Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τρίτη 26 Ιανουαρίου 2016

Membranes, Vol. 6, Pages 11: Ling’s Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

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Materials, Vol. 9, Pages 74: Properties of Non-Structural Concrete Made with Mixed Recycled Aggregates and Low Cement Content

In spite of not being legally accepted in most countries, mixed recycled aggregates (MRA) could be a suitable raw material for concrete manufacturing. The aims of this research were as follows: (i) to analyze the effect of the replacement ratio of natural coarse aggregates with MRA, the amount of ceramic particles in MRA, and the amount of cement, on the mechanical and physical properties of a non-structural concrete made with a low cement content; and (ii) to verify if it is possible to achieve a low-strength concrete that replaces a greater amount of natural aggregate with MRA and that has a low cement content. Two series of concrete mixes were manufactured using 180 and 200 kg/m3 of CEM II/A-V 42.5 R type Portland cement. Each series included seven concrete mixes: one with natural aggregates; two MRA with different ceramic particle contents; and one for each coarse aggregate replacement ratio (20%, 40%, and 100%). To study their properties, compressive and splitting tensile strength, modulus of elasticity, density, porosity, water penetration, and sorptivity, tests were performed. The results confirmed that the main factors affecting the properties analyzed in this research are the amount of cement and the replacement ratio; the two MRAs used in this work presented a similar influence on the properties. A non-structural, low-strength concrete (15 MPa) with an MRA replacement ratio of up to 100% for 200 kg/m3 of cement was obtained. This type of concrete could be applied in the construction of ditches, sidewalks, and other similar civil works.

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Sustainability, Vol. 8, Pages 114: Technology Evaluation and Selection of 3DIC Integration Using a Three-Stage Fuzzy MCDM

For the purpose of the sustainable development in the global semiconductor industry, emerging three-dimensional integrated circuit (3DIC) integration technologies have demonstrated their importance as potential candidates for extending the lifespan of Moore's Law. This study aimed to explore a technology selection process involving a three-stage fuzzy multicriteria decision-making (MCDM) approach to facilitate the effective assessment of emerging 3DIC integration technologies. The fuzzy Delphi method was first used to determine the important criteria. The fuzzy analytic hierarchy process (fuzzy AHP) was then adopted to derive the weights of the criteria. The fuzzy technique for order of preference by similarity to ideal solution (fuzzy TOPSIS) was finally deployed to rate the alternatives. Empirical results indicate that market potential, time-to-market, and heterogeneous integration are the top three decision criteria for the selection of 3DIC integration technologies. Furthermore, 2.5D through-silicon interposer (TSI) is of primary interest to the Taiwanese semiconductor industry, followed by 3DIC through-silicon via (TSV), 3D packaging, and 3D silicon TSV (Si TSV). The proposed three-stage fuzzy decision model may potentially assist industry practitioners and government policy-makers in directing research and development investments and allocating resources more strategically.

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Systems, Vol. 4, Pages 10: Challenges while Updating Planning Parameters of an ERP System and How a Simulation-Based Support System Can Support Material Planners

In an Enterprise Resource Planning (ERP) system, production planning is influenced by a variety of parameters. Previous investigations show that setting parameter values is highly relevant to a company's target system. Parameter settings should be checked and adjusted, e.g., after a change in environmental factors, by material planners. In practice, updating the parameters is difficult due to several reasons. This paper presents a simulation-based decision support system, which helps material planners in all stages of decision-making processes. It will present the system prototype's user interface and the results of applying the system to a case study.

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Nutrients, Vol. 8, Pages 64: Effects of Oral Exposure Duration and Gastric Energy Content on Appetite Ratings and Energy Intake in Lean Men

Studies show that longer oral exposure to food leads to earlier satiation and lowers energy intake. Moreover, higher energy content of food has been shown to lead to higher satiety. Up to now, it has not been studied systematically how oral exposure duration and gastric energy content interact in satiety regulation. Thirty-seven men (22 ± 4 years, 22 ± 2 kg/m2) participated in a randomized cross-over trial, in which we independently manipulated: (1) oral exposure duration by modified sham feeding (MSF) for 1 or 8 min; and (2) energy content of gastric load (GL) by a nasogastric tube: 100 kcal/500 mL or 700 kcal/500 mL. Outcome measures were appetite ratings and subsequent energy intake from an ad libitum meal. Energy intake was 35% lower after the GLs with 700 kcal than with 100kcal (p < 0.0001). All appetite ratings were lower in the 700 kcal than in the 100 kcal treatments (area under the curve (AUC); p-values ≤ 0.002); fullness was higher and prospective consumption was lower in the 8 min than in the 1 min MSF treatments (AUC; p-values ≤ 0.02). In conclusion, the current showed that a GL of 700 kcal/500 mL vs. 100 kcal/500 mL increased satiety and lowered energy intake. No additional effects of oral exposure duration could be observed, presumably due to the high contrast in energy between the manipulations. Future research should also focus on the role of oral exposure as such and not only the duration.

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Changing the course of pancreatic cancer – Focus on recent translational advances

Publication date: Available online 25 January 2016
Source:Cancer Treatment Reviews
Author(s): Milind Javle, Talia Golan, Anirban Maitra
In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents.Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.

