants were inset into a 3D-printed dual chamber benchtop device. Custom-synthesized 7-nm iron core nanoparticles were modified with different polyethylene glycol chains to yield two sizes of SPIONs (NP-PEG600 and NP-PEG3000) and applied to the benchtop model with and without a magnetic field. Histologic analysis of the RWM was performed using transmission electron microscopy (TEM) and confocal microscopy. RESULTS: Over a 4-h period, 19.5 ± 1.9% of NP-PEG3000 and 14.6 ± 1.9% of NP-PEG600 were transported across the guinea pig RWM. The overall transport increased by 1.45× to 28.4 ± 5.8% and 21.0 ± 2.0%, respectively, when a magnetic field was applied. Paraformaldehyde fixation of the RWM decreased transport significantly (NP-PEG3000: 7.6 ± 1.5%; NP-PEG600: 7.0 ± 1.6%). Confocal and electron microscopy analysis demonstrated nanoparticle localization throughout all cellular layers and layer-specific transport characteristics within RWM. CONCLUSION: The guinea pig RWM explant benchtop model allows for targeted and practical investigations of transmembrane transport in the development of nanoparticle drug delivery vehicles. The presence of a magnetic field increases SPION delivery by 45%-50% in a nanoparticle size- and cellular layer-dependent manner. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

National Trends in Orthopaedic Pain Management from 2016 to 2020.

INTRODUCTION: Effective pain management is vital in orthopaedic care, impacting postoperative recovery and patient well-being. This study aimed to discern national and regional pain prescription trends among orthopaedic surgeons through Medicare claims data, using geospatial analysis to ascertain opioid and nonopioid usage patterns across the United States. METHODS: Physician-level Medicare prescription databases from 2016 to 2020 were filtered to orthopaedic surgeons, and medications were categorized into opioids, muscle relaxants, anticonvulsants, and NSAIDs. Patient demographics were extracted from a Medicare provider demographic data set, while county-level socioeconomic metrics were obtained primarily from the American Community Survey. Geospatial analysis was conducted using Geoda software, using Moran I statistic for cluster analysis of pain medication metrics. Statistical trends were analyzed using linear regression, Mann-Whitney U test, and multivariate logistic regression, focusing on prescribing rates and hotspot/coldspot identification. RESULTS: Analysis encompassed 16,505 orthopaedic surgeons, documenting more than 396 million days of pain medication prescriptions: 57.42% NSAIDs, 28.57% opioids, 9.84% anticonvulsants, and 4.17% muscle relaxants. Annually, opioid prescriptions declined by 4.43% ( P < 0.01), while NSAIDs rose by 3.29% ( P < 0.01). Opioid prescriptions dropped by 210.73 days yearly per surgeon ( P < 0.005), whereas NSAIDs increased by 148.86 days ( P < 0.005). Opioid prescriptions were most prevalent in the West Coast and Northern Midwest regions, and NSAID prescriptions were most prevalent in the Northeast and South regions. Regression pinpointed spine as the highest and hand as the lowest predictor for pain prescriptions. DISCUSSION: On average, orthopaedic surgeons markedly decreased both the percentage of patients receiving opioids and the duration of prescription. Simultaneously, the fraction of patients receiving NSAIDs dramatically increased, without change in the average duration of prescription. Opioid hotspots were located in the West Coast, Utah, Colorado, Arizona, Idaho, the Northern Midwest, Vermont, New Hampshire, and Maine. Future directions could include similar examinations using non-Medicare databases.

Cotinuous precision separation of gold using a metal-organic framework/polymer composite.

Critical metals of environmental and economic relevance can be found within complex mixtures, such as mine tailings, electronic waste and wastewater, at trace amounts. Specifically, gold is a critical metal that carries desired redox active properties in various applications, including modern electronics, medicine and chemical catalysis. Here we report the structuring of sub-micron Fe-BTC/PpPDA crystallites into larger 250µm or 500µm granules for continuous packed bed experiments for the precision separation of gold. The Structured Fe-BTC/PpPDA is highly crystalline and porous with a BET surface area of 750 m2g-1. Further, the hybrid nanocomposite material maintains its selectivity for gold ions over common inorganic interferents. The structuring approach reported prevents excessive pressure drop and ensures stability over time and operation in a packed bed column. Further, we demonstrate that the Structured Fe-BTC/PpPDA can concentrate at least 42 wt% of gold under a dynamic continuous flow operation. These findings highlight the potential of Structured Fe-BTC/PpPDA for practical applications in industry, particularly in the selective capture of gold from complex mixtures.

