Integrins play a role in stress relaxation of perivascular adipose tissue.

Perivascular adipose tissue (PVAT) is known for being anti-contractile in healthy tissues. We discovered a new function of PVAT, the ability to stress relax and maintain a tone in response to a stretch. This is of note because stress relaxation has been attributed to smooth muscle, of which PVAT has none that is organized in a functional layer. We test the hypothesis the interactions of integrins with collagen play a role in stress relaxation. Our model is the thoracic aorta of the male Dahl SS rat. The PVAT and aorta were physically separated for most assays. Results from single nuclei RNA sequencing (snRNAseq) experiments, histochemistry and isometric contractility were also used. Masson Trichrome staining made evident the expression of collagen in PVAT. From snRNA seq experiments of the PVAT, mRNA for multiple collagen and integrin isoforms were detected: the α1 and ß1 integrin were most highly expressed. Pharmacological inhibition of integrin/collagen interaction was effected by the specific α1ß1 distintegrin obtustatin or general integrin inhibitor RGD peptide. RGD peptide but not obtustatin increased the stress relaxation. Cell-cell communication inference identified integrins αv and α5, two major RGD motif containing isoforms, as potential signaling partners of collagens. Collectively, these findings validate that stress relaxation can occur in a non-smooth muscle tissue, doing so in part through integrin-collagen interactions that may not include α1ß1 heterodimers. The importance of this lies in considering PVAT as a vascular layer that possesses mechanical functions.

Innervation of adipocytes is limited in mouse perivascular adipose tissue.

Perivascular adipose tissue (PVAT) regulates vascular tone by releasing anticontractile factors. These anticontractile factors are driven by processes downstream of adipocyte stimulation by norepinephrine; however, whether norepinephrine originates from neural innervation or other sources is unknown. The goal of this study was to test the hypothesis that neurons innervating PVAT provide the adrenergic drive to stimulate adipocytes in aortic and mesenteric perivascular adipose tissue (aPVAT and mPVAT), and white adipose tissue (WAT). Healthy male and female mice (8-13 wk) were used in all experiments. Expression of genes associated with synaptic transmission were quantified by qPCR and adipocyte activity in response to neurotransmitters and neuron depolarization was assessed in AdipoqCre+;GCaMP5g-tdTf/WT mice. Immunostaining, tissue clearing, and transgenic reporter lines were used to assess anatomical relationships between nerves and adipocytes. Although synaptic transmission component genes are expressed in adipose tissues (aPVAT, mPVAT, and WAT), strong nerve stimulation with electrical field stimulation does not significantly trigger calcium responses in adipocytes. However, norepinephrine consistently elicits strong calcium responses in adipocytes from all adipose tissues studied. Bethanechol induces minimal adipocyte responses. Imaging neural innervation using various techniques reveals that nerve fibers primarily run alongside blood vessels and rarely branch into the adipose tissue. Although nerve fibers are associated with blood vessels in adipose tissue, they demonstrate limited anatomical and functional interactions with adjacent adipocytes, challenging the concept of classical innervation. These findings dispute the significant involvement of neural input in regulating PVAT adipocyte function and emphasize alternative mechanisms governing adrenergic-driven anticontractile functions of PVAT.NEW & NOTEWORTHY This study challenges prevailing views on neural innervation in perivascular adipose tissue (PVAT) and its role in adrenergic-driven anticontractile effects on vasculature. Contrary to existing paradigms, limited anatomical and functional connections were found between PVAT nerve fibers and adipocytes, underscoring the importance of exploring alternative mechanistic pathways. Understanding the mechanisms involved in PVAT's anticontractile effects is critical for developing potential therapeutic interventions against dysregulated vascular tone, hypertension, and cardiovascular disease.

Validity of Acoustic Measures Obtained Using Various Recording Methods Including Smartphones With and Without Headset Microphones.

