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Abstract Background Stenotrophomonas maltophilia, a multidrug-resistant gram-negative bacteria (GNB), is an emerging nosocomial pathogen. This study assessed the clinical outcomes of GNB infections in surgical intensive care unit (SICU) patients post-abdominal surgery, focusing on the differences between S. maltophilia and other GNBs, including Pseudomonas aeruginosa. Methods A retrospective study was conducted on SICU patients at Kaohsiung Chang Gung Memorial Hospital from 2010 to 2020, who developed GNB infections following abdominal surgery. Results Of 442 patients, 237 had S. maltophilia and 205 had non-S. maltophilia GNB infections (including 81 with P. aeruginosa). The overall mortality rate was 44.5%, and S. maltophilia infection emerged as a significant contributor to the mortality rate in patients with GNB infections. S. maltophilia patients had longer mechanical ventilation and SICU stays, with a 30-day mortality rate of 35.4%, higher than the non-S. maltophilia GNB (22.9%) and P. aeruginosa (21%) groups. In-hospital mortality was also higher in the S. maltophilia group (53.2%) compared to the non-S. maltophilia GNB (34.6%) and P. aeruginosa groups (29.6%). Risk factors for acquiring S. maltophilia included a higher Sequential Organ Failure Assessment score and prior broad-spectrum antibiotics use. Older age, polymicrobial infections, and elevated bilirubin were associated with increased 30-day mortality in S. maltophilia patients. Conclusion S. maltophilia infections in post-abdominal surgery patients are linked to higher mortality than non-S. maltophilia GNB and P. aeruginosa infections, emphasizing the need for early diagnosis and treatment to improve outcomes.

Background Dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. Methods and Results The ELUCIDATE trial was a prospective, open‐label, randomized, active‐controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add‐on or standard‐of‐care group. Speckle‐tracking echocardiography–based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53–2.84]; P=0.005), LV end‐systolic volume (5.51 mL [95% CI, 0.86–10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42–6.09]; P

Abstract We have successfully generated oligonucleotide aptamers (Apts) and monoclonal antibodies (mAbs) targeting the recombinant nucleocapsid (N) protein of SARS-CoV-2. Apts were obtained through seven rounds of systematic evolution of ligands by exponential enrichment (SELEX), while mAbs were derived from the 6F6E11 hybridoma cell line. Leveraging these Apts and mAbs, we have successfully devised two innovative and remarkably sensitive detection techniques for the rapid identification of SARS-CoV-2 N protein in nasopharyngeal samples: the enzyme-linked aptamer-antibody sandwich assay (ELAAA) and the hybrid lateral flow strip (hybrid-LFS). ELAAA exhibited an impressive detection limit of 0.1 ng/mL, while hybrid-LFS offered a detection range of 0.1 – 0.5 ng/mL. In the evaluation using ten nasopharyngeal samples spiked with known N protein concentrations, ELAAA demonstrated an average recovery rate of 92%. Additionally, during the assessment of five nasopharyngeal samples from infected individuals and ten samples from healthy volunteers, hybrid-LFS displayed excellent sensitivity and specificity. Our study introduces a novel and efficient on-site approach for SARS-CoV-2 detection in nasopharyngeal samples. The reliable hybrid Apt-mAb strategy not only advances virus diagnostic methods but also holds promise in combating the spread of related diseases.

In this study, we conducted tests on the seeds from four Taiwanese native Camellia species (C. japonica, C. furfuracea, C. laufoshanensis, and C. formosensis) and three commercialized species (C. oleifera, C. brevistyla, and C. sinensis) for comparison. We examined various aspects of these species, such as seed oil content, suitability for mechanical pressing, volatile components (edible flavor), and oil stability (suitability for cooking), to assess the feasibility of using these four native Taiwanese Camellia seeds as sources of edible oil. The results from solvent extraction tests and mechanical pressing experiments confirm that the seeds from C. furfuracea, C. japonica, and C. laufoshanensis have high oil contents, and their oils are suitable for extraction via the popular mechanical pressing method, with oil yields comparable to or higher than those of the commercialized Camellia species. The volatile components of the oils were collected using MonoTrap adsorbents and analyzed with a thermal desorption system coupled with gas chromatography–mass spectrometry (ATD-GC/MS), primarily consisting of alcohols, ketones, and aldehydes. The results of oxidative stability tests reveal that the seed oils from C. japonica, C. furfuracea, and C. laufoshanensis are higher than or equally stable to those from the commercialized Camellia species. After six months of storage, the stability of these three Camellia seed oils remained relatively high, demonstrating that the seed oils from C. japonica, C. furfuracea, and C. laufoshanensis can withstand high temperatures and can be easily preserved for future applications.

In modern society, people have busy and competitive lives, with different stresses causing fatigue and overwork, which may ultimately harm their health. We investigated the beneficial effects of Astragalus polysaccharide (rAPS) on fatigue and exercise performance. Forty male Institute of Cancer Research (ICR) mice were randomly divided into four groups according to body weight (BW): control group (distilled water), 1-fold dose group (0.70 g rAPS/kg BW/day), 2-fold dose group (1.40 g rAPS/kg BW/day) and a 5-fold dose group (3.50 g rAPS/kg BW/day). In terms of exercise performance, rAPS supplementation significantly improved grip strength performance and time to exhaust-loaded swim times when compared with controls (p

Ventilator-associated pneumonia (VAP) is a critical hospital-acquired infection following non-cardiac surgeries, leading to poor outcomes. This study identifies VAP risk factors in non-cardiac surgical patients and determines the causative pathogens. A retrospective analysis with 1:4 propensity-score matching was conducted on patients in a surgical intensive care unit (ICU) from 2010 to 2020 at a private tertiary medical center. Among 99 VAP patients, the mortality rate was 64.7%. VAP risk factors included prolonged mechanical ventilation (odds ratio [OR] 6.435; p < 0.001), repeat intubation (OR 6.438; p < 0.001), lower oxygenation levels upon ICU admission (OR 0.950; p < 0.001), and undergoing gastrointestinal surgery (OR 2.257; p = 0.021). The 30-day mortality risk factors in the VAP group were late-onset VAP (OR 3.450; p = 0.022), inappropriate antibiotic treatment (OR 4.083; p = 0.041), and undergoing gastrointestinal surgeries (OR 4.776; p = 0.019). Nearly half of the Gram-negative infections were resistant strains, and a third were polymicrobial infections. Non-cardiac surgical patients with VAP face adverse hospital outcomes. Identifying high-risk patients and understanding VAP’s resistant and microbial nature are crucial for appropriate treatment and improved health outcomes.

