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KCNQ4 is a voltage-gated K+ channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4p.W277S/p.W277S mice than in the Kcnq4+/+ and Kcnq4+/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation.
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Células Ciliadas Vestibulares , Canais de Potássio KCNQ , Camundongos Transgênicos , Animais , Canais de Potássio KCNQ/metabolismo , Canais de Potássio KCNQ/genética , Células Ciliadas Vestibulares/metabolismo , Células Ciliadas Vestibulares/patologia , Camundongos , Fenilenodiaminas/farmacologia , Carbamatos/farmacologia , Vestíbulo do Labirinto/metabolismo , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiopatologiaRESUMO
High temperature requirement A serine peptidase 1 (HTRA1) is a serine protease involved in an array of signaling pathways. It is also responsible for the regulation of protein aggregates via refolding, translocation, and degradation. It has subsequently been found that runaway proteolytic HTRA1 activity plays a role in a variety of diseases, including Age-Related Macular Degeneration (AMD), osteoarthritis, and Rheumatoid Arthritis. Selective inhibition of serine protease HTRA1 therefore offers a promising new strategy for the treatment of these diseases. Herein we disclose structure-activity-relationship (SAR) studies which identify key interactions responsible for binding affinity of small molecule inhibitors to HTRA1. The study results in highly potent molecules with IC50's less than 15 nM and excellent selectivity following a screen of 35 proteases.
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Serina Peptidase 1 de Requerimento de Alta Temperatura A , Serina Endopeptidases , Serina Peptidase 1 de Requerimento de Alta Temperatura A/metabolismo , Relação Estrutura-Atividade , Humanos , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/síntese química , Estrutura Molecular , Relação Dose-Resposta a Droga , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese químicaRESUMO
Introduction: Dysphagia is a common complication in patients with cervical spinal cord injury (C-SCI) and can cause various pulmonary complications, such as aspiration pneumonia and mechanical airway obstruction increasing mortality and morbidity. This study evaluated the clinical factors that predict dysphagia in patients with traumatic and non-traumatic C-SCI. Methods: Ninety-eight patients with C-SCI were retrospectively enrolled in this study and were divided into those with and without dysphagia. Clinical factors such as age, sex, tracheostomy, spinal cord independence measure, pulmonary function test (PFT) including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FVC/FEV1, American Spinal Cord Injury Association score, Berg Balance Scale, and surgical approach were investigated retrospectively. Results: Multivariate logistic regression analysis revealed that FVC and the presence of tracheostomy were significantly correlated with dysphagia in patients with C-SCI (p < 0.05). FVC and the presence of tracheostomy are useful tools for detecting dysphagia in patients with C-SCI. Conclusion: Considering the results of our study, early PFTs, especially FVC, in patients with C-SCI and early initiation of dysphagia management and treatment in patients with C-SCI and tracheostomy will be advantageous in lowering the mortality and morbidity due to pulmonary aspiration in these patients.
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Background: The vestibular phenotypes of patients with genetic hearing loss are poorly understood. Methods: we performed genetic testing including exome sequencing and vestibular function tests to investigate vestibular phenotypes and functions in patients with genetic hearing loss. Results: Among 627 patients, 143 (22.8%) had vestibular symptoms. Genetic variations were confirmed in 45 (31.5%) of the 143 patients. Nineteen deafness genes were linked with vestibular symptoms; the most frequent genes in autosomal dominant and recessive individuals were COCH and SLC26A4, respectively. Vestibular symptoms were mostly of the vertigo type, recurrent, and persisted for hours in the genetically confirmed and unconfirmed groups. Decreased vestibular function in the caloric test, video head impulse test, cervical vestibular-evoked myogenic potential, and ocular vestibular-evoked myogenic potential was observed in 42.0%, 16.3%, 57.8%, and 85.0% of the patients, respectively. The caloric test revealed a significantly higher incidence of abnormal results in autosomal recessive individuals than in autosomal dominant individuals (p = 0.011). The genes, including SLC26A4, COCH, KCNQ4, MYH9, NLRP3, EYA4, MYO7A, MYO15A, and MYH9, were heterogeneously associated with abnormalities in the vestibular function test. Conclusions: In conclusion, diverse vestibular symptoms are commonly concomitant with genetic hearing loss and are easily overlooked.
