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This study investigated the vocal and early speech development of Korean-acquiring children with hearing loss (HL) who underwent early auditory amplification compared to their typical hearing (TH) counterparts. The research focused on phonological characteristics of child vocalisation based on samples collected from naturalistic home environments. One-day home recordings using a Language ENvironment Analysis (LENA) recorder were obtained from 6 children with HL and 12 children with TH who ranged from 17 to 23 months of age in Korean monolingual environments. Child volubility, canonical babbling ratio (CBR), consonant distributions, and utterance structures of vocalisations were evaluated through qualitative and quantitative analyses of vocalisation samples collected from LENA recordings. The findings revealed that children with HL displayed comparable vocalisation levels to children with TH, with no significant differences in volubility and CBR. In consonant and utterance shape inventories, noticeable quantitative and qualitative differences were observed between children with HL and those with TH. The study also suggested both universal and language-specific production patterns, revealing the early effects of ambient language on consonant distributions and utterance structures within their vocalisation repertoire. This study emphasised the role of auditory input and the importance of early auditory amplification to support speech development in children with HL.
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OBJECTIVES: The study aimed to investigate the predictive potential of language environment and vocal development status measures obtained through integrated analysis of Language ENvironment Analysis (LENA) recordings during the prelinguistic stage for subsequent speech and language development in Korean-acquiring children. Specifically, this study explored whether measures from both LENA-automated analysis and human coding at 6-8 months and 12-14 months of age predict vocabulary and phonological development at 18-20 months. METHOD: One-day home recordings from 20 children were collected using a LENA recorder at 6-8 months, 12-14 months, and 18-20 months. Both LENA-automated measures and measures from human coding were obtained from recordings at 6-8 months and 12-14 months. The number of different words, consonant inventory, and utterance structure inventory were identified from recordings of 18-20 months. Correlation and multiple regression analyses were performed to investigate whether measures related to early language environment and child vocalization at 6-8 months and 12-14 months were predictive of vocabulary and phonological measures at 18-20 months. RESULTS: The results showed that the two main LENA-automated measures, conversational turn count (CTC) and child vocalization count, were positively correlated with all vocabulary and phonological measures at 18-20 months. Multiple regression analysis revealed that CTC during the prelinguistic stages was the most significant predictor of a number of different words, consonant inventory, and utterance structure inventory at 18-20 months. Also, adult word count in LENA-automated measures, child-directed speech ratio, and canonical babbling ratio measured by human coding significantly predicted some vocabulary and phonological measures at 18-20 months. CONCLUSION: This study highlights the multifaceted nature of language acquisition and collectively emphasizes the value of considering both quantitative and qualitative aspects of language input to understand early language development in children.
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Lenguaje Infantil , Desarrollo del Lenguaje , Habla , Vocabulario , Humanos , Masculino , Femenino , Lactante , Habla/fisiología , Fonética , Medición de la Producción del Habla/métodosRESUMEN
Background Among the cleft types, bilateral cleft lip and palate (BCLP) generally requires multiple surgical procedures and extended speech therapy to achieve normal speech development. This study aimed to describe speech outcomes in 5-year-old Korean children with BCLP and examine whether normal speech could be achieved before starting school. Methods The retrospective study analyzed 52 children with complete BCLP who underwent primary palatal surgery at a tertiary medical center. Three speech-language pathologists made perceptual judgments on recordings from a speech follow-up assessment of 5-year-old children. They assessed the children's speech in terms of articulation, speech intelligibility, resonance, and voice using the Cleft Audit Protocol for Speech-Augmented-Korean Modification. Results The results indicated that at the age of five, 65 to 70% of children with BCLP presented articulation and resonance within normal or acceptable ranges. Further, seven children with BCLP (13.5%) needed both additional speech therapy and palatal surgery for persistent velopharyngeal insufficiency and speech problems even at the age of five. Conclusion This study confirmed that routine follow-up speech assessments are essential as a substantial number of children with BCLP require secondary surgical procedures and extended speech therapy to achieve normal speech development.
