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1.
Proc Natl Acad Sci U S A ; 120(9): e2219394120, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36802437

RESUMO

Vocal fatigue is a measurable form of performance fatigue resulting from overuse of the voice and is characterized by negative vocal adaptation. Vocal dose refers to cumulative exposure of the vocal fold tissue to vibration. Professionals with high vocal demands, such as singers and teachers, are especially prone to vocal fatigue. Failure to adjust habits can lead to compensatory lapses in vocal technique and an increased risk of vocal fold injury. Quantifying and recording vocal dose to inform individuals about potential overuse is an important step toward mitigating vocal fatigue. Previous work establishes vocal dosimetry methods, that is, processes to quantify vocal fold vibration dose but with bulky, wired devices that are not amenable to continuous use during natural daily activities; these previously reported systems also provide limited mechanisms for real-time user feedback. This study introduces a soft, wireless, skin-conformal technology that gently mounts on the upper chest to capture vibratory responses associated with vocalization in a manner that is immune to ambient noises. Pairing with a separate, wirelessly linked device supports haptic feedback to the user based on quantitative thresholds in vocal usage. A machine learning-based approach enables precise vocal dosimetry from the recorded data, to support personalized, real-time quantitation and feedback. These systems have strong potential to guide healthy behaviors in vocal use.


Assuntos
Canto , Distúrbios da Voz , Voz , Humanos , Retroalimentação , Distúrbios da Voz/etiologia , Voz/fisiologia , Prega Vocal/fisiologia
2.
Proc Natl Acad Sci U S A ; 119(46): e2214164119, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36343234

RESUMO

A quantitative understanding of the coupled dynamics of flow and particles in aerosol and droplet transmission associated with speech remains elusive. Here, we summarize an effort that integrates insights into flow-particle dynamics induced by the production plosive sounds during speech with skin-integrated electronic systems for monitoring the production of these sounds. In particular, we uncover diffusive and ballistic regimes separated by a threshold particle size and characterize the Lagrangian acceleration and pair dispersion. Lagrangian dynamics of the particles in the diffusive regime exhibit features of isotropic turbulence. These fundamental findings highlight the value in skin-interfaced wireless sensors for continuously measuring critical speech patterns in clinical settings, work environments, and the home, based on unique neck biomechanics associated with the generation of plosive sounds. We introduce a wireless, soft device that captures these motions to enable detection of plosive sounds in multiple languages through a convolutional neural network approach. This work spans fundamental flow-particle physics to soft electronic technology, with implications in monitoring and studying critical speech patterns associated with aerosol and droplet transmissions relevant to the spread of infectious diseases.


Assuntos
Eletrônica , Fala , Aerossóis , Tamanho da Partícula , Movimento (Física)
3.
Ann Allergy Asthma Immunol ; 132(4): 457-462.e2, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37977324

RESUMO

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Estudos Prospectivos , Eosinófilos , Anticorpos Monoclonais/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antiasmáticos/uso terapêutico
4.
Lung ; 202(4): 405-414, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38847887

RESUMO

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.


Assuntos
Asma , Tosse , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Sons Respiratórios , Índice de Gravidade de Doença , Humanos , Tosse/fisiopatologia , Tosse/psicologia , Asma/complicações , Asma/fisiopatologia , Asma/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Sons Respiratórios/fisiopatologia , Adulto , República da Coreia/epidemiologia , Sistema de Registros , Inquéritos e Questionários
5.
Lung ; 202(1): 41-51, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38252134

RESUMO

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Adulto , Humanos , Antiasmáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Eosinófilos , Eosinofilia Pulmonar/tratamento farmacológico , Pulmão
6.
Proc Natl Acad Sci U S A ; 118(46)2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34750249

RESUMO

The causes of the Mid-Pleistocene Transition, the shift from ∼41-ky to 100-ky interglacial-glacial cycles and more intense ice ages, remain intensely debated, as this fundamental change occurred between ∼1,250 and 650 ka without substantial changes in astronomical climate forcings. Recent studies disagree about the relative importance of events and processes in the Northern and Southern Hemispheres, as well as whether the shift occurred gradually over several interglacial-glacial cycles or abruptly at ∼900 ka. We address these issues using a north-to-south reconstruction of the Atlantic arm of the global meridional overturning ocean circulation, a primary means for distributing heat around the globe, using neodymium (Nd) isotopes. Results reveal a period of intense erosion affecting the cratonic shields surrounding the North Atlantic between Marine Isotope Stages (MIS) 27 and 25 (∼980 and 950 ka), reflected by unusually low Nd isotope ratios in deep North Atlantic seawater. This episode preceded a major ocean circulation weakening between MIS 25 and 21 (950 and 860 ka) that coincided with the first ∼100-ky-long interglacial-glacial onset of Northern Hemisphere glaciation at around 2.4 to 2.8 Ma. The data point to a Northern Hemisphere-sourced initiation for the transition, possibly induced through regolith loss and increased exposure of the crystalline bedrock, which would lead to increased friction, enabling larger ice sheets that are characteristic of the 100-ky interglacial-glacial cycles.

