bluuebunny/crossref_metadata_2025 huggingface dataset:
HealthSouth, Inc.: An Instructional Case Examining Auditors' Legal Liability
Authors: Daigle Ronald J. , Louwers Timothy J. , Morris Jan Taylor
Published: June 2013

This instructional case explores auditors' legal liability under the Securities Exchange Act of 1934 by asking students to assume the role of either the plaintiffs' (investors') or defendants' (Ernst & Young's) legal counsel. By using publicly available documents and testimony (provided on a dedicated website for this instructional case) in their arguments, students not only explore in depth one of the more egregious accounting scandals of the new millennium, but also are exposed to the plaintiff's burden of proof and the defendant's defenses in a Rule 10b-5 action. Additionally, by understanding the root causes of the fraud and why it took so long to uncover, students can better understand a number of the provisions set forth by the Sarbanes-Oxley Act of 2002. Results of a student survey after completion of the case indicate that case objectives were met. Students also report enjoying the case materials and welcoming other cases using similar types of materials.
Buyer and Seller at Odds: The Economic Consequences of Holding Appreciated Assets in a C Corporation
Authors: Gore Richard A.
Published: June 2013

A business holding appreciated assets is worth less to its owner if it is held in a C corporation than the fair market value of the assets. This fact arises from the double tax imposed on C corporations. One naive solution to this issue is for the shareholder to structure the sale of the business as a sale of stock in the corporation. What is often overlooked with this suggestion, however, is that the buyer will demand a discount in the price of the business if the deal is structured as a purchase of stock as opposed to a direct purchase of the assets. This economic reality is driven by the fact that the buyer forgoes the future tax savings from the step-up in basis in the appreciated assets of the target corporation in a stock acquisition. To illustrate this economic reality, this case study requires students to determine the present value of the future forgone tax savings to the buyer and to use that information along with the tax consequences to the seller to negotiate a compromise final purchase/sale agreement between the parties.
Mitochondrial Substrate Availability and Its Role in Lipid-Induced Insulin Resistance and Proinflammatory Signaling in Skeletal Muscle
Authors: Lipina Christopher , Macrae Katherine , Suhm Tamara , Weigert Cora , Blachnio-Zabielska Agnieszka , Baranowski Marcin , Gorski Jan , Burgess Karl , Hundal Harinder S.
Published: June 2013

The relationship between glucose and lipid metabolism has been of significant interest in understanding the pathogenesis of obesity-induced insulin resistance. To gain insight into this metabolic paradigm, we explored the potential interplay between cellular glucose flux and lipid-induced metabolic dysfunction within skeletal muscle. Here, we show that palmitate (PA)-induced insulin resistance and proinflammation in muscle cells, which is associated with reduced mitochondrial integrity and oxidative capacity, can be attenuated under conditions of glucose withdrawal or glycolytic inhibition using 2-deoxyglucose (2DG). Importantly, these glucopenic-driven improvements coincide with the preservation of mitochondrial function and are dependent on PA oxidation, which becomes markedly enhanced in the absence of glucose. Intriguingly, despite its ability to upregulate mitochondrial PA oxidation, glucose withdrawal did not attenuate PA-induced increases in total intramyocellular diacylglycerol and ceramide. Furthermore, consistent with our findings in cultured muscle cells, we also report enhanced insulin sensitivity and reduced proinflammatory tone in soleus muscle from obese Zucker rats fed a 2DG-supplemented diet. Notably, this improved metabolic status after 2DG dietary intervention is associated with markedly reduced plasma free fatty acids. Collectively, our data highlight the key role that mitochondrial substrate availability plays in lipid-induced metabolic dysregulation both in vitro and in vivo.
Autologous Pancreatic Islet Transplantation in Human Bone Marrow
Authors: Maffi Paola , Balzano Gianpaolo , Ponzoni Maurilio , Nano Rita , Sordi Valeria , Melzi Raffaella , Mercalli Alessia , Scavini Marina , Esposito Antonio , Peccatori Jacopo , Cantarelli Elisa , Messina Carlo , Bernardi Massimo , Del Maschio Alessandro , Staudacher Carlo , Doglioni Claudio , Ciceri Fabio , Secchi Antonio , Piemonti Lorenzo
Published: June 2013

The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans.
NH2-Terminal Pro–Brain Natriuretic Peptide and Risk of Diabetes
Authors: Lazo Mariana , Young J. Hunter , Brancati Frederick L. , Coresh Josef , Whelton Seamus , Ndumele Chiadi E. , Hoogeveen Ron , Ballantyne Christie M. , Selvin Elizabeth
Published: June 2013

