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Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

Background: One key population related to achieving the global goal of hepatitis C virus (HCV) elimination is people who inject drugs (PWID). By surveying opioid agonist treatment (OAT) programs nationwide in Taiwan, this study aimed to examine (1) the current status of HCV care cascade provision by OAT programs and (2) the opinions of the programs' directors on integrating the HCV care cascade into OAT programs., Methods: From September to November 2022, questionnaires were sent via administrative networks to case managers for information on daily operation and routine booking and to directors for information on the HCV care cascade of 185 OAT programs. The responses of the 125 OAT programs that provided information from both case managers and directors were included for subsequent analyses., Results: Among the 125 OAT programs, 91 (73 %) offered HCV antibody testing, and 69 (55 %) offered HCV treatment services. The provision of HCV antibody testing was associated with being general hospital- or psychiatric hospital-based and having more care team personnel, whereas the provision of HCV treatment was associated with being general hospital-based. However, on-site HCV treatment was found to be rarely offered, and the future willingness to do so remained low., Conclusion: Our survey revealed that the provision of HCV screening and treatment in OAT programs in Taiwan has substantial room for improvement. Increasing the number of care personnel for satellite-dispensing OAT programs is key to expanding the service for HCV screening, as more issues related to multidisciplinary medical resources are involved in the provision of HCV treatment. Our results point to some options that might help accomplish these goals., Competing Interests: Declaration of competing interest We declare that we have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)-SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP-SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs., Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro . Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms., Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs., Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA., The Translational Potential of This Article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors.)

The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVβ3 and α5β1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVβ3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins. Two asparagines, N481 and N501, on the Wild-type spike receptor-binding domain have been previously shown to have deamidation half-lives of 16.5 and 123 days, respectively, which may occur during the viral life cycle. Deamidation of Omicron subvariant N405 may recover the ability to interact with RGD-binding integrins. Thus, herein, all-atom molecular dynamics simulations of the Wild-type and Omicron subvariant spike protein receptor-binding domains were conducted to investigate the potential for asparagines, the Omicron subvariant N405 in particular, to assume the optimized geometry for deamidation to occur. In summary, the Omicron subvariant N405 was primarily found to be stabilized in a state unfavourable for deamidation after hydrogen bonding with downstream E406. Nevertheless, a small number of RGD or RGisoD motifs on the Omicron subvariant spike proteins may restore the ability to interact with RGD-binding integrins. The simulations also provided structural clarification regarding the deamidation rates of Wild-type N481 and N501 and highlighted the utility of tertiary structure dynamics information in predicting asparagine deamidation. Further work is needed to characterize the effects of deamidation on spike-integrin interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The intertidal zone, due to its location in the transition zone of terrestrial and marine ecosystems, is seriously disturbed by anthropogenic activities such as fuel combustion and industrial production, causing significant increase in dissolved organic matter (DOM). However, the distribution and properties of DOM in intertidal sediments at the large scale and their correlations with local socio-economic indicators remain unclear. In this study, we collected sediment samples from 13 intertidal zones across 11 coastal provinces in China and analyzed optical properties and compositions of sedimentary DOM. The results showed that the physico-chemical properties of sediment, such as pH and texture, affected the content of organic matter, thereby influencing the concentration of sedimentary DOM indirectly. The contents of fulvic acid- and protein-like components were relatively higher than humic acid-like component at all sampling sites. Moreover, urbanization could lead to the release of aromatic and humified organic matters into intertidal zones. Unlike coal, oil consumption exhibited positive correlation with SUVA 254 , indicating that the combustion of oil released more aromatic compounds. These findings revealed the impact of anthropogenic activities on sedimentary DOM and provided theoretical basis for predicting and regulating intertidal carbon sink., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The essential cause of phosphorus scarcity and phosphorus-induced risks, i.e. phosphorus dilemma, mainly lies in current low phosphorus flow efficiency (PFE) in agricultural systems. Improving PFE largely depends on secondary phosphorus retention along the phosphorus flow chain from phosphate mining to terrestrial agricultural systems, to aquatic systems, and ultimately to seabed deposition. Our review found that aquatic systems will have the opportunity and growing capacity to retain seaward secondary phosphorus carried by the runoff, due to its location between land and water systems, its ability of converting secondary phosphorus from both land and aquatic systems into aquatic products, and its rapid expansion with low PFE. However, a knowledge gap exists in secondary phosphorus retention in aquatic systems compared to in terrestrial systems. Although the phosphorus retention literature continues to grow in environmental and agricultural & biological sciences, only 8.8% of the documents are related to aquatic systems with few quantification studies. Based on the literature with phosphorus retention quantification since 1979, we divided the reported phosphorus interceptors into abiotic and biotic groups, further into 7 categories and more subcategories. By 2020, eight categories of interceptors had been reported, increased from only one interceptor in 1979. However, most of them focused on wetlands, only a few studies on aquatic organisms which concentrated in 8 countries before 2000. Thus, it is urgent to emphasize aquatic systems' secondary phosphorus retention capacity and its systemic benefits for a sustainable phosphorus use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Coral reefs worldwide are receding because of detrimental human activities, and cryopreservation of coral larvae would ensure that their genetic biodiversity is not irremediably lost. In recent years, the vitrification and laser warming of coral propagules has demonstrated promising results. During cryopreservation, cellular membranes undergo substantial reconfigurations that may affect survival. Fat enrichment may alter the physical proprieties of cell membranes and improve resistance to low temperatures. Therefore, the aim of this study was to determine whether supplementation of exogenous lipids using liposomes would improve cryosurvival and further development of the vitrified and laser-warmed coral larvae of Seriatopora caliendrum and Pocillopora verrucosa. A vitrification solution (VS) composed of 2 M ethylene glycol (EG), 1 M propylene glycol (PG), 40% (w/v) Ficoll, and 10% gold nanoparticles (at a final concentration of 1.2 × 10 18 particles/m 3 and an optimised emission wavelength of 535 nm) was chosen. Coral larvae were subjected to vitrification with VS incorporating one of four lipid classes: phosphatidylcholine (PC), phosphatidylethanolamine (PE), erucic acid (EA), and linoleic acid (LA). Warming was achieved using a single laser pulse (300 V, 10 ms pulse width, 2 mm laser beam diameter). A significantly higher vitality rate was observed in S. caliendrum larvae subjected to vitrification and laser warming with EA-incorporated VS, and P. verrucosa larvae vitrified and