bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors' Factors of Nutritional Status of Male Chronic Obstructive Pulmonary Disease Patients
Authors: Pirabbasi Elham , Najafiyan Mahin , Cheraghi Maria , Shahar Suzana , Abdul Manaf Zahara , Rajab Norfadilah , Abdul Manap Roslina
Published: November 2012

Chronic obstructive pulmonary disease (COPD) is a systemic disease that leads to weight loss and muscle dysfunction resulting in an increase in mortality. This study aimed to determine the prevalence rate of malnutrition and nutritional status and also factors associated with nutritional status. A total of 149 subjects were involved in the cross-sectional study. The study was conducted at two medical centers in Kuala Lumpur, Malaysia. The results of the study showed that malnutrition was more prevalent (52.4%) in the subjects with severe stages of COPD as compared to mild and moderate COPD stages (26.2%) (P<0.05). Fat-free mass depletion as assessed using fat-free mass index (FFMI) affected 41.9% of the subjects. Plasma vitamin A, peak expiratory flow (PEF), and handgrip were the predictors for body mass index (BMI) (R2=0.190, P<0.001). Plasma vitamin A and force expiratory volume in one second (FEV1) were the predictors of FFMI (R2=0.082, P=0.007). BMI was the predictor of respiratory factors, that is, FEV1% predicted (R2=0.052, P=0.011). It can be concluded that there is a need to identify malnourished COPD patients for an appropriate nutrition intervention.
A New Strategy to Find Targets for Anticancer Therapy: Chemokine CXCL14/BRAK Is a Multifunctional Tumor Suppressor for Head and Neck Squamous Cell Carcinoma
Authors: Hata Ryu-Ichiro
Published: November 2012

In order to find a suppressor(s) of tumor progression in vivo for head and neck squamous cell carcinoma (HNSCC), we searched for molecules downregulated in HNSCC cells when the cells were treated with epidermal growth factor (EGF), whose receptor is frequently overactivated in HNSCC. The expression of BRAK, which is also known as CXC chemokine ligand 14 (CXCL14), was downregulated significantly by the treatment of HNSCC cells with EGF as observed by cDNA microarray analysis followed by reverse-transcriptase polymerase chain reaction analysis and western blotting. The EGF effect on the expression of CXCL14/BRAK was attenuated by the copresence of inhibitors of the EGF receptor, MEK, and ERK. The rate of tumor formation in vivo of BRAK-expressing vector-transfected tumor cells in athymic nude mice or SCID mice was significantly lower than that of mock vector-transfected ones. In addition tumors formed in vivo by the BRAK-expressing cells were significantly smaller than those of the mock-transfected ones. These results indicate that CXCL14/BRAK is a chemokine having suppressive activity toward tumor progression of HNSCC in vivo. Our approach will be useful to find new target molecules to suppress progression of tumors of various origins in addition to HNSCC.
Estrogen Abolishes Protective Effect of Erythropoietin against Cisplatin-Induced Nephrotoxicity in Ovariectomized Rats
Authors: Pezeshki Zahra , Nematbakhsh Mehdi , Mazaheri Safoora , Eshraghi-Jazi Fatemeh , Talebi Ardeshir , Nasri Hamid , Safari Tahereh , Mansouri Azam , Ashrafi Farzaneh
Published: November 2012

Introduction. Nephrotoxicity is one the side effect of cisplatin therapy and erythropoietin has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompained with estrogen has not been studied in female. Methods. 27 ovariectomized female Wistar rats divided into five groups. Groups 1 & 2 received estradiol valerate (0.5 mg/kg/week) for four weeks, and single dose of cisplatin (7 mg/kg, ip) was administrated at the end of week 3. Then the group 1 was treated with erythropoietin (100 U/kg/day), and the group 2 received vehicle during week 4. Groups 3 and 4 were treated similar to group 1 and 2, except for placebo instead estradiol valerate. Group5 (negative control) received placebo during the study. Animals were killed at the end of week 4. Results. In non-erythropoietin treated rats, cisplatin significantly increased the serum levels of blood urea nitrogen and creatinine (P<0.05). However, these biomarkers significantly decreased by erythropoietin (P<0.05). The weight loss, kidney weight, and kidney tissue damage score in rats treated with cisplatin but without estradiol were significantly less than the values in similar group when estradiol was present (P<0.05). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present.
Continuous Measurement of Cerebral Oxygenation with Near-Infrared Spectroscopy after Spontaneous Subarachnoid Hemorrhage
Authors: Maslehaty Homajoun , Krause-Titz Ulf , Petridis Athanassios K. , Barth Harald , Mehdorn Hubertus Maximilian
Published: November 2012

