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1.
Lang Speech Hear Serv Sch ; 55(3): 756-766, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38630019

ABSTRACT

PURPOSE: The purpose of the present study was to investigate the relationship between speechreading ability, phonological skills, and word reading ability in typically developing children. METHOD: Sixty-six typically developing children (6-7 years old) completed tasks measuring word reading, speechreading (words, sentences, and short stories), alliteration awareness, rhyme awareness, nonword reading, and rapid automatized naming (RAN). RESULTS: Speechreading ability was significantly correlated with rhyme and alliteration awareness, phonological error rate, nonword reading, and reading ability (medium effect sizes) and RAN (small effect size). Multiple regression analyses showed that speechreading was not a unique predictor of word reading ability beyond the contribution of phonological skills. A speechreading error analysis revealed that children tended to use a phonological strategy when speechreading, and in particular, this strategy was used by skilled speechreaders. CONCLUSIONS: The current study provides converging evidence that speechreading and phonological skills are positively related in typically developing children. These skills are likely to have a reciprocal relationship, and children may benefit from having their attention drawn to visual information available on the lips while learning letter sounds or learning to read, as this could augment and strengthen underlying phonological representations.


Subject(s)
Lipreading , Phonetics , Reading , Humans , Child , Male , Female
2.
Q J Exp Psychol (Hove) ; : 17470218231218990, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38012815

ABSTRACT

Words that appear in many contexts/topics are recognised faster than those occurring in fewer contexts (Nation, 2017). However, contextual diversity benefits are less clear in word learning studies. Mak et al. (2021) proposed that diversity benefits might be enhanced if new word meanings are anchored before introducing diversity. In our study, adults (N = 288) learned meanings for eight pseudowords, four experienced in six topics (high diversity) and four in one topic (low diversity). All items were first experienced five times in one topic (anchoring phase), and results were compared to Norman et al. (2022) which used a similar paradigm without an anchoring phase. An old-new decision post-test (did you learn this word?) showed null effects of contextual diversity on written form recognition accuracy and response time, mirroring Norman et al.. A cloze task involved choosing which pseudoword completed a sentence. For sentences situated in a previously experienced context, accuracy was significantly higher for pseudowords learned in the low diversity condition, whereas for sentences situated in a new context, accuracy was non-significantly higher for pseudowords learned in the high diversity condition. Anchoring modulated these effects. Low diversity item accuracy was unaffected by anchoring. However, for high diversity items, accuracy in familiar contexts was better in the current experiment (anchoring) than in Norman et al. (non-anchoring), but accuracy in new contexts did not differ between the two experiments. These results suggest that anchoring facilitates meaning use in familiar contexts, but not generalisation to new contexts, nor word recognition in isolation.

3.
PLoS One ; 18(10): e0286592, 2023.
Article in English | MEDLINE | ID: mdl-37878655

ABSTRACT

BACKGROUND: Post-lingual deafness represents a critical challenge for adults' well-being with substantial public health burdens. One treatment of choice has been cochlear implants (CI) for people with severe to profound hearing loss (HL). Since 2018, Chile has implemented a high-cost policy to cover CI treatment, the "Ley Ricarte Soto" (LRS) health policy. However, wide variability exists in the use of this device. To date, no related study has been published on policy evaluation in Chile or other Latin American countries. OBJECTIVES: This study aimed to evaluate the impact of the LRS policy on the treatment success and labour market inclusion among deaf or hard of hearing (DHH) adults using CI. We examined and characterised outcomes based on self-reports about treatment success and occupation status between 2018 and 2020. DESIGN: We performed a prospective study using hospital clinical records and an online questionnaire with 76 DHH adults aged >15 who had received CIs since the introduction of the LRS policy in 2018. Using univariate and multivariate regression models, we investigated the relationship between demographic, audiological, and social determinants of health and outcomes, including treatment success for social inclusion (International Outcome inventory for Hearing Aids and CIs assessment: IOI-HA) and occupation status for labour market inclusion. RESULTS: Our study showed elevated levels of treatment success in most of the seven sub-scores of the IOI-HA assessment. Similarly, around 70% of participants maintained or improved their occupations after receiving their CI. We found a significant positive association between treatment success and market inclusion. Participants diagnosed at younger ages had better results than older participants in both outcomes. Regarding social determinants of health, findings suggested participants with high social health insurance and a shorter commute time to the clinic had better results in treatment success. For labour market inclusion, participants with high education levels and better pre- CI occupation had better post-CI occupation status. CONCLUSIONS: In evaluating the LRS policy for providing CIs for DHH adults in Chile, we found positive effects relating to treatment success and occupation status. Our study supports the importance of age at diagnosis and social determinants of health, which should be assessed by integrating public services and bringing them geographically closer to each beneficiary. Although evidence-based guidelines for candidate selection given by the LRS policy might contribute to good results, these guidelines could limit the policy access to people who do not meet the requirements of the guidelines due to social inequalities.


