Validation of the 10-Item Unilateral Vocal Fold Paralysis-Handicap Index quality of life questionnaire.

OBJECTIVES: To validate and test the reliability of the 10-Item Unilateral Vocal Fold Paralysis-Voice Handicap Index (UVFP-HI-10) quality of life (QoL) questionnaire for patients with UVFP. DESIGN: Prospective describe study based on perceptive surveys. PARTICIPANTS: We recruited 61 patients with UVFP and 53 healthy individuals comprised the control group. MAIN OUTCOME MEASURES: Both the patients and controls completed the UVFP-HI-10 questionnaire. A statistical analysis was performed to assess the internal consistency and validity of the survey. In addition, maximum phonation time (MPT) was used to objectively measure patient QoL. RESULTS: Internal consistency was high (α = .914) and the correlation with MPT was significant (rs = -0.722). The estimated marginal mean in the discriminant validity study was around seven times higher in the UVFP group compared to the controls. The UVFP-HI-10 cut-off value was more than 0.9 and the sensitivity and specificity were more than 0.8. CONCLUSIONS: The UVFP-HI-10 is a self-administered patient-reported outcome questionnaire with a high reliability and excellent criterion-based validity. This questionnaire can be used to evaluate specific clinical complaints (e.g., vocalisation, swallowing, and breathing) in terms of their impact on QoL in patients with UVFP. Thus, its use is appropriate as a basic assessment tool as part of a specific UVFP treatment protocol.

Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly.

Human mitoribosomes are macromolecular complexes essential for translation of 11 mitochondrial mRNAs. The large and the small mitoribosomal subunits undergo a multistep maturation process that requires the involvement of several factors. Among these factors, GTP-binding proteins (GTPBPs) play an important role as GTP hydrolysis can provide energy throughout the assembly stages. In bacteria, many GTPBPs are needed for the maturation of ribosome subunits and, of particular interest for this study, ObgE has been shown to assist in the 50S subunit assembly. Here, we characterize the role of a related human Obg-family member, GTPBP5. We show that GTPBP5 interacts specifically with the large mitoribosomal subunit (mt-LSU) proteins and several late-stage mitoribosome assembly factors, including MTERF4:NSUN4 complex, MRM2 methyltransferase, MALSU1 and MTG1. Interestingly, we find that interaction of GTPBP5 with the mt-LSU is compromised in the presence of a non-hydrolysable analogue of GTP, implying a different mechanism of action of this protein in contrast to that of other Obg-family GTPBPs. GTPBP5 ablation leads to severe impairment in the oxidative phosphorylation system, concurrent with a decrease in mitochondrial translation and reduced monosome formation. Overall, our data indicate an important role of GTPBP5 in mitochondrial function and suggest its involvement in the late-stage of mt-LSU maturation.

Incidencia de la hiperostosis esquelética difusa idiopática sobre un modelo clínico de disfagia / Incidence of diffuse idiopathic skeletal hyperostosis from a model of dysphagia

OBJETIVO: Relacionar la clínica de disfagia con la enfermedad de Forestier-Rotes-Querol o hiperostosis esquelética difusa idiopática (HEDI), desorden por osificación del ligamento cervical anterior común y calcificaciones en otras articulaciones. PACIENTES Y MÉTODOS: Revisión del historial clínico-radiológico de 455 pacientes que en 5 años consultaron en nuestro centro por disfagia, remitidos desde Atención Primaria o diferentes especialidades. El diagnóstico de HEDI se estableció en función de los criterios descritos por Resnick. RESULTADOS: Sobre un volumen total de 32.544 pacientes atendidos, el 1,4% consultó por disfagia alta. En 51 casos con esta sintomatología -el 11,2% de los sujeto- pudieron verificarse datos congruentes con los hallazgos radiológicos diagnósticos de HEDI. La incidencia observada fue de 7:100.000 habitantes-año. Dos casos con disfagia severa mejoraron con la retirada del hueso cervical neoformado. CONCLUSIONES: La HEDI supone una osificación interarticular anquilosante habitualmente sistémica pero asintomática. Al manifestarse, distorsiona principalmente las funciones de cuello y vías altas, generando sobre todo disfagia. Unos pocos casos requieren cirugía liberadora de estas calcificaciones

OBJECTIVE: To relate symptoms of dysphagia to Forestier-Rotes Querol disease or diffuse idiopathic skeletal hyperostosis (DISH), a disorder due to ossification in the anterior longitudinal ligament and calcifications in other entheses. PATIENTS AND METHODS: Review of clinical and radiological findings in 455 outpatients attended at our Centre with dysphagia, for 5 years, referred from dental, trauma, neurological or primary health care. A diagnosis of DISH was established using Resnick's criteria. RESULTS: We detected 51 cases with dysphagia consistent with DISH diagnostic criteria - 11.2% of subjects suffering this symptom- out of 32544 outpatients attended. An incidence of 7:100000 inhabitants per year was observed. Two cases showed significant improvement after removing the new bone in the spine. CONCLUSIONS: DISH is an ankylosing ossification between the joints, frequently systemic but showing no clinical symptoms. When symptoms manifest, neck movements and upper airways are involved, mainly dysphagia. A few cases need surgery to relieve the calcification processes

Incidence of diffuse idiopathic skeletal hyperostosis from a model of dysphagia. / Incidencia de la hiperostosis esquelética difusa idiopática sobre un modelo clínico de disfagia.

OBJECTIVE: To relate symptoms of dysphagia to Forestier-Rotes Querol disease or diffuse idiopathic skeletal hyperostosis (DISH), a disorder due to ossification in the anterior longitudinal ligament and calcifications in other entheses. PATIENTS AND METHODS: Review of clinical and radiological findings in 455 outpatients attended at our Centre with dysphagia, for 5years, referred from dental, trauma, neurological or primary health care. A diagnosis of DISH was established using Resnick's criteria. RESULTS: We detected 51 cases with dysphagia consistent with DISH diagnostic criteria - 11.2% of subjects suffering this symptom- out of 32544 outpatients attended. An incidence of 7:100000 inhabitants per year was observed. Two cases showed significant improvement after removing the new bone in the spine. CONCLUSIONS: DISH is an ankylosing ossification between the joints, frequently systemic but showing no clinical symptoms. When symptoms manifest, neck movements and upper airways are involved, mainly dysphagia. A few cases need surgery to relieve the calcification processes.

Longitudinal expression profiling of CD4+ and CD8+ cells in patients with active to quiescent giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA. METHODS: We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls. RESULTS: Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months. CONCLUSIONS: This is the first longitudinal gene expression study undertaken to identify robust transcriptomic biomarkers of GCA. Our results show cell type-specific transcript expression profiles, novel gene-phenotype associations, and uncover important biological pathways for this disease. In the acute phase, the gene-phenotype relationships we have identified could provide insight to potential disease severity and as such guide in initiating appropriate patient management.