Discovery of CRN04894: A Novel Potent Selective MC2R Antagonist.

A novel class of nonpeptide melanocortin type 2 receptor (MC2R) antagonists was discovered through modification of known nonpeptide MC4R ligands. Structure-activity relationship (SAR) studies led to the discovery of 17h (CRN04894), a highly potent and subtype-selective first-in-class MC2R antagonist, which demonstrated remarkable efficacy in a rat model of adrenocorticotrophic hormone (ACTH)-stimulated corticosterone secretion. Oral administration of 17h suppressed ACTH-stimulated corticosterone secretion in a dose-dependent manner at doses ≥3 mg/kg. With its satisfactory pharmaceutical properties, 17h was advanced to Phase 1 human clinical trials in healthy volunteers with the goal of moving into patient trials to evaluate CRN04894 for the treatment of ACTH-dependent diseases, including congenital adrenal hyperplasia (CAH) and Cushing's disease (CD).

Impact of BMI on Dyspnea and Need for Surgical Intervention in Bilateral Vocal Fold Immobility.

OBJECTIVE: Bilateral vocal fold paralysis (BVFP) and posterior glottic stenosis (PGS) are causes of bilateral vocal fold immobility (BVFI) and may cause shortness of breath, stridor, and need for surgical intervention. Although increased body mass index (BMI) is associated with restrictive breathing patterns in patients with normal upper airways, it is unclear how BMI impacts dyspnea and need for surgical intervention in BVFI patients. STUDY DESIGN: Retrospective cohort study. SETTING: Three tertiary academic centers in the United States. METHODS: Demographics, BMI, Dyspnea Index (DI), etiology, presence of tracheostomy and surgical intervention (dilation, tracheostomy, cordotomy, arytenoidectomy, open reconstruction) were collected. Primary outcomes included dyspnea measured by DI and need for surgery to improve airway. Linear regressions were performed to assess continuous outcomes. Mann-Whitney U-test was utilized to assess categorical outcomes. RESULTS: Among 121 patients, 52 presented with BVFP and 69 with PGS. Previous neck surgery was the most common cause of BVFI (40.2%). 44.3% of patients received a tracheostomy. Through multivariate linear regression, increased BMI was significantly associated with increased DI in the entire cohort (ß = .43, P = .016). Increased BMI was also associated with need for any surgical intervention (odds ratio [OR] = 1.07, 95% confidence interval [CI] = [1.01-1.13]) in the overall cohort. When stratifying our data, BMI was only significantly associated with DI in BVFP (ß = .496) and need for surgical intervention in PGS (OR = 1.11, 95% CI = [1.01-1.21]), although a positive trend was seen in all analyses. CONCLUSION: Increased BMI may correlate with worsening dyspnea symptoms and need for surgical intervention in patients with BVFI. Weight-loss-related counseling may benefit symptom management.

Resilient forward osmosis membranes against microplastics fouling enhanced by MWCNTs/UiO-66-NH2 hybrid nanoparticles.

The escalating presence of microplastics (MPs) in wastewater necessitates the investigation of effective tertiary treatment process. Forward osmosis (FO) emerges as an effective non-pressurized membrane process, however, for the effective implementation of FO systems, the development of fouling-resistance FO membranes with high-performance is essential. This study focuses on the integration of MWCNT/UiO-66-NH2 as metal-organic frameworks (MOFs) and multi-wall carbon nanotubes (MWCNT) nanocomposites in thin film composite (TFC) FO membranes, harnessing the synergistic power of hybrid nanoparticles in FO membranes. The results showed that the addition of MWCNT/UiO-66-NH2 in the aqueous phase during polyamide formation changed the polyamide surface structure, and enhanced membranes' hydrophilicity by 44%. The water flux of the modified FO membrane incorporated with 0.1 wt% MWCNTs/UiO-66-NH2 increased by 67% and the reverse salt flux decreased by 22% as in comparison with the control membrane. Moreover, the modified membrane showed improved antifouling behavior against both organic foulant and MPs. The MWCNT/UiO-66-NH2 membrane experienced 35% flux decline while the control membrane experienced 65% flux decline. This proves that the integration of MWCNT/UiO-66-NH2 nanoparticles into TFC FO membranes is a viable approach in creating advanced FO membranes with high antifouling propensity with potential to be expanded further to other membrane applications.