Subject(s)
Cochlear Implantation , Cochlear Implants , Deafness , Hearing Loss , Adult , Humans , Social Change , Prospective Studies , Chile , Cochlear Implantation/methods , Hearing Loss/therapy , Health Policy , Deafness/surgery
4.
J Clin Med ; 12(17)2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37685824

ABSTRACT

(1) Background: While spoken language learning delays are assumed for deaf and hard of hearing (DHH) children after cochlear implant (CI), many catch up with their hearing peers. Some DHH children with CIs, however, show persistent delays in language, despite protective factors being in place. This suggests a developmental language disorder (DLD). However, at present there is little consensus on how to diagnose DLD in DHH children. (2) Methods: Given the lack of consensus in this area, a set of case studies provides an appropriate first step. The goal of this paper is to show the plausibility of a DLD diagnosis, following careful analysis of protective and risk factors. A retrospective case study review was conducted for three children. Their long-term language outcomes up to four years after CI were considered in the context of access to sound, speech sound discrimination, social skills and non-verbal cognition. (3) Results: It was possible to posit DLD in one child who had experienced good access to sound, alongside good speech discrimination abilities and social development, and normal non-verbal cognition, but who presented with severe language learning difficulties. (4) Conclusions: Finding markers for DLD in DHH children is important for diagnosis and intervention. The implications for clinical practice are discussed.

5.
J Commun Disord ; 100: 106275, 2022.
Article in English | MEDLINE | ID: mdl-36327573

ABSTRACT

PURPOSE: This study investigates the relationship between pre-linguistic social communication skills and age of cochlear implant for future language outcomes in a large sample of deaf children. METHOD: A retrospective cohort study of records from 75 children. Pre-implant data included Age at Implant, pre-linguistic communication (social, symbolic and speech) skills, and non-verbal ability. Receptive and expressive language development data at 1 year, 2 years and 4 years post implant were analysed to investigate the relationships between pre-implant factors and language outcomes, in particular pre-linguistic social communication skills in early and late implanted children. RESULTS: Age at Implant was the strongest correlate of post implant expressive and receptive language outcomes. The sample was divided into early implanted (<18 month) and late implanted (>18 months) children. In the early implanted group, pre-linguistic social communication skills were the strongest pre-implant correlate of language outcomes four years post-implant. In the late implanted group, there were no significant pre-implant correlates of language outcomes. CONCLUSIONS: Long term language outcomes after cochlear implantation are the product of a set of communicative, cognitive and environmental factors. Early pre-implant social communication skills are an important consideration for clinicians who guide parents as to likely long-term outcomes post cochlear implantation. Social communication skills are particularly important for children who receive implants before the age of 18 months.


Subject(s)
Cochlear Implantation , Cochlear Implants , Deafness , Speech Perception , Child , Humans , Infant , Retrospective Studies , Deafness/surgery , Deafness/rehabilitation , Language Development , Linguistics , Communication
6.
Rev. chil. fonoaudiol. (En línea) ; 21(1): 1-14, 2022. ilus, tab
Article in Spanish | LILACS | ID: biblio-1437237