laser warmed using PE-incorporated VS achieved a significantly higher settlement rate. Our study demonstrated that supplementation of exogenous lipids with liposomes enhances coral larvae cryotolerance and improves cryopreservation outcomes. Lipid enrichment may play a key role in cryobanking coral propagules, and in propagule development after thawing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Berberine (BBR) is an important natural product with poor gastrointestinal behavior includes low permeability, P-glycoprotein efflux, and mass elimination in the intestine. The aim of this study was to develop a novel nanoemulsion (NE) to improve the hypoglycemic efficacy of BBR. NE was prepared and characterized by morphology and droplet size detection, stored stability, in vitro intestinal lipolysis and metabolism, Caco-2 cells transport, in situ single-pass intestinal perfusion, oral bioavailability in rats, and hypoglycemic efficacy in high-fat diet and streptozocin-induced mice. BBR-loaded NE exhibits small droplet size (30.56 ± 0.35 nm) and good stability. NE could remain intact after lipolysis and protect BBR against the intestinal metabolism mediated by CYP2D6 and CYP3A4. Cells transport and intestinal perfusion studies revealed that NE decreases the P-glycoprotein efflux of BBR by 2-fold and enhances its permeability by 5.5-fold. Consequently, NE increased the oral bioavailability of BBR in rats by 212.02%. Compared to BBR control, blood glucose level of diabetic mice by NE was decreased by 3-fold. This novel NE provides a promising carrier to improve the hypoglycemic efficacy of BBR by overcoming its gastrointestinal deficiency, which may offer a product for the therapy of diabetes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a 4 month-old boy with catecholaminergic polymorphic ventricular tachycardia carrying the double heterozygous mutations RyR2-A1855D and SCN10A-Q1362H. PBMCs were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carry RyR2-A1855D and SCN10A-Q1362H mutations and have a normal karyotype. They will be useful for studying the pathogenesis of CPVT patients with ≥2 variants., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study compared survival between definitive chemoradiotherapy (CRT) and esophagectomy alone among patients with locoregional esophageal squamous cell carcinoma (SCC)., Methods: Data were obtained from the Taiwan Cancer Registry between 2008 and 2014. Included were 5,487 patients with clinical I, II, or III esophageal SCC who received definitive CRT or esophagectomy alone. Patients were stratified according to clinical stage. Overall survival was compared between patients treated with definitive CRT versus esophagectomy alone, and between patients in the three different clinical stages. Propensity-matched analysis along with univariate and multivariate analysis were performed., Results: Treatment was with definitive CRT in 4,251 patients (77.50%) and esophagectomy alone in 1,236 (22.50%). Propensity score matching produced 1,020 patients for comparison. The overall survival rates at 1, 2, and 3 years were 60.92%, 34.96%, and 26.14%, respectively, for propensity-matched patients treated with definitive CRT and were 71.15%, 56.50%, and 46.17%, respectively, for propensity-matched patients treated with esophagectomy alone (p < 0.001). Multivariate analysis showed treatment strategy was an independent prognostic factor. Esophagectomy alone was associated with significantly better overall survival than definitive CRT for patients with clinical stage I/II disease. There was no survival risk difference between definitive CRT and esophagectomy only for patients with clinical stage III disease., Conclusions: Esophagectomy alone could provide better survival than definitive CRT for patients with clinical stage I/II esophageal SCC. However, definitive CRT and esophagectomy yield similar overall survival rates in clinical stage III patients., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Paraquat (PQ) as an herbicide has been demonstrated to impair dopaminergic (DAergic) neurons and highly correlate with the etiology of Parkinson's disease (PD). WNT/β-CATENIN signaling is known for the specification and neurogenesis of midbrain DAergic neurons and implicated as a therapeutic target in treating many diseases, such as cancer and degenerative diseases. LGK974, a WNT pathway inhibitor, is currently under clinical trial for patients with malignancies. Since the exact role of WNT/β-CATENIN signaling in mediating PD is undetermined, LGK974 was used to examine its effect on the PQ-induced cell model of PD. LGK974 attenuated PQ-induced apoptosis and released mitochondrial pro-poptotic molecules in human neuroblastoma SH-SY5Y cell. PQ increased the levels of β-CATENIN, non-phosphorylated (Ser33/37/Thr41) β-CATENIN, and phosphorylated glycogen synthase kinase (GSK)-3α/β. PQ also increased the nuclear translocation of β-CATENIN, which can be attenuated by LKG974. Furthermore, LGK974 attenuated the PQ-induced release of mitochondrial proapoptotic factors and WNT agonist 1-induced cell death. Taken together, we have shown for the first time that LGK974 mediated through the WNT/β-CATENIN pathway to prevent PQ-induced cell death., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Thymoma is a common neoplasm in the anterior mediastinum but rarely arises from the middle mediastinum. We report 3 patients with thymoma that arose from the middle mediastinum. Surgical resections were performed with dissection of the azygos vein, which led to safe separation of the tumors from mediastinal structures. Although rare, thymoma should be included in the differential diagnosis for middle mediastinal tumors., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Tracheal resection and reconstruction are traditionally approached with a right lateral thoracotomy or a median sternotomy. The thoracoscopic approach is usually applied in lung resection surgery in most hospitals but seldom used in tracheal resection. Three or more incisions are usually created during a thoracoscopic tracheal resection. We prescribed a method of single-incision thoracoscopic tracheal resection and reconstruction in a case of squamous cell carcinoma of the right tracheal wall., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This study prepares biodegradable bone scaffolds helping the recovery of damaged tibias of rats. Polyvinyl alcohol (PVA) plied yarns are fabricated into hollow braids. The braids are combined with hydroxyapatite (HA)/gelatin/PVA mixtures and processed using freeze-thawing and freeze-drying processes in order to form bone scaffolds. These bone scaffolds are observed by scanning electron scope (SEM) and tested for compression strength. Afterwards, recovery of damaged bone, the morphology of the bone, and the histological observation are evaluated. Results indicate a small amount of HA helps in enhancing the compressive strength of bone scaffolds. Results of in vivo assay indicate the damaged tibias of rats recover and function well eight weeks after the implantation, and exhibit a normal morphology. Histological observation confirms the bone scaffolds gradually decompose, allowing tissue infiltration and facilitating ossification. This study successfully produces bone scaffolds with satisfactory mechanical properties helping in the recovery of damaged tibias of rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Alcohol-related dementia (ARD) is a heterogeneous long-term cognitive problem that can develop in the course of alcoholism. Current understanding of ARD remains limited., Methods: We conducted a systematic review to synthesize available data on the epidemiology of ARD, through searching the relevant studies in the PubMed, PsycINFO, and ALOIS. "Alcohol" and "dementia" were used as keywords., Results: We included articles published between January 1, 1991 and February 29, 2016, where language was not limited. Of the 9 identified articles, the prevalence of ARD ranged from 1.19/1000 in multiday admission patients residing in the United Kingdom to 25.6% in elderly clinic alcoholics from the United States. The proportion of ARD in early-onset dementia taken from 3 studies was approximately 10%, whereas only 1.28% in late-onset dementia taken from 1 study., Conclusions: Considering the relatively high proportion of ARD in early-onset dementia and its potentially reversible course, future investigation into ARD is necessary., (Copyright © 2017. Published by Elsevier Inc.)