Current Practices in Voice Data Collection and Limitations to Voice AI Research: A National Survey.

INTRODUCTION: Accuracy and validity of voice AI algorithms rely on substantial quality voice data. Although commensurable amounts of voice data are captured daily in voice centers across North America, there is no standardized protocol for acoustic data management, which limits the usability of these datasets for voice artificial intelligence (AI) research. OBJECTIVE: The aim was to capture current practices of voice data collection, storage, analysis, and perceived limitations to collaborative voice research. METHODS: A 30-question online survey was developed with expert guidance from the voicecollab.ai members, an international collaborative of voice AI researchers. The survey was disseminated via REDCap to an estimated 200 practitioners at North American voice centers. Survey questions assessed respondents' current practices in terms of acoustic data collection, storage, and retrieval as well as limitations to collaborative voice research. RESULTS: Seventy-two respondents completed the survey of which 81.7% were laryngologists and 18.3% were speech language pathologists (SLPs). Eighteen percent of respondents reported seeing 40%-60% and 55% reported seeing >60 patients with voice disorders weekly (conservative estimate of over 4000 patients/week). Only 28% of respondents reported utilizing standardized protocols for collection and storage of acoustic data. Although, 87% of respondents conduct voice research, only 38% of respondents report doing so on a multi-institutional level. Perceived limitations to conducting collaborative voice research include lack of standardized methodology for collection (30%) and lack of human resources to prepare and label voice data adequately (55%). CONCLUSION: To conduct large-scale multi-institutional voice research with AI, there is a pertinent need for standardization of acoustic data management, as well as an infrastructure for secure and efficient data sharing. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1333-1339, 2024.

Trends in Response Rate to US News & World Report Best Hospitals Reputation Survey, 2015 to 2023.

Reputation score has been shown to be the strongest predictor of ranking in the US News & World Reports (USNWR) Best Hospitals report. However, the extent to which physicians participate in the underlying USNWR reputation survey is not well-characterized. We conducted a retrospective cross-sectional study of USNWR public methodology reports from 2015 to 2023 to characterize trends in physician response rates by specialty, region, and Doximity membership. Overall response rates declined between 2015 (24.0%) and 2023 (8.9%). In 2023, rates ranged from 4.7% (psychiatry) to 13.9% (otolaryngology). Otolaryngology had the highest response rate among all specialties between 2017 and 2023. Within otolaryngology, both response rates (25.0% to 13.9%) and count (2106 to 1724 physicians) declined between 2015 and 2023. Among Doximity members, response rates were consistently higher for otolaryngologists in the Northeast and Midwest compared to other regions. Though hospital rankings often influence where patients seek care, our findings suggest USNWR reputation scores may not be reliable or representative.