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Nutrients, Vol. 8, Pages 66: Impact of Food Rations and Supplements on Micronutrient Status by Trimester of Pregnancy: Cross-Sectional Studies in the Maela Refugee Camp in Thailand

Micronutrient fortified flour (MFF), supplementary food rations and micronutrient (MN) supplements may prevent deficiencies among pregnant women. Objectives of cross-sectional surveys in 2004 (n = 533) and 2006 (n = 515) were to assess the impact of new food rations (flour, oil) and supplements on MN status by trimester of pregnancy in the Maela refugee camp. Hemoglobin, iron status, zinc, retinol, β-carotene and tryptophan decreased, while α-/γ-tocopherol and 5-methyltetrahydrofolate (5-MTHF) increased from first to third trimester. In 2006, mean zinc and α-tocopherol for each trimester was significantly higher than in 2004. The weeks of supplemented thiamine and folic acid were positively correlated with thiamine diphosphate (TDP) and 5-MTHF, but not for ferrous sulfate as iron deficiency was observed in 38.5% of third-trimester women. Frequent consumption of fish paste and owning a garden or animal were associated with significantly higher iron status, retinol, β-carotene, and 5-MTHF. In conclusion, MFF and supplementary oil were most likely to explain improved zinc and α-tocopherol status, while thiamine and folate supplements ensured high TDP and 5-MTHF in late pregnancy. MN supplements, MN-rich staple food, small gardens, and programs to improve iron compliance are promising strategies to prevent MN deficiencies during pregnancy in vulnerable populations.

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Molecules, Vol. 21, Pages 146: Poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) Copper Complex Grafted Solid Catalyst for Oxidative Polymerization of 2,6-Dimethylphenol

A new solid phase catalyst, poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) copper(I) complex, grafted onto polystyrene particles, has been employed for the oxidative polymerization of 2,6-dimethylphenol using an aqueous biphasic (water/toluene) solvent system. The solid catalyst was synthesized by first grafting N-(4-vinylbenzyl)-1,4,7-triaza-cyclononane onto polystyrene particles using a radical mediated polymerization method and next by creating the polymer-metal complex of copper-triazacyclononane with these modified particles. Poly(2,6-dimethyl-1,4-phenylene oxide) was successfully obtained from the polymerization of 2,6-dimethylphenol using this new metal-organic solid phase catalyst.

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Molecules, Vol. 21, Pages 145: Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents

In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.

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Polymers, Vol. 8, Pages 31: Highly Active and Isospecific Styrene Polymerization Catalyzed by Zirconium Complexes Bearing Aryl-substituted [OSSO]-Type Bis(phenolate) Ligands

[OSSO]-type dibenzyl zirconium(IV) complexes 9 and 10 possessing aryl substituents ortho to the phenoxide moieties (ortho substituents, phenyl and 2,6-dimethylphenyl (Dmp)) were synthesized and characterized. Upon activation with dMAO (dried methylaluminoxane), complex 9 was found to promote highly isospecific styrene polymerizations ([mm] = 97.5%–99%) with high molecular weights Mw up to 181,000 g·mmol−1. When the Dmp-substituted pre-catalyst 10/dMAO system was used, the highest activity, over 7700 g·mmol(10)−1·h−1, was recorded involving the formation of precisely isospecific polystyrenes of [mm] more than 99%.

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Membranes, Vol. 6, Pages 11: Ling’s Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174



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Materials, Vol. 9, Pages 74: Properties of Non-Structural Concrete Made with Mixed Recycled Aggregates and Low Cement Content

In spite of not being legally accepted in most countries, mixed recycled aggregates (MRA) could be a suitable raw material for concrete manufacturing. The aims of this research were as follows: (i) to analyze the effect of the replacement ratio of natural coarse aggregates with MRA, the amount of ceramic particles in MRA, and the amount of cement, on the mechanical and physical properties of a non-structural concrete made with a low cement content; and (ii) to verify if it is possible to achieve a low-strength concrete that replaces a greater amount of natural aggregate with MRA and that has a low cement content. Two series of concrete mixes were manufactured using 180 and 200 kg/m3 of CEM II/A-V 42.5 R type Portland cement. Each series included seven concrete mixes: one with natural aggregates; two MRA with different ceramic particle contents; and one for each coarse aggregate replacement ratio (20%, 40%, and 100%). To study their properties, compressive and splitting tensile strength, modulus of elasticity, density, porosity, water penetration, and sorptivity, tests were performed. The results confirmed that the main factors affecting the properties analyzed in this research are the amount of cement and the replacement ratio; the two MRAs used in this work presented a similar influence on the properties. A non-structural, low-strength concrete (15 MPa) with an MRA replacement ratio of up to 100% for 200 kg/m3 of cement was obtained. This type of concrete could be applied in the construction of ditches, sidewalks, and other similar civil works.

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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174



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Sustainability, Vol. 8, Pages 114: Technology Evaluation and Selection of 3DIC Integration Using a Three-Stage Fuzzy MCDM

For the purpose of the sustainable development in the global semiconductor industry, emerging three-dimensional integrated circuit (3DIC) integration technologies have demonstrated their importance as potential candidates for extending the lifespan of Moore's Law. This study aimed to explore a technology selection process involving a three-stage fuzzy multicriteria decision-making (MCDM) approach to facilitate the effective assessment of emerging 3DIC integration technologies. The fuzzy Delphi method was first used to determine the important criteria. The fuzzy analytic hierarchy process (fuzzy AHP) was then adopted to derive the weights of the criteria. The fuzzy technique for order of preference by similarity to ideal solution (fuzzy TOPSIS) was finally deployed to rate the alternatives. Empirical results indicate that market potential, time-to-market, and heterogeneous integration are the top three decision criteria for the selection of 3DIC integration technologies. Furthermore, 2.5D through-silicon interposer (TSI) is of primary interest to the Taiwanese semiconductor industry, followed by 3DIC through-silicon via (TSV), 3D packaging, and 3D silicon TSV (Si TSV). The proposed three-stage fuzzy decision model may potentially assist industry practitioners and government policy-makers in directing research and development investments and allocating resources more strategically.

