bluuebunny/crossref_metadata_2025 huggingface dataset:
Dealing with oxidative stress and iron starvation in microorganisms: an overviewThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Benjamin Julie-Anna M. , Desnoyers Guillaume , Morissette Audrey , Salvail Hubert , Massé Eric
Published: April 2010

Iron starvation and oxidative stress are 2 hurdles that bacteria must overcome to establish an infection. Pathogenic bacteria have developed many strategies to efficiently infect a broad range of hosts, including humans. The best characterized systems make use of regulatory proteins to sense the environment and adapt accordingly. For example, iron–sulfur clusters are critical for sensing the level and redox state of intracellular iron. The regulatory small RNA (sRNA) RyhB has recently been shown to play a central role in adaptation to iron starvation, while the sRNA OxyS coordinates cellular response to oxidative stress. These regulatory sRNAs are well conserved in many bacteria and have been shown to be essential for establishing a successful infection. An overview of the different strategies used by bacteria to cope with iron starvation and oxidative stress is presented here.
Targeted deletion of NF-κB p50 diminishes the cardioprotection of histone deacetylase inhibition
Authors: Zhang L. X. , Zhao Y. , Cheng G. , Guo T. L. , Chin Y. E. , Liu P. Y. , Zhao T. C.
Published: April 2010

We have recently demonstrated that the inhibition of histone deacetylases (HDAC) protects the heart against ischemia-reperfusion (I/R) injury. The mechanism by which HDAC inhibition confers myocardial protection remains unknown. The purpose of this study is to investigate whether the disruption of NF-κB p50 would eliminate the protective effects of HDAC inhibition. Wild-type and NF-κB p50-deficient mice were treated with trichostatin A (TSA; 0.1 mg/kg ip), a potent inhibitor of HDACs. Twenty-four hours later, the hearts were perfused in Langendorff model and subjected to 30 min of ischemia and 30 min of reperfusion. Inhibition of HDACs by TSA in wild-type mice produced marked improvements in left ventricular end-diastolic pressure, left ventricular rate pressure product, and the reduction of infarct size compared with non-TSA-treated group. TSA-induced cardioprotection in wild-type animals was absent with genetic deletion of NF-κB p50 subunit. Notably, Western blot displayed a significant increase in nuclear NF-κB p50 and the immunoprecipitation demonstrated a remarkable acetylation of NF-κB p50 at lysine residues following HDAC inhibition. EMSA exhibited a subsequent increase in NF-κB DNA binding activity. Luciferase assay demonstrated an activation of NF-κB by HDAC inhibition. The pretreatment of H9c2 cardiomyoblasts with TSA (50 nmol/l) decreased cell necrosis and increased in cell viability in simulated ischemia. The resistance of H9c2 cardiomyoblasts to simulated ischemia by HDAC inhibition was eliminated by genetic knockdown of NF-κB p50 with transfection of NF-κB p50 short interfering RNA but not scrambled short interfering RNA. These results suggest that NF-κB p50 acetylation and activation play a pivotal role in HDAC inhibition-induced cardioprotection.
MBMS—IP Multicast/Broadcast in 3G Networks
Authors: Hartung Frank , Horn Uwe , Huschke Jörg , Kampmann Markus , Lohmar Thorsten
Published: April 2010

In this article, the Multimedia Broadcast and Multicast Service (MBMS) as standardized in 3GPP is presented. With MBMS, multicast and broadcast capabilities are introduced into cellular networks. After an introduction into MBMS technology, MBMS radio bearer realizations are presented. Different MBMS bearer services like broadcast mode, enhanced broadcast mode and multicast mode are discussed. Streaming and download services over MBMS are presented and supported media codecs are listed. Service layer components as defined in Open Mobile Alliance (OMA) are introduced. For a Mobile TV use case capacity improvements achieved by MBMS are shown. Finally, evolution of MBMS as part of 3GPP standardization is presented.
Comparison of Fuzzy Clustering Methods and Their Applications to Geophysics Data
Authors: Miller David J. , Nelson Carl A. , Cannon Molly Boeka , Cannon Kenneth P.
Published: April 2010

