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Described here is the evaluation of a luciferase (luc) and respiratory syncytial virus (RSV) messenger RNA / lipid nanoparticle (mRNA/LNP) vaccine using a Needle-free Injection System, Tropis®, from PharmaJet® (Golden, Colorado USA). Needle-free jet delivery offers an alternative to needle/syringe. To perform this assessment, compatibility studies with Tropis were first performed with a luc mRNA/LNP and compared to needle/syringe. Although minor changes in particle size and encapsulation efficiency were observed when using Tropis on the benchtop, in vitro luciferase activity remained the same. Next, the luc mRNA/LNP was administered to rats intramuscularly using Tropis or needle/syringe and tracking of the injection and distribution was performed. Lastly, an mRNA encoding a prefusion-stabilized F protein from RSV was delivered intramuscularly using both Tropis and needle/syringe at 1 and 5 mcg mRNA. An equivalent IgG response was observed using both Tropis and needle/syringe. The cell mediated immune (CMI) response was also evaluated, and responses to RSV-F were detected from animals immunized with needle/syringe at all dose levels, and from the animals immunized with Tropis in the 5 and 25 ug groups. These results indicated that delivery of mRNA/LNPs with Tropis is a potential means of administration and an alternative to needle/syringe.

Teachers lack effective curriculum-based instruments to assess their students' scientific competence that would provide information for modifying their inquiry instruction. The main purpose of this study was to develop and validate a Curriculum-Based Scientific Competence (CBSC) test to assess students' scientific competence in a 1-semester Grade 9 curriculum. The initial 51-item CBSC test was administered to 318 Grade 10 students from 4 schools. The Rasch partial credit model was used to analyse the quality of the CBSC test. The final 44-item CBSC test demonstrated satisfactory item fit, threshold, and test reliability. Further, a 23-item PISA test was used to measure criterion validity. Results indicated that the CBSC test was valid for assessing students' scientific competencies and can distinguish the effect of inquiry instruction from that of traditional instruction. A CBSC test would provide teachers the summative assessment of scientific competency for examining the effect of inquiry-based teaching. The model of development and validation of the CBSC test through the cooperation of teachers and researchers for each semester of a science programme is recommended.

Drug-induced vascular injury (DIVI), defined as arterial medial degeneration/necrosis usually associated with perivascular inflammation, is frequently observed in the mesenteric arteries of rats but the relevance to humans remains a hurdle for drug development. Here, we describe the evaluation of commercially available optical imaging biomarkers using a rat DIVI model. Male Sprague Dawley rats were administered 10 mg/kg/day of a proprietary soluble guanylate cyclase activator (sGCa). Optical agents, AngioSense for the detection of vessel permeability, MMPSense for the detection of activated matrix metalloproteinases (MMPs), and IntegriSense for the detection of α v β 3 integrin, were injected via tail vein 24 hours before fluorescence (FL) ex vivo imaging. Imaging found a statistically significant difference in FL from all optical agents between treated and vehicle groups (p < .05). Mesenteric arteries were further analyzed by histopathology, flow cytometry, and immunohistochemistry. Histopathology confirmed perivascular inflammation and/or arterial medial degeneration in the sGCa-treated animals. Flow cytometry of digested arteries revealed myeloid cells as a main source of MMPSense signal. Immunohistochemical analysis further identified elevated MMP-9 expression within arterial walls and surrounding tissue of treated animals. Together, these data demonstrate that MMPSense and AngioSense are sensitive optical imaging biomarkers for the quantification of DIVI in rat mesenteric arteries.

Chlamydia trachomatis is a bacterial sexually transmitted disease with over 1.3 million cases reported to the CDC in 2010. While Chlamydia infection is easily treated with antibiotics, up to 70% of infections are asymptomatic and go untreated. The current mouse model relies on invasive upper genital tract gross pathology readouts at ~60–80 days postinfection. High throughput optical imaging through the use of biomarkers has been successfully used to quickly evaluate several disease processes. Here we evaluate Neutrophil Elastase 680 (Elastase680) for its ability to measure Chlamydia muridarum associated inflammation in live mice using fluorescence molecular tomography (FMT) and In Vivo Imaging System (IVIS). Optical imaging was able to distinguish with statistical significance between vaccinated and nonvaccinated mice as well as mock-challenged and challenged mice 2 weeks after challenge which was 9 weeks sooner than typical gross pathological assessment. Immunohistochemistry confirmed the presence of neutrophils and correlated well with both in vivo and ex vivo imaging. In this report we demonstrate that Elastase680 can be used as a molecular imaging biomarker for inflammation associated with chlamydial infection in a mouse model and that these biomarkers can significantly decrease the time for pathology evaluation and thus increase the rate of therapeutics discovery.

