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Hsin-Yi Huang,1,2,* Ming-Chen Wang,2,* Zhi-Yu Chen,1 Wen-Ying Chiu,1 Ko-Hua Chen,3,4 I-Chan Lin,4,5 Wei-Chung Vivian Yang,6 Chi-Chang Wu,7 Ching-Li Tseng1,8,9 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan; 3Department of Ophthalmology, Taipei Veterans General Hospital, Taipei City, Taiwan; 4Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan; 5Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 6PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan; 7Department of Electronic Engineering, Feng Chia University, Taichung City, Taiwan; 8International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan; 9International PhD Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan *These authors contributed equally to this work Introduction: Dry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye. Methods: To explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin–epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated “GEH”. The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit’s model. Results: The synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of IL1B and IL6 in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered. Conclusion: We successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES. Keywords: gelatin nanoparticles, epigallocatechin gallate, EGCG, hyaluronic acid, HA, dry-eye syndrome, DES, anti-inflammation

Medical device-associated infection remains a critical problem in the healthcare setting. Different clinical- or device-related methods have been attempted to reduce the infection rate. Among these approaches, creating a surface with bactericidal cationic functionality has been proposed. To do so, a sophisticated multi-step chemical procedure would be needed. Instead, a simple immersion approach was utilized in this investigation to render the titanium and polypropylene surface with the quaternary ammonium functionality by using a mussel-inspired novel lab-synthesized biomimetic catechol-terminated polymer, PQA-C8. The chemical oxidants, CuSO 4 /H 2 O 2 , as well as dopamine, were added into the novel PQA-C8 polymer immersion solution for one-step surface modification. Additionally, a two-step immersion scheme, in which the polypropylene substrate was first immersed in the dopamine solution and then in the PQA-C8 solution, was also attempted. Surface analysis results indicated the surface characteristics of the modified substrates were affected by the immersion solution formulation as well as the procedure utilized. The antibacterial assay has shown the titanium substrates modified by the one-step dopamine + PQA-C8 mixtures with the oxidants added and the polypropylene modified by the two-step scheme exhibited bacterial reduction percentages greater than 90% against both Gram-positive S. aureus and Gram-negative E. coli and these antibacterial substrates were non-cytotoxic.

Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Triple-negative breast cancer (TNBC) represents a formidable challenge due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, rendering it unresponsive to conventional hormonal and targeted therapies. This study introduces the development of mesoporous nanoreactors (NRs), specifically mPDA@CuO 2 NRs, as acid-triggered agents capable of self-supplying H 2 O 2 for chemodynamic therapy (CDT). To enhance therapeutic efficacy, these NRs were further modified with immune checkpoint antagonists, specifically anti-PD-L1 and anti-CD24 antibodies, resulting in the formation of dual antibody-aided mesoporous nanoreactors (dAb PD-L1/CD24 -mPDA@CuO 2 NRs). These NRs were designed to combine CDT and checkpoint blockade immunotherapy (CBIT) for precise targeting of 4T1 TNBC cells. Remarkably, dAb PD-L1/CD24 -mPDA@CuO 2 NRs exhibited tumor-targeted CDT triggered by H 2 O 2 and successfully activated immune cells including T cells and macrophages. This integrated approach led to a remarkable inhibition of tumor growth by leveraging the collaborative effects of the therapies. The findings of this study introduce a novel and promising strategy for the integrative and collaborative treatment of refractory cancers, providing valuable insights into addressing the challenges posed by aggressive breast cancer, particularly TNBC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Vesicular trafficking involving SNARE proteins play a crucial role in the delivery of cargo to the target membrane. Arf-like protein 1 (Arl1) is an important regulator of the endosomal trans -Golgi network (TGN) and secretory trafficking. In yeast, ER stress-enhances Arl1 activation and Golgin Imh1 recruitment to the late-Golgi. Although Arl1 and Imh1 are critical for GARP-mediated endosomal SNARE-recycling transport in response to ER stress, their downstream effectors are unknown. Here, we report that the SNARE-associated protein Sft2 acts downstream of the Arl1-Imh1 axis to regulate SNARE recycling upon ER stress. We first demonstrated that Sft2 is required for Tlg1/Snc1 SNARE-recycling transport under tunicamycin-induced ER stress. Interestingly, we found that Imh1 regulates Tlg2 retrograde transport to the late-Golgi under ER stress, which in turn is required for Sft2 targeting to the late-Golgi. We further showed that Sft2 with 40 amino acids deleted from the N-terminus exhibits defective mediation of SNARE recycling and decreased association with Tlg1 under ER stress. Finally, we demonstrated that Sft2 is required for GARP-dependent endosome-to-Golgi transport in the absence of Rab protein Ypt6. This study highlights Sft2 as a critical downstream effector of the Arl1-Imh1 axis, mediating the endosome-to-Golgi transport of SNAREs.

