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1.
Cell Cycle ; 21(11): 1153-1165, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35311459

RESUMO

We examined the apoptotic response of two glioblastoma cells, p53 wild type U87 and p53 mutated T98G, to doxorubicin, bortezomib, and vorinostat, which respectively target DNA, 26S proteasome and histone deacetylase, to clarify p53's function in apoptosis. We demonstrated that doxorubicin induced apoptosis in U87 cells but not in T98G cells. The level of p53 was definitively correlated to the extent of DNA damage and apoptosis initiation. Dominant-negative p53 reduced p21 expression, but did not affect doxorubicin-induced apoptosis, so the transcriptional activity of p53 seemed not to participate in doxorubicin-induced apoptosis. However, p53 concentrated into the nucleus during heavy apoptosis. Bortezomib could induce apoptosis in U87 with high sensitivity and T98G cells with low sensitivity. In contrast, vorinostat promoted apoptosis in both U87 and T98G cells and reduced the basal level of p53 in U87 cells, indicating that p53 played no role in the vorinostat-induced apoptosis. To clearly define the role of p53 in bortezomib- and doxorubicin-induced apoptosis, we combined doxorubicin with bortezomib to treat U87 cells to assess this combination's effect on apoptosis and p53 status. Interestingly, the combination of doxorubicin with bortezomib engendered compound stress, resulting in a synergistic outcome for apoptosis in U87 cells. However, the amounts of p53 in the total count and in the nucleus were much lower with the combination than with doxorubicin alone, suggesting that p53 played no role in either the compound stress, doxorubicin-only or bortezomib-induced apoptosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35258725

RESUMO

The effects of air pollution on sleep and dementia remain unclear. The objective of this study was to investigate the effects of air pollution on cognitive function as mediated by the sleep cycle. A cross-sectional study design was conducted to recruit 4866 subjects on which PSG had been performed. Fifty of them were further given a cognitive function evaluation by the MMSE and CASI as well as brain images by CT and MRI. Associations of 1-year air pollution parameters with sleep parameters, cognitive function, and brain structure were examined. We observed that O3 was associated with a decrease in arousal, an increase in the N1 stage, and a decrease in the N2 stage of sleep. NO2 was associated with an increase in the N1 stage, a decrease in the N2 stage, and an increase in REM. PM2.5 was associated with a decrease in the N1 stage, increases in the N2 and N3 stages, and a decrease in REM. The N1 and N2 stages were associated with cognitive decline, but REM was associated with an increase in cognitive function. The N1 stage was a mediator of the effects of PM2.5 on the concentration domain of the MMSE. O3 was associated with an increase in the pars orbitalis volume of the left brain. NO2 was associated with increases in the rostral middle frontal volume, supramarginal gyrus volume, and transverse temporal volume of the left brain, and the pars opercularis volume of the right brain. PM2.5 was associated with increases in the pars triangularis volume of the left brain and the fusiform thickness of the right brain. In conclusion, we observed that air pollution was associated with cognitive decline by mediating effects on the sleep cycle with changes in the brain structure in controlling executive, learning, and language functions in adults.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35239114

RESUMO

Obstructive sleep apnea (OSA) is associated with seasonal variations. The objective of this study was to examine associations of ambient relative humidity (RH) and temperature on sleep parameters. We conducted a cross-sectional study by retrospectively recruiting 5204 adults from a sleep center in Taipei, Taiwan. Associations of 1-night polysomnography with ambient RH and temperature in 1-day, 7-day, 1-month, 6-month, and 1-year averages were examined using linear regression models and a mediation analysis. RH increase was associated with snoring index decrease and apnea/hypopnea index (AHI) increase. Temperature increase was associated with decreases in sleep efficiency and the AHI, and increases in the wake time after sleep onset and snoring index. RH increase was inversely associated with non-rapid eye movement (NREM) sleep stage I (N1), III (N3), and rapid eye movement (REM) sleep, but positively associated with the NREM sleep stage II (N2) stage. Temperature increase was associated with N1, N2, and N3 sleep. An increase in RH was associated with an increase in the arousal index and a decrease in the < 95% arterial oxygen saturation (SaO2) among total, REM, and NREM sleep, whereas a temperature increase was associated with a decrease in the arousal index and an increase in < 95% SaO2 among total, REM, and NREM sleep. An increase in RH was associated with increases in the time spent in a supine posture and the supine AHI. An increase in temperature was associated with decreases in the supine posture, supine AHI, and non-supine AHI. The N3 sleep stage was an important mediator in increasing the supine AHI with a long-term increase in RH. But the N1 and N2 sleep stages mediated a decrease in the supine AHI with an increase in RH. In conclusion, ambient RH and temperature were associated with alterations in sleep parameters in adults, which were mediated by the sleep cycle. An understanding of outdoor environments has important implications for diagnostic classifications in the supine dominance of OSA in adults.