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BACKGROUND: Mutations in mitochondrial DNA (mtDNA) are associated with several genetic disorders, including sensorineural hearing loss. However, the prevalence of mtDNA mutations in a large cohort of Korean patients with hearing loss has not yet been investigated. Thus, this study aimed to investigate the frequency of mtDNA mutations in a cohort of with pre- or post-lingual hearing loss of varying severity. METHODS: A total of 711 Korean families involving 1,099 individuals were evaluated. Six mitochondrial variants associated with deafness (MTRNR1 m.1555A>G, MTTL1 m.3243A>G, MTCO1 m.7444G>A and m.7445A>G, and MTTS1 m.7471dupC and m.7511T>C) were screened using restriction fragment length polymorphism. The prevalence of the six variants was also analyzed in a large control dataset using whole-genome sequencing data from 4,534 Korean individuals with unknown hearing phenotype. RESULTS: Overall, 12 of the 711 (1.7%) patients with hearing loss had mtDNA variants, with 10 patients from independent families positive for the MTRNR1 m.1555A>G mutation and 2 patients positive for the MTCO1 m.7444G>A mutation. The clinical characteristics of patients with the mtDNA variants were characterized by post-lingual progressive hearing loss due to the m.1555A>G variant (9 of 472; 1.9%). In addition, 18/4,534 (0.4%) of the Korean population have mitochondrial variants associated with hearing loss, predominantly the m.1555A>G variant. CONCLUSION: A significant proportion of Korean patients with hearing loss is affected by the mtDNA variants, with the m.1555A>G variant being the most prevalent. These results clarify the genetic basis of hearing loss in the Korean population and emphasize the need for genetic testing for mtDNA variants.
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Perda Auditiva Neurossensorial , Perda Auditiva , Humanos , Prevalência , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Mutação , DNA Mitocondrial/genética , República da Coreia/epidemiologiaRESUMO
Genetic hearing loss is the most common hereditary sensorial disorder. Though more than 120 genes associated with deafness have been identified, unveiled causative genes and variants of diverse types of hearing loss remain. Herein, we identified a novel nonsense homozygous variant in CEP250 (c.3511C>T; p.Gln1171Ter) among the family members with progressive moderate sensorineural hearing loss in nonsyndromic autosomal recessive type but without retinal degeneration. CEP250 encodes C-Nap1 protein belonging to the CEP protein family, comprising 30 proteins that play roles in centrosome aggregation and cell cycle progression. The nonsense variant in CEP250 led to the early truncating protein of C-Nap1, which hindered centrosome localization; heterologous expression of CEP250 (c.3511C>T) in NIH3T3 cells within cilia expression condition revealed that the truncating C-Nap1 (p.Gln1171Ter) was not localized at the centrosome but was dispersed in the cytosol. In the murine adult cochlea, Cep250 was expressed in the inner and outer hair cells. Knockout mice of Cep250 showed significant hair cell degeneration and progressive hearing loss in auditory brainstem response. In conclusion, a nonsense variant in CEP250 results in a deficit of centrosome localization and hair cell degeneration in the cochlea, which is associated with the progression of hearing loss in humans and mice.