Fuzzy clustering algorithms are helpful when there exists a dataset with subgroupings of points having indistinct boundaries and overlap between the clusters. Traditional methods have been extensively studied and used on real-world data, but require users to have some knowledge of the outcome a priori in order to determine how many clusters to look for. Additionally, iterative algorithms choose the optimal number of clusters based on one of several performance measures. In this study, the authors compare the performance of three algorithms (fuzzy c-means, Gustafson-Kessel, and an iterative version of Gustafson-Kessel) when clustering a traditional data set as well as real-world geophysics data that were collected from an archaeological site in Wyoming. Areas of interest in the were identified using a crisp cutoff value as well as a fuzzyα-cut to determine which provided better elimination of noise and non-relevant points. Results indicate that theα-cut method eliminates more noise than the crisp cutoff values and that the iterative version of the fuzzy clustering algorithm is able to select an optimum number of subclusters within a point set (in both the traditional and real-world data), leading to proper indication of regions of interest for further expert analysis
An Objective Evaluation Method for Image Restoration
Authors: Lakshmi A. , Rakshit Subrata
Published: April 2010

Accurate image restoration is of paramount importance for low‐level vision, computer vision, and various other fields. Numerous complex restoration algorithms have been stated in the literature. Performance of these restoration algorithms differs with the nature of the image and distortion. These algorithms are evaluated either qualitatively or quantitatively by comparing the restored image with the original image. The practical drawback of this quantitative comparison is the requirement for the original image. In this paper, we propose a measure, with theoretical grounding, to objectively evaluate the restoration algorithms with no knowledge about the original image. This measure analyses the deblurring as well as the denoising nature of the restoration method. The main utility of this measure will be in designing automatic restoration systems. Effectiveness of this measure is substantiated with experimental results.
Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis
Authors: Uranga Romina M. , Keller Jeffrey N.
Published: April 2010

Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use) to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.
Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma
Authors: Rahman Ruman , Smith Stuart , Rahman Cheryl , Grundy Richard
Published: April 2010

Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs) produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.
A Continuum Model for Water Transport in the Ionomer-Phase of Catalyst Coated Membranes for PEMFCs
Authors: Gurau Vladimir , Mann J. Adin
Published: April 2010

We study the problem of water transport in the ionomer-phase of catalyst coated membranes (CCMs) for proton exchange membrane fuel cells (PEMFCs), where microscopic-scale phenomena at the distributed interfaces between structural components control the water management. Existing models for water transport in CCMs describe the transport in systems which consist exclusively of an ionomer-phase. Interfacial water fluxes across distributed interfaces representing various mechanisms of water transfer between ionomer and catalyst layer pores are not captured properly in these models. Here we develop a continuum model for water transport in CCMs using the method of volume averaging. Water is exchanged between ionomer and the catalyst layer pores by electro-osmotic discharge (EOD) through the three-phase boundary (TPB) regions and by sorption and desorption across the ionomer-pore interfaces. While the former mechanism does not affect directly the water content in the ionomer-phase, it represents an effective mechanism for water transfer during fuel cell operation and controls directly the water saturation in the catalyst pores.
Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer
Authors: Greiner Jochen , Küfer Rainer , Reske Sven N. , Martin Volker , Döhner Hartmut , Ringhoffer Mark
Published: April 2010

The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11) C-Choline positron emission tomography/computerized tomography (PET/CT). After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 . The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.
Shannon Wavelets for the Solution of Integrodifferential Equations
Authors: Cattani Carlo
Published: April 2010

Shannon wavelets are used to define a method for the solution of integrodifferential equations.
This method is based on (1) the Galerking method, (2) the Shannon wavelet representation, (3) the decorrelation
of the generalized Shannon sampling theorem, and (4) the definition of connection coefficients.
The Shannon sampling theorem is considered in a more general approach suitable for analysing
functions ranging in multifrequency bands. This generalization coincides with the Shannon wavelet
reconstruction of L2(ℝ) functions. Shannon wavelets are C∞‐functions and their any order derivatives can be analytically defined by some kind of a finite hypergeometric series (connection coefficients).
Novel Nanocomposite Optical Plastics: Dispersion of Titanium in Polyacrylates
Authors: Suri Gunjan , Tyagi Mukti , Seshadri Geetha , Verma Gurcharan Lal , Khandal Rakesh Kumar
Published: April 2010