7.
Sensors (Basel) ; 24(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38544142

RESUMO

Recent advancements in image segmentation have been notably driven by Vision Transformers. These transformer-based models offer one versatile network structure capable of handling a variety of segmentation tasks. Despite their effectiveness, the pursuit of enhanced capabilities often leads to more intricate architectures and greater computational demands. OneFormer has responded to these challenges by introducing a query-text contrastive learning strategy active during training only. However, this approach has not completely addressed the inefficiency issues in text generation and the contrastive loss computation. To solve these problems, we introduce Efficient Query Optimizer (EQO), an approach that efficiently utilizes multi-modal data to refine query optimization in image segmentation. Our strategy significantly reduces the complexity of parameters and computations by distilling inter-class and inter-task information from an image into a single template sentence. Furthermore, we propose a novel attention-based contrastive loss. It is designed to facilitate a one-to-many matching mechanism in the loss computation, which helps object queries learn more robust representations. Beyond merely reducing complexity, our model demonstrates superior performance compared to OneFormer across all three segmentation tasks using the Swin-T backbone. Our evaluations on the ADE20K dataset reveal that our model outperforms OneFormer in multiple metrics: by 0.2% in mean Intersection over Union (mIoU), 0.6% in Average Precision (AP), and 0.8% in Panoptic Quality (PQ). These results highlight the efficacy of our model in advancing the field of image segmentation.

8.
Int J Mol Sci ; 25(2)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38255844

RESUMO

REV-ERBα and its paralog, REV-ERBß, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBß to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer.


Assuntos
Neoplasias Ósseas , Transtornos Cronobiológicos , Osteossarcoma , Humanos , Técnicas de Cultura de Células , Osteossarcoma/genética , Isoformas de Proteínas , Receptores Citoplasmáticos e Nucleares
9.
Artigo em Inglês | MEDLINE | ID: mdl-37268246

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

10.
BMC Musculoskelet Disord ; 24(1): 540, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393227

RESUMO

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, the amount of moderate- to high-intensity physical activity significantly decreased. Therefore, the epidemiology of musculoskeletal diseases could possibly have changed. We assessed changes in the incidence of and variance in non-traumatic orthopedic diseases before and after the COVID-19 pandemic in Korea. METHODS: This study included data from the Korea National Health Insurance Service, which covers the entire Korean population (approximately 50 million), from January 2018 to June 2021. Using International Classification of Diseases, Tenth Revision codes, 12 common orthopedic diseases were evaluated, including cervical disc disorders, lumbar disc disorders, forward head posture, myofascial pain syndrome, carpal tunnel syndrome, tennis elbow, frozen shoulder, rheumatoid arthritis, gout, hip fracture, distal radius fracture, and spine fracture diseases. "Pre-COVID-19" was the period until February 2020, and "COVID-19 pandemic period" was the period starting March 2020. Differences in the mean incidence and variance of diseases before and during the COVID-19 pandemic were compared. RESULTS: In most cases, the incidence of orthopedic diseases decreased at the beginning of the pandemic and then increased thereafter. Among the 12 diseases, the incidence of three diseases showed a statistically significant change. The incidence of myofascial pain syndrome (P < 0.001) was lower during the COVID-19 pandemic than during the pre-COVID-19 period. The incidences of frozen shoulder (P < 0.001) and gout (P = 0.043) were higher during the COVID-19 pandemic than during the pre-COVID-19 period. However, no statistical difference in disease variations was observed between the two periods. CONCLUSIONS: The incidence of orthopedic diseases varied during the COVID-19 pandemic among the Korean population. Although the incidence of myofascial pain syndrome was lower, that of frozen shoulder and gout was higher during the COVID-19 pandemic than during the pre-COVID-19 period. No disease variations during the COVID-19 pandemic were found.