ABSTRACT

La adquisición de lengua oral representa un desafío para niñas/os sordas/os o con pérdida auditiva (NSPA) que utilizan audífonos o implante coclear (CI). Tomar decisiones a tiempo durante el tratamiento con dispositivos es esencial y requiere de evaluaciones adecuadas. Dos instrumentos usados en la toma de decisiones son las escalas "Categories of Auditory Performance Index II" (CAP-II) y "Speech Intelligibility Rating Scale" (SIR). Estas escalas han mostrado ser útiles para la evaluación continua del desarrollo de habilidades auditivas y de la lengua oral en variados idiomas, pero estas no están disponibles para el español chileno. El objetivo de este estudio es crear traducciones en español chileno de las escalas CAP-II y SIR, las que puedan ser usadas como auto-reporte online por padres y cuidadores con el fin de asistir a profesionales en el monitoreo del progreso de niños/as NSPA, considerando las restricciones impuestas por el COVID-19. El método usado en el proceso comienza con la traducción de una propuesta de auto-reporte de las versiones originales en inglés de las escalas CAP-II y SIR. Finalmente, las versiones en español chileno fueron testeadas en 107 padres-cuidadores de niñas/os NSPA con CI. Los resultados sugieren que estos instrumentos serían adecuados para su uso en el contexto chileno.


Spoken language acquisition is challenging for very young deaf or hard-of-hearing children (DHH) who wear hearing aids or cochlear implants (CI). Timely decision-making for treatment is essential for these children and requires suitable assessments. Two such assessments are the Categories of Auditory Performance Index II (CAP-II) and the Speech Intelligibility Rating Scale (SIR). These have been shown to be helpful for the ongoing evaluation of developing speech perception and spoken language skills in various languages, but they are not available in Chilean Spanish. This study aimed to create a Chilean Spanish translation of the CAP-II and SIR, appropriate for online self-administration by parents-caregivers in Chile, to assist professionals in monitoring DHH children's progress, considering the COVID-19 restrictions. The methods used in the process started with translating a self-report proposal from the original English versions of the CAP-II and SIR scales. Finally, the Chilean Spanish versions were tested in 107 Chilean parents-caregivers of DHH children with CIs. The results suggest these instruments are suitable for use in a Chilean context.


Subject(s)
Humans , Child , Adult , Parents/psychology , Speech Perception , Cochlear Implants , Hearing Aids , Hearing Loss , Hearing Tests , Translations , Online Systems , Chile , Cross-Cultural Comparison , Outcome Assessment, Health Care , Caregivers/psychology , Deafness/therapy , Self Report
7.
J Speech Lang Hear Res ; 63(11): 3775-3785, 2020 11 13.
Article in English | MEDLINE | ID: mdl-33108258

ABSTRACT

Purpose Speechreading (lipreading) is a correlate of reading ability in both deaf and hearing children. We investigated whether the relationship between speechreading and single-word reading is mediated by phonological awareness in deaf and hearing children. Method In two separate studies, 66 deaf children and 138 hearing children, aged 5-8 years old, were assessed on measures of speechreading, phonological awareness, and single-word reading. We assessed the concurrent relationships between latent variables measuring speechreading, phonological awareness, and single-word reading. Results In both deaf and hearing children, there was a strong relationship between speechreading and single-word reading, which was fully mediated by phonological awareness. Conclusions These results are consistent with ideas from previous studies that visual speech information contributes to the development of phonological representations in both deaf and hearing children, which, in turn, support learning to read. Future longitudinal and training studies are required to establish whether these relationships reflect causal effects.


Subject(s)
Deafness , Lipreading , Child , Child, Preschool , Hearing , Humans , Phonetics , Reading , Vocabulary
8.
J Speech Lang Hear Res ; 62(8): 2882-2894, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31336055

