Healthcare providers' perceived acceptability of a warning signs intervention for rural hospital-to-home transitional care: A cross-sectional study.

INTRODUCTION: There is a pressing need for transitional care that prepares rural dwelling medical patients to identify and respond to the signs of worsening health conditions. An evidence-based warning signs intervention has the potential to address this need. While the intervention is predominantly delivered by nurses, other healthcare providers may be required to deliver it in rural communities where human health resources are typically limited. Understanding the perspectives of other healthcare providers likely to be involved in delivering the intervention is a necessary first step to avert consequences of low acceptability, such as poor intervention implementation, uptake, and effectiveness. This study examined and compared nurses' and other healthcare providers' perceived acceptability of an evidence-based warning signs intervention proposed for rural transitional care. METHODS: A cross-sectional design was used. The convenience sample included 45 nurses and 32 other healthcare providers (e.g., physical and occupational therapists, physicians) who self-identified as delivering transitional care to patients in rural Ontario, Canada. In an online survey, participants were presented with a description of the warning signs intervention and completed established measures of intervention acceptability. The measures captured 10 intervention acceptability attributes (effectiveness, appropriateness, risk, convenience, relevance, applicability, usefulness, frequency of current use, likelihood of future use, and confidence in ability to deliver the intervention). Ratings ≥ 2 indicated acceptability. Data analysis included descriptive statistics, independent samples t-tests, as well as effect sizes to quantify the magnitude of any differences in acceptability ratings between nurses and other healthcare providers. RESULTS: Nurses and other healthcare providers rated all intervention attributes > 2, except the attributes of convenience and frequency of current use. Differences between the two groups were found for only three attributes: nurses' ratings were significantly higher than other healthcare providers on perceived applicability, frequency of current use, and the likelihood of future use of the intervention (all p's < .007; effect sizes .58 - .68, respectively). DISCUSSION: The results indicate that both participant groups had positive perspectives of the intervention on most of the attributes and suggest that initiatives to enhance the convenience of the intervention's implementation are warranted to support its widespread adoption in rural transitional care. However, the results also suggest that other healthcare providers may be less receptive to the intervention in practice. Future research is needed to explore and mitigate the possible reasons for low ratings on perceived convenience and frequency of current use of the intervention, as well as the between group differences on perceived applicability, frequency of current use, and the likelihood of future use of the intervention. CONCLUSIONS: The intervention represents a tenable option for rural transitional care in Ontario, Canada, and possibly other jurisdictions emphasizing transitional care.

Printing Drugs onto Nails for Effective Treatment of Onychomycosis.

Inkjet printing (IJP) is an emerging technology for the precision dosing of medicines. We report, for the first time, the printing of the antifungal drug terbinafine hydrochloride directly onto nails for the treatment of onychomycosis. A commercial cosmetic nail printer was modified by removing the ink from the cartridge and replacing it with an in-house prepared drug-loaded ink. The drug-loaded ink was designed so that it was comparable to the commercial ink for key printability properties. Linear drug dosing was shown by changing the lightness of the colour selected for printing (R2 = 0.977) and by printing multiple times (R2 = 0.989). The drug loads were measured for heart (271 µg), world (205 µg) and football (133 µg) shapes. A disc diffusion assay against Trpytophan rubrum showed inhibition of fungal growth with printed-on discs. In vitro testing with human nails showed substantial inhibition with printed-on nails. Hence, this is the first study to demonstrate the ability of a nail printer for drug delivery, thereby confirming its potential for onychomycosis treatment.

Engineered neural tissue made using clinical-grade human neural stem cells supports regeneration in a long gap peripheral nerve injury model.

