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Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host-microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced branching in BfaGCs, and mice monocolonized with this mutant strain had impaired colonic natural killer T (NKT) cell regulation, implying structure-specific immunomodulatory activity. The sphinganine chain branching of BfaGCs is a critical determinant of NKT cell activation, which induces specific immunomodulatory gene expression signatures and effector functions. Co-crystal structure and affinity analyses of CD1d-BfaGC-NKT cell receptor complexes confirmed the interaction of BfaGCs as CD1d-restricted ligands. We present a structural and molecular-level paradigm of immunomodulatory control by interactions of endobiotic metabolites with diet, microbiota and the immune system.
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Aminoácidos de Cadeia Ramificada/imunologia , Aminoácidos de Cadeia Ramificada/metabolismo , Bacteroides fragilis/metabolismo , Galactosilceramidas/imunologia , Galactosilceramidas/metabolismo , Microbioma Gastrointestinal/imunologia , Simbiose/imunologia , Aminoácidos de Cadeia Ramificada/química , Animais , Antígenos CD1d/imunologia , Bacteroides fragilis/genética , Humanos , Camundongos , Modelos Animais , Modelos Moleculares , Células T Matadoras Naturais/citologia , Células T Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologiaRESUMO
Repositioning is a common guideline for the prevention of pressure injuries of bedridden or wheelchair patients. However, frequent repositioning could deteriorate the quality of patient's life and induce secondary injuries. This paper introduces a method for continuous multi-site monitoring of pressure and temperature distribution from strategically deployed sensor arrays at skin interfaces via battery-free, wireless ionic liquid pressure sensors. The wirelessly delivered power enables stable operation of the ionic liquid pressure sensor, which shows enhanced sensitivity, negligible hysteresis, high linearity and cyclic stability over relevant pressure range. The experimental investigations of the wireless devices, verified by numerical simulation of the key responses, support capabilities for real-time, continuous, long-term monitoring of the pressure and temperature distribution from multiple sensor arrays. Clinical trials on two hemiplegic patients confined on bed or wheelchair integrated with the system demonstrate the feasibility of sensor arrays for a decrease in pressure and temperature distribution under minimal repositioning.
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Líquidos Iônicos , Cadeiras de Rodas , Humanos , Temperatura , Tecnologia sem Fio , PeleRESUMO
Background and Objectives: To find the differences in ocular axial length, keratometric measurements, and intraocular lens (IOL) power in patients with Graves' disease (GD) after treatment with a thionamide antithyroid drug (ATD), methimazole. Materials and Methods: The medical charts of 28 patients (4 males and 24 females; mean age: 47.2 ± 21.2 years) were studied. Each patient was examined twice using an IOL Master Device and keratometry at the first visit (before ATD treatment) and after 1 month of ATD treatment. The IOL power was calculated for each patient using the Hoffer Q, SRK-2, and SRK/T formulas according to axial length. Results: After 1 month, the axial length increased (right and left eyes: p < 0.001 and p = 0.05, respectively). Based on keratometry, changes in the horizontal and vertical optical power [in diopters (D)] were not statistically significant. However, the IOL power changed after 1 month of ATD treatment in 64.3% of the patients. In 14 patients (50%), there was a 0.5-1.0 D IOL power decrease in single eyes; in two patients (7.1%), an IOL power decrease of 0.5-1.0 D in both eyes; and in two patients (7.1%), a 0.5 D IOL power increase in single eyes. The calculated IOL power values were lower after ATD treatment (right and left eyes, p = 0.010 and p = 0.018, respectively). Conclusions: The IOL power changed in 64.3% of GD patients after ATD treatment. Therefore, avoiding cataract surgery at the early stage of ATD treatment would be appropriate for selecting a more accurate IOL power.