PURPOSE: The goal of this study was to assess various recording methods, including combinations of high- versus low-cost microphones, recording interfaces, and smartphones in terms of their ability to produce commonly used time- and spectral-based voice measurements. METHOD: Twenty-four vowel samples representing a diversity of voice quality deviations and severities from a wide age range of male and female speakers were played via a head-and-thorax model and recorded using a high-cost, research standard GRAS 40AF (GRAS Sound & Vibration) microphone and amplification system. Additional recordings were made using various combinations of headset microphones (AKG C555 L [AKG Acoustics GmbH], Shure SM35-XLR [Shure Incorporated], AVID AE-36 [AVID Products, Inc.]) and audio interfaces (Focusrite Scarlett 2i2 [Focusrite Audio Engineering Ltd.] and PC, Focusrite and smartphone, smartphone via a TRRS adapter), as well as smartphones direct (Apple iPhone 13 Pro, Google Pixel 6) using their built-in microphones. The effect of background noise from four different room conditions was also evaluated. Vowel samples were analyzed for measures of fundamental frequency, perturbation, cepstral peak prominence, and spectral tilt (low vs. high spectral ratio). RESULTS: Results show that a wide variety of recording methods, including smartphones with and without a low-cost headset microphone, can effectively track the wide range of acoustic characteristics in a diverse set of typical and disordered voice samples. Although significant differences in acoustic measures of voice may be observed, the presence of extremely strong correlations (rs > .90) with the recording standard implies a strong linear relationship between the results of different methods that may be used to predict and adjust any observed differences in measurement results. CONCLUSION: Because handheld smartphone distance and positioning may be highly variable when used in actual clinical recording situations, smartphone + a low-cost headset microphone is recommended as an affordable recording method that controls mouth-to-microphone distance and positioning and allows both hands to be available for manipulation of the smartphone device.

A cell atlas of thoracic aortic perivascular adipose tissue: a focus on mechanotransducers.

Perivascular adipose tissue (PVAT) is increasingly recognized for its function in mechanotransduction. However, major gaps remain in our understanding of the cells present in PVAT, as well as how different cells contribute to mechanotransduction. We hypothesized that snRNA-seq would reveal the expression of mechanotransducers, and test one (PIEZO1) to illustrate the expression and functional agreement between single-nuclei RNA sequencing (snRNA-seq) and physiological measurements. To contrast two brown tissues, subscapular brown adipose tissue (BAT) was also examined. We used snRNA-seq of the thoracic aorta PVAT (taPVAT) and BAT from male Dahl salt-sensitive (Dahl SS) rats to investigate cell-specific expression mechanotransducers. Localization and function of the mechanostransducer PIEZO1 were further examined using immunohistochemistry (IHC) and RNAscope, as well as pharmacological antagonism. Approximately 30,000 nuclei from taPVAT and BAT each were characterized by snRNA-seq, identifying eight major cell types expected and one unexpected (nuclei with oligodendrocyte marker genes). Cell-specific differential gene expression analysis between taPVAT and BAT identified up to 511 genes (adipocytes) with many (≥20%) being unique to individual cell types. Piezo1 was the most highly, widely expressed mechanotransducer. The presence of PIEZO1 in the PVAT but not the adventitia was confirmed by RNAscope and IHC in male and female rats. Importantly, antagonism of PIEZO1 by GsMTX4 impaired the PVAT's ability to hold tension. Collectively, the cell compositions of taPVAT and BAT are highly similar, and PIEZO1 is likely a mechanotransducer in taPVAT.NEW & NOTEWORTHY This study describes the atlas of cells in the thoracic aorta perivascular adipose tissue (taPVAT) of the Dahl-SS rat, an important hypertension model. We show that mechanotransducers are widely expressed in these cells. Moreover, PIEZO1 expression is shown to be restricted to the taPVAT and is functionally implicated in stress relaxation. These data will serve as the foundation for future studies investigating the role of taPVAT in this model of hypertensive disease.

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.

How New Developments in Pharmacology Receptor Theory Are Changing (Our Understanding of) Hypertension Therapy.

