RESUMO
In 2019, the National Evidence-based Healthcare Collaborating Agency (NECA) in Korea established a health technology reassessment (HTR) system to manage the life cycle of health technologies and develop operational measures promoting the efficient use of healthcare resources. The purpose of this study is to introduce the detailed implementation process and practical functional methods of the HTR implemented by NECA.The HTR is a structured multidisciplinary method for analyzing health technologies currently used in the healthcare system based on the latest information on parameters, such as clinical safety, effectiveness, and cost-effectiveness of optimizing the use of healthcare resources as well as social and ethical issues. All decision-making stages of the HTR are carefully reviewed and transparently managed. The HTR committee makes significant decisions, and the subcommittee decides the details related to the assessment process.Since the pilot began in 2018, 262 cases have been reassessed, of which, 126 cases (48.1 percent) were health services not covered by the National Health Insurance (NHI). Over the past 5 years, approximately 130 recommendations for the in-use technologies were determined by the HTR committee. In the near future, it will be necessary to officially develop and establish a Korean HTR system and a legal foundation to optimize the NHI system.
Assuntos
Avaliação da Tecnologia Biomédica , Análise Custo-Benefício , Tomada de Decisões , Programas Nacionais de Saúde/organização & administração , República da Coreia , Avaliação da Tecnologia Biomédica/organização & administraçãoRESUMO
AIM: To analyse the prevalence of posttraumatic stress disorder (PTSD) and examine its related factors among nurses who worked during the coronavirus disease 2019 (COVID-19) pandemic in Daegu, South Korea. BACKGROUND: Nurses are a high-risk population for PTSD, especially during the COVID-19 pandemic. This study was conducted to identify the nursing work environmental factors that should be addressed to reduce PTSD. METHODS: Using a cross-sectional design, 365 nurses were enrolled. Their characteristics (intrapersonal, interpersonal, organizational, and COVID-19-related) and PTSD Checklist-5 scores were analysed. RESULTS: The average PTSD score was 14.98 ± 15.94, and 16.5% of the participants had a high risk of PTSD. Nurses were more likely to have PTSD if they were married (odds ratio = 3.02, p = .013) and when nurse managers' abilities, leadership, and support of nurses were low (odds ratio = 3.81, p < .001). CONCLUSIONS: The nursing work environment was found to be associated with PTSD. Therefore, interventions are necessary to increase nurse managers' abilities, leadership, and support for nurses to reduce the risk of PTSD among nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Effective professional and social support and interventions to improve nurse managers' abilities, leadership, and support of nurses are needed to reduce PTSD.
Assuntos
COVID-19 , Enfermeiros Administradores , Transtornos de Estresse Pós-Traumáticos , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologiaRESUMO
Patient-derived xenograft (PDX) murine models are employed for preclinical research on cancers, including non-small cell lung cancers (NSCLCs). Even though lung squamous cell carcinomas (LUSCs) show the highest engraftment rate among NSCLCs, half of them nevertheless show PDX failure in immunodeficient mice. Here, using immunohistochemistry and RNA sequencing, we evaluated the distinct immunohistochemical and gene expression profiles of resected LUSCs that showed successful engraftment. Among various LUSCs, including the basal, classical, secretory, and primitive subtypes, those in the non-engrafting (NEG) group showed gene expression profiles similar to the pure secretory subtype with positivity for CK7, whereas those in the engrafting (EG) group were similar to the mixed secretory subtype with positivity for p63. Pathway analysis of 295 genes that demonstrated significant differences in expression between NEG and EG tumors revealed that the former had enriched expression of genes related to the immune system, whereas the latter had enriched expression of genes related to the cell cycle and DNA replication. Interestingly, NEG tumors showed higher infiltration of B cells (CD19+) and follicular dendritic cells (CD23+) in lymph follicles than EG tumors. Taken together, these findings suggest that the PDX cancer model of LUSC represents only a certain population of LUSCs and that CD19- and CD23-positive tumor-infiltrating immune cells in the original tumors may negatively influence PDX engraftment in immunodeficient mice.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Transplante de Neoplasias , Animais , Antígenos CD19/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Perfilação da Expressão Gênica , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos SCID , Neoplasias Experimentais , Receptores de IgE/metabolismoRESUMO