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Doença de Graves , Lentes Intraoculares , Facoemulsificação , Adulto , Idoso , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Refração Ocular , Estudos RetrospectivosRESUMO
INTRODUCTION: This study aimed to compare the performance of dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in evaluating bone mineral density (BMD) of patients with Duchenne muscular dystrophy and scoliosis. METHODOLOGY: Twenty-nine participants (mean age 19.72 ± 6.13 years) underwent whole spine radiography, DXA before and after traction, and QCT alone without traction. Scoliosis and vertebral rotation angles obtained before and after traction were compared, and BMD values from DXA were compared to those obtained via QCT. The scoliosis angle, presented as Cobb's angle of L1-L4, was measured. RESULTS: Cobb's angle significantly decreased from 30.38° ± 24.83° before traction to 22.78° ± 20.41° after traction (p < 0.0001) and the Z-score decreased from -1.88 ± 1.59 to -2.86 ± 2.16 (p < 0.0001). Changes in rotation angle, BMD, and bone mineral content were not significant. Post-traction BMD values and Z-scores showed a higher correlation with QCT measurements than pretraction. Moreover, pre and post-traction Z-scores (≤-1.1 and -1.36, respectively) were more accurate in identifying patients with osteoporosis according to QCT scans compared with the preexisting Z-score of -2 or less. CONCLUSION: Lumbar BMD measured via DXA and scoliosis allowed a more accurate diagnosis of osteoporosis when traction was applied.
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Absorciometria de Fóton , Densidade Óssea , Vértebras Lombares/diagnóstico por imagem , Distrofia Muscular de Duchenne/diagnóstico por imagem , Escoliose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Tração , Absorciometria de Fóton/métodos , Humanos , Vértebras Lombares/patologia , Masculino , Distrofia Muscular de Duchenne/patologia , Escoliose/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
Although progressive cardiac dysfunction is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), their cardiac function measured by conventional echocardiography has been generally interpreted as normal at a young age. We aimed to determine whether two-dimensional speckle tracking echocardiography (STE) or tissue Doppler imaging (TDI) could be used for early identification and detection of cardiac dysfunction in young patients with DMD. Thirteen pediatric patients (mean age, 9.69 ± 2.2 years) with DMD and 26 age-matched healthy children (mean age, 9.65 ± 2.2 years) were included in the study. All patients were examined via conventional echocardiography, TDI, and STE. Standard echocardiographic measurements of left ventricular (LV) systolic and diastolic function were obtained. Myocardial velocities including peak-systolic and early- and late-diastolic myocardial velocities were calculated in longitudinal direction in the interventricular septum, using TDI. Speckle tracking analyses were performed by acquiring apical four-, three-, and two-chamber views with the highest possible frame rates. Conventional parameters were similar between the two groups, but heart rates were higher in patients with DMD than in controls. The results of LV diastolic function evaluated using TDI showed that annular peak velocity during early diastole (e'; 10.9 ± 1.7 vs. 14.6 ± 1.7 cm/s), e'/a' ratio (2.0 ± 0.5 vs. 3.0 ± 0.5), E/e' ratio (9.4 ± 1.4 vs. 7.3 ± 0.8), and myocardial performance index (0.46 ± 0.05 vs. 0.36 ± 0.06) of the mitral septal annulus among patients with DMD differed significantly from those of healthy children. A significant decrease in global longitudinal systolic strain was found in patients with DMD (- 16.6 ± 3.7 vs. - 21.2 ± 2.1), with a marked decrease in the LV basal inferolateral and basal inferior walls. In young patients with DMD who have global normal systolic function, reductions in systolic deformation parameters as well as reduced early diastolic myocardial velocities can be detected particularly in the basal inferolateral LV walls. The prognostic significance of these findings warrants further longitudinal follow-up.
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Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Distrofia Muscular de Duchenne/complicações , Disfunção Ventricular Esquerda/etiologia , Criança , Ventrículos do Coração/fisiopatologia , Humanos , Variações Dependentes do Observador , Prognóstico , Estudos Prospectivos , Medição de Risco , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
OBJECTIVES: In the subjects with high cervical spinal cord injury (SCI), The difference of respiratory muscle strength and pulmonary function according to supine and sitting position were investigated whether there are changes in the tendency. METHODS: Twenty-three subjects with high cervical SCI and 23 subjects with low cervical and thoracic SCI were evaluated. The reference neurological level of injury for dividing the groups was fifth cervical vertebrae (C5). SCI severity was classified as motor-complete SCI. The supine and sitting forced vital capacity (FVC), percent of the predicted FVC (FVC%), maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), MEP / MIP ratio, and peak cough flow (PCF) were compared. RESULTS: The significantly higher FVC, FVC% in the low cervical and thoracic SCI group was identified in the supine position than the sitting position. The same tendency was observed in the high cervical SCI group. In the comparison of respiratory muscle strength, higher values of supine MEP and MIP were found only in the high cervical SCI group. PCF is more positively correlated with MIP than with MEP in all groups. CONCLUSION: We found that the supine position is more advantageous for the strong breathing and larger lung capacity in patients with high cervical SCI. The positive correlation between PCF and MIP in the patients with high cervical SCI was also confirmed. These results may be used to establish a pulmonary rehabilitation strategy for patients with high cervical SCI.
