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Purpose: When the speech motor system encounters errors, it generates adaptive responses to compensate for the errors. Unlike errors induced by formant-shift perturbations, errors induced by formant-clamp perturbations do not correspond with the speaker's speech (i.e., degraded motor-to-auditory correspondence). We previously showed that adaptive responses to formant-clamp perturbations are smaller than responses to formant-shift perturbations when perturbations are introduced gradually. This study examined responses to formant-clamp and formant-shift perturbations when perturbations are introduced suddenly. Method: One group of participants ( n = 30) experienced gradually introduced formant-clamp and formant-shift perturbations, and another group ( n = 30) experienced suddenly introduced formant-clamp and formant-shift perturbations. We designed the perturbations based on participant-specific vowel configurations such that a participant's first and second formants of /ɛ/ were perturbed toward their /æ/. To estimate adaptive responses, we measured formant changes (0–100 ms of the vowel) in response to the formant perturbations. Results: We found that (a) the difference between responses to formant-clamp and formant-shift perturbations was smaller when the perturbations were introduced suddenly and (b) responses to suddenly introduced (but not gradually introduced) formant-shift perturbations positively correlated with responses to formant-clamp perturbations. Conclusions: These results showed that the speech motor system responds to errors induced by formant-shift and formant-clamp perturbations more differently when perturbations are introduced gradually than suddenly. Overall, the quality of errors (formant-shift vs. formant-clamp) and the manner of introducing errors (gradually vs. suddenly) modulate the speech motor system's evaluations of and responses to errors. Supplemental Material: https://doi.org/10.23641/asha.22406422

The public in southwestern Taiwan’s Kaohsiung City have expressed concern over risk of arsenic (As) to people living in six villages of that city nearby a coastal heavy-industrial area. To investigate, we first analyzed urinary total As (TAs) levels in 328 adult subjects from the Nutrition and Health Survey in Taiwan in 2005-2008 (NAHSIT 2005-8). We found the top three highest median urinary TAs levels in residents from the Penghu islands (150.90 µg/L, n = 21) and the upper northern region (78.04 µg/L, n = 56) and the southern region (75.21 µg/L, n = 33) of Taiwan. Then, urinary TAs levels in 1,801 and 1,695 voluntary adult residents of the above-mentioned six villages in 2016 and 2018 respectively were compared with those from the top three highest TAs levels of NAHSIT 2005-8. Median urinary As levels were 84.60 µg/L in 2016 and 73.40 µg/L in 2018, similar to those in the southern region of Taiwan, but far below those in the Penghu islands (p < 0.05). Finally, in 2020, we interviewed 116 healthy adult residents from the same six villages and analyzed one-spot urine samples of total inorganic-related As (TiAs), a summation of As3+, As5+, monomethylarsonic acid, and dimethylarsinic acid. Subjects consuming seafood 2 days before urine sampling (n = 15) were significantly higher TiAs levels than those not (n = 101, p = 0.028). These findings suggest that seafood consumption is probably the main source of urinary TAs and TiAs in people residing close to that coastal heavy-industrial area.

Background/Purpose: The FUT2 gene is a histo-blood group antigen (HBGA) that determines the susceptibility to Norovirus (NoV) infection. This study investigated the clinical significance of the FUT2 gene profile and HBGA expression in NoV infection. Methods: Fecal specimens were collected from children in Chang-Gung Children's Hospital with acute gastroenteritis (AGE). The medical records were reviewed for clinical data. The viral etiology of gastroenteritis was validated using molecular methods. Genomic DNA was isolated from saliva or whole blood with the Puregene B Kit, according to the manufacturers' instructions. Single-nucleotide polymorphisms (SNPs) were determined by real-time PCR assays. Results: FUT2 gene DNA was examined in 98 children with AGE. NoV was detected by RT-PCR in 44 patients (44.8%), while 54 (55.2%) had non-NoV AGE. Of the 44 NoV patients, 38 (86.3%) were secretors (no G428A mutation) and six (13.7%) were non-secretors (G428A mutation). Of the 54 non-NoV AGE patients, 28 (51.9%) were secretors and 20 (48.1%) were non-secretors. NoV-infected patients who were secretors had more frequent vomiting (P