Background: The public health strategy of increasing access to comprehensive home or community-based healthcare services and emergency home visits is intent on reducing the overcrowding of emergency departments. However, scientific evidence regarding the association between home-based healthcare services and emergency department uses is surprisingly insufficient and controversial so far. The present retrospective study identified the risk factors for emergency department visits among patients receiving publicly-funded homecare services., Methods: The personal demographic and medical information, caregiver characteristics, and behaviours related to homecare services and emergency department visits from the medical records and structured questionnaires of 108 patients who were recipients of integrated homecare services in a regional hospital in southern Taiwan between January 1, 2020, and December 31, 2020, were collected. After screening the potential predictor variables using the preliminary univariate analyses, the multivariate logistic regression with best subset selection approach was conducted to identify best combination of determinants to predict unplanned emergency department utilizations., Results: Best subset selection regression analysis showed Charlson Comorbidity Index (odds ratio (OR)=1.33, 95% CI=1.05 to 1.70), male caregiver (OR=0.18, 95% CI=0.05 to 0.66), duration of introducing homecare services (OR=0.97, 95% CI=0.95 to 1.00), working experience of dedicated nurses (OR=0.89, 95% CI=0.79 to 0.99) and number of emergency department utilizations within previous past year before enrollment (OR=1.54, 95% CI=1.14 to 2.10) as significant determinants for unplanned emergency department visits., Conclusions: The present evidence may help government agencies propose supportive policies to improve access to integrated homecare resources and promote appropriate care recommendations to reduce unplanned or nonurgent emergency department visits among patients receiving homecare services., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

When it comes to predicting experimental values of molecular properties with deep learning, the key problem is the lack of sufficient experimental data for training. We propose a method that consists of pretraining a graph neural network that aims to reproduce first-principles quantum mechanical results, followed by fine-tuning of a fully connected neural network against experimental results. The combined pretraining and fine-tuning model is expected to yield molecular properties close to experimental accuracy. This is made possible because first-principles quantum mechanical methods are often qualitatively correct or semiquantitatively accurate; thus, a calibration of the calculation results against high-precision but limited experiment data can improve accuracy greatly. Moreover, the method is highly efficient, as first-principles quantum mechanical calculation is bypassed. To demonstrate this, we apply the combined model to determine the experimental heats of formation of organic molecules made of H, C, O, N, or F atoms (up to 30 atoms), where mere 405 experimental data are used. The overall mean absolute error is 1.8 kcal/mol for these molecules.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Researchers have emphasized the importance of examining how different factors affect men's and women's functional status over time. To date, the literature is unclear about whether sex affects the rate of change in disability in middle to older age. Researchers have further emphasized the importance of examining how different factors affect men's and women's functional status over time. We examined (a) sex differences in disability trends and (b) the determinants of the rate of change in disability for men and women 50 years and older., Methods: This study utilized the Taiwan Longitudinal Study on Aging Survey, a nationally representative database (four waves of survey data 1996-2007, N = 3429). We modeled and compared the differences in disability trends and the influences of determinants on trends among men and women using multiple-indicator and multiple-group latent growth curves modeling (LGCM). Equality constraints were imposed on 10 determinants across groups., Results: Once disability began, women progressed toward greater disability 18% faster than men. Greater age added about 1.2 times the burden to the rate of change in disability for women than men (p < 0.001). More comorbidities also added significantly more burden to baseline disability and rate of change in disability among women than men (p < 0.001), but women benefited more from higher education levels in lower baseline disability and slower rate of change. Having a better social network was associated with lower baseline disability among women only (p < 0.05). For both men and women, physically active leisure-time activities were beneficial in lower baseline disability (p men and women  < 0.001) and rate of change in disability (p men  < 0.01; p women  < 0.05), with no significant differences between groups., Conclusions: Age may widen the sex gap in the rate of change in disability. However, both sexes benefit from participating in leisure-time activities. Promoting health literacy improves health outcomes and physical function among women., (© 2021. The Author(s).)