Reliability of Electronic Health Records in Recording Veterans' Tobacco Use Status.

INTRODUCTION: The prevalence of tobacco use in the Veteran population and among Veterans Health Administration patients remains high, resulting in significant health and economic consequences. This problem has generated many tobacco research studies and clinical interventions, which often rely upon tobacco use status data previously recorded in electronic health records (EHR). Therefore, the consistency and reliability of these data are critical. The Veterans Health Administration uses an extensive EHR system where tobacco use status can be documented either as free text (FT) or as health factors (HF). The current literature assessing the reliability of HF and FT data is limited. This analysis evaluated the agreement between HF and FT tobacco use status data. MATERIALS AND METHODS: This retrospective study included Veterans who underwent coronary revascularization and had tobacco use statuses recorded as both HF and FT. These statuses were categorized as "Current," "Former," or "Never." The closest recorded status to the index date (date of revascularization procedure) for each subject in both datasets was chosen, and Cohen's kappa statistic was calculated to measure the agreement between HF and FT. Implausible tobacco use status changes within each dataset were quantified to assess trustworthiness. Agreement between HF and FT data was first measured for all subjects (n = 1,095), which included those who had implausible status changes in either dataset and then measured again for subjects (n = 770) without any implausible status changes in either dataset. This study was exempt from institutional review board review. RESULTS: Overall, 14.3% and 17.7% of all subjects had implausible tobacco use status changes in HF and FT data, respectively. For all subjects (n = 1,095), including those with implausible data, there was "moderate" agreement between HF and FT data (kappa = 0.49; 95% CI, 0.44-0.53). For subjects without implausible data (n = 770), the strength of agreement between HF and FT data was "good" (kappa = 0.64; 95% CI, 0.59-0.69). CONCLUSIONS: Agreement between HF and FT data that document the tobacco use statuses of Veterans varied because of implausible data. HF data had fewer implausible tobacco use statuses, but FT data were recorded more frequently. Although HF and FT data can be reasonably relied upon to determine the tobacco use statuses of Veterans, researchers and clinicians must be aware of implausible data and consider methods to overcome this limitation. Future studies should investigate the ways of improving the consistency of EHR documentation by health care providers and benchmark HF and FT data against a gold standard like biochemical verification to determine accuracy.

Disparities in Access to Robotic Knee Arthroplasty: A Geospatial Analysis.

BACKGROUND: The utilization of robotic knee arthroplasty (RKA) continues to increase across the United States. The aim of this geospatial analysis was to elucidate if RKA is distributed uniformly across the United States or if disparities exist in patient access. METHODS: Publicly available provider-finding functions for 5 major manufacturers of RKA systems were used to obtain the practice locations of surgeons performing RKA along with their associated RKA system manufacturer. The average travel distance for each county to the nearest RKA surgeon was calculated and Moran's index clustering analysis was used to find hotspots and coldspots of RKA access. A logistic regression model was used to identify the predictive odds ratios between robotic hotspots and coldspots with county-level sociodemographic variables. Of the 34,216 currently practicing orthopedic surgeons in 2022, 2,571 have access to robotic assistance for knee arthroplasty. RESULTS: Hotspots of increased travel time were predominantly in West South Central and West North Central census regions. Hotspots were significantly more rural and consisted of predominantly White populations, with lower median income and health insurance coverage. CONCLUSIONS: The results of the current study align with existing literature, demonstrating absolute geographic access disparities for rural and economically disadvantaged populations. Additionally, relative access disparities persist for minority populations and individuals with high comorbidity burdens residing in urban areas.

Estimating the United States Patient Population Size Meeting Audiologic Candidacy for Cochlear Implantation.