Chronic kidney disease (CKD) frequently correlates with cardiovascular complications. Soluble suppression of tumorigenicity 2 (sST2) and Galectin-3 (Gal-3) are emerging as cardiac markers with potential relevance in cardiovascular risk prediction. The cardiothoracic ratio (CTR), a metric easily obtainable from chest radiographs, has traditionally been used to assess cardiac size and the potential for cardiomegaly. Understanding the correlation between these cardiac markers and the cardiothoracic ratio (CTR) could provide valuable insights into the cardiovascular prognosis of CKD patients. This study aimed to explore the relationship between sST2, Gal-3, and the CTR in individuals with CKD. Plasma concentrations of sST2 and Gal-3 were assessed in a cohort of 123 CKD patients by enzyme-linked immunosorbent assay (ELISA). On a posterior-to-anterior chest X-ray view, the CTR was determined by comparing the widths of the heart to that of the thorax. The mean concentration of sST2 in the study participants ranged from 775.4 to 4475.6 pg/mL, and the mean concentration of Gal-3 ranged from 4.7 to 9796.0 ng/mL. Significant positive correlations were observed between sST2 and the CTR (r = 0.291, p < 0.001) and between Gal-3 and the CTR (r = 0.230, p < 0.01). Our findings indicate that elevated levels of sST2 and Gal-3 are associated with an increased CTR in CKD patients. This relationship may enable better cardiovascular risk evaluation for CKD patients. Further studies are warranted to explore the clinical implications of these associations.

Introduction: Hematuria is a worrisome symptom in children and is sometimes associated with urinary tract infections (UTIs). This study aimed to identify useful clinical factors that can predict UTIs in hematuria patients without pyuria in the pediatric emergency department (ED). Methods: We retrospectively recruited patients with hematuria from the pediatric ED. Clinical symptoms, urine biochemistry and microscopic examination results, and blood laboratory tests were analyzed to identify the predictors of UTIs. Patients were divided into the verbal group (age ≥ 2 years) and non-verbal group (age < 2 years) for identifying predictors of UTIs. Causes of hematuria were also investigated. Results: A total of 161 patients with hematuria without pyuria were evaluated. Among symptoms, dysuria was significantly correlated with UTIs. Regarding urine biochemistry data, urine esterase and urine protein > 30 mg/dl were found to be significant parameters for predicting UTIs, while urine esterase and urine nitrite showed significant differences in children with age < 2 years. In the urine microscopic examinations, urine red blood cells (RBC) > 373/µL in children aged ≥ 2 years and urine RBC > 8/µL in children aged < 2 years were associated with UTIs. In addition, UTIs and urinary tract stones were found to be the top two causes of hematuria. Conclusions: Dysuria, urine esterase, urine nitrite, and urine protein may be useful parameters for predicting UTIs in pediatric patients with hematuria but no pyuria in the ED. In addition, a UTI was the most commonly identified etiology of hematuria without pyuria, followed by urinary tract stones.

BackgroundThe COVID-19 pandemic has had a significant impact on pediatric patients, increasing their vulnerability to psychological fragility. The aim of this study was to investigate the epidemiology and clinical spectrum of pediatric psychological fragility and suicide attempts in the emergency department (ED) before and after the onset of the COVID-19 outbreak.MethodsA total of 340 pediatric patients admitted to the ED for psychological fragility between 2019 and 2022 were retrospectively collated and categorized according to three periods: pre pandemic, pandemic, and post pandemic. Epidemiological and clinical information were analyzed and compared among the three groups. Moreover, patients with suicidal ideation or suicidal attempts and types of substance use disorders in children with suicidal attempts sent to the ED were analyzed.ResultsThe proportion of psychological fragility increased during the pandemic period (0.4%) and the post-pandemic period (0.8%) compared to that in the pre-pandemic period (0.28%). Suicide ideation was the highest before the pandemic period (0.04%), while suicidal attempts were the highest in the post pandemic period (0.42%). Significantly elevated trends in suicide attempts involving overdose and injury were observed among the three groups (p

Background The angiotensin receptor–neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin–angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2‐center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin–angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74‐year follow‐up, phenogroup assignment provided improved prognostic discrimination beyond Meta‐Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P

Aim: The mobile network quality in ambulances can be variable and limited. This pilot study aimed to identify a suitable network setting for recognizing agonal respiration under limited network conditions. Methods: We recruited five emergency medical technicians, and each participant viewed 30 real-life videos with different resolutions, frame rates, and network scenarios. Thereafter, they reported the respiration pattern of the patient and identified agonal respiration cases. The time at which agonal respiration was identified was also recorded. The answers provided by the five participants were compared with those of two emergency physicians to compare the accuracy and time delay in breathing pattern recognition. Results: The overall accuracy for initial respiratory pattern recognition was 80.7% (121/150). The accuracy for normal breathing was 93.3% (28/30), for not breathing was 96% (48/50), and for agonal breathing was 64.3% (45/70). There was no significant difference in successful recognition between video resolutions. However, the rate of time delay in recognizing agonal respiration less than 10 seconds between 15-fps group and 30-fps group had statistical significance (21% vs 52%, p = 0.041). Conclusion: The frame rate emerges as one of critical factors in agonal respiration recognition through telemedicine, outweighing the significance of video resolution.