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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174



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Systems, Vol. 4, Pages 10: Challenges while Updating Planning Parameters of an ERP System and How a Simulation-Based Support System Can Support Material Planners

In an Enterprise Resource Planning (ERP) system, production planning is influenced by a variety of parameters. Previous investigations show that setting parameter values is highly relevant to a company's target system. Parameter settings should be checked and adjusted, e.g., after a change in environmental factors, by material planners. In practice, updating the parameters is difficult due to several reasons. This paper presents a simulation-based decision support system, which helps material planners in all stages of decision-making processes. It will present the system prototype's user interface and the results of applying the system to a case study.

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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174



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Nutrients, Vol. 8, Pages 64: Effects of Oral Exposure Duration and Gastric Energy Content on Appetite Ratings and Energy Intake in Lean Men

Studies show that longer oral exposure to food leads to earlier satiation and lowers energy intake. Moreover, higher energy content of food has been shown to lead to higher satiety. Up to now, it has not been studied systematically how oral exposure duration and gastric energy content interact in satiety regulation. Thirty-seven men (22 ± 4 years, 22 ± 2 kg/m2) participated in a randomized cross-over trial, in which we independently manipulated: (1) oral exposure duration by modified sham feeding (MSF) for 1 or 8 min; and (2) energy content of gastric load (GL) by a nasogastric tube: 100 kcal/500 mL or 700 kcal/500 mL. Outcome measures were appetite ratings and subsequent energy intake from an ad libitum meal. Energy intake was 35% lower after the GLs with 700 kcal than with 100kcal (p < 0.0001). All appetite ratings were lower in the 700 kcal than in the 100 kcal treatments (area under the curve (AUC); p-values ≤ 0.002); fullness was higher and prospective consumption was lower in the 8 min than in the 1 min MSF treatments (AUC; p-values ≤ 0.02). In conclusion, the current showed that a GL of 700 kcal/500 mL vs. 100 kcal/500 mL increased satiety and lowered energy intake. No additional effects of oral exposure duration could be observed, presumably due to the high contrast in energy between the manipulations. Future research should also focus on the role of oral exposure as such and not only the duration.

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Changing the course of pancreatic cancer – Focus on recent translational advances

Publication date: Available online 25 January 2016
Source:Cancer Treatment Reviews
Author(s): Milind Javle, Talia Golan, Anirban Maitra
In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents.Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.

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Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: a lost cause?

Publication date: Available online 25 January 2016
Source:Cancer Treatment Reviews
Author(s): Angela Lamarca, Emma Elliott, Jorge Barriuso, Alison Backen, Mairéad G. McNamara, Richard Hubner, Juan W. Valle
BackgroundChemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients.MethodsEligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy. The primary end-point was overall-response (OR) rate; secondary end-points were progression-free survival (PFS), overall survival (OS), disease-stabilisation (DS) and disease-control (DC) rates.ResultsOf 6,434 studies screened, 20 were eligible: one randomised phase III trial, 2 randomised phase II studies, 10 single-arm phase II trials and 7 retrospective analyses including a total of 264 patients (median of 11 patients per study, range 6-49); and employing multiple chemotherapy schedules. The mean "median PFS" and "median OS" were 16.9 months (95%-confidence interval (CI) 3.8-30.04) and 32.2 months (95%-CI 10.4-54.2), respectively. The non-weighted mean OR, DS and DC rates were 11.5% (95%-CI 5.8-17.2), 56.5% (95%-CI 38.1-74.9) and 70.7% (95%-CI 54.9-86.5), respectively. In studies including both pNETs and non-pNET patients, meta-analysis showed a lower OR-rate in the non-pNET patients when compared to pNETs [odds ratio (OR) 0.35 (95% CI 0.18-0.66); however significance was lost when high-risk bias studies were excluded in a sensitivity analysis [OR 0.45 (95% CI 0.19-1.07); p-value 0.07].ConclusionStudies were of evidence level-C with heterogeneous populations and treatments; and small patient numbers. Well-designed, prospective studies are needed to adequately evaluate the role of chemotherapy in this setting.

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Hypoxia enhances the effect of lipopolysaccharide-stimulated IL-1β expression in human periodontal ligament cells

Abstract

Oral infection is inflammatory disease caused by bacteria. A major component of gram negative bacteria membrane associated with inflammation is lipopolysaccharide (LPS). Currently, evidence presenting the combined effect of LPS and hypoxia to inflammatory response in human periodontal ligament cells (HPDLs) was yet lacking. Here, we studied whether the influence of oxygen on LPS-stimulated inflammatory cytokines in HPDLs. HPDLs were stimulated with LPS in normoxia and hypoxia for 24 h. The mRNA and protein expression of inflammatory cytokines were examined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular mechanisms of these effects were investigated by chemical inhibitors and small interfering RNA (siRNA). The results showed that LPS-stimulated IL-1β, IL-6, IL-8 in HPDLs in both hypoxia and normoxia. Hypoxia condition enhanced the effect of LPS-stimulated cytokines expression. Apigenin, the hypoxia-inducible factors (HIF)-1α inhibitor, totally prevented LPS-stimulated IL-1β expression in both normoxia and hypoxia. Similar to knockout HIF-1α gene expression by siRNA did \not prevent LPS-stimulated IL-1β expression. These data concluded that hypoxia increased virulence of LPS-stimulated IL-1β production in HPDLs.



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Nanomaterials, Vol. 6, Pages 25: Composites of Quasi-Colloidal Layered Double Hydroxide Nanoparticles and Agarose Hydrogels for Chromate Removal

Composite hydrogels were prepared that consisted of quasi-colloidal layered double hydroxide (LDH) nanoparticles and agarose via the electrophoretic method, starting from three different agarose concentrations of 0.5, 1, and 2 wt/v%. The composite hydrogel was identified to have a uniform distribution of LDH nanoparticles in agarose matrix. Microscopic studies revealed that the composite hydrogel had a homogeneous quasi-colloidal state of LDHs, while the simple mixture of LDH powder and agarose hydrogels did not. It was determined that agarose concentration of the starting hydrogel did not significantly influence the amount of LDH that developed in the composite. The chromate scavenging efficiency of the composite hydrogel and corresponding agarose or mixture hydrogel was evaluated with respect to time, and chromate concentration. In general, the composite hydrogels exhibited much higher chromate removal efficacy compared with agarose or mixture hydrogels. Through estimating chromate adsorption by LDH moiety in the composite or mixture hydrogel, it was suggested that the agarose component facilitated the stability and dispersibility of the quasi-colloidal state of LDH nanoparticles in the composite resulting in high adsorption efficacy. From Freundlich isotherm adsorption fitting, composites were determined to possess beneficial cooperative adsorption behavior with a high adsorption coefficient.

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Diseases, Vol. 4, Pages 8: Acknowledgement to Reviewers of Diseases in 2015

The editors of Diseases would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...]

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Three-dimensional assessment of anatomical balance and oral appliance treatment outcome in obstructive sleep apnoea

Abstract

Purpose

Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnoea (OSA). However, MAS are not equally efficacious across all patients and the reasons are not well understood. Craniofacial and upper airway structure individually influence MAS response. We aimed to assess anatomical balance, defined as the ratio of upper airway soft tissue (ST) volume to maxillomandibular enclosure volume, between MAS treatment responders and non-responders.

Methods

OSA patients (apnoea-hypopnea index (AHI) >10 h−1) were recruited for MAS treatment. Magnetic resonance imaging of the upper airway was performed during wakefulness without and with MAS in situ. Images were processed for volumetric analysis of upper airway soft tissues (tongue, soft palate, paraphayrngeal fat pads and lateral pharyngeal walls) and three-dimensional cephalometry to acquire intra-mandibular space area (IMA) and total maxillomandibular (Mm) volume. Anatomical balance ratios were compared between MAS treatment responders (AHI <10 h−1 + 50 % reduction) and non-responders.

Results

Image analysis was completed in 69 patients (68 % male, age 50.5 ± 10.1 years, BMI 29.6 ± 5.0 kgm2, AHI 27.0 ± 14.7 h−1) including 36 responders. Soft tissue volumes did not differ between MAS responders and non-responders. Non-responders had increased ST/IMA compared to responders (4.9 ± 0.6 vs. 4.6 ± 0.6, p = 0.031). In multivariate logistic regression with AHI and BMI, ST/IMA was the only predictive variable (p = 0.036, ROC AUC 0.7). However, changes in ST/Mm did not directly relate to treatment response.

Conclusions

Anatomical imbalance assessed by intra-mandibular space area was associated with poor MAS treatment response. However, changes in anatomical balance with mandibular advancement did not reflect treatment outcome as static imaging may not adequately capture improvements in upper airway function.



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An oral appliance with or without elastic bands to control mouth opening during sleep—a randomized pilot study

Abstract

Background

Oral appliances (OAs) hold the lower jaw forward to reduce obstructive sleep apneas. Some OA designs allow mouth opening, which influences the forward positioning of the lower jaw. The aim of this pilot study was to compare the efficacy of an adjustable, custom-made OA (Narval®) in its original design, which allowed mouth opening, with the same OA with elastic bands that restricted mouth opening.

Methods

Consecutive patients with an apnea-hypopnea index (AHI) of ≥15 were randomized to start with an OA either with or without elastic bands in a single-blinded, crossover, pilot study. The patients underwent acclimatization and titration. After 3 weeks use of each device, they had renewed sleep apnea recordings and responded to questionnaires. Washout periods took place between the tests.

Results

Ten subjects with a median AHI of 19.7 (interquartile range (IQR) 17.3 to 31.8) were included. The AHI decreased to 3.1 (IQR 1.5–14.7) (p < 0.01) with the OA and to 5.1 (IQR 2.4–14.3) (p < 0.01) with the OA with elastic bands, with no difference between them (p = 0.7). The two subjects with severe obstructive sleep apnea (OSA) almost halved their supine AHI with, as compared to without, elastic bands. The majority of the patients preferred to use the elastic bands.

Conclusions

This pilot study indicates that elastic bands markedly reduced the supine AHI in two subjects with severe sleep apnea as compared to without elastic bands. The majority of the patients preferred the use of elastic bands, although no significant difference in the AHI was observed with versus without the elastic bands in the whole sample.



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Association between continuous positive airway pressure and circulating omentin levels in patients with obstructive sleep apnoea

Abstract

Purpose

Inflammation and oxidative stress play important roles in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). Omentin is expressed in visceral adipose tissue and is associated with the inflammatory response. The aim of this study was to assess the relationship between OSAS and omentin based on a comparison of its serum levels at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.

Methods

Ninety-six newly diagnosed OSAS patients and 31 non-apnoeic controls were enrolled in this study. Blood samples were obtained in the morning after polysomnography. Within the OSAS group, 30 patients were started on CPAP therapy and then reassessed clinically, including a blood test for serum omentin and other biochemical analysis, at 3 months.

Results

Serum omentin levels were significantly lower in the OSAS group than in the control group (27.7 ± 7.6 and 42.5 ± 5.2 ng/mL, P < 0.001). In the subgroup analysis, omentin concentrations were significantly lower in patients with severe OSAS than in those with mild/moderate OSAS (P < 0.001). Circulating omentin levels were significantly correlated with the apnoea–hypopnoea index (AHI), mean SaO2, oxygen desaturation index, and serum C-reactive protein levels. Treatment with CPAP resulted in a significant increase in circulating omentin levels after 3 months, from 22.7 ± 1.4 to 41.2 ± 3.3 ng/mL (P < 0.001).

Conclusions

OSAS is associated with low serum omentin levels, and these levels can be reversed by effective CPAP treatment.



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Construct validity and factor structure of the Pittsburgh Sleep Quality Index among pregnant women in a Pacific-Northwest cohort

Abstract

Purpose

Poor sleep quality during pregnancy is associated with adverse obstetric and neuropsychiatric outcomes. Despite its routine use as a sleep quality assessment scale among men and non-pregnant women, the psychometric properties of the Pittsburgh Sleep Quality Index (PSQI) have not been assessed among US pregnant women. We sought to evaluate the construct validity and factor structure of the PSQI among 1488 pregnant women.

Methods

A structured interview was used to collect information about demographics and sleep characteristics in early pregnancy. The Patient Health Questionnaire-9 (PHQ-9) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were used to assess symptoms of depression, anxiety, and stress. Consistency indices, exploratory and confirmatory factor analyses (EFA and CFA), correlations, and logistic regression procedures were used.

Results

The reliability coefficient, Cronbach's alpha for the PSQI items was 0.74. Results of the EFA showed that a rotated factor solution for the PSQI contained two factors with eigenvalues >1.0 accounting for 52.8 % of the variance. The PSQI was significantly positively correlated with the PHQ-9 (r s = 0.48) and DASS-21 (r s = 0.42) total scores. Poor sleepers (PSQI global score >5) had increased odds of experiencing depression (OR = 6.47; 95 % CI = 4.56–9.18), anxiety (OR = 3.59; 95 % CI = 2.45–5.26), and stress (OR = 4.37; 95 % CI = 2.88–6.65) demonstrating evidence of good construct validity. CFA results corroborated the two-factor structure finding from the EFA and yielded reassuring measures indicating goodness of fit (comparative fit index = 0.975) and accuracy (root mean square error of approximation = 0.035).

Conclusions

The PSQI has good construct validity and reliability for assessing sleep quality among pregnant women.



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Racial disparity in adherence to positive airway pressure among US veterans

Abstract

Purpose

Despite advances in continuous positive airway pressure (CPAP) technology, compliance with CPAP therapy remains suboptimal. Studies conducted since the advent of objective CPAP recording have noted that African Americans (AA) may use CPAP less than Whites. We sought to confirm this finding among a large sample of veterans and examine effect modifiers of the differential usage.

Methods

A retrospective cohort of 233 AA and 1939 White Veterans Administration (VA) patients who had a sleep study between January 2003 and October 2006 and received CPAP therapy by the end of 2007. CPAP compliance was summarized at 2 weeks and 6 months post CPAP receipt.

Results

AAs were significantly less adherent than Whites even when controlling for age, gender, marital status, median household income for zip code, BMI, comorbidities, and obstructive sleep apnea (OSA) severity. AAs with severe OSA were 3 times more likely to use CPAP than AAs with mild/moderate OSA (p ≤ 0.001); a much smaller but still statistically significant difference was seen for Whites.

Conclusions

CPAP compliance is considerably lower in AAs than in Whites, though severity of OSA modifies this association. These findings are not readily explained by differences in demographics or comorbidity.



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IJMS, Vol. 17, Pages 151: Microglia-Mediated Neuroinflammation and Neurotrophic Factor-Induced Protection in the MPTP Mouse Model of Parkinson’s Disease-Lessons from Transgenic Mice

Parkinson's disease (PD) is a neurodegenerative disease characterised by histopathological and biochemical manifestations such as loss of midbrain dopaminergic (DA) neurons and decrease in dopamine levels accompanied by a concomitant neuroinflammatory response in the affected brain regions. Over the past decades, the use of toxin-based animal models has been crucial to elucidate disease pathophysiology, and to develop therapeutic approaches aimed to alleviate its motor symptoms. Analyses of transgenic mice deficient for cytokines, chemokine as well as neurotrophic factors and their respective receptors in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have broadened the current knowledge of neuroinflammation and neurotrophic support. Here, we provide a comprehensive review that summarises the contribution of microglia-mediated neuroinflammation in MPTP-induced neurodegeneration. Moreover, we highlight the contribution of neurotrophic factors as endogenous and/or exogenous molecules to slow the progression of midbrain dopaminergic (mDA) neurons and further discuss the potential of combined therapeutic approaches employing neuroinflammation modifying agents and neurotrophic factors.

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Bismu(2)-bis(diphenylphosphino)methane-1 : 2 kappa P-2 : P `;2 : 3 kappa P-2 : P `-dichlorido-1 kappa Cl,3 kappa Cl-triangulo-trigold(I) hexafluorophosphate

In the title compound, [Au3Cl2(C25H22P2)(2)](PF6), the cation possesses a triangular Au-3 core [Au-Au distances 3.1525 (4), 3.2770 (4) and 3.1922 (4) angstrom], two sides of which are bridged by dppm ligands [dppm = bis(diphenylphosphino) methane]. One phenyl group is disordered over two positions in a 0.65:0.35 ratio. The structure of the cation is compared with those in three other salts reported previously.

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A Bioactivity-Based Method for Screening, Identification of Lipase Inhibitors, and Clarifying the Effects of Processing Time on Lipase Inhibitory Activity of Polygonum Multiflorum

Traditional Chinese medicine (TCM) has been used for the treatment of many complex diseases. However, the bioactive components are always undefined. In this study, a bioactivity-based method was developed and validated to screen lipase inhibitors and evaluate the effects of processing on the lipase inhibitory activity of TCM by ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). The results showed that both Polygonum multiflorum and processed P. multiflorum extracts had inhibitory effect against lipase with IC50 values of 38.84 μg/mL and 190.6 μg/mL, respectively. Stilbenes, phenolic acid, flavonoids, and anthraquinones were considered to be the potential lipase inhibitors. Eleven potential lipase inhibitors were simultaneously determined by UHPLC. Principal component analysis (PCA) was employed in exploring the effects of processing time on lipase inhibitory activity of P. multiflorum. Compared with conventional methods, a bioactivity-based method could quantitatively analyze lipase inhibitory activity of individual constituent and provide the total lipase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying lipase inhibitors from traditional Chinese medicines.