OBJECTIVE: This study aimed to estimate the size of the United States candidacy pool meeting expanded Center for Medicare Services criteria for cochlear implantation. STUDY DESIGN: Retrospective cross-sectional. SETTING: Tertiary care center. METHODS: Preimplantation audiometric data from 486 patients seen at a single academic medical center were collected retrospectively and used to generate a predictive model of AzBio score based on audiometric pure tone thresholds. This model was then used to estimate nationally representative cochlear implantation (CI)-candidacy using pure tone averages included in the National Health and Nutrition Examination Survey. Qualitative and quantitative analyses were performed. RESULTS: We find that the estimated prevalence of CI candidacy in individuals 65 years of age or older is expected to more than double with a change in the CI candidacy criteria from ≤40% to ≤60% (from 1.42%, 95% confidence interval [1.33, 1.63] to 3.73% [2.71, 6.56]) on speech testing. We also found the greatest absolute increase in candidacy in the 80+ age group, increasing from 4.14% [3.72, 5.1] of the population meeting the ≤40% criteria to 12.12% [9.19, 18.35] meeting the ≤60% criteria. CONCLUSION: The United States population size meeting expanded CMS audiologic criteria for cochlear implantation is estimated to be 2.5 million adults and 2.1 million age 65 or older. Changing the CI candidacy criteria from ≤40% to ≤60% on CI testing has the greatest effect on the eligible patient population in the >65-year-old age group. The determination of utilization rates in newly eligible patients will require further study.

Cochlear Implant Electrode Array Design and Speech Understanding.

OBJECTIVE: Cochlear implant electrode arrays are categorized based on their design as lateral wall (LW) and perimodiolar (PM) electrode arrays. The objective of this study was to investigate the effect of LW versus PM designs on postoperative speech perception across multiple manufacturers and over long follow-up durations. DESIGN: Retrospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: A total of 478 adult cochlear implant recipients, implanted between the years 1992 and 2017. INTERVENTIONSS: PM versus LW cochlear implants. MAIN OUTCOMES AND MEASURES: Postoperative Consonant-Nucleus-Consonant Word (CNC-w) and Hearing in Noise Test (HINT) scores between 6 months and 5 years. RESULTS: Across 478 patients, approximately one-third received LW (n = 176, 36.8%), whereas 302 patients received a PM array (63.2%). The PM group had higher CNC-w scores from 6 months to 2 years (52 [interquartile range, 38-68] versus 48 [31-62], p = 0.036) and from 2 to 5 years (58 [43-72] versus 48 [33-66], p < 0.001). Multivariable analysis of patient-averaged scores indicated that the PM group had greater improvement from preoperative scores at all time points after the initial 6 months for both CNC-w ( ß = 4.4 [95% confidence interval, 0.6-8.3], p = 0.023) and HINT testing ( ß = 4.5 [95% confidence interval, 0.3-8.7], p = 0.038). CONCLUSIONS: This study indicates that PM electrode arrays are associated with small increases in postoperative speech perception scores, relative to LW arrays, when assessed across manufacturers, over long time durations, and using multiple outcome instruments. These findings may help guide surgeon selection and patient counseling of cochlear implant arrays.

Unknown QRS Morphology Change at Peak Exercise: To Stop or to Continue?

Electrocardiogram changes during stress tests are well standardized and understood. We present and explain a reversible QRS morphology change at peak exercise previously unreported. (Level of Difficulty: Intermediate.).

Astrocytes of the eye and optic nerve: heterogeneous populations with unique functions mediate axonal resilience and vulnerability to glaucoma.

The role of glia, particularly astrocytes, in mediating the central nervous system's response to injury and neurodegenerative disease is an increasingly well studied topic. These cells perform myriad support functions under physiological conditions but undergo behavioral changes - collectively referred to as 'reactivity' - in response to the disruption of neuronal homeostasis from insults, including glaucoma. However, much remains unknown about how reactivity alters disease progression - both beneficially and detrimentally - and whether these changes can be therapeutically modulated to improve outcomes. Historically, the heterogeneity of astrocyte behavior has been insufficiently addressed under both physiological and pathological conditions, resulting in a fragmented and often contradictory understanding of their contributions to health and disease. Thanks to increased focus in recent years, we now know this heterogeneity encompasses both intrinsic variation in physiological function and insult-specific changes that vary between pathologies. Although previous studies demonstrate astrocytic alterations in glaucoma, both in human disease and animal models, generally these findings do not conclusively link astrocytes to causative roles in neuroprotection or degeneration, rather than a subsequent response. Efforts to bolster our understanding by drawing on knowledge of brain astrocytes has been constrained by the primacy in the literature of findings from peri-synaptic 'gray matter' astrocytes, whereas much early degeneration in glaucoma occurs in axonal regions populated by fibrous 'white matter' astrocytes. However, by focusing on findings from astrocytes of the anterior visual pathway - those of the retina, unmyelinated optic nerve head, and myelinated optic nerve regions - we aim to highlight aspects of their behavior that may contribute to axonal vulnerability and glaucoma progression, including roles in mitochondrial turnover and energy provisioning. Furthermore, we posit that astrocytes of the retina, optic nerve head and myelinated optic nerve, although sharing developmental origins and linked by a network of gap junctions, may be best understood as distinct populations residing in markedly different niches with accompanying functional specializations. A closer investigation of their behavioral repertoires may elucidate not only their role in glaucoma, but also mechanisms to induce protective behaviors that can impede the progressive axonal damage and retinal ganglion cell death that drive vision loss in this devastating condition.