ABSTRACT

Purpose We developed and evaluated in a randomized controlled trial a computerized speechreading training program to determine (a) whether it is possible to train speechreading in deaf children and (b) whether speechreading training results in improvements in phonological and reading skills. Previous studies indicate a relationship between speechreading and reading skill and further suggest this relationship may be mediated by improved phonological representations. This is important since many deaf children find learning to read to be very challenging. Method Sixty-six deaf 5- to 7-year-olds were randomized into speechreading and maths training arms. Each training program was composed of a 10-min sessions a day, 4 days a week for 12 weeks. Children were assessed on a battery of language and literacy measures before training, immediately after training, and 3 months and 11 months after training. Results We found no significant benefits for participants who completed the speechreading training, compared to those who completed the maths training, on the speechreading primary outcome measure. However, significantly greater gains were observed in the speechreading training group on one of the secondary measures of speechreading. There was also some evidence of beneficial effects of the speechreading training on phonological representations; however, these effects were weaker. No benefits were seen to word reading. Conclusions Speechreading skill is trainable in deaf children. However, to support early reading, training may need to be longer or embedded in a broader literacy program. Nevertheless, a training tool that can improve speechreading is likely to be of great interest to professionals working with deaf children. Supplemental Material https://doi.org/10.23641/asha.8856356.


Subject(s)
Child Language , Computer-Assisted Instruction/methods , Deafness/rehabilitation , Lipreading , Patient Education as Topic/methods , Child , Child, Preschool , Communication Aids for Disabled , Deafness/psychology , Female , Humans , Language Tests , Literacy , Male , Phonetics , Reading
9.
Dyslexia ; 24(1): 84-105, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28921775

ABSTRACT

Research has linked family risk (FR) of reading difficulties (RD) with children's difficulties in emergent literacy development. This study is the first to apply parents' self-report of RD as a proxy for FR in a large sample (n = 1171) in order to test group differences in children's emergent literacy. Emergent literacy, the home literacy environment and children's interest in literacy and letters were compared across different groups of FR children around the school entry. The FR children performed lower in emergent literacy compared with not-FR children. Furthermore, when comparing FR children with one parent reporting RD and children with both parents reporting RD, moderate group differences were found in Emergent Literacy. Finally, parents' self-report of RD was a significant contributor of emergent literacy after controlling for the home literacy environment, children's gender, their interest in literacy and letters, months in kindergarten, vocabulary and parents' education. Our findings suggest that schools should monitor the reading development of children with parents self-reporting RD closely - especially if both parents self-report RD. © 2017 The Authors. Dyslexia published by John Wiley & Sons Ltd.


Subject(s)
Dyslexia/psychology , Literacy , Parents/psychology , Reading , Child , Child, Preschool , Female , Humans , Male , Schools , Self Report , Vocabulary
10.
J Deaf Stud Deaf Educ ; 22(2): 233-242, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28426889

ABSTRACT

Forty-one children with severe-profound prelingual hearing loss were assessed on single word reading, reading comprehension, English vocabulary, phonological awareness and speechreading at three time points, 1 year apart (T1-T3). Their progress was compared with that of a group of hearing children of similar nonverbal IQ, initially reading at the same level. Single word reading improved at each assessment point for the deaf children but there was no growth in reading comprehension from T2 to T3. There were no differences between children with cochlear implants and those with hearing aids on either reading measure but orally educated children had higher scores than children who signed in the classroom. English vocabulary and speechreading were the most consistent longitudinal predictors of reading for the deaf children. Phonological awareness was the most consistent longitudinal predictor for the hearing group and also a concurrent predictor of reading at T3 for both groups. There were many more significant correlations among the various measures for the deaf children than the hearing at both T1 and T3, suggesting that skills underpinning reading, including phonological awareness and vocabulary, are more closely related for deaf children. Implications of these findings for of deaf children's literacy are explored.


Subject(s)
Deafness/psychology , Reading , Child , Comprehension , Female , Humans , Intelligence , Male , Phonetics , Sign Language , Vocabulary
11.
J Speech Lang Hear Res ; 60(3): 701-711, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28241207

ABSTRACT

Purpose: In this study, we compared the language and literacy of two cohorts of children with severe-profound hearing loss, recruited 10 years apart, to determine if outcomes had improved in line with the introduction of newborn hearing screening and access to improved hearing aid technology. Method: Forty-two children with deafness, aged 5-7 years with a mean unaided loss of 102 DB, were assessed on language, reading, and phonological skills. Their performance was compared with that of a similar group of 32 children with deafness assessed 10 years earlier and also a group of 40 children with normal hearing of similar single word reading ability. Results: English vocabulary was significantly higher in the new cohort although it was still below chronological age. Phonological awareness and reading ability had not significantly changed over time. In both cohorts, English vocabulary predicted reading, but phonological awareness was only a significant predictor for the new cohort. Conclusions: The current results show that vocabulary knowledge of children with severe-profound hearing loss has improved over time, but there has not been a commensurate improvement in phonological skills or reading. They suggest that children with severe-profound hearing loss will require continued support to develop robust phonological coding skills to underpin reading.


