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Ching-Fang Chien,1 Poyin Huang,1,2 Sun-Wung Hsieh1,2 1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 2Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan Abstract: Quetiapine is an atypical antipsychotic agent which is also prescribed for delirium due to its anti-dopaminergic effects; aphasia is an unusual side effect associated with the drug. Here, we report the case of an 83-year-old woman who was prescribed quetiapine (50 mg per day) for delirium. Unexpected, global aphasia occurred 3 days after treatment began. Complete recovery occurred following discontinuation of the drug. A brain computed tomography scan excluded intracranial hemorrhage and the laboratory results confirmed that no exacerbation of infection or electrolyte imbalances were present. During the aphasic episode, the patient’s condition did not deteriorate and no new neurological symptoms occurred. We suspect that the occurrence of aphasia was directly due to an adverse reaction to quetiapine. To our knowledge, this is the first case report of reversible, global aphasia as a side effect of quetiapine. We propose that this occurrence of aphasia may be due to the action of quetiapine as a dopamine receptor antagonist. Clinicians should use quetiapine with caution, especially in elderly patients. On observation of aphasia, a review of the patient’s medical history is required to assess for the usage of quetiapine. Keywords: aphasia, quetiapine, insomnia, delirium

Yin-Meng Tsai,1 Wan-Ling Chang-Liao,1 Chao-Feng Chien,1 Lie-Chwen Lin,1,2 Tung-Hu Tsai,1,31Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 2National Research Institute of Chinese Medicine, 3Department of Education and Research, Taipei City Hospital, Taipei, TaiwanBackground: Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome.Methods: Curcumin encapsulated in low (5000–15,000) and high (40,000–75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples.Results: There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (Cmax) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 µg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC.Conclusion: Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods.Keywords: absorption, duodenum, molecular weight, poly(lactic-co-glycolic acid), PLGA, relative oral bioavailability

Purpose: The ProSeal™ laryngeal mask airway (PLMA™) may be difficult to insert because of its large soft cuff, even when using a dedicated introducer tool. The purpose of this study was to investigate whether introduction of a stylet (Flexi-Slip™) in the drainage tube improved insertion characteristics compared with the standard introducer.Methods: In this randomized controlled trial, 160 adults were allocated randomly to either the Introducer group (n = 80) or to the Flexi-Slip stylet group (n = 80). In the Introducer group, the PLMA was inserted with an introducer as described in the manufacturer's instructions. In the Flexi-Slip stylet group, a Flexi-Slip stylet was inserted into the drainage tube of the PLMA and bent to form a near 90° angle at the junction of the cuff and the airway tube. The primary outcome measurement was the success rate at first attempt. Insertion time, visible blood staining, and complications were also noted.Results: Success at first attempt was more frequent with the Flexi-Slip stylet than with the introducer (100% vs 86%, respectively; P = 0.001). Overall time (mean ± standard deviation) taken for successful placement was shorter with the Flexi-Slip stylet than with the introducer (19.9 ± 5.6 sec vs 28.4 ± 15.2 sec, respectively; P < 0.001). The incidences of blood staining and postoperative sore throat were lower in the Flexi-Slip stylet group than in the Introducer group (4% vs 15%, respectively; P = 0.015 and 8% vs 23%, respectively; P = 0.008).Conclusion: Insertion of the PLMA with a Flexi-Slip stylet has a higher success rate at first attempt, requires less time, and results in fewer airway complications than the introducer technique. [ABSTRACT FROM AUTHOR]

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) is an early and significant prodromal marker for Parkinson's disease (PD). While the association between RBD and PD has been well-documented, the underlying pathophysiology differentiating PD patients with RBD (PD-RBD +) from those without RBD (PD-RBD-) remained unclear. This study aims to investigate the possible relationship between RBD and striatal dopamine depletion in de novo PD patients., Methods: A retrospective, cross-sectional study was conducted on 151 PD patients. We used standard questionnaires and measurements to assess motor and nonmotor symptoms. The dopaminergic function was assessed utilizing Tc-99 m TRODAT-1 SPECT imaging, and statistical analyses were performed to compare dopamine transporter (DAT) binding between patients with or without probable RBD (pRBD)., Results: The PD-pRBD + group exhibited significantly lower DAT binding in the caudate nucleus (OR 0.618; 95% CI 0.392-0.618; p = 0.039) and putamen (OR 0.554; 95% CI 0.319-0.962; p = 0.036) compared to the PD-pRBD- group. The PD-pRBD + group also had a higher prevalence of non-motor symptoms, including depression (OR 7.499; 95% CI 2.770-20.299; p < 0.001) and constipation (OR 2.356; 95% CI 1.090-5.092; p = 0.029). Although trends toward increased dementia (12.3% in PD-pRBD + , 6.4% in PD-pRBD-, p = 0.266) and falls (16.4% in PD-pRBD + , 11.5% in PD-pRBD-, p = 0.482) were observed in the PD-pRBD + group, these did not reach statistical significance., Conclusion: The presence of RBD in PD patients is associated with greater striatal dopaminergic dysfunction, suggesting a distinct subtype with potentially faster disease progression. These findings highlight the importance of early RBD identification in PD patients to guide more personalized interventions., Competing Interests: Declarations. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Stroke is one of the leading causes of disability worldwide. Stroke-in-evolution is an essential issue as it is often associated with a worse outcome. Central motor conduction time (CMCT) is the time required for neural impulses to travel through the central nervous system to the target muscles. CMCT prolongation indicates dysfunction of the corticospinal tract. This study aims to investigate the impact of CMCT on clinical features and MRI characteristics in patients with acute ischemic stroke. A total of 94 patients with suspected acute ischemic stroke, with an average age of 67.13 ± 10.73 years old and 69.15 % being male, were enrolled in this study. All patients underwent evaluation for stroke risk factors, medical record review, CMCT examination (with CMCT (+) indicating CMCT prolongation), cranial MRI examinations, and data analysis. Compared to CMCT (-), the number of CMCT (+) subjects was significantly higher in all groups except the "Ever Stroke" group. The CMCT (+) group exhibited significantly higher values of "NIHSS" and "mRS" compared to the CMCT (-) group. After ANCOVA adjustment, the number of CMCT (+) subjects remained significantly higher only in the radiologically classified "New Pyramidal Lesion on MRI" and clinically classified "Stroke-In-Evolution" groups. In conclusion, CMCT serves as both a diagnostic indicator of acute ischemic stroke with weakness accompanied by new pyramidal lesions on brain MRI, rather than weakness associated with old lesions on brain MRI, and as a predictive marker for stroke progression during hospitalization., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS., Methods: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week., Results: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not., Conclusions: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited., Objective: The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan., Methods: Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint., Results: We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml., Conclusions: We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose.