Introduction In this study, the combination of TEMPO-oxidized sacchachitin nanofibers (TOSCNFs) with chitosan-activated platelet-rich plasma (cPRP) was evaluated for remedying dry eye syndrome (DES). Methods TOSCNFs, designated T050SC, were generated. T050SC combined with chitosan-activated (cPRP) was formulated as eye drops for application for severe DES. To evaluate the effects of cPRP and TOSCNFs on the repair of corneal injury, in vitro studies were conducted using Statens Seruminstitut rabbit corneal (SIRC) epithelial cells for cell proliferation and cell migration assays, and a severe DES animal model using rabbits was established with benzalkonium chloride (BAC) treatment for the evaluation. Results Results showed that the optimal eye formulation contained PRP activated by 350 μg/mL of the low-molecular-weight chitosan group (L3) combined with 300 μg/mL TO50SC (L3+T050SC). In the WST-1 cell-proliferation assay, L3 and L3+TO50SC significantly increased Statens SIRC cell proliferation after 24 hrs of incubation. In the SIRC cell migration assay, the L3+TO50SC group showed a wound-healing efficiency of 89% after 24-hr treatment. After 5 days of treatment, Schirmer's test results did not simulate the dry eye animal model. Typical cornea appearance and eye fluorescein staining results showed that the L3 group had the best effect on improving cornea haze and epithelial damage. Conclusion This study has determined that TOSCNFs effectively promoted the healing effect on severe cases of corneal damage, and also might enhance the clinical application and medical potential of PRP in ophthalmology.

There is controversial evidence on the best choice for root-end filling materials in follow-up periods and treatment protocols. The purpose of this study was to evaluate the effectiveness of different root-end filling materials in modern surgical endodontic treatment.A total of 16 studies with a minimum follow-up of 12-months were qualified to be reviewed, involving randomized control trials and observational studies in PubMed, Cochrane library and Scopus until September 1, 2021. The outcome of modern surgical endodontic treatment was assessed based on clinical and radiographic success. Direct comparisons were combined to estimate indirect comparisons, and the estimated effect size was analyzed using the odds ratio (OR). The comparative effectiveness of all materials for target outcomes were shown as P-score.Within this network meta-analysis, mineral trioxide aggregate (MTA) had superior effects among all root-end filling materials at 12-months follow-up. (MTA: OR, 2.03; 95% CI, 0.84-4.91; P-score, 0.86; reference material, gutta-percha). In further sensitivity analyses, MTA, calcium silicate-based root repair material (RRM) and super EBA cement (Super EBA) were associated with significantly higher success rates at 12-months follow-up. (MTA: OR, 5.62; 95% CI, 1.58-19.99; P-score, 0.88; RRM: OR, 5.23; 95% CI, 1.05-25.98; P-score, 0.74; Super EBA: OR, 3.99; 95% CI, 1.06-15.04; P-score, 0.54; reference material, gutta-percha).MTA remains the best choice for root-end filling materials of modern surgical endodontic treatment at the 12-month follow-up. Comparative randomized clinical trials in the long-term follow-up are warranted in future investigations.

Two decades have passed since the September 11 attacks by Islamist militants that shocked the world. Despite this, Islamophobia remains a common phenomenon. In Taiwan, the 2014 12-year Basic Education Curriculum amendments emphasize cultural and global understanding as core competencies. With more than 6 years of implementation, it would be therefore interesting to learn what elementary school students think of Islam. Anchoring on the concepts of intercultural competency development, stereotypes are said to be related to cognitive knowledge, intercultural behavioral abilities, and attitudes. A survey instrument was developed and validated to collect information on stereotypes, skills in intercultural interaction, and attitudes toward Islam. Additionally, cognitive knowledge of Islam was also tested. A total of 712 students participated in the study. Structural equation modelling was used to test the mediating role of cognitive knowledge and intercultural behavioral skills within the relationship between cultural stereotypes and intercultural affects. Findings show that behavioral skills alone are not enough to diminish the negative aspects of stereotypes. Importantly, it is only with the help of cognitive knowledge that the relationship between stereotypes and intercultural affects are improved. It is hoped that by understanding the importance of proper curriculum content, more sustainable coexistence can be established.

Nursing information system introduction is an important measure for hospital nursing departments to promote the clinical practice of nursing with both efficiency and quality. A comparison of two cross-sectional study designs was adopted, and the information systems success model, as proposed by DeLone and McLean (2003), was used to explore the effectiveness of the six dimensions of system quality, information quality, service quality, use, user satisfaction, and net benefits at 6 and 12 months after the introduction launch of the nursing information system in hospitals. Multiple regression analysis was used across the two cross-sectional studies. The research results found that the nursing information system conformed to the information systems success model, and half a year to 1 year after the introduction of the nursing information system, use affected the nursing information system net benefits via the mediator variable of user satisfaction; however, the effect of full mediation changed to partial mediation effect with time. The research results can be used as a reference for hospitals and nursing administrators for the newly developed nursing information system.

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24–36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. Results: For enrolled 1845 patients, SICH rates were ≥ 2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281–0.846], p = 0.0106), the ECASS II (adjusted RR: 0.318 [0.130–0.776], p = 0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048–0.957], p = 0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of < 130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24–36 h. Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of < 130 mg/dL is supposed to a candidate marker for predicting SICH within 24–36 h.