A surgical autograft remains the clinical gold-standard therapy for gap repair following peripheral nerve injury, however, challenges remain with achieving full recovery and reducing donor-site morbidity. Engineered Neural Tissue (EngNT) manufactured using differentiated CTX0E03 human stem cells (EngNT-CTX) has been developed as a potential 'off the shelf' allogeneic autograft replacement. Ensheathed within a collagen membrane developed to facilitate biomechanical integration, EngNT-CTX was used to bridge a critical-length (15 mm) sciatic nerve gap injury in athymic nude rats. The effectiveness of EngNT-CTX was compared to an autograft using outcome measures that assessed neuronal regeneration and functional recovery at 8 and 16 weeks. At both time points EngNT-CTX restored electrophysiological nerve conduction and functional reinnervation of downstream muscles to the same extent as the autograft. Histological analysis confirmed that more motor neurons had successfully regenerated through the repair in EngNT-CTX in comparison to the autograft at 8 weeks, which was consistent with the electrophysiology, with the number of motor neurons similar in both groups by 16 weeks. The total number of neurons (motor + sensory) was greater in autografts than EngNT-CTX at 8 weeks, indicating that more sensory fibres may have sprouted in those animals at this time point. In conclusion, this study provides evidence to support the effectiveness of EngNT-CTX as a replacement for the nerve autograft, as the functional regeneration assessed through histological and electrophysiological outcome measures demonstrated equivalent performance. STATEMENT OF SIGNIFICANCE: Following injury a peripheral nerve has the capacity to regenerate naturally, however, in the case of severe damage where there is a gap the current gold-standard microsurgical intervention is an autograft. This is associated with serious limitations including tissue availability and donor-site morbidity. Tissue engineering aims to overcome these limitations by building a construct from therapeutic cells and biomaterials as a means to mimic and replace the autograft. In this study engineered neural tissue (EngNT) was manufactured using human stem cells (CTX) to bridge a critical-length gap injury. When compared to the autograft in an animal model the EngNT-CTX construct restored function to an equivalent or greater extent.

Collaborative Development of an Older Adult Experience Survey for Specialized Geriatric Services.

BACKGROUND: While generic, site, and disease-specific patient experience surveys exist, such surveys have limited relevance to frail, medically complex older adults attending appointment-based specialized geriatric services (SGS). The study objective was to develop and evaluate a patient experience survey specific to this population. METHODS: Using established survey research methods, this study was conducted collaboratively with older adults (patients and family members/friends) at three Ontario sites offering SGS. The study was done in three phases: Phase One-literature review, evidence alignment, and operationalization of core survey items; Phase Two-cognitive interviews and refinement; and Phase Three-pilot testing, survey item analysis, and refinement. RESULTS: Based on an evidence-informed framework, the "Older Adult Experience Survey" includes 12 core items, two global rating items, two open-ended questions, and two demographic questions. The summed 12 core items demonstrated acceptable internal consistency (Cronbach's alpha: 0.83), and the correlation between the summed score and a global question was 0.59, providing evidence of construct validity. The survey also demonstrated face and content validity. CONCLUSION: This open access, collaboratively developed, psychometrically sound patient experience survey can be used to assess, then improve, the clinical experience and quality of care of older adults attending appointment-based SGS clinics/programs.

Rapidly formed stable and aligned dense collagen gels seeded with Schwann cells support peripheral nerve regeneration.

OBJECTIVE: Gel aspiration-ejection (GAE) has recently been developed for the rapid production of dense, anisotropic collagen gel scaffolds with adjustable collagen fibrillar densities. In this study, a GAE system was applied to produce aligned Schwann cells within a type-1 collagen matrix to generate GAE-engineered neural tissues (GAE-EngNT) for potential nerve tissue engineering applications. APPROACH: The stability and mechanical properties of the constructs were investigated along with the viability, morphology and distribution of Schwann cells. Having established the methodology to construct stable robust Schwann cell-loaded engineered neural tissues using GAE (GAE-EngNTs), the potential of these constructs in supporting and guiding neuronal regeneration, was assessed both in vitro and in vivo. MAIN RESULTS: Dynamic mechanical analysis strain and frequency sweeps revealed that the GAE-EngNT produced via cannula gauge number 16 G (∼1.2 mm diameter) exhibited similar linear viscoelastic behaviors to rat sciatic nerves. The viability and alignment of seeded Schwann cells in GAE-EngNT were maintained over time post GAE, supporting and guiding neuronal growth in vitro with an optimal cell density of 2.0 × 106 cells ml-1. An in vivo test of the GAE-EngNTs implanted within silicone conduits to bridge a 10 mm gap in rat sciatic nerves for 4 weeks revealed that the constructs significantly promoted axonal regeneration and vascularization across the gap, as compared with the empty conduits although less effective regeneration compared with the autograft groups. SIGNIFICANCE: Therefore, this is a promising approach for generating anisotropic and robust engineered tissue which can be used with Schwann cells for peripheral nerve repair.

Targeted cell imaging properties of a deep red luminescent iridium(iii) complex conjugated with a c-Myc signal peptide.