Background/purpose: Anti-resorptive agents are commonly used in cancer patients with bone metastasis or multiple myeloma (MM). An adverse event termed medication-related osteonecrosis of the jaws (MRONJ) was discovered in patients using these agents but relatively little attention has been paid to its prognosis. Our aims were to find out the treatment outcomes and prognostic indicators of MRONJ in cancer patients who received zoledronic acid as antiresorptive therapy., Methods: We retrospectively surveyed a cohort of 133 cancer patients who received zoledronic acid. A total of 150 MRONJ lesions were included for investigation. Cumulative complete response rate after treatment was calculated with the Kaplan-Meier method, and significance was examined with the log-rank tests. Cox regression was used for univariate and multivariate analyses of prognostic factors., Results: The cumulative complete response rate of all patients at 24 months was 53.2%, and those of patients with MM, breast cancer and prostate cancer were 27.8%, 60.7% and 68.0%, respectively. Having MM was identified as an independent prognostic factor in a multivariate analysis with adjusted hazard ratios of 0.28 (95% confidence interval, 0.09-0.83)., Conclusion: For cancer patients with ONJ related to zoledronic acid, patients with MM endure a worse treatment outcome., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study analysed the landing performance and muscle activity of athletes in forefoot strike (FFS) and rearfoot strike (RFS) patterns. Ten male college participants were asked to perform two foot strikes patterns, each at a running speed of 6 km/h. Three inertial sensors and five EMG sensors as well as one 24 G accelerometer were synchronised to acquire joint kinematics parameters as well as muscle activation, respectively. In both the FFS and RFS patterns, according to the intraclass correlation coefficient, excellent reliability was found for landing performance and muscle activation. Paired t tests indicated significantly higher ankle plantar flexion in the FFS pattern. Moreover, biceps femoris (BF) and gastrocnemius medialis (GM) activation increased in the pre-stance phase of the FFS compared with that of RFS. The FFS pattern had significantly decreased tibialis anterior (TA) muscle activity compared with the RFS pattern during the pre-stance phase. The results demonstrated that the ankle strategy focused on controlling the foot strike pattern. The influence of the FFS pattern on muscle activity likely indicates that an athlete can increase both BF and GM muscles activity. Altered landing strategy in cases of FFS pattern may contribute both to the running efficiency and muscle activation of the lower extremity. Therefore, neuromuscular training and education are required to enable activation in dynamic running tasks.

Background: The literature emphasizes the importance of matching the demand and supply of endocrinology and metabolism (EM) specialists. This study analyzed the current status of EM specialists in Taiwan. The gender effects on the workplace of EM specialists were also evaluated., Methods: The number of internal medicine (IM) specialists was obtained from the websites of the Ministry of Health and Welfare. Data about EM specialists were retrieved from the database of the Endocrine Society of the Republic of China (ESROC; Taiwan). Differences in age distribution and workplace levels or locations between female and male EM specialists were analyzed., Results: Since 1988, 809 physicians were certified as EM specialists. The average age of 739 EM specialists (509 male, 230 female) who remained as active members of the ESROC was 49.9 ± 11.1 years. The age distribution (p < 0.001) and workplace location (p = 0.043) were significantly different between male and female EM specialists. Divided by decades, the ratio of female-to-male EM specialists revealed an increasing tendency (p < 0.001). The percentage of EM specialists among IM specialists, certified 2 years previously, declined from 14.0% in 2017 to 7.9% and 8.3% in 2018 and 2019, respectively., Conclusion: The female-to-male ratio of EM specialists increased gradually. Compared to males, female EM specialists were relatively younger, and more of them had clinical practice in northern Taiwan. The percentage of IM specialists becoming EM specialists declined in the last 2 years. The equilibrium between the supply and demand of EM specialists deserves further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: This study analyzed the effects of the General Medicine Faculty Training Program (GMFTP), which was implemented in 2009. The training program includes a 7-hour basic training (BT) to introduce ways of teaching and assessing the 6 core competencies identified by the Accreditation Council for Graduate Medical Education, and a 40-hour clinical training program., Methods: Physicians from different hospitals attended the GMFTPs. Since 2010, we have been using quick tests to assess trainees' familiarity of core competencies. Knowledge improvement (KI) was defined as the difference between post-BT and pre-BT test scores. Since 2013, we have been annually mailing questionnaires to assess trainees' teaching confidence (TC) of core competencies. We analyzed the correlations between trainees' characteristics, KIs, and TCs., Results: Between year 2009 and 2017, a total of 319 attending physicians (257 male, 62 female), with a mean age of 39.1 ± 6.2 years, completed the GMFTPs. Significant KI (32.6-55.4) was noted. There were no correlations between trainees' characteristics and KIs. The mean TCs for the 6 core competences were all above 4.0 (based on a 5-point Likert scale). TCs were positively correlated with age during GMFTP training, age when responding to the questionnaire, and duration between training and the last time responding to the questionnaire. TC showed no correlation with sex, hospitals, departments, or KI., Conclusion: Knowledge of teaching core competencies improved immediately after BT, but KIs did not correlate with TCs in long-term follow-up. After the training program, physicians' teaching confidence increased over time., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The Arf and Rab/Ypt GTPases coordinately regulate membrane traffic and organelle structure by regulating vesicle formation and fusion. Ample evidence has indicated that proteins in these two families may function in parallel or complementarily; however, the manner in which Arf and Rab/Ypt proteins perform interchangeable functions remains unclear. In this study, we report that a Golgi-localized Arf, Arl1, could suppress Ypt6 dysfunction via its effector golgin, Imh1, but not via the lipid flippase Drs2. Ypt6 is critical for the retrograde transport of vesicles from endosomes to the trans-Golgi network (TGN), and its mutation leads to severe protein mislocalization and growth defects. We first overexpress the components of the Arl3-Syt1-Arl1-Imh1 cascade and show that only Arl1 and Imh1 can restore endosome-to-TGN trafficking in ypt6-deleted cells. Interestingly, increased abundance of Arl1 or Imh1 restores localization of the tethering factor Golgi associated retrograde-protein (GARP) complex to the TGN in the absence of Ypt6. We further show that the N-terminal domain of Imh1 is critical for restoring GARP localization and endosome-to-TGN transport in ypt6-deleted cells. Together, our results reveal the mechanism by which Arl1-Imh1 facilitates the recruitment of GARP to the TGN and compensates for the endosome-to-TGN trafficking defects in dysfunctional Ypt6 conditions.