Subject(s)
Hearing Loss , Literacy , Child , Child, Preschool , Cochlear Implants , Cohort Studies , Female , Hearing Aids , Hearing Loss/psychology , Hearing Loss/rehabilitation , Hearing Tests , Humans , Male , Persons With Hearing Impairments , Phonetics , Reading , Regression Analysis , Time Factors , Treatment Outcome , Vocabulary
12.
Res Dev Disabil ; 48: 13-24, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26524726

ABSTRACT

BACKGROUND: Vocabulary knowledge and speechreading are important for deaf children's reading development but it is unknown whether they are independent predictors of reading ability. AIMS: This study investigated the relationships between reading, speechreading and vocabulary in a large cohort of deaf and hearing children aged 5 to 14 years. METHODS AND PROCEDURES: 86 severely and profoundly deaf children and 91 hearing children participated in this study. All children completed assessments of reading comprehension, word reading accuracy, speechreading and vocabulary. OUTCOMES AND RESULTS: Regression analyses showed that vocabulary and speechreading accounted for unique variance in both reading accuracy and comprehension for deaf children. For hearing children, vocabulary was an independent predictor of both reading accuracy and comprehension skills but speechreading only accounted for unique variance in reading accuracy. CONCLUSIONS AND IMPLICATIONS: Speechreading and vocabulary are important for reading development in deaf children. The results are interpreted within the Simple View of Reading framework and the theoretical implications for deaf children's reading are discussed.


Subject(s)
Correction of Hearing Impairment , Deafness , Lipreading , Reading , Vocabulary , Adolescent , Child , Child, Preschool , Correction of Hearing Impairment/methods , Correction of Hearing Impairment/psychology , Deafness/diagnosis , Deafness/psychology , Deafness/rehabilitation , Education of Hearing Disabled/methods , Female , Hearing Aids , Hearing Tests/methods , Humans , Language Tests , Male , Persons With Hearing Impairments/psychology , Phonetics , Task Performance and Analysis
13.
Pflugers Arch ; 466(7): 1421-35, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24114173

ABSTRACT

The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other effects, has been shown to be involved in nociceptive processing both in the central and peripheral nervous systems. Anandamide is thought to be synthesised by several enzymatic pathways both in a Ca(2+)-sensitive and Ca(2+)-insensitive manner, and rat primary sensory neurons produce anandamide. Here, we show for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca(2+)-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl, the common substrate of the anandamide-synthesising pathways, results in anandamide production which is not changed by the removal of extracellular Ca(2+). We also show that anandamide, which has been synthesised in primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl induces a transient receptor potential vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by concomitant activation of the cannabinoid type 1 receptor. Finally, we show that sub-populations of transient receptor potential vanilloid type 1 ion channel-expressing primary sensory neurons also express some of the putative Ca(2+)-insensitive anandamide-synthesising enzymes. Together, these findings indicate that anandamide synthesised by primary sensory neuron via a Ca(2+)-insensitive manner has an excitatory rather than an inhibitory role in primary sensory neurons and that excitation is mediated predominantly through autocrine signalling. Regulation of the activity of the Ca(2+)-insensitive anandamide-synthesising enzymes in these neurons may be capable of regulating the activity of these cells, with potential relevance to controlling nociceptive processing.