A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λ ex = 550 nm; λ em = 677 nm) cyclometalated organometallic iridium(iii) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18-24 h incubation show that Ir-CMYC concentrations of 80-100 µM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(iii) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 µM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M-1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex.

Screen Printing to Create 3D Tissue Models.

3D printing has revolutionized making tissue models, but the instruments are often quite expensive, and the approach can involve heat and/or shear forces that can damage cells. As a complement to more traditional 3D printing approaches, we looked at screen printing. Screen printing is an additive manufacturing technique used to pattern inks through screens supporting patterns onto different surfaces. It has a wide range of applications ranging from traditional printing to printing electric circuit boards. Taking cues from this we have developed a process of screen printing live cells along with a suitable scaffold on to different surfaces to generate in vitro models. The process is not only inexpensive and simple to use, but it also offers a wide range of advantages like the ability to use a range of bioinks limited only by their gelation time, printing on different surfaces, and the ability to autoclave all of the major components. In this paper, we present the screen assembly and the setup we used to print the cells along with the resolution and limits of features printed and the effect of the printing on the cells.

Towards dual SPECT/optical bioimaging with a mitochondrial targeting, 99mTc(i) radiolabelled 1,8-naphthalimide conjugate.

A series of six different 1,8-naphthalimide conjugated dipicolylamine ligands (L1-6) have been synthesised and characterised. The ligands possess a range of different linker units between the napthalimide fluorophore and dipcolylamine chelator which allow the overall lipophilicity to be tuned. A corresponding series of Re(i) complexes have been synthesised of the form fac-[Re(CO)3(L1-6)]BF4. The absorption and luminescence properties of the ligands and Re(i) complexes were dominated by the intramolecular charge transfer character of the substituted fluorophore (typically absorption ca. 425 nm and emission ca. 520 nm). Photophysical assessments show that some of the variants are moderately bright. Radiolabelling experiments using a water soluble ligand variant (L5) were successfully undertaken and optimised with fac-[99mTc(CO)3(H2O)3]+. Confocal fluorescence microscopy showed that fac-[Re(CO)3(L5)]+ localises in the mitochondria of MCF-7 cells. SPECT/CT imaging experiments on naïve mice showed that fac-[99mTc(CO)3(L5)]+ has a relatively high stability in vivo but did not show any cardiac uptake, demonstrating rapid clearance, predominantly via the biliary system along with a moderate amount cleared renally.

An Optimized Collagen-Fibrin Blend Engineered Neural Tissue Promotes Peripheral Nerve Repair.

Tissue engineering approaches in nerve regeneration often aim to improve results by bridging nerve defects with conduits that mimic key features of the nerve autograft. One such approach uses Schwann cell self-alignment and stabilization within collagen gels to generate engineered neural tissue (EngNT). In this study, we investigated whether a novel blend of fibrin and collagen could be used to form EngNT, as before EngNT design a beneficial effect of fibrin on Schwann cell proliferation was observed. A range of blend formulations was tested in terms of mechanical behavior (gel formation, stabilization, swelling, tensile strength, and stiffness), and lead formulations were assessed in vitro. A 90% collagen 10% fibrin blend was found to promote SCL4.1/F7 Schwann cell viability and supported the formation of aligned EngNT, which enhanced neurite outgrowth in vitro (NG108 cells) compared to formulations with higher and lower fibrin content. Initial in vivo tests in an 8 mm rat sciatic nerve model using rolled collagen-fibrin EngNT rods revealed a significantly enhanced axonal count in the midsection of the repair, as well as in the distal part of the nerve after 4 weeks. This optimized collagen-fibrin blend therefore provides a novel way to improve the capacity of EngNT to promote regeneration following peripheral nerve injury.

The Effect of Hypothermic and Cryogenic Preservation on Engineered Neural Tissue.

This study explored different approaches to preserve engineered neural tissue (EngNT), a stabilized, cellular collagen hydrogel containing columns of aligned Schwann cells for nervous system repair. The ability to preserve EngNT without disrupting cellular and extracellular components and structures is important for clinical translation and commercialization. Stabilized cellular gels and EngNT constructs were preserved under various conditions and cell survival assessed using live/dead microscopy and metabolic assay. Optimal survival was recorded in hypothermic (4°C) conditions for 2-3 days using Hibernate®-A media and, for longer-term cryogenic storage (liquid nitrogen), using a mixture of 60% Dulbecco's modified Eagle's medium, 30% fetal bovine serum, and 10% dimethyl sulfoxide. Functionality and structure of preserved EngNT were assessed in coculture with dorsal root ganglion neurons, which indicated that alignment of Schwann cells and the ability of EngNT to support and guide neuronal regeneration were not disrupted. The identification of conditions that preserve EngNT will inform development of storage and transport methodologies to support clinical and commercial translation of this technology and other therapies based on cellular hydrogels.