4.
J Clin Neurosci ; 98: 37-44, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35131723

RESUMO

PURPOSE: Obstructive sleep apnea syndrome (OSAS) has mostly been examined using in-laboratory polysomnography (Lab-PSG), which may overestimate severity. This study compared sleep parameters in different environments and investigated the association between the plasma levels of neurochemical biomarkers and sleep parameters. METHODS: Thirty Taiwanese participants underwent Lab-PSG while wearing a single-lead electrocardiogram patch. Participants' blood samples were obtained in the morning immediately after the recording. Participants wore the patch for the subsequent three nights at home. Sleep disorder indices were calculated, including the apnea-hypopnea index (AHI), chest effort index, and cyclic variation of heart rate index (CVHRI). The 23 eligible participants' derived data were divided into the normal-to-moderate (N-M) group and the severe group according to American Association of Sleep Medicine (AASM) guidelines (Lab-PSG) and the recommendations of a previous study (Rooti Rx). Spearman's correlation was used to examine the correlations between sleep parameters and neurochemical biomarker levels. RESULTS: The mean T-Tau protein level was positively correlated with the home-based CVHRI (r = 0.53, p < 0.05), whereas no significant correlation was noted between hospital-based CVHRI and the mean T-tau protein level (r = 0.25, p = 0.25). The home-based data revealed that the mean T-Tau protein level in the severe group was significantly higher than that in the N-M group (severe group: 24.75 ± 6.16 pg/mL, N-M group: 19.65 ± 3.90 pg/mL; p < 0.05). Furthermore, the mean in-hospital CVHRI was higher than the mean at-home values (12.16 ± 13.66 events/h). CONCLUSION: Severe OSAS patients classified by home-based CVHRI demonstrated the higher T-Tau protein level, and CVHRI varied in different sleep environments.


Assuntos
Doenças Neurodegenerativas , Apneia Obstrutiva do Sono , Biomarcadores , Frequência Cardíaca , Humanos , Projetos Piloto , Apneia Obstrutiva do Sono/diagnóstico , Proteínas tau
5.
PLoS One ; 17(1): e0262138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35051222

RESUMO

We previously revealed the origin of mammalian simple-type glycogen synthase kinase interaction protein (GSKIP), which served as a scavenger and a competitor in the Wnt signaling pathway during evolution. In this study, we investigated the conserved and nonconserved regions of the composite-type GSKIP by utilizing bioinformatics tools, site-directed mutagenesis, and yeast two-hybrid methods. The regions were denoted as the pre-GSK3ß binding site, which is located at the front of GSK3ß-binding sites. Our data demonstrated that clustered mitochondria protein 1 (CLU1), a type of composite-type GSKIP that exists in the mitochondria of all eukaryotic organisms, possesses the protein known as domain of unknown function 727 (DUF727), with a pre-GSK3ß-binding site and a mutant GSK3ß-binding flanking region. Another type of composite-type GSKIP, armadillo repeat containing 4 (ARMC4), which is known for cilium movement in vertebrates, contains an unintegrated DUF727 flanking region with a pre-GSK3ß-binding site (115SPxF118) only. In addition, the sequence of the GSK3ß-binding site in CLU1 revealed that Q126L and V130L were not conserved, differing from the ideal GSK3ß-binding sequence of simple-type GSKIP. We further illustrated two exceptions, namely 70 kilodalton heat shock proteins (Hsp70/DnaK) and Mitofilin in nematodes, that presented an unexpected ideal GSK3ß-binding region with a pre-GSK3ß sequence; this composite-type GSKIP could only occur in vertebrate species. Furthermore, we revealed the importance of the pre-GSK3ß-binding site (118F or 118Y) and various mutant GSK3ß-binding sites of composite-type GSKIP. Collectively, our data suggest that the new composite-type GSKIP starts with a DUF727 domain followed by a pre-GSK3ß-binding site, with the subsequent addition of the GSK3ß-binding site, which plays vital roles for CLU1, Mitofilin, and ARMC4 in mitochondria and Wnt signaling pathways during evolution.