Several studies have demonstrated accelerated brain aging in Alzheimer's dementia (AD). Previous studies have also reported that facial asymmetry increases with age. Because obtaining facial images is much easier than obtaining brain images, the aim of this work was to investigate whether AD exhibits accelerated aging patterns in facial asymmetry. We developed new facial asymmetry measures to compare Alzheimer's patients with healthy controls. A three-dimensional camera was used to capture facial images, and 68 facial landmarks were identified using an open-source machine-learning algorithm called OpenFace. A standard image registration method was used to align the three-dimensional original and mirrored facial images. This study used the registration error, representing landmark superimposition asymmetry distances, to examine 29 pairs of landmarks to characterize facial asymmetry. After comparing the facial images of 150 patients with AD with those of 150 age- and sex-matched non-demented controls, we found that the asymmetry of 20 landmarks was significantly different in AD than in the controls ( p < 0.05). The AD-linked asymmetry was concentrated in the face edge, eyebrows, eyes, nostrils, and mouth. Facial asymmetry evaluation may thus serve as a tool for the detection of AD.

Objectives: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with Alzheimer's disease (AD), causing burdens on caregivers. Behavioral and psychological symptoms of dementia and subclinical epileptiform discharge (SED) increased with the disease course of AD. However, the interaction between them was still unknown. The present study aimed to evaluate the associations between SED and BPSD., Methods/design: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography (EEG) for 13 min was performed to detect SED. Behavioral and psychological symptoms of dementia was assessed by neuropsychiatric inventory (NPI) questionnaires. The occurrence of BPSD subsyndromes was compared between patients with and without SED., Results: Two hundred sixty-three adult patients qualified for the inclusion criteria and were enrolled in this study. The mean age of patients was 80.2 years, and approximately 62% were women. 17.1% of patients showed SED on EEG. Apathy was the most commonly reported BPSD subsyndrome in this cohort. There was no significant difference in the prevalence of BPSD between patients with and without SED. (75.6% vs. 67.4%, p = 0.2806). However, the NPI score of irritability subsyndrome was significantly higher in the SED (+) group (2.6 ± 3.7 vs. 1.2 ± 2.7, p = 0.0028). In addition, subclinical epileptiform discharge in the frontal lobe was associated with a considerably higher occurrence of hyperactivity subsyndrome, including irritability., Conclusions: SED may not be a direct cause of BPSD, but the presence of SED may affect the manifestation of BPSD., (© 2023 John Wiley & Sons Ltd.)

Introduction: The Apolipoprotein E ( APOE ) epsilon (ε) 4 allele is a well-established risk factor for late-onset Alzheimer's disease (AD). Reports on white ancestry populations have showed that age, sex, and ethnicity have different effects on the association between APOE genotype and AD. However, studies on Asian populations such as Taiwan Chinese populations are limited. This study aimed to evaluate the association between APOE genotype and AD in a Taiwan Chinese population, and to explore if the association varies by age and sex., Methods: We conducted a case-control study in 725 patients with AD and 1,067 age- and sex- matched controls without dementia from a Taiwan Chinese population. Logistic regression models were used to test the association between AD and APOE genotypes. Secondary analyses considered age (<75 or ≥75 years old), and sex stratified models., Results: The risk of AD was significantly increased for people with at least one copy of APOE ε4 (OR = 2.52, 95% CI = 2.01-3.17, p < 0.001) and in a dose-dependent manner. Our results did not show an statistically significance different in AD risk when women and men carrying APOEε4 were compared. Despite not reaching statistical significance, the risk of APOE ε4 for AD was higher among younger participants (OR = 3.21, 95% CI = 2.26-4.56, p < 0.001) compared to older ones (OR = 2.13, 95% CI = 1.53-2.97, p < 0.001). When considering both sex and age, the risk of AD was higher among older men carrying APOE ε4 (OR = 2.64, 95% CI = 1.51-4.60 in men; OR = 1.90, 95% CI = 1.26-2.86 in women), while women carrying APOE ε4 appeared to have an increased risk at a younger age (OR = 3.29, 95% CI = 2.20-4.93 in women; OR = 2.91, 95% CI = 1.40-6.05 in men)., Discussion: The APOE ε4 allele represents a major risk factor for AD in the Taiwanese population. The effect of APOE ε4 allele on AD risk appeared to be stronger among men aged 75 years or more and among younger women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Lee, Chien, Chang, Li and Yang.)