Subject(s)
Action Potentials , Arachidonic Acids/metabolism , Calcium/metabolism , Endocannabinoids/metabolism , Phosphatidylethanolamines/pharmacology , Polyunsaturated Alkamides/metabolism , Sensory Receptor Cells/metabolism , Animals , Arachidonic Acids/biosynthesis , Cells, Cultured , Endocannabinoids/biosynthesis , Ganglia, Spinal/cytology , Ganglia, Spinal/enzymology , Ganglia, Spinal/metabolism , Group IB Phospholipases A2/genetics , Group IB Phospholipases A2/metabolism , Lysophospholipase/genetics , Lysophospholipase/metabolism , Male , Mice , Mice, Inbred C57BL , Phosphatidylethanolamines/chemistry , Phosphoric Diester Hydrolases/genetics , Phosphoric Diester Hydrolases/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/metabolism , Rats , Rats, Sprague-Dawley , Sensory Receptor Cells/enzymology , Sensory Receptor Cells/physiology , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism
14.
Nucleic Acids Res ; 41(22): 10228-40, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24049078

ABSTRACT

Oestrogen receptor α (ERα) is a nuclear receptor that is the driving transcription factor expressed in the majority of breast cancers. Recent studies have demonstrated that the liver receptor homolog-1 (LRH-1), another nuclear receptor, regulates breast cancer cell proliferation and promotes motility and invasion. To determine the mechanisms of LRH-1 action in breast cancer, we performed gene expression microarray analysis following RNA interference for LRH-1. Interestingly, gene ontology (GO) category enrichment analysis of LRH-1-regulated genes identified oestrogen-responsive genes as the most highly enriched GO categories. Remarkably, chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) to identify genomic targets of LRH-1 showed LRH-1 binding at many ERα binding sites. Analysis of select binding sites confirmed regulation of ERα-regulated genes by LRH-1 through binding to oestrogen response elements, as exemplified by the TFF1/pS2 gene. Finally, LRH-1 overexpression stimulated ERα recruitment, while LRH-1 knockdown reduced ERα recruitment to ERα binding sites. Taken together, our findings establish a key role for LRH-1 in the regulation of ERα target genes in breast cancer cells and identify a mechanism in which co-operative binding of LRH-1 and ERα at oestrogen response elements controls the expression of oestrogen-responsive genes.


Subject(s)
Breast Neoplasms/genetics , Estrogen Receptor alpha/metabolism , Gene Expression Regulation, Neoplastic , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Breast Neoplasms/metabolism , COS Cells , Chlorocebus aethiops , Female , MCF-7 Cells , Response Elements
15.
J Speech Lang Hear Res ; 56(2): 416-26, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23275416

ABSTRACT

PURPOSE: In this article, the authors describe the development of a new instrument, the Test of Child Speechreading (ToCS), which was specifically designed for use with deaf and hearing children. Speechreading is a skill that is required for deaf children to access the language of the hearing community. ToCS is a deaf-friendly, computer-based test that measures child speechreading (silent lipreading) at 3 psycholinguistic levels: (a) Words, (b) Sentences, and (c) Short Stories. The aims of the study were to standardize the ToCS with deaf and hearing children and to investigate the effects of hearing status, age, and linguistic complexity on speechreading ability. METHOD: Eighty-six severely and profoundly deaf children and 91 hearing children participated. All children were between the ages of 5 and 14 years. The deaf children were from a range of language and communication backgrounds, and their preferred mode of communication varied. RESULTS: Speechreading skills significantly improved with age for both groups of children. There was no effect of hearing status on speechreading ability, and children from both groups showed similar performance across all subtests of the ToCS. CONCLUSION: The ToCS is a valid and reliable assessment of speechreading ability in school-age children that can be used to measure individual differences in performance in speechreading ability.


Subject(s)
Deafness/rehabilitation , Hearing , Lipreading , Psycholinguistics/methods , Psycholinguistics/standards , Speech Perception , Adolescent , Child , Child, Preschool , Correction of Hearing Impairment/methods , Correction of Hearing Impairment/standards , Deafness/diagnosis , Diagnosis, Computer-Assisted , Female , Humans , Language Development , Male , Photic Stimulation/methods , Psycholinguistics/instrumentation , Reproducibility of Results
16.
ChemMedChem ; 7(11): 1909-14, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22961990

ABSTRACT

Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substituted at the position C-7 of the benzothiophene ring, might generate an inactive protein conformation through binding and thus antagonize this nuclear receptor.