Objective. The aim of our prospective study was to investigate the applicability and the diagnostic value of near-infrared spectroscopy (NIRS) in SAH patients using the cerebral oximeter INVOS 5100C.Methods. Measurement of cerebral oximetry was done continuously after spontaneous SAH. Decrease of regional oxygen saturation (rSO2) was analyzed and interpreted in view of the determined intrinsic and extrinsic factors. Changes of rSO2values were matched with the values of ICP, tipO2, and TCD and the results of additional neuroimaging.Results. Continuous measurement of rSO2was performed in nine patients with SAH (7 females and 2 males). Mean measurement time was 8.6 days (range 2–12 days). The clinical course was uneventful in 7 patients without occurrence of CVS. In these patients, NIRS measured constant and stable rSO2values without relevant alterations. Special findings are demonstrated in 3 cases.Conclusion. Measurement of rSO2with NIRS is a safe, easy to use, noninvasive additional measurement tool for cerebral oxygenation, which is used routinely during vascular and cardiac surgical procedures. NIRS is applicable over a long time period after SAH, especially in alert patients without invasive probes. Our observations were promising, whereby larger studies are needed to answer the open questions.
Fitted, Green, and Volunteered: Legal and Survey Complexities of Future Boundary Systems
Authors: Bennett Rohan M. , Molen Paul van der , Zevenbergen Jaap A.
Published: November 2012

The disparity between the legal understanding of boundaries and their surveyed location is explained. The impacts of this disparity on three boundary fabrics issues: survey-accuracy; greening cadastres; and crowd-sourced cadastres are then examined. The features are selected based on contemporary discourse within the domain of land administration. Survey-accuracy is found to be a confused, misused, and often politicized term. The concept of idealization precision should be revisited and embedded into both curriculum and cadastral design. Green boundaries, at least some forms, are already handled in some systems; however, newer varieties require better tools for adjudication, demarcation, survey, recording, and adherence. Crowdsourced data can be understood as a re-emergence of deeds style registration with its associated benefits and disadvantages. It might support existing cadastral systems, particularly those that lack complete coverage; however, it may also be used to publicize discontent with these existing systems. The paper illustrates lessons, threats, and opportunities for land practitioners involved with the establishment and maintenance of the legal boundary fabric.
Regulatory Mechanisms of Injury and Repair after Hepatic Ischemia/Reperfusion
Authors: Lentsch Alex B.
Published: November 2012

Hepatic ischemia/reperfusion injury is an important complication of liver surgery and transplantation. The mechanisms of this injury as well as the subsequent reparative and regenerative processes have been the subject of thorough study. In this paper, we discuss the complex and coordinated responses leading to parenchymal damage after liver ischemia/reperfusion as well as the manner in which the liver clears damaged cells and regenerates functional mass.
A Neutraceutical by Design: The Clinical Application of Curcumin in Colonic Inflammation and Cancer
Authors: Soni D. , Salh B.
Published: November 2012

Unquestionably, the natural food additive curcumin, derived from the colorful spice turmeric used in many Asian cuisines, possesses a diverse array of biological activities. These range from its anti-inflammatory, antineoplastic, and metabolic modifying properties to surprising roles in disorders ranging from Alzheimer's disease to cystic fibrosis. Its effects on growth factor receptors, signaling molecules, and transcription factors, together with its epigenetic effects are widely considered to be extraordinary. These pleiotropic attributes, coupled with its safety even when used orally at well over 10 g/day, are unparalleled amongst pharmacological agents. However, there is one drawback; apart from the luminal gastrointestinal tract where its pharmacology predicts that reasonable drug levels can be attained, its broader use is hampered by its poor solubility and hence near undetectable plasma levels. Medicinal chemistry and nanotechnology have resulted in the generation of compounds where the modified drug or its delivery system has improved matters such that this shortcoming has been addressed to some extent, with the surprising finding that it remains safe to use. It is predicted that either the parental compound or its derivatives may eventually find a place in the therapeutic management protocols of several conditions.
The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and Function at Multiple Subcellular Locations
Authors: Henderson Beric R.
Published: November 2012

Inherited mutations in theBRCA1gene predispose to a higher risk of breast/ovarian cancer. The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization signals that enable it to shuttle between specific sites within the nucleus and cytoplasm, including DNA repair foci, centrosomes, and mitochondria. BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways. This paper will focus on the transport, dynamics, and multiple intracellular destinations of BRCA1 with emphasis on how regulation of these events has impact on, and determines, a broad range of important cellular functions.
Uptake and effectiveness of interventions to reduce claw lesions in 40 dairy herds in the UK
Authors: Barker ZE , Wright JL , Blowey RW , Amory JR , Green LE
Published: November 2012