Brain natriuretic peptide (BNP) has an established role in cardiovascular disease (CVD). However, recent animal studies suggest direct metabolic effects of BNP. To determine the association of BNP with the risk of diabetes, we conducted a prospective analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study. We included 7,822 men and women without history of diabetes, CVD, or reduced kidney function at baseline. At baseline, NH2-terminal (NT)-proBNP, a cleavage product of BNP, was inversely associated with adiposity, fasting glucose, insulin, and cholesterol but positively associated with blood pressure and C-reactive protein levels. During a median follow-up of 12 years, 1,740 participants reported a new diagnosis of diabetes or medication use for diabetes. Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment including fasting glucose. The adjusted HRs for diabetes were 1.0 (reference), 0.84 (95% CI 0.74–0.96), 0.79 (95% CI 0.68–0.90), and 0.75 (95% CI 0.64–0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively (P for trend <0.001). This inverse association was robust across sex, race, and obesity subgroups. Our results extend animal studies and support a direct and important metabolic role of BNP in humans.
ADAMTS13 Predicts Renal and Cardiovascular Events in Type 2 Diabetic Patients and Response to Therapy
Authors: Rurali Erica , Noris Marina , Chianca Antonietta , Donadelli Roberta , Banterla Federica , Galbusera Miriam , Gherardi Giulia , Gastoldi Sara , Parvanova Aneliya , Iliev Ilian , Bossi Antonio , Haefliger Carolina , Trevisan Roberto , Remuzzi Giuseppe , Ruggenenti Piero ,   for the BENEDICT Study Group
Published: June 2013

In patients with diabetes, impaired ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) proteolysis of highly thrombogenic von Willebrand factor (VWF) multimers may accelerate renal and cardiovascular complications. Restoring physiological VWF handling might contribute to ACE inhibitors’ (ACEi) reno- and cardioprotective effects. To assess how Pro618Ala ADAMTS13 variants and related proteolytic activity interact with ACEi therapy in predicting renal and cardiovascular complications, we genotyped 1,163 normoalbuminuric type 2 diabetic patients from BErgamo NEphrologic DIabetes Complications Trial (BENEDICT). Interaction between Pro618Ala and ACEi was significant in predicting both renal and combined renal and cardiovascular events. The risk for renal or combined events versus reference Ala carriers on ACEi progressively increased from Pro/Pro homozygotes on ACEi (hazard ratio 2.80 [95% CI 0.849–9.216] and 1.58 [0.737–3.379], respectively) to Pro/Pro homozygotes on non-ACEi (4.77 [1.484–15.357] and 1.99 [0.944–4.187]) to Ala carriers on non-ACEi (8.50 [2.416–29.962] and 4.00 [1.739–9.207]). In a substudy, serum ADAMTS13 activity was significantly lower in Ala carriers than in Pro/Pro homozygotes and in case subjects with renal, cardiovascular, or combined events than in diabetic control subjects without events. ADAMTS13 activity significantly and negatively correlated with all outcomes. In patients with diabetes, ADAMTS13 618Ala variant associated with less proteolytic activity, higher risk of chronic complications, and better response to ACEi therapy. Screening for Pro618Ala polymorphism may help identify patients with diabetes at highest risk who may benefit the most from early reno- and cardioprotective therapy.
Existence of positive solutions for nonlocal boundary value problem of fractional differential equation
Authors: Liu Xiping , Lin Legang , Fang Haiqin
Published: June 2013

In this paper, we study a type of nonlinear fractional differential equations multi-point boundary value problem with fractional derivative in the boundary conditions. By using the upper and lower solutions method and fixed point theorems, some results for the existence of positive solutions for the boundary value problem are established. Some examples are also given to illustrate our results.
Systems Designed with an Ionic Liquid and Molecular Solvents to Investigate the Kinetics of an SNAr Reaction
Authors: Salari Hadi , Hallett Jason P. , Padervand Mohsen , Gholami Mohammad Reza
Published: June 2013

The microscopic features of binary solvent systems formed by molecular solvents (methanol, ethanol, 2-methylpropan-2-ol, water, pyridine, acetonitrile, 1-propanol, 2-propanol, dimethylformamide) and the ionic liquid ([bmim]BF4) as cosolvent were used to select mixed solvents with particular characteristics. Molecular-microscopic solvent parameters corresponding to these binary mixtures were utilised to study the kinetics of the nucleophilic substitution reaction between 2-chloro-3,5-dinitropyridine and aniline to investigate and compare the effects of the solvents on a model chemical reaction. For these mixtures, the solvation behaviour is dominated by both the dipolarity/polarisability and hydrogen bonding interactions of the media. In these solutions, the rate constants of the reaction decrease with the mole fraction of ionic liquid.
Ab initio study of the reaction between silylene germylidene (H2Si = Ge:) and ethene to form a bis-heterocyclic compound containing Si and Ge
Authors: Liu Dongting , Lian Zhenxia , Lu Xiuhui
Published: June 2013

