Improving Precision Force Control With Low-Frequency Error Amplification Feedback: Behavioral and Neurophysiological Mechanisms

Although error amplification (EA) feedback has been shown to improve performance on visuomotor tasks, the challenge of EA is that it concurrently magnifies task-irrelevant information that may impair visuomotor control. The purpose of this study was to improve the force control in a static task by preclusion of high-oscillatory components in EA feedback that cannot be timely used for error correction by the visuomotor system. Along with motor unit behaviors and corticomuscular coherence, force fluctuations (Fc) were modeled with non-linear SDA to contrast the reliance of the feedback process and underlying neurophysiological mechanisms by using real feedback, EA, and low-frequency error amplification (LF-EA). During the static force task in the experiment, the EA feedback virtually potentiated the size of visual error, whereas the LF-EA did not channel high-frequency errors above 0.8 Hz into the amplification process. The results showed that task accuracy was greater with the LF-EA than with the real and EA feedback modes, and that LF-EA led to smaller and more complex Fc. LF-EA generally led to smaller SDA variables of Fc (critical time points, critical point of Fc, the short-term effective diffusion coefficient, and short-term exponent scaling) than did real feedback and EA. The use of LF-EA feedback increased the irregularity of the ISIs of MUs but decreased the RMS of the mean discharge rate, estimated with pooled MU spike trains. Beta-range EEG–EMG coherence spectra (13–35 Hz) in the LF-EA condition were the greatest among the three feedback conditions. In summary, amplification of low-frequency errors improves force control by shifting the relative significances of the feedforward and feedback processes. The functional benefit arises from the increase in the common descending drive to promote a stable state of MU discharges

Epidemiology of acute otitis media among young children: A multiple database study in Taiwan

Background/PurposeAcute otitis media (AOM) is a common complication of upper respiratory tract infection (URTI) among children. The purpose of this study was to evaluate the epidemiology of AOM among young children in Taiwan, including the age incidence and seasonality by combining multiple databases.MethodsTwo country-based questionnaire survey studies had been conducted to evaluate the experience of otitis media (OM) among young children: one in 2007 and the other between 2005 and 2010. The number of OM cases (5% of population younger than 7 years) in 2005 and annual visiting rates for URTI from 2005 to 2010 obtained from the National Health Insurance Research Database of Taiwan were collected and comprised the third database. The fourth database comprised ambulatory visits of children with OM to a medical center in central Taiwan between 2005 and 2010.ResultsData from a total of 1099 questionnaires were entered into Database I in 2007, and data from 9705 questionnaires between 2005 and 2010 comprised Database II. There were 86,702 children (younger than 7 years, representing 5% of the whole population for this age group) retrieved from Database III in 2007, and 5,904 cases of OM in children between 2005 and 2010 in a hospital. In Database I, 7.46% children experienced at least one episode of AOM compared with 9.21% in Database II for children aged 5 years and younger. In Database III, 13.2% children younger than 7 years had AOM in 2005. The peak season of AOM among children was from March to May (Databases III and IV).ConclusionAOM was thought to be a very common disease among children; however, this comparative analysis showed that the overall prevalence of AOM among children younger than 5 years was only 20%, much lower than in other countries. AOM was more prevalent during the spring season, and still was similarly common after age 2 years

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Using principal component analysis to develop a single-parameter screening tool for metabolic syndrome