In the final year of a three-year study of lameness in dairy cattle, 40 herds were allocated to either an intervention (22) or control (18) group. Farms in the intervention group were visited by a veterinarian who made up to 16 recommendations to reduce the incidence of lameness based on potential risks for lameness observed at that visit. Farms in the control group were visited and the same observations were made, but no changes recommended. All farms were visited on three further occasions to score the locomotion of all cows and collect information on changes made to the farm. Before intervention, the mean herd size, lactation average milk yield per cow and prevalence of severely lame cows were 122, 8,157 I and 9.85% for the control group and 109, 7,807 I and 9.14% for the intervention group. After the intervention there were no significant differences between the treatments in terms of the change in prevalence of severely lame cows or the change in rate of sole ulcer, white line disease or digital dermatitis. The overall uptake of recommendations was 41.3%. There were no significant correlations between the percentage of risks addressed and the rate of sole ulcer or prevalence of severely lame cows and only a non-significant trend for white line disease. Improvements to cubicle dimensions were associated with a reduction in the rate of sole ulcer, and changing nutrition and adding biotin to the ration were associated with a reduction in white line disease. Conversely, increasing the amount of sawdust to cubicle floors was associated with increased rate of sole ulcer and white line disease and improving cubicle dimensions was associated with increased rate of white line disease.
The effects of level of support for animal protection organisations on attitudes to the use of animals and other social issues
Authors: Phillips CJC , Izmirli S
Published: November 2012

Animal protection issues are being advanced increasingly by Non-Government Organisations, yet the views of their supporters are little understood. We surveyed attitudes towards animals and other social issues in 3,462 university students from over 103 universities in eleven European and Asian countries. The extent to which those respondents that supported animal protection organisations had more concern for animals than those who did not support such organisations was investigated, and whether this concern was generalised to other world social issues. Of the respondents, 36% sometimes and 6% very often supported animal protection organisations and 2% identified themselves as key members. Supporters and key members had increased scores on indices that measured their concerns for animal welfare (+ 6%), animals in experimentation (+ 7%), and other major social issues (+ 5%), compared with non-supporters. Supporters were also likely to have lived with pets for longer, suggesting that this was one of the drivers for their increased concern for animals. Key members of the organisations rated the sentience of humans lower (-9%) than other students rated them, and nearer to that of animals. The level of support for the organisations was directly related to avoidance of poultry, pork and beef meat. It is concluded that support for animal protection organisations is an indicator of attitudes towards animals and other social issues, and food consumption habits.
A 10-Year Dataset of Basic Meteorology and Soil Properties in Central Sudan
Authors: Ardö Jonas
Published: November 2012

Meteorological data and soil data have been collected at a site in the central Sudan from 2002 to 2012. The site is a sparse savanna in the semiarid region of Sudan. In addition to basic meteorological variables, soil properties (temperature, water content, and heat flux) and radiation (global radiation, net radiation, and photosynthetic active radiation) were measured. The dataset has a temporal resolution of 30 minutes and provides general data for calibration and validation of ecosystem models and remote-sensing-based assessments, and it is relevant for studies of ecosystem properties and processes.
HAART rollout in the new fiscal and economic environment
Authors: Moatti J
Published: November 2012

The trend towards universal access for HIV prevention and treatment that was initiated at the beginning of the 21st century (international donor funding has been multiplied by 3 to reach 27 billion US$ in 2010) has been threatened by the 2008–9 economic crisis which currently translates in a fiscal crisis for most developed countries (including the US, France and the UK – the main donors for HIV/AIDS). Other advances such as the drastic drop in ARV drug prices are also threatened (generic first line drugs close to marginal cost, insufficient drop in second line drug prices, etc.). The presentation will discuss the negative consequences of slowing down and delaying universal access on macro‐economic growth in the most affected countries and suggest alternative sources of funding such as the financial transaction tax recently introduced by the French Parliament.
Solid‐State Dye‐Sensitized Solar Cells Using a Novel Class of Ullazine Dyes as Sensitizers
Authors: Dualeh Amalie , Humphry‐Baker Robin , Delcamp Jared Heath , Nazeeruddin Mohammad Khaja , Grätzel Michael
Published: November 2012

Here we present the photovoltaic performance of solid‐state dye‐sensitized solar cells (DSCs) using a series of ullazine‐based metal‐free organic sensitizers and spiro‐MeOTAD as a hole‐transport material. A maximum of 4.95% power conversion efficiency measured under standard AM 1.5G illumination (100 mW cm−2) was achieved with the best performing ullazine dye, and was further improved to 5.40% through co‐sensitization with the triphenylamine‐based organic sensitizer, D35. This study investigates the effect of the molecular structure of the ullazine sensitizer on the performance in solid‐state DSCs.
Aromatics from Lignocellulosic Biomass: Economic Analysis of the Production of p‐Xylene from 5‐Hydroxymethylfurfural
Authors: Lin Zhaojia , Ierapetritou Marianthi , Nikolakis Vladimiros
Published: November 2012

A novel production of biobased p‐xylene from hydroxymethylfurfual has been investigated and presented. This is an important part of a process for the production of aromatics from lignocellulosic biomass. The detailed flow sheets are designed based on laboratory experiments by Leshkov et al. and William et al. and economic analysis has been performed. The minimum biobased p‐xylene cost is estimated as $3,962/metric ton, of which the main contribution comes from the HMF cost. Sensitivity analysis has been used to assess the impact of uncertainties of economic parameters and also to determine the most significant reaction factor in the technological development, i.e., selectivity and conversion. It has been shown that high selectivity is favored at the same yield. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2079–2087, 2013
Myosin Isoform Fiber Type and Fiber Size in the Tail of the Virginia Opossum (Didelphis virginiana)
Authors: Hazimihalis P.J. , Gorvet M.A. , Butcher M.T.
Published: November 2012

