bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Virtual Reality Exercises in STroke Rehabilitation (EVREST): Rationale, Design, and Protocol of a Pilot Randomized Clinical Trial Assessing the Wii Gaming System
Authors: Saposnik G. , Mamdani M. , Bayley M. , Thorpe K.E. , Hall J. , Cohen L.G. , Teasell R.
Published: January 2010

Background

Evidence suggests that increasing intensity of rehabilitation results in better motor recovery. Limited evidence is available on the effectiveness of an interactive virtual reality gaming system for stroke rehabilitation. EVREST was designed to evaluate feasibility, safety and efficacy of using the Nintendo Wii gaming virtual reality (VRWii) technology to improve arm recovery in stroke patients.

Methods

Pilot randomized study comparing, VRWii versus recreational therapy (RT) in patients receiving standard rehabilitation within six months of stroke with a motor deficit of ≥3 on the Chedoke-McMaster Scale (arm). In this study we expect to randomize 20 patients. All participants (age 18–85) will receive customary rehabilitative treatment consistent of a standardized protocol (eight sessions, 60 min each, over a two-week period).

Outcome measures

The primary feasibility outcome is the total time receiving the intervention. The primary safety outcome is the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, will be measured by the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at the four-week follow-up visit. From November, 2008 to September, 2009 21 patients were randomized to VRWii or RT. Mean age, 61 (range 41–83) years. Mean time from stroke onset 25 (range 10–56) days.

Conclusions

EVREST is the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation. The results of this study will serve as the basis for a larger multicentre trial. ClinicalTrials.gov registration# NTC692523
The strong relationship between bipolar and substance‐use disorder
Authors: Swann Alan C.
Published: January 2010

Bipolar disorder and substance‐use disorders commonly occur in the same individual. In fact, bipolar disorder has a higher prevalence of substance‐use disorders than any other psychiatric illness. Individuals with both disorders have a more severe course of bipolar disorder, including earlier onset, more frequent episodes, and more complications, including anxiety‐ and stress‐related disorders, aggressive behavior, legal problems, and suicide. Bipolar and substance‐use disorders share common mechanisms, including impulsivity, poor modulation of motivation and responses to rewarding stimuli, and susceptibility to behavioral sensitization. Studies of potential treatments for bipolar substance‐use disorder have paid scant attention to the combined disorders. The most promising treatment strategies are those that address their shared mechanisms.
Psychological morbidity in catheterized prostate‐enlarged men in a Nigerian hospital
Authors: Ilesanmi Roslyn , Adejumo Prisca
Published: January 2010

This paper describes a cross‐sectional study investigating the level of psychological morbidity occasioned by long‐term indwelling urethral catheters among men with a clinical diagnosis of an enlarged prostate gland. A survey of 100 purposely selected men who had experienced catheterization for a minimum of 2 weeks was conducted. The tool used was the short version of the general health questionnaire (GHQ‐12), which measures psychological morbidity in individuals. These men were attending the urology clinic at the University College Hospital, Ibadan, Nigeria. The length of time participants had a catheter in situ was correlated with respondents' score on the GHQ‐12. Results supported the hypothesis that lengthy periods of catheterization are associated with depressive symptoms, particularly in the early period of catheterization (0–9 months). Thirty‐two percent of the sample scored above the threshold value of 5 on the GHQ‐12, denoting psychological morbidity. Findings also suggested that men in the early stage of catheterization are high‐yield targets for psychological intervention; therefore, nurses must be sensitive to the emotional impact of catheterization and consider the mental health of individuals within the holistic framework. There is the need for emphasis on individualized assessment of urological patients for appropriate interventions and the provision of quality nursing care.
GnRH blockers: a changing paradigm in the management of prostate cancer
Authors: Drudge‐Coates Lawrence
Published: January 2010

For more than 60 years, androgen deprivation therapy, first with orchidectomy and more recently with gonadotrophin‐releasing hormone (GnRH) agonists, has been a key treatment approach in the management of advanced prostate cancer. In spite of showing comparable survival benefits, these two treatments are associated with both physical and psychological issues, with notable effects on patient quality of life.

The development of GnRH blockers provides a new class of hormonal agent with a different, direct mode of action. Degarelix, a newly approved GnRH blocker, has displayed a fast, profound and sustained suppression of testosterone and prostate‐specific antigen levels without subsequent tumour flare effects. This paper considers the current evidence for this new treatment approach and how this may impact on current urology nursing practice.
Cryoablation for prostate cancer: an overview about background, procedure and nurses' responsibilities
Authors: Hieronymi Susanne , Witzsch Ulrich
Published: January 2010

Cryoablation was introduced in clinical practice for the treatment of skin lesions more than 100 years ago. Treatment to other areas of the body followed including the liver, lungs, bones, corneas and nerves, with applications extended to use in analgesia. The potential of using cryoablation for treatment of the prostate has been recognized as a therapeutic option for more than half a century. However, early results were unsatisfactory due to poor oncological outcome and the high morbidity of the procedure. Cryotherapy has evolved dramatically during the last decades with an improvement in technique, resulting in a significant reduction of complication rates and improved outcome for patients.

