Search

Tsung-You Tsai,1,&ast; Huang-Kai Kao,2,3,&ast; Yenlin Huang,4 Ya-Ting Chang,5 Chi-Kuang Young,1 Shao-Yu Hung,3 Yu-Sun Chang,5 Jau-Song Yu,1,5,6 Kai-Ping Chang1,2,5 1Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan; 5Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan; 6Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan&ast;These authors contributed equally to this workCorrespondence: Kai-Ping Chang, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, No. 5, Fu-Hsing St, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext.3967, Fax +886-3-3979361, Email dr.kpchang@gmail.comPurpose: Plasma matrix metalloproteinase-1 (MMP-1) is a collagenase encoded by the MMP-1 gene. However, the prognostic value of plasma MMP-1 levels in oral cavity squamous cell carcinoma (OSCC) has yet to be elucidated. The study is the first to use a cohort of OSCC patients to assess the association of plasma MMP-1 levels with clinicopathological factors/survival outcomes in OSCC patients.Patients and Methods: A total of 677 patients were retrospectively enrolled, including 276 oral potentially malignant disease (OPMD) and 401 OSCC patients from 2013 to 2021. Pretreatment plasma MMP-1 levels were measured with an enzyme-linked immunosorbent assay, and the values were compared between OPMD and OSCC patients. Furthermore, the association of plasma MMP-1 levels and clinicopathological characteristics/survival outcomes in OSCC patients was investigated.Results: Plasma MMP-1 levels were significantly higher in OSCC patients than in OPMD patients (p = 0.04). In the OSCC group, plasma MMP-1 levels were significantly higher in females, tumor depth ≥ 10 mm, advanced pT classification and advanced overall stage (p = 0.04, < 0.001, < 0.001, 0.002, respectively). Higher plasma MMP-1 levels were significantly associated with poorer overall, disease-specific, disease-free, locoregional recurrence-free and distant metastasis-free survival (p = 0.003, 0.02, 0.005, 0.01, 0.001, respectively). Multivariate analysis revealed that plasma MMP-1 levels were a significant predictor for overall, disease-free, and distant metastasis-free survival (p = 0.03, 0.02, and 0.010, respectively).Conclusion: Plasma MMP-1 levels are associated with more severe clinicopathological manifestations and can also be regarded as a significant prognostic factor for OSCC posttreatment outcomes.Keywords: oral cancer, MMP, squamous cell carcinoma, ELISA, OSCC

Yu-Shan Chang,1,2 Liang-Yi Lee,3 I-Te Lee1,2,4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Mingdao High School, Taichung City, Taiwan; 4School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: I-Te LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Taichung City, 40705, TaiwanEmail itlee@vghtc.gov.twPurpose: High glucose concentrations and swings are associated with endothelial dysfunction. We examined the effects of variability in fasting plasma glucose on peripheral artery disease (PAD) in patients with diabetes mellitus (DM).Patients and Methods: In this screening study for the risk factors of PAD, we retrospectively collected data on the ankle-brachial index (ABI) and the percentage of mean arterial pressure (%MAP) at the ankle between August 01, 2016 and July 31, 2017. We defined low ABI ≤ 0.90, high %MAP ≥ 45%, or both as high-risk PAD and others as low-risk PAD. We compared the standard deviation (SD) of the first fasting plasma glucose data available each year after January 01, 2007.Results: In 2577 patients, a higher SD of annual fasting glucose was observed in those with an ABI ≤ 0.90 than in patients with an ABI > 0.90 (2.6 ± 2.1 vs 2.2 ± 2.3, P = 0.009), and in patients with %MAP ≥ 45% than in those with %MAP < 45% (2.4 ± 2.1 vs 2.2 ± 2.3, P = 0.034). A high-risk PAD was significantly associated with the SD (P = 0.032) but not with the mean (P = 0.338) of annual fasting glucose. The former was an independent risk factor for high-risk PAD (odds ratio = 1.424; 95% CI = 1.118‒1.814; P = 0.004).Conclusion: Variability but not mean of annual fasting plasma glucose was significantly associated with a high risk of PAD in patients with DM.Keywords: ankle-brachial index, arterial stiffness, lower extremity arterial disease, percentage of the mean arterial pressure, standard deviation