Human fibroblast-like synoviocytes (FLSs) play a role in joint synovial inflammation in rheumatoid arthritis (RA). Some evidence indicates that particulate matter (PM) in air pollution could contribute to the progression of RA. However, more research is needed to clarify this relationship. Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E 2 (PGE 2 ) are implicated in various inflammatory diseases. Resveratrol, a polyphenol found mainly in grapes and red wine, has antioxidant and anti-inflammatory activities. In the present study, we demonstrated that resveratrol reduced PM-induced COX-2/PGE 2 expression in human FLSs, and attenuated PM-enhanced NADPH oxidase activity and ROS generation. In addition, PM induced Akt, ERK1/2, or p38 MAPK activation, which was inhibited by resveratrol. Finally, we demonstrated that PM enhanced NF-κB p65 phosphorylation and the NF-κB promoter activity, which were reduced by pretreatment with a ROS inhibitor or resveratrol. Thus, we concluded that resveratrol functions as a suppressor of PM-induced inflammatory signaling pathways by inhibiting COX-2/PGE 2 expression., (Copyright © 2017. Published by Elsevier Ltd.)

Fibrosis is an exaggerated form of tissue repair that occurs with serious damage or repetitive injury and ultimately leads to organ failure due to the excessive scarring. Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown. We studied this by deletion of Trpc6 in mice and found it decreased unilateral ureteral obstruction-induced interstitial fibrosis and blunted increased mRNA expression of fibrosis-related genes in the ureteral obstructed kidney relative to that in the kidney of wild-type mice. Administration of BTP2, a pyrazol derivative known to inhibit function of several TRPC channels, also ameliorated obstruction-induced renal fibrosis and gene expression in wild-type mice. BTP2 inhibited carbachol-activated TRPC3 and TRPC6 channel activities in HEK293 cells. Ureteral obstruction caused over a 10-fold increase in mRNA expression for TRPC3 as well as TRPC6 in the kidneys of obstructed relative to the sham-operated mice. The magnitude of protection against obstruction-induced fibrosis in Trpc3 and Trpc6 double knockout mice was not different from that in Trpc6 knockout mice. Klotho, a membrane and soluble protein predominantly produced in the kidney, is known to confer protection against renal fibrosis. Administration of soluble klotho significantly reduced obstruction-induced renal fibrosis in wild-type mice, but not in Trpc6 knockout mice, indicating that klotho and TRPC6 inhibition act in the same pathway to protect against obstruction-induced renal fibrosis. Thus klotho and TRPC6 may be pharmacologic targets for treating renal fibrosis., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Health risk of residents dwelling around e-waste recycling zones has been a global concern, but has not been adequately examined. The present study was intended to evaluate the potential health risk of residents through inhalation exposure to size-fractionated particle-bound heavy metals in a typical e-waste recycling zone, South China. Anthropogenic metals (Zn, Se, Pb, Sb, As, and Cd) were predominantly enriched in fine particles (Dp<1.8μm), whereas the crustal elements (Ti, Fe, and Co) tended to accumulate in coarse particles (Dp>1.8μm). Although the daily inhalation intakes of the target metals were significantly lower than those through food consumption and ingestion of house dust, the hazard quotients of total metals for adults (95% CI: 1.0-5.5) and children (95% CI: 3.0-17) were greater than 1. Moreover, the incremental lifetime cancer risks of five carcinogenic metals (Cr, Co, Ni, As, and Cd) for adults and children were 1.3×10(-3) (95% CI: 4.1×10(-4)-3.0×10(-3)) and 3.9×10(-3) (95% CI: 1.3×10(-3)-8.6×10(-3)), respectively, substantially higher than the acceptable cancer risk range of 10(-6)-10(-4). All these findings suggested that health risks were high for local residents dwelling around the e-waste recycling zone through inhalation exposure to particle-bound heavy metals, for both adults and children., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Triclosan (TCS) is a broad spectrum antibacterial agent mainly used in Pharmaceutical and Personal Care Products. Its increasing use over recent decades have raised its concentration in the environment, with commonly detectable levels found along the food web-from aquatic organisms to humans in the ecosystem. To date, there is shortage of information on how to investigate TCS's systematic risk on exposed organisms including humans, due to the paucity of systematic information on TCS flows in the anthroposphere. Therefore, a more holistic approach to mass flow balancing is required, such that the systematic risk of TCS in all environmental matrices are evaluated. From the perspective of Substance Flow Analysis (SFA), this review critically summarizes the current state of knowledge on TCS production, consumption, discharge, occurrence in built and natural environments, its exposure and metabolism in humans, and also the negative effects of TCS on biota and humans. Recent risk concerns have mainly focused on TCS removal efficiencies and metabolism, but less attention is given to the effect of mass flows from source to fate during risk exposure. However, available data for TCS SFA is limited but SFA can derive logical systematic information from limited data currently available for systematic risk assessment and reduction, based on mass flow analysis. In other words, SFA tool can be used to develop a comprehensive flow chart and indicator system for the risk assessment and reduction of TCS flows in the anthroposphere, thereby bridging knowledge gaps to streamline uncertainties related to policy-making on exposure pathways within TCS flow-lines. In the final analysis, specifics on systematic TCS risk assessment via SFA, and areas of improvement on human adaptation to risks posed by emerging contaminants are identified and directions for future research are suggested., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Aims: There is growing evidence of an increased prevalence