Assuntos
Proteínas do Domínio Armadillo/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitocôndrias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Animais , Proteínas do Domínio Armadillo/química , Proteínas do Domínio Armadillo/genética , Sítios de Ligação , Clonagem Molecular , Sequência Conservada , Evolução Molecular , Humanos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Filogenia , Ligação Proteica , Conformação Proteica , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/química , Análise de Sequência de DNA , Técnicas do Sistema de Duplo-Híbrido , Via de Sinalização Wnt
6.
Cells ; 11(2)2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35053358

RESUMO

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood-brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1ß and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Inflamação/complicações , Neurônios/patologia , Piridinas/uso terapêutico , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/etiologia , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comportamento Animal/efeitos dos fármacos , Lesões Encefálicas/fisiopatologia , Citocinas/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Biológicos , Atividade Motora/efeitos dos fármacos , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Piridinas/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais , Hemorragia Subaracnóidea/fisiopatologia , Receptor 4 Toll-Like/metabolismo , Vasoespasmo Intracraniano/patologia , Vasoespasmo Intracraniano/fisiopatologia
7.
Nat Commun ; 13(1): 102, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013238

RESUMO

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/ .


Assuntos
Aminoácidos/química , Antineoplásicos/química , Software , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , /farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bases de Dados de Proteínas , Desenho de Fármacos/métodos , Humanos , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Ligação Proteica , Conformação Proteica em alfa-Hélice , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Relação Estrutura-Atividade
8.
Environ Sci Pollut Res Int ; 29(8): 11865-11873, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34553281

RESUMO

Fine particulate matter (PM2.5) has been linked to cardiopulmonary disease and systemic effects in humans. However, few studies have investigated the particle bioreactivity in Chinese megacities during haze episodes. The objective of this study was to determine the contributions of chemical components in PM2.5 to particle bioreactivity in Chinese megacities during haze episodes. PM2.5 samples were collected in 14 megacities across China from 23 December 2013 to 16 January 2014. Average PM2.5 concentrations ranged 88.92~199.67 µg/m3. Organic carbon (OC), elemental carbon (EC), anions, and cations per unit of PM2.5 were linked to cellular bioreactivity (i.e., reactive oxygen species (ROS) as assessed by dichlorodihydrofluorescein diacetate (DCFH) and inflammation as assessed by interleukin (IL)-6 in A549 cells). The contributions of chemicals in PM2.5 to ROS and inflammation were examined by the Pearson correlation coefficient and random forests. These results indicated that OC, Ca2+, SO42-, Cl-, F-, K+, and NO3- contributed to ROS production, whereas OC, Cl-, EC, K+, F-, Na+, and Ca2+ contributed to inflammation. In conclusion, PM2.5-contained OC and acidic ions are important in regulation of oxidative stress and inflammation during haze episodes. Our findings suggest that severe haze PM2.5 events cause deterioration in air quality and may adversely affect human health.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , China , Cidades , Monitoramento Ambiental , Humanos , Íons/análise , Tamanho da Partícula , Material Particulado/análise , Estações do Ano
9.
Environ Sci Pollut Res Int ; 29(4): 6140-6150, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34448140