Ovarian carcinoma immunoreactive antigen domain 2 (OCIAD2) has been reported to show significantly higher expression in invasive lung adenocarcinoma than in lung adenocarcinoma in situ, and its abnormal expression is associated with poorer prognosis of the patients. However, the cellular function of OCIAD2 in this tumor remains poorly understood. In the present study, we first validated that OCIAD2 showed higher expression in human lung adenocarcinoma tissues or cell lines than in normal lung tissue or immortalized normal bronchial epithelial cells. OCIAD2 was localized predominantly at the mitochondrial membrane in lung adenocarcinoma cells. Interestingly, suppression of OCIAD2 led to loss of mitochondrial structure and a reduction in the number of mitochondria. Moreover, OCIAD2 suppression led to downregulation of cellular growth, proliferation, migration, and invasion, and upregulation of mitochondria-related apoptosis. We also showed that OCIAD2 suppression induced a decrease in mitochondrial membrane potential and release of cytochrome c. Transcriptional profiling using RNA sequencing revealed a total of 137 genes whose expression was commonly altered after OCIAD2 knockdown in three lung adenocarcinoma cell lines (A549, HCC827, and PC9). Pathway enrichment analysis of those genes demonstrated significant enrichment in apoptotic signaling or endoplasmic reticulum (ER) stress pathways. Our data suggest that OCIAD2 inhibits the mitochondria-initiated apoptosis and thus promotes the survival of lung cancer cells. Therefore, OCIAD2 may be an effective target for treatment of lung adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Mitocôndrias/genética , Proteínas de Neoplasias/genética , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Western Blotting , Linhagem Celular Tumoral , Ontologia Genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/genética , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas de Neoplasias/metabolismo , RNA-Seq/métodos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The expression of Ras-specific guanine nucleotide-releasing factor 2 (RasGRF2) in lung adenocarcinomas was examined using immunohistochemistry in relation to clinicopathological characteristics and prognosis. In comparison to low expression, high expression of RasGRF2 was more closely associated with poor prognosis. Interestingly, expression of phosphorylated epithelial cell transforming 2 (pECT2), which - like RasGRF2 - is also a guanine-nucleotide exchange factor, was also associated with prognosis, and patients with high expression of both RasGRF2 and pECT2 had a much poorer outcome than those who were negative for both.
Assuntos
Adenocarcinoma de Pulmão/patologia , Fator 2 de Liberação do Nucleotídeo Guanina/metabolismo , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores ras de Troca de Nucleotídeo Guanina/metabolismoRESUMO
This study examined the acoustic characteristics of American English liquids /ɹ/, /l/, and /ɹl/ produced by 14 adult learners of English (L2) and 13 native speakers of English. Several temporal and spectral measures were examined, including a novel measure to describe the relative timing of the maximum constriction during liquid production. The results indicated that L2 speakers rely more on duration contrasts to distinguish the three liquids than spectral contrasts. Reduced spectral differences among the liquids in L2 speakers are discussed concerning the influence of the native language of L2 speakers.
Assuntos
Multilinguismo , Acústica , Idioma , Fonética , República da Coreia , Acústica da Fala , Estados UnidosRESUMO
The landscape of genetic alterations in disease models such as transgenic mice or mice with carcinogen-induced tumors has provided a huge amount of information that has shed light on the process of tumorigenesis in human non-small-cell lung cancer (NSCLC). We have previously identified stratifin (SFN) as a potent oncogene, and generated SFN-transgenic (Tg-SPC-SFN+/- ) mice, which express human SFN (hSFN) only in the lung. Here, we have found that carcinogen nicotine-derived nitrosaminoketone (NNK)-induced tumors developing in Tg-SPC-SFN+/- mice show a similar histology to human lung adenocarcinoma and exhibit high hSFN expression. In order to compare the genetic characteristics of Tg-SPC-SFN+/- tumors and human lung adenocarcinoma, the former were subjected to whole-exome sequencing. Interestingly, Tg-SPC-SFN+/- tumors showed the distinct distribution of exonic mutations and high number of mutated genes and transversion. Moreover, Tg-SPC-SFN+/- tumors showed 73 genes that were commonly detected in more than 2 tumors, mutations of which were also found in human lung adenocarcinoma. The expression levels of some of these genes were significantly associated with the clinical outcome of lung adenocarcinoma patients. Additionally, mutated genes in Tg-SPC-SFN+/- tumors were closely associated with key canonical pathways such as PI3K/AKT signaling and apoptosis signaling. These results suggest that SFN overexpression is a universal abnormality in human lung adenocarcinogenesis and Tg-SPC-SFN+/- tumors recapitulate key features of major human lung adenocarcinoma. Therefore, Tg-SPC-SFN+/- mice provide a useful model for clarifying the molecular mechanism underlying lung adenocarcinogenesis.
