Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses.

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whether Shank3 facilitates the development of atherosclerosis. Using Gene Set Enrichment Analysis software (Version No.: GSEA-4.0.3), we analyzed the data obtained from Shank3 knockout mice (Gene Expression Omnibus database), a human population-based study cohort (from Taiwan's National Health Insurance Research Database), and a Shank3 knockdown cellular model. Shank3 knockout upregulated the expression of genes of cholesterol homeostasis and fatty acid metabolism but downregulated the expression of genes associated with inflammatory responses. Individuals with autism had higher risks of hyperlipidemia (adjusted hazard ratio (aHR): 1.39; p < 0.001), major adverse cardiac events (aHR: 2.67; p < 0.001), and stroke (aHR: 3.55; p < 0.001) than age- and sex-matched individuals without autism did. Shank3 downregulation suppressed tumor necrosis factor-α-induced fatty acid synthase expression; vascular cell adhesion molecule 1 expression; and downstream signaling pathways involving p38, Jun N-terminal kinase, and nuclear factor-κB. Thus, Shank3 may influence the development of early-onset atherosclerosis and CVD in ASD. Furthermore, regulating Shank3 expression may reduce inflammation-related disorders, such as atherosclerosis, by inhibiting tumor necrosis factor-alpha-mediated inflammatory cascades.

Behavioral and Neural Assessments of Auditory Skill Development After Hearing Instrument Fitting in Children: Case Reports and Clinical Implications.

PURPOSE: The purpose of this study was to comprehensively monitor the auditory skill development of children with hearing loss after hearing instrument fitting, and a battery of four assessments was proposed. METHOD: This battery was designed to fill the gap in speech discrimination in clinically available evaluations. The battery includes both behavioral and neural assessments. On the other hand, both tests in structured settings (sound-treated booth) and daily life were included in the battery. The four assessments include visual reinforced infant speech discrimination (VRISD), cortical auditory evoked potentials (CAEP), Auditory Skills Checklist (ASC), and Parents' Evaluation of Aural/Oral Performance of Children (PEACH). RESULTS: Two cases were reported, and their clinical implications were discussed. CONCLUSIONS: The proposed comprehensive assessment battery is suitable for evaluating children who are developmentally appropriate for visual reinforcement audiometry. More importantly, the VRISD assessment fills in the current gap, which is the discrimination stage, for the available clinical tests for assessing auditory developmental stages.

Development of the Mandarin Phoneme Detection Score Sheet as a Screening Tool.

BACKGROUND AND OBJECTIVES: Hearing thresholds across frequencies must be obtained for hearing aid fitting. Narrow-band noise (NBN) and speech sounds are often used as stimuli in pediatric audiologic assessments to elicit children's attention due to their wider frequency ranges as compared to pure tones. However, obtaining complete responses across frequency ranges is challenging in pediatric practice. Therefore, we developed a frequency-specific phoneme screening tool, the Mandarin Phoneme Detection Score Sheet, to help clinicians evaluate aided performance in pediatric practice. SUBJECTS AND METHODS: A total of 30 adults with typical hearing and 30 children aged 3-12 years with hearing loss were recruited. Threshold ranges for the aided detection of Mandarin phonemes and NBN were measured using 95% confidence intervals. A stepwise regression analysis was then performed to identify the Mandarin phonemes that can predict NBN detection performance. RESULTS: The Mandarin Phoneme Detection Score Sheet was developed based on the results of the regression analysis. It was shown that the phonemes /ɤ, a, tɕh/ could predict detection performance at different frequencies. CONCLUSIONS: The Mandarin Phoneme Detection Score Sheet can allow audiologists and early intervention professionals to determine the benefits of hearing aids for pediatric patients in the early stage of hearing loss conditions.

Spontaneous perirenal urinoma induced by NSAID-associated acute interstitial nephritis.