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Força Muscular/fisiologia , Músculos Respiratórios/fisiopatologia , Postura Sentada , Traumatismos da Medula Espinal/fisiopatologia , Decúbito Dorsal , Adulto , Vértebras Cervicais , Feminino , Humanos , Masculino , Pressões Respiratórias Máximas , Pessoa de Meia-Idade , Postura , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Vértebras Torácicas , Capacidade VitalRESUMO
The presence of fragmented QRS is a known marker of heterogeneous ventricular activation around the myocardial scar area. We validated whether fragmented QRS shows any association with ventricular dysfunction, fibrosis, or ventricular arrhythmias in patients with Duchenne muscular dystrophy (DMD). Thirty-seven patients with DMD were evaluated using electrocardiography (ECG), echocardiography, cardiac magnetic resonance, and 24-h Holter monitoring. Associations between fragmented QRS and ventricular dysfunction, fibrosis, or ventricular arrhythmia were investigated. Fragmented QRS complexes were present in 31 of 37 (83.7%) patients, and they were associated with a significantly lower left ventricular ejection fraction along with an increased left ventricular Tei index as evaluated by echocardiography, and more frequent ventricular arrhythmia as indicated using 24-hour Holter monitoring compared with patients without fragmented QRS. The number of leads with fragmented QRS correlated negatively with left ventricular ejection fraction both using echocardiography (r = -0.616) and CMR (r = -0.516). Further, the number of leads with fragmented QRS showed a significant correlation with several other echocardiographic measurements (mitral Em and Sm, and left ventricular Tei index), and 2-dimensional speckle-tracking echocardiography derived global left ventricular longitudinal strain. The frequency of ventricular arrhythmia observed using Holter monitoring showed a significant positive correlation with the frequency of fragmented QRS on ECG (r = 0.674). There was a positive trend of correlation between fragmented QRS and the amount of myocardial fibrosis as assessed by late gadolinium enhancement using CMR, but the statistical significance of the relationship was low (r = 0.433, p = 0.056). Fragmentation of QRS complexes is associated with degrees of left ventricular dysfunction, fibrosis, and ventricular arrhythmias in patients with DMD.
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Arritmias Cardíacas/diagnóstico , Ecocardiografia , Eletrocardiografia Ambulatorial , Imagem Cinética por Ressonância Magnética , Distrofia Muscular de Duchenne/complicações , Disfunção Ventricular Esquerda/diagnóstico , Adolescente , Adulto , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Criança , Eletrocardiografia , Fibrose/diagnóstico , Fibrose/diagnóstico por imagem , Humanos , Imagem Multimodal , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto JovemRESUMO
Recently, small-molecule covalent inhibitors have been accepted as a practical tool for targeting previously "undruggable" proteins. The high target selectivity of modern covalent inhibitors is now alleviating toxicity concerns regarding the covalent modifications of proteins. However, despite the tremendous clinical success of current covalent inhibitors, there are still unmet medical needs that covalent inhibitors have not yet addressed. This review categorized representative covalent inhibitors based on their mechanism of covalent inhibition: conventional covalent inhibitors, targeted covalent inhibitors (TCIs), and expanded TCIs. By reviewing both Food and Drug Administration (FDA)-approved drugs and drug candidates from recent literature, we provide insight into the future direction of covalent inhibitor development.
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Cell-based assays can monitor virus infection at a single-cell level with high sensitivity and cost-efficiency. For this purpose, it is crucial to develop molecular probes that respond selectively to physiological changes in live cells. We report stimuli-responsive light-emitters built on a T-shaped benzimidazole platform, and consecutive borylation reactions to produce a library of homologs displaying systematic changes in fluorescence quantum yield and environmental sensitivity. We find that certain fluorophores localize selectively at the endoplasmic reticulum, and interact with proteins involved in the stress signaling pathways. Notably, the mono-borylated compound responds selectively to the stress conditions by enhancing fluorescence, and detects avian influenza virus infection at the single-cell level. Our findings demonstrate the unprecedented practical utility of the stress-responsive molecular probes to differentiate cellular states for early diagnosis.
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Vírus da Influenza A , Influenza Aviária , Animais , Benzimidazóis , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/metabolismo , Vírus da Influenza A/fisiologia , Influenza Aviária/diagnóstico , Influenza Aviária/metabolismo , Sondas Moleculares/metabolismoRESUMO
Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.
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Técnicas Biossensoriais , Fontes de Energia Elétrica , Úlcera por Pressão , Pressão , Temperatura , Tecnologia sem Fio , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Desenho de Equipamento , Monitorização Fisiológica , Pele , Termografia/instrumentação , Termografia/métodosRESUMO
PURPOSE: To determine the incidence of keratoconus and to determine its possible association with common systemic diseases using a nationwide cohort. METHODS: This retrospective nationwide cohort study included 1,025,340 subjects from the Korean National Health Insurance Service-National Sample Cohort database from 2004 to 2013. Estimates for incidence rates of keratoconus were identified. After 1 : 5 matching using propensity scores, associations between keratoconus and certain systemic comorbidities were determined using multivariate logistic regression analysis. RESULTS: The incidence during the same period was 15.1 cases per 100,000 person-years. Adjusted logistic regression analysis after propensity score matching revealed significant associations between keratoconus and allergic rhinitis (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.63-2.13; p < 0.001), asthma (OR: 1.20; 95% CI: 1.06-1.36; p < 0.001), atopic dermatitis (OR: 1.33; 95% CI: 1.13-1.56; p < 0.001), and diabetes mellitus (DM) (OR: 1.35; 95% CI: 1.15-1.58; p < 0.001). CONCLUSION: Estimates of the incidence of keratoconus may help in the planning of eye-care policies, and the results of this study determined the associations between allergic diseases and keratoconus. Conflicting results regarding the association between keratoconus and DM should be further evaluated.
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We report two cases of postictal urinary retention in pediatric patients with cognitive impairment. Two girls with intellectual disabilities, concomitant cerebral palsy (case 1) and Rett syndrome (case 2), developed urinary retention following seizures. Their caregivers brought them to the hospital with complaints of abdominal distension. After excluding neurological progression, they were referred to the rehabilitation clinic for the evaluation and management of postictal urinary retention. We followed two different approaches in each case to restore normal urination. While serial manual cystometrograms were performed in case 1, clean intermittent catheterization with a voiding diary was performed in case 2 until restoration of normal urination. Based on these pediatric cases of successfully managed postictal urinary retention, we suggest that more attention may be needed for children with cognitive impairment to diagnose and manage postictal urinary retention.
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A 43-year-old woman suffered from drooling and dysphagia after a stroke in the left posterior inferior cerebellar artery territory. Videofluoroscopic swallowing study showed compatible findings of cricopharyngeal dysphagia. Despite the injection of botulinum neurotoxin, no symptom improvement was achieved and pharyngeal dystonia was considered as the cause. Medications for dystonia dramatically helped with saliva control and resulted in a small improvement in the progression of food from the pharyngeal to esophageal phase. After adjusting the drug dose, the patient was able to perform social activities without drooling. Moreover, she could consume food orally; however, this was limited to small amounts of liquid, and the main method of nutrition support was via an orogastric tube. Therefore, we suggest that physicians should make a differential diagnosis of combined dystonia in patients complaining of dysphagia by esophageal manometry and electromyography.