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Pathogenic variants of KCNQ4 cause symmetrical, late-onset, progressive, high-frequency-affected hearing loss, which eventually involves all frequencies with age. To understand the contribution of KCNQ4 variants to hearing loss, we analyzed whole-exome and genome sequencing data from patients with hearing loss and individuals whose hearing phenotypes were unknown. In KCNQ4, we identified seven missense variants and one deletion variant in 9 hearing loss patients and 14 missense variants in the Korean population with an unknown hearing loss phenotype. The p.R420W and p.R447W variants were found in both cohorts. To investigate the effects of these variants on KCNQ4 function, we performed whole-cell patch clamping and examined their expression levels. Except for p.G435Afs*61, all KCNQ4 variants exhibited normal expression patterns similar to those of wild-type KCNQ4. The p.R331Q, p.R331W, p.G435Afs*61, and p.S691G variants, which were identified in patients with hearing loss, showed a potassium (K+) current density lower than or similar to that of p.L47P, a previously reported pathogenic variant. The p.S185W and p.R216H variants shifted the activation voltage to hyperpolarized voltages. The channel activity of the p.S185W, p.R216H, p.V672M, and p.S691G KCNQ4 proteins was rescued by the KCNQ activators retigabine or zinc pyrithione, whereas p.G435Afs*61 KCNQ4 proteins were partially rescued by sodium butyrate, a chemical chaperone. Additionally, the structure of the variants predicted using AlphaFold2 showed impaired pore configurations, as did the patch-clamp data. Our findings suggest that KCNQ4 variants may be overlooked in hearing loss that starts in adulthood. Some of these variants are medically treatable; hence, genetic screening for KCNQ4 is important.
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Surdez , Perda Auditiva , Humanos , Linhagem , Perda Auditiva/genética , Surdez/genética , Audição , Mutação de Sentido Incorreto , Canais de Potássio KCNQ/genéticaRESUMO
OBJECTIVES: Despite growing interest in the genetic contribution to cochlear implant (CI) outcomes, only a few studies with limited samples have examined the association of CI outcomes with genetic etiologies. We analyzed CI outcomes using known predictors and genetic testing results to obtain a comprehensive understanding of the impact of genetic etiologies. DESIGN: We retrospectively reviewed the medical records and images of patients who underwent cochlear implantation and genetic testing at a single tertiary medical institution, between May 2008 and December 2020. After excluding those whose speech test results were unavailable, and those in whom the implant was removed due to complications, such as infection or device failure, 203 patients were included in this study. The participants were categorized into adult (≥19 years), child (2-18 years), and infant (<24 months) groups. Outcomes were measured based on categories of auditory perception, monosyllable, disyllable, and sentence scores. For the infant group, the Infant-Toddler Meaningful Auditory Integration Scale score was used. RESULTS: Among the 203 participants, a causative genetic variant was identified in 117 (57.6%) individuals. The presence of a causative variant was significantly associated with better CI outcomes in the infant group (ß = 0.23; 95% confidence interval, 0.01 to 0.47; p = 0.044), but not in the child and adult groups. In the genetically confirmed patients without cochlear malformation, genetic variants involving the spiral ganglion was a poor prognostic factor in the child group (ß = -57.24; 95% confidence interval, -90.63 to -23.75; p = 0.004). CONCLUSIONS: The presence of known genetic etiology of hearing loss was associated with better CI outcomes in the infant group, but not in the child and adult groups. A neural-type genetic variant was a poor prognostic factor in the genetically diagnosed child subgroup without cochlear malformation. Careful genetic counseling should be performed before cochlear implantation.
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Implante Coclear , Implantes Cocleares , Percepção da Fala , Adulto , Lactente , Humanos , Implante Coclear/métodos , Estudos Retrospectivos , Resultado do Tratamento , Testes GenéticosRESUMO
Background: Although it is generally agreed that vitamin D is important for bone health, the role of vitamin D in preventing fractures in children and adolescents remains unclear. Therefore, this study aimed to investigate the prevalence of vitamin D deficiency and insufficiency in healthy Korean children with fractures. Our secondary aim was to compare serum vitamin D levels before and during the coronavirus disease 2019 (COVID-19) outbreak. Methods: We evaluated 334 patients with fractures who were surgically treated at our institution between 2018 and 2019 before the onset of COVID-19 (group I). In addition, we collected data on the serum 25(OH)D levels of 210 patients who visited our pediatric department for evaluation of short stature (group II) and the serum 25(OH)D levels of the patients with fractures during the COVID-19 pandemic period (group III). A serum 25(OH)D level of <20 ng/mL was considered deficient, between 20 and 32 ng/mL was insufficient, and ≥32 ng/mL was considered sufficient. Results: The mean age was 8.1 ± 3.5 years in group I, 8.2 ± 3.7 years in group II, and 8.6 ± 3.5 years in group III. The prevalence of vitamin D deficiency was 53.0% in group I and 32.9% in group II. The mean serum 25(OH)D level was lower in group I than in group II (20.0 ± 7.3 ng/ml vs. 23.2 ± 6.9 ng/ml, p < 0.001). The mean serum 25(OH)D level of younger patients (<10 years) in group III was lower than that of the younger patients in the prepandemic period (21.4 ± 7.2 ng/mL vs. 19.2 ± 6.8 ng/mL, p=0.037). Conclusions: We observed a high prevalence of vitamin D deficiency/insufficiency in children with fractures who required surgical treatment. During the COVID-19 pandemic, the serum vitamin D levels became even lower, especially in younger children.