Although it is regarded as a minimally invasive therapy, there are several nursing aspects that have to be observed pre‐ intra‐ and postoperatively which are essential to ensure that the patient's recovery is effected and that all benefits of a minimally invasive therapy are achieved.
Determination of Polyphenols, Flavonoids, and Antioxidant Capacity in Colored Chickpea (Cicer arietinum L.)
Authors: Segev Aharon , Badani Hana , Kapulnik Yoram , Shomer Ilan , Oren‐Shamir Michal , Galili Shmuel
Published: January 2010

ABSTRACT:  Dry legumes are staple and potentially functional food, being a good source of polyphenols, flavonoids, and antioxidant activity. The objective of this study was to determine the total polyphenol content (TPC), total flavonoid content (TFC), and their relation with antioxidant capacity in 17 chickpea lines having colored seed coats (black, red, brown, green, rubiginous, gray, yellow, cream, or beige). The seed coat usually contains more than 95% of these compounds. In this study, both TPC and TFC varied significantly among different lines and were highly correlated to antioxidant activity. Colored seeds contained up to 13‐, 11‐, and 31‐fold more TPC, TFC, and antioxidant activity, respectively, than cream‐ and beige‐color seeds. Thus, colored chickpea could be a potentially functional food in addition to its traditional role of providing dietary proteins and dietary fibers.
Thermal Behavior of Potato Starch and Water‐Vaporization Behavior of Its Paste Controlled with Amino Acid and Peptide‐Rich Food Materials
Authors: Sakauchi Satoshi , Hattori Makoto , Yoshida Tadashi , Yagishita Takahiro , Ito Koichi , Akemitsu Shin‐ichi , Takahashi Koji
Published: January 2010

ABSTRACT:  The particular effect of 4 kinds of amino acid and peptide‐rich food material (APRM) containing different charged amino acid contents on the gelatinization and retrogradation behavior of potato starch granules and on the water‐vaporization behavior was analyzed by differential scanning calorimetry, rapid viscoanalysis, x‐ray diffractometry, thermal gravimetry‐differential thermal analysis, and pulsed NMR. APRM with a high‐charged amino acid content produced unique gelatinization and retrogradation behavior in terms of an elevated gelatinization temperature, reduced viscosity, higher setback, and lower retrograded starch melting enthalpy. The recovered x‐ray diffraction intensity decreased with increasing charged amino acid content. APRM with high‐charged amino acid content could provide an improved paste having easy vaporization of external water in the swollen starch granules due to the reduced swelling.
New Automated Microwave Heating Process for Cooking and Pasteurization of Microwaveable Foods Containing Raw Meats
Authors: Huang Lihan , Sites Joseph
Published: January 2010

ABSTRACT:  A new microwave heating process was developed for cooking microwaveable foods containing raw meats. A commercially available inverter‐based microwave oven was modified for pasteurization of mechanically tenderized beef, inoculated with Escherichia coli O157:H7 (approximately 5 log10 CFU/g) and packaged in a 12‐oz CPET tray containing 150‐mL de‐ionized water. The new microwave heating system was equipped with an infrared sensor and a proportional feedback mechanism to allow temperature controlled microwave heating. A 2‐stage heating strategy was adopted to cook the product. In the primary heating stage, the sample surface temperature was increased to an initial temperature set‐point (ITSP, 65, 70, 75, or 80 °C). In the secondary heating stage, the heating was continued with a small fraction of microwave power. The effect of ITSP, hold time (0 to 3 min), and sample elevation (0, 0.03, and 0.07 m above turntable) on inactivation of E. coli O157:H7 and background microflora was evaluated. It was observed that only a small number (approximately 1.3 logs) of E. coli O157:H7 and background microflora were inactivated in the primary heating stage. The elevation 0.07 m, which was in the proximity of the geometric center of the metal cavity, was more effective in inactivating both E. coli O157:H7 and background microflora. Substantially more bacteria were inactivated in the secondary heating stage. Complete inactivation of E. coli and background microflora was observed with heating at temperatures above 70 °C for more than 1 min. This study demonstrated a new approach for ensuring the safety of microwaveable products containing raw meats.
Machine learning classifiers for glaucoma diagnosis based on classification of retinal nerve fibre layer thickness parameters measured by Stratus OCT
Authors: Bizios Dimitrios , Heijl Anders , Hougaard Jesper Leth , Bengtsson Boel
Published: January 2010

Purpose:  To compare the performance of two machine learning classifiers (MLCs), artificial neural networks (ANNs) and support vector machines (SVMs), with input based on retinal nerve fibre layer thickness (RNFLT) measurements by optical coherence tomography (OCT), on the diagnosis of glaucoma, and to assess the effects of different input parameters.

Methods:  We analysed Stratus OCT data from 90 healthy persons and 62 glaucoma patients. Performance of MLCs was compared using conventional OCT RNFLT parameters plus novel parameters such as minimum RNFLT values, 10th and 90th percentiles of measured RNFLT, and transformations of A‐scan measurements. For each input parameter and MLC, the area under the receiver operating characteristic curve (AROC) was calculated.