The mechanism of the cycloaddition reaction between singlet state silylene germylidene (H2Si = Ge:) and ethene has been investigated with the CCSD(T)//MP2/6-31G* method; from the potential energy profile, we predict that the reaction has one dominant reaction pathway. This dominant pathway has the two reactants firstly forming a Si-heterocyclic four-membered ring germylene (INT1) through a [2 + 2] cycloaddition reaction. Due to the sp3 hybridisation of the Ge: atom in INT1, the latter further combines with ethene to form a bis-heterocyclic product containing Si and Ge (P2).
Kinetic studies of manganese(III) and cobalt(II) Schiff base complexes as synthetic hydrolases for p-nitrophenyl picolinate in CTAB surfactant micellar solution
Authors: Zhang Jin , Tang Ying , Li Jian-Zhang
Published: June 2013

Four symmetrical bis-Schiff bases with either benzo-10-aza-crown ether or morpholino pendants and their Mn(III) and Co(II) complexes have been employed as models for hydrolase enzymes by studying the kinetics of their hydrolysis reactions with p-nitrophenyl picolinate (PNPP) in buffered CTAB micellar solution. A kinetic model of PNPP cleavage catalysed by these complexes is proposed. The effects of complex structures and reaction temperature on the rate of PNPP hydrolysis have been examined. All four complexes exhibit higher catalytic activity in the buffered CTAB micellar solution and the rate increases with pH of the buffer at 25 °C. The complexes containing two crown ether group exhibit higher catalytic activities than their crown-free analogues, and the catalytic activity of the phenyl-bridged Schiff base complex is larger than that of the ethyl-bridged Schiff base complex for the same substituents and metal. The catalytic activity of the manganese(III) complex exceeds that of the cobalt(II) complex in catalysing hydrolysis of PNPP under the same ligand.
Single electron transfer in SNAr process: Reactions of 2,4,6-tris(trifluoromethanesulfonyl)anisole with anilines in dimethyl sulfoxide
Authors: Guesmi N. El , Boubaker T. , Goumont R.
Published: June 2013

Second-order rate constants ( k1) have been measured spectrophotometrically for reactions of 2,4,6-tris(trifluoromethanesulfonyl)anisole 1 with 4-X-substituted anilines (X = OH, OCH3, CH3, H, I and Cl) 2a–f in dimethyl sulfoxide (DMSO) at 25 °C. The Hammett plot is nonlinear, i.e. the anilines having an electron-donating substituent exhibit positive deviations from the log k1 versus correlation. The Hammett plot consists of two intersecting straight lines, i.e. ρ=– 1.40 for electron-withdrawing substituents (X = I and Cl) while ρ=– 3.26 for electron-donating substituents (X = OH, OCH3 and CH3). The Brønsted-type plot is also nonlinear with a change in slope from a small value (βnuc=0.50) to a large value (βnuc = 1.29 at p Ka=4.58). This change could be interpreted in terms of a change in mechanism from a polar SNAr process to a single electron transfer. On the other hand, the experimental data show that the rate constants ( k1) values exhibit good correlation with the oxidation potentials ( E°) of the aniline nucleophiles and are consistent with the suggested mechanism.
The Allylic Rearrangements (Claisen and Thio-Claisen) and Decomposition Reactions of Allyl Formate and its Sulfur Analogue: Density Function Theory Study and Nucleus-Independent Chemical Shifts
Authors: Shiroudi Abolfazl , Zahedi Ehsan
Published: June 2013

Theoretical studies of the Claisen and thio-Claisen allylic (3,3-sigmatropic) rearrangements and decomposition reactions of allyl formate (1) and allyl dithioformate (2), have been performed using density functional theory (DFT) and B3LYP and MPW1PW91 methods with a 6-31++G** basis set. Of these DFT, the values for activation parameters obtained with the B3LYP/6-31++G** method are in good agreement with the available experimental data. Transition states optimised at the B3LYP/6-31++G** level of theory were used for calculating the nucleus-independent chemical shift (NICS). Our results indicate that the magnitudes of the aromatic characters of the transition states are not in agreement with the activation energies and therefore these reactions are not controlled by aromaticity, but are controlled kinetically by the aromaticity of the transition states.
An Efficient Synthesis of Functionalised 2-(heteroaryl)-3H-benzo[f] Chromen-3-ones and Antibacterial Evaluation
Authors: Gomha Sobhi M. , Abdel-Aziz Hassan M.
Published: June 2013

An efficient synthesis of 19 2-(heteroaryl)-3 H-benzo[f]chromen-3-ones is described via reaction of 2-(3-hydroxyacry-loyl)-3 H-benzo[f]chromen-3-one with various heterocyclic amines and active methylene compounds. The synthesised compounds, 18 of which are novel, were characterised on the basis of their elemental analysis and spectral data. Eight of the synthesised products were evaluated as antibacterial agents.
Rhodium-catalysed Nucleophilic Ring Opening Reaction of 1- and 3-ethoxy-5,8-epoxy-5,8-dihydroisoquinolines
Authors: Kelebekli Latif
Published: June 2013