Assuntos
Proteínas 14-3-3/genética , Adenocarcinoma de Pulmão/induzido quimicamente , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Carcinógenos/farmacologia , Exorribonucleases/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Mutação/genética , Células A549 , Animais , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Sequenciamento do Exoma/métodosRESUMO
In this study, the relationship between the acoustic and articulatory kinematic domains of speech was examined among nine neurologically healthy female speakers using two derived relationships between tongue kinematics and F2 measurements: (1) second formant frequency (F2) extent to lingual displacement and (2) F2 slope to lingual speed. Additionally, the relationships between these paired parameters were examined within conversational, more clear, and less clear speaking modes. In general, the findings of the study support a strong correlation for both sets of paired parameters. In addition, the data showed significant changes in articulatory behaviors across speaking modes including the magnitude of tongue motion, but not in the speed-related measures.
RESUMO
The clinicopathological implications of ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) in lung adenocarcinoma were investigated. The expression of OCIAD2 in 191 surgically resected lung adenocarcinomas was examined using immunohistochemistry. OCIAD2 expression was quantified using the H-score and dichotomized as high or low. High OCIAD2 protein expression was significantly correlated with vascular invasion (P = 0.0018), lymphatic permeation (P = 0.049), T factor (P = 0.0024), and pathological stage (P = 0.0003). High OCIAD2 expression was significantly associated with poorer overall survival (OS) (n = 191, P = 0.0325). In peripheral-type lung adenocarcinomas (n = 161), high OCIAD2 expression was significantly associated with both poorer OS (P = 0.0214) and poorer disease-free survival (P = 0.0496). Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) showed weaker OCIAD2 expression than invasive adenocarcinoma. Among small adenocarcinomas measuring 2 cm or less in greatest dimension classified according to the Noguchi's classification (n = 79), invasive adenocarcinomas showed significantly higher OCIAD2 expression than non-invasive adenocarcinomas (P = 0.0007). Interestingly, OCIAD2 was expressed heterogeneously even within a tumor, and its expression was higher in areas of invasion than in areas of in situ spread. Our results suggest that OCIAD2 could be a useful prognostic biomarker of lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/análise , Proteínas de Neoplasias/biossíntese , Adenocarcinoma de Pulmão/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: This study investigated coarticulatory effects on schwa. The purpose was to establish a viable phonetic environment and analysis for future studies of coarticulation, particularly in motor speech disorders. METHOD: Seven female adults read 2 phrases containing 4 target words in a CVC structure embedded in the carrier phrases, "Put a CVC here" and "Get CVC a puppy." A 3D electromagnetic articulography system was used to track lingual movements during schwa production. Two indices of coarticulation were employed: (a) tongue position difference between the temporal midpoint (grand mean of each speaker) and the onset/offset of schwa immediately following or preceding a transconsonantal vowel and (b) tongue position differences between the grand mean of each speaker and each utterance repetition, both measured at the temporal midpoint of the schwa. RESULTS: Both measures indicated that schwa is significantly influenced by transconsonantal corner vowels. The magnitude of coarticulation effects on schwa varied among the 4 corner vowels in the order of /i/>/É/ = /æ/>/u/. CONCLUSION: Findings support the use of schwa in future studies when examining coarticulatory effects in people with and without motor speech disorders. Some methodological issues such as selection of measurement points and speech stimuli are also discussed.
Assuntos
Fonética , Distúrbios da Fala/fisiopatologia , Língua/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Movimento , Espectrografia do Som , Acústica da Fala , Língua/fisiopatologia , Adulto JovemRESUMO
Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1-). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3'UTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage.