BACKGROUND:Type 2 diabetes results from failure of the β-cells to compensate for increased insulin demand due to abnormal levels of metabolic factors. The ob/ob(lep-/-) mouse has been extensively studied as an animal model of type 2 diabetes. Previous studies have shown a correlation between β-cell function and bioluminescent imaging in lean genetically engineered mice. The ability to noninvasively monitor β-cell function in ob/ob mice could provide new information on β-cell regulation in type 2 diabetes. METHODS:To create the B6 Albino ob/ob MIP-luc mice (ob/ob-luc), the ob/ob mouse was crossed with the CD1 MIP-luc mouse. All mice were backcrossed over multiple generations to ensure the genetic background of the transgenic mice was over 96% similar to the background of the original ob/ob mouse. Animal weight, blood glucose levels, insulin in plasma, and in vivo bioluminescence (BLI) were monitored weekly or biweekly for up to 70 weeks of age. BL imaging was performed using IVIS Spectrum (Perkin Elmer) and calculated by integrating the bioluminescence signal between 5 and 10 min after i.v. injection of D-luciferin. Insulin immunohistochemistry determined islet beta cell count and insulin secretion assay determined islet insulin function. RESULTS:There were significant increases in BLI and insulin levels as the ob/ob-luc mice aged while glucose levels gradually decreased. Ob/ob-luc were sacrificed at different time points to determine ex vivo BLI, islet function and total β-cell numbers using a cell counting training algorithm developed for the Vectra image analysis system (Perkin Elmer). The number of β-cells increased as the mice aged and all three ex vivo measurements correlated with BLI. CONCLUSIONS:The ob/ob-luc mice can serve as a model of metabolic stress, similar to human type 2 diabetes using BLI as a surrogate marker for β-cell function.

Background/purpose: MicroRNA (miRNA) alterations play important roles in the neoplastic process of oral squamous cell carcinoma (OSCC). Upregulation of miR-10b and miR-372 and downregulation of miR-375 are frequent events in OSCC. The aberrances of these miRNAs in oral potentially malignant lesions (OPMD) were studied to determine their status during the establishment of OSCC. Materials and methods: Cytobrushed sampling was used to collect epithelial cells from 11 OSCC and 34 OPMD lesions and matched normal mucosa. The expression levels of miR-10b, miR-372, and miR-375 were analyzed using quantitative reverse transcription polymerase chain reaction analysis. The clinical implications of these aberrances were further investigated. Results: Both miR-10b and miR-372 were upregulated in OPMD, but only miR-10b expression was upregulated in OSCC comparing to control. miR-375 was downregulated in OPMD and tended to be downregulated in OSCC. Dysplastic OPMD could be distinguished based on miR-372 expression level; miR-375 expression levels facilitated discrimination between OPMD and OSCC. The combined analysis of miR-375 and miR-372 remarkably enhanced the accuracy of differentiating OPMD from OSCC. Conclusion: Aberrant miR-10b. miR-372, and miR-375 expression occurs early during oral carcinogenesis. The detection of miR-372 and miR-375 expression using cytobrush samples may assist in differentiating between OPMD and OSCC.

Background: Concurrent with population ageing, falls have become a significantly more challenging public health issue among older adults. Three years of data collected recently from a nursing home in northern Taiwan reveals an increasing trend in fall density that is primarily associated with aging, physiological decline, chronic diseases, polypharmacy, osteoporosis, and lack of exercise. The percentage of nursing home residents at high risk of falls is currently at 12.6%, and the fall rate has been reported as reaching as high as 30% annually. Purpose: A fall prevention program was implemented to reduce the fall incidence rate to 18%, with secondary goals of improving fall prevention awareness, behavior, self-efficacy, lower limb muscle strength, balance, and gait by 10% on average, respectively, between pre-test and post-test. Resolution: From September 30, 2023 to February 29, 2024, a health promotion activity and fall prevention exercise course were implemented using an interdisciplinary team collaboration model over a six-week period, providing individualized exercise for the participants. Result: The study included 20 older adults with an average age of 88 years. Most (90%; n = 18) had chronic diseases, 25% (n = 5) were on more than nine medications, 70% (n = 14) had reduced bone mass, and 40% (n = 8) were at high risk of falls, with a fall incidence rate of 30% during the immediately preceding year. Post-intervention, the fall incidence rate dropped to 5%, fall prevention awareness, behavior, and self-efficacy increased by 18.3%, and lower limb muscle strength, balance, and gait improved by 11.7%. The post-test results in fall prevention awareness, behavioral changes, self-efficacy, and lower limb strength, balance, and gait were all significantly better than pre-test results, with all results achieving statistical significance. Conclusion: The project results support the positive effects of the developed intervention effectively on elderly physical fitness and fall risk, providing valuable insights for the implementation of fall prevention strategies in nursing homes. [ABSTRACT FROM AUTHOR]