Urinoma, defined as the urine leakage beyond the urinary tract, is commonly induced by blunt trauma or urinary tract obstruction by stone, intra-abdominal malignancy, or retroperitoneal fibrosis. Spontaneous urinoma is rare and parenchymal pathologic change is rarely mentioned when urinoma is found. We present a case of a 28-year-old woman with bilateral flank pain induced by spontaneous urinoma. The lady received chronic analgesics because of migraine. After intravenous ketorolac injection, bilateral perirenal urinoma developed. Renal biopsy showed acute interstitial nephritis associated with nonsteroid anti-inflammatory drug (NSAID). After discontinuing the medication, urinoma subsided, and the patient was discharged with normal serum creatinine. This was the first case of urinoma induced by NSAID-related interstitial nephritis, and pathophysiology and management of spontaneous urinoma are discussed.

Comparison of Newborn Hearing Screening in Well-Baby Nursery and NICU: A Study Applied to Reduce Referral Rate in NICU.

OBJECTIVES: To determine whether newborn hearing screening in a well-baby nursery (WBN) and neonatal intensive care unit (NICU) nursery: 1) meet three targeted, screening, referral, and diagnostic follow-up rates; 2) compare the average age of diagnosis for infants admitted to the WIN and NICU; and 3) determine prevalence of hearing loss in neonatal population; and 4) try to find a practical newborn hearing screening time algorithm to reduce refer rate in NICU. MATERIALS AND METHODS: It examined 15,624 newborns in the WBN (13,676) and NICU (1948) screened for congenital HL using AABR. The variables analyzed in it were the screening rate, referral rate, follow-up rate, diagnostic rate and diagnostic age, prevalence rate, degrees of congenital bilateral HL. The study was approved by the hospital's institutional review board (13MMHISO23). RESULTS: The screening rates were 99.8% and 99.6% in the WBN and NICU groups, respectively, without significant difference. The referral rates were 0.7% and 2.8% in the WBN and NICU groups, with significant difference. Furthermore, the diagnostic follow-up rates were 76.7% and 89.1% in the WBN and NICU groups, without significant difference. The average initial diagnostic ages were 1.9 months and 3.8 months in the WBN and NICU groups, with significant difference. The prevalence of congenital bilateral hearing loss were 0.27% and 1.6% in the WBN and NICU groups, with significant difference. CONCLUSION: The screening, referral and follow-up rate in the WBN and NICU groups were equivalent to the quality indicators. For NICU group, screening and diagnostic follow up were performed later than those in WBN group; however the lower referral rate in our NICU group was successfully achieved in this study and can be applied clinically. The prevalence of congenital bilateral hearing loss was higher in the NICU group than in the WBN group.

The Performance Analysis of the Map-Aided Fuzzy Decision Tree Based on the Pedestrian Dead Reckoning Algorithm in an Indoor Environment.

Hardware sensors embedded in a smartphone allow the device to become an excellent mobile navigator. A smartphone is ideal for this task because its great international popularity has led to increased phone power and since most of the necessary infrastructure is already in place. However, using a smartphone for indoor pedestrian navigation can be problematic due to the low accuracy of sensors, imprecise predictability of pedestrian motion, and inaccessibility of the Global Navigation Satellite System (GNSS) in some indoor environments. Pedestrian Dead Reckoning (PDR) is one of the most common technologies used for pedestrian navigation, but in its present form, various errors tend to accumulate. This study introduces a fuzzy decision tree (FDT) aided by map information to improve the accuracy and stability of PDR with less dependency on infrastructure. First, the map is quickly surveyed by the Indoor Mobile Mapping System (IMMS). Next, Bluetooth beacons are implemented to enable the initializing of any position. Finally, map-aided FDT can estimate navigation solutions in real time. The experiments were conducted in different fields using a variety of smartphones and users in order to verify stability. The contrast PDR system demonstrates low stability for each case without pre-calibration and post-processing, but the proposed low-complexity FDT algorithm shows good stability and accuracy under the same conditions.

The relationship between cortical auditory evoked potential (CAEP) detection and estimated audibility in infants with sensorineural hearing loss.