Assuntos
Adenocarcinoma/patologia , Apoptose/genética , Regulação Neoplásica da Expressão Gênica/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Células A549 , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Chaperonas Moleculares , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
Alterations of epidermal growth factor receptor (EGFR) expression frequently occur in early-stage lung adenocarcinoma. Ubiquitin-specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway. Here, we examined the correlation between USP8 expression and the expression or mutation status of EGFR, as well as the clinicopathological features of lung adenocarcinoma and patient outcome. Expression of EGFR and USP8 in surgically resected specimens of lung adenocarcinoma (82 cases) was examined by immunohistochemistry. Overexpression of EGFR was mutually correlated with that of USP8, and was also associated with clinicopathological features including pathological subtype, lymphatic permeation, and vascular invasion. Moreover, patients who had USP8-positive tumors had a significantly poorer outcome than those who were USP8-negative, not only overall but also patients who were EGFR-negative. Although EGFR was expressed in invasive adenocarcinoma but not in adenocarcinoma in situ (AIS), USP8 was overexpressed in not only invasive adenocarcinoma but also 38.1% of AIS cases. In vitro, USP8 regulated the expression and half-life of EGFR in immortalized AIS cells, and also cell proliferation. Our findings indicate that overexpression of USP8 in lung adenocarcinoma is an early event during the course of tumor progression, and is related to EGFR expression.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Endopeptidases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Ubiquitina Tiolesterase/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Biomarcadores Tumorais/genética , Linhagem Celular , Intervalo Livre de Doença , Diagnóstico Precoce , Endopeptidases/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Receptores ErbB/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Ubiquitina Tiolesterase/genéticaRESUMO
The aim of this study was to examine the incidence and trends of clinically relevant venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) after hip and knee replacement arthroplasty (HKRA) in Korea. Between January 1 and December 31, 2010, 22,127 hip replacement arthroplasty (HRA) patients and 52,882 knee replacement arthroplasty (KRA) patients were enrolled in the analysis using the administrative claims database of the Health Insurance Review and Assessment Service (HIRA). All available parameters including procedure history and clinically relevant VTE during the 90 days after HKRA were identified based on diagnostic and electronic data interchange (EDI) codes. The overall incidence of VTE, DVT, and PE during the 90 days was 3.9% (n=853), 2.7% (n=597), and 1.5% (n=327) after HRA, while the incidence was 3.8% (n=1,990), 3.2% (n=1,699), and 0.7% (n=355) after KRA. The incidence of VTE after HKRA was significantly higher in patients who had previous VTE history (odds ratio [OR], 10.8 after HRA, OR, 8.5 after KRA), chronic heart failure (2.1, 1.3), arrhythmia (1.8, 1.7), and atrial fibrillation (3.4, 2.1) than in patients who did not. The VTE incidence in patients with chemoprophylaxis was higher than that in patients without chemoprophylaxis. The incidence of VTEs revealed in this retrospective review was not low compared with the results of the studies targeting other Asian or Caucasian populations. It may warrant routine prevention including employment of chemoprophylaxis. However, the limitation of the reviewed data mandates large scale prospective investigation to affirm this observation.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Tromboembolia Venosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Razão de Chances , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/epidemiologiaRESUMO
The analysis of vocal expression is a critical endeavor for psychological and clinical sciences and is an increasingly popular application for computer-human interfaces. Despite this, and despite advances in the efficiency, affordability, and sophistication of vocal analytic technologies, there is considerable variability across studies regarding what aspects of vocal expression are studied. Vocal signals can be quantified in a myriad of ways, and their underlying structure, at least with respect to "macroscopic" measures from extended speech, is presently unclear. To address this issue, we evaluated the psychometric properties-notably, the structural and construct validity-of a systematically defined set of global vocal features. Our analytic strategy focused on (a) identifying redundant variables among this set, (b) employing principal components analysis (PCA) to identify nonoverlapping domains of vocal expression, (c) examining the degrees to which the vocal variables are modulated as a function of changes in speech task, and (d) evaluating the relationship between the vocal variables and cognitive (i.e., verbal fluency) and clinical (i.e., depression, anxiety, and hostility) variables. Spontaneous speech samples from 11 independent studies of young adults (>60 s in length), employing one of three different speaking tasks, were examined (N = 1,350). Confounding variables (i.e., sex, ethnicity) were statistically controlled for. The PCA identified six distinct domains of vocal expression. Collectively, vocal expression (defined in terms of these domains) was modulated as a function of speech task and was related to the cognitive and clinical variables. These findings provide empirically grounded implications for the study of vocal expression in psychological and clinical sciences.
