Induction of a single dose of streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus.

Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague-Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway.

Acoustic change complex for assessing speech discrimination in normal-hearing and hearing-impaired infants.

OBJECTIVE: This study examined (1) the utility of a clinical system to record acoustic change complex (ACC, an event-related potential recorded by electroencephalography) for assessing speech discrimination in infants, and (2) the relationship between ACC and functional performance in real life. METHODS: Participants included 115 infants (43 normal-hearing, 72 hearing-impaired), aged 3-12 months. ACCs were recorded using [szs], [uiu], and a spectral rippled noise high-pass filtered at 2 kHz as stimuli. Assessments were conducted at age 3-6 months and at 7-12 months. Functional performance was evaluated using a parent-report questionnaire, and correlations with ACC were examined. RESULTS: The rates of onset and ACC responses of normal-hearing infants were not significantly different from those of aided infants with mild or moderate hearing loss but were significantly higher than those with severe loss. On average, response rates measured at 3-6 months were not significantly different from those at 7-12 months. Higher rates of ACC responses were significantly associated with better functional performance. CONCLUSIONS: ACCs demonstrated auditory capacity for discrimination in infants by 3-6 months. This capacity was positively related to real-life functional performance. SIGNIFICANCE: ACCs can be used to evaluate the effectiveness of amplification and monitor development in aided hearing-impaired infants.

Corrigendum: Comorbidity of auditory processing, attention, and memory in children with word reading difficulties.

[This corrects the article DOI: 10.3389/fpsyg.2019.02383.].

Comparative Studies of Palmatine with Metformin and Glimepiride on the Modulation of Insulin Dependent Signaling Pathway In Vitro, In Vivo & Ex Vivo.

(1) Insulin resistance, a symptom of type 2 diabetes mellitus (T2DM), is caused by the inactivation of the insulin signaling pathway, which includes IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin (biguanide) and glimepiride (sulfonylurea) are both drugs that are derivatives of urea, and they are widely used as first-line drugs for the treatment of type 2 diabetes mellitus. Palmatine has been previously reported to possess antidiabetic and antioxidant properties. (2) The current study compared palmatine to metformin and glimepiride in a type 2 diabetes model for ADME and insulin resistance via the PI3K/Akt/GLUT4 signaling pathway: in vitro, in vivo, ex vivo, and in silico molecular docking. (3) Methods: Differentiated L6 skeletal muscle cells and soleus muscle tissue were incubated in standard tissue culture media supplemented with high insulin and high glucose as a cellular model of insulin resistance, whilst streptozotocin (STZ)-induced Sprague Dawley rats were used as the diabetic model. The cells/tissue/animals were treated with palmatine, while glimepiride and metformin were used as standard drugs. The differential gene expression of PI3K, IRS-1, PKC-α, AKT2, and GLUT4 was evaluated using qPCR. (4) Results: The results revealed that the genes IRS-PI3K-IRS-1-PKC-AKT2 were significantly down-regulated, whilst PKC-α was upregulated significantly in both insulin-resistant cells and tissue animals. Interestingly, palmatine-treated cells/tissue/animals were able to reverse these effects. (5) Conclusions: Palmatine appears to have rejuvenated the impaired insulin signaling pathway through upregulation of the gene expression of IRS-1, PI3K, AKT2, and GLUT4 and downregulation of PKC-expression, according to in vitro, in vivo, and ex vivo studies.

Parkin deficiency exacerbates fasting-induced skeletal muscle wasting in mice.

Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disease manifesting itself with tremors, muscle stiffness, bradykinesia, dementia, and depression. Mutations of mitochondrial E3 ligase, PARKIN, have been associated with juvenile PD. Previous studies have characterized muscle atrophy and motor deficits upon loss of functional Parkin in fly and rodent models. However, the mechanisms behind pathophysiology of Parkin deficient muscle remains to be elusive. Here, results suggested that knock down of Parkin significantly increases proteolytic activities in skeletal muscle cell line, the C2C12 myotubes. However, the atrogene levels increase moderately in Parkin deficient cell line. To further investigate the role of Parkin in skeletal muscle atrophy, Parkin knock out (KO) and wild type mice were subjected to 48 h starvation. After 48 h fasting, a greater reduction in skeletal muscle weights was observed in Parkin KO mice as compared to age matched wild type control, suggesting elevated proteolytic activity in the absence of Parkin. Subsequent microarray analyses revealed further enhanced expression of FOXO and ubiquitin pathway in fasted Parkin KO mice. Furthermore, a greater reduction in the expression of cytoskeleton genes was observed in Parkin KO mice following 48 h fasting. Collectively, these results suggest that Parkin deficiency exacerbates fasting-induced skeletal muscle wasting, through upregulating genes involved in catabolic activities in skeletal muscle.

Acoustic Change Complex Evoked by Horizontal Sound Location Change in Young Adults With Normal Hearing.

Acoustic change complex (ACC) is a cortical auditory-evoked potential induced by a change of continuous sound stimulation. This study aimed to explore: (1) whether the change of horizontal sound location can elicit ACC; (2) the relationship between the change of sound location and the amplitude or latency of ACC; (3) the relationship between the behavioral measure of localization, minimum audible angle (MAA), and ACC. A total of 36 normal-hearing adults participated in this study. A 180° horizontal arc-shaped bracket with a 1.2 m radius was set in a sound field where participants sat at the center. MAA was measured in a two-alternative forced-choice setting. The objective electroencephalography recording of ACC was conducted with the location changed at four sets of positions, ±45°, ±15°, ±5°, and ±2°. The test stimulus was a 125-6,000 Hz broadband noise of 1 s at 60 ± 2 dB SPL with a 2 s interval. The N1'-P2' amplitudes, N1' latencies, and P2' latencies of ACC under four positions were evaluated. The influence of electrode sites and the direction of sound position change on ACC waveform was analyzed with analysis of variance. Results suggested that (1) ACC can be elicited successfully by changing the horizontal sound location position. The elicitation rate of ACC increased with the increase of location change. (2) N1'-P2' amplitude increased and N1' and P2' latencies decreased as the change of sound location increased. The effects of test angles on N1'-P2' amplitude [F(1.91,238.1) = 97.172, p < 0.001], N1' latency [F(1.78,221.90) = 96.96, p < 0.001], and P2' latency [F(1.87,233.11) = 79.97, p < 0.001] showed a statistical significance. (3) The direction of sound location change had no significant effect on any of the ACC peak amplitudes or latencies. (4) Sound location discrimination threshold by the ACC test (97.0% elicitation rate at ±5°) was higher than MAA threshold (2.08 ± 0.5°). The current study results show that though the ACC thresholds are higher than the behavioral thresholds on MAA task, ACC can be used as an objective method to evaluate sound localization ability. This article discusses the implications of this research for clinical practice and evaluation of localization skills, especially for children.

Alpha synchronisation of acoustic responses in active listening is indicative of native language listening experience.

OBJECTIVE: Examine the effect of language experience on auditory evoked and oscillatory brain responses to lexical tone in passive (ACC) and active (P300) listening conditions. DESIGN: Language experience was evaluated using two groups, Mandarin- vs. English-listeners (with vs. without lexical tone experience). Two Mandarin lexical tones with pitch movement (T2 rising; T3 dipping) produced on the syllable /ba/ were used as stimuli. For passive listening, each tone was presented in a block. For active listening, each tone was the standard (80%) or deviant (20%) presented in two blocks. Presentation order was counterbalanced across participants in both tasks. STUDY SAMPLE: 10 adult Mandarin-listeners and 13 Australian-English-listeners contributed to the data. RESULTS: Both global field power (GFP) and time frequency analysis (TFA) failed to detect group differences in passive listening conditions for the ACC response. In contrast, the active listening condition revealed significant group differences for T2. GFP showed a trending significance with larger GFP (less consistent responses) in English- than Mandarin-listeners. TFA showed significantly higher alpha synchronisation (more focussed attention) for Mandarin- compared to English-listeners. CONCLUSIONS: Acoustic responses to speech is influenced by language experience but only during active listening, suggesting that focussed attention is linked to higher level language processes.