Muscle fiber type is a well studied property in limb muscles, however, much less is understood about myosin heavy chain (MHC) isoform expression in caudal muscles of mammalian tails. Didelphid marsupials are an interesting lineage in this context as all species have prehensile tails, but show a range of tail‐function depending on either their arboreal or terrestrial locomotor habits. Differences in prehensility suggest that MHC isoform fiber types may also be different, in that terrestrial opossums may have a large distribution of oxidative fibers for object carrying tasks instead of faster, glycolytic fiber types expected in mammals with long tails. To test this hypothesis, MHC isoform fiber type and their regional distribution (proximal/transitional/distal) were determined in the tail of the Virginia opossum (Didelphis virginiana). Fiber types were determined by a combination of myosin‐ATPase histochemistry, immunohistochemistry, and SDS‐PAGE. Results indicate a predominance of the fast MHC‐2A and ‐2X isoforms in each region of the tail. The presence of two fast isoforms, in addition to the slow MHC‐1 isoform, was confirmed by SDS‐PAGE analysis. The overall MHC isoform fiber type distribution for the tail was: 25% MHC‐1, 71% MHC‐2A/X hybrid, and 4% MHC‐1/2A hybrid. Oxidative MHC‐2A/X isoform fibers were found to be relatively large in cross‐section compared to slow, oxidative MHC‐1 and MHC‐1/2A hybrid fibers. A large percentage of fast MHC‐2A/X hybrids fibers may be suggestive of an evolutionary transition in MHC isoform distribution (fast‐to‐slow fiber type) in the tail musculature of an opossum with primarily a terrestrial locomotor habit and adaptive tail‐function. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
Somal and Dendritic Development of Human CA3 Pyramidal Neurons F rom Midgestation to Middle Childhood: A Quantitative Golgi Study
Authors: Lu Dahua , He Lixin , Xiang Wei , Ai Wei‐Min , Cao Ye , Wang Xiao‐Sheng , Pan Aihua , Luo Xue‐Gang , Li Zhiyuan , Yan Xiao‐Xin
Published: November 2012

The CA3 area serves a key relay on the tri‐synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre‐ and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi‐impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age‐dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.
A Carborane‐Derivative “Click” Reaction under Heterogeneous Conditions for the Synthesis of a Promising Lipophilic MRI/GdBNCT Agent
Authors: Toppino Antonio , Bova Maria Elena , Geninatti Crich Simonetta , Alberti Diego , Diana Eliano , Barge Alessandro , Aime Silvio , Venturello Paolo , Deagostino Annamaria
Published: November 2012

In this study, the Huisgen reaction has been used to functionalise a carborane cage with a lipophilic moiety and a 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron‐capture therapy (BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole units has been accomplished under both heterogeneous conditions, by the use of a Cu‐supported ionic‐liquid catalyst, and homogeneous conditions. The ability of the Gd complex of the synthesised ligand to form stable adducts with low‐density lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour melanoma cells incubated in the presence of a Gd‐complex/LDL imaging probe. It has been concluded that the high amount of intracellular boron necessary to perform BNCT can be reached even in the presence of a relatively low‐boron‐containing LDL concentration.
Toward Libraries of Biotinylated Chondroitin Sulfate Analogues: From Synthesis to In Vivo Studies
Authors: Despras Guillaume , Bernard Clémence , Perrot Anthony , Cattiaux Laurent , Prochiantz Alain , Lortat‐Jacob Hugues , Mallet Jean‐Maurice
Published: November 2012

Chondroitin sulfate‐E (CS‐E) oligosaccharidic analogues (di to hexa) were prepared from lactose. In these compounds, the 2‐acetamido group was replaced by a hydroxyl group. This modification speeded up the synthesis, and large oligosaccharides were constructed in a few steps from a lactose‐originated block. The protecting groups used were as follows; Fmoc for hydroxyl groups to be glycosylated, allyl group for anomeric position protection, and trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We took advantage of the presence of allyl group to develop a click biotinylation, through its transformation into a 3‐azido‐2‐hydroxyl propyl group in two steps (epoxidation and sodium azide epoxide opening). The biotinylating agent was a water‐soluble propargylated and biotinylated triethylene glycol (PEG). By using surface plasmon resonance (SPR), it was shown that the di‐, tetra‐, and hexasaccharides display a binding affinity and selectivity toward HSF/GSF and CXCL12 similar to that of CS‐E. A parallel study confirmed their mimicry of natural compounds, based on the hexasaccharide interaction with Otx2, a homeodomain protein involved in brain maturation, thus validating our simplification approach to synthesize bioactive GAG.
Conjugate Addition versus Cycloaddition/Condensation of Nitro Compounds in Water: Selectivity, Acid–Base Catalysis, and Induction Period
Authors: Guideri Luca , De Sarlo Francesco , Machetti Fabrizio
Published: November 2012