Polyacrylates have become the preferred materials for optical applications replacing the conventionally used glass due to their superior optical clarity. The major disadvantage with polyacrylates is their low (1.40–1.50) refractive index besides their poor impact resistance. The improvements in refractive index as well as mechanical properties can be achieved by way of incorporation of metals or metal compounds in the matrix. A novel methodology for the incorporation of high refractive index metals into low refractive index polymeric materials to improve the refractive index and impact resistance of the latter has been developed. With the in-situ formation of nanoparticles ofTiO2, the refractive index of polyacrylates improved from 1.45 to 1.53 and the Abbe number increased from 40 to 57. One of the interesting dimension of this study pertains to the possibility of tailor-making of the two key optical properties of materials by way of varying the amount ofTiO2being formed in-situ. Thermal stability and impact resistance of nano dispersed (4.3% by wt. of Ti) polyacrylates are found to be better than the neat polyacrylates. Moreover,TiO2-containing polyacrylate is of light weight. TEM, SEM, and IR analysis confirms the in-situ formation of nanoparticles ofTiO2. Gamma irradiation has been used as an eco-friendly technique for polymerization. The developed compositions can be cast polymerized into clear and bubble free material for optical applications.
Microscopic Description of 2D Topological Phases, Duality, and 3D State Sums
Authors: Kádár Zoltán , Marzuoli Annalisa , Rasetti Mario
Published: April 2010

Doubled topological phases introduced by Kitaev, Levin, and Wen supported
on two‐dimensional lattices are Hamiltonian versions of three‐dimensional
topological quantum field theories described by the Turaev‐Viro state
sum models. We introduce the latter with an emphasis on obtaining them
from theories in the continuum. Equivalence of the previous models in the
ground state is shown in case of the honeycomb lattice and the gauge group
being a finite group by means of the well‐known duality transformation between
the group algebra and the spin network basis of lattice gauge theory.
An analysis of the ribbon operators describing excitations in both types of
models and the three‐dimensional geometrical interpretation are given.
Relapsed Mantle Cell Lymphoma Presenting as “Sister Mary Joseph Nodule”
Authors: Vaughn Jennifer E. , Gopal Ajay K.
Published: April 2010

The finding of umbilical metastasis has historically been called a “Sister Mary Joseph Nodule”. A few case reports of lymphoma presenting in this manner have been documented. We report a case of relapsed mantle cell lymphoma (MCL) presenting as a Sister Mary Joseph's nodule. Although the few reports of lymphoma exhibiting umbilical metastasis suggest that patients may still expect a reasonable response to chemotherapy, this patient experienced multiple relapses, despite aggressive chemotherapy regimens. This clinical course is characteristic of the mantle cell form of non-hodgkin's lymphoma and illustrates a need to seek out more effective therapies.
Chaotic Time Series Analysis
Authors: Liu Zonghua
Published: April 2010

Chaotic dynamical systems are ubiquitous in nature and most of them does not have an explicit dynamical equation and can be only understood through the available time series. We here briefly review the basic concepts of time series and its analytic tools, such as dimension, Lyapunov exponent, Hilbert transform, and attractor reconstruction. Then we discuss its applications in a few fields such as the construction of differential equations, identification of synchronization and coupling direction, coherence resonance,
and traffic data analysis in Internet.
Implementing Adams Methods with Preassigned Stepsize Ratios
Authors: López David J. , Romay José G.
Published: April 2010

Runge‐Kutta and Adams methods are the most popular codes to solve numerically nonstiff ODEs. The Adams methods are useful to reduce the number of function calls, but they usually require more CPU time than the Runge‐Kutta methods. In this work we develop a numerical study of a variable step length Adams implementation, which can only take preassigned step‐size ratios. Our aim is the reduction of the CPU time of the code by means of the precalculation of some coefficients. We present several numerical tests that show the behaviour of the proposed implementation.
Model for a Torsional-Mode Ultrasonic Transducer for an Acousto-Optic In-Fiber Isolator
Authors: Moore Gerald T.
Published: April 2010

Torsional ultrasound modes can couple the optical polarization states in a birefringent fiber. Polarization coupling produced by interaction with a higher-order torsional mode slightly above its cutoff may provide a route to producing an in-fiber isolator suitable for use in narrow-band high-power fiber amplifiers. This paper describes a model of a transducer generating
torsional modes in a cylindrical fiber. This model predicts that almost all of the power applied to the transducer is radiated into the desired mode. The paper also discusses effects produced by acoustic absorption and the dependence of the acoustic velocity on temperature.
MexicanTrypanosoma cruzi(TCI) Strains with Different Degrees of Virulence Induce Diverse Humoral and Cellular Immune Responses in a Murine Experimental Infection Model
Authors: Espinoza B. , Rico T. , Sosa S. , Oaxaca E. , Vizcaino-Castillo A. , Caballero M. L. , Martínez I.
Published: April 2010

It is has been shown that the majority ofT. cruzistrains isolated from Mexico belong to theT. cruziI (TCI). The immune response produced in response to MexicanT. cruziI strains has not been well characterized. In this study, two MexicanT. cruziI strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro)(Qro) strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa) strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNγ, RANTES, MIG, MIP-1β, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice.
Effect of Magnesium Hydride on the Corrosion Behavior of Pure Magnesium in 0.1 M NaCl Solution
Authors: Xu Shanna , Dong Junhua , Ke Wei
Published: April 2010