Aim: Alzheimer's dementia (AD) is a slowly progressing neurodegenerative disease, characterized by beta-amyloid deposition and neurofibrillary tangles. Peripheral atherosclerosis may deteriorate these processes via endothelial cell dysfunction and microvascular impairment. Cilostazol - a phosphodiesterase 3 inhibitor - is a standard treatment for peripheral arterial occlusive disease and a potential treatment for preserving cognitive function in AD patients. We aimed to determine whether cilostazol is beneficial in AD patients with peripheral arterial occlusive disease by evaluating Cognitive Abilities Screening Instrument (CASI) domains., Methods: We conducted a retrospective case-control study of 62 AD patients in Taiwan. Thirty-one patients had peripheral arterial occlusive disease and were receiving cilostazol plus acetylcholinesterase inhibitors (AchEIs) or N-methyl d-aspartate antagonists, whereas 31 others were receiving AchEIs. Therapeutic responses were measured using neuropsychological assessments. The CASI was administered at baseline and 12 months later; different domains were analyzed between the groups using univariate and multivariate analyses., Results: Age, sex, education duration, ApoE ε4 gene status, and initial Mini-Mental State Examination scores were not different between the two groups. Except for fluency, no CASI domains showed a statistical difference between the groups. A significant difference was observed in category fluency (P = 0.010). In the logistic regression analysis, after adjusting for covariate effects, category fluency still showed a significant difference between the groups (P = 0.013)., Conclusions: In AD patients with peripheral arterial occlusive disease who have received Food and Drug Administration-approved pharmacotherapy, cilostazol, as an antiplatelet, may help to preserve general cognitive function, with significant preservation in category fluency. Geriatr Gerontol Int 2023; 23: 194-199., (© 2023 Japan Geriatrics Society.)

Neuropsychiatric symptoms (NPSs) are known to be frequent in Parkinson's disease (PD) with great impacts on the quality of life, but reports about the prevalence in institutions are few. Our aim was to investigate the prevalence of and risk factors for NPSs in institutionalized patients with PD in Taiwan. The National Health Research Institute executed a cross-sectional, community-based, observational study on residential long-term care service institutions. The diagnosis of PD was determined by physicians with the estimated Hoehn and Yahr stage of PD according to the EQ-5D-5L questionnaire. A total of 370 patients with PD (80.1 ± 9.94 years old, 55.1% females) were included, and 139 (37.6%) had more than one NPS in the prior 3 months. The top three NPSs were nighttime behavior (65 (17.6%)), depression (53 (14.3%)), and fear/anxiety (49 (13.2%)). There were no differences between those with NPS and those without NPS in terms of age, gender, education, Mini-Mental State Examination, or Hoehn and Yahr stage. However, multivariate logistic regression analysis showed that genitourinary disease (odds ratio (OR) = 3.13; 95% confidence interval (95%CI) = 1.77-5.51) and psychiatric disorders (OR = 5.18; 95%CI = 3.09-8.69) may be associated with increased risk of NPSs. Increased physical restraint was observed in residents with advanced PD. Genitourinary disease and psychiatric disorders appear to increase the risk of NPSs in institutionalized residents with PD.

Patients with Alzheimer's disease typically have initial deficits in memory. Memory testing can be categorized as verbal or nonverbal by the modality of the stimuli used. We compared the discriminative validity of selected verbal and nonverbal memory tests between non-dementia and Alzheimer's disease in Taiwan. Ninety-eight patients with mild Alzheimer's disease and 269 non-dementia individuals underwent story recall test (immediate and delayed recall), and constructional praxis test (copy and delayed recall). The receiver-operating characteristic curve and area under the curve were evaluated to compare between tests. Patients with Alzheimer's disease performed poorly across all memory tests, and the receiver-operating characteristic curve analysis indicated that story recall immediate and relayed recall, and constructional praxis delayed recall had good classification accuracy with area under the curve of .90, .87 and .87 respectively. These results provide support that both verbal and nonverbal memory tests are reliable measure for screening patients with Alzheimer's disease.

Background: In Taiwan, physical restraint is commonly used in institutions to protect residents from falling or injury. However, physical restraint should be used cautiously to avoid side effects, such as worse cognition, mobility, depression, and even death., Objectives: To identify the rate of physical restraint and the associated risk factors in institutionalized residents in Taiwan., Methods: A community-based epidemiological survey was conducted from July 2019 to February 2020 across 266 residential institutions. Among the estimated 6,549 residents being surveyed, a total of 5,752 finished the study. The questionnaires were completed by residents, his/her family or social workers. The cognition tests were conducted by specialists and a multilevel analysis approach was used to identify cognition/disability/medical history/special nursing care/BPSD risk factors for physical restraints., Results: Of the 5,752 included institutionalized residents, 30.2% (1,737) had been previously restrained. Older age, lower education level, lower cognitive function, higher dependence, residents with cerebrovascular disease, pulmonary disease, dementia, and intractable epilepsy, all contributed to a higher physical restraint rate, while orthopedic disease and spinal cord injury were associated with a lower physical restraint rate. Furthermore, residents with special nursing care had a higher restraint rate. Residents with most of the behavior and psychological symptoms were also associated with an increased restraint rate., Conclusions: We studied the rate of physical restraint and associated risk factors in institutionalized residents in Taiwan. The benefits and risks of physical restraint should be evaluated before application, and adjusted according to different clinical situations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Chien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metal and metal oxide nanoparticles, including copper nanoparticles (CuNPs), display antimicrobial activities and are regarded as promising microorganism inhibitors. Here, we explored the antimicrobial activity of CuNPs in Escherichia coli ( E. coli ) using two particle sizes (20 and 60 nm) and five concentrations (1, 5, 10, 50 and 100 μg/mL). The result showed a concentration-dependent trend of bactericidal activities for both size groups, with 20 nm particles more effective than 60 nm particles at low concentrations. The membrane disruption caused by CuNPs was confirmed by electron microscopy, PI staining and protein leaking analysis. However, the results of reactive oxygen species generation and genomic DNA damage revealed that the size and concentration of CuNPs were factors affecting the induction of multiple bactericidal mechanisms simultaneously on different scales. Further results of annexin V-PI staining supported this hypothesis by showing the shifting composition of the early-, late- and non-apoptotic dead cells across the CuNP groups. Many CuNP treatment groups were rescued when four mammalian modulators-wortmannin, necrosulfonamide, Z-VAD-FMK, and SBI-0206965-were applied separately. The results suggest the possible existence of bacterial programmed cell death pathways in E. coli which could be triggered by CuNP treatments.