How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study.

The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-ß (Aß) peptide, i.e. to the modulation of Aß aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of both ions in Aß aggregation is still controversial. Conversely the higher toxicity of the redox competent Cu ions (compared to the redox inert Zn ions) in ROS production is acknowledged. Thus the Cu ions can be considered as the main therapeutic target. Because Zn ions are present in higher quantity than Cu ions in the synaptic cleft, they can prevent detoxification of Cu by chelators unless they have an unusually high Cu over Zn selectivity. We describe a proof-of-concept study where the role of Zn on the metal swap reaction between two prototypical ligands and the Cu(Aß) species has been investigated by several complementary spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher Cu over Zn selectivity relative to the one of Aß peptide while the second one exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the ligands on Cu-induced ROS production and Aß aggregation is also reported.

Longitudinal variations of laryngeal overpressure and voice-related quality of life in spasmodic dysphonia.

OBJECTIVES/HYPOTHESIS: Adductor spasmodic dysphonia (AdSD) is a voice disorder characterized by variable symptom severity and voice disability. Those with the disorder experience a wide spectrum of symptom severity over time, resulting in varied degrees of perceived voice disability. This study investigated the longitudinal variability of AdSD, with a focus on auditory-perceptual judgments of a dimension termed laryngeal overpressure (LO) and patient self-assessments of voice-related quality of life (V-RQOL). STUDY DESIGN: Longitudinal, correlational study. METHODS: Ten adults with AdSD were followed over three time periods. At each, both voice samples and self-ratings of V-RQOL were gathered prior to their scheduled Botox injection. Voice recordings subsequently were perceptually evaluated by eight listeners for LO using a visual analog scale. RESULTS: LO ratings for all-voiced and Rainbow Passage sentence stimuli were found to be highly correlated. However, only the LO ratings obtained from judgments of AV stimuli were found to correlate moderately with self-ratings of voice disability for both the physical functioning and social-emotional subscores, as well as the total V-RQOL score. Based on perceptual judgments, LO appears to provide a reliable means of quantifying the severity of voice abnormalities in AdSD. CONCLUSIONS: Variability in self-ratings of the V-RQOL suggest that perceived disability related to AdSD should be actively monitored. Further, auditory-perceptual judgments may provide an accurate index of the potential impact of the disorder on the speaker. Similarly, LO was supported as a simple clinical measure that serves as a reliable index of voice change over time.

Exploring use of the ICF in health education.

PURPOSE: Currently, little is known regarding use of the International Classification of Functioning, Disability and Health (ICF) in health education applications. Therefore, this review sought to examine the scope of work that has been conducted regarding the application of the ICF in health education. METHODS: A review of the current literature related to use of the ICF in health education programs was conducted. Twelve electronic databases were searched in accordance with a search protocol developed by a health sciences librarian. In total, 17,878 records were reviewed, and 18 articles met the criteria for inclusion in this review. RESULTS: Current evidence regarding use of the ICF in healthcare education revealed that program and participant properties can be essential facilitators or barriers to successful education programs. In addition, gaps in comprehensive outcome measurement were revealed as areas for future attention. Educational applications of the ICF are very much a work in progress as might be expected given the ICF's existence for only a little over a decade. CONCLUSIONS: To advance use of the ICF in education, it is important to incorporate the measurement of both knowledge acquisition and behavior change related to ICF-based programs. Ultimately, widespread implementation of the ICF represents not only a substantial opportunity but also poses a significant challenge.

Examining the construct validity of the V-RQOL in speakers who use alaryngeal voice.