Results:  There were no statistically significant differences between ANNs and SVMs. The best AROCs for both ANN (0.982, 95%CI: 0.966–0.999) and SVM (0.989, 95% CI: 0.979–1.0) were based on input of transformed A‐scan measurements. Our SVM trained on this input performed better than ANNs or SVMs trained on any of the single RNFLT parameters (p ≤ 0.038). The performance of ANNs and SVMs trained on minimum thickness values and the 10th and 90th percentiles were at least as good as ANNs and SVMs with input based on the conventional RNFLT parameters.

Conclusion:  No differences between ANN and SVM were observed in this study. Both MLCs performed very well, with similar diagnostic performance. Input parameters have a larger impact on diagnostic performance than the type of machine classifier. Our results suggest that parameters based on transformed A‐scan thickness measurements of the RNFL processed by machine classifiers can improve OCT‐based glaucoma diagnosis.
Switching from Oral Cholinesterase Inhibitors to the Rivastigmine Transdermal Patch
Authors: Sadowsky C. , Perez J.A. Davila , Bouchard R.W. , Goodman I. , Tekin S.
Published: January 2010

Oral cholinesterase inhibitors (ChEIs) are associated with side effects such as nausea and vomiting. The use of transdermal patches for ChEI delivery may help to minimize these problems. The objective of this review was to consider available data from patients switching from oral ChEIs to transdermal rivastigmine treatment, and to suggest practical guidelines for patients wishing to do this. Literature database and reference list searches were performed to identify suitable publications. Data from two clinical trials and a series of open observational studies, in which patients were switched to the rivastigmine patch from oral rivastigmine, donepezil tablets, or galantamine, were evaluated. Adverse events were tabulated. In the studies reported here, nausea was reported in up to 3.2% and vomiting in up to 1.9% of patients switching to the rivastigmine patch from oral rivastigmine. Similar rates (up to 3.8% of patients for nausea and 0.8% of patients for vomiting) were reported when switching to the rivastigmine patch from donepezil tablets, and no nausea or vomiting was reported in a case study of patients switching to the rivastigmine patch from galantamine tablets. Switching regimes used in clinical trials appeared well tolerated. Data support recommendations for patients on high rivastigmine capsule doses to switch directly to the 9.5 mg/24 h rivastigmine patch, while those on lower oral rivastigmine doses should start on the 4.6 mg/24 h patch for 4 weeks before increasing to the 9.5 mg/24 h patch. This latter regimen is recommended for patients on other oral cholinesterase inhibitors if switching is medically indicated or requested by the patient or the caregiver.
Effect of process related and haze defects on 193nm immersion lithography
Authors: Tay C. J. , Quan C. , Ling M. L. , Lin Q. , Chua G. S.
Published: January 2010

In this article, the effect of a defective mask on 193nm immersion lithography with a 6% attenuated phase-shifting mask is investigated. Two types of defect are studied: process related defect and haze defect. Several factors including defect location, size, transmission, phase, and illumination settings are considered. Exposure using a standard 45nm SRAM cell shows that the printability of a defect on a mask depends on the pattern density and defect size and it is also shown that the impact of a defect on a polysilicon gate layer is worse than that on an active layer. A defect that is adjacent to a main feature causes more critical dimension (CD) variation than that between two main features. Simulation using a through pitch line and space pattern is used to investigate the impact of a haze defect. A change in transmission results in an increase in the CD variation in the main feature but not the critical defect size. However, a larger phase difference between the defect and background would increase the CD variation and reduces the critical defect size. Illumination with a low partial coherence setting increases the CD variation caused by defects.
Advanced in situ pre-Ni silicide (Siconi) cleaning at 65nm to resolve defects in NiSix modules
Authors: Yang Ruipeng , Su Na , Bonfanti Paolo , Nie Jiaxiang , Ning Jay , Li Tomi T.
Published: January 2010