The effect of magnesium hydride on the corrosion behavior of pure magnesium in 0.1 M NaCl solution was investigated using the gas collection method, potentiostatic current decay test, and in situ Raman spectrum. The formation of magnesium hydride (MgH2,Mg2H4) was observed at the cathodic region. Applying anodic potential leads to decomposition of magnesium hydride. Magnesium hydride plays an important role on the negative difference effect (NDE) in both the cathodic and anodic regions.
Pattern Recognition via the Toll-Like Receptor System in the Human Female Genital Tract
Authors: Nasu Kaei , Narahara Hisashi
Published: April 2010

The mucosal surface of the female genital tract is a complex biosystem, which provides a barrier against the outside world and participates in both innate and acquired immune defense systems. This mucosal compartment has adapted to a dynamic, non-sterile environment challenged by a variety of antigenic/inflammatory stimuli associated with sexual intercourse and endogenous vaginal microbiota. Rapid innate immune defenses against microbial infection usually involve the recognition of invading pathogens by specific pattern-recognition receptors recently attributed to the family of Toll-like receptors (TLRs). TLRs recognize conserved pathogen-associated molecular patterns (PAMPs) synthesized by microorganisms including bacteria, fungi, parasites, and viruses as well as endogenous ligands associated with cell damage. Members of the TLR family, which includes 10 human TLRs identified to date, recognize distinct PAMPs produced by various bacterial, fungal, and viral pathogens. The available literature regarding the innate immune system of the female genital tract during human reproductive processes was reviewed in order to identify studies specifically related to the expression and function of TLRs under normal as well as pathological conditions. Increased understanding of these molecules may provide insight into site-specific immunoregulatory mechanisms in the female reproductive tract.
Inflammatory Myoglandular Polyps: A Case Series of Four Patients and Review of the Literature
Authors: Hirasaki Shoji , Kanzaki Hiromitsu , Matsubara Minoru , Suzuki Seiyuu
Published: April 2010

Background. Inflammatory myoglandular polyp (IMGP) is a nonneoplastic colorectal polyp. Only a small number of cases have been reported, and the pathogenesis remains unclear.Methods. We analyzed colonoscopy and histologic findings in 4 patients with IMGP. Histologic confirmation of the inflammatory granulation tissue in the lamina propria, proliferation of smooth muscle, and hyperplastic glands with variable cystic changes formed the criteria for the selection of patients.Results. We treated four cases of IMGP and reviewed the literature on this disease. Three cases were located in the sigmoid colon or descending colon. All 4 polyps were identified as red, pedunculated lesions. All 4 cases had no symptoms. In two cases, endoscopic findings of polyps were necessary to be differentiated from juvenile polyps.Conclusions. Pedunculated lesions are the main pattern of IMGP. An analysis of endoscopic and histologic features in IMGP of the colorectum revealed that colonic IMGPs resembled juvenile polyps. On colonoscopy, IMGP should generally be taken into consideration as a differential diagnosis of peduncular polyp.
Microphthalmia-Associated Transcription Factor Controls the DNA Damage Response and a Lineage-Specific Senescence Program in Melanomas
Authors: Giuliano Sandy , Cheli Yann , Ohanna Mickaël , Bonet Caroline , Beuret Laurent , Bille Karine , Loubat Agnès , Hofman Véronique , Hofman Paul , Ponzio Gilles , Bahadoran Philippe , Ballotti Robert , Bertolotto Corine
Published: April 2010

Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated transcription factor (MITF), in which its M transcript is specifically expressed in melanocyte cells, plays a critical role in melanoma proliferation, and its specific inhibition is associated with G0-G1 growth arrest. Interestingly, decreased MITF expression has been described in senescent melanocytes, and we have observed an inhibition of MITF expression in melanoma cells exposed to chemotherapeutic drugs that induce their senescence. All these observations thereby question the role of MITF in controlling senescence in melanoma cells. Here, we report that long-term depletion of MITF in melanoma cells triggers a senescence program characterized by typical morphologic and biochemical changes associated with a sustained growth arrest. Further, we show that MITF-silenced cells engage a DNA damage response (DDR) signaling pathway, leading to p53 upregulation, which is critically required for senescence entry. This study uncovers the existence of a lineage-restricted DDR/p53 signaling pathway that is inhibited by MITF to prevent senescence and favor melanoma cell proliferation. Cancer Res; 70(9); 3813–22. ©2010 AACR.
The Deubiquitinating Enzyme USP17 Is Highly Expressed in Tumor Biopsies, Is Cell Cycle Regulated, and Is Required for G1-S Progression
Authors: McFarlane Cheryl , Kelvin Alyson A. , de la Vega Michelle , Govender Ureshnie , Scott Christopher J. , Burrows James F. , Johnston James A.
Published: April 2010