Differential proteomic profile of X- and Y- sorted Sahiwal bull semen.

The identification of differential proteins between X- and Y-sperm may be useful for immunological sexing of sperm. Hence, the present study was aimed to compare the protein profile of X- and Y-sorted Sahiwal bull semen using SDS-PAGE and Liquid Chromatography coupled with Mass Spectrometry (Nano LC-MS). Semen sample (n = 6) were categorized into three groups i.e., group I (X-sorted), group II (Y-sorted) and control group (both X- and Y- sperms). SDS PAGE revealed specific proteins of molecular weight between 18 and 24 kDa and between 30 and 37 kDa were present in X-sorted sperms. Also, band corresponding to 25 kDa was specific to Y-sorted sperms. Data obtained from Nano LC/MS is analysed by search engine database i.e., MASCOT and SEQUEST HT. Total, 241 proteins were identified, out of which 113 were differentially expressed between X- and Y-sorted sperms, in which 54 proteins showed at least two unique peptides. Out of 54 proteins, 27 were upregulated in X-sorted sample, 3 were upregulated in Y-sorted sample and 24 were differentially downregulated. Highly upregulated protein in X-sperm viz. Armadillo repeat containing 12 protein, NDC1 transmembrane nucleoporin, ß-nerve growth factor, C-type natriuretic peptide, Nucleobindin-2, Phosphoglycerate mutase 2, Calmodulin along with one uncharacterised protein having accession number F1MN9 may have potential to be used as biomarker for separating X and Y sperm.

Identification of Gender-Specific Molecular Differences in Glioblastoma (GBM) and Low-Grade Glioma (LGG) by the Analysis of Large Transcriptomic and Epigenomic Datasets.

Differences in the incidence and outcome of glioma between males and females are well known, being more striking for glioblastoma (GB) than low-grade glioma (LGG). The extensive and well-annotated data in publicly available databases enable us to analyze the molecular basis of these differences at a global level. Here, we have analyzed The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to identify molecular indicators for these gender-based differences by different methods. Based on the nature of data available/accessible, the transcriptomic profile was studied in TCGA by using DeSeq2 and in CGGA by T-test, after correction based. Only IDH1 wild-type tumors were studied in CGGA. Using weighted gene co-expression network analysis (WGCNA), network analysis was done, followed by the assessment of modular differential connectivity. Differentially affected signaling pathways were identified. The gender-based effects of differentially expressed genes on survival were determined. DNA methylation was studied as an indicator of gender-based epigenetic differences. The results clearly showed gender-based differences in both GB and LGG, whatever method or database was used. While there were differences in the results obtained between databases and methods used, some major signaling pathways such as Wnt signaling and pathways involved in immune processes and the adaptive immune response were common to different assessments. There was also a differential gender-based influence of several genes on survival. Also, the autosomal genes NOX, FRG1BP, and AL354714.2 and X-linked genes such as PUDP, KDM6A, DDX3X, and SYAP1 had differential DNA methylation and expression profile in male and female GB, while for LGG, these included autosomal genes such as CNIH3 and ANKRD11 and X-linked genes such as KDM6A, MAOB, and EIF2S3. Some, such as FGF13 and DDX3X, have earlier been shown to have a role in tumor behavior, though their dimorphic effects in males and females have not been identified. Our study thus identifies several crucial differences between male and female glioma, which could be validated further. It also highlights that molecular studies without consideration of gender can obscure critical elements of biology and emphasizes the importance of parallel but separate analyses of male and female glioma.

Enrichment analyses of diseases and pathways associated with precocious puberty using PrecocityDB.