Abstract Background Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. Methods Microbiota composition was determined through 16S rRNA V3–V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as “tri-part samples”) in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. Results Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. Conclusion This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

Abstract Background Menopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force. Methods Fifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX + PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system. Results Compared with the control and OVX + PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX + PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX + PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p = 0.005) and 0.700 (p = 0.004). Conclusion Intermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (= vBMD × CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.

Abstract Background This study assessed the performance of visceral adiposity index and body shape index in predicting diabetes mellitus (DM) risk and compared their predictive ability to that of body mass index and waist circumference. Methods Among 8249 consecutive subjects who attended the Nationwide Health Check Up System for Senior Citizens (≥ 65 years) between 2008 and 2018, we examined the associations of several adiposity indices with DM risk and explored gender differences. Results Among all adiposity indicators, Chinese visceral adiposity index (CVAI) demonstrated the highest discriminatory ability for diabetes mellitus with area under receiver operating characteristic curves (AUC) of 0.65, 0.68, and 0.66 for men, women, and all participants, respectively, and optimal cut-offs set as 126.09 in men and 117.77 in women. Compared with body shape index (ABSI), both CVAI and VAI were strongly associated with baseline DM (adjusted OR: 4.85, 95% CI: 4.05–5.82 and 4.22, 95% CI: 3.53–5.05 for 4th vs 1st quartile groups by CVAI and VAI, P

Abstract There is an established link between cardiometabolic abnormality, central arterial stiffness, and preserved ejection fraction heart failure (HFpEF). Adipocyte free fatty acid binding protein (a-FABP) has been shown to signal endothelial dysfunction through fatty acid toxicity, though its role in mediating ventricular-arterial dysfunction remains unclear. We prospectively examined the associations of a-FABP with central arterial pressure using non-invasive applanation tonometry (SphygmoCor) and cardiac structure/function (i.e., tissue Doppler imaging [TDI] and global longitudinal myocardial strain [GLS]) in patients with cardiometabolic (CM) risk (n = 150) and HFpEF (n = 50), with healthy volunteers (n = 49) serving as a control. We observed a graded increase of a-FABP across the healthy controls, CM individuals, and HFpEF groups (all paired p

Since the 1990s, the prevalence of mental illnesses, such as depression, has been increasing annually and has become a major burden on society. Due to the many side effects of antidepressant drugs, the development of a complementary therapy from natural materials is an urgent need. Therefore, this study used a complex extract of chlorella and lion's mane mushroom and evaluated its antidepressant effects. Six-month-old male senescence-accelerated mice prone-8 (SAMP8) were divided into positive control; negative control; and low, medium, and high-dose groups. All groups were treated with corticosterone (CORT) at 40 mg/Kg/day for 21- days to induce depression in the animals, and the effects of different test substances on animal behavior was observed. The positive control group was intraperitoneally injected with a tricyclic antidepressant (Fluoxetine, as tricyclic antidepressant), the control group was given ddH2O, and the test substance groups were administered test samples once daily for 21 days. The open field test (OFT) and forced swimming test (FST) were applied for behavior analyses of depression animal models. The OFT results showed that the mice in the positive control and the medium-, and high-dose groups demonstrated a significantly prolonged duration in the central area and a significantly increased travel distance. In the FST, the positive control and the medium, and high-dose groups displayed significantly reduced immobility times relative to the control group. The blood analysis results showed significant decreases in triglyceride and blood urea nitrogen levels relative to the positive control and the medium- and high-dose groups. Notably, in the positive control and the medium- and high-dose groups, brain-derived neurotrophic factor (BDNF) increase by more than in the control group. In summary, medium and high dose of extract of chlorella and lion's mane mushroom could improve depression behavior in animals and have the potential to be antidepressant health care products.

ObjectivesAfter the coronavirus disease 2019 (COVID-19) pandemic emerged, there has been a substantial decline in emergency department (ED) visits. However, the impact of the pandemic on pediatric ED (PED) visits has not been well discussed. This study aimed to compare the epidemiology and clinical characteristics of PED visits before and after the time of the COVID-19 outbreak.MethodsData of pediatric patients admitted to the PED between February 2019 and January 2021 were retrospectively collected. All patients were divided into two groups: 1 year before the COVID-19 pandemic (group 1) and 1 year after the COVID-19 outbreak (group 2). Basic demographics, clinical characteristics, triage levels, categories of diagnosis at PED, disposition, and hospitalization rates (wards and intensive care units) were further analyzed and compared between the two groups.ResultsDuring the study period, 48,146 pediatric patients were enrolled (30,823 in group 1, and 17,323 in group 2). PED visits represented a 43.8% annual decline. The most common diseases in the PED in group 1 were infectious diseases, whereas digestive system diseases were the most common diseases in group 2 (both P < 0.001). In group 2, shorter PED observational time, longer hospital stay, and higher admission rates were noted compared to those in group 1 (all P < 0.001).ConclusionDuring the COVID-19 pandemic, the proportion of respiratory system diseases and infectious diseases sharply decreased in the PED, whereas the proportion of digestive system diseases relatively increased. The COVID-19 pandemic has impacted the nature of PED visits and we should pay more attention on digestive system diseases and the rates of out-of-hospital cardiac arrest and overall mortality.

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.