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Parental communication styles and language usage may undergo changes during the course of child development, exhibiting variations across language backgrounds and cultures. This study aimed to explore how infant-parent interactions within Korean-speaking environments evolve over time through meticulous coding of day-long home audio recordings. The study examined whether the ratio and types of parental verbal responses vary based on infants' age and vocalization types. A total of 16 infants and their parents participated in all-day home recordings using the Language Environment Analysis (LENA) system. The recordings were conducted in two rounds per family when the infants were aged 9-11 months and 12-14 months, with a three-month gap between each round. The frequency and types of infant vocalizations were analyzed and the contingency and types of parental verbal responsiveness were determined based on semantic and phonetic connection, as well as temporal appropriateness. The results showed that parents did not verbally respond to approximately 50 % of the infant vocalizations in the natural home environment. However, parents' lack of verbal responses decreased significantly, and their contingent responses increased significantly with infant age. Parents were also not selectively responsive to infants' canonical vocalizations over non-canonical vocalizations. Nevertheless, parents demonstrated a higher frequency of responses that were not only linguistically meaningful but also socially appropriate and contextually relevant to infants' vocalizations as infants developed, which may play a significant role in scaffolding speech and language development.
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Comunicación , Habla , Niño , Humanos , Lactante , Habla/fisiología , Desarrollo del Lenguaje , Lenguaje , PadresRESUMEN
BACKGROUND: AIMS: To investigate the developmental trajectory of the rate and perceptual assessment of oral diadochokinesis (DDK) in typically developing children compared with adults. Also to examine the characteristics of DDK productions in children with speech sound disorders (SSD) and the relationship between DDK production and percentage of consonants correct (PCC). METHODS & PROCEDURES: Participants were 316 typically developing children and 90 children with SSD from 3 to 9 years old, as well as 20 adults with normal speech. The mono-, bi- and trisyllabic nonsense strings containing Korean tense consonants and the vowel [a] were used for DDK tasks. The number of iterations per s was measured as the DDK rate for each stimulus. The perceptual assessment of DDK productions was also performed for regularity, accuracy and rate. OUTCOMES & RESULTS: The DDK rates increased throughout childhood, but the oldest children, 9-year-olds in the current study, did not achieve adult-like rates for all mono- and trisyllabic strings. Children with SSD also did not show significant differences from typically developing children when the DDK productions were analysed using only accurate tokens. The PCC of children with SSD showed higher correlations with regularity, accuracy and rate of perceptual ratings than the timed DDK rate. CONCLUSIONS & IMPLICATIONS: This study highlighted the fact that the comprehensive evaluation of DDK productions may provide even more useful information about children's oral motor skills. WHAT THIS PAPER ADDS: What is already known on the subject Rates of DDK reflect the motor skills of the articulatory systems independently of phonological skills; therefore, the tasks are widely used in the diagnostic evaluations of speech disorders in both children and adult populations. However, a substantial number of studies have questioned the validity and usefulness of DDK rates for evaluating speech abilities. Also, the literature suggested that the measure of DDK rate alone does not provide a clear and useful indication of children's oral motor skills. DDK tasks should be analysed in terms of accuracy and consistency as well as rate. What this paper adds to the existing knowledge The literature reporting normative DDK performance has mainly been based on English speakers. As different consonants have different temporal characteristics, the linguistic and segmental features of DDK tasks can impact the DDK rate. This study established a norm for DDK rate for Korean-speaking children and investigated the developmental trajectory of DDK performance in typically developing children compared with adults. This study suggested that the comprehensive evaluation of DDK productions may provide even more useful information about children's oral motor skills by examining the characteristics of DDK productions in children with SSD. What are the potential or actual clinical implications of this work? This study provided normative data of young Korean-speaking children aged 3-9 years. Normative data in children under 5 years of age are valuable given that the majority of children referred for speech difficulty assessments are between 3 and 5 years of age, but only a few studies have provided the normative data in young children. This study showed that many children could not complete DDK tasks correctly and provided additional support for the notion that other aspects of DDK performance, including accuracy and regularity, may yield more useful diagnostic indications than timed DDK rates alone.