Cochlear implantation in unilateral hearing loss: impact of short- to medium-term auditory deprivation.

Introduction: Single sided deafness (SSD) results in profound cortical reorganization that presents clinically with a significant impact on sound localization and speech comprehension. Cochlear implantation (CI) has been approved for two manufacturers' devices in the United States to restore bilateral function in SSD patients with up to 10 years of auditory deprivation. However, there is great variability in auditory performance and it remains unclear how auditory deprivation affects CI benefits within this 10-year window. This prospective study explores how measured auditory performance relates to real-world experience and device use in a cohort of SSD-CI subjects who have between 0 and 10 years of auditory deprivation. Methods: Subjects were assessed before implantation and 3-, 6-, and 12-months post-CI activation via Consonant-Nucleus-Consonant (CNC) word recognition and Arizona Biomedical Institute (AzBio) sentence recognition in varying spatial speech and noise presentations that simulate head shadow, squelch, and summation effects (S0N0, SSSDNNH, SNHNSSD; 0 = front, SSD = impacted ear, NH = normal hearing ear). Patient-centered assessments were performed using Tinnitus Handicap Inventory (THI), Spatial Hearing Questionnaire (SHQ), and Health Utility Index Mark 3 (HUI3). Device use data was acquired from manufacturer software. Further subgroup analysis was performed on data stratified by <5 years and 5-10 years duration of deafness. Results: In the SSD ear, median (IQR) CNC word scores pre-implant and at 3-, 6-, and 12-months post-implant were 0% (0-0%), 24% (8-44%), 28% (4-44%), and 18% (7-33%), respectively. At 6 months post-activation, AzBio scores in S0N0 and SSSDNNH configurations (n = 25) demonstrated statistically significant increases in performance by 5% (p = 0.03) and 20% (p = 0.005), respectively. The median HUI3 score was 0.56 pre-implant, lower than scores for common conditions such as anxiety (0.68) and diabetes (0.77), and comparable to stroke (0.58). Scores improved to 0.83 (0.71-0.91) by 3 months post-activation. These audiologic and subjective benefits were observed even in patients with longer durations of deafness. Discussion: By merging CI-associated changes in objective and patient-centered measures of auditory function, our findings implicate central mechanisms of auditory compensation and adaptation critical in auditory performance after SSD-CI and quantify the extent to which they affect the real-world experience reported by individuals.

Astrocytes of the optic nerve exhibit a region-specific and temporally distinct response to elevated intraocular pressure.