Background: Although bisphosphonate-related osteonecrosis of the jaw (ONJ) develops mainly after tooth extractions (TEs), the strength of the association between them and how the existence of the disease among bisphosphonate (BP)-treated osteoporotic patients exposed to TE remain uncertain., Methods: A nationwide retrospective cohort study investigated the influence of alendronate and TE on the development of ONJ., Results: Incidence of ONJ following long-term alendronate therapy was 262/100,000 person-years, while no event developed in the control group on raloxifene. Overall prevalence of ONJ in osteoporotic subjects receiving alendronate was estimated at 0.34% which rose to 2.16% after TE. Multiple logistic regression analysis, adjusted for the potential confounders, showed TE (adjusted odds ratio, 9.60 [4.33-21.29]), drug duration exceeding 3 years (3.00 [1.33-6.76]), and concomitant rheumatoid arthritis (4.94 [1.64-14.90]) were independent predictors of ONJ., Conclusions: This article strengthens the relationship between ONJ and BPs. Among osteoporotic patients exposed to alendronate, TE confers a 9.6-fold increased risk for ONJ and it should be performed with caution irrespective of drug duration.

This paper reports the development of colored-yarn mixed woven fabrics by using raw white warps and multicolored-wefts, as well as a study of the influential factors on the color attributes of the resultant fabrics. Weft yarns in six colors, together with the white warp yarns, were used to create a series of fabric colors. Two types of new weft-backed structures were designed to assign the desired wefts for color mixing, as well as to reduce the white warp floats on the surface and thus, the lightness of the fabric. The effects of the proportion of yarn color components, weft density, and the introduction of black weft floats on the color attributes of fabrics, were investigated. The results show that through varying the proportion of mixing yarn color components, via fabric structure, a series of mixed red-blue and green-yellow colors for fabrics are created, respectively. Colored yarn mixed fabric presents a lowered lightness after a middle regulating layer is introduced into the structure. Compared to fabrics with a lower density, higher density fabrics possess lower lightness, higher redness and blueness in the blue-red fabrics, and higher greenness and yellowness in the yellow-green fabric. The lightness of fabric lowers after adding black yarn., Competing Interests: The authors declare no conflict of interest.