2-Ethoxy-3- and 5-chloropyridines were obtained from 2,3- and 2,5-dichloropyridine. Reaction of 2,3- and 2,5-dichlo-ropyridines with tBuLi in the presence of furan gave 1- and 3-ethoxy-5,8-epoxy-5,8-dihydroisoquinolines. The rhodium-catalysed ring-opening reaction of 1- and 3-ethoxy-5,8-epoxy-5,8-dihydroisoquinolines with 2-bromophenol furnished the isomer 7-(2-bromophenoxy)-1-ethoxy-7,8-dihydroisoquinolin-8-ol, 6-(2-bromophenoxy)-1-ethoxy-5,6-dihydroisoquinolin-5-ol and 7-(2-bromophenoxy)-3-ethoxy-7,8-dihydroisoquinolin-8-ol, 6-(2-bromophenoxy)-3-ethoxy-5,6-dihydroisoquinolin-5-ol respectively.
Prescriber and Patient Responsibilities in Treatment of Acute Respiratory Tract Infections — Essential for Conservation of Antibiotics
Authors: Van der Velden Alike , Duerden Martin , Bell John , Oxford John , Altiner Attila , Kozlov Roman , Sessa Aurelio , Pignatari Antonio , Essack Sabiha
Published: June 2013

Inappropriate antibiotic use in normally self-limiting acute respiratory tract infections (RTIs), such as sore throat and the common cold, is a global problem and an important factor for increasing levels of antibiotic resistance. A new group of international experts—the Global Respiratory Infection Partnership (GRIP)—is committed to addressing this issue, with the interface between primary care practitioners and their patients as their core focus. To combat the overuse of antibiotics in the community, and facilitate a change from prescribing empiric antibiotic treatment towards cautious deferment combined with symptomatic relief, there is a need to introduce and enhance evidence-based dialogue between primary care practitioners and their patients. Communication with patients should focus on the de-medicalisation of self-limiting viral infections, which can be achieved via a coherent globally endorsed framework outlining the rationale for appropriate antibiotic use in acute RTIs in the context of antibiotic stewardship and conservancy. The planned framework is intended to be adaptable at a country level to reflect local behaviours, cultures and healthcare systems, and has the potential to serve as a model for change in other therapeutic areas.
Neuroprotective Mechanisms of Taurine against Ischemic Stroke
Authors: Menzie Janet , Prentice Howard , Wu Jang-Yen
Published: June 2013

Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke.
Up Against The Wall: The Effects of Climate Warming on Soil Microbial Diversity and The Potential for Feedbacks to The Carbon Cycle
Authors: Pold Grace , DeAngelis Kristen
Published: June 2013

Earth’s climate is warming, and there is evidence that increased temperature alters soil C cycling, which may result in a self-reinforcing (positive), microbial mediated feedback to the climate system. Though soil microbes are major drivers of soil C cycling, we lack an understanding of how temperature affects SOM decomposition. Numerous studies have explored, to differing degrees, the extent to which climate change may affect biodiversity. While there is ample evidence that community diversity begets ecosystem stability and resilience, we know of keystone species that perform functions whose effects far outweigh their relative abundance. In this paper, we first review the meaning of microbial diversity and how it relates to ecosystem function, then conduct a literature review of field-based climate warming studies that have made some measure of microbial diversity. Finally, we explore how measures of diversity may yield a larger, more complete picture of climate warming effects on microbial communities, and how this may translate to altered carbon cycling and greenhouse gas emissions. While warming effects seem to be ecosystem-specific, the lack of observable consistency between measures is due in some part to the diversity in measures of microbial diversity.
Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure
Authors: Bossi Rossana , Vinggaard Anne , Taxvig Camilla , Boberg Julie , Bonefeld-Jørgensen Eva
Published: June 2013

Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds.
Peptide Induced Crystallization of Calcium Carbonate on Wrinkle Patterned Substrate: Implications for Chitin Formation in Molluscs
Authors: Sengupta Ghatak Anindita , Koch Marcus , Guth Christina , Weiss Ingrid
Published: June 2013