Precocious puberty (PP) is an important endocrine disorder affecting children globally. Several genes, SNPs and comorbidities are reported to be associated with PP; however, this data is scattered across scientific literature and has not been systematically collated and analysed. In this study, we present PrecocityDB as the first manually curated online database on genes and their ontology terms, SNPs, and pathways associated with PP. A tool for visualizing SNP coordinates and allelic variation on each chromosome, for genes associated with PP is also incorporated in PrecocityDB. Pathway enrichment analysis of PP-associated genes revealed that endocrine and cancer-related pathways are highly enriched. Disease enrichment analysis indicated that individuals with PP seem to be highly likely to suffer from reproductive and metabolic disorders such as PCOS, hypogonadism, and insulin resistance. PrecocityDB is a useful resource for identification of comorbid conditions and disease risks due to shared genes in PP. PrecocityDB is freely accessible at http://www.precocity.bicnirrh.res.in . The database source code and content can be downloaded through GitHub ( https://github.com/bic-nirrh/precocity ).

Design and evaluation of the effectiveness of a corpus of congruent and incongruent English sentences for the study of event related potentials.

OBJECTIVE: To design and evaluate the effectiveness of a stimulus material in eliciting the N400 event related potential (ERP). DESIGN: A set of 700 semantically congruent and incongruent sentences was developed in accordance with current linguistic norms, and validated with an electroencephalography (EEG) study, in which the influence of age and gender on the N400 ERP magnitude was analysed. STUDY SAMPLE: Forty-five normal-hearing subjects (19-57 years, 21 females) participated in the EEG study. RESULTS: The stimulus material used in the EEG study elicited a robust N400 ERP, with a morphology consistent with the literature. Results also showed no statistically significant effect of age or gender on the N400 magnitude. CONCLUSIONS: The material presented in this paper constitutes the largest complete stimulus set suitable for both auditory and text-based N400 experiments. This material may help facilitate the efficient implementation of future N400 ERP studies, as well as promote standardisation and consistency across studies.

Dichotic listening is associated with phonological awareness in Australian aboriginal children with otitis media: A remote community-based study.

OBJECTIVE: Recent literature has highlighted a link between hearing loss as a result of otitis media in the early years of life and impacted binaural processing skills in later childhood. Such findings are of particular relevance to Indigenous Australian children, who tend to experience otitis media earlier in life and for longer periods than their non-Indigenous counterparts. There is also growing interest in the effects of reduced auditory processing ability on a child's early learning of language and, specifically, on phonological awareness that contributes to word reading skills. The aim of the present study was to determine the association between hearing thresholds, dichotic listening skills and phonological awareness in children with pervasive otitis media (OM) from remote Indigenous communities of Australia who generally do not speak English as a first language. METHODS: Participants included one hundred and one children between the ages of 4.8-7.9 years (mean 6.1 years) from three separate remote Northern Territory communities. Evaluations included otoscopy, air conduction PTA, and tympanometry. All children were also assessed on the Dichotic Digits difference test (DDdT) and the Foundations of Early Literacy Assessment (FELA), assessing children's dichotic listening and phonological awareness respectively. RESULTS: The results showed that 56% of the children had middle ear dysfunctions (type B and type C on tympanometry results) in at least one ear on the day. Partial correlation showed a significant correlation, between dichotic scores and FELA with age as covariate (r = 0.45, p < 0.001). One way ANOVA showed females exhibited a significantly higher performance compared to males on FELA [F (1, 99) = 5.47, p = 0.021]. The overall regression model was found to be significant in predicting total FELA scores [F (7, 77) = 7.56, p < 0.0005]. Age and gender as well as dichotic listening scores explain 40.7% of the variance. CONCLUSIONS: The results reinforce the importance of managing the ear health of Indigenous children, clarifying the impact this has on listening and phonological awareness. These findings highlight the importance of evaluating children's listening abilities, and how poor listening can impact phonological awareness. The findings have important implications for ensuring optimal listening and learning conditions in schools in remote NT communities.