OBJECTIVES Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P

PurposeWhen the speech motor system encounters errors, it generates adaptive responses to compensate for the errors. We previously showed that adaptive responses to task-irrelevant errors are significantly smaller than responses to task-relevant errors when errors are introduced gradually. The current study aimed to examine responses to task-irrelevant and task-relevant errors when errors are introduced suddenly.MethodWe used an adaptation paradigm in which participants experienced task-relevant errors (induced by formant-shift perturbations) and task-irrelevant errors (induced by formant-clamp perturbations). For one group of participants (N = 30), we applied the perturbations gradually. The second group of participants (N = 30) received the perturbations suddenly. We designed the perturbations based on participant-specific vowel configurations such that a participant’s first and second formants of /ε/ were perturbed toward their /æ/. To estimate adaptive responses, we measured formant changes (within 0–100 ms of the vowel onset) in response to the formant perturbations.ResultsWe found that (1) the difference between adaptive responses to formant-shift and formant-clamp perturbations was the smallest for the suddenly introduced perturbations, and (2) responses to formant-shift perturbations positively correlated with responses to formant-clamp perturbations for the suddenly (but not gradually) introduced perturbations.ConclusionsThese results showed that the speech motor system responds to task-relevant errors and task-irrelevant errors more differently when errors are introduced gradually than suddenly. Overall, the speech motor system evaluates the relevance of errors and uses its evaluation to modulate its adaptive responses to errors.

Background Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

In this study, the silicon-based nanostructures were prepared by using an electrospinning method and subsequent heat treatment process. The silane was coated on the surface of nanostructures make it superhydrophobic. Firstly, a precursor solution was prepared by dissolving an appropriate amount of Polyvinylpyrrolidone (PVP) and Tetraethylorthosilicate (TEOS) in ethanol and spun the nanostructures on the silicon wafer by using a single-syringe electrospinning. Secondly, the influence of heat treatment profile on morphology of electrospun nanostructures were explored in detail. Thirdly, silane dissolved in solution and coated on the nanostructures. This work studies the improvement of the superhydrophobic properties of the nanostructured surface through different high-temperature treatments. 600°C~800°C have different topography.

Accumulation of senile plaques mainly composed of neurotoxic amyloid-beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Sestrin2 inducible by various types of stressors is known to promote autophagy and exert antioxidative effects. In this work, we revealed the molecular mechanisms underlying Aβ induction of sestrin2 and tested whether antioxidation, in addition to autophagy regulation, also contributes to its neuroprotective effects in primary rat cortical neurons. We found that Aβ25-35 triggered nuclear translocation of p65 and p50, two subunits of nuclear factor-kappaB (NF-κB), and p53. Aβ25-35-induced sestrin2 expression was abolished by the p65 siRNA, the NF-κB inhibitor SN50, and the p53 inhibitor pifithrin-alpha (PFT-α). Further, Aβ25-35 enhanced binding of p50 and p53 to sestrin2 gene promoter that was abolished respectively by the p50 shRNA and PFT-α. Both p50 shRNA and PFT-α attenuated Aβ25-35-induced expression as well as nuclear translocation of all three transcription factors, namely p65, p50, and p53. Interestingly, p50 binding to the promoters of its target genes required p53 activity, whereas p50 also negatively regulated p53 binding to its target sequences. Suppression of sestrin2 expression by siRNA enhanced Aβ25-35- and Aβ1-42-induced production of reactive oxygen species (ROS), lipid peroxidation, and formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG). In contrast, overexpression of the sestrin2 N-terminal or C-terminal fragments neutralized Aβ25-35-induced ROS production. We concluded that Aβ-induced sestrin2 contributing to antioxidant effects in neurons is in part mediated by p53 and NF-κB, which also mutually affect the expression of each other.

Purpose We continuously monitor our speech output to detect potential errors in our productions. When we encounter errors, we rapidly change our speech output to compensate for the errors. However, it remains unclear whether we adjust the magnitude of our compensatory responses based on the characteristics of errors. Method Participants ( N = 30 adults) produced monosyllabic words containing /ɛ/ (/hɛp/, /hɛd/, /hɛk/) while receiving perturbed or unperturbed auditory feedback. In the perturbed trials, we applied two different types of formant perturbations: (a) the F1 shift, in which the first formant of /ɛ/ was increased, and (b) the F1–F2 shift, in which the first formant was increased and the second formant was decreased to make a participant's /ɛ/ sound like his or her /æ/. In each perturbation condition, we applied three participant-specific perturbation magnitudes (0.5, 1.0, and 1.5 ɛ–æ distance). Results Compensatory responses to perturbations with the magnitude of 1.5 ɛ–æ were proportionally smaller than responses to perturbation magnitudes of 0.5 ɛ–æ. Responses to the F1–F2 shift were larger than responses to the F1 shift regardless of the perturbation magnitude. Additionally, compensatory responses for /hɛd/ were smaller than responses for /hɛp/ and /hɛk/. Conclusions Overall, these results suggest that the brain uses its error evaluation to determine the extent of compensatory responses. The brain may also consider categorical errors and phonemic environments (e.g., articulatory configurations of the following phoneme) to determine the magnitude of its compensatory responses to auditory errors.