Assuntos
Medida da Produção da Fala , Ansiedade , Cognição/fisiologia , Depressão/fisiopatologia , Feminino , Hostilidade , Humanos , Masculino , Análise de Componente Principal , Psicometria , Fala/fisiologia , Acústica da Fala , Medida da Produção da Fala/métodos , Adulto JovemRESUMO
BACKGROUNDS: Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal outcome. We had previously compared the expression profiles of AIS with those of eIA showing lymph node metastasis or a fatal outcome, and found that stratifin (SFN, 14-3-3 sigma) was a differentially expressed gene related to cell proliferation. Here, we performed an in vivo study to clarify the role of SFN in initiation and progression of lung adenocarcinoma. FINDINGS: Suppression of SFN expression in A549 (a human lung adenocarcinoma cell line) by siSFN significantly reduced cell proliferation activity and the S-phase subpopulation. In vivo, tumor development or metastasis to the lung was reduced in shSFN-transfected A549 cells. Moreover, we generated SFN-transgenic mice (Tg-SPC-SFN(+/-)) showing lung-specific expression of human SFN under the control of a tissue-specific enhancer, the SPC promoter. We found that Tg-SPC-SFN(+/-) mice developed lung tumors at a significantly higher rate than control mice after administration of chemical carcinogen, NNK. Interestingly, several Tg-SPC-SFN(+/-) mice developed tumors without NNK. These tumor cells showed high hSFN expression. CONCLUSION: These results suggest that SFN facilitates lung tumor development and progression. SFN appears to be a novel oncogene with potential as a therapeutic target.
Assuntos
Proteínas 14-3-3/genética , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Exorribonucleases/genética , Neoplasias Pulmonares/genética , Proteínas 14-3-3/biossíntese , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Biomarcadores Tumorais/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Exorribonucleases/biossíntese , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Transgênicos , Metástase Neoplásica , Estadiamento de Neoplasias , Nitrosaminas/toxicidade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent genome-wide association studies (GWAS) have made substantial progress in identifying disease loci. The next logical step is to design functional experiments to identify disease mechanisms. This step, however, is often hampered by the large size of loci identified in GWAS that is caused by linkage disequilibrium between SNPs. In this study, we demonstrate how integrating methylome-wide association study (MWAS) results with GWAS findings can narrow down the location for a subset of the putative casual sites. We use the disease schizophrenia as an example. To handle "data analytic" variation, we first combined our MWAS results with two GWAS meta-analyses (N = 32,143 and 21,953), that had largely overlapping samples but different data analysis pipelines, separately. Permutation tests showed significant overlapping association signals between GWAS and MWAS findings. This significant overlap justified prioritizing loci based on the concordance principle. To further ensure that the methylation signal was not driven by chance, we successfully replicated the top three methylation findings near genes SDCCAG8, CREB1 and ATXN7 in an independent sample using targeted pyrosequencing. In contrast to the SNPs in the selected region, the methylation sites were largely uncorrelated explaining why the methylation signals implicated much smaller regions (median size 78 bp). The refined loci showed considerable enrichment of genomic elements of possible functional importance and suggested specific hypotheses about schizophrenia etiology. Several hypotheses involved possible variation in transcription factor-binding efficiencies.
Assuntos
Biomarcadores/análise , Metilação de DNA , Epigenômica , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Estudos de Casos e Controles , Biologia Computacional , Bases de Dados Genéticas , Seguimentos , Humanos , Desequilíbrio de Ligação , Metanálise como AssuntoRESUMO
OBJECTIVE: This paper sought to examine perceptual and acoustic characteristics in Korean female voices, focusing on the 'breathy' quality as a function of aging. In addition, we aimed to investigate if the three selected measures, H1-H2, H1-A1, and H1-A3, demonstrated any changes along a sustained vowel production. PARTICIPANTS AND METHODS: A total of 42 participants were assigned to two age groups, young women and elderly women. All participants were asked to sustain /a/ as long and as steadily as possible. Perceptual judgments of breathiness were made on the GRBAS scale and by a direct magnitude estimation technique, while three acoustic parameters, H1-H2, H1-A1, and H1-A3, were measured at five measurement time points during the sustained vowel test. RESULTS: Results indicated that the H1-H2 and H1-A1 values were significantly lower for elderly women compared to young women, although no difference in the perceptual estimation of breathiness was found between the age groups. Among the acoustic measures, only H1-A1 was significantly regressed against the perceptual estimate of breathiness. In addition, no significant acoustic difference in the measures was found across the five measurement points. CONCLUSION: Our findings suggest that the aging voice might not be universally characterized by the breathy quality, which hints at the need for further research on ethnic diversity in vocal quality.