Decision-Making in the Treatment of Idiopathic Subglottic Stenosis: A Survey of Laryngologists.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare condition involving the subglottic larynx and upper trachea, commonly affecting Caucasian females between 30 and 50 years of age. Despite its homogeneous presentation, clinical management for iSGS is yet to be standardized, leading to variability in outcomes between predominant interventions. In recognition of the heterogenicity in iSGS treatment and the need to improve patient outcomes, this study aimed to survey laryngologists to understand the factors influencing clinical decision-making and the incorporation of new treatment modalities for iSGS. METHODS: An online survey was sent to 145 academic laryngologists. The survey assessed respondents' professional backgrounds, experience treating iSGS, treatment algorithms, and how various patient factors affect management. RESULTS: Of the 87 (60%) laryngologists who responded to the survey, the most common clinical assessments were tracheoscopy/bronchoscopy (96.8%) and pulmonary function tests (43.6%). Endoscopic dilation (ED) was the most common primary treatment offered (97.5%): 28.7% of surveyed laryngologists offer SISI as a primary treatment, and 74.7% perform SISI as a planned postoperative treatment. The most common SISI protocol was repeated injections every 4-6 weeks for a series of 1-3 total injections. Notably, 9.2% perform the Maddern procedure. Routine algorithms of care involving surgery were most often based on prior experience and prior patient outcomes (75.9%) and conversations with colleagues (64.4%). Only 31% report using the same protocol learned during their fellowship training. CONCLUSION: This survey highlights significant variation in the management of patients with iSGS. Understanding the factors that influence decision-making may lead to potential standardization in heterogeneous treatment approaches and may improve clinical outcomes. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:865-872, 2024.

Chemical and Genetic Modulation of Complex I of the Electron Transport Chain Enhances the Biotherapeutic Protein Production Capacity of CHO Cells.

Chinese hamster ovary (CHO) cells are the cell line of choice for producing recombinant therapeutic proteins. Despite improvements in production processes, reducing manufacturing costs remains a key driver in the search for more productive clones. To identify media additives capable of increasing protein production, CHOZN® GS-/- cell lines were screened with 1280 small molecules, and two were identified, forskolin and BrdU, which increased productivity by ≥40%. While it is possible to incorporate these small molecules into a commercial-scale process, doing so may not be financially feasible or could raise regulatory concerns related to the purity of the final drug substance. To circumvent these issues, RNA-Seq was performed to identify transcripts which were up- or downregulated upon BrdU treatment. Subsequent Reactome pathway analysis identified the electron transport chain as an affected pathway. CRISPR/Cas9 was utilized to create missense mutations in two independent components of the electron transport chain and the resultant clones partially recapitulated the phenotypes observed upon BrdU treatment, including the productivity of recombinant therapeutic proteins. Together, this work suggests that BrdU can enhance the productivity of CHO cells by modulating cellular energetics and provides a blueprint for translating data from small molecule chemical screens into genetic engineering targets to improve the performance of CHO cells. This could ultimately lead to more productive host cell lines and a more cost-effective method of supplying medication to patients.

Monitoring settling of anaerobic digestates using low-field MRI profiling and NMR relaxometry measurements.

Dewatering of anaerobic digestate from red meat processing was assessed using low field MRI profiling and NMR relaxometry. Samples were flocculated using a cationic flocculant (EM640CT) at dosing range (0 to 1.6% v/v) and monitored during the initial 30 min of settling via MRI profiling to assess changes in water fraction, settling time and initial settling velocity. The profiles showed decreasing settling time and increasing initial settling velocity with increased dosing, while sample porosity was observed to increase up to the optimal dosing point (0.8% v/v). Significant increases in sample variability were observed past this point due to flocculant overdosing. The samples were then analysed in terms of turbidity and NMR relaxometry. Increasing flocculant concentration caused turbidity to decrease from 210 to 13 NTU. The relaxation rate of free water showed a strong positive correlation with turbidity. T2 peaks observed before overdosing could be assigned to different water structures (free, interstitial, vicinal and hydration). An additional T2 population emerged in the T2 distributions at the optimal dosing point. Multivariate exploratory data analysis (MEDA) showed that this T2 population from the solids layer was strongly correlated with the total solids layer height and turbidity of the watery layer. This T2 peak formation may therefore be used to study opaque flocculated solids to monitor for water structures associated with flocculant overdosing. Further studies using this technique will aim to assess the potential of low field T2 relaxometry monitoring inline before mechanical dewatering, to monitor optimal flocculant dosing during continuous operations on systems with high solids concentration.