This randomized controlled trial aimed to test the effectiveness of brief face-to-face patient education in increasing influenza vaccination rate among elderly in the community. Recruitment and intervention were conducted at two general outpatient clinics in Hong Kong. 529 eligible patients were randomly assigned to intervention or control group with 1:1 allocation ratio. Patients in the intervention group received 3-min one-on-one verbal education by medical students and a pamphlet regarding influenza vaccination. Neither verbal health education nor pamphlet was given to the control group. Intention-to-treat analysis showed significantly higher vaccination rate in the intervention group compared with the control group (33.6 versus 25.0%) and the adjusted relative risk was 1.34 (95% CI 1.04-1.72; P = 0.021). Hence, brief face-to-face patient education was effective in increasing influenza vaccine uptake rate of community-dwelling elderly patients. Participants who were undecided whether to receive vaccination seemed to demonstrate larger beneficial effect (RR = 7.84; 95% CI 1.06-57.76) compared with patients who were certain of either receiving (RR = 1.16; 95% CI 0.90-1.48) or not receiving (RR = 2.18; 95% CI 0.68-6.99) the vaccine. The study also revealed that patients' intention for vaccination may not translate into action, reasons for which should be explored in future research., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Amyloidogenic processing of APP by β- and γ-secretases leads to the generation of amyloid-β peptide (Aβ), and the accumulation of Aβ in senile plaques is a hallmark of Alzheimer's disease (AD). Understanding the mechanisms of APP processing is therefore paramount. Increasing evidence suggests that APP intracellular domain (AICD) interacting proteins influence APP processing. In this study, we characterized the overexpression of AICD interactor GULP1 in a Drosophila AD model expressing human BACE and APP695. Transgenic GULP1 significantly lowered the levels of both Aβ1-40 and Aβ1-42 without decreasing the BACE and APP695 levels. Overexpression of GULP1 also reduced APP/BACE-mediated retinal degeneration, rescued motor dysfunction and extended longevity of the flies. Our results indicate that GULP1 regulate APP processing and reduce neurotoxicity in a Drosophila AD model., Competing Interests: CONFLICTS OF INTEREST There is no conflict of interest.

The ingestion of a foreign body is a common occurrence. Psychiatric patients and prisoners may swallow objects on purpose. Occasionally emergent exploratory laparotomy may be indicated if the diagnosis is uncertain, and emergent removal of the foreign body may be needed to prevent substantial risk of serious complications including perforation, fistula, or gastrointestinal bleeding.

A series of novel p-type conjugated copolymers, PTTVBDT, PTTVBDT-TPD, and PTTVBDT-DPP, cooperating benzo[1,2-b:4,5-b']dithiophene (BDT) and terthiophene-vinylene (TTV) units with/without thieno[3,4- c ]pyrrole-4,6-dione (TPD) or pyrrolo[3,4- c ]pyrrole-1,4-dione (DPP) via Stille polymerization were synthesized and characterized. Copolymer PTTVBDT shows a low-lying HOMO energy level and ordered molecular-packing behavior. Furthermore, two terpolymers, PTTVBDT-TPD and PTTVBDT-DPP, display stronger absorption ability, alower-lying HOMO energy level, and preferred molecular orientation, due to the replacement TTV-monomer units with electron-deficient groups. Furthermore, bulk-heterojunction organic solar cells were fabricated using blends of the PTTVBDT-TPD, and PC 61 BM gave the best power conversion efficiency of 5.01% under the illumination of AM 1.5G, 100 mW·cm -2 ; the short circuit current ( J sc ) was 11.65 mA·cm -2 which displayed a 43.8% improvement in comparison with the PTTVBDT/PC 61 BM device. These results demonstrate a valid strategy combining the two-dimensional molecular structure with random copolymerization strikes promising conjugated polymers to achieve highly efficient organic photovoltaics.

It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*08:03 (Pcombined=1.83 × 10(-9)) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.

Background: Thyroid cancer is the most common endocrine gland malignancy and fine-needle aspiration biopsy is widely used for thyroid nodule evaluation. Repeated aspiration biopsies are needed due to plausible false-negative results. This study aimed to investigate the overall relationship between aspiration biopsy and thyroid cancer diagnosis, and to explore factors related to shorter diagnostic time., Methods: This nationwide retrospective cohort study retrieved data from the Longitudinal Health Insurance Database in Taiwan. Subjects without known thyroid malignancies and who received the first thyroid aspiration biopsy after 2004 were followed-up from 2004 to 2009 (n = 7700). Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were used for data analysis., Results: Of 7700 newly-aspirated patients, 276 eventually developed thyroid cancer (malignancy rate 3.6%). Among the 276 patients with thyroid cancer, 61.6% underwent only one aspiration biopsy and 81.2% were found within the first year after the initial aspiration. Cox proportional hazards model revealed that aspiration frequency (HR 1.07, 95% CI 1.06-1.08), ultrasound frequency (HR 1.02, 95% CI 1.01-1.03), older age, male sex, and aspiration biopsies arranged by surgery, endocrinology or otolaryngology subspecialties were all associated with shorter time to thyroid cancer diagnosis., Conclusions: About 17.4% of thyroid cancer cases received more than two aspiration biopsies and 18.8% were diagnosed one year after the first biopsy. Regular follow-up with repeated aspiration or ultrasound may be required for patients with clinically significant thyroid nodules.