OBJECTIVE: To determine the effectiveness of objective statistical detection in CAEP testing to evaluate audibility in young infants with sensorineural hearing loss. DESIGN: CAEP recordings to speech-based stimuli were made at three presentation levels (55, 65, or 75 dB SPL) when a group of hearing-impaired infants were either aided or unaided. Later-obtained behavioral audiograms were used as the gold standard against which to evaluate the accuracy of the automatic detection of the presence/absence of CAEP responses. STUDY SAMPLE: Participants were 18 infants with confirmed sensorineural hearing loss. RESULTS: Higher sensation levels led to a greater number of present CAEP responses being detected. More CAEP waveforms were detected in the aided condition than in the unaided condition. CONCLUSION: Our results suggest that the presence/absence of CAEP responses defined by the automatic statistical criterion was effective in showing whether increased sensation levels provided by amplification were sufficient to reach the cortex. This was clearly apparent from the significant increase in cortical detections when comparing unaided with aided testing.

Intelligent sensor positioning and orientation through constructive neural network-embedded INS/GPS integration algorithms.

Mobile mapping systems have been widely applied for acquiring spatial information in applications such as spatial information systems and 3D city models. Nowadays the most common technologies used for positioning and orientation of a mobile mapping system include a Global Positioning System (GPS) as the major positioning sensor and an Inertial Navigation System (INS) as the major orientation sensor. In the classical approach, the limitations of the Kalman Filter (KF) method and the overall price of multi-sensor systems have limited the popularization of most land-based mobile mapping applications. Although intelligent sensor positioning and orientation schemes consisting of Multi-layer Feed-forward Neural Networks (MFNNs), one of the most famous Artificial Neural Networks (ANNs), and KF/smoothers, have been proposed in order to enhance the performance of low cost Micro Electro Mechanical System (MEMS) INS/GPS integrated systems, the automation of the MFNN applied has not proven as easy as initially expected. Therefore, this study not only addresses the problems of insufficient automation in the conventional methodology that has been applied in MFNN-KF/smoother algorithms for INS/GPS integrated systems proposed in previous studies, but also exploits and analyzes the idea of developing alternative intelligent sensor positioning and orientation schemes that integrate various sensors in more automatic ways. The proposed schemes are implemented using one of the most famous constructive neural networks--the Cascade Correlation Neural Network (CCNNs)--to overcome the limitations of conventional techniques based on KF/smoother algorithms as well as previously developed MFNN-smoother schemes. The CCNNs applied also have the advantage of a more flexible topology compared to MFNNs. Based on the experimental data utilized the preliminary results presented in this article illustrate the effectiveness of the proposed schemes compared to smoother algorithms as well as the MFNN-smoother schemes.

An Artificial Neural Network Embedded Position and Orientation Determination Algorithm for Low Cost MEMS INS/GPS Integrated Sensors.

Digital mobile mapping, which integrates digital imaging with direct geo-referencing, has developed rapidly over the past fifteen years. Direct geo-referencing is the determination of the time-variable position and orientation parameters for a mobile digital imager. The most common technologies used for this purpose today are satellite positioning using Global Positioning System (GPS) and Inertial Navigation System (INS) using an Inertial Measurement Unit (IMU). They are usually integrated in such a way that the GPS receiver is the main position sensor, while the IMU is the main orientation sensor. The Kalman Filter (KF) is considered as the optimal estimation tool for real-time INS/GPS integrated kinematic position and orientation determination. An intelligent hybrid scheme consisting of an Artificial Neural Network (ANN) and KF has been proposed to overcome the limitations of KF and to improve the performance of the INS/GPS integrated system in previous studies. However, the accuracy requirements of general mobile mapping applications can't be achieved easily, even by the use of the ANN-KF scheme. Therefore, this study proposes an intelligent position and orientation determination scheme that embeds ANN with conventional Rauch-Tung-Striebel (RTS) smoother to improve the overall accuracy of a MEMS INS/GPS integrated system in post-mission mode. By combining the Micro Electro Mechanical Systems (MEMS) INS/GPS integrated system and the intelligent ANN-RTS smoother scheme proposed in this study, a cheaper but still reasonably accurate position and orientation determination scheme can be anticipated.