Assuntos
Bursite , COVID-19 , Fibromialgia , Fraturas Ósseas , Gota , Degeneração do Disco Intervertebral , Doenças Musculoesqueléticas , Humanos , Estudos Retrospectivos , Incidência , Pandemias , COVID-19/epidemiologia , República da Coreia/epidemiologia
11.
J Am Soc Nephrol ; 33(9): 1726-1741, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961787

RESUMO

BACKGROUND: Ciliogenesis-associated kinase 1 (CILK1) is a ciliary gene that localizes in primary cilia and regulates ciliary transport. Mutations in CILK1 cause various ciliopathies. However, the pathogenesis of CILK1-deficient kidney disease is unknown. METHODS: To examine whether CILK1 deficiency causes PKD accompanied by abnormal cilia, we generated mice with deletion of Cilk1 in cells of the renal collecting duct. A yeast two-hybrid system and coimmunoprecipitation (co-IP) were used to identify a novel regulator, kinesin light chain-3 (KLC3), of ciliary trafficking and cyst progression in the Cilk1-deficient model. Immunocytochemistry and co-IP were used to examine the effect of KLC3 on ciliary trafficking of the IFT-B complex and EGFR. We evaluated the effects of these genes on ciliary trafficking and cyst progression by modulating CILK1 and KLC3 expression levels. RESULTS: CILK1 deficiency leads to PKD accompanied by abnormal ciliary trafficking. KLC3 interacts with CILK1 at cilia bases and is increased in cyst-lining cells of CILK1-deficient mice. KLC3 overexpression promotes ciliary recruitment of IFT-B and EGFR in the CILK1 deficiency condition, which contributes to the ciliary defect in cystogenesis. Reduction in KLC3 rescued the ciliary defects and inhibited cyst progression caused by CILK1 deficiency. CONCLUSIONS: Our findings suggest that CILK1 deficiency in renal collecting ducts leads to PKD and promotes ciliary trafficking via increased KLC3.


Assuntos
Doenças Renais Policísticas , Camundongos , Animais , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/metabolismo , Rim/metabolismo , Cílios/metabolismo , Mutação , Receptores ErbB/metabolismo
12.
Sensors (Basel) ; 23(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36679377

RESUMO

Transformer-based semantic segmentation methods have achieved excellent performance in recent years. Mask2Former is one of the well-known transformer-based methods which unifies common image segmentation into a universal model. However, it performs relatively poorly in obtaining local features and segmenting small objects due to relying heavily on transformers. To this end, we propose a simple yet effective architecture that introduces auxiliary branches to Mask2Former during training to capture dense local features on the encoder side. The obtained features help improve the performance of learning local information and segmenting small objects. Since the proposed auxiliary convolution layers are required only for training and can be removed during inference, the performance gain can be obtained without additional computation at inference. Experimental results show that our model can achieve state-of-the-art performance (57.6% mIoU) on the ADE20K and (84.8% mIoU) on the Cityscapes datasets.


Assuntos
Fontes de Energia Elétrica , Semântica , Aprendizagem , Processamento de Imagem Assistida por Computador
13.
Sensors (Basel) ; 23(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631754

RESUMO

The Voxel Transformer (VoTr) is a prominent model in the field of 3D object detection, employing a transformer-based architecture to comprehend long-range voxel relationships through self-attention. However, despite its expanded receptive field, VoTr's flexibility is constrained by its predefined receptive field. In this paper, we present a Voxel Transformer with Density-Aware Deformable Attention (VoTr-DADA), a novel approach to 3D object detection. VoTr-DADA leverages density-guided deformable attention for a more adaptable receptive field. It efficiently identifies key areas in the input using density features, combining the strengths of both VoTr and Deformable Attention. We introduce the Density-Aware Deformable Attention (DADA) module, which is specifically designed to focus on these crucial areas while adaptively extracting more informative features. Experimental results on the KITTI dataset and the Waymo Open dataset show that our proposed method outperforms the baseline VoTr model in 3D object detection while maintaining a fast inference speed.

14.
J Headache Pain ; 24(1): 98, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525107

RESUMO

BACKGROUND: Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. METHODS: Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. RESULTS: The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31-1.39 and adjusted HR = 1.31, 95% CI = 1.26-1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95-1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. CONCLUSIONS: Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Transtornos de Enxaqueca , Isquemia Miocárdica , Acidente Vascular Cerebral , Humanos , Seguimentos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/complicações , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/complicações , Doenças Cardiovasculares/epidemiologia , Incidência , Insuficiência Cardíaca/complicações , República da Coreia/epidemiologia
15.
Pharmacoepidemiol Drug Saf ; 31(11): 1153-1163, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35909258