Prospective >12 Months Outcomes After Vocal Fold Injection Medialization With Silk Microparticle-Hyaluronic Acid Material.

OBJECTIVE: Vocal fold injection medialization (VFIM) is widely used as an initial treatment for unilateral vocal fold paralysis (UVFP). Current practices employ materials that share the limitation of temporary clinical effect from variable resorption rates. A novel silk protein microparticle-hyaluronic acid-based material (silk-HA) has demonstrated cellular infiltration and tissue deposition that may portend a durable medialization effect. We report on ≥12 months outcomes after VFIM with silk-HA. METHODS: Prospective open-label study of patients with UVFP that elected treatment with VFIM with silk-HA. Blinded experts rated laryngeal stroboscopic exams. RESULTS: Seventeen patients with UVFP underwent VFIM with silk-HA. Twelve of the 17 patients have ≥12 months follow-up. Seven patients demonstrated durable treatment benefit ≥12 months after injection with median improvement of 19 (p = 0.0156) in VHI-10. There was no significant change in VHI-10 between 1 and 12 months for these patients. Blinded ratings indicated that 5/7 patients with sustained improvements in VHI-10 exhibited complete or touch glottal closure at 12 months. Two of the seven patients exhibited a small (<1 mm) glottal gap at 12 months. Seven patients experienced initial benefit with later regression 3-4 months after injection. CONCLUSION: VFIM with silk-HA can offer durable improvement in voice-related outcomes for UVFP past 12 months. A subset of patients treated with silk-HA experienced early loss of effect around 3-4 months postinjection. Clinical factors predictive of sustained treatment response to silk-HA injection require further exploration. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.

Social media emotions annotation guide (SMEmo): Development and initial validity.

The proper measurement of emotion is vital to understanding the relationship between emotional expression in social media and other factors, such as online information sharing. This work develops a standardized annotation scheme for quantifying emotions in social media using recent emotion theory and research. Human annotators assessed both social media posts and their own reactions to the posts' content on scales of 0 to 100 for each of 20 (Study 1) and 23 (Study 2) emotions. For Study 1, we analyzed English-language posts from Twitter (N = 244) and YouTube (N = 50). Associations between emotion ratings and text-based measures (LIWC, VADER, EmoLex, NRC-EIL, Emotionality) demonstrated convergent and discriminant validity. In Study 2, we tested an expanded version of the scheme in-country, in-language, on Polish (N = 3648) and Lithuanian (N = 1934) multimedia Facebook posts. While the correlations were lower than with English, patterns of convergent and discriminant validity with EmoLex and NRC-EIL still held. Coder reliability was strong across samples, with intraclass correlations of .80 or higher for 10 different emotions in Study 1 and 16 different emotions in Study 2. This research improves the measurement of emotions in social media to include more dimensions, multimedia, and context compared to prior schemes.

Emotional content and sharing on Facebook: A theory cage match.

While emotional content predicts social media post sharing, competing theories of emotion imply different predictions about how emotional content will influence the virality of social media posts. We tested and compared these theoretical frameworks. Teams of annotators assessed more than 4000 multimedia posts from Polish and Lithuanian Facebook for more than 20 emotions. We found that, drawing on semantic space theory, modeling discrete emotions independently was superior to models examining valence (positive or negative), activation/arousal (high or low), or clusters of emotions and was on par with but had more explanatory power than a seven basic emotion model. Certain discrete emotions were associated with post sharing, including both positive and negative and relatively lower and higher activation/arousal emotions (e.g., amusement, cute/kama muta, anger, and sadness) even when controlling for number of followers, time up, topic, and Facebook angry reactions. These results provide key insights into better understanding of social media post virality.

Porcine vocal fold elasticity evaluation using Brillouin spectroscopy.