The performance of the BluePoint MycoID plus kit (Bio Concept Corporation, Taichung, Taiwan), which was designed to simultaneously detect Mycobacterium tuberculosis (MTB), rifampin- and isoniazid-resistant MTB, and nontuberculous mycobacteria (NTM) was first evaluated with 950 consecutive positive cultures in Mycobacterium Growth Indicator Tube (MGIT) system (BACTEC, MGIT 960 system, Becton-Dickinson, Sparks) from clinical respiratory specimens. The discrepant results between kit and culture-based identification were finally assessed by 16S rRNA gene sequencing and clinical diagnosis. The accuracy rate of this kit for identification of all Mycobacterium species was 96.3% (905/940). For MTB identification, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the kit were 99.7%, 99.3%, 99.0% and 99.8%, respectively. For rifampicin-resistant MTB identification, the sensitivity, specificity, PPV, and NPV of the kit were 100.0%, 99.4%, 91.3%, and 100.0%, respectively, while the corresponding values of isoniazid-resistant MTB identification were 82.6%, 99.4%, 95.0%, and 97.6%, respectively. In identifying specific NTM species, the kit correctly identified 99.3% of M. abscessus (147/148) complex, 100% of M. fortuitum (32/32), M. gordonae (38/38), M. avium (39/39), M. intracellulare (90/90), M. kansasii (36/36), and M. avium complex species other than M. avium and M. intracellulare (94/94). In conclusions, the diagnostic value of the BluePoint MycoID plus kit was superior to culture method for recoveries and identification of NTM to species level. In addition, the diagnostic accuracy of BluePoint MycoID plus kit in MTB identification was similar to conventional culture method with high accuracy rate of rifampicin-resistant M. tuberculosis identification.

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S'-bis(α,α'-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.

Background: Congenital long QT syndrome (LQTS) is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients (91%) have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China., Methods: Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing., Results: Three of 16 LQTS patients (18.7%) were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was (17 ± 3) years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was (515 ± 17) ms, similar to those with single mutation or SNPs ((536 ± 74) ms, P = 0.63). Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event (P = 0.03 and 0.001, respectively), but lower percentage of them presented with sudden cardiac death (P = 0.03)., Conclusions: Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients (18.7%, 95% confidence interval: 0.04-0.46) with bigenic mutations in Taiwan. However, the severity of their clinical presentations was not higher than those patients with single mutation or SNPs.

There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.

Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.

Background/purpose: People receive electrocardiogram (ECG) examination for various reasons in a hospital setting. An important clinical practice issue may be that cardiologists need to be consulted for Brugada-type ECGs identified through routine screening. We investigated the prevalence and prognosis of patients with Brugada-type ECG in a hospital-based population in an attempt to improve the management of these patients., Methods: In 20,562 patients seeking medical care for non-cardiovascular reasons, 74,955 ECGs were performed from December 1999 to February 2001. The diagnostic criteria for Brugada-like ECG from the European Society of Cardiology were used. International Statistical Classification of Diseases codes and city residents' records were documented to indicate the reasons for visiting clinics or hospitalization and mortality outcome. Medical records were reviewed and telephone interviews were conducted., Results: Twenty-six (0.13%) of the 20,562 patients were confirmed to have Brugada-type ECGs. None of these patients had ever experienced syncope, near syncope or sudden cardiac death. After 57.1 ± 15.8 months of follow-up, there were four deaths out of the 26 patients with Brugada-type ECG (15.4%, 95% CI: 1.53-2.9%) compared with 2899 of those without (14.1%, 95% CI: 13.6-14.5%; p=0.89, log-rank test). Neither sudden cardiac death (p=0.61) nor hospitalized death (p=0.55) was different between patients with and without Brugada-type ECG., Conclusion: Patients with Brugada-type ECGs are not rare in a hospital-based population. The presence of Brugada-type ECGs in patients without syncope or sudden cardiac death was not associated with hospitalized mortality., (Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