Ubiquitination is a reversible posttranslational modification that is essential for cell cycle control, and it is becoming increasingly clear that the removal of ubiquitin from proteins by deubiquitinating enzymes (DUB) is equally important. In this study, we have identified high levels of the DUB USP17 in several tumor-derived cell lines and primary lung, colon, esophagus, and cervix tumor biopsies. We also report that USP17 is tightly regulated during the cell cycle in all the cells examined, being abundantly evident in G1 and absent in S phase. Moreover, regulated USP17 expression was necessary for cell cycle progression because its depletion significantly impaired G1-S transition and blocked cell proliferation. Previously, we have shown that USP17 regulates the intracellular translocation and activation of the GTPase Ras by controlling Ras-converting enzyme 1 (RCE1) activation. RCE1 also regulates the processing of other proteins with a CAAX motif, including Rho family GTPases. We now show that USP17 depletion blocks Ras and RhoA localization and activation. Moreover, our results confirm that USP17-depleted cells have constitutively elevated levels of the cyclin-dependent kinase inhibitors p21cip1 and p27kip1, known downstream targets of Ras and RhoA signaling. These observations clearly show that USP17 is tightly regulated during cell division and that its expression is necessary to coordinate cell cycle progression, and thus, it may be considered a promising novel cancer therapeutic target. Cancer Res; 70(8); 3329–39. ©2010 AACR.
Lipoprotein (a), Birth Weight and Neonatal Stroke
Authors: Renaud Cyrille , Bonneau Christine , Presles Emilie , Laporte Silvy , Depeyre Arnaud , Varlet Marie-Noëlle , Chabrier Stéphane ,   for the AVCnn group
Published: April 2010

Background: Elevated lipoprotein (Lp) (a) is the most common genetically determined risk factor found in babies with perinatal ischemic stroke. The influence of maternal Lp(a) has not been studied extensively to date. Objectives: To investigate the role of Lp(a) in our population of neonates with stroke. Methods: In a prospective uncontrolled cohort of term-born children with neonatal arterial ischemic stroke, Lp(a) levels were investigated in 69 mothers and 69 children. Paternal Lp(a) was not explored. Results: An increased Lp(a) level was found in 26 mothers [38%; 95% confidence interval (CI) 28–50%] and in 15 children (22%; 95% CI 13–33%). Both rates were higher than the reference range reported in the general Caucasian population (10% in adults and 5% in children). Additionally, there was a correlation between maternal and infantile Lp(a) levels (p < 0.0001) and between elevated maternal Lp(a) level and lower birth weight (p = 0.027). Conclusions: Elevated maternal Lp(a) is apparently a risk factor for neonatal arterial ischemic stroke. We speculate that the pathological mechanism of this relation may be mediated through a dysfunction of the placental vascularization.
Low Blood Pressure Is Associated with Cognitive Impairment in Very Old People
Authors: Molander Lena , Gustafson Yngve , Lövheim Hugo
Published: April 2010

Background/Aims: Hypertension is an established risk factor for dementia. However, the association between blood pressure and cognition in the very old is not fully determined and important to study considering the ageing population and the morbidity associated with cognitive impairment. Methods: This cross-sectional study included 575 individuals aged 85, 90 or 95 years and above and living in northern Sweden or Finland. Participants were interviewed and assessed using a structured protocol. Systolic (SBP) and diastolic blood pressures (DBP) were measured and pulse pressure (PP) calculated. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Data were also collected from medical charts and caregivers. Results: After adjustment for several demographic variables and diagnoses, SBP was significantly associated with MMSE in a nonlinear fashion; both high and low pressures were associated with poorer results. There was also a linear and positive association between PP and MMSE scores, but no association with DBP was found. Participants with dementia had lower blood pressure. Conclusion: After adjustment for a number of health factors, there was an association between low blood pressure and cognitive impairment. The direction of any causal relationship between blood pressure and cognition remains to be determined.
Optimal Use of Targeted Agents for Advanced Gastrointestinal Stromal Tumours
Authors: Reichardt Peter
Published: April 2010