The existing Ar plasma sputter cleaning and dilute HF dip wet cleaning techniques have drawbacks, including critical dimension change, plasma damage, poor selectivity to oxides, vacuum breakage (causing oxide formation), and queue-time control. Siconi cleaning, a newly developed cleaning process for pre-Ni silicide cleaning at 65nm, enables superior cleaning performance, including (1) selective removal of native oxide to minimize loss of Si and Ni, (2) elimination of spikes and reduction of pipe defects at the NiSi∕Si interface, and (3) elimination of the queue-time dependency for improved productivity and simplification of fabrication. In this study, the chemical mechanism, hardware configuration, and Siconi integration results are described. The formation mechanisms for both spike and pipe defects are discussed, and practical solutions to these problems are addressed in detail. A significant reduction in junction leakage current, by three orders of magnitude, was observed. In addition, the pipe defect at the wafer edge is described and discussed.
Kepler Planet-Detection Mission: Introduction and First Results
Authors: Borucki William J. , Koch David , Basri Gibor , Batalha Natalie , Brown Timothy , Caldwell Douglas , Caldwell John , Christensen-Dalsgaard Jørgen , Cochran William D. , DeVore Edna , Dunham Edward W. , Dupree Andrea K. , Gautier Thomas N. , Geary John C. , Gilliland Ronald , Gould Alan , Howell Steve B. , Jenkins Jon M. , Kondo Yoji , Latham David W. , Marcy Geoffrey W. , Meibom Søren , Kjeldsen Hans , Lissauer Jack J. , Monet David G. , Morrison David , Sasselov Dimitar , Tarter Jill , Boss Alan , Brownlee Don , Owen Toby , Buzasi Derek , Charbonneau David , Doyle Laurance , Fortney Jonathan , Ford Eric B. , Holman Matthew J. , Seager Sara , Steffen Jason H. , Welsh William F. , Rowe Jason , Anderson Howard , Buchhave Lars , Ciardi David , Walkowicz Lucianne , Sherry William , Horch Elliott , Isaacson Howard , Everett Mark E. , Fischer Debra , Torres Guillermo , Johnson John Asher , Endl Michael , MacQueen Phillip , Bryson Stephen T. , Dotson Jessie , Haas Michael , Kolodziejczak Jeffrey , Van Cleve Jeffrey , Chandrasekaran Hema , Twicken Joseph D. , Quintana Elisa V. , Clarke Bruce D. , Allen Christopher , Li Jie , Wu Haley , Tenenbaum Peter , Verner Ekaterina , Bruhweiler Frederick , Barnes Jason , Prsa Andrej
Published: January 2010

Detecting Distant Planets

More than 400 planets have been detected outside the solar system, most of which have masses similar to that of the gas giant planet, Jupiter.

Borucki
et al.

(p.
977
, published online 7 January) summarize the planetary findings derived from the first six weeks of observations with the Kepler mission whose objective is to search for and determine the frequency of Earth-like planets in the habitable zones of other stars. The results include the detection of five new exoplanets, which confirm the existence of planets with densities substantially lower than those predicted for gas giant planets.
Genetic Aspects of Pancreatitis
Authors: Whitcomb David C.
Published: January 2010

Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene × gene and gene × environmental interactions.
HIV-1 Vaccine Development After STEP
Authors: Barouch Dan H. , Korber Bette
Published: January 2010

Despite more than 25 years of concerted worldwide research, the development of a safe and effective HIV-1 vaccine remains elusive. Prototype antibody-based and T cell–based HIV-1 vaccines have failed to show efficacy in clinical trials to date. Next-generation HIV-1 vaccine candidates are in various stages of preclinical and clinical development, but key scientific obstacles pose major challenges for the field. Critical hurdles include the enormous global diversity of the virus and the challenges associated with generating broadly reactive neutralizing antibody and cellular immune responses. We review the current state of the HIV-1 vaccine field and outline strategies that are being explored to overcome these roadblocks.
Diagnosis and Treatment of Neuropsychiatric Disorders
Authors: Taber Katherine H. , Hurley Robin A. , Yudofsky Stuart C.
Published: January 2010

Neuropsychiatry is the subspecialty of psychiatry that deals with disorders at the intersection of neurology and psychiatry. Neuropsychiatric disorders are complex and incompletely understood. Neuroscience research is beginning to elucidate the biological underpinnings of many of these disorders. These advances have the potential to improve diagnosis, inform treatment selection, and facilitate development of new and better interventions.
Medicare Part D: Ongoing Challenges for Doctors and Patients
Authors: Jacobson Gretchen , Anderson Gerard
Published: January 2010

The Medicare Modernization Act was intended to improve access to prescription drugs for millions of seniors, by providing a range of benefit packages with different prices and different formularies for beneficiaries to choose from. The major challenge for physicians has been to recognize when a Medicare beneficiary has coverage versus when that patient is in the “doughnut hole” where Medicare beneficiaries do not have coverage and therefore have to pay the full cost of the drugs out-of-pocket. A second challenge is that different Medicare beneficiaries are enrolled in different drug plans, and drugs that are covered in some plans are not covered in other plans.
Hepatocellular Carcinoma: Novel Molecular Approaches for Diagnosis, Prognosis, and Therapy
Authors: Villanueva Augusto , Minguez Beatriz , Forner Alejandro , Reig Maria , Llovet Josep M.
Published: January 2010

The genomic era is changing the understanding of cancer, although translation of the vast amount of data available into decision-making algorithms is far from reality. Molecular profiling of hepatocellular carcinoma (HCC), the most common cause of death among cirrhotic patients and a fast-growing malignancy in Western countries, is enabling the advancement of novel approaches to disease diagnosis and management. Most HCCs arise on a cirrhotic liver, and predictably, an accurate genomic characterization will allow the identification of procarcinogenic signals amenable to selective targeting by chemopreventive strategies. Molecular diagnosis is currently feasible for small tumors, but it has not yet been formalized by scientific guidelines. Molecular treatment is a reality: Sorafenib confers unprecedented survival benefits in patients at advanced stages. Genomic information from tumor and nontumoral tissue will aid prognosis prediction and facilitate the identification of oncogene addiction loops, providing the opportunity for more personalized medicine.
Biological Mechanisms Linking Obesity and Cancer Risk: New Perspectives
Authors: Roberts Darren L. , Dive Caroline , Renehan Andrew G.
Published: January 2010