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JCDD, Vol. 3, Pages 4: Response to Ponamgi et al. Comments on Khalighi et al. Takotsubo Cardiomyopathy: A Long Term Follow-up Shows Benefit with Risk Factor Reduction. J. Cardiovasc. Dev. Dis., 2015, 2, 273–281.

We appreciate the thorough response given by Ponagmi et al. [1], who rightly point out that the pathophysiology and modifiable risk factors of Takotsubo Cardiomyopathy (TC) have yet to be unequivocally established. […]

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JCDD, Vol. 3, Pages 5: Acknowledgement to Reviewers of Journal of Cardiovascular Development and Disease in 2015

The editors of Journal of Cardiovascular Development and Disease would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. […]

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3D Cell-SELEX: Development of RNA aptamers as molecular probes for PC-3 tumor cell line

Publication date: Available online 25 January 2016
Source:Experimental Cell Research
Author(s): Aline G. Souza, Karina Marangoni, Patrícia T. Fujimura, Patrícia T. Alves, Márcio J. Silva, Luiz R. Goulart, Vivian A. Goulart
Human prostate cancer (PCa) is a highly heterogeneous and multifactorial disease. Current clinical biomarkers are not sufficiently accurate, thus being unable to predict the clinical outcome. Therefore, searching for new biomarkers aiming to improve diagnosis, prognosis and therapy is still required. In this study, we performed 3D Cell-SELEX against PC-3 prostate cancer cell line, a novel strategy to select specific nucleic acid ligands against spheroid cells in 3D cell culture. This original system combines Cell-SELEX, a process that exploits the cellular structure to generate specific ligands, and 3D cell culture, an approach that mimics the tissue microenvironment in vitro. In the first round of 3D Cell-SELEX, a negative selection against RWPE-1, non-tumor cell line, was performed to subtract non-tumor specific aptamers. The supernatant was used in eight additional rounds of selection, which were performed against PC-3 cell line. After nine selection cycles, eight PC-3 specific RNA aptamers were selected and sequenced. The aptamers presented sizes between 20 to 50 nucleotides-long, with low free energy (∆G < −13.6), which contributed for their spontaneous folding and high stability. Furthermore, our results showed the aptamer A4 as a specific ligand to prostate tumor cells, with dissociation constant in the nanomolar scale. Therefore, the novel 3D Cell-SELEX procedure improved the selection of PCa cell-surface ligands and the aptamer A4 has shown potential for the identification of prostate tumor cells, suggesting the application of this molecule in further screening assays for PCa.

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JCM, Vol. 5, Pages 15: Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.

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JCM, Vol. 5, Pages 16: Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells

Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor.

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JCM, Vol. 5, Pages 14: Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation

Background—To describe the results obtained after treating a non growth hormone-deficient 10-year-old girl who suffered asphyxia during delivery, resulting in important cognitive deficits, with growth hormone (GH) and neurorehabilitation. Methods—GH was administered (mg/day) at doses of 0.5 over three months followed by 0.9, every two weeks over three months, and then alternating 1.2 three days/week and 0.3 two days/week. Neurorehabilitation consisted of daily sessions of neurostimulation, speech therapy, occupational therapy and auditive stimulation. Treatment lasted nine months. Results—Scores obtained in all the areas treated showed that, at discharge, the patient clearly increased her cognitive abilities, memory and language competence index; her intelligence quotient score increased from 51 to 80, and the index of functional independence measure reached a value of 120 over 126 (maximal value). Conclusions—This case suggests that GH administration may play a role in improving cognitive deficits during neurorehabilitation in children with brain damage suffered during delivery. This agrees with the known effects of GH on cognition.

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JCM, Vol. 5, Pages 13: Epithelial-Mesenchymal Transition and Breast Cancer

Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges.

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New Study Reveals Oral Sex Can Raise Risk For Head And Neck Cancer By Seven Times – malaysiandigest.com

New Study Reveals Oral Sex Can Raise Risk For Head And Neck Cancer By Seven Times
malaysiandigest.com
Pic: http://ift.tt/1nvjOvB who love oral sex beware! A recent study has revealed a strong connection between the human papillomavirus (HPV), which can be spread through oral sex, with head and neck cancer. HPV accounts for 70 per cent of head …

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Copper complex-assisted DNA hybridization

2,2`-Bipyridine ( bpy) or 1,10-phenanthroline ( phen) metal-binding domains were covalently attached to oligonucleotides, and the influence of metal ions on the hybridization of the conjugates was investigated. Metal-binding domains were attached to oligonucleotides at 3`- and 5`-terminal positions, thus placing them in juxtaposed positions after hybridization to a common target strand. While the ligands alone had a positive effect ( increased T-m) on hybrid stability, the duplex was further stabilized by the addition of copper( I) and/or copper( II) through the formation of a metal complex in which the two short sequences are linked through Cu( bpy)(2)

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An evaluation of the relationship between two- and three-dimensional packing in self-organised monolayers and bulk crystals of amphiphilic 2,2 ‘: 6 ‘,2 ”-terpyridines

2,2 ': 6 ',2 "-Terpyridine (tpy) ligands with pendant octadecyloxy, 4-octyloxyphenyl or 4-octadecyloxyphenyl substituents at the 4`-position have been prepared and structurally characterised. Monolayers of the compounds have been prepared on highly oriented pyrolytic graphite (HOPG) and investigated by STM. The monolayer structure corresponds to the bulk crystal structure if the latter contains planar sheets. The tpy ligands are prochiral and form homochiral domains within the monolayer, providing a spectacular visual representation of the symmetry-breaking concomitant with the formation of a monolayer.