Imatinib is the recommended 1st-line treatment for a KIT-positive unresectable and/or metastatic gastrointestinal stromal tumour (GIST). However, some patients experience intolerance to imatinib and most patients will eventually experience disease progression while on imatinib treatment. Sunitinib is approved for treatment of a GIST after disease progression on, or intolerance to, imatinib therapy. Progression may occur early or later on, in treatment and is determined by factors including initial GIST genotype and mutational status. GISTs with KIT exon 11 mutations appear to be sensitive to standard dose imatinib, and patients with GISTs exhibiting KIT exon 9 mutations whose disease has progressed on imatinib 400 mg/day have been shown to respond to imatinib 800 mg/day, albeit with a higher incidence of adverse events. Sunitinib has shown clinical benefit in all major GIST mutational subtypes, particularly in patients with wild-type or KIT exon 9 genotype and against GISTs with secondary KIT exon 13 or 14 mutations. The choice between higher-dose imatinib and sunitinib after progression on standard dose imatinib is unclear, and apart from the GIST primary resistance genotype and mutational status, individual patient factors such as tumour characteristics, drug pharmacokinetics, and other clinical factors may affect response to treatment. Individualisation of therapy may help to maximise clinical benefit of therapy in these patients.
Patients’ Rights in a Technology and Market Driven-Europe
Authors: Abbing Henriette D.C. Roscam
Published: April 2010

This article deals with the impact on patients’ rights of medical and technological advances in a market oriented (European) society: what are the advantages and risks, what are the challenges that lay ahead of us? After introducing the subject matter, the first part deals with risks for patients’ rights in the European cross border context (health care, direct to the public screening offers and biomedical research). The second part sketches some of the implications of innovation in health care and medical technology for patients’ rights to autonomy and private life, particularly when third party interests are involved. The article ends with some suggestions on how best to protect patients’ rights in the perspective of innovation in health care and medical research.
Diversity and Harmonisation. Trends and Challenges in European Health Law
Authors: Hartlev Mette
Published: April 2010

European countries share a number of fundamental values and ideas, but when it comes to the organisation of health care sectors and attitudes to basic patients’ rights, there are also vast differences. Consequently, at the European level health law has to balance between the aspiration for uniformity and universal respect for fundamental rights on the one hand, and acceptance of national diversity on the other. The aim of the article is to characterise European health law in terms of both divergence and harmonisation, and to explore the tension between these two features in light of current trends and challenges.
Adding Value? EU Governance of Organ Donation and Transplantation
Authors: Farrell Anne-Maree
Published: April 2010

This article examines recent developments in EU governance of organ donation and transplantation, focusing on an analysis of the Commission’s action plan and the proposed Directive. While the aims of the plan are laudable, a number of concerns remain with respect to the timetable for the plan and the adoption of the Directive, as well as the management of ethical and risk issues. In the final analysis, the added value of EU governance initiatives in the field is likely to be measured by the extent to which they successfully address the ongoing problem of organ shortage in Member States.
News and Views Managing Novel Reproductive Injuries in the Law of Tort: The Curious Case of Destroyed Sperm
Authors: Priaulx Nicolette
Published: April 2010

In view of developments in reproductive medicine, clinical mishaps in this domain are beginning to give rise to ‘injuries’ not easily accommodated within the English law of negligence. While ‘personal injury’ is typically understood as manifesting a deleterious ‘physical’ dimension, cases involving the negligent destruction of cryopreserved sperm, as recently litigated in Yearworth & Ors v Bristol NHS Trust (2009), and other media reported mishaps in fertility treatment do not straightforwardly possess this quality. Without modification, the traditional tortious conception of ‘personal injury’ in English law will not be able to address novel claims. Critically, however, nor do alternative modes of redress seem to offer ease of application. Focusing upon the controversial Yearworth case and exploring what is seen as an unpromising framing of loss, the note argues that there is now an urgent need to rethink what counts as ‘personal injury’. Arguing for the formal recognition of ‘reproductive injury’ as an independent head of damage in negligence, and illustrating the presence of judicial support for that approach, the comment suggests that in light of the difficult challenges that lie in the wake of Yearworth, such a development may be not only desirable but necessary.
The Development of Health Law as a Way to Change Traditional Attitudes in National Legal Systems. The Influence of International Human Rights Law: What is Left for the National Legislator?
Authors: Birmontienė Toma
Published: April 2010