of osteoarthritis (OA) among people with diabetes. Synovial inflammation and increased expression of cyclooxygenase-2 (COX-2) are two key features of patients with OA. Methylglyoxal (MGO) is a common intermediate in the formation of advanced glycation end-products, and its concentration is also typically higher in diabetes. In this study, we investigated the effects of the treatment of different MGO concentrations to rabbit HIG-82 synovial cells on COX-2 expression., Main Methods: The MGO induced COX-2 mRNA expression was detected by quantitative polymerase chain reaction. The MGO induced COX-2 protein production and its signaling pathways were detected by western blotting. The nuclear factor-kappa B (NF-κB) nuclear translocation by MGO was examined by immunofluorescence., Key Findings: In the present study, we find that MGO has no toxic effects on rabbit synovial cells under the experimental conditions. Our analysis demonstrates that MGO induced COX-2 mRNA and protein production. Moreover, MGO induces p38-dependent COX-2 protein expression as well as the phosphorylations of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and Akt/mammalian target of rapamycin (mTOR)/p70S6K; however, inhibition of JNK and Akt/mTOR/p70S6K phosphorylations further activates COX-2 protein expression. Furthermore, MGO is shown to activate of nuclear factor-kappa B (NF-κB) nuclear translocation., Significance: Our results suggest that MGO can induce COX-2 expression via a p38-dependent pathway and activate NF-κB nuclear translocation in synovial cells. These results provide insight into the pathogenesis of the synovial inflammation under the diabetic condition associated with higher MGO levels., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The incorporation of hydroxyapatite (HA) nanoparticles within or on the surface of electrospun polymeric scaffolds is a popular approach for bone tissue engineering. However, the fabrication of osteoconductive composite scaffolds via benign processing conditions still remains a major challenge to date. In this work, a new method was developed to achieve a uniform coating of calcium phosphate (CaP) onto electrospun keratin-polycaprolactone composites (Keratin-PCL). Keratin within PCL was crosslinked to decrease its solubility, before coating of CaP. A homogeneous coating was achieved within a short time frame (~10min) by immersing the scaffolds into Ca(2+) and (PO4)(3-) solutions separately. Results showed that the incorporation of keratin into PCL scaffolds not only provided nucleation sites for Ca(2+) adsorption and subsequent homogeneous CaP surface deposition, but also facilitated cell-matrix interactions. An improvement in the mechanical strength of the resultant composite scaffold, as compared to other conventional coating methods, was also observed. This approach of developing a biocompatible bone tissue engineering scaffold would be adopted for further in vitro osteogenic differentiation studies in the future., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Silver nanoparticles (AgNPs) have antibacterial characteristics, and currently are applied in Ag-containing products. This study found neural cells can uptake 3-5 nm AgNPs, and investigated the potential effects of AgNPs on gene expression of inflammation and neurodegenerative disorder in murine brain ALT astrocytes, microglial BV-2 cells and neuron N2a cells. After AgNPs (5, 10, 12.5 μg/ml) exposure, these neural cells had obviously increased IL-1β secretion, and induced gene expression of C-X-C motif chemokine 13 (CXCL13), macrophage receptor with collagenous structure (MARCO) and glutathione synthetase (GSS) for inflammatory response and oxidative stress neutralization. Additionally, this study found amyloid-β (Aβ) plaques for pathological feature of Alzheimer's disease (AD) deposited in neural cells after AgNPs treatment. After AgNPs exposure, the gene expression of amyloid precursor protein (APP) was induced, and otherwise, neprilysin (NEP) and low-density lipoprotein receptor (LDLR) were reduced in neural cells as well as protein level. These results suggested AgNPs could alter gene and protein expressions of Aβ deposition potentially to induce AD progress in neural cells. It's necessary to take notice of AgNPs distribution in the environment., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The mineralizing capabilities of surface-modified dicalcium phosphate anhydrous (DCPA), reinforced and treated with nanocrystals and capped with silane, in composite resins were analyzed via thermal cycling. We compared two light-curable composites that were mixed at filler-to-resin mass ratios of 30/70 and 50/50. The strengths, elastic moduli, and topographical structures of the samples were determined after thermal cycling between 5 and 55°C in deionized water for 600 and 2400 cycles. Silane-capped particles decreased the strength but enhanced the mineralizing capability of the composites. Nanocrystal-treated filler surfaces significantly increased the strength and moduli of the composites after 600 thermal cycles. However, these values declined after 2400 thermal cycles. The nanocrystal-treated filler surfaces prevented the reduction in strength before and after 2400 thermal cycles. Prior to silane capping, the nanocrystal-treated DCPA filler surfaces exhibited good mineralization capability without compromising strength. The potential for barrier generation through mineralization yielded positive effects and prevented micro-leakages., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Triclosan (TCS) is a widely-used antimicrobial agent in many consumer products around the world, and China is a major producer and consumer of TCS. In this study substance flow analysis (SFA) was used to construct a static model of anthropogenic TCS metabolism in China in 2008. The systematic SFA results were used to determine possible exposure pathways and trends in environmental exposure potential through different pathways. TCS discharged in wastewater mainly flowed into surface water sediment, ocean, and soil, where it accumulates in aquatic and agricultural products that may pose a higher risk to