RESUMO

Epidemiological studies identified the relationship between air pollution and pulmonary tuberculosis. Effects of lung-deposited dose of particulate matter (PM) on culture-positive pulmonary tuberculosis remain unclear. This study investigates the association between lung-deposited dose of PM and pulmonary tuberculosis pleurisy. A case-control study of subjects undergoing pleural effusion drainage of pulmonary tuberculosis (case) and chronic heart failure (control) was conducted. Metals and biomarkers were quantified in the pleural effusion. The air pollution exposure was measured and PM deposition in the head, tracheobronchial, alveolar region, and total lung region was estimated by Multiple-path Particle Dosimetry (MPPD) Model. We performed multiple logistic regression to examine the associations of these factors with the risk of tuberculosis. We observed that 1-µg/m3 increase in PM10 was associated with 1.226-fold increased crude odds ratio (OR) of tuberculosis (95% confidence interval (CI): 1.023-1.469, p<0.05), 1-µg/m3 increase in PM2.5-10 was associated with 1.482-fold increased crude OR of tuberculosis (95% CI: 1.048-2.097, p < 0.05), 1-ppb increase in NO2 was associated with 1.218-fold increased crude OR of tuberculosis (95% CI: 1.025-1.447, p < 0.05), and 1-ppb increase in O3 was associated with 0.735-fold decreased crude OR of tuberculosis (95% CI: 0.542 0.995). We observed 1-µg/m3 increase in PM deposition in head and nasal region was associated with 1.699-fold increased crude OR of tuberculosis (95% CI: 1.065-2.711, p < 0.05), 1-µg/m3 increase in PM deposition in tracheobronchial region was associated with 1.592-fold increased crude OR of tuberculosis (95% CI: 1.095-2.313, p < 0.05), 1-µg/m3 increase in PM deposition in alveolar region was associated with 3.981-fold increased crude OR of tuberculosis (95% CI: 1.280-12.386, p < 0.05), and 1-µg/m3 increase in PM deposition in total lung was associated with 1.511-fold increased crude OR of tuberculosis (95% CI: 1.050-2.173, p < 0.05). The results indicate that particle deposition in alveolar region could cause higher risk of pulmonary tuberculosis pleurisy than deposition in other lung regions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pleurisia , Tuberculose Pulmonar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Casos e Controles , Exposição Ambiental/análise , Humanos , Pulmão/química , Dióxido de Nitrogênio , Material Particulado/análise
10.
J Clin Sleep Med ; 18(4): 1003-1012, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34782066

RESUMO

STUDY OBJECTIVES: Dementia is associated with sleep disorders. However, the relationship between dementia and sleep arousal remains unclear. This study explored the associations among sleep parameters, arousal responses, and risk of mild cognitive impairment (MCI). METHODS: Participants with the chief complaints of memory problems and sleep disorders, from the sleep center database of Taipei Medical University Shuang-Ho Hospital, were screened, and the parameters related to the Cognitive Abilities Screening Instrument, Clinical Dementia Rating, and polysomnography were determined. All examinations were conducted within 6 months and without a particular order. The participants were divided into those without cognitive impairment (Clinical Dementia Rating = 0) and those with MCI (Clinical Dementia Rating = 0.5). Mean comparison, linear regression models, and logistic regression models were employed to investigate the associations among obtained variables. RESULTS: This study included 31 participants without MCI and 37 with MCI (17 with amnestic MCI, 20 with multidomain MCI). Patients with MCI had significantly higher mean values of the spontaneous arousal index and spontaneous arousal index in the non-rapid eye movement stage than those without MCI. An increased risk of MCI was significantly associated with increased spontaneous arousal index and spontaneous arousal index in the non-rapid eye movement stage with various adjustments. Significant associations between the Cognitive Abilities Screening Instrument scores and the oximetry parameters and sleep disorder indexes were observed. CONCLUSIONS: Repetitive respiratory events with hypoxia were associated with cognitive dysfunction. Spontaneous arousal, especially in non-rapid eye movement sleep, was related to the risk of MCI. However, additional longitudinal studies are required to confirm their causality. CITATION: Tsai C-Y, Hsu W-H, Lin Y-T, et al. Associations among sleep-disordered breathing, arousal response, and risk of mild cognitive impairment in a northern Taiwan population. J Clin Sleep Med. 2022;18(4): 1003-1012.