Significance: The vocal folds are critically important structures within the larynx which serve the essential functions of supporting the airway, preventing aspiration, and phonation. The vocal fold mucosa has a unique multilayered architecture whose layers have discrete viscoelastic properties facilitating sound production. Perturbations in these properties lead to voice loss. Currently, vocal fold pliability is inferred clinically using laryngeal videostroboscopy and no tools are available for in vivo objective assessment. Aim: The main objective of the present study is to evaluate viability of Brillouin microspectroscopy for differentiating vocal folds' mechanical properties against surrounding tissues. Approach: We used Brillouin microspectroscopy as an emerging optical imaging modality capable of providing information about local viscoelastic properties of tissues in noninvasive and remote manner. Results: Brillouin measurements of the porcine larynx vocal folds were performed. Elasticity-driven Brillouin spectral shifts were recorded and analyzed. Elastic properties, as assessed by Brillouin spectroscopy, strongly correlate with those acquired using classical elasticity measurements. Conclusions: These results demonstrate the feasibility of Brillouin spectroscopy for vocal fold imaging. With more extensive research, this technique may provide noninvasive objective assessment of vocal fold mucosal pliability toward objective diagnoses and more targeted treatments.

A Machine-Learning Algorithm for the Automated Perceptual Evaluation of Dysphonia Severity.

OBJECTIVES: Auditory-perceptual assessments are the gold standard for assessing voice quality. This project aims to develop a machine-learning model for measuring perceptual dysphonia severity of audio samples consistent with assessments by expert raters. METHODS: The Perceptual Voice Qualities Database samples were used, including sustained vowel and Consensus Auditory-Perceptual Evaluation of Voice sentences, which were previously expertly rated on a 0-100 scale. The OpenSMILE (audEERING GmbH, Gilching, Germany) toolkit was used to extract acoustic (Mel-Frequency Cepstral Coefficient-based, n = 1428) and prosodic (n = 152) features, pitch onsets, and recording duration. We utilized a support vector machine and these features (n = 1582) for automated assessment of dysphonia severity. Recordings were separated into vowels (V) and sentences (S) and features were extracted separately from each. Final voice quality predictions were made by combining the features extracted from the individual components with the whole audio (WA) sample (three file sets: S, V, WA). RESULTS: This algorithm has a high correlation (r = 0.847) with estimates of expert raters. The root mean square error was 13.36. Increasing signal complexity resulted in better estimation of dysphonia, whereby combining the features outperformed WA, S, and V sets individually. CONCLUSION: A novel machine-learning algorithm was able to perform perceptual estimates of dysphonia severity using standardized audio samples on a 100-point scale. This was highly correlated to expert raters. This suggests that ML algorithms could offer an objective method for evaluating voice samples for dysphonia severity.

Use of the first-acquired language modulates pupil size in the processing of island constraint violations.

Introduction: Traditional studies of the population called "heritage speakers" (HS) have treated this group as distinct from other bilingual populations, e.g., simultaneous or late bilinguals (LB), focusing on group differences in the competencies of the first-acquired language or "heritage language". While several explanations have been proposed for such differences (e.g., incomplete acquisition, attrition, differential processing mechanisms), few have taken into consideration the individual variation that must occur, due to the fluctuation of factors such as exposure and use that characterize all bilinguals. In addition, few studies have used implicit measures, e.g., psychophysiological methods (ERPs; Eye-tracking), that can circumvent confounding variables such as resorting to conscious metalinguistic knowledge. Methodology: This study uses pupillometry, a method that has only recently been used in psycholinguistic studies of bilingualism, to investigate pupillary responses to three syntactic island constructions in two groups of Spanish/English bilinguals: heritage speakers and late bilinguals. Data were analyzed using generalized additive mixed effects models (GAMMs) and two models were created and compared to one another: one with group (LB/HS) and the other with groups collapsed and current and historical use of Spanish as continuous variables. Results: Results show that group-based models generally yield conflicting results while models collapsing groups and having usage as a predictor yield consistent ones. In particular, current use predicts sensitivity to L1 ungrammaticality across both HS and LB populations. We conclude that individual variation, as measured by use, is a critical factor tha must be taken into account in the description of the language competencies and processing of heritage and late bilinguals alike.