BACKGROUND: The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In both humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. Despite recognizing their importance in the progression of the disease, the reactive response of optic nerve head astrocytes remains poorly understood. METHODS: To determine the global reactive response of ONH astrocytes in glaucoma we studied their transcriptional response to an elevation in IOP induced by the microbead occlusion model. To specifically isolate astrocyte mRNA in vivo from complex tissues, we used the ribotag method to genetically tag ribosomes in astrocytes, restricting analysis to astrocytes and enabling purification of astrocyte-associated mRNA throughout the entire cell, including the fine processes, for bulk RNA-sequencing. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP) as glaucomatous changes manifest differently between the two regions. RESULTS: Astrocytes of the optic nerve exhibited a region-specific and temporally distinct response. Surprisingly, ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experimental period. Energy metabolism, particularly oxidative phosphorylation and mitochondrial protein translation emerged as highly upregulated processes in both ONH and ONP astrocytes, with the former showing additional upregulation in antioxidative capacity and proteolysis. Interestingly, optic nerve astrocytes demonstrated a limited neuroinflammatory response, even when challenged with a more severe elevation in IOP. Lastly, there were a greater number of downregulated processes in both astrocyte populations compared to upregulated processes. CONCLUSION: Our findings demonstrate an essential role for energy metabolism in the response of optic nerve astrocytes to elevated IOP, and contrary to expectations, neuroinflammation had a limited overall role. The transcriptional response profile is supportive of the notion that optic nerve astrocytes have a beneficial role in glaucoma. These previously uncharacterized transcriptional response of optic nerve astrocytes to injury reveal their functional diversity and a greater heterogeneity than previously appreciated.

Rapid isolation of intact retinal astrocytes: a novel approach.

Astrocytes are a major category of glial support cell in the central nervous system and play a variety of essential roles in both health and disease. As our understanding of the diverse functions of these cells improves, the extent of heterogeneity between astrocyte populations has emerged as a key area of research. Retinal astrocytes, which form the direct cellular environment of retinal ganglion cells somas and axons, undergo a reactive response in both human glaucoma and animal models of the disease, yet their contributions to its pathology and progression remain relatively unknown. This gap in knowledge is largely a function of inadequate isolation techniques, driven in part by the sparseness of these cells and their similarities with the more abundant retinal Müller cells. Here, we present a novel method of isolating retinal astrocytes and enriching their RNA, tested in both normal and ocular hypertensive mice, a common model of experimental glaucoma. Our approach combines a novel enzyme assisted microdissection of retinal astrocytes with selective ribosome immunoprecipitation using the Ribotag method. Our microdissection method is rapid and preserves astrocyte morphology, resulting in a brief post-mortem interval and minimizing loss of RNA from distal regions of these cells. Both microdissection and Ribotag immunoprecipitation require a minimum of specialized equipment or reagents, and by using them in conjunction we are able to achieve > 100-fold enrichment of astrocyte RNA.

Astrocytes in the Optic Nerve Are Heterogeneous in Their Reactivity to Glaucomatous Injury.

The optic nerve head is thought to be the site of initial injury to retinal ganglion cell injury in glaucoma. In the initial segment of the optic nerve directly behind the globe, the ganglion cell axons are unmyelinated and come into direct contact to astrocytes, suggesting that astrocytes may play a role in the pathology of glaucoma. As in other parts of the CNS, optic nerve head astrocytes respond to injury by characteristic changes in cell morphology and gene expression profile. Using RNA-sequencing of glaucomatous optic nerve heads, single-cell PCR, and an in-vivo assay, we demonstrate that an up-regulation of astrocytic phagocytosis is an early event after the onset of increased intraocular pressure. We also show that astrocytes in the glial lamina of the optic nerve are apparently functionally heterogeneous. At any time, even in naïve nerves, some of the cells show signs of reactivity-process hypertrophy, high phagocytic activity, and expression of genetic markers of reactivity whereas neighboring cells apparently are inactive. A period of increased intraocular pressure moves more astrocytes towards the reactive phenotype; however, some cells remain unreactive even in glaucomatous nerves.

Longitudinal Auditory Benefit for Elderly Patients After Cochlear Implant for Bilateral Hearing Loss, Including Those Meeting Expanded Centers for Medicare & Medicaid Services Criteria.