PCOSKBR2: a database of genes, diseases, pathways, and networks associated with polycystic ovary syndrome.

PolyCystic Ovary Syndrome KnowledgeBase (PCOSKBR2) is a manually curated database with information on 533 genes, 145 SNPs, 29 miRNAs, 1,150 pathways, and 1,237 diseases associated with PCOS. This data has been retrieved based on evidence gleaned by critically reviewing literature and related records available for PCOS in databases such as KEGG, DisGeNET, OMIM, GO, Reactome, STRING, and dbSNP. Since PCOS is associated with multiple genes and comorbidities, data mining algorithms for comorbidity prediction and identification of enriched pathways and hub genes are integrated in PCOSKBR2, making it an ideal research platform for PCOS. PCOSKBR2 is freely accessible at http://www.pcoskb.bicnirrh.res.in/ .

Binaural processing and phonological awareness in Australian Indigenous children from the Northern Territory: A community based study.

OBJECTIVE: Research has found that otitis media (OM) is highly prevalent in Australian Indigenous children, and repeated bouts of OM is often associated with minimal-to-moderate hearing loss. However, what is not yet clear is the extent to which OM with hearing loss impacts auditory signal processing specifically, but also binaural listening, listening in noise, and the potential impact on phonological awareness (PA) - an important, emergent literacy skill. The goal of this study was to determine whether auditory abilities, especially binaural processing, were associated with PA in children from populations with a high incidence of OM, living in a remote Australian Indigenous community in the Northern Territory (NT). METHODS: Forty-seven 5-12-year-olds from a bilingual school participated in the study. All were tested to determine hearing sensitivity (pure tone audiometry and tympanometry), with PA measured on a test specifically developed in the first language of the children. OM often results in a hearing loss that can affect binaural processing: the Dichotic Digit difference Test (DDdT) was used to evaluate the children's dichotic listening and the Listening in Spatialized Noise-sentences test (LiSN-S) was used to evaluate their abilities to listen to speech-in-noise. RESULTS: Seventeen (36%) and 16 (34%) had compromised middle ear compliance (combined Type-B and -C) in the right and left ear respectively. Six children demonstrated a bilateral mild hearing loss, and another five children demonstrated a unilateral mild hearing loss. Thirty-one children were able to complete the DDdT listening task, whereas only 24 completed the speech in noise task (LiSN-S). Forty-four children (94%) were able to complete the letter identification subtask, comprising part of the PA task. The findings revealed that age was significantly correlated with all tasks such that the older children performed better across the board. Once hearing thresholds were controlled for, PA also correlated significantly with both binaural processing tasks of dichotic listening (r = 0.59, p < 0.001) and listening to speech in noise (r = -0.56, p = 0.005); indicating a potential association between early, emergent literacy and listening skills. CONCLUSIONS: The significant correlations between phonological awareness and dichotic listening as well as phonological awareness with listening to speech-in-noise skills suggests auditory processing, rather than hearing thresholds per se, are associated to phonological awareness abilities of this cohort of children. This suggests that the ability to process the auditory signal is critical.

Cluster Analyses Reveals Subgroups of Children With Suspected Auditory Processing Disorders.