Cannabinoid Use in the Treatment of Laryngeal Dystonia and Vocal Tremor: A Pilot Investigation.

OBJECTIVES/HYPOTHESIS: Laryngeal dystonia and vocal tremor can be debilitating conditions with suboptimal treatment options. Botulinum toxin chemodenervation is typically the first-line treatment and is considered the gold standard. However, patient response to botulinum toxin varies widely. There is anecdotal evidence for the use of cannabinoids in treating laryngeal dystonia with a scarcity of research investigating this potential treatment option. The primary objective of this study is to survey patients with laryngeal dystonia and vocal tremor to gauge how some people are using cannabinoids to treat their condition and to ascertain patient perceptions of cannabinoid effectiveness. STUDY DESIGN: This is a cross-sectional survey study. METHODS: An eight-question anonymous survey was distributed to people with abductor spasmodic dysphonia adductor spasmodic dysphonia, vocal tremor, muscle tension dysphonia, and mixed laryngeal dystonia via the Dysphonia International (formerly National Spasmodic Dysphonia Association) email listserv. RESULTS: 158 responses: 25 males and 133 females, (mean [range] age, 64.9 [22-95] years). 53.8% of participants had tried cannabinoids for the purposes of treating their condition at some point, with 52.9% of this subset actively using cannabis as part of their treatment. Most participants who have used cannabinoids as a treatment rank their effectiveness as somewhat effective (42.4%) or ineffective (45.9%). Participants cited a reduction in voice strain and anxiety as reasons for cannabinoid effectiveness. CONCLUSIONS: People with laryngeal dystonia and/or vocal tremor currently use or have tried using cannabinoids as a treatment for their condition. Cannabinoids were better received as a supplementary treatment than as a stand-alone treatment.

Assessment of Patients Receiving Short-Interval Botulinum Toxin Chemodenervation Treatment for Laryngeal Dystonia and Essential Tremor of the Vocal Tract.

Importance: The gold-standard treatment for laryngeal dystonia (LD) and essential tremor of the vocal tract (ETVT) is botulinum toxin (BoNT) chemodenervation. Although safe and effective, it is not curative, and periodic injections are required. Some medical insurance companies only cover injections at a 3-month interval, though some patients benefit from injections more frequently. Objective: To determine the proportion and characteristics of patients who receive BoNT chemodenervation treatment in intervals shorter than 90 days. Design, Setting, and Participants: This retrospective cohort study across 3 quaternary care neurolaryngology specialty practices in Washington and California recruited patients who underwent at least 4 consecutive laryngeal BoNT injections for LD and/or ETVT in the past 5 years. Data were collected from March through June 2022 and analyzed from June through December 2022. Exposure: Laryngeal BoNT treatment. Main Outcomes and Measures: Biodemographic and clinical variables, injection characteristics, evolution during the 3 interinjection intervals, and lifetime laryngeal BoNT treatment data were collected from patient medical records. Logistic regression was used to assess association to the short-interval outcome, defined as an average injection interval shorter than 90 days. Results: Of 255 patients included from the 3 institutions, 189 (74.1%) were female, and the mean (SD) age was 62.7 (14.3) years. The predominant diagnosis was adductor LD (n = 199 [78.0%]), followed by adductor dystonic voice tremor (n = 26 [10.2%]) and ETVT (n = 13 [5.1%]). Seventy patients (27.5%) received short-interval injections (<90 days). The short-interval group was younger than the long-interval group (≥90 days), with a mean (SD) age of 58.6 (15.5) years and 64.2 (13.5) years, respectively, and a mean difference of -5.7 years (95% CI, -9.6 to -1.8 years). There were no patient-related differences between the short- and long-interval groups in terms of sex, employment status, or diagnosis. Conclusions and Relevance: This cohort study demonstrated that while insurance companies often mandate a 3-month or greater interval for BoNT chemodenervation financial coverage, there is a considerable subset of patients with LD and ETVT who receive short-interval treatment to optimize their vocal function. Short-interval chemodenervation injections demonstrate a similar adverse effect profile and do not appear to predispose to resistance through antibody formation.