Abstract Aims Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region‐specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored. Methods and results Among 1326 asymptomatic individuals, region‐specific VAT including peri‐aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri‐aortic adipose tissue (TAT), was assessed using multiple‐detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle‐tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI‐e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17–2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440–1927 days) of follow‐up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log‐rank P

BackgroundDespite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes.ObjectiveTo study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes.MethodsAmong 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking.ResultsPost-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e’, lower LV GLS (0.37, 95%CI 0.04–0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01–0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00–1.07], impaired GLS (aHR 0.87, 95%CI 0.78–0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90–0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69–64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01–3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79–18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well.ConclusionMenopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

Abstract Cinnamomum osmophloeum ct. linalool is one chemotype of indigenous cinnamon in Taiwan. Its leaf essential oil (LEO) and main component S-(+)-linalool both possess great anxiolytic activities. The aim of this study was to establish ultrasound-assisted microextraction (UAME) for extracting LEO from C. osmophloeum ct. linalool. The absolute content of S-(+)-linalool and chemical composition of LEO were analyzed using GC-MS and GC-FID. To obtain the optimal conditions for UAME, four parameters (ultrasonic extraction duration, power of ultrasound, times of extraction, and leaf weight of extraction) were investigated according to the S-(+)-linalool content extracted. Results showed that the optimal condition was 10 mg of leaf extracted using n-hexane in an ultrasonicator with ultrasonic power of 80 W for 1 min. Furthermore, the absolute content of S-(+)-linalool obtained by UAME (28.3 ± 0.5 mg/g leaf) was comparable with that extracted by the 30-min hydrodistillation (HD) (26.9 ± 2.7 mg/g leaf). UAME was then employed to extract S-(+)-linalool from leaves at different stages of maturity (young, semi-mature, and mature). Results indicated that only mature leaf contains large amounts of S-(+)-linalool. Of note is that the LEO extracted by UAME contains coumarin, while that extracted by HD does not. Coumarin is an important ingredient in a number of cosmetic products due to its odor-fixing properties. With UAME, the leaf of C. osmophloeum ct. linalool has potential to be used as an aromatic material for further applications. In conclusion, UAME established in the present study provides a simple and rapid method for the determination of S-(+)-linalool and chemical composition of LEO from C. osmophloeum ct. linalool.

This study was conducted to evaluate the distribution of respiratory viral pathogens in the emergency department during the coronavirus disease 2019 (COVID-19) pandemic. Between May 2020 and September 2022, patients aged between 0.1 and 98 years arrived at the emergency department of Asia University Hospital, and samples from nasopharyngeal swabs were tested by the FilmArrayTM Respiratory Panel (RP). SARS-CoV-2 positivity was subsequently retested by the cobas Liat system. There were 804 patients for whom the FilmArrayTM RP was tested, and 225 (27.9%) of them had positive results for respiratory viruses. Rhinovirus/enterovirus was the most commonly detected pathogen, with 170 (61.8%) cases, followed by adenovirus with 38 (13.8%), SARS-CoV-2 with 16 (5.8%) cases, and coronavirus 229E, with 16 (5.8%) cases. SARS-CoV-2 PCR results were positive in 16 (5.8%) cases, and there were two coinfections of SARS-CoV-2 with adenovirus and rhinovirus/enterovirus. A total of 43 (5.3%) patients were coinfected; the most coinfection was adenovirus plus rhinovirus/enterovirus, which was detectable in 18 (41.9%) cases. No atypical pathogens were found in this study. Intriguingly, our results showed that there was prefect agreement between the detection of SARS-CoV-2 conducted with the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test and the FilmArrayTM RP. Therefore, the FilmArrayTM RP assay is a reliable and feasible method for the detection of SARS-CoV-2. In summary, FilmArrayTM RP significantly broadens our capability to detect multiple respiratory infections due to viruses and atypical bacteria. It provides a prompt evaluation of pathogens to enhance patient care and clinical selection strategies in emergency departments during the COVID-19 pandemic.

The antifungal activity of leaf oils from different provenances of Cinnamomum osmophloeum was evaluated against Phellinus noxius and their chemical polymorphism. C. osmophloeum leaf oils of 15 provenances and their relative contents were classified into eight chemotypes, namely cinnamaldehyde, cinnamaldehyde/linalool, linalool, cinnamaldehyde/cinnamyl acetate, linalool/camphor, camphor/bornyl acetate, 1,8-cineole/p-cymene, and mixed types according to GC-MS, CA, and PCA. It was found that leaf oils of both cinnamaldehyde and cinnamaldehyde/cinnamyl acetate types had excellent inhibitory effects against P. noxius, and their IC50 values were 119.5 and 154.1 µg/ml, respectively. Furthermore, trans-cinnamaldehyde possessed the strongest antifungal activity among the constituents against P. noxius, and its IC50 values were 116.0 µg/ml.

Both Chamaecyparis formosensis and C. obtusa var. formosana are representative cypresses of high economic value in Taiwan, the southernmost subtropical region where cypresses are found. Both species show differences of their habitats. To find out the effects of environmental factors on the CO2 assimilation rate and the biogenic volatile organic compound (BVOC) emission of both species, saplings from both species were grown under different light intensity and temperature regimes. The results indicated that the net CO2 assimilation rates and total BVOC emission rates of both species increased with increasing light intensity. C. formosensis showed a higher magnitude of change, but C. obtusa var. formosana had considerably increased sesquiterpenoid and diterpenoid emission in BVOC under high light intensity. Both species grown under higher temperatures had significantly lower BVOC emission rates. Proteomic analyses revealed that compared to C. formosensis saplings, C. obtusa var. formosana saplings had less differentially expressed proteins in terms of protein species and fold changes in response to the growth conditions. These proteins participated mainly in photosynthesis, carbon metabolism, amino acid and protein processing, signal transduction, and stress mechanisms. These proteins might be the major regulatory factors affecting BVOC emission of these two species under different environments.

Forecasting the stock market prices is complicated and challenging since the price movement is affected by many factors such as releasing market news about earnings and profits, international and domestic economic situation, political events, monetary policy, major abrupt affairs, etc. In this work, a novel framework: deep predictor for price movement (DPP) using candlestick charts in the stock historical data is proposed. This framework comprises three steps: 1. decomposing a given candlestick chart into sub-charts; 2. using CNN-autoencoder to acquire the best representation of sub-charts; 3. applying RNN to predict the price movements from a collection of sub-chart representations. An extensive study is operated to assess the performance of the DPP based models using the trading data of Taiwan Stock Exchange Capitalization Weighted Stock Index and a stock market index, Nikkei 225, for the Tokyo Stock Exchange. Three baseline models based on IEM, Prophet, and LSTM approaches are compared with the DPP based models.