Assuntos
Disfunção Cognitiva , Síndromes da Apneia do Sono , Nível de Alerta , Disfunção Cognitiva/etiologia , Humanos , Testes Neuropsicológicos , Polissonografia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Taiwan/epidemiologia
12.
Clin Interv Aging ; 17: 589-599, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497053

RESUMO

Purpose: Severe complications, including screw loosening events and low fusion rates, in spinal fusion surgery using the traditional open method are problematic. This retrospective study aimed to evaluate the rate of screw loosening and the clinical outcomes of bone-mounted miniature robot-assisted pedicle screw placement in patients treated for degenerative spinal disease. Patients and Methods: Data were collected from the medical records of 118 patients (mean age, 69 years). Differences in clinical outcomes, including the Oswestry disability index, visual analog scale score, screw loosening rate, cage fusion rate, and complications, were evaluated among different bone mineral densities. Results: The screw loosening and cage fusion rates for all patients, normal bone mineral density, osteopenia, and osteoporosis groups were 12%, 8.6%, 13.1%, and 14%, respectively, and 85.3%, 93%, 82.5%, and 81.4%, respectively. There was a higher screw loosening rate and a lower cage fusion rate in the osteopenia and osteoporosis groups than in the normal bone density group. The accuracy of the screw placement was 97.3%. There were no statistically significant differences in the Oswestry disability index and visual analog scale scores, and no major complications for dural tear or vascular or visceral injury. Conclusion: Our study demonstrated an acceptable screw loosening rate in patients with osteoporosis compared to that in patients with normal bone mineral density. The robotic system resulted in accurate screw placement in patients with osteoporosis.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Procedimentos Cirúrgicos Robóticos , Idoso , Doenças Ósseas Metabólicas/diagnóstico por imagem , Humanos , Osteoporose/cirurgia , Radiografia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos
13.
Sensors (Basel) ; 21(23)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34884101

RESUMO

Obstructive sleep apnoea (OSA) is a global health concern, and polysomnography (PSG) is the gold standard for assessing OSA severity. However, the sleep parameters of home-based and in-laboratory PSG vary because of environmental factors, and the magnitude of these discrepancies remains unclear. We enrolled 125 Taiwanese patients who underwent PSG while wearing a single-lead electrocardiogram patch (RootiRx). After the PSG, all participants were instructed to continue wearing the RootiRx over three subsequent nights. Scores on OSA indices-namely, the apnoea-hypopnea index, chest effort index (CEI), cyclic variation of heart rate index (CVHRI), and combined CVHRI and CEI (Rx index), were determined. The patients were divided into three groups based on PSG-determined OSA severity. The variables (various severity groups and environmental measurements) were subjected to mean comparisons, and their correlations were examined by Pearson's correlation coefficient. The hospital-based CVHRI, CEI, and Rx index differed significantly among the severity groups. All three groups exhibited a significantly lower percentage of supine sleep time in the home-based assessment, compared with the hospital-based assessment. The percentage of supine sleep time (∆Supine%) exhibited a significant but weak to moderate positive correlation with each of the OSA indices. A significant but weak-to-moderate correlation between the ∆Supine% and ∆Rx index was still observed among the patients with high sleep efficiency (≥80%), who could reduce the effect of short sleep duration, leading to underestimation of the patients' OSA severity. The high supine percentage of sleep may cause OSA indices' overestimation in the hospital-based examination. Sleep recording at home with patch-type wearable devices may aid in accurate OSA diagnosis.


Assuntos
Apneia Obstrutiva do Sono , Eletrocardiografia , Hospitais , Humanos , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico
14.
Inform Health Soc Care ; : 1-16, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34886766