human health than brief exposure during consumption. Only 22% of TCS discharged was removed in the built environment with the remainder discharged into the natural environment, indicating that anthropogenic TCS metabolism in China is unsustainable. Per capita TCS consumption increased 209% from 2003 to 2012, resulting in increased discharge and accumulation in the environment. If current trends continue, it will increase to 713 mg capita(-1) yr(-1) in 2015 and 957 mg capita(-1) yr(-1) in 2020. Accordingly, annual environmental exposure potential will increase from 388 mg capita(-1) in 2008 to 557 mg capita(-1) in 2015 and 747 mg capita(-1) in 2020, indicating an increasing trend of exposure to environmental TCS. Results of Pearson correlation analysis suggested that feasible countermeasures to reduce environmental exposure potential for triclosan would include encouraging the development of small cities, raising awareness of health risks, nurturing environmentally-friendly consumer values, and improving the environmental performance of TCS-containing products., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Antidepressants, aiming at monoaminergic neurotransmission, exhibit delayed onset of action, limited efficacy, and poor compliance. Glutamatergic neurotransmission is involved in depression. However, it is unclear whether enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be a treatment for depression., Methods: We studied sarcosine, a glycine transporter-I inhibitor that potentiates NMDA function, in animal models and in depressed patients. We investigated its effects in forced swim test, tail suspension test, elevated plus maze test, novelty-suppressed feeding test, and chronic unpredictable stress test in rats and conducted a 6-week randomized, double-blinded, citalopram-controlled trial in 40 patients with major depressive disorder. Clinical efficacy and side effects were assessed biweekly, with the main outcomes of Hamilton Depression Rating Scale, Global Assessment of Function, and remission rate. The time course of response and dropout rates was also compared., Results: Sarcosine decreased immobility in the forced swim test and tail suspension test, reduced the latency to feed in the novelty-suppressed feeding test, and reversed behavioral deficits caused by chronic unpredictable stress test, which are characteristics for an antidepressant. In the clinical study, sarcosine substantially improved scores of Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function more than citalopram treatment. Sarcosine-treated patients were much more likely and quicker to remit and less likely to drop out. Sarcosine was well tolerated without significant side effects., Conclusions: Our preliminary findings suggest that enhancing NMDA function can improve depression-like behaviors in rodent models and in human depression. Establishment of glycine transporter-I inhibition as a novel treatment for depression waits for confirmation by further proof-of-principle studies., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Uromodulin (UMOD) is synthesized in the thick ascending limb and secreted into urine as the most abundant protein. Association studies in humans suggest protective effects of UMOD against calcium-containing kidney stones. Mice carrying mutations of Umod found in human UMOD-associated kidney disease (UAKD) and Umod-deficient mice exhibit hypercalciuria. The mechanism for UMOD regulation of urinary Ca(2+) excretion is incompletely understood. We examined if UMOD regulates TRPV5 and TRPV6, channels critical for renal transcellular Ca(2+) reabsorption. Coexpression with UMOD increased whole-cell TRPV5 current density in HEK293 cells. In biotinylation studies, UMOD increased TRPV5 cell-surface abundance. Extracellular application of purified UMOD upregulated TRPV5 current density within physiological relevant concentration ranges. UMOD exerted a similar effect on TRPV6. TRPV5 undergoes constitutive caveolin-mediated endocytosis. UMOD had no effect on TRPV5 in a caveolin-1-deficient cell line. Expression of recombinant caveolin-1 in these cells restored the ability of UMOD to upregulate TRPV5. Secretion of UAKD-mutant UMOD was markedly reduced and coexpression of mutant UMOD with TRPV5 failed to increase its current. Immunofluorescent studies demonstrated lower TRPV5 expression in Umod(-/-) mice compared with wild-type. UMOD upregulates TRPV5 by acting from extracellular and by decreasing endocytosis of TRPV5. The stimulation of Ca(2+) reabsorption via TRPV5 by UMOD may contribute to protection against kidney-stone formation.

Resolving the complex environmental problems of water pollution and shortage which occur during urbanization requires the systematic assessment of urban water metabolism efficiency (WME). While previous research has tended to focus on either available or virtual water metabolism, here we argue that the systematic problems arising during urbanization require an integrated assessment of available and virtual WME, using an indicator system based on material flow analysis (MFA) results. Future research should focus on the following areas: 1) analysis of available and virtual water flow patterns and processes through urban districts in different urbanization phases in years with varying amounts of rainfall, and their environmental effects; 2) based on the optimization of social, economic and environmental benefits, establishment of an indicator system for urban WME assessment using MFA results; 3) integrated assessment of available and virtual WME in districts with different urbanization levels, to facilitate study of the interactions between the natural and social water cycles; 4) analysis of mechanisms driving differences in WME between districts with different urbanization levels, and the selection of dominant social and economic driving indicators, especially those impacting water resource consumption. Combinations of these driving indicators could then be used to design efficient water resource metabolism solutions, and integrated management policies for reduced water consumption., (Copyright © 2013 Elsevier B.V. All rights reserved.)