Nano-bioscaffolds obtained from decellularized tissues have been employed in several medical applications. Nano-bioscaffolds could provide structural support for cell attachment and a suitable environment with sufficient porosity for cell growth and proliferation. In this study, a new combined method constitutes a decellularization protocol to remove the tissue and cellular molecules from porcine dermis for preparation of nano-bioscaffolds with fibrous extracellular matrix via pre- and post-treatment of supercritical fluids. The supercritical fluids-assisted nano-bioscaffolds were characterized by peptide identification, infrared spectrum of absorption, morphology, histological observations, DNA quantification, and hemocompatibility. Further, the resulting nano-bioscaffolds could be employed to obtain new cross-linked composite nano-bioscaffold containing collagen and acellular matrix.

This study aimed to increase the antibacterial activity of chitosan-polylactic acid (PLA) composite film by adding nisin and ethylenediaminetetraacetic acid (EDTA). We evaluated the mechanical, physicochemical, and antibacterial properties of various PLA composite films, as well as the enhancement effect of PLA composite films with EDTA + nisin on the preservation of grouper fillets. Films of PLA alone, PLA plus chitosan (C5), PLA plus nisin + EDTA (EN2), and PLA plus chitosan plus nisin + EDTA (C5EN1 and C5EN2) were prepared. The addition of EDTA + nisin to the chitosan-PLA matrix significantly improved the antibacterial activity of the PLA composite film, with C5EN1 and C5EN2 films showing the highest antibacterial activity among the five films. Compared with the fish samples covered by C5, the counts of several microbial categories (i.e., mesophilic bacteria, psychrotrophic bacteria, coliforms, Aeromonas, Pseudomonas, and Vibrio) and total volatile basic nitrogen content in fish were significantly reduced in the samples covered by C5EN1. In addition, the counts of samples covered by C5EN1 or C5 were significantly lower compared to the uncovered and PLA film-covered samples.

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve cognitive disability in Alzheimer’s disease model APP/PS1 mice. However, its effects on brain aging have not yet been touched upon. Here, we used senescence accelerated mouse prone 8 (SAMP8) mice as a model to elucidate the mechanism by which EAHEM delays the aging of the brain. Three-month-old SAMP8 mice were divided into three EAHEM dosage groups, administered at 108, 215 and 431 mg/kg/BW/day, respectively. During the 12th week of EAHEM feeding, learning and memory of the mice were evaluated by single-trial passive avoidance and active avoidance test. After sacrifice, the amyloid plaques, induced nitric oxidase synthase (iNOS) activity, thiobarbituric acid-reactive substances (TBARS) and 8-OHdG levels were analyzed. We found that the lowest dose of 108 mg/kg/BW EAHEM was sufficient to significantly improve learning and memory in the passive and active avoidance tests. In all three EAHEM dose groups, iNOS, TBARS and 8-OHdG levels all decreased significantly and showed a dose-dependent response. The results indicate that EAHEM improved learning and memory and delayed degenerative aging in mice brains.

Thalassemia and iron deficiency are the most common etiologies for microcytic anemia and there are indices discriminating both from common laboratory simple automatic counters. In this study a new classifier for discriminating thalassemia and non-thalassemia microcytic anemia was generated via combination of exciting indices with machine-learning techniques. A total of 350 Taiwanese adult patients whose anemia diagnosis, complete blood cell counts, and hemoglobin gene profiles were retrospectively reviewed. Thirteen prior established indices were applied to current cohort and the sensitivity, specificity, positive and negative predictive values were calculated. A support vector machine (SVM) with Monte-Carlo cross-validation procedure was adopted to generate the classifier. The performance of our classifier was compared with original indices by calculating the average classification error rate and area under the curve (AUC) for the sampled datasets. The performance of this SVM model showed average AUC of 0.76 and average error rate of 0.26, which surpassed all other indices. In conclusion, we developed a convenient tool for primary-care physicians when deferential diagnosis contains thalassemia for the Taiwanese adult population. This approach needs to be validated in other studies or bigger database.

The Taiwan Tilapia is an important aquaculture product in Taiwan. The aquatic by-products generated during Tilapia processing, such as fish bones and skin, are rich in minerals and protein. We aimed to explore the effect of a dietary supplement, comprising a mixture of fermented Tilapia by-products and Monostroma nitidum oligosaccharides as the raw materials, combined with physical training on exercise performance and fatigue. We used a mouse model that displays a phenotype of accelerated aging. Male senescence-accelerated mouse prone-8 (SAMP8) mice were divided into two control groups—with or without physical training—and supplemented with different doses (0.5 times: 412 mg/kg body weight (BW)/day; 1 time: 824 mg/kg BW/day; 2 times: 1648 mg/kg BW/day) of fermented Tilapia by-products and Monostroma nitidum oligosaccharide-containing mixture and combined with exercise training groups. Exercise performance was determined by testing forelimb grip strength and with a weight-bearing exhaustive swimming test. Animals were sacrificed to collect physical fatigue-related biomarkers. Mice dosed at 824 or 1648 mg/kg BW/day showed improvement in their exercise performance (p < 0.05). In terms of biochemical fatigue indicators, supplementation of 824 or 1648 mg/kg BW/day doses of test substances could effectively reduce blood urea nitrogen concentration and lactate concentration and increase the lactate ratio (p < 0.05) and liver glycogen content post-exercise (p < 0.05). Based on the above results, the combination of physical training and consumption of a dietary supplementation mixture of fermented Tilapia by-products and Monostroma nitidum oligosaccharides could improve the exercise performance of mice and help achieve an anti-fatigue effect.