Nitroacetates and nitroacetamides react in water as in chloroform with electron‐deficient dipolarophiles to give condensation or conjugate addition products under base catalysis. In general, high selectivity towards condensation is observed in water, with shorter induction periods than in chloroform. In water, condensations slowly occur even without base; kinetic profiles evidence the catalytic effect of the base, which should be related to the conversion into the tautomer nitronic acid. Condensations in water provide convenient access to isoxazole derivatives bearing various functional groups including ammonium, carboxy, and carboxyamide.
Metal‐Ion Metathesis in Metal–Organic Frameworks: A Synthetic Route to New Metal–Organic Frameworks
Authors: Kim Yonghwi , Das Sunirban , Bhattacharya Saurav , Hong Soonsang , Kim Min Gyu , Yoon Minyoung , Natarajan Srinivasan , Kim Kimoon
Published: November 2012

A porous metal–organic framework, Mn(H3O)[(Mn4Cl)3(hmtt)8] (POST‐65), was prepared by the reaction of 5,5′,10,10′,15,15′‐hexamethyltruxene‐2,7,12‐tricarboxylic acid (H3hmtt) with MnCl2 under solvothermal conditions. POST‐65(Mn) was subjected to post‐synthetic modification with Fe, Co, Ni, and Cu according to an ion‐exchange method that resulted in the formation of three isomorphous frameworks, POST‐65(Co/Ni/Cu), as well as a new framework, POST‐65(Fe). The ion‐exchanged samples could not be prepared by regular solvothermal reactions. The complete exchange of the metal ions and retention of the framework structure were verified by inductively coupled plasma–atomic emission spectrometry (ICP‐AES), powder X‐ray diffraction (PXRD), and Brunauer–Emmett–Teller (BET) surface‐area analysis. Single‐crystal X‐ray diffractions studies revealed a single‐crystal‐to‐single‐crystal (SCSC)‐transformation nature of the ion‐exchange process. Hydrogen‐sorption and magnetization measurements showed metal‐specific properties of POST‐65.
Lyotropic Supramolecular Helical Columnar Phases Formed by C3‐Symmetric and Unsymmetric Rigid Molecules
Authors: Wang Daoliang , Huang Youju , Li Junjun , Xu Lu , Chen Mingming , Tao Jiaojiao , Li Liangbin
Published: November 2012

Unlike thermotropic liquid‐crystalline C3‐symmetric molecules with flexible chains, the herein‐designed fully rigid three‐armed molecules (C3‐symmetric and unsymmetric) create a fancy architecture for the formation of lyotropic liquid crystals in water. First, hollow columns with triple‐stranded helices, analogous to helical rosette nanotubes, are spontaneously constructed by self‐organization of the rigid three‐armed molecules. Then, the helical nanotubes arrange into hexagonal liquid‐crystalline phases, which show macroscopic chirality as a result of supramolecular chiral symmetry breaking. Interestingly, the helical nanotubes constructed by the fully rigid molecules are robust and stable over a wide concentration range in water. They are hardly affected by ionic defects at the molecular periphery, that is, further decoration of functional groups on the molecular arms can presumably be realized without changing the helical conformation. In addition, the formed columnar phases can be aligned macroscopically by simple shear and show anisotropic ionic conductivity, which suggests promising applications for low‐dimensional ion‐conductive materials.
Barriers to Warfarin Use for Stroke Prevention in Patients With Atrial Fibrillation in Hong Kong
Authors: Lee Vivian W. Y. , Tam Cheuk Shing , Yan Bryan P. , Man Yu Cheuk , Yin Lam Yat
Published: November 2012

Background:

Oral anticoagulation medications such as warfarin reduce the risk of stroke in atrial fibrillation (AF) but have been underutilized. This study aimed to investigate physicians' perceptions of stroke prevention management and patients' knowledge of AF and warfarin therapy in Hong Kong (HK).

Hypothesis:

Both physician and patient's knowledge on warfarin use were the barriers for stroke prevention in patients with atrial fibrillation in Hong Kong.

Methods:

This prospective survey‐based study was conducted between February 2011 and April 2011 to assess physicians' perceptions of stroke prevention management, patients' knowledge of AF, and patients' knowledge of warfarin therapy. The results were scored and compared with those in foreign countries.

Results:

Sixty‐two physicians and 114 warfarin users were recruited in the study. The average score of HK physicians in the knowledge of stroke prevention therapy in AF patients was lower than that of Australian (AUS) family physicians (HK 2.48 vs AUS 4.02 out of 7). The mean scores of AF patients in Hong Kong regarding the knowledge of AF were lower than that of United Kingdom (UK) (HK 1.16 vs UK 2.24 out of 4) (P < 0.001) and that of Finland (FIN) (HK 2.77 vs FIN 5.94 out of 8) (P < 0.001), respectively. The mean score of AF patients in Hong Kong regarding the knowledge of warfarin therapy was lower than that of AF patients in the United States (US) (HK 2.39 vs US 3.92).