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COVID-19 , Fraturas Ósseas , Deficiência de Vitamina D , Adolescente , COVID-19/complicações , COVID-19/epidemiologia , Criança , Pré-Escolar , Surtos de Doenças , Fraturas Ósseas/epidemiologia , Humanos , Pandemias , Prevalência , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologiaRESUMO
Background: This study aimed to evaluate the injury mechanism of medial epicondylar fractures in children and adolescents and its association with increased carrying angle (CA) as a predisposing factor. Materials and Methods: We evaluated 37 patients with medial epicondylar fractures who were surgically treated at our institution. Medical records and plain radiographs were reviewed to determine the mechanism of injury and the humerus-elbow-wrist angle (HEWA) and CA of the uninjured arm. To evaluate the effect of coronal alignment on specific fracture type, we compared the CA and HEWA of the 23 patients with medial epicondylar fracture who were injured by falling onto an outstretched hand (group I) with age- and sex-matched controls of 23 patients who had sustained extension-type supracondylar fractures (group II). Results: The mean age at injury was 11.7 ± 2.8 years (range, 5 to 16 years). Of the 37 patients, 23 (62.2%) recalled the injury mechanism as falling onto an outstretched hand and 10 patients (27.0%) were injured while arm wrestling, and in one patient (2.7%), the injury was associated with elbow dislocation. In the case-matched analysis, the mean HEWA of group I was 13.1 ± 2.8° (range, 7.1° to 19.8°) and the mean CA was 17.7 ± 2.7° (range, 13.0° to 22.2°). These angles were significantly increased in group I (p=0.003 and p=0.001, respectively). Conclusion: Falling onto an outstretched hand is the most common injury mechanism in patients with medial epicondylar fractures, and these fractures are associated with an increased CA.
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Lesões no Cotovelo , Articulação do Cotovelo , Fraturas do Úmero , Adolescente , Criança , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype-phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype-genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss.
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Intracellular accumulation of mutant proteins causes proteinopathies, which lack targeted therapies. Autosomal dominant hearing loss (DFNA67) is caused by frameshift mutations in OSBPL2. Here, we show that DFNA67 is a toxic proteinopathy. Mutant OSBPL2 accumulated intracellularly and bound to macroautophagy/autophagy proteins. Consequently, its accumulation led to defective endolysosomal homeostasis and impaired autophagy. Transgenic mice expressing mutant OSBPL2 exhibited hearing loss, but osbpl2 knockout mice or transgenic mice expressing wild-type OSBPL2 did not. Rapamycin decreased the accumulation of mutant OSBPL2 and partially rescued hearing loss in mice. Rapamycin also partially improved hearing loss and tinnitus in individuals with DFNA67. Our findings indicate that dysfunctional autophagy is caused by mutant proteins in DFNA67; hence, we recommend rapamycin for DFNA67 treatment.Abbreviations: ABR: auditory brainstem response; ACTB: actin beta; CTSD: cathepsin D; dB: decibel; DFNA67: deafness non-syndromic autosomal dominant 67; DPOAE: distortion product otoacoustic emission; fs: frameshift; GFP: green fluorescent protein; HsQ53R-TG: human p.Q53Rfs*100-transgenic: HEK 293: human embryonic kidney 293; HFD: high-fat diet; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSHL: non-syndromic hearing loss; OHC: outer hair cells; OSBPL2: oxysterol binding protein-like 2; SEM: scanning electron microscopy; SGN: spiral ganglion neuron; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TG: transgenic; WES: whole-exome sequencing; YUHL: Yonsei University Hearing Loss; WT: wild-type.