We here present the nucleation and growth of calcium carbonate under the influence of synthetic peptides on topographically patterned poly(dimethylsiloxane) (PDMS) substrates, which have a controlled density of defects between the wrinkles. Experiments with two lysine-rich peptides derived from the extracellular conserved domain E22 of the mollusc chitin synthase Ar-CS1, AKKKKKAS (AS8) and EEKKKKKES (ES9) on these substrates showed their influence on the calcium carbonate morphology. A transition from polycrystalline composites to single crystalline phases was achieved with the peptide AS8 by changing the pH of the buffer solution. We analyzed three different pH values as previous experiments showed that E22 interacts with aragonite biominerals more strongly at pH 7.75 than at pH 9.0. At any given pH, crystals appeared in characteristic morphologies only on wrinkled substrates, and did not occur on the flat, wrinkle-free PDMS substrate. These results suggest that these wrinkled substrates could be useful for controlling the morphologies of other mineral/peptide and mineral/protein composites. In nature, these templates are formed enzymatically by glycosyltransferases containing pH-sensitive epitopes, similar to the peptides investigated here. Our in vitro test systems may be useful to gain understanding of the formation of distinct 3D morphologies in mollusc shells in response to local pH shifts during the mineralization of organic templates.
Prevention of Intra-Abdominal Adhesion by Bi-Layer Electrospun Membrane
Authors: Jiang Shichao , Wang Wei , Yan Hede , Fan Cunyi
Published: June 2013

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.
Use of Heat Stress Responsive Gene Expression Levels for Early Selection of Heat Tolerant Cabbage (Brassica oleracea L.)
Authors: Park Hyun , Jung Won , Lee Sang , Song Jun , Kwon Suk-Yoon , Kim HyeRan , Kim ChulWook , Ahn Jun , Cho Hye
Published: June 2013

Cabbage is a relatively robust vegetable at low temperatures. However, at high temperatures, cabbage has disadvantages, such as reduced disease tolerance and lower yields. Thus, selection of heat-tolerant cabbage is an important goal in cabbage breeding. Easier or faster selection of superior varieties of cabbage, which are tolerant to heat and disease and have improved taste and quality, can be achieved with molecular and biological methods. We compared heat-responsive gene expression between a heat-tolerant cabbage line (HTCL), “HO”, and a heat-sensitive cabbage line (HSCL), “JK”, by Genechip assay. Expression levels of specific heat stress-related genes were increased in response to high-temperature stress, according to Genechip assays. We performed quantitative RT-PCR (qRT-PCR) to compare expression levels of these heat stress-related genes in four HTCLs and four HSCLs. Transcript levels for heat shock protein BoHsp70 and transcription factor BoGRAS (SCL13) were more strongly expressed only in all HTCLs compared to all HSCLs, showing much lower level expressions at the young plant stage under heat stress (HS). Thus, we suggest that expression levels of these genes may be early selection markers for HTCLs in cabbage breeding. In addition, several genes that are involved in the secondary metabolite pathway were differentially regulated in HTCL and HSCL exposed to heat stress.
Bioactive Secondary Metabolites of a Marine Bacillus sp. Inhibit Superoxide Generation and Elastase Release in Human Neutrophils by Blocking Formyl Peptide Receptor 1
Authors: Yang Shun-Chin , Lin Chwan-Fwu , Chang Wen-Yi , Kuo Jimmy , Huang Yin-Ting , Chung Pei-Jen , Hwang Tsong-Long
Published: June 2013

It is well known that overwhelming neutrophil activation is closely related to acute and chronic inflammatory injuries. Formyl peptide receptor 1 (FPR1) plays an important role in activation of neutrophils and may represent a potent therapeutic target in inflammatory diseases. In the present study, we demonstrated that IA-LBI07-1 (IA), an extract of bioactive secondary metabolites from a marine Bacillus sp., has anti-inflammatory effects in human neutrophils. IA significantly inhibited superoxide generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated neutrophils, but failed to suppress the cell responses activated by non-FPR1 agonists. IA did not alter superoxide production and elastase activity in cell-free systems. IA also attenuated the downstream signaling from FPR1, such as the Ca2+, MAP kinases and AKT pathways. In addition, IA inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analogue of FMLP, to FPR1 in human neutrophils and FPR1-transfected HEK293 cells. Taken together, these results show that the anti-inflammatory effects of IA in human neutrophils are through the inhibition of FPR1. Also, our data suggest that IA may have therapeutic potential to decrease tissue damage induced by human neutrophils.
Isocyanate-Functionalized Chitin and Chitosan as Gelling Agents of Castor Oil
Authors: Gallego Rocío , Arteaga Jesús , Valencia Concepción , Franco José
Published: June 2013

The main objective of this work was the incorporation of reactive isocyanate groups into chitin and chitosan in order to effectively use the products as reactive thickening agents in castor oil. The resulting gel-like dispersions could be potentially used as biodegradable lubricating greases. Three different NCO–functionalized polymers were obtained: two of them by promoting the reaction of chitosan with 1,6-hexamethylene diisocyanate (HMDI), and the other by using chitin instead of chitosan. These polymers were characterized through 1H-NMR, FTIR and thermogravimetric analysis (TGA). Thermal and rheological behaviours of the oleogels prepared by dispersing these polymers in castor oil were studied by means of TGA and small-amplitude oscillatory shear (SAOS) measurements. The evolution and values of the linear viscoelasticity functions with frequency for –NCO–functionalized chitosan- and chitin-based oleogels are quite similar to those found for standard lubricating greases. In relation to long-term stability of these oleogels, no phase separation was observed and the values of viscoelastic functions increase significantly during the first seven days of ageing, and then remain almost constant. TGA analysis showed that the degradation temperature of the resulting oleogels is higher than that found for traditional lubricating greases.
Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization
Authors: Guo Yuh-Cherng , Chang Che-Mai , Hsu Wen-Li , Chiu Siou-Jin , Tsai Yao-Ting , Chou Yii-Her , Hou Ming-Feng , Wang Jaw-Yan , Lee Mei-Hsien , Tsai Ke-Li , Chang Wei-Chiao
Published: June 2013

Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF)-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.
Observation of Human Retinal Remodeling in Octogenarians with a Resveratrol Based Nutritional Supplement
Authors: Richer Stuart , Stiles William , Ulanski Lawrence , Carroll Donn , Podella Carla
Published: June 2013

Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function. Effects have lasted for one year or longer when taken daily, at which point one patient required initiation of anti-VEGF agents. Unanticipated systemic benefits were observed. Conclusions: Preliminary observations support previous publications in animals and humans. Restoration of structure and visual function in octogenarians with daily oral consumption of L/RV is documented. Applications include failure on AREDS II supplements, refusing or failing conventional anti-VEGF therapy, adjunct therapy to improve RPE function, and compassionate use in medically underserved or economically depressed third-world countries.
Fluctuating Entanglements in Single-Chain Mean-Field Models
Authors: Schieber Jay , Indei Tsutomu , Steenbakkers Rudi
Published: June 2013

We consider four criteria of acceptability for single-chain mean-field entangled polymer models: consistency with a multi-chain level of description, consistency with nonequilibrium thermodynamics, consistency with the stress-optic rule, and self-consistency between Green–Kubo predictions and linear viscoelastic predictions for infinitesimally driven systems. Each of these topics has been considered independently elsewhere. However, we are aware of no molecular entanglement model that satisfies all four criteria simultaneously. Here we show that an idea from Ronca and Allegra, generalized to arbitrary flows, can be implemented in a slip-link model to create a model that does satisfy all four criteria. Aside from the direct benefits of agreement, the result modifies the relation between the initial relaxation modulus G(0) and the entanglement molecular weight Me. If this implementation is correct, current estimates for Me would require modification that brings their values more in line with estimates based on topological analysis of molecular dynamics simulations.
Non-Invasive Continuous Glucose Monitoring with Multi-Sensor Systems: A Monte Carlo-Based Methodology for Assessing Calibration Robustness
Authors: Zanon Mattia , Sparacino Giovanni , Facchinetti Andrea , Talary Mark , Mueller Martin , Caduff Andreas , Cobelli Claudio
Published: June 2013

In diabetes research, non-invasive continuous glucose monitoring (NI-CGM) devices represent a new and appealing frontier. In the last years, some multi-sensor devices for NI-CGM have been proposed, which exploit several sensors measuring phenomena of different nature, not only for measuring glucose related signals, but also signals reflecting some possible perturbing processes (temperature, blood perfusion). Estimation of glucose levels is then obtained combining these signals through a mathematical model which requires an initial calibration step exploiting one reference blood glucose (RBG) sample. Even if promising results have been obtained, especially in hospitalized volunteers, at present the temporal accuracy of NI-CGM sensors may suffer because of environmental and physiological interferences. The aim of this work is to develop a general methodology, based on Monte Carlo (MC) simulation, to assess the robustness of the calibration step used by NI-CGM devices against these disturbances. The proposed methodology is illustrated considering two examples: the first concerns the possible detrimental influence of sweat events, while the second deals with calibration scheduling. For implementing both examples, 45 datasets collected by the Solianis Multisensor system are considered. In the first example, the MC methodology suggests that no further calibration adjustments are needed after the occurrence of sweat events, because the “Multisensor+model” system is able to deal with the disturbance. The second case study shows how to identify the best time interval to update the model’s calibration for improving the accuracy of the estimated glucose. The methodology proposed in this work is of general applicability and can be helpful in making those incremental steps in NI-CGM devices development needed to further improve their performance.
Simultaneous/Selective Detection of Dopamine and Ascorbic Acid at Synthetic Zeolite-Modified/Graphite-Epoxy Composite Macro/Quasi-Microelectrodes
Authors: Ilinoiu Elida , Manea Florica , Serra Pier , Pode Rodica
Published: June 2013

The present paper aims to miniaturize a graphite-epoxy and synthetic zeolite-modified graphite-epoxy composite macroelectrode as a quasi-microelectrode aiming in vitro and also, envisaging in vivo simultaneous electrochemical detection of dopamine (DA) and ascorbic acid (AA) neurotransmitters, or DA detection in the presence of AA. The electrochemical behavior and the response of the designed materials to the presence of dopamine and ascorbic acid without any protective membranes were studied by cyclic voltammetry and constant-potential amperometry techniques. The catalytic effect towards dopamine detection was proved for the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode, allowing increasing the sensitivity and selectivity for this analyte detection, besides a possible electrostatic attraction between dopamine cation and the negative surface of the synthetic zeolite and electrostatic repulsion with ascorbic acid anion. Also, the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode gave the best electroanalytical parameters for dopamine detection using constant-potential amperometry, the most useful technique for practical applications.
Regulation of Human Cytomegalovirus Transcription in Latency: Beyond the Major Immediate-Early Promoter
Authors: Reeves Matthew , Sinclair John
Published: June 2013

Lytic infection of differentiated cell types with human cytomegalovirus (HCMV) results in the temporal expression of between 170–200 open reading frames (ORFs). A number of studies have demonstrated the temporal regulation of these ORFs and that this is orchestrated by both viral and cellular mechanisms associated with the co-ordinated recruitment of transcription complexes and, more recently, higher order chromatin structure. Importantly, HCMV, like all herpes viruses, establishes a lifelong latent infection of the host—one major site of latency being the undifferentiated haematopoietic progenitor cells resident in the bone marrow. Crucially, the establishment of latency is concomitant with the recruitment of cellular enzymes that promote extensive methylation of histones bound to the major immediate early promoter. As such, the repressive chromatin structure formed at the major immediate early promoter (MIEP) elicits inhibition of IE gene expression and is a major factor involved in maintenance of HCMV latency. However, it is becoming increasingly clear that a distinct subset of viral genes is also expressed during latency. In this review, we will discuss the mechanisms that control the expression of these latency-associated transcripts and illustrate that regulation of these latency-associated promoters is also subject to chromatin mediated regulation and that the instructive observations previously reported regarding the negative regulation of the MIEP during latency are paralleled in the regulation of latent gene expression.
The Fourth Phase of Water: Beyond Solid, Liquid, and Vapor. By Gerald H. Pollack, Ebner & Sons Publishers, 2013; 357 Pages. Price US $29.95, ISBN 978-0-9626895-4-3
Authors: Lin Shu-Kun
Published: June 2013

The following paragraphs are reproduced from the website of the publisher [1]. Professor Pollack takes us on a fantastic voyage through water, showing us a hidden universe teeming with physical activity that provides answers so simple that any curious person can understand. In conversational prose, Pollack lays a simple foundation for understanding how changes in water’s structure underlie most energetic transitions of form and motion on earth.
Clinical Characteristics and Outcomes of Peritoneal Dialysis–Related Peritonitis with Different Trends of Change in Effluent white Cell count: A Longitudinal Study
Authors: Xu Rong , Chen Yuan , Luo Suping , Xu Ying , Zheng Bo , Zheng Yingdong , Dong Jie
Published: June 2013

Background

Effluent white cell count (WCC) is among the important prognostic factors for peritonitis outcome, but its trend has never been studied. We aimed to explore the clinical characteristics and outcomes of peritonitis episodes having different trends in effluent WCC change in the first 5 days.

Methods

For each peritonitis episode, we examined the patient's demographic and biochemical data, serial effluent WCC, and organisms cultured. Peritonitis- associated death and transfer to hemodialysis were defined as treatment failure.

Results

Based on the trend of effluent WCC in the first 5 days, we divided 190 peritonitis episodes into group A (WCC persistently declined), group B (WCC declined after a transient increase), group C (WCC increased after a transient decline), and group D (WCC persistently increased). In group A, peritonitis was caused mostly by gram-positive organisms, and effluent WCC declined the most quickly, leading to a good prognosis. Although the elevation of effluent WCC was prolonged in group B, and the infections were, compared with those in group A, more often caused by gram-negative organisms, outcomes were not worse. In group C, the effluent WCC was more likely to be higher than 100/μL on day 5, and the infection was, compared with those in groups A and B, less likely to be caused by gram-positive organisms. Accordingly, membership in group C independently predicted the worst outcome of peritonitis even adjusted for age, sex, and causative organism.

Conclusions

Different trends of change in effluent WCC during the early stage of peritonitis represent different clinical patterns and outcomes. Further investigation for optimizing outcomes is required.
L'hôpital malade de l'« efficience »
Authors: Blouses Docteurs
Published: June 2013

Médecins hospitaliers depuis de nombreuses années, nous disons ici notre désarroi et notre colère face à certaines pratiques inacceptables dans nos hôpitaux. Le rationnement des soins qui les caractérise aujourd’hui se traduit par une augmentation des risques et des inégalités d’accès pour les patients, en particulier en matière de transport (brancardage et ambulances). De son côté, relégué au rang de simple facteur de (mauvaise) production, le personnel hospitalier ne peut plus exercer correctement son métier de soignant. En particulier les médecins, qui se trouvent face à une injonction contradictoire : responsables des soins, ils se voient refuser les moyens de les prodiguer correctement. Enfin, on constate un renforcement de l’écart entre ce qui est réellement fait dans les établissements et les comptes rendus officiels qui en sont donnés. Par ce texte, nous entendons alerter sur ces évolutions qui menacent la santé des patients.
Faire payer le patient : une politique absurde
Authors: Batifoulier Philippe
Published: June 2013

Faire payer le patient est une stratégie à la mode, et les tickets modérateurs, franchises médicales et participation forfaitaire se sont largement développés, en France comme ailleurs. Il s’agit d’organiser le renoncement aux soins pour raison financière pour lutter contre les gaspillages. Disposer d’une assurance maladie généreuse encouragerait une consommation de soins sans utilité pour la santé. Une telle conception n’est pas seulement erronée. Elle s’est avérée tragique : faire payer le patient nuit en effet gravement à son état de santé et alimente les inégalités. En mettant des barrières financières à l’entrée du système de soins, elle prive de soins ceux qui en ont le plus besoin. C’est aussi dès lors une stratégie absurde car elle active des dépenses nouvelles, notamment par des mécanismes de retard de soins et de report vers l’hôpital.
Le care capacitant. Une alternative au paradigme néoclassique de la responsabilité individuelle
Authors: Léonard Christian
Published: June 2013

Les contraintes que la crise économique et financière fait peser sur les budgets publics semblent exacerber les velléités de rendre financièrement responsables les allocataires sociaux, et en particulier les patients. À l’aide de l’exemple des statines, médicaments utilisés pour réduire le taux de cholestérol, nous illustrons toute la complexité d’une démarche qui vise à déterminer les contours de la responsabilité individuelle des patients à l’égard de leur état de santé et des dépenses de soins. Des systèmes de « carottes » et « bâtons » sont ainsi préconisés pour inciter le patient à adopter un comportement « sanitairement correct » d’une part, et à devenir un consommateur de soins économe d’autre part. Contrairement à la logique de la rationalité économique, nous proposons une approche de libération de l’individu au moyen d’actes simples et concrets de «  care capacitant ». Nous relions ainsi care , liberté et responsabilité tant individuelle que collective dans un processus progressif de renforcement des capacités de l’individu à devenir acteur de sa santé et, de manière plus générale, de son existence.
L'assistance entre charité et soupçon. Sur la distribution alimentaire dans une petite ville du nord de la France
Authors: Cary Paul , Roi Claire-Sophie
Published: June 2013

Cet article repose sur l’observation de type socio-ethnographique du fonctionnement d’une association catholique de distribution de l’aide alimentaire dans une petite ville du nord de la France, aux indicateurs socio-économiques très dégradés. Après avoir décrit la façon dont une dizaine de bénévoles âgés continue à prendre en charge la distribution mensuelle d’une centaine de colis, nous montrons que le maintien de cette forme d’assistance s’explique par un contexte local dans lequel le contrôle social des pauvres va de pair avec un multi-positionnement des notables dans les nombreuses structures d’assistance. La confluence entre une conception de l’aide fondée sur la charité et un discours contemporain de défiance envers la dépendance produit des formes de prise en charge particulièrement stigmatisantes et contraignantes pour les bénéficiaires.
Construction identificatoire en psychanalyse familiale. Complexes et imagos
Authors: Jaïtin Rosa
Published: June 2013

L’auteur introduit une réflexion sur la construction psychique appuyée sur le modèle des nouvelles familles où les processus identificatoires se complexifient. Pour aborder la question, elle interroge la place qu’occupent les complexes dans la psychanalyse familiale actuelle. Au complexe d’Œdipe classique, les postfreudiens en ajoutent trois autres : le complexe de sevrage, le complexe d’intrusion et le complexe fraternel. La résolution de ceux-ci oblige à placer la construction des imagos dans la perspective groupale de la famille. Seul un groupe peut aider à se défaire de l’imago maternelle archaïque. De même, seul un groupe fraternel peut s’opposer et se différencier du couple parental en accédant à la différenciation générationnelle.Une situation clinique de thérapie familiale psychanalytique illustre la question des nouvelles familles dans leurs multiples groupes d’appartenance. Mais l’introduction d’Internet (Skype), dans le cours de la thérapie, permet à l’un des pères de participer virtuellement au processus thérapeutique.