Mei-Hsuen Huang,1 Yu-Fan Liu,2,3 Oswald Ndi Nfor,4 Shu-Yi Hsu,4 Wei-Yong Lin,5– 7 Yuan-Shiun Chang,1 Yung-Po Liaw4,8 1Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; 2Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan; 3Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan; 5Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; 6Department of Medical Research, China Medical University Hospital, Taichung, 40447, Taiwan; 7Brain Diseases Research Center, China Medical University, Taichung, 40402, Taiwan; 8Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, TaiwanCorrespondence: Yung-Po LiawDepartment of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110, Sec. 1 Jianguo N. Road, Taichung City, 40201, TaiwanTel +886-4-24730022 ext.11838Fax +886-4-23248179Email Liawyp@csmu.edu.twYuan-Shiun ChangDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung, 40402, TaiwanTel +886-4-22053366 ext. 5502Fax +886-4-22083362Email yschang@mail.cmu.edu.twPurpose: We investigated the interactive effect of rs10506151 polymorphism of the Leucine-rich repeat kinase 2 (LRRK2) gene and type 2 diabetes (T2D) on neurodegenerative disease (ND) risk.Materials and Methods: Data of 17, 927 participants in the Taiwan Biobank (TWB) assessed between 2008 and 2015 were linked to healthcare records in the National Health Insurance Research Database (NHIRD). The odd ratios (ORs) and 95% confidence intervals (CIs) for NDs were determined using logistic regression analysis.Results: There were 145 cases with NDs, and 28.28% (n = 41) of these individuals had T2D. Associations of neurodegenerative disorders with LRRK2 rs10506151 variant and T2D were not significant. The corresponding ORs (95% CI) for NDs were 1.06 (0.75– 1.49) in CA/AA compared to CC individuals and 0.93 (0.63– 1.39) in those with T2D compared to non-diabetic participants. However, we found evidence of a significant interaction between rs10506151 and T2D (p = 0.0073). After stratification by genotypes of rs10506151, the OR for NDs was 0.37 (CI, 0.17– 0.82) in CA/AA individuals with T2D and 1.41 (0.88– 2.27) in their CC counterparts. When CA/AA individuals with T2D represented the reference group, the OR (95% CI) was 1.74 (0.81– 3.73) in CC individuals with no T2D, 2.47 (CI, 1.14– 5.38) in CA/AA individuals with no T2D, and 2.34 (CI, 1.07– 5.11) in CC individuals with T2D.Conclusion: Our data indicated that the risk of NDs was significantly lower among diabetic individuals with combined CA/AA of the LRRK2 rs10506151 variant in Taiwan.Keywords: polymorphism, neurodegenerative disorders, diabetes, variation

Ying-Shuang Chang,1 Hung-Wei Kan,2 Yu-Lin Hsieh1,3 1Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 2Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan; 3Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan Background: Skin denervation that develops in patients with diabetes mellitus as a neuropathic manifestation is known as diabetic peripheral neuropathy (DPN). Skin denervation is parallel to neuronal injuries that alter intracellular signaling. To date, the correlation between nerve injury and the activation of intracellular responses to neuropathic manifestations has not been elucidated; specifically, whether activating transcription factor 3 (ATF3) is responsible for neuronal injury and a critical molecule that modulates the activation of intracellular protein kinase C epsilon (p-PKCε) and pain development in DPN is a crucial question. Methods: To address, ATF3 knockout (atf3−/− group, C57/B6 genetic background) and wild-type mice (atf3+/+ group) received a single dose of streptozotocin (200 mg/kg) to generate a mouse model of DPN. Results: Both atf3+/+ and atf3−/− mice exhibited hyperglycemia and the same pathology of skin denervation at posttreatment month 2, but only atf3+/+ mice developed thermal hyperalgesia (P

Background and purposePrecision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study.Materials and methodsDiffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract.ResultsFor the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was

© 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is mad

The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge betweenness centrality, we identify specific white matter regions involved in a large number of shortest paths, some containing highly connected rich club edges while others are relatively isolated within individual modules. Overall, these findings reveal an intricate relationship between white matter anatomy and the structural connectome, motivating further exploration of EDI for biomarkers of cognition and behavior.

Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria.