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Trastorno Fonológico , Habla , Adulto , Humanos , Niño , Preescolar , Trastorno Fonológico/diagnóstico , Trastornos del Habla/diagnóstico , Lenguaje , Pruebas de Articulación del Habla , FonéticaRESUMEN
The study examined the link between Korean-speaking children's vowel production and its perception by inexperienced adults and also observed whether ongoing vowel changes in mid-back vowels affect adults' perceptions when the vowels are produced by children. This study analyzed vowels in monosyllabic words produced by 20 children, ranging from 2 to 6 years old, with a focus on gender distinction, and used them as perceptual stimuli for word perception by 20 inexperienced adult listeners. Acoustic analyses indicated that F0 was not a reliable cue for distinguishing gender, but the first two formants served as reliable cues for gender distinction. The results confirmed that the spacing of the two low formants is linguistically and para-linguistically important in identifying vowel types and gender. However, a pair of non-low back vowels caused difficulties in correct vowel identification. Proximal distance between the vowels could be interpreted to result in the highest mismatch between children's production and adults' perception of the two non-low back vowels in the Korean language. We attribute the source of the highest mismatch of the two non-low back vowels to the ongoing sound change observed in high and mid-back vowels in adult speech. The ongoing vowel change is also observed in the children's vowel space, which may well be shaped after the caregivers whose non-low back vowels are close to each other.
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OBJECTIVE: This study investigated vocalization and language environment longitudinally in infants with cleft palate (CP) based on day-long audio recordings collected in their natural environments. DESIGN: Language Environment Analysis (LENA) data from all-day recordings at home were collected at 3-month intervals for infants from 4-6 to 16-18 months of age. The recordings were analyzed using experimentally blinded human coding as well as LENA automated analysis. PARTICIPANTS: Ten infants with CP (± cleft lip) and 10 age-matched infants without CP. MAIN OUTCOME MEASURES: Several measurements were obtained from the LENA automated analysis software. In addition, human coded measurements of vocalization and language environment, including the true canonical babbling ratio and the infant-directed speech ratio, were analyzed for each time point of data collection for each infant. Statistical analyses were performed to conduct group and age comparisons for each measure of vocalization and language environment. RESULTS: No group differences emerged in number of syllables produced. Infants with CP exhibited late onset and fewer productions of canonical syllables compared to infants without CP. Infants with CP did not show significant differences from infants without CP in measures related to language environment across ages. CONCLUSION: This study provides detailed information through naturalistic all-day home recordings about vocal development and early language environments in infants with CP before and after palatal repair. Clinical implications for early intervention are discussed.
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Labio Leporino , Fisura del Paladar , Humanos , Lactante , Lenguaje , Desarrollo del Lenguaje , Estudios Longitudinales , Trastornos del HablaRESUMEN
This study compared vocal development in Korean- and English-learning infants and examined ambient-language effects focusing on predominant utterance shapes. Vocalization samples were obtained from 14 Korean-learning children and 14 English-learning children, who ranged in age from 9 to 21 months, in monolingual environments using day-long audio recordings. The analyzers, who were blind to participants' demographic information, identified utterance shapes to determine functional vocal repertoires through naturalistic listening simulating the caregiver's natural mode of listening. The results showed no cross-linguistic differences in the amount of vocal output or the proportion of canonical syllables. However, the infants from the two language backgrounds showed differences regarding the predominant canonical utterance shapes. The percentage of VCV utterances in Korean-learning children was higher than in English-learning children while CV syllables predominated in the English-learning children. We speculate that the difference between the predominant utterance shapes of Korean- and English-learning children could be associated with differences in early lexical items typically acquired in the two language groups.