Background: Alzheimer’s dementia (AD) is a degenerative disease that impairs cognitive function, initially, and then motor or other function, eventually. Motor coordination function impairment usually accompanies cognition impairment but it is seldom examined whether it can reflect the clinical outcomes of AD. Methods: 113 clinically diagnosed AD patients with a mean age of 78.9 ± 6.9 years underwent an annual neuropsychological assessment using the Mini-Mental State Examination (MMSE), the Cognitive Abilities Screening Instrument (CASI), the Sum of Boxes of Clinical Dementia Rating (CDR-SB), and the CDR. The cerebral coordination function was evaluated through correlations among 15 joints with a kinetic depth sensor annually. An intra-individual comparison of both cognitive and motor coordination functions was performed to examine their correlations. Results: The changes in coordination function in the lower limbs can significantly reflect the clinical outcomes, MMSE (p < 0.001), CASI (p = 0.006), CDR (p < 0.001), and CDR-SB (p < 0.001), but the changes in upper limbs can only reflect the clinical outcome in CDR (p < 0.001). Conclusions: The use of a kinetic depth sensor to determine the coordination between joints, especially in lower limbs, can significantly reflect the global functional and cognitive outcomes in AD. Such evaluations could be another biomarker used to evaluate non-cognitive outcomes in AD for clinical and research purposes.

Study Objectives: Chronic insomnia disorder (CID) is a common sleep disorder, with a prevalence ranging from 6%-10% worldwide. Individuals with CID experience more fragmented sleep than healthy control patients do. They awaken frequently during the night and have a higher risk of injury from falling. Awakening from different sleep stages may have different effects on postural stability and waking performance. However, limited research has been conducted on this topic., Methods: This prospective randomized crossover study was conducted between January 2015 and January 2017. We included 20 adults aged 20-65 years who fulfilled the diagnosis criteria for CID. Participants underwent 2 overnight polysomnography studies with an interval of at least 7 days. They were awakened during either rapid eye movement (REM) sleep or stage N1/N2 sleep alternatively. We compared measurements of static postural stability, vigilance scores, and neuropsychological tests between REM sleep and stage N1/N2 sleep awakening., Results: Polysomnography parameters between the 2 nights were comparable. Participants who were awakened from REM sleep had worse static postural stability than those with stage N1/N2 sleep awakening. Compared with stage N1/N2 sleep awakening, larger mean sway areas of center of pressure ( P = .0413) and longer center-of-pressure mean distances ( P = .0139) were found in REM sleep awakening. There were no statistically significant differences in vigilance scores or neuropsychological tests between the 2 nights., Conclusions: REM sleep awakening was associated with worse static postural stability than was stage N1/N2 sleep awakening. No statistically significant differences were found in waking performance in alertness or in neuropsychological tests between stage N1/N2 and REM sleep awakening., Citation: Yeh W-C, Chuang Y-C, Yen C-W, et al. Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study. J Clin Sleep Med. 2022;18(8):1983-1992., (© 2022 American Academy of Sleep Medicine.)