With the ban of conventional cigarettes from public spaces, electronic cigarette (E-cig) liquids have emerged as a nicotine replacement treatment for smoking cessation. However, consumers possess little knowledge of the ingredients and health effects of E-cig liquids following exposure. This study evaluated hair cell damage and developmental toxicities following gestational exposure to E-cig liquids. Zebrafish embryos were exposed to E-cig liquids at different concentrations (0.1%, 0.2%, and 0.4%). Embryonic developmental toxicity and hair cell damage was evaluated at 6 and 7 d, respectively, after fertilization. The average number of hair cells in the anterior lateral line (ALL) and posterior lateral line (PLL) following E-cig exposure was compared to that of the control. Morphological abnormalities and heart rate were evaluated. E-cig liquids significantly damaged the hair cells in the ALL, compared to the control (control; 52.85 ± 5.29 cells, 0.1% E-cig; 49.43 ± 7.70 cells, 0.2% E-cig; 40.68 ± 12.00 cells, 0.4% E-cig; 32.14 ± 20.75%; n = 29–40; p < 0.01). At high concentrations, E-cig liquids significantly damaged the hair cells in the PLL (control; 36.88 ± 5.43 cells, 0.1% E-cig; 33.06 ± 5.21 cells, 0.2% E-cig; 30.95 ± 8.03 cells, 0.4% E-cig; 23.72 ± 15.53%, n = 29–40; p < 0.01). No morphological abnormalities in body shape, somites, notochord, tail, and pectoral fin were observed; however, abnormalities were observed in the dorsal fin and heart rate at high concentrations. Thus, gestational exposure to E-cigs significantly damaged hair cells in a concentration-dependent manner and induced developmental toxicities to the dorsal fin and heart rate at high concentrations. [ABSTRACT FROM AUTHOR]

Objective: To compare the patient characteristics, clinical features and outcomes of adult patients hospitalised with pandemic (H1N1) 2009 influenza and seasonal influenza.Design and Setting: Retrospective medical record review of all patients admitted to Liverpool Hospital, Sydney, with laboratory-confirmed influenza from the initiation of the "PROTECT" phase of the pandemic response on 17 June until the end of our study period on 31 July 2009.Main Outcome Measures: Severity of illness; requirement for admission to the intensive care unit (ICU) and/or invasive ventilation; mortality.Results: Sixty-four adults were admitted to Liverpool Hospital with influenza, 48 with pandemic (H1N1) 2009 influenza and 16 with seasonal influenza. Thirteen patients were admitted to the ICU. Seven required invasive ventilation, with 2 patients requiring ongoing extracorporeal membrane oxygenation (ECMO). Five patients died (mortality rate, 8%) with two deaths occurring after the study period. Patients with pandemic (H1N1) 2009 influenza were younger and less likely to be immunocompromised than patients with seasonal influenza. However, the clinical features of pandemic (H1N1) 2009 influenza and seasonal influenza were similar.Conclusions: Our findings show that the clinical course and outcomes of pandemic (H1N1) 2009 influenza virus are comparable to those of the current circulating seasonal influenza in Sydney. The high number of hospital admissions reflects a high incidence of disease in the community rather than an enhanced virulence of the novel pandemic influenza virus. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by lambda-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1beta (IL-1beta), tumor necrosis factor (TNF-alpha), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after lambda-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after lambda-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1beta, tumor necrosis factor-alpha, NO and MDA which were induced by lambda-carrageenan. The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1beta production and the level of TNF-alpha in the inflamed tissues. [ABSTRACT FROM AUTHOR]