Abstract Background Metabolic syndrome (MS) is an important current public health problem faced worldwide. To prevent an "epidemic" of this syndrome, it is important to develop an easy single-parameter screening technique (such as waist circumference (WC) determination recommended by the International Diabetes Federation). Previous studies proved that age is a chief factor corresponding to central obesity. We intended to present a new index based on the linear combination of body mass index, and age, which could enhance the area under the receiver operating characteristic curves (AUCs) for assessing the risk of MS. Methods The labour law of the Association of Labor Standard Law, Taiwan, states that employers and employees are respectively obligated to offer and receive routine health examination periodically. Secondary data analysis and subject's biomarkers among five high-tech factories were used in this study between 2007 and 2008 in northern Taiwan. The subjects included 4712 males and 4196 females. The first principal component score (FPCS) and equal-weighted average (EWA) were determined by statistical analysis. Results Most of the metabolic and clinical characteristics were significantly higher in males than in females, except high-density lipoprotein cholesterol level. The older group (>45 years) had significantly lower values for height and high-density lipoprotein cholesterol level than the younger group. The AUCs of FPCS and EWA were significantly larger than those of WC and waist-to-height ratio. The low specificities of EWA and FPCS were compensated for by their substantially high sensitivities. FPCS ≥ 0.914 (15.4%) and EWA ≥ 8.8 (6.3%) were found to be the most prevalent cut off points in males and females, respectively. Conclusions The Bureau of Health Promotion, Department of Health, Taiwan, had recommended the use of WC ≥ 90 cm for males and ≥ 80 cm for females as singular criteria for the determination of central obesity instead of multiple parameters. The present investigation suggests that FPCS or EWA is a good predictor of MS among the Taiwanese. However, the use of FPCS is not computationally feasible in practice. Therefore, we suggest that EWA be used in clinical practice as a simple parameter for the identification of those at risk of MS.</p

The Atacama Large Millimeter/submillimeter Array (ALMA) Band-1 Receiver

The Atacama Large Millimeter/submillimeter Array(ALMA) Band 1 receiver covers the 35-50 GHz frequency band. Development of prototype receivers, including the key components and subsystems has been completed and two sets of prototype receivers were fully tested. We will provide an overview of the ALMA Band 1 science goals, and its requirements and design for use on the ALMA. The receiver development status will also be discussed and the infrastructure, integration, evaluation of fully-assembled band 1 receiver system will be covered. Finally, a discussion of the technical and management challenges encountered will be presented

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p

Impact of Ancestral Differences and Reassessment of the Classification of Previously Reported Pathogenic Variants in Patients With Brugada Syndrome in the Genomic Era: A SADS-TW BrS Registry

Brugada syndrome (BrS) is a heritable disease that results in sudden cardiac death. In the exome/genomic era, certain reported pathogenic variants in some genetic diseases have been reclassified as benign owing to their high frequency in some ancestries. In the present study, we comprehensively reassessed all previously reported pathogenic variants of BrS. We collected all pathogenic variants of BrS reported in the Human Gene Mutation Database and ClinVar throughout April 2017. We compared the minor allele frequency (MAF) of each variant among different ancestries by searching public whole-genome and exome databases. After considering the maximum credible allele frequency, variants with a MAF ≥ 0.001 were considered to be of questionable pathogenicity. We also investigated the percentage of SCN5A variants with a MAF ≥ 0.001 in 124 BrS patients from the Han Chinese population. We collected a total of 440 BrS variants, of which 18 had a MAF ≥ 0.001. There was a greater percentage of non-SCN5A variants with a MAF ≥ 0.001 than of SCN5A variants (21.8 versus 1.6%, p &lt; 0.0001). There were fewer frameshift and nonsense mutations than missense mutations (0.9 versus 5.6%, p = 0.032). Of the 18 variants, 14 (77.8%) were present only in the reference Asian population. In our cohort, we identified two SCN5A variants (p.A226V and p.V1340I) with MAFs ≥ 0.001 (0.45%). In conclusion, ancestral differences are important when considering the pathogenicity of BrS variants, especially in the case of missense variants and non-SCN5A variants, which may be pathogenic in some ancestries but only disease-predisposing in others

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma

PurposeUterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma.Materials and methodsThis is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen.ResultsFifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events.ConclusionUse of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma

Semienzymatic cyclization of disulfide-rich peptides using sortase A

Background: Sortase A (SrtA) is a transpeptidase capable of catalyzing the formation of amide bonds. Results: SrtA was used to backbone-cyclize disulfide-rich peptides, including kalata B1, -conotoxin Vc1.1, and SFTI-1. Conclusion: SrtA-mediated cyclization is applicable to small disulfide-rich peptides. Significance: SrtA-mediated cyclization is an alternative to native chemical ligation for the cyclization of small peptides of therapeutic interest