Subject(s)
Raloxifene Hydrochloride/analogs & derivatives , Raloxifene Hydrochloride/pharmacology , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , COS Cells , Chlorocebus aethiops , Drug Design , Female , Humans , Ligands , Models, Molecular , Protein Conformation/drug effects , Receptors, Cytoplasmic and Nuclear/chemistry , Receptors, Cytoplasmic and Nuclear/metabolism
17.
J Deaf Stud Deaf Educ ; 16(3): 289-304, 2011.
Article in English | MEDLINE | ID: mdl-21307357

ABSTRACT

The emerging reading and spelling abilities of 24 deaf and 23 hearing beginning readers were followed over 2 years. The deaf children varied in their language backgrounds and preferred mode of communication. All children were given a range of literacy, cognitive and language-based tasks every 12 months. Deaf and hearing children made similar progress in literacy in the beginning stages of reading development and then their trajectories began to diverge. The longitudinal correlates of beginning reading in the deaf children were earlier vocabulary, letter-sound knowledge, and speechreading. Earlier phonological awareness was not a longitudinal correlate of reading ability once earlier reading levels were controlled. Only letter name knowledge was longitudinally related to spelling ability. Speechreading was also a strong longitudinal correlate of reading and spelling in the hearing children. The findings suggested that deaf and hearing children utilize slightly different reading strategies over the first 2 years of schooling.


Subject(s)
Education of Hearing Disabled , Learning , Reading , Child , Child, Preschool , Cognition , Communication , Educational Status , Female , Humans , Language , Linguistics , Longitudinal Studies , Male , Memory, Short-Term , Persons With Hearing Impairments/psychology , Phonetics , Pilot Projects , Reference Values , Time Factors , Vocabulary
18.
Breast Cancer Res Treat ; 128(2): 357-68, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20730598

ABSTRACT

Estrogen receptor-α (ERα) positive breast cancer frequently responds to inhibitors of ERα activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ERα in ERα-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ERα over-expression in ERα-positive breast cancer cells, we over-expressed ERα in the MCF-7 breast cancer cell line using adenovirus gene transduction. ERα over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ERα transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ERα-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ERα remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ERα could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation , Drug Resistance, Neoplasm , Estrogen Receptor alpha/metabolism , Estrogens/pharmacology , Adenoviridae/genetics , Antineoplastic Agents, Hormonal/therapeutic use , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Blotting, Western , Breast Neoplasms/genetics , Cell Cycle , Estrogen Receptor alpha/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tamoxifen/therapeutic use , Tumor Cells, Cultured
19.
Breast Cancer Res Treat ; 127(2): 385-96, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20607599

ABSTRACT

Estrogen receptor-α (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.


Subject(s)
Breast Neoplasms/physiopathology , Gene Expression Regulation, Neoplastic , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Estrogen/metabolism , Amino Acid Sequence , Animals , Aromatase/metabolism , Base Sequence , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , COS Cells , Cell Line, Tumor , Cell Proliferation , Chlorocebus aethiops , Female , Gene Order , Hep G2 Cells , Humans , Molecular Sequence Data , Promoter Regions, Genetic/genetics , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Estrogen/genetics , Sequence Alignment
20.
J Exp Child Psychol ; 107(3): 229-43, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20570282

ABSTRACT

The development of reading ability in a group of deaf children was followed over a 3-year period. A total of 29 deaf children (7-8 years of age at the first assessment) participated in the study, and every 12 months they were given a battery of literacy, cognitive, and language tasks. Earlier vocabulary and speechreading skills predicted longitudinal growth in reading achievement. The relations between reading and the predictor variables showed developmental change. Earlier reading ability was related to later phonological awareness skills, suggesting that deaf children might develop their phonological awareness through reading. Deaf children who had the most age-appropriate reading skills tended to have less severe hearing losses and earlier diagnoses and also preferred to communicate through speech. The theoretical implications of the role for speechreading, vocabulary and phonological awareness in deaf children's literacy are discussed.


Subject(s)
Child Development , Education of Hearing Disabled , Hearing Loss/physiopathology , Reading , Child , Cognition , Educational Status , Female , Humans , Language Tests , Longitudinal Studies , Male , Phonetics , Predictive Value of Tests , Task Performance and Analysis , Vocabulary
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