Abstract Chondrosarcoma is a malignant primary bone tumor. Sirtuin-1 (SIRT1), which is a member of sirtuin family, plays a dual role either in cancer promotion or suppression. There is no report about the role of SIRT1 in the human chondrosarcoma cells. Resveratrol is a potent activator of SIRT1. However, its effects on chondrosarcoma have not been extensively studied. Here, we investigated the role of SIRT1 induction by resveratrol in human chondrosarcoma cell growth and tumor progression. Resveratrol significantly decreased cell viability and induced cell apoptosis in human chondrosarcoma cells in a dose-dependent manner. The protein expression and activity of SIRT1 were activated after treatment with resveratrol. Resveratrol significantly inhibited NF-κB signaling by deacetylating the p65 subunit of NF-κB complex, which could be reversed by siRNA-SIRT1 transfection or deacetylation inhibitor MS-275. Resveratrol induced-apoptosis involved a caspase-3-mediated mechanism. Both siRNA-SIRT1 transfection and MS-275 significantly inhibited the resveratrol-induced caspase-3 cleavage and activity in human chondrosarcoma cells. Moreover, in vivo chondrosarcoma xenograft study revealed a dramatic reduction in tumor volume and the increased SIRT1 and cleaved caspase-3 expressions in tumors by resveratrol treatment. These results suggest that resveratrol induces chondrosarcoma cell apoptosis via a SIRT1-activated NF-κB deacetylation and exhibits anti-chondrosarcoma activity in vivo.

Abstract Background Intermittent parathyroid hormone (PTH) can be used to treat osteoporosis of the spine and hip. However, whether it can be used to treat osteoporosis of the mandible is unclear. The purpose of this study was to explore the influence of applying intermittent PTH to ovariectomized rats on the trabecular bone microarchitecture of the mandible and femoral head. Methods Eighteen female rats were divided into three groups: the healthy group, ovariectomized (OVX) group, and OVX + PTH group. The OVX group and OVX + PTH group had an OVX at 8 weeks of age. The OVX + PTH group received intermittent PTH therapy for 12 weeks. The mandibles and femurs of all rats were removed at 20 weeks and were then scanned using microcomputed tomography (micro-CT). Results From the micro-CT analysis, the trabecular bone microarchitecture of the mandible and femoral head are offered as follows: (1) The bone volume fraction and trabecular thickness in the OVX group were lower than those in the healthy group. (2) The bone volume fraction and trabecular thickness in the OVX + PTH group approximated those in the healthy group. Conclusion The conclusions of this study regarding the trabecular bone microarchitecture of the mandible and femoral head are offered as follows: (1) The BV/TV and TbTh in the OVX group were lower than those in the healthy group. (2) The BV/TV and TbTh in the OVX + PTH group approximated those in the healthy group, therefore, intermittent PTH displayed high efficacy for treating femoral or mandibular deterioration of bone microstructure resulting from loss of ovarian function. Osteoporosis of the femur or mandible in the rats was ameliorated by intermittent PTH therapy.

Shewanella algae is an emerging pathogen widely distributed in aquatic environment. Bacteremia is a major manifestation of S. algae infections, and there are increasing reports of antibiotic-resistant strains. However, little is known about the genomic characteristics of human bacteremic S. algae. Here, we report the results of the whole-genome sequencing of colistin-resistant S. algae TYL, a blood isolate. Chromosome-encoded pmrC associated with colistin resistance and blaOXA-55 gene intrinsic to S. algae was identified. Continuous surveillance for the emergence of S. algae is needed.

Erinacine A-enriched Hericium erinaceus mycelia is a well-established potential therapeutic agent for neurodegenerative disorders. However, the effect of erinacine A-enriched H. erinaceus mycelia on promoting longevity remains unclear. This is the first study to investigate the effect of erinacine A-enriched H. erinaceus mycelia on lifespan-prolonging activity in Drosophila melanogaster and senescence-accelerated P8 (SAMP8) mice. Two hundred D. melanogaster and 80 SAMP8 mice of both sexes were randomly divided into four groups and were administered with either the standard, low-dose, mid-dose, or high-dose erinacine A-enriched H. erinaceus mycelia. After treatment, the lifespan was measured in D. melanogaster, and the lifespan, food intake and oxidative damage were evaluated in SAMP8 mice. Results showed that supplementation with erinacine A-enriched H. erinaceus mycelia extended the lifespan in both D. melanogaster and SAMP8 by a maximum of 32% and 23%, respectively, compared to the untreated controls. Moreover, erinacine A-enriched H. erinaceus mycelia decreased TBARS levels and induced the anti-oxidative enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Together, these findings suggest that erinacine A-enriched H. erinaceus mycelia supplement could promote longevity, mediated partly through the induction of endogenous antioxidants enzymes.

This research prepared chitosan–PLA plastic films by extrusion, analyzed the physical and mechanical properties and antibacterial activity of the fabricated plastic films, and used them to preserve grouper fillet. We added chitosan (220 kDa, 93% DD) in the weight ratio of 0.5–2% into the PLA to prepare the chitosan–PLA films. With the increasing chitosan dosage, both the water vapor transmission rate and moisture content of chitosan–PLA films increased. Among the three doses of chitosan (0.5%, 1%, and 2%) added to PLA, 0.5% chitosan–PLA film had the highest antibacterial activity. This plastic film had an inhibitory efficiency of over 95% against Escherichia coli, Pseudomonas fluorescens, and Staphylococcus aureus. The action of covering the fish fillet with 0.5% chitosan–PLA film significantly reduced several microbes’ counting (i.e., mesophiles, psychrophiles, coliforms, Pseudomonas, Aeromonas, and Vibrio) and total volatile basic nitrogen (TVBN) value in the grouper fillets stored at 4 °C. Thus, such action prolongs the fish fillets’ shelf life to up to at least nine days, and this 0.5% chitosan–PLA film shows promising potential for preserving refrigerated fish.