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Lenguaje Infantil , Lenguaje , Niño , Humanos , Lactante , Desarrollo del Lenguaje , Aprendizaje , Lingüística , República de CoreaRESUMEN
BACKGROUND: This study aimed to identify the initial diagnostic characteristics and treatment status of children with submucous cleft palate (SMCP) and to examine the relationship between the timing of surgical correction and the degree of articulation and resonance improvement. METHODS: This retrospective study included 72 children diagnosed with SMCP between 2008 and 2016. The evaluation criteria were the age of the initial visit, total number of visits, age at the end of treatment, speech problems, resonance problems, and speech therapy. RESULTS: Children with SMCP first visited the hospital at an average age of 34.32 months, and speech problems were identified at an average age of 48.53 months. Out of 72 children, 46 underwent surgery at an average age of 49.74 months. Four of these children required secondary surgery at an average age of 83.5 months. Among the children who underwent surgery before 3 years of age, 70% exhibited articulation improvements, with mild-to-moderate hypernasality. Articulation improvements showed no statistically significant differences according to age at the time of surgery. However, children who underwent surgery before 4 years had a better hypernasality rating than those who underwent surgery after 4 years of age. CONCLUSIONS: Children with SMCP tend to undergo delayed treatment because the anatomical symptoms in some children with SMCP are unclear, and surgical interventions are considered only after speech problems are clarified. Starting interventions as early as possible reduces the likelihood of receiving secondary surgery and speech therapy, while increasing expectations for positive speech function at the end.
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OBJECTIVE: The purpose of this study was to determine whether test-retest nasalance score variability differs between Korean children with and without cleft palate (CP) and vowel context influences variability in nasalance score. PARTICIPANTS: Thirty-four 3-to-5-year-old children with and without CP participated in the study. METHODS: Three 8-syllable speech stimuli devoid of nasal consonants were used for data collection. Each stimulus was loaded with high, low, or mixed vowels, respectively. All participants were asked to repeat the speech stimuli twice after the examiner, and an immediate test-retest nasalance score was assessed with no headgear change. RESULTS: Children with CP exhibited significantly greater absolute difference in nasalance scores than children without CP. Variability in nasalance scores was significantly different for the vowel context, and the high vowel sentence showed a significantly larger difference in nasalance scores than the low vowel sentence. The cumulative frequencies indicated that, for children with CP in the high vowel sentence, only 8 of 17 (47%) repeated nasalance scores were within 5 points. CONCLUSIONS: Test-retest nasalance score variability was greater for children with CP than children without CP, and there was greater variability for the high vowel sentence(s) for both groups.
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Fisura del Paladar/fisiopatología , Fonación , Habla , Calidad de la Voz , Preescolar , Femenino , Humanos , Masculino , Nariz , Medición de la Producción del HablaRESUMEN
This study longitudinally investigated vocal development in Korean children from 9 to 18 months of age with and without cleft palate (CP). Utterance samples were collected from 24 children with and without CP at 9, 12, 15 and 18 months of age. Each utterance was categorised into levels of vocalisation using the Korean-translated version of the Stark Assessment of Early Vocal Development-Revised (SAEVD-R). The results showed children with CP produced a significantly higher rate of precanonical vocalisations (the combination of Levels 1, 2, and 3) and a lower rate of Level 4 and 5 vocalisations than children without CP. Both groups showed decreases in Levels 1 and 2 and increases in Level 5 from 9 to 18 months of age. A significant increase in the proportion of Level 4 vocalisations across age was observed only in children without CP. Young Korean children with CP showed lower proportions of advanced vocalisation levels characterised by canonical and complex syllable structures across 9 and 18 months of age compared to children without CP.
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Desarrollo Infantil/fisiología , Lenguaje Infantil , Fisura del Paladar/complicaciones , Voz/fisiología , Labio Leporino , Femenino , Humanos , Lactante , Masculino , República de Corea , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The purpose of this study was to determine whether age and vowel contexts influence test-retest nasalance score variability in typically developing Korean children. PARTICIPANTS: Forty-five 3- to 5-year-old children with normal speech and resonance participated in the study. METHODS: All subjects were asked to repeat three 4-syllable speech stimuli in high, low, or mixed vowel contexts twice after the examiner. An immediate test-retest nasalance score was assessed with no headgear change. Test and retest variability in nasalance scores was examined based on the absolute difference in nasalance scores of the first and second repetition for each stimulus. RESULTS: A significant main effect of the vowel context on variability in nasalance scores was found, but the effect of age on nasalance variability was not significant. Mean absolute difference in nasalance scores for the stimuli in the high vowel contexts was significantly greater than for the stimuli in the low and mixed vowel contexts. CONCLUSIONS: The results suggested that variability in nasalance scores might not decrease with age and tend to show considerable individual variations. Increased variability in nasalance scores in the high vowel context might be associated with aerodynamic and acoustic characteristics resulting from physiological aspects of the vowel /i/.