RESUMO

(a) Objective: Obstructive sleep apnea syndrome (OSAS) is typically diagnosed through polysomnography (PSG). However, PSG incurs high medical costs. This study developed new models for screening the risk of moderate-to-severe OSAS (apnea-hypopnea index, AHI ≥15) and severe OSAS (AHI ≥30) in various age groups and sexes by using anthropometric features in the Taiwan population.(b) Participants: Data were derived from 10,391 northern Taiwan patients who underwent PSG.(c) Methods: Patients' characteristics - namely age, sex, body mass index (BMI), neck circumference, and waist circumference - was obtained. To develop an age- and sex-independent model, various approaches - namely logistic regression, k-nearest neighbor, naive Bayes, random forest (RF), and support vector machine - were trained for four groups based on sex and age (men or women; aged <50 or ≥50 years). Dataset was separated independently (training:70%; validation: 10%; testing: 20%) and Cross-validated grid search was applied for model optimization. Models demonstrating the highest overall accuracy in validation outcomes for the four groups were used to predict the testing dataset.(d) Results: The RF models showed the highest overall accuracy. BMI was the most influential parameter in both types of OSAS severity screening models.(e) Conclusion: The established models can be applied to screen OSAS risk in the Taiwan population and those with similar craniofacial features.

17.
Sci Rep ; 11(1): 20983, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697379

RESUMO

Recessive variants of the SLC26A4 gene are an important cause of hereditary hearing impairment. Several transgenic mice with different Slc26a4 variants have been generated. However, none have recapitulated the auditory phenotypes in humans. Of the SLC26A4 variants identified thus far, the p.T721M variant is of interest, as it appears to confer a more severe pathogenicity than most of the other missense variants, but milder pathogenicity than non-sense and frameshift variants. Using a genotype-driven approach, we established a knock-in mouse model homozygous for p.T721M. To verify the pathogenicity of p.T721M, we generated mice with compound heterozygous variants by intercrossing Slc26a4+/T721M mice with Slc26a4919-2A>G/919-2A>G mice, which segregated the c.919-2A > G variant with abolished Slc26a4 function. We then performed serial audiological assessments, vestibular evaluations, and inner ear morphological studies. Surprisingly, both Slc26a4T721M/T721M and Slc26a4919-2A>G/T721M showed normal audiovestibular functions and inner ear morphology, indicating that p.T721M is non-pathogenic in mice and a single p.T721M allele is sufficient to maintain normal inner ear physiology. The evidence together with previous reports on mouse models with Slc26a4 p.C565Y and p.H723R variants, support our speculation that the absence of audiovestibular phenotypes in these mouse models could be attributed to different protein structures at the C-terminus of human and mouse pendrin.


Assuntos
Perda Auditiva/genética , Transportadores de Sulfato/química , Transportadores de Sulfato/genética , Animais , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Perda Auditiva/metabolismo , Perda Auditiva/patologia , Homozigoto , Humanos , Masculino , Camundongos , Mutação de Sentido Incorreto , Fenótipo , Domínios Proteicos , Especificidade da Espécie , Transportadores de Sulfato/metabolismo
18.
J Pers Med ; 11(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34683176

RESUMO

Hearing impairment is a frequent human sensory impairment. It was estimated that over 50% of those aged >75 years experience hearing impairment in the United States. Several hearing impairment-related factors are detectable through screening; thus, further deterioration can be avoided. Early identification of hearing impairment is the key to effective management. However, hearing screening resources are scarce or inaccessible, underlining the importance of developing user-friendly mobile health care systems for universal hearing screening. Mobile health (mHealth) applications (apps) act as platforms for personalized hearing screening to evaluate an individual's risk of developing hearing impairment. We aimed to evaluate and compare the accuracy of smartphone-based air conduction and bone conduction audiometry self-tests with that of standard air conduction and bone conduction pure-tone audiometry tests. Moreover, we evaluated the use of smartphone-based air conduction and bone conduction audiometry self-tests in conductive hearing loss diagnosis. We recruited 103 patients (206 ears) from an otology clinic. All patients were aged ≥20 years. Patients who were diagnosed with active otorrhea was excluded. Moderate hearing impairment was defined as hearing loss with mean hearing thresholds >40 dB. All patients underwent four hearing tests performed by a board-certified audiologist: a smartphone-based air conduction audiometry self-test, smartphone-based bone conduction audiometry self-test, standard air-conduction pure-tone audiometry, and standard bone conduction pure-tone audiometry. We compared and analyzed the results of the smartphone-based air conduction and bone conduction audiometry self-tests with those of the standard air conduction and bone conduction pure-tone audiometry tests. The sensitivity of the smartphone-based air conduction audiometry self-test was 0.80 (95% confidence interval CI = 0.71-0.88) and its specificity was 0.84 (95% CI = 0.76-0.90), respectively. The sensitivity of the smartphone-based bone conduction audiometry self-test was 0.64 (95% CI = 0.53-0.75) and its specificity was 0.71 (95% CI = 0.62-0.78). Among all the ears, 24 were diagnosed with conductive hearing loss. The smartphone-based audiometry self-tests correctly diagnosed conductive hearing loss in 17 of those ears. The personalized smartphone-based audiometry self-tests correctly diagnosed hearing loss with high sensitivity and high specificity, and they can be a reliable screening test to rule out moderate hearing impairment among the population. It provided patients with moderate hearing impairment with personalized strategies for symptomatic control and facilitated individual case management for medical practitioners.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34639340