Assuntos
Envelhecimento/fisiologia , Povo Asiático , Espectrografia do Som , Acústica da Fala , Percepção da Fala , Distúrbios da Voz/etnologia , Distúrbios da Voz/fisiopatologia , Qualidade da Voz/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fonética , República da Coreia , Medida da Produção da Fala , Adulto JovemRESUMO
We analyzed national data collected by the Health Insurance Review and Assessment Service in Korea from 2007 to 2011; 1) to document procedural numbers and procedural rate of bipolar hemiarthroplasty (BH), primary and revision total hip arthroplasties (THAs), 2) to stratify the prevalence of each procedure by age, gender, and hospital type, and quantified, 3) to estimate the revision burden and evaluate whether the burden is changed over time. Our final study population included 60,230 BHs, 40,760 primary THAs, and 10,341 revision THAs. From 2007 to 2011, both the number and the rate of BHs, primary THAs increased steadily, whereas there was no significant change in revision THAs. Over the 5 yr, the rate of BHs and primary THAs per 100,000 persons significantly increased by 33.2% and 21.4%, respectively. The number of revision THAs was consistent over time. The overall annual revision burden for THA decreased from 22.1% in 2007 to 18.9% in 2011. In contrast to western data, there were no changes in the number and rate of revision THAs, and the rates of primary and revision THAs were higher for men than those for women. Although 5 yr is a short time to determine a change in the revision burden, there have been significant decreases in some age groups.
Assuntos
Artroplastia de Quadril/estatística & dados numéricos , Fraturas do Quadril/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/economia , Bases de Dados Factuais , Feminino , Hemiartroplastia/economia , Hemiartroplastia/estatística & dados numéricos , Fraturas do Quadril/epidemiologia , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores SexuaisRESUMO
PURPOSE: This study examined speech changes induced by deep-brain stimulation (DBS) in speakers with Parkinson's disease (PD) using a set of auditory-perceptual and acoustic measures. METHOD: Speech recordings from nine speakers with PD and DBS were compared between DBS-On and DBS-Off conditions using auditory-perceptual and acoustic analyses. Auditory-perceptual ratings included voice quality, articulation precision, prosody, speech intelligibility, and listening effort obtained from 44 listeners. Acoustic measures were made for voicing proportion, second formant frequency slope, vowel dispersion, articulation rate, and range of fundamental frequency and intensity. RESULTS: No significant changes were found between DBS-On and DBS-Off for the five perceptual ratings. Four of six acoustic measures revealed significant differences between the two conditions. While articulation rate and acoustic vowel dispersion increased, voicing proportion and intensity range decreased from the DBS-Off to DBS-On condition. However, a visual examination of the data indicated that the statistical significance was mostly driven by a small number of participants, while the majority did not show a consistent pattern of such changes. CONCLUSIONS: Our data, in general, indicate no-to-minimal changes in speech production ensued from DBS stimulation. The findings are discussed with a focus on large interspeaker variability in PD in terms of their speech characteristics and the potential effects of DBS on speech.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Humanos , Acústica , Inteligibilidade da Fala/fisiologia , Qualidade da Voz , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Encéfalo , Acústica da FalaRESUMO
PURPOSE: Despite the general agreement that dysarthria characteristics are largely language-independent, few efforts have attempted a systematic comparison across languages. To examine the role of native languages in the perception of speech characteristics of dysarthria secondary to Parkinson's disease (PD), auditory-perceptual ratings of dysarthria, and confidence level of the judgments were compared between two listener groups: language-matched and language-crossed. METHOD: A total of 60 listeners (35 native speakers of Korean and 25 native speakers of American English) estimated speech abnormality for 20 speech dimensions using a visual analog scale method for both language-matched and language-crossed speech stimuli. Speech stimuli were passage readings of the respective languages obtained from individuals with and without PD. RESULTS: For speech dimension ratings, eight of 20 speech dimensions revealed significant differences in response to PD speech between the two listener groups, for most of which, language-crossed listeners' estimation was lower (i.e., more impaired) than language-matched listeners. For confidence-level ratings, language-matched listeners were less confident in the ratings of speakers with PD compared to the language-crossed listeners. CONCLUSIONS: The data support both language-universal and language-specific aspects in perceiving dysarthria characteristics, such that native language plays a role, especially when rating articulatory- and rhythmic-related characteristics. The findings are discussed with respect to the role of linguistic information, such as phonetic inventories and prosodic structures, in perceiving dysarthria characteristics.