PURPOSE: The construct validity of the Voice-Related Quality of Life (V-RQOL; Hogikyan & Sethuraman, 1999) measure was evaluated in a sample of 109 individuals who have undergone total laryngectomy. METHOD: A principal components factor analysis was performed on participant responses to the 10-question V-RQOL measure. RESULTS: Factor analysis of the V-RQOL in our alaryngeal sample confirmed the presence of two factors (physical and social-emotional), which is consistent with the identified domains in the current V-RQOL. However, the current data indicate that some of the questions proposed by the original authors of the V-RQOL (Questions 7 and 9) do not align with their proposed domains in this postlaryngectomy sample. CONCLUSION: The results indicate that some V-RQOL questions do not align with their proposed domains. Consequently, an alternative scoring algorithm may be warranted for alaryngeal populations, and the authors make suggestions for this change that are simple and efficient. Based on the findings of the present factor analysis, use of this modified scoring procedure may serve to increase the sensitivity of the V-RQOL for those who are laryngectomized and use alaryngeal methods of voice and speech. Consequently, the value and application of the V-RQOL may be expanded in the clinical setting.

Knowledge flow and exchange in interdisciplinary primary health care teams (PHCTs): an exploratory study.

OBJECTIVE: Improving the process of evidence-based practice in primary health care requires an understanding of information exchange among colleagues. This study explored how clinically oriented research knowledge flows through multidisciplinary primary health care teams (PHCTs) and influences clinical decisions. METHODS: This was an exploratory mixed-methods study with members of six PHCTs in Ontario, Canada. Quantitative data were collected using a questionnaire and analyzed with social network analysis (SNA) using UCINet. Qualitative data were collected using semi-structured interviews and analyzed with content analysis procedures using NVivo8. RESULTS: It was found that obtaining research knowledge was perceived to be a shared responsibility among team members, whereas its application in patient care was seen as the responsibility of the team leader, usually the senior physician. PHCT members acknowledged the need for resources for information access, synthesis, interpretation, or management. CONCLUSION: Information sharing in interdisciplinary teams is a complex and multifaceted process. Specific interventions need to be improved such as formalizing modes of communication, better organizing knowledge-sharing activities, and improving the active use of allied health professionals. Despite movement toward team-based models, senior physicians are often gatekeepers of uptake of new evidence and changes in practice.

Auditory-perceptual speech outcomes and quality of life after total laryngectomy.

OBJECTIVE: (1) To determine potential relationships between speech intelligibility, acceptability, and self-reported quality of life (QOL) after total laryngectomy and (2) to determine whether relationships are stronger when QOL is measured by a head and neck cancer-specific or discipline-specific QOL scale. STUDY DESIGN: Cross-sectional. SETTING: University-based laboratory and speech clinic. SUBJECTS AND METHODS: Twenty-five laryngectomized individuals completed disease-specific (University of Washington Quality of Life; UW-QOL) and discipline-specific (Voice Handicap Index-10; VHI-10) QOL scales. They also provided audio recordings that included the Sentence Intelligibility Test (SIT) and a reading passage. Thirty-three listeners transcribed the SIT sentences to yield intelligibility scores. Fifteen additional listeners judged speech acceptability of the reading passage using rating scales. RESULTS: The QOL scores were moderate across the UW-QOL physical (mean = 77.63) and social-emotional (mean = 78.02) subscales and the VHI-10 (mean = 17.91). Speech acceptability and intelligibility varied across the samples, with acceptability only moderately related to intelligibility (r = 0.41, P < .05). Relationships were weak between ratings of intelligibility and self-reported QOL (range, r = 0.00-0.22) and weak to moderate between acceptability with QOL (range, r = 0.01-0.46). The only statistically significant, but moderate, relationship was found between speech acceptability with the UW-QOL speech subscore (r = 0.46, P < .05). CONCLUSION: Listeners' ratings of speech acceptability and intelligibility were not strongly predictive of disease-specific or voice-related QOL, suggesting that listener-rated and patient-reported outcomes are complementary.

Nature and the natural environment as health facilitators: the need to reconceptualize the ICF environmental factors.

PURPOSE: This work examines the environmental factors component of the International Classification of Functioning, Disability, and Health (ICF) relative to current health-facilitating evidence about natural environmental factors. We argue that the environmental factors component warrants reconceptualization in order to offer an extended and more systematic framework for identifying and measuring health-facilitating natural environmental factors. METHOD: Current evidence highlighting the potential health-facilitating benefits of natural environmental factors is synthesized and considered in the context of the ICF framework and its coding system. RESULTS: In its current form, the ICF's conceptual framework and coding system are inadequate for identifying and measuring natural environmental factors in individuals and groups with and/or without health conditions. CONCLUSION: The ICF provides an advanced framework for health and disability that reflects contemporary conceptualizations about health. However, given the scope of emerging evidence highlighting positive health and well-being outcomes associated with natural environmental factors, we believe the environmental factors component requires further advancement to reflect this current knowledge. Reconceptualizing the environmental factors component supports a more holistic interpretation of the continuum of environmental factors as both facilitators and barriers. In doing so, it strengthens the ICF's utility in identifying and measuring health-facilitating natural environmental factors.