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Quantification of single-stranded nucleic acid and oligonucleotide interactions with metal ions by affinity capillary electrophoresis: part I

The interactions between oligonucleotides and inorganic cations have been measured by capillary zone electrophoresis. With increasing concentrations of divalent cations (Ca2+, Mg2+, Mn2+ and Ni2+) in the running buffer, the migration behavior was evaluated by calculation of the binding constants. Besides these fundamental studies of binding equilibria, different buffer components, tris(hydroxymethyl)aminomethane and 3-(N-morpholino)propanesulfonic acid, have been investigated and their effects on metal ion binding quantified.

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Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy.

Mammalian target of rapamycin (mTOR), a central regulator of growth and metabolism, has tissue-specific functions depending on whether it is part of mTOR complex 1 (mTORC1) or mTORC2. We have previously shown that mTORC1 is required for adaptive cardiac hypertrophy and maintenance of function under basal and pressure-overload conditions. In the present study, we aimed to identify functions of mTORC2 in the heart.; Using tamoxifen-inducible cardiomyocyte-specific gene deletion, we generated mice deficient for cardiac rapamycin-insensitive companion of mTOR (rictor), an essential and specific component of mTORC2. Under basal conditions, rictor deficiency did not affect cardiac growth and function in young mice and also had no effects in adult mice. However, transverse aortic constriction caused dysfunction in the rictor-deficient hearts, whereas function was maintained in controls after 1 week of pressure overload. Adaptive increases in cardiac weight and cardiomyocyte cross-sectional area, fibrosis, and hypertrophic and metabolic gene expression were not different between the rictor-deficient and control mice. In control mice, maintained function was associated with increased protein levels of rictor, protein kinase C (PKC)βII, and PKCδ, whereas rictor ablation abolished these increases. Rictor deletion also significantly decreased PKCε at baseline and after pressure overload. Our data suggest that reduced PKCε and the inability to increase PKCβII and PKCδ abundance are, in accordance with their known function, responsible for decreased contractile performance of the rictor-deficient hearts.; Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart.

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PH-sensitive Ru(II) and Os(II) bis(2,2 `: 6 `,2 “-terpyridine) complexes: a photophysical investigation

We have investigated the photophysical properties of two metal complexes, [M(tpy-py)(2)][PF6](2), where tpy-py = 4-(4-pyridyl)2,2`:6`,2"-terpyridine and M = Ru(II) or Os(II), in acetonitrile and aqueous solutions at room temperature. Because the 4-pyridyl unit on the 4`-position of each tpy ligand contains a basic nitrogen atom, both of these compounds can exist in three different protonation states. We observed that the absorption and luminescence spectra of these compounds vary on changing the pH, because the protonation of the pendant pyridine unit makes it an electron acceptor by lowering the energy of its pi* orbital. We employed the absorption and luminescence spectral changes to study the acid-base reactions for these complexes, and found that the two protonation stages exhibit different pK(a) values both in the electronic ground state and in the lowest (emitting) excited state. The absorption spectra and luminescence spectra and lifetimes of the deprotonated, mono-protonated and bis-protonated forms were also determined. While the absorption spectra of the variously protonated forms of both compounds can be intepreted in terms of a linear combination of two different and independent chromophores, namely M(tpy-py) and M(tpy-pyH(+)), the corresponding luminescence spectra exhibit a more complex behaviour, suggesting that the coupling between the two ligands in the lowest excited state is not negligible. Interestingly, at a low pH the luminescence of the Ru complex is switched on, whereas that of the Os complex is strongly quenched upon protonation of the pendant pyridine units. These compounds are of interest because they exhibit a luminescent signal in the red or far red spectral region that can be switched on or off by protons in solution. Hence, they could find applications as luminescent pH sensors and as molecular switches where a low-energy emission signal can be controlled by a chemical acid-base stimulation. (c) 2006 Elsevier B.V. All rights reserved.

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Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease.

Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology.; To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD.; In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data.; Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the International Genomics of Alzheimer's Project sample, diagnosis of sporadic AD served as the phenotype of interest.; In the discovery sample, we detected significant enrichment for genes constituting the calcium signaling pathway, especially those related to the elevation of cytosolic calcium (P = 2 × 10-4). This enrichment was replicated in 2 additional samples of healthy young individuals (P = .02 and .04, respectively) and a sample of healthy elderly participants (P = .004). Hippocampal activation (P = 4 × 10-4) and the risk for sporadic AD (P = .01) were also significantly enriched for genes related to the elevation of cytosolic calcium.; By detecting consistent significant enrichment in independent cohorts of young and elderly participants, this study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes in cognitive health and disease, contributing to the understanding and potential treatment of hippocampus-dependent cognitive pathology.

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Bismu(2)-bis(diphenylphosphino)methane-1 : 2 kappa P-2 : P `;2 : 3 kappa P-2 : P `-dichlorido-1 kappa Cl,3 kappa Cl-triangulo-trigold(I) hexafluorophosphate

In the title compound, [Au3Cl2(C25H22P2)(2)](PF6), the cation possesses a triangular Au-3 core [Au-Au distances 3.1525 (4), 3.2770 (4) and 3.1922 (4) angstrom], two sides of which are bridged by dppm ligands [dppm = bis(diphenylphosphino) methane]. One phenyl group is disordered over two positions in a 0.65:0.35 ratio. The structure of the cation is compared with those in three other salts reported previously.

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A Bioactivity-Based Method for Screening, Identification of Lipase Inhibitors, and Clarifying the Effects of Processing Time on Lipase Inhibitory Activity of Polygonum Multiflorum

Traditional Chinese medicine (TCM) has been used for the treatment of many complex diseases. However, the bioactive components are always undefined. In this study, a bioactivity-based method was developed and validated to screen lipase inhibitors and evaluate the effects of processing on the lipase inhibitory activity of TCM by ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). The results showed that both Polygonum multiflorum and processed P. multiflorum extracts had inhibitory effect against lipase with IC50 values of 38.84 μg/mL and 190.6 μg/mL, respectively. Stilbenes, phenolic acid, flavonoids, and anthraquinones were considered to be the potential lipase inhibitors. Eleven potential lipase inhibitors were simultaneously determined by UHPLC. Principal component analysis (PCA) was employed in exploring the effects of processing time on lipase inhibitory activity of P. multiflorum. Compared with conventional methods, a bioactivity-based method could quantitatively analyze lipase inhibitory activity of individual constituent and provide the total lipase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying lipase inhibitors from traditional Chinese medicines.

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JCDD, Vol. 3, Pages 4: Response to Ponamgi et al. Comments on Khalighi et al. Takotsubo Cardiomyopathy: A Long Term Follow-up Shows Benefit with Risk Factor Reduction. J. Cardiovasc. Dev. Dis., 2015, 2, 273–281.

We appreciate the thorough response given by Ponagmi et al. [1], who rightly point out that the pathophysiology and modifiable risk factors of Takotsubo Cardiomyopathy (TC) have yet to be unequivocally established. […]

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JCDD, Vol. 3, Pages 5: Acknowledgement to Reviewers of Journal of Cardiovascular Development and Disease in 2015

The editors of Journal of Cardiovascular Development and Disease would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. […]

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Analysis of bacterial communities associated with potting media

Background: Potting media are commonly used by growers in different parts of the world for potted plants, raising seedlings and for improving soil characteristics. This study was conducted to characterize bacterial communities occurring in 13 commercial potting media products originating from seven countries.FindingsBacteria were isolated using serial dilution. Identification to the species level was based on phylogenetic analysis of the 16S rRNA gene. The analysis showed the association of 13 bacterial species with the different potting media samples, namely Arthrobacter livingstonensis, Kocuria flava, Leifsonia lichenia, Bacillus vallismortis, Bacillus pumilus, Staphylococcus warneri, Burkholderia phenazinium, Burkholderia sp., Ralstonia pickettii, Rhodanobacter spathiphylli, Rhodanobacter sp., Pseudomonas thivervalensis and Chryseobacterium gallinarum. Bacterial densities in the samples ranged from 8 × 10 7 to 1.2 × 10 9 colony forming units per gram of substrate. Conclusions: The study shows the isolation of some potential plant and human bacterial pathogens. However, most of the isolated species were either biocontrol species or saprophytes. The study questions the ways by which these bacterial species were introduced into potting media. To the best of our knowledge, this appears to be the first report of most of the isolated bacteria from potting media, except B. pumilus.

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U.K. audit shows failure to track urgent findings

2016_01_25_15_16_53_413_take_action_buttA U.K. audit has found that patients are being put at risk, because in only…

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Rupture of distal anterior cerebral artery aneurysm presenting only subdural hemorrhage without subarachnoid hemorrhage: a case report

Intracranial aneurysm rupture usually manifests with subarachnoid hemorrhage, often combined with intracerebral hemorrhage with intraventricular hemorrhage extension. In rare cases, however, these aneurysms present only as subdural hematomas. Recently, we treated a 48-years-old female patient who presented only with subdural hematoma. Interestingly, she did not have a history of trauma. Computed tomography angiography and digital subtraction angiography revealed a 5 × 3 mm sized aneurysm at the A3–A4 junction of the left anterior cerebral artery. On admission, emergency operation (clipping and hematoma evacuation) was performed to protect against re-bleeding. Along with postoperative intensive care, the patient returned to normal daily life with only a mild headache. Given that patients may present with atraumatic acute subdural hematoma, the clinician must bear in mind the possibility of intracranial vascular pathology and obtain angiographic scans to evaluate for any underlying conditions to prevent patient deaths.

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Short-term assessment of BCR repertoires of SLE patients after high dose glucocorticoid therapy with high-throughput sequencing

We analyze and assess BCR repertoires of SLE patients before and after high dose glucocorticoid therapy to address two fundamental questions: (1) After the treatment, how the BCR repertoire of SLE patient change on the clone level? (2) How to screen putative autoantibody clone set from BCR repertoire of SLE patients? The PBMCs of two SLE patients (P1 and P2) at different time points were collected, and DNA of these samples were extracted. High-throughput sequencing technology was applied in detection of BCR repertoire. Finally, we used bioinformatic methodology to analyse sequence data. We found that these two patients lost some IGHV3 family genes usage after treatment compared with before treatment. For pairing of IGHV–IGHJ gene, no significant change was shown for each patient. In addition, analyses of the composition of H-CDR3 showed overall AA compositions of H-CDR3 at three time points in each SLE patients were very similar, and the results of H-CDR3 AA usage that had the same length (14 AA) and the same position were similar. Antinuclear antibody tests of SLE patients showed that level of some antinuclear antibodies reduced after treatment; however, there was no sign that the percentage of autoantibody clones in BCR repertoires would reduce. High dose glucocorticoid treatment in short term will have little impact on composition of BCR repertoire of SLE patient. Treatment can reduce the amount of autoantibody in the protein level, but may not reduce the percentage of autoantibody clones in BCR repertoire in the clonal level.

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