Conclusions:

The barriers of warfarin use for AF patients in Hong Kong were related to both physicians and patients. Many Hong Kong physicians did not comply with international recommendations of stroke prevention in AF patients, and AF patients had a low knowledge level about the disease and warfarin therapy.

Presented at the International Congress of Cardiology, Hong Kong, Peoples Republic of China, February 24‐26, 2012.

This study was supported by the School of Pharmacy, the Chinese University of Hong Kong.

The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Universal fluorescent labeling of amplification products using locked nucleic acids
Authors: Asari Masaru , Oka Kumiko , Omura Tomohiro , Maseda Chikatoshi , Tasaki Yoshikazu , Shiono Hiroshi , Matsubara Kazuo , Matsuda Mitsuyoshi , Shimizu Keiko
Published: November 2012

Amplification/hybridization‐based genetic analyses using primers containing locked nucleic acids (LNAs) present many benefits. Here, we developed a novel design for universal fluorescent PCR using LNAs. Universal fluorescent PCR generates intermediate nonlabeled fragments and final fluorescent fragments in a two‐step amplification process that uses locus‐specific primers with universal tails and universal fluorescent primers. In this study, a few standard nucleotides were replaced with LNAs only in the fluorescent universal primers. The sequence of the fluorescent universal primer significantly affected the amplification efficiency. For primers with three LNAs, the fluorescent primers with stable M13(‐47) sequences provided the most efficient signal (approximately tenfold higher than the primers with M13(‐21) sequences at lower Tm values). Moreover, AT‐rich LNA substitutions in the fluorescent primers produced much lower amplification efficiencies than GC‐rich substitutions. GC‐rich LNAs produced greater differences in Tm values among primers, and resulted in the preferential production of fluorescently labeled amplicons. The specificity and sensitivity of LNA‐containing fluorescent primers were assessed by genotyping eight STRs in Japanese individuals, and full STR profiles could be generated using as little as 0.25 ng of genomic DNA. The method permitted clear discrimination of alleles and represents sensitive STR genotyping at a reduced cost.
Epithelial‐to‐mesenchymal transition of human lung alveolar epithelial cells in a microfluidic gradient device
Authors: Kim Su Hwan , Hwang Sae Mi , Lee Jong Min , Kang Jin Hyun , Chung Il Yup , Chung Bong Geun
Published: November 2012

Epithelial‐to‐mesenchymal transition (EMT), a process in which epithelial cells undergo phenotypic transitions to fibrotic cells, is induced by stimulants including transforming growth factor‐beta1 (TGF‐β1). In the present study, we developed a microfluidic gradient device to reproduce EMT in A549 human lung alveolar epithelial cells in response to TGF‐β1 gradients. The device was directly mounted on the cells that had grown in cell culture plates and produced a stable concentration gradient of TGF‐β1 with negligible shear stress, thereby providing a favorable environment for the anchorage‐dependent cells. A549 cells elongated with the characteristic spindle‐shaped morphological changes with upregulation of alpha‐smooth muscle actin, a mesenchyme marker, in a gradient‐dependent manner, suggestive of EMT progression. We observed that at higher TGF‐β1 concentrations ranging from 5 to 10 ng/mL, the cultures in the microfluidic device allowed to quantitatively pick up subtle differences in the EMT cellular response as compared with plate cultures. These results suggest that the microfluidic gradient device would accurately determine the optimal concentrations of TGF‐β1, given that epithelial cells of different tissue origins greatly vary their responses to TGF‐β1. Therefore, this microfluidic device could be a powerful tool to monitor EMT induced by a variety of environmental stresses including cigarette smoke with high sensitivity.
Improved correspondence of resting‐state networks after macroanatomical alignment
Authors: Frost Martin A. , Esposito Fabrizio , Goebel Rainer
Published: November 2012

Resting state brain activity, as measured with functional magnetic resonance imaging (fMRI) in the absence of stimulation, is widely investigated in clinical, pharmacological, developmental and cross‐species neuroscience research. However, despite the general and broad interest in understating the nature of resting state networks (RSNs), there has not been a thorough investigation into the relationship between these functional networks and their adherence to underling brain anatomy. We acquired resting state fMRI data from 10 subjects and extracted individual and group RSN maps respectively using independent component analysis (ICA) and self organising group‐level ICA (sogICA). Cortex based alignment (CBA), an advanced surface based alignment technique which uses individual curvature information to align individual subjects' brains to a dynamic group average, was used to maximise anatomical correspondence across subjects. Cross subject spatial correlations of the RSN maps (independent components) were carried out with and without CBA. Seven RSNs, which are amongst the most reported and studied networks, were identified. We observed a systematic gain in the spatial correlation in all of them following CBA, although this gain was not uniform across RSNs. The observed increase in similarity of the functional RSNs after anatomical alignment illustrates that these functional networks are indeed related to underlying macroanatomical features. Moreover, our results demonstrate that by correcting for individual anatomical differences, advanced surface based alignment techniques increase the overlap of corresponding resting state networks across subjects, thereby providing a useful means to improve resting state group statistics with no need for substantial smoothing. Hum Brain Mapp 35:673–682, 2014. © 2012 Wiley Periodicals, Inc.
Stochastic dynamic causal modeling of working memory connections in cocaine dependence
Authors: Ma Liangsuo , Steinberg Joel L. , Hasan Khader M. , Narayana Ponnada A. , Kramer Larry A. , Moeller F. Gerard
Published: November 2012