Body mass index, as an approximation of body adiposity, is associated with increased risk of several common and less common malignancies in a sex- and site-specific manner. These findings implicate sex- and cancer site–specific biological mechanisms underpinning these associations, and it is unlikely that there is a “one system fits all” mechanism. Three main candidate systems have been proposed—insulin and the insulin-like growth factor–I axis, sex steroids, and adipokines—but there are shortfalls to these hypotheses. In this review, three novel candidate mechanisms are proposed: obesity-induced hypoxia, shared genetic susceptibility, and migrating adipose stromal cells. While public health policies aimed at curbing the underlying causes of the obesity epidemic are being implemented, there is a parallel need to better understand the biological processes linking obesity and cancer as a prerequisite to the development of new approaches to prevention and treatment.
Mechanisms of Cell Protection by Heme Oxygenase-1
Authors: Gozzelino Raffaella , Jeney Viktoria , Soares Miguel P.
Published: January 2010

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism underlying this cytoprotective effect relies on the ability of HO-1 to catabolize free heme and prevent it from sensitizing cells to undergo programmed cell death. This cytoprotective effect inhibits the pathogenesis of a variety of immune-mediated inflammatory diseases.
GPCR Interacting Proteins (GIPs) in the Nervous System: Roles in Physiology and Pathologies
Authors: Bockaert Joël , Perroy Julie , Bécamel Carine , Marin Philippe , Fagni Laurent
Published: January 2010

G protein-coupled receptors (GPCRs) are key transmembrane recognition molecules for regulatory signals such as light, odors, taste hormones, and neurotransmitters. In addition to activating guanine nucleotide binding proteins (G proteins), GPCRs associate with a variety of GPCR-interacting proteins (GIPs). GIPs contain structural interacting domains that allow the formation of large functional complexes involved in G protein-dependent and -independent signaling. At the cellular level, other functions of GIPs include targeting of GPCRs to subcellular compartments and their trafficking to and from the plasma membrane. Recently, roles of GPCR-GIP interactions in central nervous system physiology and pathologies have been revealed. Here, we highlight the role of GIPs in some important neurological and psychiatric disorders, as well as their potential for the future development of therapeutic drugs.
LPA Receptors: Subtypes and Biological Actions
Authors: Choi Ji Woong , Herr Deron R. , Noguchi Kyoko , Yung Yun C. , Lee Chang-Wook , Mutoh Tetsuji , Lin Mu-En , Teo Siew T. , Park Kristine E. , Mosley Alycia N. , Chun Jerold
Published: January 2010

Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an extracellular signaling molecule by binding to and activating at least five known G protein–coupled receptors (GPCRs): LPA1–LPA5. They are encoded by distinct genes named LPAR1–LPAR5 in humans and Lpar1–Lpar5 in mice. The biological roles of LPA are diverse and include developmental, physiological, and pathophysiological effects. This diversity is mediated by broad and overlapping expression patterns and multiple downstream signaling pathways activated by cognate LPA receptors. Studies using cloned receptors and genetic knockout mice have been instrumental in uncovering the significance of this signaling system, notably involving basic cellular processes as well as multiple organ systems such as the nervous system. This has further provided valuable proof-of-concept data to support LPA receptors and LPA metabolic enzymes as targets for the treatment of medically important diseases that include neuropsychiatric disorders, neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis, and cancer.
Close Encounters of the Small Kind: Adverse Effects of Man-Made Materials Interfacing with the Nano-Cosmos of Biological Systems
Authors: Shvedova Anna A. , Kagan Valerian E. , Fadeel Bengt
Published: January 2010

Engineered nanomaterials have unique physico-chemical properties that make them promising for many technological and biomedical applications, including tissue regeneration, drug and gene delivery, and in vivo monitoring of disease processes. However, with the burgeoning capabilities to manipulate structures at the nano-scale, intentional as well as unintentional human exposures to engineered nanomaterials are set to increase. Nanotoxicology is an emerging discipline focused on understanding the properties of engineered nanomaterials and their interactions with biological systems, and may be viewed as the study of the undesirable interference between man-made nanomaterials and cellular nanostructures or nanomachines. In this review, we discuss recognition of engineered nanomaterials by the immune system, our primary defense system against foreign invasion. Moreover, as oxidative stress is believed to be one of the major deleterious consequences of exposure to nanomaterials, we explore triggering of pro- and antioxidant pathways as well as biomarkers of oxidative stress. Finally, we highlight in vivo studies of the toxicological outcomes of engineered nanomaterials, including carbon nanotubes, with an emphasis on inflammation and genotoxic responses.
Toxicological Disruption of Signaling Homeostasis: Tyrosine Phosphatases as Targets
Authors: Samet James M. , Tal Tamara L.
Published: January 2010