In this work, poly(acrylic acid-co-sodium acrylate) P(AA-SA) latex particles were prepared by inverse miniemulsion polymerization and used as a pH buffering agent for application. The polymerization was quickly initiated by a redox initiator (ammonium persulfate/sodium metabisulfite) at 0-5 degrees C. Thus the possibility of monomer dissolving in a solvent was reduced, which enhanced the degree of droplet nucleation. The effects of costabilizer and the ratio of SA/(AA+SA) in functional latex particles on the nucleation mechanism and emulsion stability were investigated. The apparent pK(a) values of the synthesized P(AA-SA) latex particles were determined by titration experiments. Their properties on pH buffering were also studied, including the pH temporal response and pH buffering ability. The results showed that sodium hydroxide, which was introduced as the costabilizer to enhance the osmotic pressure and to increase the deprotonation of acrylic acid, was effective in guaranteeing droplet nucleation predominantly. Meanwhile, the surfactant concentration was controlled to be less than its critical micelle concentration (CMC) value to avoid micellar nucleation. Furthermore, the P(AA-SA) latex particles thus synthesized were found to be an excellent material for pH buffering. The pH temporal response was very rapid and related to the crosslinking degree of the latex particles. The terminal range of pH buffering for latex particles was controllable by the ratio of SA/(AA+SA).

Graves' disease (GD) is a common organ-specific autoimmune disorder inherited as a complex trait. Although there has not been consensus regarding the genuine susceptibility alleles, many population-based genetic studies showed association of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with GD. In contrast, evidence utilizing family-based studies came only from the Caucasian population. Here we performed a family-based association study in the Han population in Taiwan. We enrolled 374 affected individuals and 347 unaffected family members in 151 GD pedigrees. Four single-nucleotide polymorphisms (SNP) and a short tandem repeat polymorphism (STRP) at CTLA4 were genotyped. Association of GD with a novel risk SNP at the 5' upstream region, CTLA4&#95;-1722&#95;T/C (rs733618), was demonstrated (P=0.0096). We also replicated the association signal of a coding SNP, CTLA4&#95;+49&#95;G/A (rs231775, P=0.0219). A common haplotype composed of CTLA4&#95;-1722&#95;T/C and CTLA4&#95;(AT)n (an STRP marker: UniSTS:48500) showed protective effect (P=0.0004). Our results of family-based association study, taken together with those from the Caucasian population, provide evidence that CTLA4 confers susceptibility to GD across different ethnic backgrounds.

The design, fabrication and measurement of a silicon-on-insulator (SOI) two-dimensional photonic crystal ring resonator are demonstrated in this study. The structure of the photonic crystal is comprised of silicon nano-rods arranged in a hexagonal lattice on an SOI wafer. The photonic crystal ring resonator allows for the simultaneous separation of light at wavelengths of 1.31 and 1.55mum. The device is fabricated by e-beam lithography. The measurement results confirm that a 1.31mum/1.55mum wavelength ring resonator filter with a nano-rod photonic crystal structure can be realized.

Nano-sized TiO(2) or SiO(2)/TiO(2) particles were prepared by hydrolysis and condensation reactions in aqueous media, followed by mixing with poly(AA-co-MMA) latex to form different composites, then blending with poly(ethylene terephthalate), PET. The TGA results of composites indicated that negative charged latexes had greater interaction with TiO(2)/ or SiO(2)/TiO(2) particles through strong electrostatic forces, while cationic latexes incorporated with TiO(2) or SiO(2)/TiO(2) particles by pH induced coagulation, carbonyl group chelation and hydrogen bonding. The soapless latex polymer particles showed lower ability of adsorption to TiO(2) particles due to the decrease of total surface area of these larger particles. If SiO(2)/TiO(2) particles were used instead of TiO(2) particles, unexpected high adsorption result was observed. Morphology results observed by SEM showed that PET blended with positive charged composites was more homogeneous than PET blended with negative charged composites. DSC results also indicated that the T(g) of PET was increased, melting temperatures (T(m) or T(m)(')) were increased, and the temperature range of crystallization was narrowed after blending with the composites. The presence of composites affected the mobility and packing of PET molecular chains therefore changing the thermal properties of PET.