Clinical approach to monitoring variability associated with adductor spasmodic dysphonia.

OBJECTIVES: Adductor spasmodic dysphonia (ADSD) is a voice disorder characterized by considerable intra- and intersubject variability. Although objective, acoustic measures of voice may provide a metric for ADSD, such measures can be inefficient in documenting such characteristics. This project integrated a simple auditory-perceptual measure termed "laryngeal overpressure" (LO) with measures of acoustic variability. METHODS: Ten adults diagnosed with ADSD were sequentially followed over a period of 3 to 6 months. Standard voice recordings were obtained at each point, and acoustic measures were gathered. Additionally, three experienced listeners then rated LO using a visual analogue scale, and acoustic variability was assessed relative to the measure of LO. RESULTS: Listener ratings of LO did not differ across the three-sentence stimuli and were highly correlated (r  =  .828 and .909 for naive and experienced listeners, respectively). A strong correlation was identified between the acoustic measure of harmonics to noise ratio and the all-voiced sentence stimuli (r  =  .710). CONCLUSION: LO appears to provide an easy clinical method of documenting voice change over time in those with ADSD. Although additional methods of voice monitoring may be used, the use of LO may provide the opportunity for a standard and reliable approach to the clinical monitoring of voice variability in those presenting with ADSD.

Sequential requirements for the GTPase domain of the mitofusin Fzo1 and the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion.

The ability of cells to respire requires that mitochondria undergo fusion and fission of their outer and inner membranes. The means by which levels of fusion 'machinery' components are regulated and the molecular details of how fusion occurs are largely unknown. In Saccharomyces cerevisiae, a central component of the mitochondrial outer membrane (MOM) fusion machinery is the mitofusin Fzo1, a dynamin-like GTPase. We demonstrate that an early step in fusion, mitochondrial tethering, is dependent on the Fzo1 GTPase domain. Furthermore, the ubiquitin ligase SCF(Mdm30) (a SKP1-cullin-1-F-box complex that contains Mdm30 as the F-box protein), which targets Fzo1 for ubiquitylation and proteasomal degradation, is recruited to Fzo1 as a consequence of a GTPase-domain-dependent alteration in the mitofusin. Moreover, evidence is provided that neither Mdm30 nor proteasome activity are necessary for tethering of mitochondria. However, both Mdm30 and proteasomes are critical for MOM fusion. To better understand the requirement for the ubiquitin-proteasome system in mitochondrial fusion, we used the N-end rule system of degrons and determined that ongoing degradation of Fzo1 is important for mitochondrial morphology and respiration. These findings suggest a sequence of events in early mitochondrial fusion where Fzo1 GTPase-domain-dependent tethering leads to recruitment of SCF(Mdm30) and ubiquitin-mediated degradation of Fzo1, which facilitates mitochondrial fusion.

Voice-related quality of life (V-RQOL) outcomes in laryngectomees.

BACKGROUND: Laryngeal cancer has a significant impact on patients. This study compared the Voice-Related Quality of Life (V-RQOL) outcomes specific to 3 different postlaryngectomy voice rehabilitation methods. METHODS: We conducted a retrospective review of 75 patients with laryngectomy from our V-RQOL questionnaire database. RESULTS: The database included 18 electrolaryngeal speech (ELS), 15 esophageal speech (ES), and 42 tracheoesophageal speech (TES) patients. Pairwise comparisons of V-RQOL outcomes showed that TES was perceived to be better than ELS (p < .001). ES was perceived as better than ELS, but this was driven by a difference in the total and social-emotional V-RQOL scores (p < .05). There was no difference between TES and ES groups. Only ELS showed a positive correlation with time after surgery and older age. CONCLUSIONS: Patients using TES had similar V-RQOL outcomes compared to ES and both performed significantly better than ELS. For ELS, the total V-RQOL score was better with longer time after surgery and older age.