The protein tyrosine phosphatases (PTPs) consist of a diverse group of enzymes whose activity opposes that of the tyrosine kinases. As such, the PTPs have critical roles in maintaining signaling quiescence in resting cells and in restoring homeostasis by effecting signal termination. Interest in these enzymes has increased in recent years following the discovery that the activity of PTPs is modulated through redox mechanisms during signaling. The molecular features that enable redox regulation of PTPs during physiological signaling also render them highly susceptible to oxidative and electrophilic inactivation by a broad spectrum of structurally disparate xenobiotic compounds. The loss of PTP activity results in a profound disregulation of protein phosphotyrosine metabolism, leading to widespread and persistent activation of signaling cascades in the cell.
The RNA Polymerase I Transcription Machinery: An Emerging Target for the Treatment of Cancer
Authors: Drygin Denis , Rice William G. , Grummt Ingrid
Published: January 2010

The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that inactivate tumor suppressors, hyperactivate oncogenes, and upregulate protein kinases, all of which promote Pol I transcription and drive cell proliferation. The intimate balance between Pol I transcription and growth-factor signaling is perturbed in cancer cells, indicating that upregulation of rRNA synthesis is mandatory for all tumors. Though the emerging picture of transcriptional regulation reveals an unexpected level of complexity, we are beginning to understand the multiple links between rRNA biogenesis and cancer. In this review, we discuss experimental data and potential strategies to downregulate rRNA synthesis and induce an antiproliferative response in cancer cells.
Impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and humans
Authors: Blomme Bram , Van Steenkiste Christophe , Vanhuysse Jacques , Colle Isabelle , Callewaert Nico , Van Vlierberghe Hans
Published: January 2010

The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the impact of etiology on the alteration of N-glycosylation and whether other characteristics of liver patients could have an influence on N-glycosylation. In human liver patients, no specific alteration could be found to make a distinction according to etiological factor, although alcoholic patients had a significant higher mean value for the GlycoCirrhoTest. Undergalactosylation did not show a significantly different quantitative alteration in the cirrhotic and noncirrhotic population of all etiologies. Importantly, patients with an elevation of total bilirubin level (>2 mg/dl) had a strong increase of glycans modified with α1–6 fucose. The fucosylation index was therefore significantly higher in fibrosis/cirrhosis and hepatocellular carcinoma patients with elevated total bilirubin levels irrespective of etiology. Furthermore, in a multiple linear regression analysis, only markers for cholestasis significantly correlated with the fucosylation index. In mouse models of chronic liver disease, the fucosylation index was uniquely significantly increased in mice that were induced with a common bile duct ligation. Mice that were chronically injected with CCl4 did not show this increase. Apart from this difference, common changes characteristic to fibrosis development in mice were observed. Finally, mice induced with a partial portal vein ligation did not show biological relevant changes indicating that portal hypertension does not contribute to the alteration of N-glycosylation.
Angiotensin-(1–7) improves cardiac remodeling and inhibits growth-promoting pathways in the heart of fructose-fed rats
Authors: Giani Jorge F. , Muñoz Marina C. , Mayer Marcos A. , Veiras Luciana C. , Arranz Cristina , Taira Carlos A. , Turyn Daniel , Toblli Jorge E. , Dominici Fernando P.
Published: January 2010

The present study examined whether chronic treatment with angiotensin (ANG)-(1–7) reduces cardiac remodeling and inhibits growth-promoting signaling pathways in the heart of fructose-fed rats (FFR), an animal model of insulin resistance. Sprague-Dawley rats were fed either normal rat chow (control) or the same diet plus 10% fructose in drinking water. For the last 2 wk of a 6-wk period of the corresponding diet, control and FFR were implanted with osmotic pumps that delivered ANG-(1–7) (100 ng·kg−1·min−1). A subgroup of each group of animals (control or FFR) underwent a sham surgery. We determined heart weight, myocyte diameter, interstitial fibrosis, and perivascular collagen type III deposition as well as the phosphorylation degree of ERK1/2, JNK1/2, and p38MAPK. FFR showed a mild hypertension that was significantly reduced after ANG-(1–7) treatment. Also, FFR displayed higher ANG II circulating and local levels in the heart that remained unaltered after chronic ANG-(1–7) infusion. An increased heart-to-body weight ratio, myocyte diameter, as well as left ventricular fibrosis and perivascular collagen type III deposition were detected in the heart of FFR. Interestingly, significant improvements in these cardiac alterations were obtained after ANG-(1–7) treatment. Finally, FFR that received ANG-(1–7) chronically displayed significantly lower phosphorylation levels of ERK1/2, JNK1/2, and p38MAPK. The beneficial effects obtained by ANG-(1–7) were associated with normal values of Src-homology 2-containing protein-tyrosine phosphatase-1 (SHP-1) activity in the heart. In conclusion, chronic ANG-(1–7) treatment ameliorated cardiac hypertrophy and fibrosis and attenuated the growth-promoting pathways in the heart. These findings show an important protective role of ANG-(1–7) in the heart of insulin-resistant rats.
Effect of airway opening on production of exhaled particles
Authors: Almstrand Ann-Charlotte , Bake Björn , Ljungström Evert , Larsson Per , Bredberg Anna , Mirgorodskaya Ekaterina , Olin Anna-Carin
Published: January 2010