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions < 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement < 0.05) mainly in the NW phenotypes (p interaction < 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.

Background: Remote cardiac rhythm monitoring and diagnosis has been well incorporated in the telehealth service model. The prevalence and incidence of abnormal ventricular beats, based on utilizing a symptom-driven portable remote electrocardiography (ECG) device, remains less well explored. Methods: We studied 339 consecutive study participants, which included 192 individuals from outpatient clinics who were enrolled via a symptom-driven protocol; 147 participated in a heart rhythm screening program. All participants underwent 24-hour data transfer using a handheld portable electrocardiogram (ECG) device (DailyCare Biomedical Inc., Taoyuan City, Taiwan) with automatic ECG wavelet data extraction software (InstantCheck, version 4.0; DailyCare Biomedical Inc., Taoyuan City, Taiwan). Results: Among 1152 data transferred (98.4% success rate), we noticed 32.5% of the study participants had evidence of cardiac arrhythmias with permanent or paroxysmal atrial fibrillation (AF) constituting 50.9% of arrhythmias. Individuals with a history of heart failure (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.69–6.74), diabetes (OR, 3.03; 95% CI, 1.67–5.49), and cardiovascular disease (OR, 3.71; 95% CI, 2.05–6.7) had a higher AF risk. Both populations had an age-related increase in AF, even in multivariate models (OR, 1.72; 95% CI, 1.31–2.24 per +decade). Conclusion: The handheld ECG device shows clinical feasibility with high rate for AF detection with a similar trend toward a higher prevalence with aging from different settings. These data suggested that portable ECG device via remote care system may aid in clinical diagnosis, therapeutic interventions, or patient referral for cardiac arrhythmias.

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction.

Overexpression of the amyloid precursor protein (APP) and the hyperphosphorylation of the tau protein are vital in the understanding of the cause of Alzheimer’s disease (AD). As a consequence, regulation of the expression of both APP and tau proteins is one important approach in combating AD. The APP and tau proteins can be targeted at the levels of transcription, translation and protein structural integrity. This paper reports the utilization of a bi-cistronic vector containing either APP or tau internal ribosome entry site (IRES) elements flanked by β-galactosidase gene (cap-dependent) and secreted alkaline phosphatase (SEAP) (cap-independent) to discern the mechanism of action of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist. Results indicate that memantine could reduce the activity of both the APP and tau IRES at a concentration of ~10 μM (monitored by SEAP activity) without interfering with the cap-dependent translation as monitored by the β-galactosidase assay. Western blot analysis of the tau protein in neuroblastoma (N2A) and rat hippocampal cells confirmed the halting of the expression of the tau proteins. We also employed this approach to identify a preparation named NB34, extracts of Boussingaultia baselloides (madeira-vine) fermented with Lactobacillus spp., which can function similarly to memantine in both IRES of APP and Tau. The water maze test demonstrated that NB34 could improve the spatial memory of a high fat diet induced neurodegeneration in apolipoprotein E-knockout (ApoE−/−) mice. These results revealed that the bi-cistronic vector provided a simple, and effective platform in screening and establishing the mechanistic action of potential compounds for the treatment and management of AD.

The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice.Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom.We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion).This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice.

Taiwanofungus camphoratus is a rare and valuable medicinal mushroom indigenous to Taiwan. It has traditionally been used to promote good health. This study aimed to explore the immunomodulatory effects of “Leader Deluxe Taiwanofungus camphoratus capsule” (LDAC). LDAC is a healthy food product composed of fruiting body extract and solid-state-cultivated mycelia of T. camphoratus. Two complementary studies were performed. In the first, LDAC was orally administered to BABL/c female mice for 6 weeks as part of a non-specific immune study. In the second, mice were treated with LDAC for 8 weeks and immunized with ovalbumin (OVA) in a specific immune study. LDAC increased the growth of splenic immune cells and enhanced the activity of macrophages and natural killer cells. It increased the levels of interleukin (IL)-2, interferon (IFN)-γ, serum immunoglobulin (Ig)G, and OVA-IgG, and decreased the levels of IL-4, IL-5, tumor necrosis factor (TNF)-α, serum IgE, and OVA-IgE. Thus, the findings of this study strongly supported the idea that LDAC possesses immunomodulatory activity.

The senescence-accelerated prone (SAMP8) mouse model shows age-dependent deterioration in learning and memory and increased oxidative stress in the brain. We previously showed that healthy subjects on a six-week supplementation of a chicken meat hydrolysate (ProBeptigen®/CMI-168) demonstrated enhanced and sustained cognitive performance up until two weeks after the termination of supplementation. In this study, we investigate the effect of ProBeptigen on the progression of age-related cognitive decline. Three-month old SAMP8 mice were orally administered different doses of ProBeptigen (150,300 or 600 mg/kg/day) or saline daily for 13 weeks. Following ProBeptigen supplementation, mice showed lower scores of senescence and improved learning and memory in avoidance tasks. ProBeptigen treatment also increased antioxidant enzyme activity and dopamine level while reducing protein and lipid peroxidation and mitochondrial DNA damage in the brain. Microarray analysis of hippocampus revealed several processes that may be involved in the improvement of cognitive ability by ProBeptigen, including heme binding, insulin growth factor (IGF) regulation, carboxylic metabolic process, oxidation−reduction process and endopeptidase inhibition. Genes found to be significantly altered in both ProBeptigen treated male and female mice include Mup1, Mup17, Mup21, Ahsg and Alb. Taken together, these results suggest a potential anti-aging effect of ProBeptigen in alleviating cognitive deficits and promoting the antioxidant defense system.