Study Objectives: Epilepsy is characterized by disrupted sleep architecture. Studies on sleep macro- and microstructure revealed that patients with epilepsy experience disturbed rapid eye movement (REM) sleep; however, no consensus has been reached on non-REM (NREM) sleep changes. Cyclic alternating pattern (CAP) is a marker of sleep instability that occurs only during NREM sleep. This meta-analysis investigated CAP differences between patients with epilepsy and healthy controls., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in searching PubMed, Embase, and Cochrane Central database for studies comparing polysomnographic sleep microstructures between patients with epilepsy and healthy controls. A meta-analysis using a random-effects model was performed. We compared CAP rates, percentages of phase A1, A2, A3 subtypes, and phase B durations between patients with epilepsy and healthy controls., Results: A total of 11 studies, including 209 patients with epilepsy and 197 healthy controls, fulfilled the eligibility criteria. Compared with healthy controls, patients with epilepsy had significantly increased CAP rates and decreased A1 subtype percentages, and patients with sleep-related epilepsy had increased A3 subtype percentages. Subgroup analyses revealed that antiseizure medications (ASMs) decreased CAP rates and increased phase B durations but did not affect the microstates of phase A in patients with sleep-related epilepsy., Conclusions: This meta-analysis detected statistically significant differences in CAP parameters between patients with epilepsy and healthy controls. Our findings suggest patients with epilepsy experience NREM sleep instability. ASMs treatment may decrease NREM instability but did not alter the microstates of phase A., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Limb-shaking syndrome is a special manifestation of transient ischemic attack, resulting from internal carotid artery (ICA) occlusion. Extra-articular manifestations of rheumatoid arthritis (RA) are likely to occur in patients with severe or active RA. RA may accelerate atherosclerotic processes through inflammation. Here, we present a case of ICA occlusion related to poorly controlled RA that presented with continuous hand shaking., Patient Concerns: A 73-year-old man with a history of poorly controlled RA developed total occlusion of the right ICA in recent 4 months. He presented with 2 days of continuous and rhythmic left-hand shaking before admission., Diagnosis: The patient was suspected to have transient ischemic attack resulting from ICA occlusion., Interventions: Antiplatelets and antiepileptic drugs were used for continuous nonepileptic focal myoclonus. A disease-modifying antirheumatic drug-based regimen for RA was developed to prevent further atherosclerosis., Outcomes: Following the initial intervention, continuous hand shaking subsided on hospital day 7. Prednisolone was titrated as an active RA control. At the 6-month follow-up visit, neither painful wrist swelling nor recurrent shaking of the hand was noted., Lessons: Continuous hand shaking (nonepileptic focal myoclonus) can be the initial presentation of ICA occlusion in patients with poorly controlled RA. Every patient with RA should be treated aggressively with anti-rheumatic agents since RA is an independent risk factor for stroke. Additionally, every patient with RA should be surveyed for ICA stenosis, especially in those with poor control., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Compared to healthy controls, adults with epilepsy have a disrupted sleep architecture. Changes in sleep macrostructure may be associated with the refractoriness of epilepsy. However, there is no consensus regarding the changes in sleep architecture in patients with epilepsy. This meta-analysis aimed to elucidate the differences in sleep architecture between patients with epilepsy and healthy controls., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The PubMed, Embase, and Cochrane Central databases were searched (until May 2021) for studies comparing polysomnographic sleep macrostructures between patients with epilepsy and healthy controls. A meta-analysis was performed using a random-effects model. The percentage of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were compared between patients with epilepsy and healthy controls., Results: Overall, 24 studies involving 789 patients with epilepsy and 599 healthy controls fulfilled the eligibility criteria. Compared to healthy controls, patients with focal epilepsy had decreased REM sleep and SE. Patients with generalised epilepsy had increased SWS and decreased SE. Subgroup analyses focussed on the potential effect of seizure control on sleep architecture. The results revealed that both antiseizure medication (ASM)-untreated and treated patients had decreased SE. ASM treatment may restore REM sleep in patients with generalised epilepsy but not in patients with focal epilepsy., Conclusions: This meta-analysis revealed statistically significant differences in the sleep macrostructure between patients with epilepsy and healthy controls. There were significant differences in the sleep macrostructure between ASM-untreated patients and healthy controls, which may be an intrinsic change attributable to epilepsy., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Alzheimer's disease (AD) is the most common type of dementia. Aging is a risk factor for both AD and seizures. Subclinical epileptiform discharge (SED) has no evident clinical manifestation in patients with AD. Therefore, SED is liable to be overlooked in these patients since electroencephalography is not routinely performed in clinical settings. Previous studies about the association between SED and AD have yielded inconsistent results., Objective: The current study aimed to evaluate the prevalence of SED and its effect on AD severity and clinical outcomes., Methods: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography for 13 minutes was performed to detect SED. Clinical outcomes of patients with and without SED were assessed by neuropsychological tests [Cognitive Abilities Screening Instrument (CASI), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)]., Results: 288 patients (mean age 80.5 years, 60.4% female) were enrolled in this study. Fifty-seven (19.8%) out of 288 patients with AD had SED. The prevalence of SED increased with the severity of cognitive impairment. Compared with patients without SED, those with SED showed significantly greater decline in CASI (-9.32 versus -3.52 points, p = 0.0001) and MMSE (-2.52 versus -1.12 points, p = 0.0042) scores in one year., Conclusion: SED may play a significant role in AD progression and is a potential therapeutic target.

Background: Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture., Methods: PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy., Results: Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE., Conclusions: This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare and heterogeneous clinico-neuroradiological syndrome characterized by headache, altered mental status, seizures, and visual disturbances. Hypertension and immunosuppression are two of the main factors that predispose an individual to RPLS. However, RPLS can develop when no major risk factors are present. RPLS has been reported in pediatric nephrotic patients, but rarely in adults., Case Presentation: A 42-year-old Asian woman with nephrotic syndrome presented with seizures, headaches, and nausea. Her blood pressure was controlled, and no immunosuppressants had been prescribed. All symptoms and tests indicated RPLS following infection with pneumonia, which was successfully treated by immediate administration antibiotic and anti-epileptic medications. Seizures did not recur during a 2-year follow-up period., Conclusions: When patients with nephrotic syndrome have an infection, RPLS symptoms should be investigated thoroughly. With early diagnosis and appropriate treatment of RPLS, morbidity and mortality can be prevented.

In recent years, many city governments around the world have begun to use information and communication technology to increase the management efficiency of on-street parking. Among various experimental smart parking projects, deployment of wireless magnetic sensors and smart parking meters are quite common. However, using wireless magnetic sensors can only detect the occupancy of parking spaces without the knowledge of who are currently using these parking spaces; human labor is still needed to issue the parking bills. In contrast, smart parking meters based on image recognition can detect the occupancy of parking spaces along with the license plate numbers, but the cost of deploying smart parking meters is relatively high. In this research, we investigate the feasibility of building an on-street parking management system mainly based on low-cost Bluetooth beacons. Specifically, beacon transmitters are installed in the vehicles, and beacon receivers are deployed along the roadside parking spaces. By processing the received beacon signals using Kalman filter, our system can detect the occupancy of parking spaces as well as the identification of the vehicles. Although distance estimation using the received signal strength is not accurate, our experiments show that it suffices for correct detection of parking occupancy.

The type VI secretion system (T6SS) is a widespread bacterial nanoweapon used for delivery of toxic proteins into cell targets and contributes to virulence, anti-inflammatory processes, and interbacterial competition. In the model phytopathogenic bacterium Pseudomonas syringae pv. tomato ( Pst ) DC3000, two T6SS gene clusters, HSI-I and HSI-II, were identified, but their functions remain unclear. We previously reported that hcp2 , located in HSI-II, is involved in competition with enterobacteria and yeast. Here, we demonstrated that interbacterial competition of Pst DC3000 against several Gram-negative plant-associated bacteria requires mainly HSI-II activity. By means of a systematic approach using in-frame deletion mutants for each gene in the HSI-II cluster, we identified genes indispensable for Hcp2 expression, Hcp2 secretion and interbacterial competition ability. Deletion of PSPTO&#95;5413 only affected growth in interbacterial competition assays but not Hcp2 secretion, which suggests that PSPTO&#95;5413 might be a putative effector. Moreover, PSPTO&#95;5424, encoding a putative σ 54 -dependent transcriptional regulator, positively regulated the expression of all three operons in HSI-II. Our discovery that the HSI-II gene cluster gives Pst DC3000 the ability to compete with other plant-associated bacteria could help in understanding a possible mechanism of how phytopathogenic bacteria maintain their ecological niches., (Copyright © 2020 Chien, Liu, Lu, Sung, Chen and Lin.)

