Comparison of mycophenolic acid with cyclophosphamide for the treatment of pediatric lupus nephritis: A retrospective study from a tertiary center hospital in Taiwan.

BACKGROUND: This study aimed to compare the efficacy of mycophenolic acid (MPA) and cyclophosphamide (CYC) for treating pediatric lupus nephritis (pLN). METHODS: Data on patients with pLN class III, IV, and V, diagnosed by renal biopsy, were collected from the Databank of Kaohsiung Veterans General Hospital between February 2005 and December 2020. The study included 31 pLN patients. Of these, 15 received MPA (MPA group) and 16 received CYC (CYC group). Systemic lupus erythematosus disease activity index score, laboratory findings, complete remission (CR), and partial remission (PR) were assessed at 6, 12, and 24 months. RESULTS: In the MPA group, CR occurred in 7/15 (47%) patients at month 6 and in 11/15 (73%) at months 12 and 24. In the CYC group, CR was reached in 5/16 (31%) patients at month 6, in 8/16 (50%) at month 12, and in 9/16 (56%) at month 24. PR was seen in 3/15 (20%) patients in the MPA group and in 3/16 (19%) in the CYC group at month 24. The cumulative probability of CR and PR showed no statistically significant difference between the two groups. However, the estimated glomerular filtration rate (eGFR) improved significantly in the MPA group at months 6, 12 and 24 compared to that in the CYC group (p < 0.05). CONCLUSION: The efficacy of MPA is similar to that of CYC for pLN treatment, with MPA providing a significant improvement in eGFR after pLN induction therapy at months 6,12 and 24.

Examining the Predictors of Turnover Behavior in Newly Employed Certified Nurse Aides: A Prospective Cohort Study.

Background: The turnover rate of nurse aides in Taiwan is high. However, the predictors of turnover behavior in the newly employed are still unclear. Objective: To examine the predictors of turnover behavior in newly employed licensed nurse aides. Methods: A longitudinal study design was used and subjects were newly employed certified nurse aides from a nurse aid training association in Taiwan. A total of five questionnaire surveys were conducted. The questionnaire was mainly used to collect information on turnover behavior, personal socioeconomic background, workplace psychosocial hazards, worker health hazards, and musculoskeletal disorders. Results: A total of 300 participants were recruited in the study. Cox regression analysis results showed that short working experience (hazard ratio [HR] = 0.21, p < 0.01), work as non-home nurse aides (HR = 0.58, p = 0.01), low monthly salary (HR = 0.68, p < 0.01), high work mental load (HR = 1.01, p = 0.01), low workplace justice (HR = 0.97, p < 0.01), high workplace violence (HR = 1.60, p < 0.01), high burnout (HR = 1.01, p = 0.04), poor mental health (HR = 1.06, p = 0.04), and high total number of musculoskeletal disorder sites (HR = 1.08, p = 0.01) contribute to a higher risk of turnover. Conclusion: The results indicated that employment period, work as a home nurse aide, monthly salary, work mental load, workplace justice, workplace violence, work-related burnout, mental health, and total number of musculoskeletal disorder sites are predictors of turnover behavior in newly employed certified nurse aides.

Association of Internet Addiction with Family Functionality, Depression, Self-Efficacy and Self-Esteem among Early Adolescents.

Early adolescents usually have worse self-control and poor time management abilities. They are a higher-risk group for Internet addiction than older adolescents or adults. This study aims to explore the prevalence of Internet addiction and associated factors in early adolescents. Participants included 451 fifth and sixth-grade students in Central Taiwan. This study adopted a cross-sectional design and a structured questionnaire that consisted of demographics, Young's Internet Addiction Test, the Centre for Epidemiological Studies-Depression scale, the General Self-Efficacy Scale and the Rosenberg Self-Esteem Scale. The participants were 50.8% male, and the mean age was 11.35, with a range of 10.33-12.92 years. A total of 33.7% of all participants were prone to Internet addiction. The results showed that participants who were male and had high money allowance, poor family atmosphere, parents who did not limit Internet usage time, high depression, low self-efficacy and low self-esteem were more prone to Internet addiction. A multiple logistic regression analysis revealed that being male, having parents who did not limit Internet usage time and higher degrees of depression were the associated factors of Internet addiction in early adolescents. The phenomenon of Internet addiction among early adolescents seems to be increasing. Improving family functionality and individual mental health may be effective ways to reduce Internet addiction.

Lack of Acute Toxicity and Mutagenicity from Recombinant Epinephelus lanceolatus Piscidin Expressed in Pichia pastoris.

The antimicrobial peptide (AMP) piscidin was identified from Epinephelus lanceolatus and demonstrated to possess antimicrobial and immune-related functions. Supplementation of feed with recombinant Epinephelus lanceolatus piscidin (rEP)-expressing yeast pellets may minimize the excessive use of antibiotics and control pathogens in aquaculture or animal husbandry. However, before implementing rEP as a supplement, it is necessary to understand whether it harbors any toxicity. Since toxicological information on the topic is scarce, the present investigation was carried out to test whether rEP exhibits allergenic and/or toxic effects. In an oral acute toxicity test (OECD 425), Sprague Dawley (SD) rats were administered rEP dissolved in reverse osmosis water, yielding an LD50 > 5000 mg/kg (no observed animal death). The compound was therefore classified as non-toxic by oral administration. In an acute respiratory toxicity test (OECD 403), heads and noses of SD rats were exposed to liquid aerosol for 4 h (the highest concentration that could be administered without causing any animal death), and a lethal concentration (LC50) > 0.88 mg/L was obtained. The mass medium aerodynamics diameter (MMAD) of rEP aerosol particles was 8.18 µm and mass medium aerodynamics diameter (GSD) was 3.04, which meant that 25.90% could enter the airway (<4 µm) of a rat, and 58.06% (<10 µm) could be inhaled by humans. An ocular irritation test (OECD 405) with rEP powder was performed on New Zealand White (NZW) rabbits. Signs of irritation included conjunctival swelling and diffuse flushing 1 h after administration. The signs were less apparent after 24 h and disappeared after 72 h. The classification assigned to the powder was mild eye irritation. Skin sensitization was performed for a local lymphoproliferative test (OECD 442B) using BALB/c mice, with the highest soluble concentration of the rEP considered to be 100% test substance; formulations were diluted to 50% and 25%, and bromodeoxyuridine (BrdU) incorporation was used to measure the degree of lymphocyte proliferation. The stimulation indexes (SIs) were 1.06 (100%), 0.44 (50%), and 0.77 (25%), all of which were less than the cutoff value for a positive sensitization result (1.6). Negative response was also seen in the bacterial reverse mutation test (OECD 471), and no chromosomal effects on Chinese hamster ovary (CHO)-K1 cells were observed (OECD 487). Based on these six toxicity tests, rEP showed neither acute toxic effects in experimental animals nor mutagenicity. Thus, rEP can be considered safe for use in subsequent research on its application as a feed additive for poultry, cattle, or aquatic animals.

Incidental pharyngoesophageal diverticulum mistaken for a thyroid nodule: Report of two cases.

Pharyngeal or Zenker's diverticulum is an infrequent disorder that results from an outpouching of pharyngeal mucosa through a weakened area in the posterior pharyngeal wall. As it may mimic a thyroid nodule on ultrasonography (US), accurate diagnosis is important to ensure appropriate treatment. Fine-needle aspiration (FNA) is recommended for the initial evaluation of thyroid nodules. We report the FNA diagnosis of two cases of Zenker's diverticulum that were suspected to be thyroid nodules on US. Pap stained aspirate smears showed findings characteristic of Zenker's diverticulum: benign squamous cells, bacteria, and vegetable debris and the absence of colloid and/or thyroid epithelial cells. US and CT findings were consistent with the diagnosis.

Green and efficient production of octyl hydroxyphenylpropionate using an ultrasound-assisted packed-bed bioreactor.

A solvent-free system to produce octyl hydroxyphenylpropionate (OHPP) from p-hydroxyphenylpropionic acid (HPPA) and octanol using immobilized lipase (Novozym® 435) as a catalyst in an ultrasound-assisted packed-bed bioreactor was investigated. Response-surface methodology (RSM) and a three-level-three-factor Box-Behnken design were employed to evaluate the effects of reaction temperature (x1), flow rate (x2) and ultrasonic power (x3) on the percentage of molar production of OHPP. The results indicate that the reaction temperature and flow rate were the most important variables in optimizing the production of OHPP. Based on a ridge max analysis, the optimum conditions for OHPP synthesis were predicted to consist of a reaction temperature of 65°C, a flow rate of 0.05 ml/min and an ultrasonic power of 1.74 W/cm² with a yield of 99.25%. A reaction was performed under these optimal conditions, and a yield of 99.33 ± 0.1% was obtained.

Optimization of ultrasound-accelerated synthesis of enzymatic caffeic acid phenethyl ester by response surface methodology.

The ultrasound-accelerated enzymatic synthesis of caffeic acid phenethyl ester (CAPE) from caffeic acid and phenethyl alcohol was investigated in this study. A commercial immobilized lipase from Candida antarctica, called Novozym® 435, was used as the catalyst. A 5-level-4-factor central-composite rotatable design (CCRD) and response surface methodology (RSM) were employed to evaluate the effects of reaction time, substrate molar ratio, enzyme amount, and ultrasonic power on percent molar conversion of CAPE. The results indicated that reaction time, substrate molar ratio, and ultrasonic power significantly affected percent molar conversion, whereas enzyme amount did not. A model for synthesis of CAPE was established. Based on ridge max analysis, the optimum condition for CAPE synthesis was predicted to be reaction time 9.6 h, substrate molar ratio 1:71, enzyme amount 2938 PLU, and ultrasonic power 2 W/cm(2) with the molar conversion value of 96.03 ± 5.18%. An experiment was performed under this optimal condition and molar conversion of 93.08 ± 0.42% was obtained.

Continuous production of lipase-catalyzed biodiesel in a packed-bed reactor: optimization and enzyme reuse study.

An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed-bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert-butanol solvent system. Response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1°C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 ± 2.07% and 82.81 ± .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed-bed reactor for continuous biodiesel synthesis.

Optimization of ultrasound-accelerated synthesis of enzymatic octyl hydroxyphenylpropionate by response surface methodology.

The ultrasound-accelerated enzymatic synthesis of octyl hydroxyphenylpropionate (OHPP) from p-hydroxyphenylpropionic acid (HPPA) and octanol was investigated in this study. A commercially available immobilized lipase from Candida antarctica, Novozym 435, was used as the biocatalyst. A three-level-three-factor Box-Behnken design experiment and response surface methodology were used to evaluate the effects of temperature, reaction time, and enzyme activity on percent yield of OHPP. The results indicated that temperature and enzyme activity significantly affected percent yield, whereas reaction time did not. A model for the synthesis of OHPP was established. Based on a ridge max analysis, the optimum conditions for OHPP synthesis were predicted to use a reaction temperature of 58.8°C, a reaction time of 14.6 h, and an enzyme activity of 410.5 PLU with a yield of 98.5%. A reaction was performed under these optimal conditions, and a yield of 97.5% ± 0.1% was obtained.

Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy.

Conventionally, liver fibrosis is diagnosed using histopathological techniques. The traditional method is time-consuming in that the specimen preparation procedure requires sample fixation, slicing, and labeling. Our goal is to apply multiphoton microscopy to efficiently image and quantitatively analyze liver fibrosis specimens bypassing steps required in histological preparation. In this work, the combined imaging modality of multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) was used for the qualitative imaging of liver fibrosis of different METAVIR grades under label-free, ex vivo conditions. We found that while MAF is effective in identifying cellular architecture in the liver specimens, it is the spectrally distinct SHG signal that allows the characterization of the extent of fibrosis. We found that qualitative SHG imaging can be used for the effective identification of the associated features of liver fibrosis specimens graded METAVIR 0 to 4. In addition, we attempted to associate quantitative SHG signal to the different METAVIR grades and found that an objective determination of the extent of disease progression can be made. Our approach demonstrates the potential of using multiphoton imaging in rapid classification of ex vivo liver fibrosis in the clinical setting and investigation of liver fibrosis-associated physiopathology in animal models in vivo.

Optimized enzymatic synthesis of caffeic acid phenethyl ester by RSM.

In this study, optimization of enzymatic synthesis of caffeic acid phenethyl ester (CAPE), catalyzed by immobilized lipase (Novozym 435) from Candida antarctica was investigated. Novozym 435 was used to catalyze caffeic acid and 2-phenylethanol in an isooctane system. Response surface methodology (RSM) and 5-level-4-factor central-composite rotatable design (CCRD) were employed to evaluate the effects of synthesis parameters, such as reaction temperature (30-70 degrees C), reaction time (24-72 hours), substrate molar ratio of caffeic acid to 2-phenylethanol (1:10-1:90) and enzyme amounts (100-500 PLU) on percentage conversion of CAPE by direct esterification. Reaction temperature and time had significant effects on percent conversion. On the basis of ridge max analysis, the optimum conditions for synthesis were: reaction time 59 hours, reaction temperature 69 degrees C, substrate molar ratio 1:72 and enzyme amount 351 PLU. The molar conversion of predicted values and actual experimental values were 91.86+/-5.35% and 91.65+/-0.66%, respectively.

Protective effects from carnosine and histidine on acetaminophen-induced liver injury.

Protective effects of carnosine or histidine against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined. Each compound, at 0.5, 1, or 2 g/L, was added into the drinking water for 4 wk. Acute liver injury was induced by acetaminophen treatment intraperitoneally (i.p. 350 mg/kg body weight). Acetaminophen treatment significantly depleted hepatic GSH and ascorbic acid levels, increased hepatic level of malonyldialdehyde (MDA), reactive oxygen species (ROS), and oxidized glutathione (GSSG), as well as decreased hepatic activity of glutathione peroxidase (GPX), catalase, and superoxide dismutase (SOD) (P < 0.05). However, the pre-intake of carnosine or histidine significantly alleviated acetaminophen-induced oxidative stress by increasing GSH content, decreasing MDA, ROS, and GSSG formations, and retaining activity of GPX, catalase, and SOD in liver (P < 0.05). The pre-intake of these compounds also significantly retarded subsequent acetaminophen-induced increase of cytochrome P450 2E1 activity (P < 0.05). Acetaminophen treatment increased the hepatic levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and monocyte chemoattractant protein (MCP)-1 (P < 0.05). The pre-intake of carnosine or histidine significantly diminished acetaminophen-induced elevation of these cytokines (P < 0.05). The impact of these compounds on mRNA expression of GPX, TNF-alpha, and MCP-1 indicated that these compounds could act at a transcription level. These results support that carnosine and histidine are potent hepatoprotective agents.

Visualization of hepatobiliary excretory function by intravital multiphoton microscopy.

Intravital imaging of hepatobiliary excretion is vital for elucidating liver metabolism. In this work, we describe a novel method to observe the intravital dynamics of the uptake, processing, and excretion of an organic anion, 6-carboxyfluorescein diacetate (6-CFDA) in the hepatobiliary system. This is achieved by the use of multiphoton microscopy and an intravital hepatic imaging chamber. The high-quality images show sequential uptake and processing of 6-CFDA from the hepatocytes and the subsequent excretion into bile canaliculi within approximately 50 min. This is a promising technique to study intravital hepatic physiology and metabolism.