Long-term anterior thalamus stimulation for intractable epilepsy.

BACKGROUND: Deep brain stimulation (DBS) has re-emerged as an alternative therapy for intractable epilepsy. In this study, we investigated the feasibility, efficacy and safety of long-term anterior thalamic nucleus (ATN) stimulation for intractable epilepsy. METHODS: In this open-label pilot study of electrical stimulation of the ATN, we investigated four cases of intractable epilepsy (one man with generalized seizure, and three woman with partial seizure and secondary generalization; age range, 18-45 years), with a follow up of 2 years. Under the indication of bilateral or nonlocalized epileptic foci, each patient underwent stereotactic implantation of a quadripolar stimulating electrode in the bilateral ATN, guided by single-unit microelectrode recording. The stimulator was turned on after a sham period of 2-4 weeks. Seizure frequency was monitored and compared with the pre-implantation baseline. Twenty-one similar cases reported in the literature during the past 20 years were reviewed. RESULTS: Insertion into and stimulation through electrodes implanted in the ATN decreased seizure frequency, with a mean reduction rate of 49.6% in the current series. Two patients had seizure reductions of > or = 60%, with complete remission achieved in one patient. These findings were consistent with those in four other investigations of intractable epilepsy, which showed an overall rate of 45-55% in seizure reduction. One of our patients suffered a small frontal hemorrhage, and a second patient had extension erosion over the scalp; however, no resultant major or permanent neurological deficits were observed. CONCLUSIONS: Based on our study results and literature review, it appears reasonable to conclude that long-term ATN stimulation is a safe and effective treatment for seizure reduction in patients with intractable epilepsy.

Electrical stimulation of the anterior nucleus of the thalamus for intractable epilepsy: a long-term follow-up study.

PURPOSE: The anterior nucleus of the thalamus (ANT) modulates temporal lobe and hypothalamic activities, and relays information to the cingulate gyrus and entorhinal cortex. Deep brain stimulation (DBS) of the ANT has been reported to decrease seizure activity in a limited number of human subjects. However, long-term effect of chronic ANT stimulation on such patients remains unknown. We report long-term follow-up results in four patients receiving ANT stimulation for intractable epilepsy. METHODS: Four patients underwent stereotactic implantation of quadripolar stimulating electrodes in the bilateral ANT, guided by single-unit microelectrode recording. Electrode location was confirmed by postoperative magnetic resonance imaging (MRI). The stimulator was activated 2-4 weeks following electrode insertion; initial stimulation parameters were 4-5 V, 90-110 Hz, and 60-90 micros. Seizure frequency was monitored and compared with preimplantation baseline frequency. Intelligence quotient (IQ) test and auditory P300 response were performed before and after implantation of electrodes. RESULTS: Four patients (one man with generalized seizures, and three women with partial seizures and secondary generalization) aged 18-45 years old were studied with mean follow-up period of 43.8 months. The four patients demonstrated a sustained effect of 49% (range, 35-76%) seizure reduction to ANT stimulation. Simple insertion of DBS electrodes (Sham period, no stimulation) produced a mean reduction in seizures of 67% (range, 44-94%). One patient was seizure-free for 15 months with anticonvulsant medications. One patient had a small frontal hemorrhage and a second patient had extension erosion over scalp; no resultant major or permanent neurological deficit was observed. Preoperative IQ index and auditory P300 were not significantly different with those after electrodes implantation. CONCLUSIONS: Implantation of electrodes in the ANT and subsequent stimulation is associated with a significant reduction in seizure frequency. However, our study could not differentiate whether the implantation itself, the subsequent stimulation or postimplantation drug manipulation had the greatest impact. These experimental results prompt further controlled study in a large patient population.