BACKGROUND: Many hypertension therapeutics were developed prior to major advances in drug receptor theory. Moreover, newer drugs may take advantage of some of the newly understood modalities of receptor function. GOAL: The goal of this review is to provide an up-to-date summary of drug receptor theory. This is followed by a discussion of the drug classes recognized for treating hypertension to which new concepts in receptor theory apply. RESULTS: We raise ideas for mechanisms of potential new antihypertensive drugs and whether they may take advantage of new theories in drug-receptor interaction.

Perivascular Adipose Tissue Remodels Only after Elevation of Blood Pressure in the Dahl SS Rat Fed a High-Fat Diet.

INTRODUCTION: Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure. METHODS: The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet. A PCR array of ECM genes was performed with cDNA from adventitia and PVAT after 8 and 24 weeks. A gene regulatory network of the differentially expressed genes (DEGs) (HF 2-fold > con) was created using Cytoscape. RESULTS: After 8 weeks, 29 adventitia but 0 PVAT DEGs were found. By contrast, at 24 weeks, PVAT possessed 47 DEGs while adventitia had 3. Top DEGs at 8 weeks in adventitia were thrombospondin 1 and collagen 8a1. At 24 weeks, thrombospondin 1 was also a top DEG in PVAT. The transcription factor Adarb1 was identified as a regulator of DEGs in 8-week adventitia and 24-week PVAT. CONCLUSION: These data support that PVAT responds biologically once blood pressure is elevated.

ß-arrestin biased signaling is not involved in the hypotensive actions of 5-HT7 receptor stimulation: use of Serodolin.

The 5-hydroxytryptamine 7 receptor (5-HT7) is necessary for 5-HT to cause a concentration-dependent vascular relaxation and hypotension. 5-HT7 is recognized as having biased signaling, transduced through either Gs or ß -arrestin. It is unknown whether 5-HT7 signals in a biased manner to cause vasorelaxation/hypotension. We used the recently described ß-arrestin selective 5-HT7 receptor agonist serodolin to test the hypothesis that 5-HT7 activation does not cause vascular relaxation or hypotension via the ß -arrestin pathway. Isolated abdominal aorta (no functional 5-HT7) and vena cava (functional 5-HT7) from male Sprague Dawley rats were used in isometric contractility studies. Serodolin (1 nM - 10 µM) did not change baseline tone of isolated tissues and did not relax the endothelin-1 (ET-1)-contracted vena cava or aorta. In the aorta, serodolin acted as a 5-HT2A receptor antagonist, evidenced by a rightward shift in 5-HT-induced concentration response curve [pEC50 5-HT [M]: Veh = 5.2 +/- 0.15; Ser (100 nM) = 4.49 +/- 0.08; p < 0.05]. In the vena cava, serodolin acted as a 5-HT7 receptor antagonist, shifting the concentration response curve to 5-HT left and upward (%10 µM NE contraction; Veh = 3.2 +/- 1.7; Ser (10 nM) = 58 +/- 11; p < 0.05) and blocking relaxation of pre-contracted tissue to the 5-HT1A/7 agonist 5-carboxamidotryptamine. In anesthetized rats, 5-HT or serodolin was infused at 5, 25 and 75 µg/kg/min, iv. Though 5-HT caused concentration-dependent depressor responses, serodolin caused an insignificant small depressor responses at all three infusion rates. With the final dose of serodolin on board, 5-HT was unable to reduce blood pressure. Collectively the data indicate that serodolin functions as a 5-HT7 antagonist with additional 5-HT2A blocking properties. 5-HT7 activation does not cause vascular relaxation or hypotension via the ß -arrestin pathway.

A Cell Atlas of Thoracic Aortic Perivascular Adipose Tissue: a focus on mechanotransducers.