Ferrofluids, which are stable dispersions of magnetic particles, behave as liquids that have strong magnetic properties. Nanoparticles of magnetite with a mean diameter of 10-15 nm, which are in the range of superparamagnetism, are usually prepared by the traditional method of co-precipitation from ferrous and ferric electrolyte solution. When diluted, the ferrofluid dispersions are not stable if anionic or cationic surfactants are used as the stabilizer. This work presents an efficient way to prepare a stable aqueous nanomagnetite dispersion. A stable ferrofluid containing Fe3O4 nanoparticles was synthesized via co-precipitation in the presence of poly(acrylic acid) oligomer. The mechanism, microstructure, and properties of the ferrofluid were investigated. The results indicate that the PAA oligomers promoted the nucleation and inhibited the growth of the magnetic iron oxide, and the average diameter of each individual Fe3O4 particle was smaller than 10 nm. In addition, the PAA oligomers provided both electrostatic and steric repulsion against particle aggregation, and the stability of dispersions could be controlled by adjusting the pH value of solution. A small amount of Fe2O3 was found in the nanoparticles but the superparamagnetic behavior of the nanoparticles was not affected.

A core-shell copolymer latex with thermal-responsive properties was prepared and its potential application as a vehicle for drug targeting was investigated in this work, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and chitosan was prepared as the core and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. By using soapless dispersion polymerization, the poly(NIPAAm-chitosan) crosslinked copolymer latex was synthesized first. Then the monomers of MAA and MMA were added to continue the reaction to obtain the core-shell copolymer latex. The weight ratio of MAA/MMA and the concentration of shell monomers (MAA and MMA) in the feed of the reaction mixture had been changed to investigate their effects on the particle size, reaction rate, zeta-potential, specific surface area, and surface functional groups of the latex particles. The swelling and thermoresponsive behavior of the film made from these core-shell latices were also studied under different pH values of buffer solution. The model drug (caffeine) could be merged inside the copolymer particles and protected from releasing through the transport process effectively. And the thermoresponsive property of these copolymer particles significantly enhances the ligand (protein) conjugation that shows the potential of the latex being applied on the targeting drug carrier.

This study demonstrates the use of photonic crystal directional couplers to separate light of wavelengths 1.31 and 1.55microm. The photonic crystal structure consists of InAlGaAs nano-rods arranged in square lattice. The coupling length of the light in the directional coupler at a wavelength of 1.31microm was designed to be four times greater than that at 1.55microm. This behavior helps in designing devices to split the two wavelengths. The devices are fabricated by e-beam lithography and conventional photolithography. The measurement results confirm that 1.31microm/1.55microm directional couplers can be realized in PC structures formed by nano-rods.

In this work, the properties of poly(vinyl alcohol) (PVA) and PVA/chitosan blended membranes were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and electron spectroscopy for chemical analysis (ESCA). The SEM photographs show the PVA/chitosan blended membrane undergoes dramatic changes on the surface and bulk structure during the membrane formation. The DSC analysis shows that PVA and chitosan are not very compatible in the PVA/chitosan blended membrane, whereas the combination of two polymer chains of constitutionally different features is revealed. In addition, the surface of the PVA/chitosan blended membrane is enriched with nitrogen atoms at the ESCA analysis. These reflect the PVA membrane can be modified by blending with chitosan that in turn may affect the biocompatibility of the blended membrane. Therefore, adhesion and growth of fibroblasts on the PVA as well as PVA/chitosan blended membranes were investigated. Cell morphologies on the membranes were examined by SEM and cell viability was studied using MTT assay. It was observed that the PVA/chitosan blended membrane was more favorable for the cell culture than the pure PVA membrane. Cells cultured on the PVA/chitosan blended membrane had good spreading, cytoplasm webbing and flattening and were more compacting than on the pure PVA membrane. Consequently, the PVA/chitosan blended membrane may spatially mediate cellular response that can promote cell attachment and growth, indicating the PVA/chitosan blended membrane should be useful as a biomaterial for cell culture.

Aim of Study: To determine whether a homemade rapid urease test (RUT) (1 mL of 10% urea broth in distilled water plus one drop of 1% phenol red as indicator, cost/test USD0.19) was reliable when compared to histology in the diagnosis of HP infection., Method: Prospective consecutive sampling of patients who underwent outpatient oesophagogastroduodenoscopy and antral biopsies from October 1996 to January 1997. RUT and histology examinations were done on all specimens. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the RUT were calculated accordingly., Results: Amongst our 140 patients, the sensitivity, specificity, positive and negative predictive values and accuracy of RUT were 94%, 99%, 99%, 95% and 96% respectively. Seventy-seven percent of the positive RUTs can be detected within 1 hour., Conclusion: Our homemade RUT is an inexpensive test with good sensitivity and specificity for HP infection.