Background The peculiarities of T-tubule morphology and distribution in the atrium – and how they contribute to excitation-contraction coupling – are just beginning to be understood. Objective To determine T-tubule density in the intact, live right and left atria in a large animal and to determine intra-regional differences in T-tubule organization within each atrium. Methods Using confocal microscopy, T-tubules were imaged in both atria in intact, Langendorf-perfused normal dog hearts loaded with di-4-ANEPPS. T-tubules were imaged in large populations of myocytes from the endocardial surface of each atrium. Computerized data analysis was performed using a new MatLab routine, AutoTT. Results There was a large percentage of myocytes that had no T-tubules in both atria with a higher percentage in the right atrium (25.1%) than in the left (12.5%, p<0.02). The density of transverse and longitudinal T-tubule elements was very low in cells that did contain T-tubules but there were no significant differences in density between left atrial appendage, the pulmonary vein – posterior left atrium, right atrial appendage and right atrial free wall. In contrast, there were significant differences in sarcomere spacing and cell width between different regions of the atria. Conclusion There is a sparse T-tubule network in atrial myocytes throughout both dog atria, with significant numbers of myocytes in both atria – the right atrium more so than the left - having no T-tubules at all. These regional differences in T-tubule distribution, along with differences in cell width and sarcomere spacing, may have implications for the emergence of substrate for atrial fibrillation.
A highly organized transverse‐tubule (TT) system is essential to normal Ca2+ cycling and cardiac function. We explored the relationship between the progressive disruption of TTs and resulting Ca2+ cycling during the development of heart failure (HF). Confocal imaging was used to measure Ca2+ transients and 2‐D z‐stack images in left ventricular epicardial myocytes of intact hearts from spontaneously hypertensive rats (SHR) and Wistar‐Kyoto control rats. TT organization was measured as the organizational index (OI) derived from a fast Fourier transform of TT organization. We found little decrease in the synchrony of Ca2+ release with TT loss until TT remodeling was severe, suggesting a TT “reserve” characterized by a wide range of TT remodeling with little effect on synchrony of release but beyond which variability in release shows an accelerating sensitivity to TT loss. To explain this observation, we applied a computational model of spatially distributed Ca2+ signaling units to investigate the relationship between OI and excitation‐contraction coupling. Our model showed that release heterogeneity exhibits a nonlinear relationship on both the spatial distribution of release units and the separation between L‐type Ca2+ channels and ryanodine receptors. Our results demonstrate a unique relationship between the synchrony of Ca2+ release and TT organization in myocytes of intact rat ventricle that may contribute to both the compensated and decompensated phases of heart failure.
Purpose The aim of the study was to assess how the use of a mild-gain hearing aid can affect hearing handicap, motivation, and attitudes toward hearing aids for middle-age, normal-hearing adults who do and do not self-report trouble hearing in background noise. Method A total of 20 participants (45–60 years of age) with clinically normal-hearing thresholds (< 25 dB HL) were enrolled in this study. Ten self-reported difficulty hearing in background noise, and 10 did not self-report difficulty hearing in background noise. All participants were fit with mild-gain hearing aids, bilaterally, and were asked to wear them for 2 weeks. Hearing handicap, attitudes toward hearing aids and hearing loss, and motivation to address hearing problems were evaluated before and after participants wore the hearing aids. Participants were also asked if they would consider purchasing a hearing aid before and after 2 weeks of hearing aid use. Results After wearing the hearing aids for 2 weeks, hearing handicap scores decreased for the participants who self-reported difficulty hearing in background noise. No changes in hearing handicap scores were observed for the participants who did not self-report trouble hearing in background noise. The participants who self-reported difficulty hearing in background noise also reported greater personal distress from their hearing problems, were more motivated to address their hearing problems, and had higher levels of hearing handicap compared to the participants who did not self-report trouble hearing in background noise. Only 20% (2/10) of the participants who self-reported trouble hearing in background noise reported that they would consider purchasing a hearing aid after 2 weeks of hearing aid use. Conclusions The use of mild-gain hearing aids has the potential to reduce hearing handicap for normal-hearing, middle-age adults who self-report difficulty hearing in background noise. However, this may not be the most appropriate treatment option for their current hearing problems given that only 20% of these participants would consider purchasing a hearing aid after wearing hearing aids for 2 weeks.
ImportanceThe addition of over-the-counter hearing aid (HA) options has transformed the way individuals can access hearing health care (HHC). However, although critical to their adoption and use, consumer attitudes and opinions about direct-to-consumer (DTC) models of health care are often understudied.ObjectiveTo assess how recent DTC market changes in HHC delivery may be associated with consumer choice and attitudes towards specific HHC models.Design, Setting, and ParticipantsA mixed-methods survey, distributed online between March 22 and 25, 2022, using Qualtrics Survey Panels. Participants were US residents older than 50 years with no previous hearing aid experience, enrolled using consecutive sampling. A minimum of 1000 completed responses was set; once the 70% threshold was met, any future respondent who identified as White would not be given the survey.Main Outcomes and MeasuresRespondents were asked to report their level of comfort with using different variations of DTC-HHC and asked about their previous experience with other DTC health care models. Respondents then reported which model (in-person vs online) of HHC they would most likely pursue.ResultsOf 1377 respondents, 1037 were included in the survey study (mean [SD] age, 61.4 [7.84] years; 714 [69.0%] were female; 674 [65.0%] were White). Most respondents reported discomfort with pursuing hearing aids via DTC pathways, with 84% (874 of 1037) indicating they would pursue HHC via an in-person model. Individuals who were older (odds ratio [OR], 0.95; 95% CI, 0.92-0.98), reported an income greater than $150 000 (OR, 0.29; 95% CI, 0.08-0.91), and were not interested in HA (OR, 0.42; 95% CI, 0.23-0.79) were less likely to pursue HHC online. Those who had previous experience with DTC health care (OR, 1.97; 95% CI, 1.27-3.02), and did not have (OR, 2.61; 95% CI, 1.59-4.31) or were uncertain (OR, 2.05; 95% CI, 1.13-3.70) about their insurance coverage for HA were more likely to pursue HHC online.Conclusions and RelevanceCurrent consumer attitudes and opinions found in this survey study suggest that DTC-HHC may not find immediate acceptance by most potential HA seekers in the US.
Researchers have endeavored to subclassify depressive illness based on pathophysiological mechanism. One model relates to hypothalamic-pituitary-adrenal (HPA) axis overactivation with a shift from corticotropin-releasing hormone (CRH) driven regulation to arginine vasopressin (AVP) driven regulation. Given the mixed literature, we compared plasma AVP levels in healthy controls to patients with major depressive disorder (MDD). Plasma samples from 33 patients and 12 controls were collected at baseline, 8 weeks, and 12 weeks of treatment and measured by immunochemical assay. Patients who were treatment responders trended toward lower AVP levels than non-responders. Patients were stratified into low and high AVP groups based on median split. Within the low AVP group, patients whose current episode lasted longer than a year had significantly higher baseline AVP levels than patients whose current episode was less than 6 months. Female patients in the low AVP group had significantly higher baseline AVP levels than male patients. Given the association between stress, HPA axis activation, immune dysregulation, and depression, we also measured concentrations of inflammatory biomarkers. We found a significant negative correlation between IL-10 and baseline AVP levels, within the low AVP subgroup. Given inconsistent data, HPA axis overactivation may be present within a subset of depressed patients.
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