Perivascular adipose tissue (PVAT) is increasingly recognized for its function in mechanotransduction. To examine the cell-specificity of recognized mechanotransducers we used single nuclei RNA sequencing (snRNAseq) of the thoracic aorta PVAT (taPVAT) from male Dahl SS rats compared to subscapular brown adipose tissue (BAT). Approximately 30,000 nuclei from taPVAT and BAT each were characterized by snRNAseq, identifying 8 major cell types expected and one unexpected (nuclei with oligodendrocyte marker genes). Cell-specific differential gene expression analysis between taPVAT and BAT identified up to 511 genes (adipocytes) with many (≥20%) being unique to individual cell types. Piezo1 was the most highly, widely expressed mechanotransducer. Presence of PIEZO1 in the PVAT was confirmed by RNAscope® and IHC; antagonism of PIEZO1 impaired the PVAT's ability to hold tension. Collectively, the cell compositions of taPVAT and BAT are highly similar, and PIEZO1 is likely a mechanotransducer in taPVAT.

Implementation of Esophageal Screening in an Outpatient Hospital-Based Setting: A Quality Improvement Project.

PURPOSE: Despite evidence supporting interconnectivity of oropharyngeal and esophageal swallowing, evaluation and treatment are dichotomized. When the videofluoroscopic swallowing study (VFSS) only considers oropharyngeal swallowing, the full scope of swallowing impairment may be missed. A lower rate of esophageal screening in an outpatient hospital setting may result from lack of speech-language pathologist (SLP) training and understanding of screening feasibility. This project was an internal quality improvement project (QIP) at Mayo Clinic in Arizona to (a) educate and train SLPs on conducting the Robust Esophageal Screening Test (REST) and (b) determine the feasibility of REST protocol implementation in a multidisciplinary swallow clinic. METHOD: Fishbone analysis was used to identify potential causes of the gap in quality. Six Sigma methodology was used to outline the QIP. SLPs were trained in the REST protocol. To ensure adequate training, reliability ratings were assessed with the Cohen's kappa statistic. Esophageal screening via REST was implemented as an adjunct to the standard protocol during VFSS over a 3-month period for referred patients with dysphagia. Clinical findings were recorded. RESULTS: All clinical rater SLPs reached the threshold of κ = .8 to ensure adequate rater reliability. Among 136 outpatients who underwent esophageal screening via REST, 100 patients completed the full REST screening and 36 completed a partial REST screening. Of the 100 full screenings, 80 patients had a failed screening, which indicated a potential esophageal swallowing impairment. Findings were discussed by members of the multidisciplinary dysphagia care team. CONCLUSIONS: The results of this QIP show that focusing on assessment of dysfunction and interplay across the swallowing continuum can substantially improve patient care by expediting and specifying next steps of the multidisciplinary dysphagia care team.

Chemerin is resident to vascular tunicas and contributes to vascular tone.

The adipokine chemerin may support blood pressure, evidenced by a fall in mean arterial pressure after whole body antisense oligonucleotide (ASO)-mediated knockdown of chemerin protein in rat models of normal and elevated blood pressure. Although the liver is the greatest contributor of circulating chemerin, liver-specific ASOs that abolished hepatic-derived chemerin did not change blood pressure. Thus, other sites must produce the chemerin that supports blood pressure. We hypothesize that the vasculature is a source of chemerin independent of the liver that supports arterial tone. RNAScope, PCR, Western blot analyses, ASOs, isometric contractility, and radiotelemetry were used in the Dahl salt-sensitive (SS) rat (male and female) on a normal diet. Retinoic acid receptor responder 2 (Rarres2) mRNA was detected in the smooth muscle, adventitia, and perivascular adipose tissue of the thoracic aorta. Chemerin protein was detected immunohistochemically in the endothelium, smooth muscle cells, adventitia, and perivascular adipose tissue. Chemerin colocalized with the vascular smooth muscle marker α-actin and the adipocyte marker perilipin. Importantly, chemerin protein in the thoracic aorta was not reduced when liver-derived chemerin was abolished by a liver-specific ASO against chemerin. Chemerin protein was similarly absent in arteries from a newly created global chemerin knockout in Dahl SS rats. Inhibition of the receptor Chemerin1 by the receptor antagonist CCX832 resulted in the loss of vascular tone that supports potential contributions of chemerin by both perivascular adipose tissue and the media. These data suggest that vessel-derived chemerin may support vascular tone locally through constitutive activation of Chemerin1. This posits chemerin as a potential therapeutic target in blood pressure regulation.NEW & NOTEWORTHY Vascular tunicas synthesizing chemerin is a new finding. Vascular chemerin is independent of hepatic-derived chemerin. Vasculature from both males and females have resident chemerin. Chemerin1 receptor activity supports vascular tone.