The development of health law as a sovereign subject of law could be seen as a correlative result of the development of international human rights law. From the perspectives of human rights law, health law gives us a unique possibility to change the traditional point of reference — from the regulation of medical procedures, to the protection of human rights as the main objective of law. At the end of the twentieth and the beginning of this century, human rights law and the most influential international instrument — the European Convention on Human Rights (and the jurisprudence of the ECHR) has influenced health care so much that it has became difficult to draw a line between these subjects. Health law sometimes directly influences and even aspires to change the content of Convention rights that are considered to be traditional. However, certain problems of law linked to health law are decided without influencing the essence of rights protected by the Convention, but just by construing the particularities of application of a certain right. In some cases by further developing the requirements of protection of individual rights that are also regulated by the health law, the ECHR even “codifies” some fields of health law (e.g., the rights of persons with mental disorders). The recognition of worthiness and diversity of human rights and the development of their content raise new objectives for national legislators when they regulate the national legal system. Here the national legislator is often put into a quandary whether to implement the standards of human rights that are recognized by the international community, or to refuse to do so, taking account of the interests of a certain group of the electorate.
Transitioning: Academic and Social Performance of African Immigrant Students in an American High School
Authors: Njue John , Retish Paul
Published: April 2010

Student achievement data in schools are often analyzed in terms of ethnic and racial parameters. Such data categorize African immigrant students as African Americans, thus creating an impression of homogeneity within the African American racial group. Given that these immigrant students relocate to the United States with cultural backgrounds that shape their views on educational opportunities, their school experiences render a unique perspective on the dynamics of schooling in the United States. Students enroll in schools where their racial status is an important defining characteristic. Their response to the school system and the racial and social dynamics that accompany this status has definite implications for their academic and social school experiences.
Studies of the Toxicological Potential of Capsinoids XIV: A 26-week Gavage Toxicity Study of Dihydrocapsiate in Rats
Authors: Kodama Terutaka , Masuyama Takeshi , Kayahara Takashi , Tsubuku Shoji , Ohishi Takumi , Wagner Bernard M. , Bernard Bruce K.
Published: April 2010

To further evaluate the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate, CAS No. 205687-03-2), a 26—week gavage toxicity study was conducted in Sprague-Dawley rats (20/sex/group). Test animals received either dihydrocapsiate, 100, 300, or 1000 mg/kg/day, or vehicle (medium-chain triglyceride) by gavage and were observed for antemortem and postmortem signs of toxicity including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. After the end of the dosing period, reversibility was assessed (10/sex/group for the control and 1000 mg/kg groups) following a 4-week recovery period. There were no adverse or toxicological changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, or histopathology. It was concluded that the no observable adverse effect level (NOAEL) of dihydrocapsiate was 1000 mg/kg/day for both sexes in this 26—week gavage study.
Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: Potential TB vaccine candidate antigen
Authors: Cifuentes Diana P , Ocampo Marisol , Curtidor Hernando , Vanegas Magnolia , Forero Martha , Patarroyo Manuel E , Patarroyo Manuel A
Published: April 2010

Background

To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells.

Results

The gene encoding Rv0679c was detected in all strains of the M. tuberculosis complex (MTC), but was only transcribed in M. tuberculosis H37Rv, M. tuberculosis H37Ra and M. africanum. Anti-Rv0679c antibodies specifically recognized the protein in M. tuberculosis H37Rv sonicate and showed its localization on mycobacterial surface. Four HABPs inhibited invasion of M. tuberculosis to target cells by up to 75%.

Conclusions

The results indicate that Rv0679c HABPs and in particular HABP 30979 could be playing an important role during M. tuberculosis invasion of host cells, and therefore could be interesting research targets for studies aimed at developing strategies to control tuberculosis.
Why Is Health Reform So Difficult?
Authors: Brady David W. , Kessler Daniel P.
Published: April 2010

This article examines the possibilities for health care reform in the 111th Congress. It uses a simple model of policy making to analyze the failure of Congress to pass the Clinton health plan in 1993–1994. It concludes that the factors that created gridlock in the 103rd Congress are likely to have a similar impact in the present.
Federal Trade Commission Regulation of Food Advertising to Children: Possibilities for a Reinvigorated Role
Authors: Mello Michelle M.
Published: April 2010

Growing awareness of the role that food and beverage advertising plays in the epidemic of childhood obesity has prompted calls for stricter oversight of advertising practices. The food and beverage industries have taken voluntary steps in this direction, but many commentators have called for increased government regulation. The mission of the Federal Trade Commission (FTC) makes it an obvious candidate to lead a new regulatory effort. However, the FTC has a troubled history in the area of children's advertising regulation, and several political and legal factors constrain its ability to act. This article reviews those obstacles as well as the opportunities that exist at present to expand FTC oversight of food advertising to children. The FTC has considerable latitude to regulate individual food advertisements more rigorously, either on the basis that they are deceptive or on the basis that they are unfair. Broader rule making under the unfairness authority would require congressional intervention to expand the FTC's scope of authority, but there exist possibilities for rule making under the deception doctrine. Finally, the FTC could strengthen its efforts to encourage the food industry to regulate its own advertising practices more stringently and could provide mechanisms for making voluntary initiatives more meaningful.
Mary Rowlandson and the Phenomenology of Patient Suffering
Authors: Arsić Branka
Published: April 2010