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Desarrollo Infantil/fisiología , Fonación/fisiología , Fonética , Calidad de la Voz/fisiología , Niño , Lenguaje Infantil , Femenino , Humanos , Masculino , República de CoreaRESUMEN
This study presents clinical outcomes of primary cleft palate surgery, including rate of oronasal fistula development, rate of velopharyngeal insufficiency (VPI) requiring secondary surgery, and speech outcomes. We examined the effect of cleft type on the clinical outcomes. Retrospective analysis was performed using clinical records of all patients who received a primary palatoplasty at the Cleft Palate Clinic at Seoul Asan Medical Center, South Korea, between 2007 and 2012. The study included 292 patients with nonsyndromic overt cleft palate (± cleft lip). The results revealed that the rate of oronasal fistula was 7.9% and the incidence of VPI based on the rate of secondary palatal surgery was 19.2%. The results showed that 50.3% of all the patients had received speech therapy and 28.8% and 51.4% demonstrated significant hypernasality and articulatory deficits, respectively. The results of the rate of VPI and speech outcomes were significantly different in terms of cleft type. Except for the rate of oronasal fistula, patients with cleft palate generally exhibited better clinical outcomes compared to those with bilateral or unilateral cleft lip and palate. This study suggests that several factors, including cleft type, should be identified and comprehensively considered to establish an optimal treatment regimen for patients with cleft palate.
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Labio Leporino/epidemiología , Labio Leporino/cirugía , Fisura del Paladar/epidemiología , Fisura del Paladar/cirugía , Fístula Oral/epidemiología , Procedimientos Quirúrgicos Orales/estadística & datos numéricos , Adolescente , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/epidemiología , Procedimientos de Cirugía Plástica/estadística & datos numéricos , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Insuficiencia Velofaríngea/epidemiología , Adulto JovenRESUMEN
Inhibitor of apoptosis proteins (IAPs) plays an important role in controlling cancer cell survival. IAPs have therefore attracted considerable attention as potential targets in anticancer therapy. In this study, we investigated the anti-tumor effect of AZD5582, a novel small-molecule IAP inhibitor, in human pancreatic cancer cells. Treating human pancreatic cancer cells with AZD5582 differentially induced apoptosis, dependent on the expression of p-Akt and p-XIAP. Moreover, the knockdown of endogenous Akt or XIAP via RNA interference in pancreatic cancer cells, which are resistant to AZD5582, resulted in increased sensitivity to AZD5582, whereas ectopically expressing Akt or XIAP led to resistance to AZD5582. Additionally, AZD5582 targeted cIAP1 to induce TNF-α-induced apoptosis. More importantly, AZD5582 induced a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL. Interestingly, ectopically expressing XIAP and cIAP1 inhibited the AZD5582-induced decrease of Mcl-1 protein, which suggests that AZD5582 elicits Mcl-1 decrease for apoptosis induction by targeting of XIAP and cIAP1. Taken together, these results indicate that sensitivity to AZD5582 is determined by p-Akt-inducible XIAP phosphorylation and by targeting cIAP1. Furthermore, Mcl-1 in pancreatic cancer may act as a potent marker to analyze the therapeutic effects of AZD5582.
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Alquinos/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Oligopéptidos/uso terapéutico , Neoplasias Pancreáticas/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Alquinos/química , Animales , Anexina A5/química , Apoptosis , Muerte Celular , Doxiciclina/química , Femenino , Humanos , Immunoblotting , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Oligopéptidos/química , Neoplasias Pancreáticas/tratamiento farmacológico , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: The purpose of this study was to collect nasalance scores for normal Korean-speaking children and adults and to determine whether age, vowel contexts, and stimulus length influence nasalance scores. METHODS: Fifty-seven children aged 4-6 years and 17 adults participated in the study. Mean nasalance scores were obtained for eight sentences devoid of nasal consonants divided into the vowel/a/and/i/contexts; the sentences consisted of 4, 8, 16, and 31 syllables. All subjects were asked to repeat the speech stimuli twice after the examiner. The headset of the nasometer was replaced between the first and second recordings. An average value of the nasalance scores from the two recordings for each stimulus was calculated and used in the statistical analysis as a representative measure for each subject. RESULTS: Mean and standard deviations of nasalance scores were obtained for each speech stimulus and each age group. The statistical analysis indicated significant effects of age and vowel context and a significant interaction between age and the vowel context on nasalance scores. However, the effect of stimulus length on nasalance scores was not significant. All speakers had higher nasalance scores for the vowel/i/contexts than for the vowel/a/contexts. Adults had higher nasalance scores compared to children in both vowel contexts. CONCLUSIONS: These normal nasalance values from Korean-speaking children aged 4-6 years will provide important reference information for resonance assessment of children with cleft palate who have been considered for secondary palatal surgery. The results of the study suggest that subjects' age and the vowel content of speech stimuli should be carefully considered when interpreting the nasalance scores.