Although reduced working memory brain activation has been reported in several brain regions of cocaine‐dependent subjects compared with controls, very little is known about whether there is altered connectivity of working memory pathways in cocaine dependence. This study addresses this issue by using functional magnetic resonance imaging‐based stochastic dynamic causal modeling (DCM) analysis to study the effective connectivity of 19 cocaine‐dependent subjects and 14 healthy controls while performing a working memory task. Stochastic DCM is an advanced method that has recently been implemented in SPM8 that can obtain improved estimates, relative to deterministic DCM, of hidden neuronal causes before convolution with the hemodynamic response. Thus, stochastic DCM may be less influenced by the confounding effects of variations in blood oxygen level‐dependent response caused by disease or drugs. Based on the significant regional activation common to both groups and consistent with previous working memory activation studies, seven regions of interest were chosen as nodes for DCM analyses. Bayesian family level inference, Bayesian model selection analyses, and Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine‐dependent subjects had large differences compared with the control subjects in the strengths of prefrontal–striatal modulatory (B matrix) DCM parameters. These findings are consistent with altered cortical–striatal networks that may be related to reduced dopamine function in cocaine dependence. As far as we are aware, this is the first between‐group DCM study using stochastic methodology. Hum Brain Mapp 35:760–778, 2014. © 2012 Wiley Periodicals, Inc.
Endoplasmic reticulum stress induces hepatic steatosis via increased expression of the hepatic very low-density lipoprotein receptor
Authors: Jo Hyunsun , Choe Sung Sik , Shin Kyung Cheul , Jang Hagoon , Lee Jae Ho , Seong Je Kyung , Back Sung Hoon , Kim Jae Bum
Published: November 2012

Recent evidence suggests that obese animals exhibit increased endoplasmic reticulum (ER) stress in the liver and adipose tissue. Although ER stress is closely associated with lipid homeostasis, it is largely unknown how ER stress contributes to hepatic steatosis. In this study, we demonstrate that the induction of ER stress stimulates hepatic steatosis through increased expression of the hepatic very low-density lipoprotein receptor (VLDLR). Among the unfolded protein response sensors, the protein kinase RNA-like ER kinase–activating transcription factor 4 signaling pathway was required for hepatic VLDLR up-regulation. In primary hepatocytes, ER stress–dependent VLDLR expression induced intracellular triglyceride accumulation in the presence of very low-density lipoprotein. Moreover, ER stress–dependent hepatic steatosis was diminished in the livers of VLDLR-deficient and apolipoprotein E–deficient mice compared with wild-type mice. In addition, the VLDLR-deficient mice exhibited decreased hepatic steatosis upon high-fat diet feeding.

Conclusion

: These data suggest that ER stress–dependent expression of hepatic VLDLR leads to hepatic steatosis by increasing lipoprotein delivery to the liver, which might be a novel mechanism explaining ER stress–induced hepatic steatosis.
Hepatitis C virus promotes t-helper (Th)17 responses through thymic stromal lymphopoietin production by infected hepatocytes
Authors: Lee Hai-Chon , Sung Sung-Sang J. , Krueger Peter D. , Jo Yoon-Ah , Rosen Hugo R. , Ziegler Steven F. , Hahn Young S.
Published: November 2012

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Here we report that infection of hepatic cells by HCV stimulates nuclear factor kappa B (NFκB)-dependent production of thymic stromal lymphopoietin (TSLP). Hepatocyte-derived TSLP in turn conditions dendritic cells (DCs) to drive T-helper (Th)17 differentiation. The TSLP secreted by HCV-infected hepatoma cells is capable of activating human monocyte-derived DCs by up-regulating the expression of CD40, CD86, CCL17, CCL22, and CCL20 which are activating markers of DCs. In addition, the production of key cytokines for Th17 differentiation, transforming growth factor beta (TGF-β), interleukin (IL)-6, and IL-21, is enhanced by human monocytes upon coculture with HCV-infected cells. Importantly, the blockade of TSLP using neutralizing antibody prevented the activation and maturation of DCs as well as the production of Th17 differentiation cytokines. DC conditioning by TSLP secreted from HCV-infected cells activated naïve CD4+ T lymphocytes, resulting in Th17 differentiation. Furthermore, we can detect substantial levels of hepatocyte TSLP in fibrotic liver tissue from chronic HCV patients. Thus, blockade of TSLP released by HCV-infected hepatocytes may suppress the induction/maintenance of hepatic Th17 responses and halt the progression of chronic liver disease to fibrosis and liver failure.