For monitoring compliance of methadone or buprenorphine maintenance patient, a method for the simultaneous determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, opiates (morphine, codeine, 6-monoacetylmorphine) in urine by superficially porous liquid chromatography tandem mass spectrometry was developed and validated. After enzyme digestion and liquid-liquid extraction, reverse-phase separation was achieved in 5.2 min and quantification was performed by multiple reaction monitoring. Chromatographic separation was performed at 40 °C on a reversed phase Poroshell column with gradient elution. The mobile phase consisted of water and methanol, each containing 0.1% formic acid, at a flow rate of 0.32 mL/min. Intra-day and inter-day precision were less than 12.1% and accuracy was between -9.8% and 13.7%. Extraction efficiencies were more than 68%. Although ion suppression was detected, deuterated internal standards compensated for these effects. Carryover was minimal, less than 0.20%. All analytes were stable at room temperature for 16 h, 4 °C for 72 h, and after three freeze-thaw cycles. The assay also fulfilled compound identification criteria in accordance with the European Commission Decision 2002/657/EC. We analyzed 62 urine samples from patients received maintenance therapy and found that 54.8% of the patient samples tested were detected for morphine, codeine, or 6-monoacetylmorphine. This method provides a reliable and simultaneous quantification of opiates, maintenance drugs, and their metabolites in urine samples. It facilitates the routine monitoring in individuals prescribed the drug to ensure compliance and help therapeutic process., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Lithium (LiCl) and carbamazepine (CBZ), the common mood stabilizers, are thought to be effective treatments for bipolar disorder. The aim of the present study was to investigate whether LiCl as well as CBZ has similar effects on the bipolar disorder-associated cognitive dysfunctions in rats, particularly the spatial learning and depressive responses. Adult male Wistar rats were administered intracerebroventricularly with 5μl of 10(-3)M ouabain on session 1, and then received an intraperitoneal injection of LiCl or CBZ for 4 sessions (1 session/2days). For the behavioral tests, all rats were subjected to the water maze 15min for spatial learning and the forced swimming test 5min for depression on each session. The present results showed that ouabain resulted in increased latency and longer distance traveled to reach the hidden platform in the water maze, indicating that ouabain impaired the spatial learning. However, ouabain did not affect swimming velocity in the water maze and depressive responses in the forced swimming test. LiCl treatment decreased the ouabain-enhanced latency and the total distance, but not the velocity, swam to reach the hidden platform in the water maze task. Additionally, LiCl did not result in changes of any depressive indices, such as struggling behavior, swimming behavior, and floating behavior. Likewise, CBZ did not affect any behavioral indices of spatial learning and depression. A linear regression analysis suggested that LiCl, but not CBZ, could predict the decreased latency and total distance traveled except the velocity of swimming in the water maze and depressive behaviors. In summary, the present results suggested that lithium provided a better therapeutic effect than CBZ for ouabain-caused dysfunctions of spatial learning in a rat model of bipolar disorder., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Background: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival., Methods: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index., Results: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142)., Conclusions: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Parkinsonism might precede, coincide, or follow the behavioral or language-predominant cognitive impairments characteristic of frontotemporal dementia (FTD). In this study, we analyze the hexanucleotide repeat expansions within C9orf72 gene in various parkinsonian syndromes because it is a recently identified important genetic cause of FTD. The expanded hexanucleotide repeat is only identified in our familial FTD patients but not in patients with predominant parkinsonism. The lack of association between abnormal C9orf72 repeat expansion and parkinsonian syndromes might imply pathogenic mechanisms other than tau or Lewy body pathology., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients., (Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.)

Pure polymer films cannot meet the diverse range of controlled release and material properties demanded for the fabrication of medical implants or other devices. Additives are added to modulate and optimize thin films for the desired qualities. To characterize the property trends that depend on additive concentration, an assay was designed which involved casting a single polyester poly(lactic-co-glycolic acid) (PLGA) film that blends a linear gradient of any PLGA-soluble additive desired. Four gradient PLGA films were produced by blending polyethylene glycol or the more hydrophobic polypropylene glycol. The films were made using a custom glass gradient maker in conjunction with a 180 cm film applicator. These films were characterized in terms of thickness, percent additive, total polymer (PLGA+additive), and controlled drug release using drug-like fluorescent molecules such as coumarin 6 (COU) or fluorescein diacetate (FDAc). Material properties of elongation and modulus were also accessed. Linear gradients of additives were readily generated, with phase separation being the limiting factor. Additive concentration had a Pearson's correlation factor (R) of >0.93 with respect to the per cent total release after 30 days for all gradients characterized. Release of COU had a near zero-order release over the same time period, suggesting that coumarin analogs may be suitable for use in PLGA/polyethylene glycol or PLGA/polypropylene glycol matrices, with each having unique material properties while allowing tuneable drug release. The gradient casting method described has considerable potential in offering higher throughput for optimizing film or coating material properties for medical implants or other devices., (Copyright © 2012. Published by Elsevier Ltd.)

Objective: The aim of the study was to investigate the association of plasma amino-terminal propeptide of procollagen type III (PIIINP) with subclinical left ventricular (LV) systolic dysfunction in patients with aortic stenosis (AS) and normal LV ejection fraction., Methods: The study was performed in 57 AS patients with normal LV ejection fraction and in 30 control subjects with normal aortic valve and normal LV ejection fraction. Tissue Doppler and speckle tracking image were performed to assess LV diastolic and systolic function. Plasma PIIINP level was measured by specific radioimmunoassay., Results: In AS patients, LV systolic longitudinal strain was significantly reduced (-17.1 ± 2.1 vs. -18.8 ± 1.4%, P<0.001) and plasma PIIINP was increased compared with controls (2.5 ± 0.6 vs. 2.1 ± 0.4 μg/l, P<0.001). A significant correlation was found between LV systolic longitudinal strain and PIIINP (r=-0.67, P<0.001). In patients with abnormal LV diastolic function, LV systolic longitudinal strain was reduced compared with patients with normal LV diastolic function (-16.3 ± 1.5 vs. -18.8 ± 2.1%, P<0.001) and plasma PIIINP was increased (2.8 ± 0.5 vs. 2.0 ± 0.3 μg/l, P<0.001). A stepwise multivariate regression analysis revealed that LV systolic longitudinal strain and diastolic blood pressure were independent predictors of plasma PIIINP (multiple r=0.71, P<0.001)., Conclusions: Plasma PIIINP is associated with subclinical LV systolic dysfunction (the impaired LV systolic long axis function) in patients with AS and normal LV ejection fraction. In addition, the impaired LV systolic