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Medición de la Producción del Habla , Habla , Calidad de la Voz , Adulto , Factores de Edad , Pueblo Asiatico , Niño , Preescolar , Femenino , Humanos , Lenguaje , Masculino , Nariz , Valores de Referencia , República de Corea , Adulto JovenRESUMEN
OBJECTIVE: This study investigated the effectiveness of a parent-implemented intervention on children's speech-language development and parents' interaction styles. METHODS: Seventeen children with cleft palate (CP) and their mothers participated in all sessions of a parent-implemented intervention program. Nine children with CP and their mothers who did not receive the intervention were included to examine the full effectiveness of the program. The intervention program consisted of four phases, pre-intervention test, parent training, parent-implemented intervention at children's home for 3 months, and post-intervention test. Children's language and speech measures and maternal measures from pre- and post-intervention tests were compared between groups (intervention vs. no intervention). RESULTS: Children who received a parent-implemented intervention exhibited significant improvement in language measures based on standardized tests and quantitative language and speech measures from spontaneous utterances. The children in the intervention group showed a significantly greater extent of change in expressive vocabulary size, number of total words, and mean length of utterance than did those who did not receive the intervention. Mothers who received the training showed a significantly decreased number of different words, increased responsiveness, and decreased non-contingent utterances for children's communication acts compared to those who did not receive the training. CONCLUSIONS: The results of the study support the effectiveness of parent-implemented early intervention on positive changes in children's speech-language development and mothers' use of communication strategies.
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Fisura del Paladar/psicología , Intervención Educativa Precoz , Desarrollo del Lenguaje , Madres , Adulto , Niño , Preescolar , Fisura del Paladar/complicaciones , Fisura del Paladar/cirugía , Comunicación , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Habla , VocabularioRESUMEN
YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells. Treatment of human gastric cancer cells with YM155 differentially induced cell death dependent on the stability of cIAP1 as well as survivin. Transfection with cIAP1 expression plasmids decreased cell sensitivity to YM155, whereas knockdown of endogenous cIAP1 using RNA interference enhanced sensitivity to YM155. In addition, double knockdown of survivin and cIAP1 significantly induced cell death in the YM155-resistant cell line, MKN45. We also showed that YM155 induced autoubiquitination and proteasome-dependent degradation of cIAP1. Surprisingly, survivin affected the stability of cIAP1 through binding, contributing to cell sensitivity to YM155. Thus, our findings reveal that YM155 sensitizes human gastric cancer cells to apoptotic cell death by degrading cIAP1, and furthermore, cIAP1 in gastric cancer cells may act as a PD marker for YM155 treatment.