In order to make a correct diagnosis of idiopathic Parkinson's disease (PD), it is essential to exclude atypical parkinsonian features, such as early dementia, fall, and autonomic dysfunction. Rheumatoid arthritis (RA), which is a systemic inflammatory disorder, although most patients present in a polyarticular manner. Still some may also present with extra-articular involvement including skin, lung, heart, and the central or peripheral nervous systems. A possible pathogenetic link between RA and PD are proposed. However, the coexistence of RA and progressive supranuclear palsy (PSP) is rarely reported. Here, we report a parkinsonian patient with a newly diagnosed flare-up RA presenting with early falls, postural instability and supra-nuclear gaze palsy, which suggestive of clinically probable PSP. Furthermore, the parkinsonian features respond to anti-rheumatic agents, but not levodopa. Finally, the patient looks like a clinical possible PD. In summary, Parkinsonian patient with newly diagnosed flare-up RA can present with clinically probable PSP. Unbearably painful limb contracture is a clue of the coexistence of RA. Both typical and atypical parkinsonian features respond dramatically to anti-rheumatic medication, but not levodopa.

GacS/GacA is a conserved two-component system that functions as a master regulator of virulence-associated traits in many bacterial pathogens, including Pseudomonas spp., that collectively infect both plant and animal hosts. Among many GacS/GacA-regulated traits, type III secretion of effector proteins into host cells plays a critical role in bacterial virulence. In the opportunistic plant and animal pathogen Pseudomonas aeruginosa, GacS/GacA negatively regulates the expression of type III secretion system (T3SS)-encoding genes. However, in the plant pathogenic bacterium Pseudomonas syringae, strain-to-strain variation exists in the requirement of GacS/GacA for T3SS deployment, and this variability has limited the development of predictive models of how GacS/GacA functions in this species. In this work we re-evaluated the function of GacA in P. syringae pv. tomato DC3000. Contrary to previous reports, we discovered that GacA negatively regulates the expression of T3SS genes in DC3000, and that GacA is not required for DC3000 virulence inside Arabidopsis leaf tissue. However, our results show that GacA is required for full virulence of leaf surface-inoculated bacteria. These data significantly revise current understanding of GacS/GacA in regulating P. syringae virulence., (© 2019 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Recent advances in next generation sequencing technology allow us to retrieve the whole genome sequence of a requested bacterium in less than a day. Thus, development of quick, easy and efficient means to systemically analyze the functions of all genes is required in the post-genome era. Here, a procedure of finding a suitable chromosome integration site and developing a gene disruption system into a knock-in system in Gram-negative bacteria is proposed. As a proof of concept, we successfully modified a sacB-based gene knock-out strategy into a site-specific gene integration system to deliver a DNA fragment into the genome site between 313,520bp and 313,521bp of the model phytopathogenic bacterium, Pseudomonas syringae pv. tomato (Pst) DC3000. The expression levels of avrPtoB and hcp2 integrated using this method exhibited steady and similar expression levels as those in the wild type. In the future, this concept could allow us to easily develop gene replacement and delivery systems at the same time using a counter-selectable suicide vector-based allelic exchange strategy, and facilitate functional genomics studies of any bacterium whose genome has been sequenced., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Little is known about the effects of tensile forces on osteoclastogenesis by human monocytes in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study we consider the effects of tensile force on osteoclastogenesis in human monocytes. The cells were treated with receptor activator of nuclear factor κB ligand (RANKL) to promote osteoclastogenesis. Then,expression and secretion of cathepsin K were examined. RANKL and the formation of osteoclasts during the osteoclast differentiation process under continual tensile stress were evaluated by Western blot. It was also found that -100 kPa or lower induces RANKL-enhanced tartrate-resistant acid phosphatase activity in a dose-dependent manner. Furthermore, an increased tensile force raises the expression and secretion of cathepsin K elevated by RANKL, and is concurrent with the increase of TNF-receptor-associated factor 6 induction and nuclear factor κB activation. Overall, the current report demonstrates that tensile force reinforces RANKL-induced osteoclastogenesis by retarding osteoclast differentiation. The tensile force is able to modify every cell through dose-dependent in vitro RANKL-mediated osteoclastogenesis, affecting the fusion of preosteoclasts and function of osteoclasts. However, tensile force increased TNF-receptor-associated factor 6 expression. These results are in vitro findings and were obtained under a condition of tensile force. The current results help us to better understand the cellular roles of human macrophage populations in osteoclastogenesis as well as in alveolar bone remodeling when there is tensile stress.