long axis function and increased plasma PIIINP concentration are most marked in patients with abnormal LV diastolic function., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Paraquat (PQ) was demonstrated to induce dopaminergic neuron death and is used as a Parkinson's disease (PD) mimetic; however, its mechanism remains contradictory. Alternatively, minocycline is a second-generation tetracycline and is undergoing clinical trials for treating PD with an unresolved mechanism. We thus investigated the molecular mechanism of minocycline in preventing PQ-induced cytotoxicity. In this study, minocycline was effective in preventing PQ-induced apoptotic cell death, which involves the cleavages of poly (ADP-ribose) polymerase (PARP) and caspase 3 and increased fluorescence intensity of annexin V-FITC. In addition, PQ also quickly induced alterations of unfolded protein responses (UPRs) and subsequently dysfunction of the mitochondria (such as the decrease in membrane potential and increase in membrane permeability and superoxide formation). Finally, the mechanism of minocycline in preventing PQ-induced apoptosis might be mediated by attenuating endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which respectively results in caspase-12 activation and the release of H2O2, HtrA2/Omi, and Smac/Diablo. Thus, minocycline could possibly be used to treat other neurodegenerative disorders with similar pathologic mechanisms., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated the usefulness of infrared thermography in evaluating patients at high risk for lower extremity peripheral arterial disease (PAD), including severity, functional capacity, and quality of life., Methods: A total of 51 patients (23 males; age 70 ± 9.8 years) were recruited. They completed three PAD-associated questionnaires, including walking impairment, vascular quality of life, and 7-day physical activity recall questionnaires before a 6-minute walking test (6MWT). Ankle-brachial index (ABI) and segmental pressure were analyzed for PAD diagnosis and stenotic level assessment. The cutaneous temperature at shin and sole were recorded by infrared thermography before and after the walk test. Detailed demographic information and medication list were obtained., Results: Twenty-eight subjects had abnormal ABI (ABI <1), while PAD was diagnosed in 20. No subjects had non-compressible artery (ABI >1.3). Demographic profiles and clinical parameters in PAD and non-PAD patients were similar, except for age, smoking history, and hyperlipidemia. PAD patients walked shorter distances (356 ± 102 m vs 218 ± 92 m; P < .001). Claudication occurred in 14 patients, while seven failed in completing the 6MWT. The rest temperatures were similar in PAD and non-PAD patients. However, the post-exercise temperature dropped in the lower extremities with arterial stenosis, but was maintained or elevated slightly in the extremities with patent arteries (temperature changes at sole in PAD vs non-PAD patients: -1.25 vs -0.15°C; P < .001). The exercise-induced temperature changes at the sole were not only positively correlated with the 6MWD (Spearman correlation coefficient = 0.31, P = .03), but was also correlated with ABI (Spearman correlation coefficient = 0.48, P < .001) and 7-day physical activity recall scores (Spearman correlation coefficient = 0.30, P = .033)., Conclusion: By detecting cutaneous temperature changes in the lower extremities, infrared thermography offers another non-invasive, contrast-free option in PAD evaluation and functional assessment., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Diabetic foot ulcers (DFUs) superimposed by infection and ischaemia may result in amputation without prompt and adequate management. We investigated whether the diabetic foot ulcer treatment programme (DFUTP) involving immediate debridement within 12 h, flap coverage and/or revascularisation improved the outcome of patients with infected DFUs., Method: Between 2006 and 2009, we randomly enrolled 350 patients in the DFUTP group and compared them with control patients (the non-DFUTP group, n = 386) in Taiwan. Inclusion criteria consisted of infected diabetic foot ulcers with or without ischaemia. The risk factors, dynamics and outcome of amputation and re-amputation were analysed in terms of patient demographics, glycaemic control and infection., Result: The results of logistic regression analyses indicated that risk factors of amputation in both groups were HbA1c (odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.31-2.02) and C reactive protein (OR = 1.12, 95% CI 1.01-1.24). The DFUTP group showed a lower amputation rate than the non-DFUTP group (p = 0.001). The association between the amputation and University of Texas (UT) classification was not statistically significant. The Kaplan-Meier estimate showed that the time to complete recovery of the sugar level in the DFUTP group was faster than in the non-DFUTP group (p = 0.001). For patients at stage D, the hospital stay in the non-DFUTP group was longer than in the DFUTP group (p = 0.014)., Conclusion: The DFUTP provides an effective treatment programme for decreasing the amputation rate with infected DFUs. Immediate debridement and flap reconstruction decrease the amputation and re-amputation rate respectively., (Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Thin films of poly(lactic acid-co-glycolic acid) (PLGA) incorporating paclitaxel typically have slow release rates of paclitaxel of the order of 1 μg day(-1) cm(-2). For implementation as medical devices a range of zero order release rates (i.e. 1-15 μg day(-1) cm(-2)) is desirable for different tissues and pathologies. Eight and 35 kDa molecular weight polyethylene glycol (PEG) was incorporated at 15%, 25% and 50% weight ratios into PLGA containing 10 wt.% paclitaxel. The mechanical properties were assessed for potential use as medical implants and the rates of release of paclitaxel were quantified as per cent release and the more clinically useful rate of release in μg day(-1) cm(-2). Paclitaxel quantitation was correlated with the release of PEG from PLGA, to further understand its role in paclitaxel/PLGA release modulation. PEG release was found to correlate with paclitaxel release and the level of crystallinity of the PEG in the PLGA film, as measured by Raman spectrometry. This supports the concept of using a phase separating, partitioning compound to increase the release rates of hydrophobic drugs such as paclitaxel from PLGA films, where paclitaxel is normally homogeneously distributed/dissolved. Two formulations are promising for medical device thin films, when optimized for tensile strength, elongation, and drug release. For slow rates of paclitaxel release an average of 3.8 μg day(-1) cm(-2) using 15% 35k PEG for >30 days was achieved, while a high rate of drug release of 12 μg day(-1) cm(-2) was maintained using 25% 8 kDa PEG for up to 12 days., (Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Although participants with dissociation proneness showed inefficient cognitive inhibition, whether and under what stimulus-task contexts dissociators show inefficient memory inhibition remains inconclusive. This study investigated the relationship between trait dissociation and basic operation of memory control using a non-clinical sample. To reduce the involvement of strategic control and the influence of emotionality, the retrieval-practice paradigm was adopted to examine unintentional memory inhibition of neutral materials. Both the low- and middle-dissociation groups showed the forgetting effect, resulting from suppressing competing memories while retrieving a target. In contrast, the high-dissociation group did not show the forgetting effect although their performance in the baseline condition and in recalling practiced items was comparable to the other two groups. High dissociation proneness is linked with weakened memory inhibition that may cause diverse memory problems in clinical patients.