Comprehensive knowledge of the left atrium (LA) and its pathophysiology has emerged as an important clinical and research focus in the heart failure (HF) arena. Although studies on HF focusing on investigating left ventricular remodeling are numerous, those on atrial structural and functional changes have received comparatively less attention. Studies on LA remodeling have recently received increasing attention, and LA pressure (LAP) has become a novel target for advanced monitoring and is a potential therapeutic approach for treating HF. Various devices specifically designed for the direct measurement of LAP have been developed to optimize HF treatment by reducing LAP. This review focuses on LA hemodynamic monitoring and effective LAP decompression. [ABSTRACT FROM AUTHOR]

Background/Purpose: Neurological dysfunction is a common condition necessitating prolonged mechanical ventilation (PMV). We investigated the clinical features and outcomes of patients with acute neurological diseases requiring PMV. Methods: This retrospective observational study was conducted at the Respiratory Care Center (RCC) of Chang Gung Memorial Hospital, Taiwan, between January 2011 and January 2014. The main outcome was weaning success, defined as successful withdrawal from mechanical ventilator support for more than 5 days. Results: The study included 103 patients with acute stroke and brain trauma receiving PMV. Weaning success was reported in 63 (61%) patients and weaning failure was reported in 40 (39%) patients. Patients in the weaning failure group were older and had a lower RCC Glasgow Coma Scale (GCS) score (6.0 vs 7.9, p = 0.005), lower albumin level (2.8 vs 3.1, p = 0.015), longer RCC stay (28.7 vs 21.3 days, p = 0.017), and higher in-hospital mortality rate (47% vs 9%, p

Background: Cancer-associated venous thromboembolism (VTE) is a distinct pathological entity with much higher incidence and unique risk factors compared to general VTE. A previous study reported that cancer associated-VTE incidence in Taiwan is much lower than that reported for western countries and also lower than our anecdotal observations. To address this issue further, we initiated an investigation locally using a more detailed approach than used previously with comprehensive review of medical records to gain new insight into the incidence and risk factors for cancer-associated VTE. Methods: Medical records of all adult patients with lung, pancreatic and gastric cancers, and lymphoma diagnosed from January 2011 to December 2013 in National Taiwan University Hospital indexed through the local cancer registry database were reviewed. VTE patients were identified through diagnosis coding and comprehensive medical chart review. Results: Among 5620 consecutive lung, gastric and pancreatic cancer, and lymphoma patients, VTE was diagnosed in 246 (4.4%). Overall VTE incidence was 36.3 per 1000 patient-year. Multivariate analysis showed that not only high but also low body mass index (BMI) was associated with VTE risk with different cutoff levels by gender. Mildly to moderately anemic patients were at higher risk of VTE. Activated partial thromboplastin time (aPTT) had proportionally and reversely correlation to VTE risk. Conclusion: We reported higher incidence of cancer associated VTE in Taiwan. Low BMI and short aPTT were found to be related to higher VTE risk that was not reported before.

Abstract Surgery is traditionally a male-dominated field, and gender differences exist despite the growing numbers of female surgeons. A handful of studies have evaluated the condition in Asian societies. We aimed to examine the difference between female and male surgeons in urology, general surgery, and gynecology by analyzing a nationwide, population-based database. We identified surgeons with a clinical experience of six to thirteen years between 1995 to 2013 from the National Health Insurance Research Database. We collected patient numbers and revenue per month in outpatient and inpatient care, as well as monthly numbers of surgeries conducted by female and male surgeons in urology, general surgery, and gynecology, for analysis. Original student’s t-test and wilcoxon rank sum test was used to compare the differences between female and male surgeons, and p values less than 0.05 were considered statistically significant. Female urologists and general surgeons had a significantly higher ratio of female patients in Taiwan. Female urologists had patient numbers, revenues, and numbers of surgeries comparable to male urologists. In contrast, female general surgeons had significantly less involvement in outpatient and inpatient care and had low monthly revenues. Female general surgeons contradictorily performed more oncological surgeries per month than males. However, the difference in numbers of oncological surgeries was not significant after excluding breast cancer surgeries. Female gynecologists had a similar amount of outpatients and outpatient revenue but significantly less inpatient care and numbers of surgeries per month. A gender-based gap exists among surgeons in Taiwan. The gap between females and males appeared narrower in urology than in general surgery and gynecology. Management of diseases related to female sex organs, including breast, were more common among female surgeons. Efforts should be made to decrease gender stereotypes, to ensure that patients receive the best care regardless of the sex of the surgeons.