RESUMO

As part of the new measures to prevent the spread of the 2019 coronavirus disease (COVID-19), medical students were advised to wear a mask in class and avoid touching their faces. Few studies have analyzed the influence of health education on the frequency of face- and smartphone-touching behaviors during the COVID-19 pandemic. This research compared the frequency of in-class face- and smartphone-touching behaviors of medical students before and after the delivery of personal hygiene education during the COVID-19 pandemic. A behavioral observational study was conducted involving medical students at Taipei Medical University. Eighty medical students were recruited during a lecture on otorhinolaryngology. All medical students were required to wear a mask. Their face- and smartphone-touching behavior was observed by viewing the 4 k resolution video tape recorded in class. The recording lasted for 2 h, comprising 1 h prior to the health educational reminder and 1 h afterwards. The frequencies of hand-to-face contact and hand-to-smartphone contact were analyzed before and after the delivery of health education emphasizing personal hygiene. Comprehensive health education and reminders effectively reduce the rate of face- and smartphone-touching behaviors.


Assuntos
COVID-19 , Pandemias , Humanos , Higiene , Pandemias/prevenção & controle , SARS-CoV-2 , Smartphone
20.
J Mol Diagn ; 23(10): 1279-1291, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34325055

RESUMO

Recessive variants in GJB2 are the most common genetic cause of sensorineural hearing impairment. However, in many patients, only one variant in the GJB2 coding region is identified using conventional sequencing strategy (eg, Sanger sequencing), resulting in nonconfirmative diagnosis. Conceivably, there might be other unidentified pathogenic variants in the noncoding region of GJB2 or other deafness-causing genes in these patients. To address this, a next-generation sequencing-based diagnostic panel targeting the entire GJB2 gene and the coding regions of 158 other known deafness-causing genes was designed and applied to 95 patients with nonsyndromic sensorineural hearing impairment (including 81 Han Taiwanese and 14 Mongolian patients) in whom only a single GJB2 variant had been detected using conventional Sanger sequencing. The panel confirmed the genetic diagnosis in 24 patients (25.3%). Twenty-two of them had causative variants in several deafness-causing genes other than GJB2, including MYO15A, MYO7A, TECTA, POU4F3, KCNQ4, SLC26A4, OTOF, MT-RNR1, MITF, WFS1, and USH2A. The other two patients had causative variants in GJB2, including a Taiwanese patient with a mosaic maternal uniparental disomy c.235delC variant (approximately 69% mosaicism) and a Mongolian patient with compound heterozygous c.35dupG and c.35delG variants, which occurred at the same site. This study demonstrates the utility of next-generation sequencing in clarifying the genetic diagnosis of hearing-impaired patients with nonconfirmative GJB2 genotypes on conventional genetic examinations.


Assuntos
Alelos , Conexina 26/genética , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Heterozigoto , Homozigoto , Síndromes de Usher/diagnóstico , Síndromes de Usher/genética , Frequência do Gene , Genes Recessivos , Testes Genéticos/métodos , Perda Auditiva Neurossensorial/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mongólia/epidemiologia , Mosaicismo , Fenótipo , Taiwan/epidemiologia , Dissomia Uniparental , Síndromes de Usher/epidemiologia
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