Variations in Practices and Preferences of Vocal Fold Injection Materials: A National Survey.

BACKGROUND: Vocal fold injection augmentation (VFI) is a common procedure for the treatment of glottic insufficiency. Material options for VFI and decisions regarding material selection are not standardized and often based on clinician preference. OBJECTIVE: This study aims to understand the variations in provider preference and utilization of injectable materials for VFI. METHODS: A 40-question survey was sent to 158 academic laryngologists. Questions pertained to the type of injectable materials used including brand preferences and rationale for preferences. RESULTS: Ninety-seven of the 158 laryngologists contacted participated in the survey (61.4%). The most frequently used injectable materials were Hyaluronic Acid (HA)-based products. Carboxymethylcellulose (CMC)-based products were preferred for trial augmentation (57.2%), HA-based products were preferred for acute/subacute vocal fold paralysis, presbyphonia, and sulcus/scar (54.2%, 61.5%, 44.7%, 41.7% respectively), and Calcium Hydroxyapatite (CaHA)-based products were preferred for long-term paralysis (28.1%). CMC-based products were discontinued by 21.8% of participants, largely due to quick material resorption. 17.8% of participants discontinued HA-based products largely due to adverse events and 26.0% abandoned CaHA-based products mostly due to inflammatory properties causing vocal fold stiffness and material unpredictability. Over 30% of respondents reported wanting to reinitiate micronized alloderm Cymetra® as an available injectable. CONCLUSION: Our survey demonstrated that there are significant variations in practice and preferences in regard to injectable material selection for VFI. As there is limited data on the direct material comparison, understanding the rationale behind these variations is crucial to guide new providers in material selection and provide information to patients undergoing these procedures. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:1176-1183, 2023.

NMR Surface Relaxivity in a Time-Dependent Porous System.

We demonstrate an unexpected decay-recovery behavior in the time-dependent ^{1}H NMR relaxation times of water confined within a hydrating porous material. Our observations are rationalized by considering the combined effects of decreasing material pore size and evolving interfacial chemistry, which facilitate a transition between surface-limited and diffusion-limited relaxation regimes. Such behavior necessitates the realization of temporally evolving surface relaxivity, highlighting potential caveats in the classical interpretation of NMR relaxation data obtained from complex porous systems.

Detection of honey adulteration using benchtop 1H NMR spectroscopy.

High magnetic field NMR spectroscopy featuring the use of superconducting magnets is a powerful analytical technique for the detection of honey adulteration. Such high field NMR systems are, however, typically housed in specialised laboratories, require cryogenic coolants, and necessitate specialist training to operate. Benchtop NMR spectrometers featuring permanent magnets are, by comparison, significantly cheaper, more mobile and can be operated with minimal expertise. The lower magnetic fields used in such systems, however, result in limited spectral resolution, which diminishes their ability to perform quantitative composition analysis. These limitations may be overcome by implementing a recently developed field-invariant model-based fitting method which is defined by the underlying quantum mechanical properties of the nuclear spin system; this method is applied here to quantify the sugar composition of honey using benchtop 1H NMR (43 MHz) spectroscopy. The detection of adulteration of 26 honey samples with brown rice syrup is quantitatively demonstrated to a minimum adulterant concentration of 5 wt%. Honey adulteration with corn syrup, glucose syrup and wheat syrup was also quantitatively detected using this approach. Our NMR detection of adulteration was shown to be invariant with time over 60 days of storage.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.