Noninvasive technique for measurement of heartbeat regularity in zebrafish (Danio rerio) embryos

<p>Abstract</p> <p>Background</p> <p>Zebrafish (<it>Danio rerio</it>), due to its optical accessibility and similarity to human, has emerged as model organism for cardiac research. Although various methods have been developed to assess cardiac functions in zebrafish embryos, there lacks a method to assess heartbeat regularity in blood vessels. Heartbeat regularity is an important parameter for cardiac function and is associated with cardiotoxicity in human being. Using stereomicroscope and digital video camera, we have developed a simple, noninvasive method to measure the heart rate and heartbeat regularity in peripheral blood vessels. Anesthetized embryos were mounted laterally in agarose on a slide and the caudal blood circulation of zebrafish embryo was video-recorded under stereomicroscope and the data was analyzed by custom-made software. The heart rate was determined by digital motion analysis and power spectral analysis through extraction of frequency characteristics of the cardiac rhythm. The heartbeat regularity, defined as the rhythmicity index, was determined by short-time Fourier Transform analysis.</p> <p>Results</p> <p>The heart rate measured by this noninvasive method in zebrafish embryos at 52 hour post-fertilization was similar to that determined by direct visual counting of ventricle beating (<it>p </it>> 0.05). In addition, the method was validated by a known cardiotoxic drug, terfenadine, which affects heartbeat regularity in humans and induces bradycardia and atrioventricular blockage in zebrafish. A significant decrease in heart rate was found by our method in treated embryos (<it>p </it>< 0.01). Moreover, there was a significant increase of the rhythmicity index (p < 0.01), which was supported by an increase in beat-to-beat interval variability (<it>p </it>< 0.01) of treated embryos as shown by Poincare plot.</p> <p>Conclusion</p> <p>The data support and validate this rapid, simple, noninvasive method, which includes video image analysis and frequency analysis. This method is capable of measuring the heart rate and heartbeat regularity simultaneously via the analysis of caudal blood flow in zebrafish embryos. With the advantages of rapid sample preparation procedures, automatic image analysis and data analysis, this method can potentially be applied to cardiotoxicity screening assay.</p

USE JD-R THEORY TO EXPLORE THE RELATIONSHIP BETWEEN EMPLOYEE EXPERIENCE AND EMPLOYEE ENGAGEMENT—TAKING JOB DEMANDS AS THE MODERATING VARIABLE

Past research has proven that employee experience has a positive impact on employee engagement. Based on the conceptual framework of Job Demands-Resources model (JD-R) model, this study regards efficient employee experience as a job resource to explore the impact of "employee experience" and” job demands” on employee engagement in organizations. Work requirements are further divided into challenge demand and hindrance demand. This study adopts the experimental design of the scenario method and uses two two-factor independent sample designs, namely 2x2(employee experience is high / employee experience is low x challenging job demands is high / challenging job demands is low) and 2x2(employee experience is high / employee experience is low x hindering job demands is high / hindering job demands is low).A total of 176 valid questionnaires were collected. The research results found that when employee experience is high, employee engagement is higher than when employee experience is low. Employee experience and job demands have an interactive effect on employee engagement. When employee experience is high, employee engagement will be higher when challenging job demands are added than when hindering job demands are added. It is expected that the results of this study can help in theoretical and practical application

α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Investigating Zero-Shot Generalizability on Mandarin-English Code-Switched ASR and Speech-to-text Translation of Recent Foundation Models with Self-Supervision and Weak Supervision

This work evaluated several cutting-edge large-scale foundation models based on self-supervision or weak supervision, including SeamlessM4T, SeamlessM4T v2, and Whisper-large-v3, on three code-switched corpora. We found that self-supervised models can achieve performances close to the supervised model, indicating the effectiveness of multilingual self-supervised pre-training. We also observed that these models still have room for improvement as they kept making similar mistakes and had unsatisfactory performances on modeling intra-sentential code-switching. In addition, the validity of several variants of Whisper was explored, and we concluded that they remained effective in a code-switching scenario, and similar techniques for self-supervised models are worth studying to boost the performance of code-switched tasks.Comment: Submitted to ICASSP 2024 Self-supervision in Audio, Speech and Beyond worksho

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17) and 9.0% (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory

Konsep Demokrasi Politik Dalam Islam

Coexistence of chronic rhinosinusitis (CRS) with asthma appears to impair asthma control. Type-2 innate lymphoid cells (ILC2s) respond to the cytokines of thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, thus contributing to airway diseases such as CRS and asthma. We investigate whether the augmented Th2-cytokines in CRS might be related to sinonasal tract ILC2s corresponding to enhanced IL-25, IL-33 and TSLP release in severe asthmatics, and be involved in asthma control. Twenty-eight asthmatics (12 non-severe and 16 severe) with CRS receiving nasal surgery were enrolled. The predicted FEV1 inversely associated with CRS severity of CT or endoscopy scores. Higher expression of Th2-driven cytokines (IL-4, IL-5, IL-9, and IL-13), TSLP, IL-25 and IL-33 in nasal tissues was observed in severe asthma. Severe asthmatics had higher ILC2 cell counts in their nasal tissues. ILC2 counts were positively correlated with Th2-cytokines. Nasal surgery significantly improved asthma control and lung function decline in severe asthma and CRS. The higher expression of IL-33/ILC2 axis-directed type 2 immune responses in nasal tissue of CRS brought the greater decline of lung function in severe asthma. ILC2-induced the upregulated activity of Th2-related cytokines in asthmatics with CRS may contribute to a recalcitrant status of asthma control

Taiwanese Dermatological Association consensus for the management of atopic dermatitis

AbstractBackground/ObjectiveThis report describes the 2014 consensus of the Taiwanese Dermatological Association (TDA) regarding the treatment of atopic dermatitis (AD). The TDA consensus is distributed to practices throughout Taiwan to provide recommendations for therapeutic approaches for AD patients to improve their quality of life.MethodsThe information in the consensus was agreed upon by a panel of national experts at TDA AD consensus meetings held on March 16, May 4, and June 29, 2014. The consensus was in part based on the 2013 Asia–Pacific AD guidelines and the guidelines of the American Academy of Dermatology, with modification to reflect the clinical practice in Taiwan.ResultsThe amendments were drafted after scientific discussions focused on the quality of evidence, risk, and benefits; all the consensus contents were voted on by the participating dermatologists, with approval by at least 75% for inclusion.ConclusionThe consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies