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Background: Ageism is prejudice or discrimination against different age groups, particularly older people. As senior nursing students in the last year of their studies prepare to enter the workforce, it is imperative to understand their level of ageism because of the high probability that they will care for older people during their nursing careers due to the global aging population. However, most research has focused on nursing students' knowledge and attitudes regarding older adults, and few studies have specifically investigated ageism among senior nursing students., Objective: This study aimed to understand ageism among senior nursing students and associated factors., Design: This was a cross-sectional descriptive study., Settings and Participants: In total, 249 senior students from 16 four-year Bachelor of Science in Nursing programs in Taiwan were recruited. Inclusion criteria were (1) a senior student enrolled in a Bachelor of Science in Nursing program and (2) the ability to read Chinese., Methods: Data were collected using an online questionnaire consisting of two parts: demographic characteristics and the Fraboni Scale of Ageism. The frequency, percentage, mean, standard deviation, t-test, one-way analysis of variance, Pearson product-moment correlation, and multiple linear regression were used to analyze data., Results: The average score for ageism among senior nursing students was 61.60 ± 7.73, out of a maximum of 116. Having a higher level of concern about ageism issues and having had grandparents who were primary caregivers during childhood were linked to a lower degree of ageism. The only predictor of senior nursing students' ageism was the extent of their concern about ageism issues (F = 18.47, p < .001)., Conclusions: Senior nursing students demonstrated a moderate level of ageism. Faculty members should develop strategies to increase nursing students' awareness of ageism issues and develop appropriate interventions to prevent and improve their ageist attitudes., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The study aimed to translate the Geriatric Anxiety Inventory into traditional Chinese (GAI-TC), examine its psychometric properties, and identify the optimal cutoff point. This research recruited 337 older adults from two community activity centers. Structured questionnaires were used, including demographic information and characteristics, the GAI-TC, and the State-Trait Anxiety Inventory (STAI). Cronbach's α of the GAI-TC was 0.93. The intraclass correlation coefficient was 0.90. The content validity index was 1.0. An exploratory factor analysis revealed that three factors in the GAI-TC, including cognition anxiety, impact of anxiety, and somatic anxiety, explained 59.46 % of the variance. The criterion-related validity showed a significant positive correlation between the GAI-TC and STAI, with an optimal cutoff of 9/10 for detecting anxiety in older persons living in the community. The GAI-TC had good reliability and validity and can provide professionals with a tool for the early identification of anxiety among older adults., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased p AMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Background: The Critical Thinking Disposition Scale is a valid and reliable tool for assessing an individual's attitudes towards critical thinking. However, it is unclear if the scale can be used with Vietnamese nursing students., Objectives: This study aimed to translate the scale into Vietnamese and examine the psychometric properties of the Vietnamese version of the Critical Thinking Disposition Scale (CTDS-V)., Settings: Data were collected from senior nursing students at four universities in southern Vietnam in October and December 2022., Participants: In total, 398 senior nursing students participated in this study., Methods: A cross-cultural adaptation of the CTDS-V was carried out with participants obtained through convenience sampling. Data were collected through an online survey. The study evaluated the validity of the CTDS-V by examining the content validity, concurrent validity, and construct validity, employing both Exploratory and Confirmatory Factor Analyses. The study also reported the internal consistency reliability using Cronbach's alpha and test-retest stability of the CTDS-V., Results: The CTDS-V had a good content validity index with a score of at least 0.85 for each item and an excellent overall content validity index of 0.96. Exploratory Factor Analysis identified two factors, critical openness, and reflective scepticism, with 11 items. Confirmatory Factor Analysis provided an acceptable fit model and supported the factor structure of the original scale. Cronbach's alpha coefficient of the scale was 0.88, and those of the two subscales were each 0.84. The test-retest stability of the CTDS-V was good with an intraclass correlation coefficient of 0.98 (95 % confidence interval = 0.96, 0.99)., Conclusions: This study indicated that the CTDS-V is a valid and reliable tool for assessing the critical thinking disposition of nursing students. The scale is short, rendering it feasible for regular use in education and research., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acupuncture has been shown as an effective traditional Chinese medicine treatment method, especially for pain relief. Recently, laser acupuncture is becoming increasingly popular, thanks to its noninvasive and painless nature and effectiveness in treating diseases, proven by many studies (for example, some previous studies showed that low-power laser stimulation is able to increase the power of alpha rhythms and theta waves). In our prior work, we developed a novel laser acupuncture model that emulates lifting-and-thrusting operation commonly used in traditional needle acupuncture and showed its benefit in improving cardiac output and peripheral circulation. By extending our previous studies, in this work, we perform extensive experiments to understand the effect of such a system on electrodermal activity (EDA) of acupoints, pulse characteristics, and brainwave, to further verify its efficacy. In particular, we found that laser stimulation could cause significant changes in EDA of acupoints, pulse amplitude, pulse-rate-variability (PRV), and acupoint conductance, as a function of laser power and stimulation time. In addition, laser acupuncture with the lifting-and-thrusting operation has more significant effect on increasing the power of alpha and theta frequency bands as compared to laser acupuncture without the lifting-and-thrusting operation. Finally, given sufficient stimulation time (e.g., > 20 min), the performance of a low-powered laser acupuncture with the lifting-and-thrusting operation could be comparable to that of traditional needle acupuncture., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Kun-Chan Lan et al.)

Aim: To understand the prevalence of depressive symptoms among foreign caregivers and the associated factors., Design: A cross-sectional study., Methods: Data from 178 Indonesian foreign caregivers, selected based on convenience and snowball sampling in Taiwan, were collected between July 2019 and February 2020 using questionnaires. Stepwise multiple linear regression was used to identify the factors associated with depressive symptoms., Results: Approximately 30.3% of the foreign caregivers displayed depressive symptoms. The symptoms were more prevalent among the participants who were younger; had more social support; shared a bed with others; and experienced higher work-related stress, more loneliness and physical discomfort. The findings suggest that nurses or nurse practitioners visiting patients at home should not only deliver care for them but also show concern for the psychological well-being of the foreign caregivers of these patients. Moreover, interventions should be developed to alleviate or prevent the emergence of depressive symptoms among foreign caregivers., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Acupuncture plays an important role in traditional Chinese medicine (TCM) and is one kind of an inexpensive and effective treatment. However, some people might be reluctant to receive acupuncture treatment due to fear of pain. Laser acupuncture, thanks to its painless and infection-free advantages, has recently become an alternative choice to traditional acupuncture. The accuracy of acupuncture point positioning has a decisive influence on the quality of laser acupuncture. In this study, built on top of our prior work, we proposed a low-cost automated acupoint positioning system for laser acupuncture. By integrating several machine learning algorithms and computer vision techniques, we design and implement a robot-assisted laser acupuncture system on top of a smartphone. Our contributions include the following: (a) development of an effective acupoint estimation algorithm with a localization error less than 5 mm; (b) implementation of a smartphone-controlled automated laser acupuncture system with lift-thrust function, as a point-of-care device, that can be used by patients to relieve their symptoms at home., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Kun-Chan Lan et al.)

Currently, the majority of commercially available laser acupuncture instruments are still hand-held and only support single-point stimulation. Simultaneous multi-point stimulation improves the therapeutic efficacy of laser acupuncture by stimulating multiple acupoints at the same time. A "2-dimensional (2-D) galvo mirror" was utilized as a positioning laser acupuncture device for multi-acupoints stimulation. Due to its ability to perform 2-D fast scanning, a single laser beam was reflected by the mirror and stimulated multiple acupuncture points simultaneously. This introduction to the new system, presents its architecture, and shows some initial results. This initial stage of development was focused on the acupoints of the human forearm. This proposed system is the first low-cost, noncontact laser acupuncture system that enables continuous multi-acupoint stimulation with a single laser beam. Notably, it is technically feasible to develop this technique into a whole-body laser acupuncture stimulation system., Competing Interests: No financial conflicts of interest exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Acupuncture manipulation is one of the key factors affecting the performance of acupuncture in Traditional Chinese Medicine. Lift-thrust and twirl-twist are two of the most commonly used manipulation methods for needle acupuncture. We previously have developed a novel laser acupuncture model that emulates lift-thrust operation. In this study, we intend to show the effectiveness of such a model by applying it on the Neiguan acupoint (PC6). Stimulation was reported to be beneficial for improving cardiac output and peripheral circulation. Therefore, we hypothesized that the stimulation of laser acupuncture may increase the temperature of the subjects' fingertip due to increased peripheral blood flow. A thermal imager was used to measure the temperature change of subjects' fingertips. Through regression analysis, it has been shown that while PC6 is stimulated, laser acupuncture with lift-thrust operation caused a more rapid, stable, and lasting temperature rise of fingertip than that without lift-thrust operation. On the contrary, we observe no significant temperature change when a sham point nearby PC6 (a point which is not traditionally defined as the acupoint) was stimulated. Our results suggest the emulation of manipulation methods such as the lift-thrust operation could be a potential direction for the future development of laser acupuncture., Competing Interests: The authors declare no conflicts of interest regarding the publication of this work., (Copyright © 2019 Kun-Chan Lan et al.)

Objective: Using a case study to discuss the effects of traditional Chinese medicine (TCM) treatments on Type 1 diabetes mellitus., Clinical Features: A 4-year-old girl with sudden polyuria and nocturia (fasting plasma glucose level: 270mg/dL) was diagnosed with type 1 diabetes. Although multiple daily insulin injections were applied, her plasma glucose levels were still unstable. Therefore, she received a complementary TCM therapy by taking modified Liu-Wei-Di-Huang-Wan (3.0g/day; three times daily) for 3 months. After the treatments, her plasma glucose levels appeared to be more stable. HbA 1c 6.5% and insulin injections were reduced to only once a day., Conclusions: The results suggest that complementary TCM therapy has the ability to assist some patients with type 1 diabetes mellitus in controlling their plasma glucose levels., (Copyright © 2016. Published by Elsevier Ltd.)

Lifting and thrusting constitute an important manipulation method in traditional Chinese acupuncture. Lifting and thrusting enables the implementation of various features, such as reinforcement and reduction, which enhance acupuncture effectiveness. Laser acupuncture stimulates acupoints through laser light, which is a noninvasive treatment, but can still achieve effects similar to those obtained from traditional acupuncture. Lifting and thrusting can be achieved by moving the laser focal point back and forth, thus concentrating the energy, as does the tip of the acupuncture needle when it is moved upward and downward in the acupoint. This article presents a novel optical design of a laser acupuncture device, in which a focus-tunable lens is used to move the position of the focused light in order to achieve the lifting and thrusting mechanism through programmable changes to the control current of the focus-tunable lens. The device employs an infrared laser with a wavelength of 808 nm and a maximum power of 150 mW. The focus-tunable lens used in this study had a diopter of -10 to +5. The results revealed that by controlling the lens diopter, the focused light can be moved from 4.5 to 9.5 cm. Therefore, the range of the lift and thrust for the laser acupuncture device was 5 cm. The area of the focal point was approximately 6×10(-3) mm2, which is comparable to that of the commonly used traditional acupuncture needle tip. Because the components are immobile, no additional space is required for the moving lens. Therefore, the size of the laser acupuncture head can be minimized, and the effectiveness of focus tuning can be improved.

Silver nanoparticles have been used in various fields, and several synthesis processes have been developed. The stability and dispersion of the synthesized nanoparticles is vital. The present article describes a novel approach for one-step synthesis of silver nanoparticles-embedded chitosan particles. The proposed approach was applied to simultaneously obtain and stabilize silver nanoparticles in a chitosan polymer matrix in-situ. The diameter of the synthesized chitosan composite particles ranged from 1.7 mm to 2.5 mm, and the embedded silver nanoparticles were measured to be 15 ± 3.3 nm. Further, the analyses of ultraviolet-visible spectroscopy, energy dispersive spectroscopy, and X-ray diffraction were employed to characterize the prepared composites. The results show that the silver nanoparticles were distributed over the surface and interior of the chitosan spheres. The fabricated spheres had macroporous property, and could be used for many applications such as fungicidal agents in the future.

Floating treatment wetlands (FTWs) consist of emergent macrophytes that are placed on a floating mat in a pond for water treatment and aesthetic purposes. FTWs may have unique advantages with respect to treating urban runoff within existing retention ponds for excess nutrients. However, research is lacking in providing guidance on performance of specific species for treating urban runoff, and on timing of harvest. Harvesting is needed to remove nutrients permanently from the retention pond. We investigated vegetation effects on FTWs on nitrogen (N) and phosphorus (P) removal performance and storage in above-ground FTW macrophyte tissues. The study evaluated pickerelweed (PW, Pontederia cordata L.) and softstem bulrush (SB, Schoenoplectus tabernaemontani) over time in microcosms flushed with water obtained from a nearby urban retention pond in northern Virginia near Washington, DC. While the literature exhibits a wide range of experimental sizes, using the term mesocosm, we have chosen the term microcosm to reflect the small size of our vessel; and do not include effects of sediment. The experiment demonstrated PW outperformed SB for P and N removal. Based upon analysis of the accumulated nutrient removal over time, a harvest of the whole PW and SB plants in September or October is recommended. However, when harvesting only the aerial parts, we recommend harvesting above-ground PW tissues in July or August to maximize nutrient removal. This is because PW translocates most of its nutrients to below-ground storage organs in the fall, resulting in less nutrient mass in the above-ground tissue compared to the case in the summer (vegetative stage). Further research is suggested to investigate whether vegetation can be overly damaged from multiple harvests on an annual basis in temperate regions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel laser-acupuncture system was developed that can be used to implement the manipulation methods of traditional acupuncture, such as lifting and thrusting. A 780 nm laser diode with a maximum power of 90 mW was used as the light source. The focus point of the laser beam was adjustable by changing the position of the lens, facilitating the implementation of the lifting and thrusting methods of traditional Chinese medicine and achieving various stimulation depths at the acupuncture point. The images for the light spots from the outlet of the emulated laser acupuncture were captured at various distances and their sizes were calculated. The result showed that the diameter of the focused light spot (i.e., at the focus point) was 0.11 mm, which is close to the diameter of commonly used needles (with diameters of approximately 0.22 mm). The area of the light spot 1 cm from the focus point was approximately 50 times larger, indicating that the unit power might be 1/50 of the power of the focus point. To study the effect of emulated laser acupuncture on human meridians, after stimulating the Shenmen point (HT7) of five subjects and obtaining their Ryodoraku values of the heart meridian and the small-intestine meridian, a paired t test showed that the laser stimulation incorporating lifting and thrusting was significantly higher than the laser stimulation without lifting and thrusting (p<0.05). The result is consistent with traditional acupuncture in that acupuncture incorporating lift and thrust is more effective than that without lift and thrust.

We report dual pH-responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)-shell (chitosan) structure with dual pH-responsive drug release function. The fabricated core-shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core-shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core-shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core-shell microcapsules were a potential candidate of dual-drug carriers., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enzymes have a wide variety of applications in diverse biotechnological fields, and the immobilization of enzymes plays a key role in academic research or industrialization due to the stabilization and recyclability it confers. In this study, we immobilized the Brassica oleracea chlorophyllase 1 (BoCLH1) or Candida rugosa lipase (CRL) in magnetic iron oxide nanoparticles-loaded alginate composite beads. The catalytic activity and specific activity of the BoCLH1 and CRL entrapped in magnetic alginate composite beads were evaluated. Results show that the activity of immobilized BoCLH1 in magnetic alginate composite beads (3.36±0.469 U/g gel) was higher than that of immobilized BoCLH1 in alginate beads (2.96±0.264 U/g gel). In addition, the specific activity of BoCLH1 beads (10.90±1.521 U/mg protein) was higher than that immobilized BoCLH1 in alginate beads (8.52±0.758 U/mg protein). In contrast, the immobilized CRL in magnetic alginate composite beads exhibited a lower enzyme activity (11.81±0.618) than CRL immobilized in alginate beads (94.83±7.929), and the specific activity of immobilized CRL entrapped in magnetic alginate composite beads (1.99±0.104) was lower than immobilized lipase in alginate beads (15.01±1.255). A study of the degradation of magnetic alginate composite beads immersed in acidic solution (pH 3) shows that the magnetic alginate composite beads remain intact in acidic solution for at least 6 h, indicating the maintenance of the enzyme catalytic effect in low-pH environment. Finally, the enzyme immobilized magnetic alginate composite beads could be collected by an external magnet and reused for at least six cycles.

The application of floating treatment wetlands (FTWs) in point and non-point source pollution control has received much attention recently. Although the potential of this emerging technology is supported by various studies, quantifying FTW performance in urban retention ponds remains elusive due to significant research gaps. Actual urban retention pond water was utilized in this mesocosm study to evaluate phosphorus and nitrogen removal efficiency of FTWs. Multiple treatments were used to investigate the contribution of each component in the FTW system with a seven-day retention time. The four treatments included a control, floating mat, pickerelweed (Pontederia cordata L.), and softstem bulrush (Schoenoplectus tabernaemontani). The water samples collected on Day 0 (initial) and 7 were analyzed for total phosphorus (TP), total particulate phosphorus, orthophosphate, total nitrogen (TN), organic nitrogen, ammonia nitrogen, nitrate-nitrite nitrogen, and chlorophyll-a. Statistical tests were used to evaluate the differences between the four treatments. The effects of temperature on TP and TN removal rates of the FTWs were described by the modified Arrhenius equation. Our results indicated that all three FTW designs, planted and unplanted floating mats, could significantly improve phosphorus and nitrogen removal efficiency (%, E-TP and E-TN) compared to the control treatment during the growing season, i.e., May through August. The E-TP and E-TN was enhanced by 8.2% and 18.2% in the FTW treatments planted with the pickerelweed and softstem bulrush, respectively. Organic matter decomposition was likely to be the primary contributor of nutrient removal by FTWs in urban retention ponds. Such a mechanism is fostered by microbes within the attached biofilms on the floating mats and plant root surfaces. Among the results of the four treatments, the FTWs planted with pickerelweed had the highest E-TP, and behaved similarly with the other two FTW treatments for nitrogen removal during the growth period. The temperature effects described by the modified Arrhenius equation revealed that pickerelweed is sensitive to temperature and provides considerable phosphorus removal when water temperature is greater than 25 °C. However, the nutrient removal effectiveness of this plant species may be negligible for water temperatures below 15 °C. The study also assessed potential effects of shading from the FTW mats on water temperature, DO, pH, and attached-to-substrate periphyton/vegetation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This paper demonstrates a simple and easy approach for the one-step synthesis of Fe₃O₄-chitosan composite particles with tadpole-like shape. The length and diameter of the particles were adjustable from 638.3 μm to ca. 798 μm (length), and from 290 μm to 412 μm (diameter) by varying the flow rate of the dispersed phase. Mitoxantrone was used as the model drug in the drug release study. The encapsulation rate of the drug was 71% for chitosan particles, and 69% for magnetic iron oxide-chitosan particles, respectively. The iron oxide-chitosan composite particles had a faster release rate (up to 41.6% at the third hour) than the chitosan particles (about 24.6%). These iron oxide-chitosan composite particles are potentially useful for biomedical applications, such as magnetic responsive drug carriers, magnetic resonance imaging (MRI) enhancers, in the future., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A core-shell gelatin-alginate composite used for intestine-released oral delivery drug carrier was synthesized through microfluidic technique. At the fixed continuous phase flow rate, the size of the core-shell gelatin-alginate microparticles increases with the dispersed phase flow rate, and monodispersity can be retained (the variation coefficient for the diameter distribution can be kept less than 10%). The fabricated microparticles could remain intact in gastric juice for at least 3 h, indicating that the gelatin core could be well protected by alginate shell in acid environment. However, the alginate shell of the microparticles would swell or collapse in alkali environment in half an hour, assuring the controlled drug release in intestinal juice. The fabricated uniform core-shell gelatin-alginate microparticles were potential as pH-responsive drug carriers., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Applications of poly(l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA) microspheres are widely used in the biomedical and pharmaceutical fields. The effects of PLA/PLGA on microsphere properties when using conventional particulate preparation methods are not easily defined due to the uncontrollable particle size and size distribution. This study was aimed to synthesize uniform PLA and PLGA microspheres using a phenol formaldehyde resin-based microfluidic chip, which has the advantage of being solvent-resistant, flexible, and is readily disassembled for cleaning. The proposed chip can rapidly fabricate reproducible PLA and PLGA microspheres. Uniform emulsion droplets can be achieved by hydrodynamic flow focusing. After solvent evaporation, the free-flowing PLA and PLGA microspheres have a high level of morphological uniformity and size, allowing for a clear comparison of material effects. The results indicate that the sizes of the PLA and PLGA microspheres for the various flow rates of dispersed/continuous phases are very similar. The PLA/PLGA materials do not have a significant effect on particle size, but the particle surface indicates a different morphology. The result of the cytotoxicity evaluation shows no difference between PLA and PLGA and ensures the biocompatibility of both prepared PLA and PLGA microspheres for biomedical and pharmaceutical applications in the future., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bacterial and cancer cells that are resistant to current specific therapy have become an increasingly important public health problem over the past several decades. Consequently, the search for new anti-infection and anti-cancer treatments of drug resistant microbes has attracted a lot of attention. Recently, nanostructures have been shown to be efficient antimicrobial agents that do not induce drug-resistance. The present study reviews the advances in anti-pathogenic bio-hybrid nanostructures over the past decade. Three important issues are presented and discussed. First, the review focuses on the anti-pathogenic activity of the most common types of metallic / metal oxide nanoparticles. It not only reviews the progress of antimicrobial characteristics for various types of nanoparticles under different fabrication processes, but it also tabulates some specific findings over the past decade. Secondly, it reviews the use of polymeric, gold and iron-oxide nanoparticles as effective chemotheraputic drug carriers or for gene transduction in cancer treatment. Finally, some new advances made in Taiwan in anti-pathogenic research using nanotechnology were addressed in brief at the end of this paper. We highlighted the advances of the photo-controlled targeted drug-delivery system and the development of nanoparticles of traditional Chinese herbs, both of which representing important milestones in the last decade.

This study develops a new solvent-compatible microfluidic chip based on phenol formaldehyde resin (PFR). In addition to its solvent-resistant characteristics, this microfluidic platform also features easy fabrication, organization, decomposition for cleaning, and reusability compared with conventional chips. Both solvent-dependent (e.g., polycaprolactone) and nonsolvent-dependent (e.g., chitosan) microparticles were successfully prepared. The size of emulsion droplets could be easily adjusted by tuning the flow rates of the dispersed/continuous phases. After evaporation, polycaprolactone microparticles ranging from 29.3 to 62.7 μm and chitosan microparticles ranging from 215.5 to 566.3 μm were obtained with a 10% relative standard deviation in size. The proposed PFR microfluidic platform has the advantages of active control of the particle size with a narrow size distribution as well as a simple and low cost process with a high throughput.

Oil-chitosan composite spheres were synthesized by encapsulation of sunflower seed oil in chitosan droplets, dropping into NaOH solution and in situ solidification. Hydrophilic materials (i.e., iron oxide nanoparticles) and lipophilic materials (i.e., rhodamine B or epirubicin) could be encapsulated simultaneously in the spheres in a one step process. The diameters of the prepared spheres were 2.48 ± 0.11 mm (pure chitosan spheres), 2.31 ± 0.08 mm (oil-chitosan composites), 1.49 ± 0.15 mm (iron-oxide embedded oil-chitosan composites), and 1.69 ± 0.1 mm (epirubicin and iron oxide encapsulated oil-chitosan composites), respectively. Due to their superparamagnetic properties, the iron-oxide embedded oil-chitosan composites could be guided by a magnet. A lipophilic drug (epirubicin) could be loaded in the spheres with encapsulation rate measured to be 72.25%. The lipophilic fluorescent dye rhodamine B was also loadable in the spheres with red fluorescence being observed under a fluorescence microscope. We have developed a novel approach to an in situ process for fabricating oil-chitosan composite spheres with dual encapsulation properties, which are potential multifunctional drug carriers.

This paper demonstrates a facile approach for the in situ synthesis of size-controllable superparamagnetic chitosan micro-beads with a saturation magnetization value as high as ca. 35.3 emu g -1 at room temperature. The proposed process utilized the electrostatic droplets (ESD) technique, which is quite effective in producing uniform-sized polymer beads. A sodium hydroxide solution was employed for both the solidification of chitosan and the co-precipitation of ferro-gels containing both ferrous and ferric cations. The diameter of the beads was very uniform (each relative standard deviation was below 3.4%) and adjustable from 84 μm to ca. 555 μm by varying the electrostatic field. Cell viability tests indicated that the superparamagnetic chitosan particles were eco-friendly and had a high potential for biological applications. The results show that the superparamagnetic chitosan particles achieved superior results in magnetic-responsive drug release as well as heavy metal removal (e.g. copper ions). This study demonstrated that the appropriate magnetic field intensity for different release patterns is predictable, which allows for better application of microcapsules as a smart drug carrier. In addition, the proposed chitosan particles serve as an alternative material for the adsorption of heavy metal ions from contaminated industrial effluents, while their superparamagnetic properties are advantageous in that they make the chitosan particles guidable by an external magnetic field.

This study reports a facile method for the synthesis of hemispherical and discoidal chitosan microparticles by a combination of microfluidic technology and gelation strategy at an oil/water interface. Utilizing microfluidic emulsification in a cross-junction channel, the formation of regular droplets was achieved. Following the ionic gelation procedure at the liquid-liquid interface of the gelling solution and oil solution in the reservoir pool, either hemispherical or discoidal chitosan microparticles were obtained. Special emphasis was put on the interface reaction of emulsion gelation parameters such as ionic crosslinkers, density modifiers, and surfactants, to tailor the morphologies of chitosan particles ranging from 160 to 750 μm. In addition, the proposed microfluidic device is capable of generating relatively uniform microparticles with a well-controllable shape and size. Being a simple, low-cost and high-throughput process is an added advantage. The synthesized hemispherical and discoidal chitosan microparticles can be applied to many applications in the pharmaceutical and biomedical arena., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of the in vitro study show that an approx. 30% higher drug release rate was obtained by using continuous ultrasound irradiation (9-Watt, 180 min), and an approx. 16% higher drug release rate was obtained by using pulsatile ultrasound irradiation (9-Watt, 60 min) compared to without ultrasound activation. For the in vivo study, the anti-inflammatory test with carrageenan-induced rat's paw edema shows that diclofenac-loaded microcapsules followed by ultrasound irradiation (9-Watt, 60 min) contributed to an 81% inhibition rate, which was significantly higher than diclofenac only (approx. 60% higher). In addition, because of their heat conducting properties, gold nanoparticles encapsulated in the diclofenac-loaded microcapsules resulted in better drug release efficiency, but tended to depress the anti-inflammation effect., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This study presents the development of a robust aluminum-based microfluidic chip fabricated by conventional mechanical micromachining (computer numerical control-based micro-milling process). It applied the aluminum-based microfluidic chip to form poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating CdSe/ZnS quantum dots (QDs). A cross-flow design and flow-focusing system were employed to control the oil-in-water (o/w) emulsification to ensure the generation of uniformly-sized droplets. The size of the droplets could be tuned by adjusting the flow rates of the water and oil phases. The proposed microfluidic platform is easy to fabricate, set up, organize as well as program, and is valuable for further applications under harsh reaction conditions (high temperature and/or strong organic solvent systems). The proposed method has the advantages of actively controlling the droplet diameter, with a narrow size distribution, good sphericity, as well as being a simple process with a high throughput. In addition to the fluorescent PLGA microparticles in this study, this approach can also be applied to many applications in the pharmaceutical and biomedical area.

Macroporous chitosan spheres encapsulating superparamagnetic iron oxide nanoparticles were synthesized by a facile and effective one-step fabrication process. Ferro-gels containing ferrous cations, ferric cations and chitosan were dropped into a sodium hydroxide solution through a syringe pump. In addition, a sodium hydroxide solution was employed for both gelation (chitosan) and co-precipitation (ferrous cations and ferric cations) of the ferro-gels. The results showed that the in-situ co-precipitation of ferro-ions gave rise to a radial morphology with non-spheroid macro pores (large cavities) inside the chitosan spheres. The particle size of iron oxide can be adjusted from 2.5 nm to 5.4 nm by tuning the concentration of the sodium hydroxide solution. Using Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra, the synthesized nanoparticles were illustrated as Fe(3)O(4) nanoparticles. In addition, the prepared macroporous chitosan spheres presented a super-paramagnetic behaviour at room temperature with a saturation magnetization value as high as ca. 18 emu/g. The cytotoxicity was estimated using cell viability by incubating doses (0∼1000 µg/mL) of the macroporous chitosan spheres. The result showed good viability (above 80%) with alginate chitosan particles below 1000 µg/mL, indicating that macroporous chitosan spheres were potentially useful for biomedical applications in the future.

This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture.

This paper demonstrates a proof-of-concept approach for encapsulating the insulin and Fe3O4 nanoparticles into size-controllable alginate microcapsules utilizing the electrostatic droplets (ESD) technique. We have established that the combination of ESD and external gelation is quite effective in producing uniform-sized polymer particles. In addition, using the external gelation technique, the droplets containing a sodium-alginate were gelled in situ by immersion in Ca(2+), Ba(2+), or Cu(2+) ions for a few minutes. The results show that different-type divalent cations caused various surface features to appear on the microcapsules (e.g., cracking, orange peel, pitting, splitting, wrinkling, etc.). The particle size can be adjusted from a few micrometers to ca. 1,000 μm by electrostatic force. The microcapsules can be made magnetic by incorporating a super-paramagnetic nanomaterial (e.g., Fe3O4 nanoparticles) during the preparation. The composite magnetic microcapsules are potential candidates for a magnetic-responsive drug delivery system. In addition, our results show that the encapsulation and in vitro release of a model drug, insulin, can enhance the effect of the controlled release. These microcapsules are addressable by an external magnetic field and are capable of loading a model drug and releasing it in a highly differential drug release profile. We have demonstrated that the appropriate magnetic field intensity for different release patterns is predictable, which enables a better application of microcapsules as a smart drug carrier.

Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R∕B ratio, and R∕G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R∕G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

We investigate the possibility of using ALA-derived PpIX fluorescence spectroscopy for the detection of epithelial hyperkeratosis (EH) or epithelial dysplasia (ED) lesions in oral submucous fibrosis (OSF) patients that could not be found by autofluorescence spectroscopy. Twenty percent of ALA solution gel was applied onto oral neoplasia and surrounding normal tissue [normal oral mucosa (NOM)] for 90 min. Fluorescence emission spectra were measured under 410 nm excitation. Generally, the most intense fluorescence emission peaks occurred at 460 and 630 nm. The ratios of the area under red peak (630+/-10 nm) to the area under blue peak (460+/-10 nm), denoted as RB, were calculated. We found that OSF mucosa has the lowest RB value, followed by NOM, EH on OSF, and ED on OSF. An ANOVA test showed significant differences between OSF, NOM, EH on OSF, and ED on OSF (p<0.05). However, measurements of autofluorescence (i.e., before ALA application) show no significant differences between OSF, NOM, EH on OSF, and ED on OSF (ANOVA test, p>0.05). These results indicate that ALA-induced PpIX fluorescence spectroscopy could be used to identify the premalignant lesions on oral fibrotic mucosa, which could not be found by autofluorescence.

The pseudobulb of Oncidium orchid is a storage organ for supplying water, minerals and carbohydrates to the developing inflorescence. Different patterns of mannan, starch and pectin metabolism were observed in the pseudobulb of three developmental stages by histochemical staining and high performance anion exchange chromatographic (HPAEC) analysis. Copious pectin was strongly stained by ruthenium red in young pseudobulbs demonstrating that mannan and pectin were preferentially accumulated in the young pseudobulb sink at inflorescence pre-initiation stage. Concomitant with the emergence of the inflorescence, mannan and pectin decreased gradually and converted to starch. The starch, synthesized at the inflorescence developing stage, was eventually degraded at the floral development stage. A systematic survey on the subtractive EST (expression sequence tag) library of pseudobulb in the inflorescence pre-initiation stage revealed the presence of five groups of gene homologues related to sucrose, mannan, starch, pectin and other carbohydrate metabolism. The transcriptional level of 13 relevant genes related to carbohydrate metabolism was characterized from pseudobulbs of three different developmental stages. The specific activities of the enzymes encoded by these genes were also assayed. The expression profiles of these genes show that the transcriptional levels largely correlated with the enzyme activities, which were associated with the respective carbohydrate pools. These results demonstrated a novel functional profile of polysaccharide mobilization pathway as well as their relevant gene expression in the pseudobulb of Oncidium orchid during the flowering process.

We compared the performance of three widely used linear multivariate methods for autofluorescence spectroscopic tissues differentiation. Principal component analysis (PCA), partial least squares (PLS), and multivariate linear regression (MVLR) were compared for differentiating at normal, tubular adenoma/epithelial dysplasia and cancer in colorectal and oral tissues. The methods' performances were evaluated by cross-validation analysis. The group-averaged predictive diagnostic accuracies were 85% (PCA), 90% (PLS), and 89% (MVLR) for colorectal tissues; 89% (PCA), 90% (PLS), and 90% (MVLR) for oral tissues. This study found that both PLS and MVLR achieved higher diagnostic results than did PCA.

Background and Objectives: Time-resolved autofluorescence spectroscopy has been used for effectively distinguishing normal tissues from precancers and cancers in various organs. The aim of this study was to find out the possibility of using time-resolved autofluorescence spectroscopy to differentiate normal oral mucosa (NOM) from oral premalignant lesions including verrucous hyperplasia (VH), epithelial hyperplasia (EH), and epithelial dysplasia (ED)., Study Design/materials and Methods: Time-resolved autofluorescence spectra at 633 nm under 410-nm excitation were recorded for 15 VH, 9 EH, 14 ED, and 38 NOM samples. The two-component lifetimes of the obtained curves were calculated, and a Fisher's discriminant analysis (FDA) was employed for distinguishing these tissue samples., Results: After two-component lifetimes for all samples being calculated, a two-dimensional scatter plot was developed, in which 76 oral tissue samples were separated into three groups by FDA. With a leave-one-out method, the FDA algorithm gave an accuracy rate of 93% for ED, of 75% for VH and EH, and of 100% for NOM samples. In addition, all oral premalignant lesions (including VH, EH, and ED) could be distinguished from NOM samples by this FDA algorithm., Conclusions: We conclude that time-resolved autofluorescence spectroscopy at 633 nm under 410-nm excitation, based on two-component lifetime calculation and FDA, is a very sensitive technique for in vivo diagnosis of oral premalignant lesions. ., ((c) 2005 Wiley-Liss, Inc)

Background: Oral submucous fibrosis (OSF) is a chronic oral mucosal disease characterized by progressive deposition of collagen in the subepithelial connective tissue and epithelial atrophy. Previous studies have shown that at 330-nm excitation, the 380- and 460-nm emission peaks of the auto-fluorescence spectra for oral mucosal tissues reflect the collagen content in the subepithelial connective tissue and the nicotinamide adenine dinucleotide phosphate (NADH) content in the epithelial cells, respectively. Therefore, at 330-nm excitation OSF mucosa may have a higher 380-nm emission peak and a lower 460-nm emission peak than the normal oral mucosa (NOM)., Methods: To test the above hypothesis, we measured the in vivo auto-fluorescence spectra of 59 OSF mucosal sites and compared the measured spectra with auto-fluorescence spectra obtained from 15 NOM samples from 15 healthy volunteers, five samples of friction hyperkeratosis (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (FHOSF), and 29 samples of oral leukoplakia (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (OLOSF)., Results: We found that the spectrum of the OSF mucosa had a significantly higher 380-nm emission peak and a significantly lower 460-nm emission peak than the spectra of NOM, FHOSF, and OLOSF samples. When the mean (+/-SD) fluorescence intensities at 380 +/- 15 nm (I380 +/- 15 nm) and 460 +/- 15 nm (I460 +/- 15 nm) emission peaks and the mean ratio of I460 +/- 15 nm/I380 +/- 15 nm were compared between groups, we found that OSF group had a significantly higher mean value of I380 +/- 15 nm, a significantly lower mean value of I460 +/- 15 nm, and a significantly lower mean ratio of I460 +/- 15 nm/I380 +/- 15 nm than the NOM, FHOSF, and OLOSF groups (P < 0.001). However, no significant differences in the mean values of I380 +/- 15 nm, I460 +/- 15 nm, and ratio of I460 +/- 15 nm/I380 +/- 15 nm were found between NOM and FHOSF or OLOSF samples as well as between FHOSF and OLOSF samples (P > 0.05)., Conclusion: Because OSF mucosa has a very unique pattern of auto-fluorescence spectrum, we conclude that auto-fluorescence spectroscopy is a good method for real-time diagnosis of OSF.