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Surdez , Receptores de Esteroides , Animais , Humanos , Camundongos , Autofagia/genética , Surdez/genética , Células HEK293 , Camundongos Knockout , Camundongos Transgênicos , Proteínas Mutantes , Mutação/genética , Receptores de Esteroides/genética , Sirolimo/farmacologiaRESUMO
This phenotype-genotype study aimed to investigate the extent of audioprofile variability related to cochlin major domains and to identify potential ethnic-specific differences associated with COCH-related hearing loss. Eight Korean families (26 cases) were diagnosed with COCH-related hearing loss by exome sequencing. Audiometric test results were combined with those from nine published East Asian families (20 cases) and compared with those from 38 European-descent families (277 cases). Audioprofiles were created by grouping audiometric test results into age ranges by age at testing and then averaging hearing loss thresholds by frequency within age ranges. The functional impact of the identified variants was assessed in vitro by examining the intracellular trafficking, secretion, and cleavage of cochlin. In both East Asian and European-descent families segregating COCH-related hearing loss, deafness-associated variants in non-LCCL domains of cochlin were associated with hearing loss that was more severe earlier in life than hearing loss caused by variants in the LCCL domain. Consistent with this phenotypic difference, functional studies demonstrated distinct pathogenic mechanisms for COCH variants in a domain-dependent manner; specifically, a cytotoxic effect was observed for the p.Phe230Leu variant, which is located in the vWFA1 domain. No ethnic-specific differences in hearing loss progression were observed, except for those attributable to an overrepresentation of presymptomatic cases in the European-descent cohort.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Humanos , Surdez/genética , Proteínas da Matriz Extracelular/genética , Genótipo , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Mutação , Linhagem , FenótipoRESUMO
Ski-slope hearing loss (HL), which refers to increased auditory threshold at high frequencies, is common in adults. However, genetic contributions to this post-lingual HL remain largely unknown. Here, we prospectively investigated deafness-associated and novel candidate genes causing ski-slope HL. We analyzed 192 families with post-lingual HL via gene panel and/or exome sequencing. With an overall molecular diagnostic rate of 35.4% (68/192) in post-lingual HL, ski-slope HL showed a lower diagnostic rate (30.7%) compared with other conditions (40.7%). In patients who showed HL onset before the age of 40, genetic diagnostic probability was significantly lower for ski-slope HL than for other conditions. Further analysis of 51 genetically undiagnosed patients in the ski-slope HL group identified three variants in delta-like ligand 1 (DLL1), a Notch ligand, which presented in vitro gain-of-function effects on Notch downstream signaling. In conclusion, genetic diagnostic rates in post-lingual HL varied according to audiogram patterns with age-of-onset as a confounding factor. DLL1 was identified as a candidate gene causing ski-slope HL.