Abstract Background Postoperative positive pressure lung expansion is associated with decreased pulmonary complications and improved clinical outcomes. The aim of the present study was to compare the differences in post-operative pulmonary complications and clinical outcomes between two groups of study subjects who underwent cardiac surgery; one included subjects who received mechanical insufflation-exsufflation (MI-E) and the other included subjects who received intermittent positive pressure breathing (IPPB) therapy. Methods This retrospective study included 51 subjects, who underwent cardiac surgery in an intensive care unit of a tertiary hospital during the time period from June 2017 to February 2018. After liberation from mechanical ventilation, the subjects received lung expansion therapy by means of two types of positive pressure devices, MI-E (n = 21) or IPPB (n = 30). The pulmonary complications, lung function, and clinical outcomes were compared between the two groups. Results Subjects in both groups displayed similar baseline characteristics and underwent similar types of surgical procedures. Compared to subjects who received non-oscillatory therapy, those who received MI-E therapy had higher post-operative force vital capacity (58.4 ± 4.74% vs. 46.0 ± 3.70%, p = 0.042), forced expiratory volume in one second (62.4 ± 5.23% vs. 46.8 ± 3.83%, p = 0.017), and peak flow rate (67.1 ± 5.53 L vs. 55.7 ± 4.44 L p = 0.111). However, the incidence of chest pain was higher in the MI-E group (n = 13, 61.9%) than in the IPPB group (n = 4, 16.7%; odds ratio, 0.123, 95% confidence interval, 0.03–0.45; p = 0.002). The length of hospital and ICU stay, development of atelectasis, pneumonia, and pleural effusion were similar in both the groups. Conclusion Both IPPB and MI-E therapies have similar effects on preventing post-operative complications in cardiac surgery patients. However, compared to IPPB therapy, MI-E therapy was associated with better-preserved pulmonary function and higher incidence of chest pain.

The study of education systems as social phenomena has led scholars to question the role of education in modern society. The question of how to improve education naturally leads to concerns about what is wrong with the present education system. If education is meant to elevate the next generation, how can it meet the goal of ensuring a meaningful existence for those being educated? Scholars have demonstrated that education has been reduced to a process of the construction of objects, where curriculum as techne commodifies students into products with market value. We propose that the tendency of interpreting techne as technology is a perspective of the modern age, and the rules of modern education are based on the rules of modern technology, under the guidance of the paradigm of productivity. We will introduce a broader interpretation of techne which frames it as the cultivation of virtue, i.e., virtue-techne. On this basis, education could be viewed as techne in the sense of praxis (practice, exercise), rather than as fabrication in the sense of production. We highlight the rising rate of student suicides in Taiwan in recent years, where we determine the education system lacks a focus on praxis. This article investigates alternative praxis-oriented notions of education, from Aristotle's cultivation of virtue to Hadot's "spiritual exercises," to advocate for a shift away from the production paradigm. Indebted to Heidegger, we clarify his "techne as revealing" by emphasizing two frameworks for education: The first, modern education being valued by its adherence to metrics based in the paradigm of production. The second, education as a process wherein its value is derived from the life context of the participating individual. Finally, as a comparative study, we explore the current state of education in Russia and Taiwan, and present the case of one high school in Taiwan which has adopted the practice of spiritual exercises in its curriculum, including a required hike to the peak of Taiwan's tallest mountain, to cultivate a sense of (and value for) the liberated life before its students graduate.

Abstract Genome-wide association studies have identified thousands of genetic susceptibility loci associated with cancer as well as other traits and diseases. Mapping germline variation in identified genetic susceptibility regions to alterations in nearby gene expression nominates candidate genes potentially related to disease risk for further functional investigation. We developed LDexpress as an online resource that integrates population-specific linkage disequilibrium data from the 1000 Genomes (1000G) project and tissue-specific expression data from the Genotype-Tissue Expression project to better study regional germline variation impacting gene expression. LDexpress is a publicly available web tool designed to be easy to use, flexible to conduct a wide range of variant queries, and quick to efficiently investigate dozens of query variants across multiple tissue types. We demonstrate the utility of LDexpress using example genomic queries and anticipate this tool will accelerate understanding of disease etiology by uncovering associations of regional germline variation to nearby gene expression.