5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo.

OBJECTIVE: Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT7 receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation. METHODS: Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2-4 rats/sample) to evaluate 5-HT7 receptor expression. RESULTS: Topical 5-HT (1-10 nmols) or the 5-HT1/7 receptor agonist, 5-carboxamidotryptamine (10-30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 µM SB269970, a selective 5-HT7 receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT7 receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 µM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT7 receptors. CONCLUSIONS: 5-HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.

Development of a 5-HT7 receptor antibody for the rat: the good, the bad, and the ugly.

Our laboratory has a vested interest in measuring the location and expression of the 5-hydroxytryptamine (5-HT, serotonin) 7 (5-HT7) receptor in the rat. Determining tissue-specific receptor expression would aid in validating understood and potentially new tissues that support the 5-HT7 receptor-mediated fall in blood pressure, an event we are committed to understand. We contracted with 7TM Antibodies to develop deliberately and rigorously a rat 5-HT7 (r5-HT7) receptor specific antibody. Three antigens, two targeting the third internal loop and one the C terminus, were used in three rabbits to generate antibodies. As a positive control, HEK293(T or AD) cells were transfected with a plasmid for the r5-HT7 receptor also expressing a C terminus 3xFLAG tag. Naïve rat tissues were also used in Western and immunohistochemical analyses. Nine antibodies (3 from three different rabbits) detected a ~ 75 kDa protein absent in homogenates of vector control HEK293T cells. Only antibodies that recognized the C terminus of the 5-HT7 receptor [ERPERSEFVLQNSDH(Abu)GKKGHDT; antibodies 3, 6, and 9] positively and concentration-dependently identified the r5-HT7 receptor expressed in Westerns of transfected HEK293T cells. These same C terminus antibodies also successfully detected the r5-HT7 receptor in immunocytochemical test of the transfected HEK293AD cells, colocalizing with the detected FLAG sequence. In naive tissue, antibody 6 performed the best, identifying specific bands in the brain cortex in Western analysis. These same antibodies produced a more diverse band profile in the vena cava, identifying 6 major proteins. In immunohistochemical experiments, the same C-terminus antibodies, with antibody 3 performing the best, detected the 5-HT7 receptor in rat veins. This deliberate work has given rise to at least three antibodies that can be used with good confidence in r5-HT7 transfected cells, two antibodies that can be used in immunohistochemical analyses of rat tissues and in Westerns of rat brain; we are less confident of the use of these same antibodies in rat veins.

The Modified Barium Swallow Study and Esophageal Screening: A Survey of Clinical Practice Patterns.

PURPOSE: Modified barium swallow study (MBSS) is a videofluoroscopic evaluation of oropharyngeal swallowing. Views of esophageal bolus flow during MBSS are permitted under speech-language pathology practice guidelines. However, controversy exists over its implementation. Poor consensus and limited practice guidance may lead to clinical practice variations. Aims of the investigation were to (a) describe current practice patterns of speech-language pathologist visualizing bolus flow through the esophagus during the MBSS, (b) understand areas of variation when incorporating esophageal visualization during the MBSS, and (c) determine clinicians' willingness to modify MBSS procedures to include esophageal imaging. METHOD: A web-based survey (Qualtrics XM) consisting of 26 questions was distributed via web posting and e-mail to members of the American Speech-Language-Hearing Association Special Interest Group 13 and Dysphagia Café. The survey was open for 3 months. Descriptive and associative statistics were completed. Field-testing was performed prior to dissemination of the survey to address content validity. RESULTS: A total of 321 individuals participated; 265 responses were used for analysis. Ninety-three percent of respondents viewed the esophagus during the MBSS. Twelve percent followed to the proximal esophagus, 15% to the mid esophagus, 66% to the lower esophagus, and 6% to varied levels. Variability was also reported in contrast type, volume administered, and nomenclature used. Interestingly, few people (3.61%) disagreed that esophageal visualization should be performed during MBSS. CONCLUSIONS: Speech-language pathology respondents in this study visualize contrast flow through the esophagus and are enthusiastic about expanding the standard MBSS. However, results of the survey demonstrate a lack of uniformity in assessment practices. Unfortunately, this may impact the diagnostic accuracy and clinical utility when adding esophageal visualization to the MBSS. This study highlights the need for a standardized protocol and identifies current barriers and controversies that may prevent expanding the MBSS to more comprehensively evaluate individuals with dysphagia.

Skin Vascular Resistance Decreases during 5-HT-Induced Hypotension in the Rat.

A recognized vasodilator, the infusion of 5-hydroxytryptamine (5-HT, serotonin) decreases blood pressure through the reduction of total peripheral resistance in the rat. It is not clear which vascular beds/tissues are responsible for this fall. We hypothesized that an increase in blood flow within the skin, measured as an elevated temperature (T) in the thermoregulatory tail and paws, enables at least part of 5-HT-induced reduction in blood pressure through active vasodilation. The temperature of thermoregulatory regions of the skin of an anesthetized male, Sprague Dawley rats were measured using a Optris PI640 thermal camera. The blood pressure of the animal and the temperature of each paw and four locations along the tail (TL1-4) were recorded before, during, and after the infusion of 5-HT at a rate of 25 mg/min into a femoral vein. Contrary to our hypothesis, the temperature of the paws and tail was stable before and during 5-HT infusion and actually increased during the 15-min recovery period. This finding suggests that hyperemia of the skin circulation is not necessary for the fall in blood pressure observed with infused 5-HT, but that a reduction in cutaneous vascular resistance plays a part in the fall in total peripheral resistance.

The moderating and mediating role of telepresence and cognitive change in cognitive behaviour therapy delivered via videoconference.

In this study, we combined the results of two controlled trials and examined the relationships between working alliance, telepresence, cognitive change and treatment outcome. Sixty-five participants with a primary diagnosis of generalized anxiety disorder (GAD) or panic disorder with agoraphobia (PDA) received cognitive behaviour therapy delivered via videoconference. Participants completed measures of working alliance and telepresence after three psychotherapy sessions. They also completed measures of treatment outcome and dysfunctional beliefs (cognitive change) specific to PDA and GAD at pretreatment and posttreatment. Results revealed that telepresence at the fifth session moderated the relationship between the working alliance at the first and fifth sessions. As telepresence increased, its impact on the working alliance diminished. Cognitive change mediated the relationship between the working alliance at the fifth session and treatment outcome.

Voluntary Cough Testing as a Clinical Indicator of Airway Protection in Cervical Spinal Cord Injury.

OBJECTIVE: Voluntary cough testing (VCT) may be useful for determining aspiration risk in neurogenic dysphagia; however, has yet to be investigated in traumatic cervical spinal cord injury (tCSCI). The study explored if VCT may elucidate swallowing safety and kinematics related to airway protection in tCSCI survivors. METHODS: Ten inpatients, 13-73 days post-tCSCI (7 incomplete injuries), completed VCT and a modified barium swallowing study that was analyzed via the Penetration Aspiration Scale (PAS) and norm-referenced measures of swallowing events related to airway protection. Spearman rho correlations explored relations among cough airflow, median PAS, and airway protection. Mann-Whitney U tests explored group differences based on clinical airway invasion (PAS > 2) and receiver operating characteristic statistics probed the sensitivity/specificity of VCT measures. RESULTS: Safe (PAS > 2) and unsafe swallowers differed by cough volume acceleration (CVA) for the total sample and by inspiratory duration for incomplete injuries (p = 0.03, r > 0.7). A cut-off value of 24.8 L/s for CVA predicted airway invasion (AUC = 0.917, p = 0.03) with sensitivity = 100%/specificity = 75%. CVA correlated with delayed laryngeal vestibule closure during swallowing for both the total sample and for incomplete injuries (rs  > 0.6, p < 0.05). Blunted peak flow and prolonged cough phases were associated with disordered laryngeal kinematics and prolonged bolus transit during swallowing (p < 0.05). CONCLUSIONS: Reduced CVA, blunted peak flow, and prolonged cough phases reflected PAS and disrupted mechanisms of airway protection in tCSCI survivors, demonstrating promise for VCT as a clinical assessment for post-tCSCI dysphagia. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1434-1441, 2023.