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Perda Auditiva Neurossensorial , Perda Auditiva , Adulto , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Testes Auditivos , Humanos , Ligantes , Patologia Molecular , Linhagem , Sequenciamento do ExomaRESUMO
BACKGROUND: Trampoline-related fractures of the proximal tibial metaphysis are common in children and have been linked to subsequent valgus deformity of the tibia. The purpose of this study was to investigate the characteristics of trampoline-related proximal tibial fractures in young children. METHODS: We evaluated 40 patients with proximal tibial fracture after trampolining between 2013 and 2019. The median duration of follow-up was 18 months. Standing long leg radiographs were obtained at the last follow-up to evaluate angular deformity and limb length inequality in the patients. The measurements recorded include the lower limb length, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), mechanical axis deviation (MAD), and anatomical tibio-femoral angle (aTFA). The anterior tilt angle (ATA) was measured using a lateral radiograph of the tibia. RESULTS: The median age at injury was 40.0 months. Using trampoline with a heavier person was the most common mechanism of injury. aTFA and MAD were found to be increased towards the valgus at the last follow-up in our patient; however, the increase was not statistically significant (p = 0.692 and p = 0.973, respectively). The anterior tilt angle was increased in the injured leg at the last follow-up. But the change was not statistically significant (p = 0.09). CONCLUSIONS: Using trampoline with a heavier person carries the risk of trampoline-related proximal tibial fracture in young children. We did not find a significant change in limb alignment at a minimum of one year of follow-up.
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Tíbia , Fraturas da Tíbia , Pré-Escolar , Fêmur , Humanos , Radiografia , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/epidemiologiaRESUMO
The development of technology-based home fitness has emerged from the booming digital healthcare market and recent demands for at-home fitness and health equipment due to the COVID-19 pandemic. Digital healthcare company Alyce Healthcare recently developed Weelo, which is a web-based online fitness program. Weelo recommends an exercise protocol through machine-learning-enabled recognition of the user's motion and provides visual and auditory feedback. We evaluated whether Weelo improves physical and mental well-being to assess its capabilities and effectiveness. Thirty-two participants performed a total of 20 exercise sessions following the Weelo guide on a laptop. The participants were evaluated using a before and after exercise program, body composition, handgrip strength, six-minute walk test, modified star excursion balance test, short form 36, fatigue severity scale, Beck depression index, and a satisfaction survey. Overall, there was a significant improvement in muscle strength, endurance, and balance ability, as well as an improved quality of life and significant reduction in fatigue and depression. Participants showed high motivation to continue following the Weelo exercise program. In conclusion, utilizing Weelo improved physical and mental well-being and is considered to be an individual-use indoor exercise program that serves as an alternative to traditional face-to-face exercise.
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Autosomal recessive nonsyndromic hearing loss 3 (DFNB3) mainly leads to congenital and severe-to-profound hearing impairment, which is caused by variants in MYO15A. However, audiological heterogeneity in patients with DFNB3 hinders precision medicine in hearing rehabilitation. Here, we aimed to elucidate the heterogeneity of the auditory phenotypes of MYO15A variants according to the affected domain and the feasibilities for acoustic stimulation. We conducted whole-exome sequencing for 10 unrelated individuals from seven multiplex families with DFNB3; 11 MYO15A variants, including the novel frameshift c.900delT (p.Pro301Argfs*143) and nonsense c.4879G > T (p.Glu1627*) variants, were identified. In seven probands, residual hearing at low frequencies was significantly higher in the groups with one or two N-terminal frameshift variants in trans conformation compared to that in the group without these variants. This is consistent with the 56 individuals from the previously published reports that carried a varying number of N-terminal truncating variants in MYO15A. In addition, patients with missense variants in the second FERM domain had better hearing at low frequencies than patients without these variants. Subsequently, acoustic stimulation provided by devices such as hearing aids or cochlear implants was feasible in patients with one or two N-terminal truncating variants or a second FERM missense variant. In conclusion, N-terminal or second FERM variants in MYO15A allow the practical use of acoustic stimulation through hearing aids or electroacoustic stimulation for aural rehabilitation.