In numerous economic scenarios, contracting parties may not have a clear picture of all the relevant aspects. A contracting party may be unaware of what she and/or others are entitled to determine. Therefore, she may reject a contract that is too good to be true. Further, a contracting party may actively exert cognitive effort before signing a contract, so as to avoid being trapped into the contractual agreement ex post. In this paper, we propose a general framework to investigate these strategic interactions with unawareness, reasoning and cognition and intend to unify the solution concepts in the contracting context with unawareness. We build our conceptual framework upon the classical principal-agent relationship and compare the behaviors under various degrees of the unaware agent’s sophistication.

Objective: This study aims to determine the effects of curcumin and demethoxycurcumin on the internal ribosome entry site of the amyloid-β precursor protein (APP) and tau protein through a bi-cistronic reporter assay for screening of anti-Alzheimer's disease agents. Materials and Methods: A bi-cistronic assay was performed wherein the expression of the first cistron, a β-galactosidase gene under the control of a cytomegalovirus promoter, represents the canonical cap-dependent mechanism of translation initiation; while the second cistron involves the utilization of the APP or the tau IRES elements to drive the expression of secreted alkaline phosphatase (SEAP) under a cap-independent mechanism. Bioactive natural products reported to have therapeutic potential for AD such as curcumin and demethoxycurcumin were screened in an murine neuroblastoma (N2A) cell model. Western blot analyses for the expression of APP C-terminal protein, human tau-1, and phosphorylated tau at Serine 262 (p262) and Serine 396 (pS396) were done after treatment of N2A cells with the test compounds. Results: The bi-cistronic reporter assay revealed that curcumin was more effective than demethoxycurcumin, a structural analog of curcumin, in inhibiting both APP and tau IRES-dependent translation initiation. This result was further confirmed by Western blot analysis for the expression of APP C-terminal protein, human tau-1, pS262 and pS396 suggesting that curcumin may play a role in AD pathology alleviation through the inhibition of the APP and tau IRES-mediated translation mechanism. On the other hand, demethoxycurcumin was observed to inhibit the phosphorylation of both tau pS262 and pS396. Conclusion: A novel assay system using the bi-cistronic reporter constructs for the identification of compounds with activity against the translation directed by APP and tau IRES was developed. The results provide novel suggestive insights for the potential use of the mentioned compounds as prophylactic and therapeutic anti-AD agents.

Alzheimer disease (AD) is by far the most common cause of dementia globally. This neurodegenerative disorder of the brain is chronic and progressive, characterized clinically by the deterioration in the key symptoms of behavioral and cognitive abilities. Treatment options for this disease currently are limited. Deposition of amyloid-β and tau hyperphosphorylation are cardinal pathologic features of AD that lead to the formation of neuronal plaques and neurofibrillary tangles, respectively. In addition to mounting research on herbal compounds for the treatment of AD, curcuminoids and resveratrol appear to be beneficial as anti-AD agents. Curcuminoids (curcumin and demethoxycurcumin) and resveratrol possess unique properties that make them especially worthy of further studies. This review article revisits and presents the current research done on the potential of the curcuminoids curcumin and demethoxycurcumin and the polyphenolic compound resveratrol as anti-AD compounds.

OBJECTIVE:This study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats. MATERIALS AND METHODS:Twelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman's correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck. RESULTS:Regarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (rs = 0.874 and rs = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks. CONCLUSION:After the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles.

The ABO blood group system is the most important blood group system in transfusion medicine. In addition to the major A, B and O alleles, many rare alleles with weak expression of the A or B antigens on RBCs have been defined. We report here the molecular analysis of a novel Ael allele. Exons 6 and 7 of the ABO gene were PCR-amplified, cloned and sequenced for the propositus, Mr C, who is a 56-year-old Taiwanese male and was incidentally observed to have an Ael phenotype. His direct family members including wife, son and daughter were subsequently enrolled for further study. Three hundred random blood donors of AB phenotype served as control. A novel Ael allele was uncovered from the propositus and his daughter, of which a unique 816insG mutation occurred on the A102 background that results in a frame shift leading to a 37-amino acid longer polypeptide than the normal A1 transferase, a finding similar to that of Ael01 allele with 804insG. We found that the C family carried a novel Ael allele that differs molecularly from seven Ael alleles reported in the literature.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease. Platelet refractoriness is frequently seen in patients with ITP. Platelets express platelet-specific antigens and human leukocyte antigens (HLA). Platelet antibodies to platelet-specific antigens and HLA may be present, but HLA antibodies in patients with ITP have rarely been reported. Methods: Sera from 44 adult patients with ITP were screened for platelet antibodies by two flow cytometric assays. In method I, platelets from normal donor platelets were used as target cells to screen both platelet-specific antibodies and HLA class I antibodies. In method II, the FlowPRA(tm) Class I Screening Test kit was used to screen HLA class I antibodies. Fluorescein isothiocyanate (FITC)-conjugated sheep anti-human IgG Fc was used as the staining reagent in both methods. The negative serum control was from one of the normal males with AB blood group who had never received a transfusion. Sera from a pool of five highly sensitized patients were used as the positive control. Results: Of the 44 sera from patients with ITP, 31 (70.5%) were method I positive, and 28 (63.6%) were method II positive. There was no significant difference between the results of method I and method II (p = 0.439). The distribution of the results of these two tests was: both tests positive in 22 sera, method I positive and method II negative in nine sera, method I negative and method II positive in six sera, and both tests negative in seven sera. The mean platelet counts of patients with positive (41.0 ± 40.0 × 109/L) and negative (40.4 ± 26.8 × 109/L) tests by method I did not differ significantly (p = 0.643). The mean platelet counts of patients with (36.7 ± 31.5 × 109/L) and without (48.1 ± 43.6 × 109/L) HLA class I antibodies did not differ significantly (p = 0.59). Conclusion: HLA class I antibodies are frequently found in ITP. The screening of platelet antibodies including platelet-specific antibodies and unappreciated HLA class I antibodies is warranted in patients with ITP. [J Formos Med Assoc 2007;106(2):105-109]