Effect of vibration on visual display terminal work performance.

Today electronic visual displays have dramatic use in daily life. Reading these visual displays is subject to their vibration. Using a software-simulation of a vibrated environment, the study investigated the effect of vibration on visual performance and fatigue for several numerical display design characteristics including the font size and the number of digits displayed. Both the frequency and magnitude of vibration had significant effects on the reaction time, accuracy, and visual fatigue. 10 graduate students (23-30 years old; M = 25.6), randomly tested in this experiment, were offered about 25 U.S. dollars for their participation. Numbers in vertical presentation were affected more in vertical vibration than those in horizontal presentation. Analysis showed whenever the display is used in vibration environment, an increased font size may be an effective way to compensate the adverse effect of vibration. The software design of displayed materials must be designed to take the motion effect into consideration to increase the quality of the screen display.

Intact corneal stroma visualization of GFP mouse revealed by multiphoton imaging.

The aim of this work is to demonstrate that multiphoton microscopy is a preferred technique to investigate intact cornea structure without slicing and staining. At the micron resolution, multiphoton imaging can provide both large morphological features and detailed structure of epithelium, corneal collagen fibril bundles and keratocytes. A large area multiphoton cross-section across an intact eye excised from a GFP mouse was obtained by a homebuilt multiphoton microscope. The broadband multiphoton fluorescence (435-700 nm) and second harmonic generation (SHG, 360-400 nm) signals were generated by the 760 nm output of a femtosecond titanium-sapphire laser. A water immersion objective (Fluor, 40X, NA 0.8; Nikon) was used to facilitate imaging the curve ocular surface. The multiphoton image over entire cornea provides morphological information of epithelial cells, keratocytes, and global collagen orientation. Specifically, our planar, large area multiphoton image reveals a concentric pattern of the stroma collagen, indicative of the laminar collagen organization throughout the stroma. In addition, the green fluorescence protein (GFP) labeling contributed to fluorescence contrast of cellular area and facilitated visualizing of inactive keratocytes. Our results show that multiphoton imaging of GFP labeled mouse cornea manifests both morphological significance and structural details. The second harmonic generation imaging reveals the collagen orientation, while the multiphoton fluorescence imaging indicates morphology and distribution of cells in cornea. Our results support that multiphoton microscopy is an appropriate technology for further in vivo investigation and diagnosis of cornea.

Imaging human bone marrow stem cell morphogenesis in polyglycolic acid scaffold by multiphoton microscopy.

The noninvasive imaging of tissue engineering constructs is vital for understanding the physiological changes in construct formation and the design of improved products for therapeutic purposes. In this work, we use the combination of multiphoton autofluorescence and second harmonic generation (SHG) microscopy to image the physiological changes to the engineered constructs of human mesenchymal stem cells seeded in a polyglycolic acid (PGA) scaffold under induction by chondrogenic transforming growth factor-beta3. Without histological procedures, we found that multiphoton autofluorescence is useful for imaging the PGA scaffold and stem cells while SHG is useful for following the progress of extracellular matrix (ECM) formation. We found that the initial ECM formation tends to align along the PGA scaffold orientation and progressive induction alters the scaffold conformation, indicating that biomechanical forces or the chemical environment generated by chondrogenesis is sufficient for scaffold reorganization. Our results suggest that in the future this approach may be used for real-time monitoring of the physiological processes associated with tissue engineering.

Optical biopsy of liver fibrosis by use of multiphoton microscopy.

We demonstrate the application of multiphoton microscopy in diagnosing toxin- (CCl4-) induced liver fibrosis in mice. Although hepatocyte autofluorescence does not vary significantly, different degrees of necrosis and stellate cell proliferation at necrotic sites in livers with fibrosis (ex vivo) can be detected easily from multiphoton-induced autofluorescence images by use of 780-nm excitation. Our result suggests that multiphoton microscopy can be developed into an effective technique for the detection and diagnosis of liver fibrosis in vivo.