The technique of sampling exhaled air is attractive because it is noninvasive and so allows repeated sampling with ease and no risk for the patient. Knowledge of the biomarkers' origin is important to correctly understand and interpret the data. Endogenous particles, formed in the airways, are exhaled and reflect chemical composition of the respiratory tract lining fluid. However, the formation mechanisms and formation sites of these particles are unknown. We hypothesize that airway opening following airway closure causes production of airborne particles that are exhaled. The objective of this study was to examine production of exhaled particles following varying degrees of airway closure. Ten healthy volunteers performed three different breathing maneuvers in which the initial lung volume preceding an inspiration to total lung capacity was varied between functional residual capacity (FRC) and residual volume (RV). Exhaled particle number concentrations in the size interval 0.30–2.0 μm were recorded. Number concentrations of exhaled particles showed a 2- to 18-fold increase after exhalations to RV compared with exhalations where no airway closure was shown [8,500 (810–28,000) vs. 1,300 (330–13,000) particles/expired liter, P = 0.012]. The difference was most noticeable for the smaller size range of particles (<1 μm). There were significant correlations between particle concentrations for the different maneuvers. Our results show that airway reopening following airway closure is an important mechanism for formation of endogenous exhaled particles and that these particles originate from the terminal bronchioles.
Increasing Cycles of Intermittent Ischemia Can Effectively Maintain Liver Function during the Acute Phase of Ischemia Reperfusion Injury by Promotion of Bile Flow and Reduction in Bile Salt Toxicity
Authors: Peters J. , Nieuwenhuijs V.B. , Morphett A. , Porte R.J. , Padbury R.T.A. , Barritt G.J.
Published: January 2010

Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods:Liver function in the acute phase of ischemia reperfusion injury was assessed by measuring bile flow in rat livers. Phospholipid and bile salts in bile, liver marker enzymes in blood, and liver histology were measured. Aged livers were compared with young livers. Results: Clamping for 45 min reduced postperfusion bile flow to 13% of the initial value compared with 88 ± 5% for control livers (means ± SEM, n = 5–8), and substantially reduced the phospholipid:bile salt ratio in bile. Application of 3, 4, 5 and 6 cycles of INT (15 min) restored bile flow to 70 ± 11, 61 ± 4, 48 ± 2 and 35 ± 3% (p < 0.01) of the initial value, respectively, and restored the phospholipid:bile salt ratio. Multiple cycles of INT were less effective in aged rats. Conclusion: Several cycles of INT, through promotion of bile flow recovery and reduction in the cytotoxic actions of bile salts, may provide an effective clinical strategy for increasing clamping time in liver resections.
Learning Curve for Identification of Sentinel Lymph Node Based on a Cumulative Sum Analysis in Gastric Cancer
Authors: Lee J.H. , Ryu K.W. , Lee S.E. , Cho S.J. , Lee J.Y. , Kim C.G. , Choi I.J. , Kook M.C. , Kim M.J. , Park S.R. , Lee J.S. , Nam B.H. , Kim Y.W.
Published: January 2010

Background/Aims: Lymph node metastasis is the most important point to consider when deciding on the modality of resection in patients with early gastric cancer. This study was conducted to evaluate the learning curve for identification of sentinel lymph nodes in patients with gastric cancer. Methods: The investigators included the results from 2 prospective series of sentinel lymph node mapping. Cumulative sum (CUSUM) analysis was performed to assess the learning curves for identification of sentinel lymph nodes at CUSUM target success rates of 95%. Results: One surgeon performed 135 sentinel lymph node mappings for 2 prospective series. The success rate exceeded 90%. The learning period for gastric cancer sentinel node mapping was calculated to be 26 cases for achieving a 95% success rate. Multiple logistic regression analysis for successful detection of sentinel nodes showed that surgical experience of sentinel lymph node mapping was an independent factor for successful detection of sentinel nodes. Conclusions: This study suggests that the learning period for identification of sentinel lymph nodes in gastric cancer would be 26 cases. In clinical trials for gastric cancer with sentinel lymph node mapping, the learning curve should be considered to minimize bias due to surgical factors.
Biopsychosocial Impact of Voicing and General Coping Style in Teachers
Authors: Van Wijck-Warnaar A. , Van Opstal M.J.M.C. , Exelmans K. , Schaekers K. , Thomas G. , de Jong F.I.C.R.S.
Published: January 2010