Conclusion:

Hepatocyte-derived TSLP conditions DCs to drive Th17 differentiation. Treatment of TSLP neutralizing antibody in HCV-infected hepatocyte/DC coculture abrogates DC conditioning and thereby inhibits Th17 differentiation.
Preexisting epithelial diversity in normal human livers: A tissue-tethered cytometric analysis in portal/periportal epithelial cells
Authors: Isse Kumiko , Lesniak Andrew , Grama Kedar , Maier John , Specht Susan , Castillo-Rama Marcela , Lunz John , Roysam Badrinath , Michalopoulos George , Demetris Anthony J.
Published: November 2012

Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa.

Conclusion:

Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here.
Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis
Authors: Huang Chiung-Kuei , Lee Soo Ok , Lai Kuo-Pao , Ma Wen-Lung , Lin Tzu-Hua , Tsai Meng-Yin , Luo Jie , Chang Chawnshang
Published: November 2012

Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been considered as an alternative therapy, replacing liver transplantation in clinical trials, to treat liver cirrhosis, an irreversible disease that may eventually lead to liver cancer development. However, low survival rate of the BM-MSCs leading to unsatisfactory efficacy remains a major concern. Gender differences have been suggested in BM-MSCs therapeutic application, but the effect of the androgen receptor (AR), a key factor in male sexual phenotype, in this application is not clear. Using two liver cirrhosis mouse models induced by CCl4 or thioacetamide, we showed that targeting AR in the BM-MSCs improved their self-renewal and migration potentials and increased paracrine effects to exert anti-inflammatory and anti-fibrotic actions to enhance liver repair. Mechanism dissection studies suggested that knocking out AR in BM-MSCs led to improved self-renewal and migration by alteration of the signaling of epidermal growth factor receptor and matrix metalloproteinase 9 and resulted in suppression of infiltrating macrophages and hepatic stellate cell activation through modulation of interleukin (IL)1R/IL1Ra signaling. Therapeutic approaches using either AR/small interfering RNA or the AR degradation enhancer, ASC-J9®, to target AR in BM-MSCs all led to increased efficacy for liver repair.

Conclusion

: Targeting AR, a key factor in male sexual phenotype, in BM-MSCs improves transplantation therapeutic efficacy for treating liver fibrosis.
Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R‐IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high‐dose methotrexate‐based chemotherapy
Authors: Mappa Silvia , Marturano Emerenziana , Licata Giada , Frezzato Maurizio , Frungillo Niccolò , Ilariucci Fiorella , Stelitano Caterina , Ferrari Antonella , Sorarù Mariella , Vianello Fabrizio , Baldini Luca , Proserpio Ilaria , Foppoli Marco , Assanelli Andrea , Reni Michele , Caligaris‐Cappio Federico , Ferreri Andrés J. M.
Published: November 2012

Despite a high proportion of patients with primary CNS lymphoma (PCNSL) experiences failure after/during first‐line treatment, a few studies focused on salvage therapy are available, often with disappointing results. Herein, we report feasibility and activity of a combination of rituximab, ifosfamide and etoposide (R‐IE regimen) in a multicentre series of patients with PCNSL relapsed or refractory to high‐dose methotrexate‐based chemotherapy. We considered consecutive HIV‐negative patients ≤75 years old with failed PCNSL treated with R‐IE regimen (rituximab 375 mg/m2, day 0; ifosfamide 2 g/m2/day, days1–3; etoposide 250 mg/m2, day 1; four courses). Twenty‐two patients (median age 60 years; range 39–72; male/female ratio: 1:4) received R‐IE as second‐line (n = 18) or third‐line (n = 4) treatment. Eleven patients had refractory PCNSL, and 11 had relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of the 88 planned courses were actually delivered; only one patient interrupted R‐IE because of toxicity. Grade 4 hematological toxicity was manageable; a single case of grade 4 non‐hematological toxicity (transient hepatotoxicity) was recorded. Response was complete in six patients and partial in three (overall response rate = 41%; 95%CI: 21–61%). Seven patients were successfully referred to autologous peripheral blood stem cell collection; four responders were consolidated with high‐dose chemotherapy supported by autologous stem cell transplant. At a median follow‐up of 24 months, eight responders did not experience relapse, two of them died of neurological impairment while in remission. Six patients are alive, with a 2‐year survival after relapse of 25 ± 9%. We concluded that R‐IE is a feasible and active combination for patients with relapsed/refractory PCNSL. This regimen allows stem cell collection and successful consolidation with high‐dose chemotherapy and autologous transplant. Copyright © 2012 John Wiley & Sons, Ltd.