OBJECTIVE: To examine the effect of patient age on longitudinal speech understanding outcomes after cochlear implantation (CI) in bilateral hearing loss. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. PATIENTS: One thousand one hundred five adult patients with bilateral hearing loss receiving a unilateral CI between 1987 and 2022InterventionsNone. MAIN OUTCOME MEASURES: Postoperative speech recognition outcomes, including AzBio sentences, consonant-nucleus-consonant word, and Hearing in Noise Test in quiet were analyzed at short-term (<2 yr), medium-term (2-8 y), and long-term (>8 yr) term postoperative intervals. RESULTS: Eighty-six very elderly (>80 yr), 409 elderly (65-80 yr), and 709 nonelderly (18-65 yr) patients were included. Short-term postoperative AzBio scores demonstrated similar magnitude of improvement relative to preoperative scores in the very elderly (47.6, 95% confidence interval [CI], 28.9-66.4), elderly (49.0; 95% CI, 39.2-58.8), and nonelderly (47.9; 95% CI, 35.4-60.4). Scores for those older than 80 years remained stable after 2 years after implant, but in those 80 years or younger, scores continued to improve for up to 8 years (elderly: 6.2 [95% CI, 1.5-12.4]; nonelderly: 9.9 [95% CI, 2.1-17.7]) after implantation. Similar patterns were observed for consonant-nucleus-consonant word scores. Across all age cohorts, patients with preoperative Hearing in Noise Test scores between 40 and 60% had similar scores to those with preoperative scores of less than 40%, at short-term (82.4, 78.9; 95% CI, -23.1 to 10.0), medium-term (77.2, 83.9; 95% CI, -15.4 to 8.2), or long-term (73.4, 71.2; 95% CI, -18.2 to 12.2) follow-up. CONCLUSIONS: Patients older than 80 years gain significant and sustained auditory benefit after CI, including those meeting expanded Centers for Medicare & Medicaid Service criteria for implantation. Patients younger than 80 years demonstrated continued improvement over longer periods than older patients, suggesting a role of central plasticity in mediating CI outcomes as a function of age.

Tunable non-reciprocal waveguide using spoof plasmon polariton coupling to a gaseous magnetoplasmon.

We experimentally demonstrate non-reciprocal (one-way) waveguiding in a microstrip transmission line tailored to support the propagation of spoof plasmon polaritons. Time-reversal symmetry is broken by coupling the microstrip fields to a magnetized gaseous plasma discharge column thereby exciting non-reciprocal magnetoplasmons at the interface between the plasma and a surrounding quartz envelope. The magnetic bias introduces asymmetry in the dispersion of the surface plasmon polaritons at the gaseous plasma-dielectric interface, resulting in a breaking of the bidirectionality of the wave propagation in the microstrip. The isolation generated at conditions of modest magnetic bias is measured to be nearly 60 dB, and tunable by varying the plasma density through the voltage applied to the discharge. The advantage of using magnetized gaseous plasmas to produce this unidirectional waveguide structure is that it can be turned on or off at rates limited by the production and recombination of the plasma.

Anti-inflammatory activities of two new deoxygenated N-acetyl glucosamines in lipopolysaccharide-activated mouse macrophage RAW264.7 cells.

Background: Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements. Objective: We investigated the anti-inflammatory properties of two synthesized derivatives of N-acetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Methods: Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1ß, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively. Results: Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF α and IL-1ß expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. Conclusion: BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.

Cochlear Implant Revisions Over Three Decades of Experience.

IMPORTANCE: The indications, technology, and surgical technique for cochlear implantation have evolved over the last three decades. Understanding the risk of cochlear implant revision (CIR) is important for patient counseling. OBJECTIVE: The objective of this study was to analyze the rates, indications, and audiologic outcomes for CIR over three decades of experience at a single academic medical center. DESIGN: A retrospective chart review was performed at a single academic medical center for individuals who underwent cochlear implantation between 1985 and 2022. SETTING: Single academic medical center. PARTICIPANTS: Three thousand twenty-five individuals who underwent 3,934 cochlear implant operations from 1985 to 2022. EXPOSURE: Cochlear implantation. MAIN OUTCOMES AND MEASURES: Rates, indications, risk factors, and audiologic outcomes for CIR. RESULTS: There were 276 cases of CIR after primary implantation and an overall revision rate of 7.6% (95% confidence interval, 6.8-8.5%) over 37 years of follow-up with many cases of CIR secondary to Advanced Bionics vendor B and field action failure groups. CIR rates increased sharply through the early and mid-2000s and have since remained stable. Hard or soft device failure was the most common indication for CIR, accounting for 73% of cases. Pediatric patient status and previous CIR were associated with an increased risk of CIR. Audiologic outcomes after CIR were similar to those before device failure. CONCLUSIONS AND RELEVANCE: CIR remains a common procedure most often performed for device failure. Pediatric patients and those who have undergone previous CIR are at the highest risk for future CIR. Audiologic outcomes remain stable after CIR, and these data will help providers counsel patients at the risk of future CIR and understand the risk factors associated with CIR.