The bean pathogen Pseudomonas syringae pv. syringae B728a expresses homologs of the type III effectors AvrPto and AvrPtoB, either of which can trigger resistance in tomato cultivars expressing Pto and Prf genes. We found that strain B728a also elicits nonhost resistance in tomato cultivars VFNT Cherry and Moneymaker that lack Pto but express other members of the Pto family (e.g., SlFen and SlPtoC). Here, we show that the AvrPtoB homolog from B728a, termed AvrPtoBB728a (also known as HopAB1), is recognized by 'VFNT Cherry' and 'Moneymaker' when the effector is expressed in P. syringae pv. syringae 61, a strain lacking the avrPto or avrPtoB homolog. Using a gene-silencing approach, this recognition was shown to involve one or more Pto family members and Prf. AvrPtoBB728a interacted with SlFen, SlPtoC, and SlPtoD, in addition to Pto, in a yeast two-hybrid assay. In P. syringae pv. tomato DC3000, the C-terminal domain of AvrPtoB is an E3 ubiquitin ligase that ubiquitinates Fen, causing its degradation and leading to disease susceptibility. Although the C-terminal domain of AvrPtoBB728a shares 69% amino acid identity with that of AvrPtoB, we found that it has greatly reduced E3 ligase activity and is unable to ubiquitinate Fen in an in vitro ubiquitination assay. Thus, the nonhost resistance of 'VFNT Cherry' and 'Moneymaker' to B728a appears to be due to recognition of AvrPtoBB728 as a result of the effector's reduced E3 ligase activity, which prevents it from facilitating degradation of a Pto family member. We speculate that the primary plant host of B728a lacks a Fen-like protein and that, therefore, the E3 ligase of AvrPtoBB728 was unnecessary for pathogenicity and has diverged and become ineffective.

Ethnopharmacological Relevance: Gentiopicroside (GPS) is a secoiridoid glucoside isolated from the ethanol extract of Gentianae Radix with a content of 13%, which has been used for centuries in Chinese as a digestive aid., Aim of the Study: This study investigates the pharmacokinetics of GPS and its metabolic pathway for the liver ischemia/reperfusion (I/R) in rats., Materials and Methods: The experimental animals were anesthetized intraperitoneally (i.p.) with a mixture of urethane (1.0 g/kg) and α-chloralose (0.1 g/kg). A midline laparatomy was performed and the liver hilum was gently exposed. All structures in the portal triad (hepatic artery, portal vein, and bile duct) to the left and median liver lobes were occluded with silk thread for 30 min. Ischemia was followed by a sudden reperfusion after removing the occluding threads. After 60 min reperfusion, the rats received a single intravenous 5 mg/kg dose of GPS., Results: The area under concentration curve (AUC) was significantly increased; however, the clearance (Cl) was significantly decreased in the liver I/R rats. Furthermore, after pretreated with SKF-525A (50 mg/kg, i.p.), a cytochrome P450 (CYP) inhibitor, AUC, elimination half-life (t(1/2)) and the mean residence time (MRT) of GPS in rat blood were significantly increased, suggesting that CYP was involved in the metabolism of GPS. For the group without liver I/R, GPS was administered at doses of 5 mg/kg and 100 mg/kg intravenously and orally, respectively. The pharmacokinetic results indicated that the AUC was 565±95.1 and 1163±273 min μg/mL and the t(1/2) of GPS was 71±9 and 106±17 min after intravenous and oral administration, respectively. The oral bioavailability of GPS was 10.3±2.4% in the rats., Conclusions: The status of I/R might prolong the disposition of GPS, and the plasma concentration of GPS in the liver I/R injury rats was significantly increased. The increased body exposure of GPS in the treatment of liver I/R may result from the decreased metabolism of GPS mediated by CYP in the liver., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Polylactic-co-glycolic acid (PLGA) nanoparticles have been used to increase the relative oral bioavailability of hydrophobic compounds and polyphenols in recent years, but the effects of the molecular weight of PLGA on bioavailability are still unknown. This study investigated the influence of polymer molecular weight on the relative oral bioavailability of curcumin, and explored the possible mechanism accounting for the outcome., Methods: Curcumin encapsulated in low (5000-15,000) and high (40,000-75,000) molecular weight PLGA (LMw-NPC and HMw-NPC, respectively) were prepared using an emulsification-solvent evaporation method. Curcumin alone and in the nanoformulations was administered orally to freely mobile rats, and blood samples were collected to evaluate the bioavailability of curcumin, LMw-NPC, and HMw-NPC. An ex vivo experimental gut absorption model was used to investigate the effects of different molecular weights of PLGA formulation on absorption of curcumin. High-performance liquid chromatography with diode array detection was used for quantification of curcumin in biosamples., Results: There were no significant differences in particle properties between LMw-NPC and HMw-NPC, but the relative bioavailability of HMw-NPC was 1.67-fold and 40-fold higher than that of LMw-NPC and conventional curcumin, respectively. In addition, the mean peak concentration (C(max)) of conventional curcumin, LMw-NPC, and HMw-NPC was 0.028, 0.042, and 0.057 μg/mL, respectively. The gut absorption study further revealed that the HMw-PLGA formulation markedly increased the absorption rate of curcumin in the duodenum and resulted in excellent bioavailability compared with conventional curcumin and LMw-NPC., Conclusion: Our findings demonstrate that different molecular weights of PLGA have varying bioavailability, contributing to changes in the absorption rate at the duodenum. The results of this study provide the rationale for design of a nanomedicine delivery system to enhance the bioavailability of water-insoluble pharmaceutical compounds and functional foods.

The safety of herbal products is one of the major concerns for the modernization of traditional Chinese medicine, and pharmacokinetic data of medicinal herbs guide us to design the rational use of the herbal formula. This article reviews the advantages of the automated blood sampling (ABS) systems for pharmacokinetic studies. In addition, three commonly used sample preparative methods, protein precipitation, liquid-liquid extraction and solid-phase extraction, are introduced. Furthermore, the definition, causes and evaluation of matrix effects in liquid chromatography-mass spectrometry (LC/MS) analysis are demonstrated. Finally, we present our previous works as practical examples of the application of ABS systems and LC/MS for the pharmacokinetic studies of Chinese medicinal herbs.