Background and Objectives: For effective management of oral neoplasia, autofluorescence spectroscopy was conducted on patients with different characteristics of oral lesions in vivo. This study tested the possibility of using a multivariate statistical algorithm to differentiate human oral premalignant and malignant lesions from benign lesions or normal oral mucosa., Study Design/materials and Methods: A fiber optics-based fluorospectrometer was used to measure the autofluorescence spectra from healthy volunteers (NOM) and patients with oral lesions of submucous fibrosis (OSF), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). A partial least-squares and artificial neural network (PLS-ANN) classification algorithm was used to characterize these oral lesions to discriminate premalignant (ED) and malignant (SCC) tissues from "benign" (NOM, OSF, and EH) tissues., Results: The normalized and centerized spectra of the different kinds of samples showed similar but divergent patterns. Our PLS-ANN classification algorithm could differentiate "premalignant and malignant" tissues from "benign" tissues with a sensitivity of 81%, a specificity of 96%, and a positive predictive value of 88%., Conclusions: We conclude that the PLS-ANN classification algorithm based on autofluorescence spectroscopy at 330-nm excitation is useful for in vivo diagnosis of OSF as well as oral premalignant and malignant lesions., (Copyright 2003 Wiley-Liss, Inc.)

Background and Objectives: To test whether autofluorescence spectroscopy can be used for the diagnosis of oral neoplasia in a high-risk population, we characterized the in vivo autofluorescence spectra from oral submucous fibrosis (OSF) lesions and oral premalignant and malignant lesions in both OSF and non-OSF patients., Study Design/materials and Methods: Autofluorescence emission spectra were measured under the excitation wavelength of 330 nm, using a Xenon lamp-based fluorospectrometer coupled to a handheld optical fiber probe. Autofluorescence spectroscopies were analyzed among patients with OSF lesions, and oral lesions of epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinomas (SCC) and normal oral mucosa (NOM) of healthy volunteers., Results: We found that the most intensely autofluorescence emission peaks occurred at 380 nm and 460 nm. For comparing the spectral patterns among different groups of oral lesions and NOM, ratios of the area under the spectrum of 460+/-10 nm to that under the spectrum of 380+/-10 nm (denoted as A(460+/-10nm)/A(380+/-10nm)) were calculated. The mean ratio values increased gradually from OSF to NOM, to EH and ED, and to SCC. The ANOVA test showed significant differences in the ratio value among all categories of samples (P<0.01). On the other hand, we found that EH, ED, and SCC lesions on OSF patients had distorted autofluorescence intensity. The mean ratio values of EH, ED, and SCC between non-OSF and OSF patients show significant differences. Furthermore, an ANOVA test showed NOM is not distinguishable from EH and ED lesions on oral fibrotic mucosa (P>0.05)., Conclusions: Autofluorescence spectroscopy can be used to diagnose EH, ED, and SCC lesions in non-OSF patients but not in OSF patients., (Copyright 2003 Wiley-Liss, Inc.)

Background: Our previous ex vivo study has shown that autofluorescence spectroscopy at 330-nm excitation can discriminate specimens of normal buccal pouch mucosa (normal), epithelial hyperkeratosis (hyperkeratosis), epithelial dysplasia (dysplasia), and squamous cell carcinoma (SCC) taken from DMBA-treated hamsters by using the method of partial least-squares discriminant analysis (PLSDA)., Methods: This study used a fiber optics-based fluorescence spectroscopy system to measure the autofluorescence spectra of 23 normal, 14 hyperkeratosis, 28 dysplasia, and 10 SCC samples in vivo. PLSDA with cross-validation was used to analyze the autofluorescence spectral data of all samples., Results: We found that at 330-nm excitation, the autofluorescence spectra of all samples had two main peaks: one at 380 nm and the other at 460 nm. The hyperkeratosis samples had a higher 380-nm emission peak (EP) and a lower 460-nm EP than normal samples. On the contrary, the dysplasia samples had a lower 380-nm EP and a higher 460-nm EP than normal samples. Furthermore, the SCC samples had a much lower 380-nm EP and a much higher 460-nm EP than all other samples. To quantify the spectral changes during the progression of oral carcinogenesis, ratios of the area under the spectrum of 380 +/- 15 nm to that under the spectrum of 460 +/- 15 nm (denoted as A(380 +/- 15 nm)/A(460 +/- 15 nm)) for all samples were calculated. The mean ratio values of A(380 +/- 15 nm)/A(460 +/- 15 nm) decreased gradually from hyperkeratosis to normal, to dysplasia, and to SCC samples. Significant differences in this mean ratio were found between any two groups of normal, hyperkeratosis, dysplasia, and SCC samples. By choosing proper thresholds, PLSDA with cross-validation could provide an accurate identification rate of 86% for hyperkeratosis, of 87% for normal, and of 89% for dysplasia samples. In addition, by choosing a proper threshold, we could separate benign (normal and hyperkeratosis) from dysplasia or SCC tissues with a sensitivity of 92% and a specificity of 95%., Conclusion: Our results indicate that the autofluorescence spectroscopy technique is a useful diagnostic tool for in vivo diagnosis of oral pre-cancers and cancers in DMBA-induced hamster buccal pouch carcinogenesis model.