Objective: The aim of the study was to explore the general coping style of female teachers with a relatively low voice handicap compared with teachers with a relatively high voice handicap. Patients and Methods: A cross-sectional questionnaire survey was conducted among 450 teachers using the Voice Handicap Index (VHI) and the Utrecht Coping List (UCL). A group of 400 subjects quasi-randomly selected from the general population were used as controls. Results: Teachers with a relatively high voice handicap (VHI ≧75th percentile) scored lower on the UCL subscale ‘active confrontation or dealing with the problem’ (p = 0.001) and higher on the UCL subscale ‘passive reaction pattern’ (p = 0.006), compared to teachers with a relatively low voice handicap (VHI ≤25th percentile). Among the general population, it was found that subjects with a relatively high voice handicap scored higher on the UCL subscales ‘avoidance/waiting’ (p = 0.001) and ‘passive reaction pattern’ (p < 0.001) than those with a relatively low voice handicap. From the groups with a relatively high total VHI score, the teachers scored higher on the scale ‘seeking for social support’ than the general population (p = 0.022). However, this had already been found in the total groups. The general population scored higher than the teachers on the subscale ‘avoidance/waiting’ (p = 0.027). There was no significant difference on the other subscales of the UCL. Conclusion: The coping style of the teachers with a relatively high VHI score may lead to less optimal problem solving possibilities and consequently increased vulnerability, problems and less psychosomatic well-being. Training coping strategies in the curriculum of student teachers may contribute to their response when they experience voice problems during their teaching career. With a view to self-efficacy, adequate coping strategies need to be taught to teachers.
Correlation between Acoustic Parameters and Voice Handicap Index in Dysphonic Teachers
Authors: Niebudek-Bogusz E. , Woznicka E. , Zamyslowska-Szmytke E. , Sliwinska-Kowalska M.
Published: January 2010

Objective: The aim of this study was to investigate the relationship between acoustic analysis and biopsychosocial implications of voice problems, evaluated by the Voice Handicap Index (VHI). Materials and Methods: The study comprised 120 female teachers with voice disorders, evaluated by videolaryngostroboscopy. 60.8% of this group were diagnosed as having functional dysphonia and 39.2% had dysphonia with benign vocal fold masses (nodules and polyps). The controls consisted of 30 euphonic women. The correlations between VHI and acoustic analysis were assessed in both groups using the Pearson correlation coefficient and regression analysis. Results: In teachers, the total VHI score was over 5 times as high as in controls (p < 0.001). Moreover, in teachers, significant positive correlations were found between the total VHI score and the frequency perturbation parameters and amplitude perturbation parameters when both statistical methods were used. These acoustic parameters also significantly correlated with the score on the functional and emotional subscales, but rarely with the physical subscale of the VHI. Conclusions: The study revealed a significant relationship between the objective voice measurements and the VHI. The results confirmed that VHI can be a valuable tool for assessing biopsychosocial implications of occupational dysphonia and should be incorporated in multidimensional voice evaluation.
How to Successfully Achieve Salt Restriction in Dialysis Patients? What Are the Outcomes?
Authors: Ok Ercan
Published: January 2010

Despite the fact that dietary salt restriction is the most logical measure to prevent accumulation of salt and water in patients without renal function, it is not applied in most dialysis centers. In this review, the reasons for this unlucky development are analyzed. First, it appears that many dialysis patients are slightly overhydrated, but this is often not noticed and, if so, the deleterious effects in the long run are not appreciated. These consist not only of ‘drug-resistant’ hypertension, but also dilatation of the cardiac compartments leading to preventable cardiovascular events. Second, there are practical reasons why salt restriction is neglected. It is very difficult to buy salt-poor food. Salt consumption is an addiction, which can be overcome, but time and efforts are needed to achieve that. Suggestions are made how to reach that goal. Finally, examples are given how cardiac damage (often considered irreversible) can be improved or even cured by a ‘volume control’ strategy, whose crucial part is serious salt restriction.
An Approach to Addressing Depression in Patients with Chronic Kidney Disease
Authors: Finkelstein Fredric O. , Wuerth Diane , Finkelstein Susan H.
Published: January 2010

Depressive symptoms and clinical depression are commonly noted in patients with end-stage renal disease and chronic kidney disease (not on dialysis). This association is important since depressive symptoms have been associated with both an impaired quality of life and increased morbidity and mortality. It is, therefore, important to develop strategies to screen patients with chronic kidney disease for depression and to develop strategies to treat clinical depression in this group of patients.
Novel Insights into the Pathobiology of the Vascular Access – Do They Translate into Improved Care?
Authors: Diskin Charles J.
Published: January 2010

While recent developments have allowed greater insight into the vascular pathobiology and intimal hyperplasia, very few of these advances have led to improved clinical care of hemodialysis vascular accesses. Indeed the most common procedure for the treatment of access stenosis and thrombosis is the same model for the creation and study of intimal hyperplasia. The evolution of our understanding of vascular thrombosis is reviewed with a current concept that includes a dynamic interplay of the biophysics, chemistry and biology of the blood vessel with the blood and its constituents. Implications for possible future interventions based on these novel concepts are offered, and the significance of improving our understanding of the pathobiology is emphasized.