Klotho is an anti-aging protein predominantly expressed in the kidney, parathyroid glands, and choroid plexus of the brain. It is a single-pass transmembrane protein with a large extracellular domain. The extracellular domain of Klotho is cleaved and released into extracellular fluid, including blood, urine, and cerebrospinal fluid. The membrane-bound full-length Klotho and secreted extracellular domain of Klotho have distinct functions. Membrane Klotho interacts with fibroblast growth factor (FGF) receptors to form high-affinity receptors for FGF23. Secreted Klotho functions as a humoral factor that regulates several ion channels and transporters, and other processes, including insulin and insulin-like growth factor signaling. This mini-review focuses on the mechanisms of regulation of cell-surface abundance of ion channels by secreted Klotho and the importance of these effects of Klotho in physiology and pathological conditions.

Background: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an important role in cytokine-induced depression and sickness behavior., Methods: Patients with chronic hepatitis C viral infection (n = 132) were assessed to examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2 genes on the development of depression during interferon (IFN)-alpha treatment; a subsample (n = 63) was assessed for the erythrocyte levels of the three main polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid. An independent "replication" sample of patients with major depression unrelated to cytokine treatment (n = 82) was also examined., Results: Twenty-eight percent of participants developed INF-alpha-induced depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes had a higher risk of IFN-alpha-induced depression (odds ratio = 3.1 and 3.5, respectively). The "at risk" PLA2 genotype was associated with lower EPA levels, and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN-alpha treatment. The PLA2 BanI GG polymorphism was also associated with more somatic symptoms of depression, both in patients with INF-alpha-induced depression and in the replication sample of patients with major depression., Conclusions: Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-alpha-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

DB-67 and its lactone homolog DB-91 are derivatives of topoisomerase I inhibitor camptothecin (CPT) with silyl moiety, which may exhibit a slower inactivation process by changed kinetics of protein binding and/or hydrolysis of its lactone ring and result in increased antitumor activity and decreased toxicity. Pharmacokinetic properties and antitumor activities of the two silatecans were studied and compared. The lactone ring of DB-91 is more stable than those of all the other CPT derivatives in mouse plasma. Both silatecans were metabolized faster than CPT in mouse and human liver microsomes. Pharmacokinetic study revealed a plasma elimination half-life (t(1/2)) of 33 and 94min for DB-67 and DB-91, respectively; similar systemic exposure in plasma between DB-67 and DB-91; and similar volume of distribution at the steady state between DB-67 and DB-91, approximately 15-fold smaller than that of CPT. While DB-91 showed limited activities, DB-67 exhibited activities against the growth of in vivo-like histocultured human tumors and s.c. xenografted human tumors in nude mice. In conclusion, DB-67 is more effective, compared to DB-91, against human tumor growth in in vitro, in vivo-like and in vivo systems. Further pre-clinical and clinical investigations of DB-67 are warranted., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Purpose: To examine the psychometric properties of the Hooked on Nicotine Checklist (HONC) on a Taiwanese sample. The HONC as a measure of nicotine dependence in adolescents is in worldwide use. Less is known regarding its psychometric properties for a Chinese population., Methods: A cross-sectional, descriptive study was conducted from January to May 2008 with 373 male adolescent smokers aged 15 to 20 years. The criterion validity of the Chinese HONC was determined using the Fagerstrom Test of Nicotine Dependence (FTND) and saliva cotinine. Because the responses to the items are dichotomous, the validity and factorial structures were examined using tetrachoric and biserial techniques by PRELIS 2 and LISREL 8.7., Results: Most of interitem correlations are between 0.3 and 0.7. Each item is highly associated with the full scale (r > .7). The HONC total score is significantly associated with the FTND (r=.58, p < .01) and with saliva cotinine levels (r=.27, p < .05). Confirmatory factor analyses were performed to compare the relative fit of three competing models. The three-correlated factor model has a better fit than other models, according to the cutoff criteria for relatively good fit. The coefficient alpha of the full scale is .83., Conclusions: The Chinese version of the HONC is a reliable and valid measure of tobacco dependence in adolescent smokers. Studies involving female adolescent and younger smokers will be needed to evaluate the applicability of the scales to the different genders and age populations.

WNK1 [with-no-lysine (K)-1] is a ubiquitous serine/threonine kinase with a unique placement of the catalytic lysine residue. Increased WNK1 expression levels in humans causes a hypertension-hyperkalemia syndrome by altering renal Na(+) and K(+) transport. The function of WNK1 outside of the kidney remains elusive. In this study, we report that Wnk1 ablation causes cardiovascular developmental defects. The developing heart of null mutant embryos has smaller chambers and reduced myocardial trabeculation at E10.5. Yolk sac vessels in the E10.5 null mutant fail to remodel into a network of large and small vessels, and embryonic vessels show defective angiogenesis that involves both arteries and veins. The arterial marker neuropilin-1 and venous marker EphB4 are ectopically expressed in mutant veins and arteries, respectively. However, the orphan nuclear receptor COUP-TFII as well as the Notch signaling pathway, which are known to be critical for angiogenesis and artery-vein specification, are not significantly altered in Wnk1(-/-) mutants. Conditional deletion of Wnk1 in endothelial cells phenotypically copies defects caused by global Wnk1 ablation. Moreover, endothelial-specific expression of a Wnk1 transgene rescues cardiovascular developmental defects in Wnk1(-/-) mice. These findings identify a novel function of WNK1 in endothelial cells that is critical for angiogenesis and heart development, raising the possibility for a role of endothelial WNK1 in the control of blood pressure and postnatal angiogenesis and cardiac growth.