This article is a contribution to the fifth part of the Common Knowledge symposium on forms of quietism. Responding to a sense that prior installments of the symposium had overlooked the phenomenology of quietism, of patient suffering, the essay details the daily life of Mary Rowlandson's captivity during King Philip's War in the 17th century and, in particular, her strategies for surviving the breakdown of every basic taxonomy that had until then structured her life in Puritan New England. Refusing either suicide or rebellion and thus reduced to maintaining “bare life,” Rowlandson demonstrated by her resilience that quietist strategies can result in kinds of triumph.
Alice—mutton: Mutton—alice
Authors: Tamen Miguel
Published: April 2010

Tamen's essay is one of a group of responses to Émilie Hache and Bruno Latour's article “Morality or Moralism?” which advocates our “sensitization” to nonhuman things. Tamen examines the picture of universal reciprocation that Hache and Latour propose, according to which, when I “bow at” (acknowledge) things, some things bow back at me, and I must treat whatever bows back as if it were like me. Unlike James Lovelock, a passage from whose work they discuss, Hache and Latour understand this picture in a sense that is essentially “honorary.” The picture or premise they propose sets up, they admit, “a promising misunderstanding.” Tamen offers two arguments in response: one against as-if locutions and another against the very notion of setting up a misunderstanding. But it is good news, Tamen concludes, that sensitization cannot be set up. To what extent we would want a “revival of scruple” to succeed is a serious question, the answer dependent on how much scruple about which things and for what reasons. However pleasing the Hache/Latour or Lovelock picture, it is easy to imagine an intemperate degree of scruple, requiring agonies of continual debate and calculation of the minutest consequences of our acts and the most unlivable alternatives.
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability
Authors: Duchi Serena , Fagnocchi Luca , Cavaliere Valeria , Hsouna Anita , Gargiulo Giuseppe , Hsu Tien
Published: April 2010

Mutations in the human von Hippel-Lindau (VHL) genes are the cause of VHL disease, which displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF). However, many other HIF-independent functions of VHL have been identified and recent evidence indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes. Many of these functions have not been verified in genetically tractable systems. Using an established follicular epithelial model in Drosophila, we show that the Drosophila VHL gene is involved in epithelial morphogenesis via stabilizing microtubule bundles and aPKC. Microtubule defects in VHL mutants lead to mislocalization of aPKC and subsequent loss of epithelial integrity. Destabilizing microtubules in ex vivo culture of wild-type egg chambers can also result in aPKC mislocalization and epithelial defects. Importantly, paclitaxel-induced stabilization of microtubules can rescue the aPKC localization phenotype in Drosophila VHL mutant follicle cells. The results establish a developmental function of the VHL gene that is relevant to its tumor-suppressor activity.
Incorporating index offence analysis into forensic clinical assessment
Authors: West Adrian G. , Greenall Paul V.
Published: April 2010

Purpose. Assessment is a core skill of clinical and forensic psychology practice and forms the basis of all ongoing engagements with offender/patients. In forensic settings, assessment involves the systematic gathering of reliable data on the characteristics of offenders and the offences which they have committed in order to develop understanding of the dynamics of offending and relevant intervention strategies. However, whilst the assessment process is aided by various protocols, no such instrument appears to exist for the assessment of an offender/patient's index offence. This paper presents a draft ‘index offence analysis guide’ designed by the present authors for this purpose and which has been piloted on prisoners and patients in secure settings.

Argument.  Evidence suggests that for various reasons, many clinicians do not routinely review crime scene data while working with offenders. However, this practice is arguably questionable, because how can decisions about admission, amenability to treatment, risk of reoffending, and discharge be made if there is limited awareness of what the offender/patient has done? The present authors argue that knowledge of the index offence is important to understanding the offender and suggest this can be obtained using a guide such as the one presented here. This is illustrated with an anonymous case.

Conclusion. Index offence analysis should be a core task of any forensic clinician engaged in the assessment of offender/patients as it can provide a better understanding of crime scene actions and offence motivations. This can help guide treatment planning and improve risk assessments.