Curcumin has considerable neuro-protective and anti-cancer properties but is rapidly eliminated from the body. By optimizing the HPLC method for analysis of curcumin, this study evaluates how the ability of curcumin to penetrate organs and different regions of the brain is affected by nanoparticulation to increase curcumin circulation time in the body. Curcumin-loaded PLGA nanoparticles (C-NPs) were prepared by the high-pressure emulsification-solvent evaporation method. The mean particle size and entrapment efficiency were 163nm and 46.9%, respectively. The release profile of C-NPs was an initial burst effect followed by sustained diffusion. In distribution studies, curcumin could be detected in the evaluated organs, including liver, heart, spleen, lung, kidney and brain. C-NPs were found mainly in the spleen, followed by the lung. Formulation significantly raised the curcumin concentration in these organs with increases in the AUC, t(1/2) and MRT of curcumin, though this was not apparent in the heart. Curcumin and C-NPs could cross the blood-brain barrier (BBB) to enter brain tissue, where it was concentrated chiefly in the hippocampus. Nanoparticulation significantly prolonged retention time of curcumin in the cerebral cortex (increased by 96%) and hippocampus (increased by 83%). These findings provide further understanding for the possible therapeutic effects of curcumin and C-NPs in further pre-clinical and clinical research., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This study has optimised the poly lactic-co-glycolic acid (PLGA) nano-formulation of curcumin to prolong its retention time in the body and improve bioavailability. High-pressure emulsification-solvent-evaporation was designed to obtain curcumin-loaded PLGA nanoparticles (C-NPs) prepared with 2% of PVA containing 20% sucrose as aqueous phase and dichloromethane as oil phase. The size and entrapment efficiency of C-NPs was 158±10nm and 46.6±13.5%, respectively. The stable storage time of C-NPs was one month at 4°C. When curcumin was formulated, a significant increase of curcumin exposure in rat plasma was revealed from the intravenous study (AUC/Dose raised 55%) and the oral study (AUC/Dose increased 21-fold). The oral bioavailability of curcumin at C-NPs was 22-fold higher than conventional curcumin. Excretion results support oral study that absorption of curcumin was significantly increased by nano-formulation. These findings demonstrate that PLGA nano-formulation could potentially be applied to increase bioavailability of hydrophobic polyphenols., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In this research we propose a fast and robust ellipse detection algorithm based on a multipass Hough transform and an image pyramid data structure. The algorithm starts with an exhaustive search on a low-resolution image in the image pyramid using elliptical Hough transform. Then the image resolution is iteratively increased while the candidate ellipses with higher resolution are updated at each step until the original image resolution is reached. After removing the detected ellipses, the Hough transform is repeatedly applied in multiple passes to search for remaining ellipses, and terminates when no more ellipses are found. This approach significantly reduces the false positive error of ellipse detection as compared with the conventional randomized Hough transform method. The analysis shows that the computing complexity of this algorithm is Θ(n(5/2)), and thus the computation time and memory requirement are significantly reduced. The developed algorithm was tested with images containing various numbers of ellipses. The effects of noise-to-signal ratio combined with various ellipse sizes on the detection accuracy were analyzed and discussed. Experimental results revealed that the algorithm is robust to noise. The average detection accuracies were all above 90% for images with less than seven ellipses, and slightly decreased to about 80% for images with more ellipses. The average false positive error was less than 2%., (© 2011 Optical Society of America)

Herbal medicines have been used to treat liver disorders for thousands of years in the East and have now become a promising therapy internationally for pathological liver conditions. Biological analysis of hepatoprotective herbs is an important issue from the pharmacokinetic perspective in developing new therapeutic managements for liver disease. The biological analysis focuses on the pretreatment methods, separation and quantification of herbal medicines in biological samples. We have compiled and discuss the biological analytical method of six herbal medicines for liver protection containing Silybum marianum(silymarin), Glycyrrhiza glabra, Scutellaria baicalensis, Schisandra chinensis, Salvia miltiorrhiza and Astragalus membranaceus. This review provides a convenient reference for researchers to reduce time-consuming method optimization., (2010 John Wiley & Sons, Ltd.)

Herb-drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of Andrographis paniculata extract (APE) and its major component, andrographolide (AG), on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats. After APE or AG pretreatment for 3 days, on the fourth day rats were administered theophylline via femoral vein cannula. The blood theophylline levels were monitored by microdialysis sampling combined with HPLC-UV. The results indicated that the clearance of theophylline was significantly increased and the area under concentration-time curve (AUC) was reduced in both AG and APE pretreated groups at low-dose theophylline administration (1mg/kg). The elimination half-life (t(1/2beta)) and mean residence time (MRT) of theophylline were shortened by 14% and 17%, respectively, in the AG pretreated group when high-dose theophylline (5mg/kg) was given. However, theophylline accumulated in rat of the group with APE pretreatment. This phenomenon suggests that some other herbal components contained in APE may interact with theophylline and retard its elimination when theophylline was administered at a high dose. Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb-drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy.

Background: Thyroid cancers with pulmonary metastases have been well documented. However, malignant pleural effusion has rarely been reported., Case Report: We present a 77-year-old patient who had Hürthle cell carcinoma of the thyroid with contralateral malignant pleural effusion. The diagnosis was based on consistency in the histopathological and immunohistochemical features of pleural fluid cytology and the final pathology of the thyroid tumor., Results: The patient was treated with total thyroidectomy and postoperative radioactive-iodine ablation. Unfortunately, he died for recurrent pleural effusion and pulmonary complication 6 months later., Conclusion: Identifying the origin of malignant pleural effusion is important to provide treatment guidance. In this report, we review the literature on diagnosis and treatment of thyroid cancer with malignant pleural effusion., (Copyright (c) 2009 S. Karger AG, Basel.)

Enone phosphonates 1 and 2 were found to be excellent dienophiles for the Diels-Alder reaction, giving phosphonate-containing polycycles, and the phosphonate group of the resulting adducts facilitated both the installation of an angular alkyl group via a reductive alkylation process and the regioselective generation of a ring junction double bond via an intramolecular Wadsworth-Horner-Emmons reaction.