Objective: Spinal muscular atrophy (SMA) is a common inherited neuromuscular disorder caused by homozygous loss of function of the survival motor neuron 1 (SMN1) gene. All SMA patients carry at least one copy of a nearly identical SMN2 gene. However, a critical nucleotide change in SMN2 results in alternative splicing and exclusion of exon 7 in the majority of SMN2 messenger RNA (mRNA), thus producing a low level of functional SMN protein. Increasing SMN protein production by promoting SMN2 exon 7 inclusion could be a therapeutic approach for SMA. It has been shown that cellular pH microenvironment can modulate pre-mRNA alternative splicing in vivo. In this study, we tested whether inhibitors of the Na+/H+ exchanger can modulate the exon 7 splicing of SMN2 mRNA METHODS: We treated SMA lymphoid cell lines with Na+/H+ exchanger inhibitors and then measured SMN2 exon 7 splicing by reverse transcriptase polymerase chain reaction and SMN protein production by Western blotting and immunofluorescenceResults: We found that treatment with an Na+/H+ exchanger inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), significantly enhances SMN2 exon 7 inclusion and SMN protein production in SMA cells. In addition, EIPA increases the number of nuclear gems in SMA cells. We further explored the underlying mechanism, and our results suggest that EIPA may promote SMN2 exon 7 inclusion through upregulation of the splicing factor SRp20 in the nucleusInterpretation: Our finding that EIPA, an inhibitor of the Na+/H+ exchanger, can increase SMN protein expression in SMA cells provides a new direction for the development of drugs for SMA treatment. However, further translational studies are needed to determine whether this finding is applicable for SMA treatment or just a proof of cellular pH effect on SMN splicing. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR)alpha, a member of the ligand-activated nuclear receptor superfamily, plays an important role in lipid metabolism and glucose homeostasis and is highly expressed in the kidney. The present studies were aimed at determining the role of PPARalpha in the pathogenesis of diabetic nephropathy using PPARalpha-knockout mice and cultured murine mesangial cells. Diabetes was induced using a low-dose streptozotocin protocol in 8-week-old male 129 SvJ PPARalpha-knockout and wild-type mice. Diabetic PPARalpha-knockout and wild-type mice developed elevated fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001). Renal functional and histopathological changes in diabetic and nondiabetic PPARalpha-knockout and wild-type mice were evaluated after 16 weeks of hyperglycemia. PPARalpha immunostaining of the cortical tubules of diabetic wild-type mice was elevated by hyperglycemia. In diabetic PPARalpha-knockout mice, renal disease with accompanying albuminuria, glomerular sclerosis, and mesangial area expansion was more severe than in diabetic wild-type mice (P < 0.05) and was accompanied by increased levels of serum free fatty acids and triglycerides (P < 0.01). Furthermore, they exhibited increased renal immunostaining for type IV collagen and osteopontin, which was associated with increased macrophage infiltration and glomerular apoptosis. There were no significant differences in these indexes of renal disease between nondiabetic PPARalpha-knockout and wild-type mice and diabetic PPARalpha wild-type mice. In vitro studies demonstrated that high glucose levels markedly increased the expression of type IV collagen, transforming growth factor-beta1, and the number of leukocytes adherent to cultured mesangial cells. Adherence of leukocytes was inhibited by the PPARalpha agonist fenofibrate. Taken together, PPARalpha deficiency appears to aggravate the severity of diabetic nephropathy through an increase in extracellular matrix formation, inflammation, and circulating free fatty acid and triglyceride concentrations. PPARalpha agonists may serve as useful therapeutic agents for type 1 diabetic nephropathy. [ABSTRACT FROM AUTHOR]

In today's global market, managing the entire supply chain has become a key factor for a successful business. Competitive pressures force companies to continuously devise ways to achieve better supply chain solutions, faster-better-cheaper. One key area is overall customer satisfaction, which translates as the ability to accurately deliver what is promised at all times. Success in such a case is directly influenced by a company's ability to make accurate promises through precise planning and execution. This also must be achieved by managing a highly variable demand that comes in a variety of forms from a number of different sources, such as e-commerce sites, digital exchanges and trading partners, etc. For these reasons companies retool key business processes and adopt new ways of doing things. Early developments in the area include single-site available-to-promise systems. In this paper we will introduce the concepts and present the design of a distributed order promising system, which enables available-to-promise/capable-to-promise for distributed enterprises. [ABSTRACT FROM AUTHOR]

Panax ginseng is a plant that has been used in traditional medicine in China for thousands of years. It is used as a general tonic or adaptogen with chronically ill patients and is frequently featured in traditional medicine prescriptions from China, Japan, and Korea used by cancer patients. The putative active compounds are the ginsenosides, of which there are more than two dozen. These compounds are found in both Panax ginseng and in other Panax species that are used in herbal medicine. Analysis of ginsenosides is being used in developing quality control assessments for ginseng, which has frequently been adulterated due to its high cost; many currently available standardized extracts do appear to contain the amounts of ginsenosides listed on package labeling. The toxicity of ginseng appears to be low: some of the reports of toxic episodes of ginseng may actually pertain to other components of multicomponent preparations. Very low incidence of toxicity has been observed in ginseng clinical trials using well-characterized preparations. Numerous pharmacological activities of ginseng and the ginsenosides have been explored: the authors review here the activities relating to cancer. Immune system modulation, antistress activities, and antihyperglycemic activities are among the most notable features of ginseng noted in laboratory and clinical analyses. Much testing has been done in humans to explore ginseng's purported antifatigue properties, but this area remains controversial. A number of investigations point to antitumor properties and other pharmacological activities related to cancer, but no trials have yet confirmed a clinically significant anticancer activity. Cancer patients may empirically find ginseng to be useful when they are fatigued, although clinical trials should be conducted to confirm its benefits. [ABSTRACT FROM AUTHOR]

Keywords:antiphospholipid syndrome; papillary muscle rupture; systemic lupus erythematosus [ABSTRACT FROM PUBLISHER]