RESUMO

BACKGROUND: In tuberculosis (TB) treatment, adverse drug reactions (ADRs) can interrupt treatment and decrease the quality of life (QoL). We aimed to prospectively investigate the incidence of ADRs to first-line anti-TB drugs and related outcomes and QoL. METHODS: Adult patients with TB who had been treated with first-line anti-TB drugs in five Korean hospitals were enrolled. ADR questionnaire surveys and blood tests were performed four times serially, and QoL was assessed on the fourth TB treatment week (±2 weeks). RESULTS: Of 410 enrolled patients with TB (males, 62%; mean age, 52.1 ± 18.1 years [those aged ≥65 years, 26.6%]), 67.8% experienced any ADRs (≥ grade 2) to TB drugs. The most common ADR was fatigue (53.2%), followed by itching (42.7%) and anorexia (41.7%). Older adult patients experienced relatively more ADRs, including anorexia, dyspepsia, rash, dizziness, anemia, abnormal hepatic/renal function tests, and increased uric acid levels (p < 0.05). Treatment regimens changed for 9.5% of patients owing to ADRs to anti-TB drugs. Patients with any ADRs and older adult patients had significantly lower QoL than their counterparts (p < 0.05). Old age (odds ratio [OR], 1.02) and being male (OR 2.65) were independently associated with ADRs, whereas active smoking (OR 4.73) and a relatively long treatment phase (OR 5.13) were independently associated with hepatotoxicity. CONCLUSION: ADRs to first-line anti-TB drugs were common and related to relatively low QoL, especially among older adults. Although 9.5% of patients had ADR-related regimen changes, most patients with ADRs completed treatments successfully.


Assuntos
Antituberculosos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Adulto , Idoso , Anorexia/induzido quimicamente , Anorexia/tratamento farmacológico , Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Ácido Úrico
16.
Respiration ; 101(5): 465-475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34915526

RESUMO

BACKGROUND: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. OBJECTIVES: We aimed to describe the characteristics of SEA and identify its patient subgroups. METHODS: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. RESULTS: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/µL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/µL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/µL), and good treatment response in terms of improved lung function and control status. CONCLUSIONS: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.


Assuntos
Asma , Eosinofilia Pulmonar , Adulto , Asma/complicações , Asma/diagnóstico , Asma/tratamento farmacológico , Eosinófilos , Volume Expiratório Forçado , Humanos , Contagem de Leucócitos , Masculino , Eosinofilia Pulmonar/tratamento farmacológico
17.
J Korean Med Sci ; 37(7): e57, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35191233

RESUMO

BACKGROUND: Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort. METHODS: Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated. RESULTS: In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266-23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083-11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL. CONCLUSION: The baseline blood eosinophil count may predict the future clinical burden of asthma.


Assuntos
Asma , Eosinófilos , Adulto , Asma/tratamento farmacológico , Estudos de Coortes , Bases de Dados Factuais , Humanos , Contagem de Leucócitos
18.
BMC Biol ; 19(1): 44, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789631

RESUMO

BACKGROUND: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. RESULTS: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. CONCLUSION: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.


Assuntos
Citocinas/genética , Músculo Esquelético/embriologia , Fatores de Processamento de RNA/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Citocinas/metabolismo , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Fatores de Processamento de RNA/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
19.
Allergy ; 76(1): 223-232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411398

RESUMO

BACKGROUND: While the clinical characteristics and outcomes of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the prevalence and features of ACO in patients with severe asthma are unclear. OBJECTIVES: Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry. METHODS: At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non-ACO groups, and the demographic and clinical characteristics of these two groups were compared. RESULTS: Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex- or current smokers (P < .001) compared with those in the non-ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non-ACO group. The ACO group used more inhaled long-acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006). CONCLUSION: Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/diagnóstico , Asma/epidemiologia , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema de Registros , República da Coreia/epidemiologia , Especialização
20.
Nano Lett ; 20(3): 1517-1525, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-31750664

RESUMO

Intraocular islet transplantation was investigated as a new procedure to treat diabetes. The development of this procedure requires close monitoring of the function of both eye and islet graft. We developed a soft, smart contact lens to monitor the intraocular pressure and applied this for noninvasive monitoring in association with the intraocular islet transplantation in diabetes. A strain sensor inside the lens can detect detailed changes in intraocular pressure by focusing the strain only in the desired, selective area of the contact lens. In addition, this smart contact lens can transmit the real-time value of the intraocular pressure wirelessly using an antenna. The wireless measurement of intraocular pressure that was obtained using this contact lens had a high correlation with the intraocular pressure measured by a rebound tonometer, thereby proving the good accuracy of the contact lens sensor. In the initial period, a slight elevation of intraocular pressure was observed, but the pressure returned to normal in the initial period after the transplantation. This type of monitoring will provide important information on potential changes in the intraocular pressure associated with the transplantation procedure, and it enables appropriate clinical safety steps to be taken, if needed.


Assuntos
Câmara Anterior , Lentes de Contato Hidrofílicas , Pressão Intraocular , Transplante das Ilhotas Pancreáticas , Animais , Câmara Anterior/fisiopatologia , Câmara Anterior/cirurgia , Monitorização Fisiológica , Ratos , Ratos Endogâmicos Lew
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