BACKGROUND: Some children appear to not hear well in class despite normal hearing sensitivity. These children may be referred for auditory processing disorder (APD) assessment but can also have attention, language, and/or reading disorders. Despite presenting with similar concerns regarding hearing difficulties in difficult listening conditions, the overall profile of deficits can vary in children with suspected or confirmed APD. The current study used cluster analysis to determine whether subprofiles of difficulties could be identified within a cohort of children presenting for auditory processing assessment. METHODS: Ninety school-aged children (7-13 years old) with suspected APDs were included in a cluster analysis. All children had their reading, language, cognition and auditory processing assessed. Parents also completed the Children's Auditory Performance Scale (CHAPS). Cluster analysis was based on tasks where age-norms were available, including word reading (Castles and Coltheart irregular and non-words test), phonological awareness (Queensland University Inventory of Literacy), language [Comprehensive Language of Assessment-4, Comprehensive Assessment of Spoken Language (CASL)], sustained attention (Continuous Performance Test), working memory (digits forward and backward), and auditory processing [Frequency Pattern Test (FPT), Dichotic Digits Test (DDT)]. Hierarchical cluster analysis was undertaken to determine the optimal number of clusters for the data, followed by a k-means cluster analysis. RESULTS: Hierarchical cluster analysis suggested a four-group solution. The four subgroups can be summarized as follows: children with (1) global deficits, n = 35; (2) poor auditory processing with good word reading and phonological awareness skills, n = 22; (3) poor auditory processing with poor attention and memory but good language skills, n = 15; and (4) poor auditory processing and attention with good memory skills, n = 18. CONCLUSION: The cluster analysis identified distinct subgroups of children. These subgroups display the variation in areas of difficulty observed across different studies in the literature (e.g., not every child with APD has an attention deficit), highlighting the heterogeneous nature of APD and the need to assess a range of skills in children with suspected APD. It would be valuable for future studies to independently verify these subgroups and to determine whether interventions can be optimized based on these subgroups.

Comorbidity of Auditory Processing, Attention, and Memory in Children With Word Reading Difficulties.

OBJECTIVES: To document the auditory processing, visual attention, digit memory, phonological processing, and receptive language abilities of individual children with identified word reading difficulties. DESIGN: Twenty-five children with word reading difficulties and 28 control children with good word reading skills participated. All children were aged between 8 and 11 years, with normal hearing sensitivity and typical non-verbal intelligence. Both groups of children completed a test battery designed to assess their auditory processing, visual attention, digit memory, phonological processing, and receptive language. RESULTS: When compared to children who were good readers, children with word reading difficulties obtained significantly lower average scores on tests of auditory processing, including the frequency pattern test, gaps in noise, frequency discrimination, Dichotic Digit difference Test, and Listening in Spatialized Noise. The two groups did not differ on the discrimination measures of sinusoidal amplitude modulation or iterated rippled noise. The results from children with word reading difficulties showed that 5 children (20%) had comorbid deficits in auditory processing, visual attention, and backward digit memory; whereas 12 children (48%) had comorbid auditory processing and visual attention deficits only, and 2 children (8%) had comorbid deficits in auditory processing and digit memory; the remaining children had only auditory processing, visual attention, or digit memory deficits. CONCLUSION: The current study highlights the general co-existence of auditory processing, memory, and visual attention deficits in children with word reading difficulties. It is also noteworthy, however, that only one fifth of the current cohort had deficits across all measured tasks. Hence, our results also show the significant individual variability inherent in children with word reading difficulties.

Electrophysiological and behavioural study of localisation in presence of noise.

OBJECTIVE: The ability to determine the location of the sound source is often important for effective communication. However, it is not clear how the localisation is affected by background noise. In the current study, localisation in quiet versus noise was evaluated in adults both behaviourally, and using MMN and P3b. DESIGN: The speech token/da/was presented in a multi-deviant oddball paradigm in quiet and in presence of speech babble at +5 dB SNR. The deviants were presented at locations that differed from the standard by 30°, 60° and 90°. STUDY SAMPLE: Sixteen normal hearing adults between the age range of 18-35 years participated in the study. RESULTS: The results showed that participants were significantly faster and more accurate at identifying deviants presented at 60° and 90° as compared to 30°. Neither reaction times nor electrophysiological measures (MMN/P3b) were affected by the background noise. The deviance magnitude (30°, 60° and 90°) did not affect the MMN amplitude, but the smaller deviant (30°) generated P3b with smaller amplitude. CONCLUSIONS: Under the stimulus paradigm and measures employed in this study, localisation ability as effectively sampled appeared resistant to speech babble interference.

Predictors of Reading Skills in Children With Listening Concerns.

