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Background Skeletal dysplasia (SD) is one of the most common inherited neonatal disorders worldwide, where the recurrent pathogenic mutations in the FGFR2, FGFR3, COL1A1, COL1A2 and COL2A1 genes are frequently reported in both non-lethal and lethal SD. The traditional prenatal diagnosis of SD using ultrasonography suffers from lower accuracy and performed at latter gestational stage. Therefore, it remains in desperate need of precise and accurate prenatal diagnosis of SD in early pregnancy. With the advancements of next-generation sequencing (NGS) technology and bioinformatics analysis, it is feasible to develop a NGS-based assay to detect genetic defects in association with SD in the early pregnancy. Methods An ampliseq-based targeted sequencing panel was designed to cover 87 recurrent hotspots reported in 11 common dominant SD and run on both Ion Proton and NextSeq550 instruments. Thirty-six cell-free and 23 genomic DNAs were used for assay developed. Spike-in DNA prepared from standard sample harboring known mutation and normal sample were also employed to validate the established SD workflow. Overall performances of coverage, uniformity, and on-target rate, and the detecting limitations on percentage of fetal fraction and read depth were evaluated. Results The established targeted-seq workflow enables a single-tube multiplex PCR for library construction and shows high amplification efficiency and robust reproducibility on both Ion Proton and NextSeq550 platforms. The workflow reaches 100% coverage and both uniformity and on-target rate are > 96%, indicating a high quality assay. Using spike-in DNA with different percentage of known FGFR3 mutation (c.1138 G > A), the targeted-seq workflow demonstrated the ability to detect low-frequency variant of 2.5% accurately. Finally, we obtained 100% sensitivity and 100% specificity in detecting target mutations using established SD panel. Conclusions An expanded panel for rapid and cost-effective genetic detection of SD has been developed. The established targeted-seq workflow shows high accuracy to detect both germline and low-frequency variants. In addition, the workflow is flexible to be conducted in the majority of the NGS instruments and ready for routine clinical application. Taken together, we believe the established panel provides a promising diagnostic or therapeutic strategy for prenatal genetic testing of SD in routine clinical practice.

Objectives To compare the efficacy of pentoxifylline with that of conventional steroid therapy in diabetic patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and to compare blood sugar levels during hospitalization. Materials and methods Medical charts were retrospectively reviewed for all diabetic patients admitted to one institution for ISSNHL between 2000 and 2015. We analyzed 298 cases; 50 patients received pulse steroid treatment (steroid group) and 248 received intravenous administration of pentoxifylline only (pentoxifylline group). Hearing change was evaluated by comparing the initial hearing tests with follow-up hearing tests for up to 3 months. Blood sugar levels were also compared between the 2 groups. Results At 3 months post-treatment, the degree of hearing recovery was similar between the 2 groups. The pure-tone average was improved from baseline by 17.9±21.2 dB in the steroid group and 18.9±20.7 dB in the pentoxifylline group (p=0.776); hearing recovery rates were also similar (40% vs 39.1%; p=0.826). During hospitalization, average fasting blood sugar levels were higher (203.9±92.0 vs 174.4±54.8 mg/dL; p=0.033) and acute hyperglycemia was more common (48.0% vs 33.1%; p=0.044) with steroid versus pentoxifylline treatment. Conclusion Hearing recovery rates did not significantly differ between steroid and pentoxifylline treatment in diabetic patients with ISSNHL, but pentoxifylline appeared to be associated with better blood sugar control.

This study investigated the development of subcortical pitch processing, as reflected by the scalp-recorded frequency-following response, during early infancy. Thirteen Chinese infants who were born and raised in Mandarin-speaking households were recruited to partake in this study. Through a prospective-longitudinal study design, infants were tested twice: at 1–3 days after birth and at three months of age. A set of four contrastive Mandarin pitch contours were used to elicit frequency-following responses. Frequency Error and Pitch Strength were derived to represent the accuracy and magnitude of the elicited responses. Paired-samples t tests were conducted and demonstrated a significant decrease in Frequency Error and a significant increase in Pitch Strength at three months of age compared to 1–3 days after birth. Results indicated the developmental trajectory of subcortical pitch processing during the first three months of life.

Nontuberculous mycobacterial otomastoiditis is rare and can be easily confused with various different forms of otitis media. We describe the case of a 50-year-old woman who presented with left-sided chronic otitis media that had persisted for more than 1 year. It was not eradicated by standard antimicrobial therapy and surgical debridement. After appropriate antibiotic therapy for nontuberculous mycobacteria was added to the therapeutic regimen, the patient improved significantly and the lesion had healed by 6 months. Based on our experience with this case, we conclude that early bacterial culture and staining for acid-fast bacilli in ear drainage material or granulation tissue should be performed when standard antimicrobial therapy fails to eradicate chronic otitis media of an un-determined origin that is accompanied by granulation tissue over the external auditory canal or middle ear. Polymerase chain reaction testing is also effective for rapid diagnosis. Surgical debridement and removal of the foreign body can successfully treat nontuberculous mycobacterial otomastoiditis only when effective antimicrobial therapy is also administered.

To investigate whether adenotonsillectomy reduces upper respiratory tract infections (URIs) in the pediatric population.We identified 415 children, aged ≤18 years who had undergone adenoidectomy and/or tonsillectomy during the period from 1999 to 2006, from the Taiwan National Health Insurance Research Database. The comparison group consisted of 1630 children without the surgery randomly selected from the same database frequency matched with sex, age and the surgery date (index date). Changes in physician visits for URIs 2-year period before and 2-year period after the index date were compared between the two groups of children.The number of outpatient visits for URIs decreased with time, children with tonsillectomy and/or adenoidectomy had a greater reduction than comparison children (mean changes, -14 times and -6 times, respectively) in the 2-year period after the index date. Multivariate analyses using generalized estimated equation revealed a significant effect in reducing URIs visits from the surgery (relative ratio=0.85, p0.0001), strongest for children undergoing both tonsillectomy and adenoidectomy (relative ratio=0.76, p0.0001). The association between surgery and the decrease in URIs was more pronounced for children aged 12 years and less.This population-based study suggests that tonsillectomy and/or adenoidectomy is associated with fewer physician visits for URIs. The association is weakened in old children.

Voice pitch carries important cues for speech perception in humans. Recent studies have shown the feasibility of recording the frequency-following response (FFR) to voice pitch in normal-hearing listeners. The presence of such a response, however, has been dependent on subjective interpretation of experimenters. The purpose of this study was to develop and test an automated procedure including a control-experimental protocol and response-threshold criteria suitable for extracting FFRs to voice pitch, and compare the results to human judgments.A set of four Mandarin tones (Tone 1 flat; Tone 2 rising; Tone 3 dipping; and Tone 4 falling) were prepared to reflect the four contrastive pitch contours. Two distinctive algorithms, short-term autocorrelation in the time domain and narrow-band spectrogram in the frequency domain, were used to estimate the Frequency Error, Slope Error, Tracking Accuracy, Pitch Strength and Pitch-Noise Ratio of the recordings from individual listeners as well as the power and false-positive rates of each algorithm.Eleven native speakers (five males; age: mean ± SD = 31.4 ± 4.7 years) of Mandarin Chinese were recruited.The results demonstrated that both algorithms were suitable for extracting FFRs and the objective measures showed comparable results to human judgments.The automated procedure used in this study, including the use of the control-experimental protocol and response thresholds used for each of the five objective indices, can be used for difficult-to-test patients and may prove to be useful as an assessment and diagnostic method in both clinical and basic research efforts.