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Antineoplásicos/farmacología , Mucosa Gástrica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Imidazoles/farmacología , Proteínas Inhibidoras de la Apoptosis/genética , Naftoquinonas/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Proteínas Inhibidoras de la Apoptosis/metabolismo , Unión Proteica , Estabilidad Proteica , Proteolisis , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Survivin , UbiquitinaciónRESUMEN
Deregulation of the PI3K-AKT/mTOR pathway due to mutation of the tumor suppressor gene PTEN frequently occurs in human prostate cancer and is therefore considered to be an attractive therapeutic target. Here, we investigated how the PTEN genotype affected the antitumor effect of NVP-BEZ235 in human prostate cancer cells. In this setting, NVP-BEZ235 induced cell death in a PTEN-independent manner. NVP-BEZ235 selectively induced apoptotic cell death in the prostate cancer cell line DU145, which harbors wild-type PTEN; however, in the PC3 cell line, which is PTEN-null, treatment with NVP-BEZ235 resulted in autophagic cell death. Consistently, NVP-BEZ235 treatment did not result in the cleavage of caspase-3; instead, it resulted in the conversion of LC3-I to LC3-II, indicating autophagic cell death; these results suggest that an alternate mechanism of cell death is induced by NVP-BEZ235 in PTEN-null prostate cancer cells. Based on our findings, we conclude that the PTEN/PI3K/Akt pathway is critical for prostate cancer survival, and targeting PI3K signaling by NVP-BEZ235 may be beneficial in the treatment of prostate cancer, independent of the PTEN genotype.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Imidazoles/farmacología , Fosfohidrolasa PTEN/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Neoplasias de la Próstata/patología , Quinolinas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Línea Celular Tumoral/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Genotipo , Humanos , Masculino , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
OBJECTIVE: The purposes of the study were to compare the temporal characteristics of nasalization between speakers with cleft palate with or without cleft lip and normal adult speakers and to investigate the relationship between acoustic temporal measures and perceived nasality. METHODS: Fifteen speakers with cleft palate with or without cleft lip and 15 speakers without cleft palate aged 13 to 45 years participated in this study. Two listeners judged the degree of nasality in speakers with cleft palate with or without cleft lip. Two distinct acoustic energies derived from the mouth and nose were recorded simultaneously while speakers were producing the speech tasks /pimip/, /pamap/, and /pumup/. Absolute and proportional measures related to nasalization duration were obtained. RESULTS: Speakers with cleft palate with or without cleft lip exhibited more extensive acoustic nasalization in the time domain than did speakers without cleft palate with or without cleft lip. Speakers without cleft palate with or without cleft lip showed larger nasalization-duration ratios in the high vowel contexts than in the low vowel context. Speakers with cleft palate with or without cleft lip did not exhibit distinct differences in nasalization-duration ratios among the vowel contexts. The acoustic measurements reflecting temporal patterns of oral-nasal acoustic impedance were related to the perception of hypernasality. CONCLUSIONS: These results suggest that the speakers with cleft palate with or without cleft lip showed longer duration of acoustic nasalization than speakers without cleft palate with or without cleft lip. Temporal characteristics of acoustic nasalization grew longer as the degree of perceived hypernasality increased. The positive correlation between temporal measures of acoustic nasalization and degree of perceived nasality suggests that temporal measures of nasalization would provide supplementary diagnostic information in relation to the degree of hypernasality.
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Labio Leporino/fisiopatología , Fisura del Paladar/fisiopatología , Cavidad Nasal , Fonación/fisiología , Acústica del Lenguaje , Calidad de la Voz , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
UNLABELLED: A significant number of bilinguals in English-speaking countries speak Korean as their first language. One such country is the United States (U.S.). As the U.S. becomes increasingly diverse, providing more effective services for culturally and linguistically diverse children is a critical issue and growing challenge for speech-language pathologists. The U.S. Census Bureau reports that the number of Korean immigrants in the U.S. has steadily increased over the past decade. As a result, a greater number of children who speak Korean as a first or second language may need speech, language, and hearing services. This paper provides a review of the literature on (1) phonological characteristics of the Korean language and (2) speech sound acquisition and developmental patterns for phonological processes in Korean children. We illustrate how language knowledge of Korean might impact the learning of English based on case studies of three Korean children speaking English in the U.S. We describe considerations for more appropriate evaluation and treatment of speech sound disorders in Korean-English-speaking children. LEARNING OUTCOMES: Readers will be able to: (1) understand phonological characteristics of the Korean language and speech sound acquisition and developmental patterns for phonological process in Korean children, (2) describe characteristics of English speech sound acquisition in successive bilingual English-Korean learners and interference patterns that result from the influence of two independent phonological and phonetic systems, and (3) describe considerations and clinical implications for the more appropriate evaluation and treatment of speech sound disorders in Korean-English speaking children.