OBJECTIVES: Previous research shows that children with reading disorders perform poorly on auditory processing (AP) tasks. Correlational studies have also shown significant associations between some AP tasks and word and nonword reading. There is less clear evidence for AP contributions to spelling and passage reading. The aim of this research was to extend current knowledge by investigating the association between a range of AP measures used clinically and children's reading of words, nonwords, and passages, as well as word spelling. DESIGN: Regression analyses were conducted on data from 90 children 7 to 13 years of age (58 males) with reported listening and/or reading concerns. All children had normal hearing sensitivity and were tested on AP tasks including the frequency pattern test (FPT), dichotic digits test, random gap detection test, and the masking level difference. Reading tasks included word, nonword, and passage reading. Phonologic processing, core language skills, nonverbal intelligence, memory, and attention were also measured. RESULTS: All multiregression analyses were fixed order with age and gender, nonverbal intelligence, core language, phoneme manipulation, and digits backward scores included in the model before AP measures. FPT was the only AP task that accounted for significant unique variance in word/nonword reading and nonword spelling, but not passage reading. CONCLUSIONS: The findings from this study failed to show an association between many clinically used AP measures and children's reading and spelling outcomes. Nevertheless, they reiterate the importance of evaluating FPT in children with word reading disorders. The findings justify further investigation into the role of this test when diagnosing children with reading or spelling disorders.

Working Memory and Extended High-Frequency Hearing in Adults: Diagnostic Predictors of Speech-in-Noise Perception.

OBJECTIVE: The purpose of this study was to identify the main factors that differentiate listeners with clinically normal or "near-normal" hearing with regard to their speech-in-noise perception and to develop a regression model to predict speech-in-noise difficulties in this population. We also aimed to assess the potential effectiveness of the formula produced by the regression model as a "diagnostic criterion" for clinical use. DESIGN: Data from a large-scale behavioral study investigating the relationship between noise exposure and auditory processing in 122 adults (30 to 57 years) was re-examined. For each participant, a composite speech-in-noise score (CSS) was calculated based on scores from three speech-in-noise measures, (a) the Speech, Spatial and Qualities of Hearing scale (average of speech items); (b) the Listening in Spatialized Noise Sentences test (high-cue condition); and (c) the National Acoustic Laboratories Dynamic Conversations Test. Two subgroups were created based on the CSS, each comprising 30 participants: those with the lowest scores and those with the highest scores. These two groups were compared for differences in hearing thresholds, temporal perception, noise exposure, attention, and working memory. They differed significantly on age, low-, high-, and extended high-frequency (EHF) hearing level, sensitivity to temporal fine structure and amplitude modulation, linguistic closure skills, attention, and working memory. A multiple linear regression model was fit with these nine variables as predictors to determine their relative effect on the CSS. The two significant predictors, EHF hearing and working memory, from this regression were then used to fit a second smaller regression model. The resulting regression formula was assessed for its usefulness as a "diagnostic criterion" for predicting speech-in-noise difficulties using Monte Carlo cross-validation (root mean square error and area under the receiver operating characteristics curve methods) in the complete data set. RESULTS: EHF hearing thresholds (p = 0.01) and working memory scores (p < 0.001) were significant predictors of the CSS and the regression model accounted for 41% of the total variance [R = 0.41, F(9,112) = 7.57, p < 0.001]. The overall accuracy of the diagnostic criterion for predicting the CSS and for identifying "low" CSS performance, using these two factors, was reasonable (area under the receiver operating characteristics curve = 0.76; root mean square error = 0.60). CONCLUSIONS: These findings suggest that both peripheral (auditory) and central (cognitive) factors contribute to the speech-in-noise difficulties reported by normal hearing adults in their mid-adult years. The demonstrated utility of the diagnostic criterion proposed here suggests that audiologists should include assessment of EHF hearing and working memory as part of routine clinical practice with this population. The "diagnostic criterion" we developed based on these two factors could form the basis of future clinical tests and rehabilitation tools and be used in evidence-based counseling for normal hearers who present with unexplained communication difficulties in noise.