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BACKGROUND: The purpose of this study was to analyze the bone age and the upper extremity segmental lengths between the affected and the unaffected side and to reveal the correlation between the difference of bone age and the upper limb length discrepancy in the unilateral spastic cerebral palsy (CP). We also evaluated the relationship between difference of bone age and hand function. METHODS: Seventy-eight patients participated in this study. The bone ages of hand-wrists of the patients were determined by the Greulich and Pyle atlas. Upper extremity segmental lengths were measured by radiograph. The side-to side length discrepancy was calculated as a percentage. Hand function was classified according to the Manual Ability Classification System (MACS). RESULTS: There was significant difference in the bone age between the affected and unaffected side (p<0.001). Segmental lengths of the upper extremities showed significant differences between the affected and unaffected side (p<0.001). The hand function of 56 patients was evaluated by MACS and the MACS level showed correlation with difference of side-to-side bone age (r=0.29, p=0.03) and all segmental upper limb length discrepancies (p<0.05). The hand function in the bone-age-delayed group was significantly better than the hand function in the bone-age-symmetrical group (p<0.01). CONCLUSIONS: The bone age of the affected side compared to the unaffected side is delayed and the hand function of the affected side is correlated with the difference of side-to-side bone age and the upper limb length discrepancy. Hand function might be helpful for predicting potential limb shortness and delayed bone age.
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Determinação da Idade pelo Esqueleto , Paralisia Cerebral/fisiopatologia , Mãos/fisiopatologia , Extremidade Superior/fisiopatologia , Adolescente , Desenvolvimento Ósseo , Criança , Pré-Escolar , Feminino , Seguimentos , Lateralidade Funcional , Humanos , Lactente , Desigualdade de Membros Inferiores , Masculino , PrognósticoRESUMO
OBJECTIVE: To determine the abnormal pulmonary function value in Korean Duchenne muscular dystrophy (DMD) patients, we performed a comparative analysis of the patients' pulmonary function value expressed as % of the overseas reference data and Korean healthy children and adolescent reference data. METHODS: We performed pulmonary function test (PFT) in a total of 27 DMD patients. We compared the patients' FVC% and FEV1% of the overseas reference data with those of the Korean children and adolescent reference data. Also, we compared the patients' MIP% and MEP% of the prediction equation data with those of the Korean children and adolescent reference data. RESULTS: Age of the subjects ranged from 8 to 16 years (12.03±2.27 years). The mean maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and peak cough flow (PCF) were 36.93±9.5 cmH2O, 45.79±17.46 cmH2O, 1.4±0.43 L, 1.45±0.45 L, 1.40±0.41 L, and 206.25±61.21 L/min, respectively. The MIP%, MEP%, and FVC% of the Korean children and adolescent reference data showed statistically significant higher values than those of the prediction equation data. CONCLUSION: We observed a clear numeric difference between Korean DMD patients' pulmonary function value expressed as % of the overseas data and inland data. To perform a precise assessment of respiratory function and to determine appropriate respiratory therapy, pulmonary function values of Korean DMD patients should be interpreted taking into account the inland normal pulmonary function test data.
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[This corrects the article on p. 851 in vol. 40, PMID: 27847715.].
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OBJECTIVE: To evaluate the care status of the amyotrophic lateral sclerosis (ALS) patients with long-term use of tracheostomy tube by caregivers of ALS patients. METHODS: A survey was conducted in the form of questionnaires to ALS patients and their caregivers. All measurements were performed by two visiting nurses. For statistical analysis, SPSS ver. 22.0 and Mann-Whitney U test on non-normal distribution were used. RESULTS: In total, 19 patients (15 males and 4 females) and their caregivers participated in the survey. In the case of patients, the average duration of care was 5.9±3.7 years, and the mean periods of illness and tracheostomy were 5.3±3.2 years and 3.0±2.6 years, respectively. Replacement intervals were 14 days in 11 patients, 7 days in 4 patients, 28 days in 2 patients, and 21 days in 1 patient. One patient was unable to provide an accurate replacement interval. Eighteen (99%) caregivers had experience of adding volume to a cuff without pressure measure in the following instances: due to patients' needs in 7 cases, air leakage in 7 cases, and no reason in 4 cases. Mean pressure of tracheostomy cuff was 40±9.4 cmH2O, and air volume of tracheostomy cuff was 6.7±3.2 mL, but real mean volume was 7.0±2.9 mL. The number of suctioning for airway clearance was a mean 27.5±18.2 times a day. CONCLUSION: According to this survey, we notice that almost all the patients and caregivers had an erroneous idea about cuff volume and pressure. Moreover, education and long-term professional care of tracheostomy cannot be overemphasized in this manner.