A Novel Grading System for Supraglottic Stenosis Based on Morphology and Functional Status.

OBJECTIVE: Currently, no classification system exists to grade the severity of supraglottic stenosis. The aim of this investigation was to (1) develop a novel grading system for supraglottic stenosis that can both enhance communication between providers and relay information about patient functional status and (2) determine the reliability of the grading system. METHODS: A retrospective analysis of patients with supraglottic stenosis at three institutions from 2010-2021 was conducted. After demographic data were collected, two focus group meetings of five laryngologists were held to develop a grading system based on functional status and morphology of stenosis seen on laryngoscopy. Three laryngologists then used the grading system to rate 20 case examples of supraglottic stenosis. Quadratic-weighted kappa coefficients were calculated to assess inter-rater and intra-rater reliabilities of the novel grading system. RESULTS: Twenty-eight patients were included. Epiglottic and arytenoid fixation were morphological features associated with worse functional outcomes such as requiring a G-tube or a tracheostomy, respectively. Inter-rater reliability was substantial to almost perfect (Kw = 0.79-0.81) and intra-rater reliability was almost perfect for all raters (0.88-1.0) when using the novel grading system. CONCLUSION: A grading system for supraglottic stenosis has been proposed with strong inter-rater and intra-rater reliabilities. The proposed system has the advantage of being descriptive of both patient functionality and morphology of the stenosis. LEVEL OF EVIDENCE: 3-According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 3 evidence Laryngoscope, 133:1442-1447, 2023.

Higher OAK (Oral Anticoagulation Knowledge) score at baseline associated with better TTR (Time in Therapeutic Range) in patients taking warfarin.

A lack in patient knowledge of warfarin therapy is associated with poor adherence. This knowledge gap may result in a lower INR Time in Therapeutic Range (TTR). To investigate association between patient anticoagulation knowledge and warfarin control. Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a Blue Cross Blue Shield of Michigan sponsored consortium of six anticoagulation management services. Patients prescribed warfarin at two MAQI2 sites completed a voluntary Oral Anticoagulation Knowledge (OAK) questionnaire at warfarin initiation and 6-month follow-up. The results of 20 OAK questions and TTRs (excluding 1st month post-initiation) were compared using chi-square tests, t-tests and multivariate analysis adjusting for SAMe-TT2R2 and days on warfarin. Of 1836 surveys distributed at warfarin initiation, 481 (26.2%) patients completed the baseline questionnaire (within 1 month post-initiation): mean OAK score: 14.6 ± 3.4. Of those, 147 (30.6%) completed 6-month follow-up surveys (OAK: 12.7 ± 5.8). Patients with TTR ≥ 70% at baseline scored higher on OAK tests than patients with TTR < 70% in unadjusted analyses (15.1 ± 3.2 v. 14.2 ± 3.5, p = 0.003) and adjusted analysis (p = 0.020). There was no unadjusted or adjusted difference in OAK scores at 6-month follow-up between patients with TTR ≥ 70% and TTR < 70%. For patients who completed baseline and follow-up surveys, there was a decrease of 2.4 points in OAK score between baseline and 6-month follow up (p < 0.001). Higher baseline, but not follow-up, OAK score is associated with better warfarin control and average OAK scores decreased between baseline and follow-up. Further studies are needed to determine what type of patient education may improve patient knowledge retention and warfarin control.