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Implantes Cocleares , Auxiliares de Audição , Miosinas/genética , Estimulação Acústica , Estudos de Viabilidade , Variação Genética , Perda Auditiva Neurossensorial , Humanos , LinhagemRESUMO
BACKGROUND: Complex regional pain syndrome type I (CRPS I) is a chronic devastating condition and a relatively common complication of distal radius fractures (DRF). The purpose of this study was to investigate the relationship of vitamin D levels in surgically treated post-menopausal women with CRPS I occurrence in DRF. METHODS: From February 2016 to March 2017, 158 surgically treated post-menopausal patients with DRF were enrolled. Exclusion criteria were (1) patients who had been taking vitamin D or osteoporosis medication at the time of injury; (2) patients with medical factors that may affect vitamin D levels; (3) patients who were reluctant to enroll in the study; and (4) patient with additional fractures, ligamentous injuries, or neuropathy. A total of 107 patients were available for final analysis. We compared the serum vitamin D levels in post-menopausal women with DRF with CRPS I (group 1) and without CRPS I (group 2). Bone mineral density (BMD) of the femur and spine, osteocalcin, alkaline phosphatase (ALP), body mass index (BMI) were also measured. RESULTS: The average age at the time of surgery was 66.5 years (range, 39-86 years). The mean follow-up period was 16.3 months after surgery. Among the 107 surgically treated DRF patients, 19 (18%) met the Budapest criteria for CRPS I during the follow-up period. The mean serum vitamin D level in group 1 (15.2 ng/ml) was significantly lower than that in group 2 (20.5 ng/ml, p = 0.027). The mean values of osteocalcin, ALP, BMI, and BMD were not significantly different between the groups. CONCLUSION: Lower vitamin D levels in post-menopausal women can increase CRPS I occurrence in distal radius fractures.
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Síndromes da Dor Regional Complexa/etiologia , Pós-Menopausa , Complicações Pós-Operatórias/etiologia , Fraturas do Rádio/cirurgia , Deficiência de Vitamina D/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The Silfverskiöld test has long been used as an important tool for determining the affected muscles of the triceps surae in patients with equinus deformity. However, the test may not reflect the altered interactions between the muscles of the triceps which are affected by spasticity. The purpose of this study was to compare the architectural properties of the triceps surae muscles complex using ultrasonography, between hemiplegic patients and typically-developing children. Specifically, we wished to examine any differences in the architecture of the three muscles with various angle configurations of the knee and ankle joints. Ultrasound images of the medial gastrocnemius, lateral gastrocnemius, and soleus were acquired from paretic (group I) and non-paretic (group II) legs of ten patients and the legs (group III) of 10 age-matched normal children. A mixed model was used to evaluate the differences in the measurements of muscle architecture among the groups and the effects of various joint configurations on the measurements within the muscles. Compared to the results of measurements in groups II and III, the fascicle length was not different in the medial gastrocnemius of a paretic leg but it was longer in the lateral gastrocnemius and shorter in the soleus; the pennation angle was smaller in both medial and lateral gastrocnemii and was not different in the soleus; and the muscle thickness was found to be reduced in the three muscles of the paretic leg. Contrary to the observations in both the medial and lateral gastrocnemii, the fascicle length was increased and the pennation angle was decreased in the soleus with an increase of knee flexion. Through the current simulation study of the Silfverskiöld test using ultrasonography, we found that the changes detected in the architectural properties of the three muscles induced by systematic variations of the position at the ankle and the knee joints were variable. We believe that the limited utility of the Silfverskiöld test should be considered in determining an appropriate operative procedure to correct the equinus deformity in patients with altered architecture of the muscles in conditions such as cerebral palsy, as the differing muscle architectures of the triceps surae complex may affect the behavior of the muscles during the Silfverskiöld test.
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A 32-year-old man presented with simultaneous dorsal dislocations of the index-to-little finger carpometacarpal (CMC) joint with carpal bone fractures. Closed reduction was unsuccessful even after general anesthesia. During open dorsal approach, we found interposed joint capsule in the CMC joints and after removal of the joint capsule open reduction was easily achieved. We placed four Kirschner wires through the CMC joint. Furthermore, the fractured dorsal fragments of the trapezoid and hamate were fixed with mini screw in each. During 1-year followup, the patient showed good recovery and no evidence of posttraumatic arthritic changes in plain X-ray. We recommend to fix the dorsal fragment of the carpal bone with screws as well as the transarticular fixation of the CMC joint in case of concurrent CMC joint fracture-dislocation of all four fingers.