Abstract A significantly negative reversion in the QuantiFERON-TB Gold In-tube (QFT-GIT) test is reported in patients on dialysis, which makes the results unreliable. The CD4 and CD8 responses of the QFT-Gold plus (QFT-Plus) may have better positive consistency, but this needs to be investigated. We enrolled dialysis patients with baseline positive QFT-GIT0 results and conducted two rounds of follow-up paired QFT-GIT1&2 and QFT-Plus1&2 tests at an interval of 6 months. The positive consistency, concordance, and discordance of the QFT results were analyzed. A total of 236 patients on dialysis were screened, and 73 participants with positive QFT-GIT0 results were enrolled. The baseline QFT-GIT0 response was higher in the 1st QFT-Plus1(+) group than in the QFT-Plus1(−) group, but insignificantly different between the 1st QFT-GIT1(+) and QFT-GIT1(−) groups. The two assays had good correlation when concurrently tested. Fifty-three subjects completed a second round of the QFT-GIT2 and QFT-Plus2. Persistent positivity was higher with the QFT-Plus2 (81.8%) than with the QFT-GIT2 (58.8%, p = 0.040). The QFT-GIT1 and QFT-Plus1 CD4 responses were higher in patients with persistent positivity than in those with negative reversion, whereas the difference of the QFT-Plus TB1 and TB2 data, representative of the CD8 response, were similar between positive persistence and negative reversion. In conclusion, the QFT-Plus provides more reliable positive consistency than does the QFT-GIT. The CD4 interferon-γ response might play a role in maintaining positivity of LTBI.

Abstract Recessive variants of the SLC26A4 gene are an important cause of hereditary hearing impairment. Several transgenic mice with different Slc26a4 variants have been generated. However, none have recapitulated the auditory phenotypes in humans. Of the SLC26A4 variants identified thus far, the p.T721M variant is of interest, as it appears to confer a more severe pathogenicity than most of the other missense variants, but milder pathogenicity than non-sense and frameshift variants. Using a genotype-driven approach, we established a knock-in mouse model homozygous for p.T721M. To verify the pathogenicity of p.T721M, we generated mice with compound heterozygous variants by intercrossing Slc26a4 +/T721M mice with Slc26a4 919-2A>G/919-2A>G mice, which segregated the c.919-2A > G variant with abolished Slc26a4 function. We then performed serial audiological assessments, vestibular evaluations, and inner ear morphological studies. Surprisingly, both Slc26a4 T721M/T721M and Slc26a4 919-2A>G/T721M showed normal audiovestibular functions and inner ear morphology, indicating that p.T721M is non-pathogenic in mice and a single p.T721M allele is sufficient to maintain normal inner ear physiology. The evidence together with previous reports on mouse models with Slc26a4 p.C565Y and p.H723R variants, support our speculation that the absence of audiovestibular phenotypes in these mouse models could be attributed to different protein structures at the C-terminus of human and mouse pendrin.

Abstract Synaptosomes are subcellular fractions prepared from brain tissues that are enriched in synaptic terminals, widely used for the study of neural transmission and synaptic dysfunction. Immunofluorescence imaging is increasingly applied to synaptosomes to investigate protein localization. However, conventional methods for imaging synaptosomes over glass coverslips suffer from formaldehyde-induced aggregation. Here, we developed a facile strategy to capture and image synaptosomes without aggregation artefacts. First, ethylene glycol bis(succinimidyl succinate) (EGS) is chosen as the chemical fixative to replace formaldehyde. EGS/glycine treatment makes the zeta potential of synaptosomes more negative. Second, we modified glass coverslips with 3-aminopropyltriethoxysilane (APTES) to impart positive charges. EGS-fixed synaptosomes spontaneously attach to modified glasses via electrostatic attraction while maintaining good dispersion. Individual synaptic terminals are imaged by conventional fluorescence microscopy or by super-resolution techniques such as direct stochastic optical reconstruction microscopy (dSTORM). We examined tau protein by two-color and three-color dSTORM to understand its spatial distribution within mouse cortical synapses, observing tau colocalization with synaptic vesicles as well postsynaptic densities.

Abstract We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15–2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05–1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality.