bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphovascular invasion is an independent predictor of oncological outcomes in patients with lymph node‐negative urothelial bladder cancer treated by radical cystectomy: a multicentre validation trial
Authors: Bolenz Christian , Herrmann Edwin , Bastian Patrick J. , Michel Maurice S. , Wülfing Christian , Tiemann Arne , Buchner Alexander , Stief Christian G. , Fritsche Hans‐Martin , Burger Maximilian , Wieland Wolf F. , Höfner Thomas , Haferkamp Axel , Hohenfellner Markus , Müller Stefan C. , Ströbel Philipp , Trojan Lutz
Published: January 2010

Study Type – Prognosis (inception cohort) Level of Evidence 1b

OBJECTIVES

To validate the association of lymphovascular invasion (LVI) with disease recurrence and cancer‐specific survival (CSS) in a multicentre cohort of patients treated with radical cystectomy (RC) for urothelial bladder cancer (UBC).

PATIENTS AND METHODS

We collected pathological and clinical data on 1099 lymph node‐negative patients treated with RC at six German institutions. LVI was defined as the presence of tumour cells within an unequivocal endothelium‐lined space in haematoxylin and eosin‐stained sections.

RESULTS

LVI was present in 295 (26.8%) patients; the presence of LVI correlated significantly with increasing tumour stage, i.e. pT1, 65 (29.4%); pT2, 88 (31.5%); pT3 110 (31.8%); and pT4 32 (38.1%) (P= 0.002) and grade (P < 0.001). In univariable analysis the presence of LVI was significantly associated with reduced recurrence‐free survival (P= 0.008) and reduced CSS (P= 0.039). On multivariable Cox regression analysis tumour stage (P < 0.001), age (>75 vs ≥75 years; P= 0.018) and LVI (P < 0.001) were identified as independent predictors of CSS.

CONCLUSIONS

Our large multicentre study confirms the independent prognostic value of LVI in patients with node‐negative UBC. LVI can be regarded as a surrogate variable for lymphatic micrometastasis in node‐negative UBC. Assessment of LVI might improve the selection of patients who are likely to benefit from adjuvant therapy after RC. The identification of factors involved in the process of LVI could reveal new therapeutic targets for UBC.
Positive margins after nephron‐sparing surgery for renal cell carcinoma: long‐term follow‐up of patients on active surveillance
Authors: Lopez‐Costea Miguel A. , Fumadó Lluís , Lorente David , Riera Luis , Miranda Eladio Franco
Published: January 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To analyse our long‐term oncological outcomes with active surveillance in patients with positive surgical margins (PSMs) after nephron‐sparing surgery (NSS) for renal cell carcinoma (RCC), as this situation is a difficult therapeutic dilemma.

PATIENTS AND METHODS

We performed open NSS for renal masses with frozen‐section analysis of any suspicious zone of the surgical bed, followed by extensive argon‐beam coagulation. In patients where the final histopathological examination of the renal mass revealed PSMs, follow‐up consisted of computed tomography (CT) every 6 months in the first 2 years and then annually up to 5 years, and thereafter we alternated ultrasonography with CT.

RESULTS

From 1995 to 2003 we had 11 cases of microscopic definitive PSMs after NSS for RCC. Two patients required nephrectomy (one for postoperative bleeding and another as an elective procedure), so nine were followed. These patients were either operated under elective (seven) or imperative (two) conditions. The histological subtype was clear cell carcinoma in three, papillary in two, chromophobe in two and hybrid oncocytic RCC in two, with a Furhman grade of 2 in six and 3 in three. The mean size was 31.4 mm, and the stage was pT1a in six, pT1b in one and pT3a in two. After a median follow‐up of 80.5 months, there was no local recurrence or distant progression.

CONCLUSIONS

In our experience, microscopic PSMs in NSS specimens can be managed conservatively with active surveillance, achieving excellent results and avoiding extensive reoperation without compromising long‐term oncological outcomes.
Fairness, Equality and Legitimacy: A Qualitative Comparative Study of Germany and the UK
Authors: Taylor‐Gooby Peter , Martin Rose
Published: January 2010

The pressures of globalization and shifts towards post‐industrialism are producing policies that increasingly emphasize the common themes of activation and of individual responsibility for outcomes. Such approaches suggest normative principles of equality of opportunity rather than of outcome, and of individual rather than collective responsibility for the outcomes achieved. Does this imply a shift towards a common normative framework for European welfare states, with implications for future policy developments? This article reports a recent qualitative study examining ideas about fairness and social provision in the very different regimes of Germany and the UK. The analysis shows that while respondents in both countries value equality of opportunity as a normative principle, those in Germany are much more likely to argue that an equal opportunity approach requires government to guarantee equal access to basic services. They are also more likely to express concerns about market freedoms which allow those who can afford it better access to health care and education. Real differences in welfare values remain, loosely following differences of regime type, despite the greater emphasis on activation and individual responsibility across European welfare states.
The Compatibility Dialectic: Mediating the Legitimate Coexistence of Islamic Law and State Law
Authors: An‐Naim Abdullahi Ahmed
Published: January 2010

Islamic Law is not now and cannot be the state law of any state, whether Muslims are the majority or minority of the population. This view does not dispute the religious authority of Islamic Law for Muslims, which exists only outside the framework of the state. Still, some principles of Islamic Law should be relevant to the public discourse, provided the argument is made in terms of what the author calls ‘civic reason’ and not simply by assertions of religious conviction. While the two are different types of normative systems, each based on its own sources of authority and legitimacy, there are possibilities of compatibility and mutual influence between Islamic Law and state law as complementary normative systems, without requiring either to conform to the nature and role of the other. This lecture examines the requirements, scope and dynamics of this dialectic relationship, whether Muslims are majority or minority.
Forced Marriage as a Harm in Domestic and International Law
Authors: Dauvergne Catherine , Millbank Jenni
Published: January 2010

This article reports on our analysis of 120 refugee cases from Australia, Canada, and Britain where an actual or threatened forced marriage was part of the claim for protection. We found that forced marriage was rarely considered by refugee decision makers to be a harm in and of itself. This finding contributes to understanding how gender and sexuality are analysed within refugee law, because the harm of forced marriage is experienced differently by lesbians, gay men and heterosexual women. We contrast our findings in the refugee case law with domestic initiatives in Europe aimed at protecting nationals from forced marriages both within Europe and elsewhere. We pay particular attention to British initiatives because they are in many ways the most far‐reaching and innovative, and thus the contrast with the response of British refugee law is all the more stark.
Property Interests in Body Parts: Yearworth v North Bristol NHS Trust
Authors: Hawes Cynthia
Published: January 2010

This note analyses Yearworth v North Bristol NHS Trust, in which the Court of Appeal accepted the existence of property interests in parts or products of the human body and considered the applicability of chattel torts where interference with such interests occurs. The writer questions whether the Court's decision to extend the law of bailment in the case was necessary, or whether the law of conversion or negligence should be available as the more appropriate causes of action.
Between trust and control: company‐level bargaining on flexible working hours in the Danish and German metal industries
Authors: Ilsøe Anna
Published: January 2010

Denmark is often highlighted as a good example of organised decentralisation in which employee bargaining power remains comparatively strong. However, comparative analysis of the Danish case rarely reflects how the social contracts between management and workers' representatives contribute to the bargaining outcome at company level. Drawing on 10 case studies in the German and Danish metal industries carried out in 2005, this article argues that the social contracts at the Danish case companies allow a more efficient use of company‐level agreements on flexible working hours than the social contracts at the German case companies.
Speculating about Divinity? God's Immanent Life and Actualistic Ontology
Authors: STRATIS JUSTIN
Published: January 2010

This article argues that counterfactual statements concerning God's life in himself are both theologically informative and genuinely warranted by Karl Barth's notion of God's ‘being‐in‐act’ as presented in § 28.1 of the Church Dogmatics. To this end, the proposed reading aims to mitigate recent emphases on divine Entscheidung as the primary category for construing Barth's theological ontology. Without offering a resolution to alleged ‘tensions’ in Barth's doctrine of God, the author nevertheless suggests that there are good reasons to prefer certain streams of Barth's thought to others, with the notion of God's love offered as a test case.
Banking on Folk Art: Banamex‐Citigroup and Transnational Cultural Citizenship
Authors: COFFEY MARY K.
Published: January 2010

This article offers two readings of The Great Masters of Mexican Folk Art, a travelling exhibition of the Fomento Cultural Banamex, AC's folk art collection that coincided with Citigroup's buyout of Banamex, Mexico's second largest bank. The first, a political economic critique, situates the exhibition within the neoliberal economic reform of the Mexican banking system and the designs of US‐based transnational banks on migrant remittances. The second, a material culture approach, focuses on the exhibitionary strategies employed to incentivise folk art consumption as a mode of cosmopolitan citizenship.
Temporal requirement of RPE‐derived VEGF in the development of choroidal vasculature
Authors: Le Yun‐Zheng , Bai Yanyan , Zhu Meili , Zheng Lixin
Published: January 2010

J. Neurochem. (2010) 112, 1584–1592.

Vascular endothelial growth factor (VEGF‐A or VEGF) is a potent growth factor for the development of retinal and choroidal vasculatures. To define the temporal requirement of the retinal pigmented epithelium (RPE)‐derived VEGF in choroidal vascular development, we generated conditional VEGF knockout mice using an inducible Cre/lox system. The loss of the RPE‐derived VEGF was confirmed with immunoblotting and immunohistochemistry. Retinal function and structure were assessed with electroretinography and histology, respectively. Choroidal vascular density was analyzed with computer‐assisted semi‐quantitative assay using fluorescently labeled choroidal flat‐mounts. Induction of RPE‐specific VEGF disruption at embryonic day 10 (E10) or E13 for 2 days caused regulatable decreases in choroidal vascular density, photoreceptor function, and photoreceptor outer nuclear layer thickness. The loss of the RPE‐produced VEGF after E15 did not cause detectable defects in choroidal vasculatures and photoreceptor function and morphology. These results suggest that the RPE‐derived VEGF plays a critical role in choroidal vascular development during organogenesis before E15.
Wild‐type Shadoo proteins convert to amyloid‐like forms under native conditions
Authors: Daude Nathalie , Ng Vivian , Watts Joel C. , Genovesi Sacha , Glaves John Paul , Wohlgemuth Serene , Schmitt‐Ulms Gerold , Young Howard , McLaurin JoAnne , Fraser Paul E. , Westaway David
Published: January 2010

J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06575.x

The cellular prion protein PrPC refolds into a β‐sheet enriched, infectivity‐associated form called PrPSc. Shadoo (Sho) is a newly discovered glycoprotein that is also expressed in the adult brain. Wild type (wt) mouse Sho consists of an arginine‐rich region, a hydrophobic central domain of five tandem A/LAAG amino acid repeats R1–R5 with similarity to the hydrophobic domain of PrPC, and a C‐terminal domain with one N‐linked carbohydrate. As some alanine‐rich proteins and PrP with a shortened C‐terminal domain form amyloid we investigated conformational properties of wt Sho and polymorphic variants with insertion/deletions centered on R3. Recombinant mouse and sheep Sho converted to an amyloid‐like form without recourse to chemical denaturation or acidification. For wt proteins this transition was marked by increased thioflavin T binding, Congo red staining, presence of fibrillar structures by electron microscopy, formation of sodium dodecyl sulfate‐resistant complexes and the generation of a C‐terminal proteinase K resistant core of 5–8 kDa. Variant Sho proteins differing within the R1–R5 region exhibited most but not all of these properties. Our studies define a proteinase K ‐resistant signature fragment for the amyloid fold of Sho and raise the question of a physiological role for this form of the wt protein.
PI3K modulates estrogen‐dependent facilitation of colon‐to‐urethra cross‐organ reflex sensitization in ovariectomized female rats
Authors: Peng Hsien‐Yu , Chen Gin‐Den , Lai Cheng‐Yuan , Hsieh Ming‐Chun , Hsu Hsao‐Hsun , Wu Hsi‐Chin , Lin Tzer‐Bin
Published: January 2010

J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06577.x

To determine the role of 17β‐estradiol and involvement of intracellular phosphatidylinositol‐3‐kinase signaling in cross‐organ sensitization between the descending colon and the urethra, we analyzed urethra reflex activity and protein expressions in lumbosacral (L6–S2) spinal dorsal horn in response to mustard oil instillation into the descending colon in ovariectomized female rats. When compared with vehicle solution, intracolonic mustard oil sensitized the NMDA receptor NR2B subunit‐dependent reflex activity and increased expression levels of phosphorylated Akt (pAkt) and phosphorylated NR2B (pNR2B) in dorsal horn. Facilitation of reflex sensitization and increases in protein expressions of pAkt and pNR2B in dorsal horn were induced after pre‐treatment with a subcutaneous injection of 17β‐estradiol (5 μg/kg), 6 h ahead of time, when compared with vehicle solution. This phenomenon was reversed both by intrathecal pre‐treatment with ICI 182780 (0.25 mg/kg, i.t.) and LY294002 (50 mg/kg, i.t.). Immunoprecipitation of dorsal horn tissue revealed a protein‐protein interaction between pAkt and pNR2B increases, 6 h following the subcutaneous 17β‐estradiol when compared with vehicle injections. Results indicate 17β‐estradiol may activate the phosphatidylinositol‐3‐kinase cascade, which subsequently phosphorylates the NR2B subunit, via spinal estrogen receptors ERα/ERβ, to facilitate NMDA‐dependent cross‐organ sensitization, which is presumed to underlie pelvic viscero‐visceral referred pain.
Analysis of Shadow Moire Technique With Phase Shifting Using Generalisation of Carre Method
Authors: Magalhaes Jr P. A. A. , Neto P. S. , de Barcellos C. S.
Published: January 2010

Abstract:  Experimental stress analysis can be conveniently investigated by classical shadow Moire technique. Moire is a non‐contact and non‐destructive technique, with a fast digitisation process. The phenomena of Moire fringes are the result of the projection of the fringes of a ruling on a certain object. It has measurement accuracy comparable with other systems and also low cost. The present study offers new algorithms for phase evaluation in measurements. Several phase‐shifting algorithms with an arbitrary but constant phase‐shift between captured intensity signs are proposed. The algorithms are similarly derived as the so‐called ‘Carre algorithm’. The idea is to develop a generalisation of Carre algorithm that is not restricted to four images. Errors and random noise in the images cannot be eliminated, but the uncertainty caused by their effects can be reduced by increasing the number of observations. An experimental analysis of the mistakes of the technique was made, as well as a detailed analysis of mistakes of the measurement. The advantages of the proposed algorithm are its precision in the measures taken, speed of processing and the immunity to noise in signs and images.
Application of Plasmons to the Determination of Surface Profile and Contact Strain Distribution
Authors: Sciammarella C. A. , Lamberti L. , Sciammarella F. M. , Demelio G. P. , Dicuonzo A. , Boccaccio A.
Published: January 2010

Abstract:  Free electrons in the surface of metals can produce surface plasmons if they are excited by evanescent waves. The surface plasmons are electromagnetic waves that by decaying can generate photons. These photons produce propagating waves that feed energy to an oscillating cavity. From this effect a Fabry–Perot like interferometer is generated. In view of this basic knowledge a truly novel application on how these plasmons can be used experimentally is introduced in this article. Essentially, by using the transformation of evanescent waves into propagating waves via the plasmon generation it is possible to perform high accuracy contouring of any metal surface as well as the determination of its contact stresses. A laser beam illuminates a glass‐air‐metal interface and through a proper optical setup it will produce double evanescent illumination. This illumination generates interference fringes that contain surface depth information as well as in‐plane strain information. In order to show the robustness of the proposed technique, three different applications are presented in the paper. First, the surface roughness mapping of a copper plate is determined and the obtained values are in statistical agreement with the data measured by a mechanical profilometer. Second, the surface profiles of nickel alloy surfaces used as calibrated standards for the determination of Ra values are obtained. The measured Ra values statistically agree with the values of the different standards. Finally, the contact strains of a copper cylinder on glass are also measured. The contact strains follow the trend predicted by the K.L. Johnson’s model of contact. Local regions (asperities) experiment large plastic deformations.
Processing, Microstructure and Mechanical Properties of Air Plasma‐Sprayed Ceria–Yttria Co‐stabilized Zirconia Coatings
Authors: Alfano M. , Di Girolamo G. , Pagnotta L. , Sun D.
Published: January 2010

Abstract:  Thermal barrier coatings (TBCs) are widely adopted to protect mechanical components in gas turbine engines operating at high temperature. Basically, the surface temperature of these components must be low enough to retain material properties within acceptable bounds and to extend component life. From this standpoint, air plasma‐sprayed (APS) ceria and yttria co‐stabilized zirconia (CYSZ) is particularly promising because it provides enhanced thermal insulation capabilities and resistance to hot corrosion. However, essential mechanical properties, such as hardness and Young’s modulus, have been less thoroughly investigated. Knowledge of Young’s modulus is of concern because it has a significant effect on strain tolerance and stress level and, hence, on durability. The focus of the present study was to determine the mechanical properties of APS CYSZ coatings. In particular, X‐ray diffraction (XRD) is adopted for phase analysis of powders and as‐sprayed coatings. In addition, scanning electron microscopy (SEM) and image analysis (IA) are employed to explore coating microstructure and porosity. Finally, the Young’s modulus of the coating is determined using nanoindentation and a resonant method. The results obtained are then discussed and a cross‐check on their consistency is carried out by resorting to a micromechanical model.
A Multilingual Mass Communication Intervention for Seniors and People with Disabilities on Medicaid: A Randomized Controlled Trial
Authors: Kurtovich Elaine , Ivey Susan L. , Neuhauser Linda , Graham Carrie , Constantine Wendy , Barkan Howard
Published: January 2010

Objectives. To evaluate the following: (1) baseline knowledge, attitudes, and behavioral intentions about Medicaid managed care (MMC) among seniors and people with disabilities (SPD) receiving Medicaid benefits; (2) SPD Medicaid beneficiaries' use of and satisfaction with a user‐designed MMC guidebook; and (3) guidebook effects on changes in MMC knowledge, attitudes, and intended behaviors of SPD beneficiaries.

Data Sources/Study Setting. Survey data collected between February and May 2008 from a random sample of SPD receiving Medicaid benefits in three California counties.

Study Design. This randomized controlled trial of 319 intervention and 373 control SPD Medicaid beneficiaries used pre‐ and postintervention telephone surveys to compare changes in MMC knowledge, attitudes, and intended behaviors.

Data Collection Methods. Baseline and follow‐up telephone interviews were conducted in English, Spanish, Cantonese, and Mandarin.

Principal Findings. Seventy‐seven percent of intervention participants reported using the guidebook. Nearly all (97.9 percent) found it somewhat or very useful. Intervention participants showed gains in knowledge, positive attitudes, and intentions to enroll in MMC that are statistically significant compared with control participants. However, knowledge levels remained low even among intervention participants.

Conclusions. Findings suggest that the guidebook is an effective way to improve recipients' MMC knowledge, confidence, and behavioral intentions.
The anti‐allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen‐induced arthritis in mice
Authors: Shiota N , Kovanen PT , Eklund KK , Shibata N , Shimoura K , Niibayashi T , Shimbori C , Okunishi H
Published: January 2010

Background and purpose:  Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti‐allergic compound with a potent membrane‐stabilizing effect on mast cells and a wide range of anti‐inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen‐induced arthritis in mice.

Experimental approach:  Tranilast (400 mg·kg−1·day−1) was orally administered for 8 weeks to mice with established collagen‐induced arthritis. Arthritis was assessed by clinical signs and X‐ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT‐PCR and Western blot analysis.*

Key results:  TNF‐α‐positive mast cells were present extensively throughout the inflamed synovium of vehicle‐treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X‐ray scores of arthritis and decreased numbers of TNF‐α‐positive mast cells and mRNA levels of TNF‐α, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin‐6, cathepsin‐K, receptor activator of nuclear factor‐κB, and of receptor activator of nuclear factor‐κB‐ligand, but increased interleukin‐10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast.

Conclusions and implications:  Tranilast possesses significant anti‐rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis.
Gangliosides induce autophagic cell death in astrocytes
Authors: Hwang Jaegyu , Lee Shinrye , Lee Jung Tae , Kwon Taeg Kyu , Kim Deok Ryong , Kim Ho , Park Hae‐Chul , Suk Kyoungho
Published: January 2010

Background and purpose: Gangliosides, sialic acid‐containing glycosphingolipids, abundant in brain, are involved in neuronal function and disease, but the precise molecular mechanisms underlying their physiological or pathological activities are poorly understood. In this study, the pathological role of gangliosides in the extracellular milieu with respect to glial cell death and lipid raft/membrane disruption was investigated.

Experimental approach: We determined the effect of gangliosides on astrocyte death or survival using primary astrocyte cultures and astrocytoma/glioma cell lines as a model. Signalling pathways of ganglioside‐induced autophagic cell death of astrocytes were examined using pharmacological inhibitors and biochemical and genetic assays.

Key results: Gangliosides induced autophagic cell death in based on the following observations. Incubation of the cells with a mixture of gangliosides increased a punctate distribution of fluorescently labelled microtubule‐associated protein 1 light chain 3 (GFP‐LC3), the ratio of LC3‐II/LC3‐I and LC3 flux. Gangliosides also increased the formation of autophagic vacuoles as revealed by monodansylcadaverine staining. Ganglioside‐induced cell death was inhibited by either a knockdown of beclin‐1/Atg‐6 or Atg‐7 gene expression or by 3‐methyladenine, an inhibitor of autophagy. Reactive oxygen species (ROS) were involved in ganglioside‐induced autophagic cell death of astrocytes, because gangliosides induced ROS production and ROS scavengers decreased autophagic cell death. In addition, lipid rafts played an important role in ganglioside‐induced astrocyte death.

Conclusions and implications: Gangliosides released under pathological conditions may induce autophagic cell death of astrocytes, identifying a neuropathological role for gangliosides.
Pro‐ulcer effects of resveratrol in mice with indomethacin‐induced gastric ulcers are reversed by l‐arginine
Authors: Guha P , Dey A , Chatterjee A , Chattopadhyay S , Bandyopadhyay SK
Published: January 2010

Background and purpose:  Although resveratrol is currently being evaluated in pre‐clinical studies as a potential cancer chemopreventive agent and cardiovascular stress‐releasing compound, treatment with resveratrol severely delays healing of pre‐existing gastric ulcers. Resveratrol treatment can also induce endothelial NOS (eNOS) expression. Here, we have attempted to modulate NO production via eNOS in order to alleviate the pro‐ulcer effects of resveratrol.

Experimental approach:  Gastric ulcers were induced in mice with a single dose of indomethacin. The effects of pretreatment with l‐arginine on the pro‐ulcer effects of resveratrol in these mice were then assessed. We measured ulcer damage scores (DS), myeloperoxidase (MPO) activity, generation of prostaglandin E2 (PGE2) and NO, along with a gene expression study.

Key results:  Resveratrol significantly aggravated damage from indomethacin‐induced gastric ulcers, and delayed healing, as shown by increased DS and MPO activity. The mRNA for cyclooxygenase (COX)‐1, but not that for COX‐2, was inhibited by resveratrol treatment, with reduced synthesis of PGE2 by gastric tissue. However, resveratrol treatment induced eNOS gene expression and shifted the eNOS/iNOS balance. l‐Arginine given before resveratrol in mice with indomethacin‐induced ulcers significantly increased tissue NO synthesis and improved ulcer healing.

Conclusions and implications:  Exogenous l‐arginine increased NO formation via raised levels of eNOS induced by resveratrol and protected against the pro‐ulcer effects of resveratrol. Therefore, l‐arginine might be useful for alleviation of the pro‐ulcer side effects of resveratrol in patients.
Acute Hepatitis B Outbreaks Related to Fingerstick Blood Glucose Monitoring in Two Assisted Living Facilities
Authors: Counard Catherine A. , Perz Joseph F. , Linchangco Purisima C. , Christiansen Demian , Ganova‐Raeva Lilia , Xia Guoliang , Jones Steven , Vernon Michael O.
Published: January 2010

OBJECTIVES: To establish the etiology for outbreaks of hepatitis B virus (HBV) infections at two assisted living facilities (ALFs) and devise appropriate control measures.

DESIGN: Multisite outbreak investigations, retrospective cohort.

SETTING: Two ALFs in Illinois.

PARTICIPANTS: Facility A residents (n=120) and Facility B residents (n=105) and nursing staff (n=6).

MEASUREMENTS: For Facility A, a retrospective cohort study to identify risk factors for HBV infection through serological testing of all residents and a medical record extraction. For Facility A and B, investigation of fingerstick blood glucose monitoring techniques. For Facility B, serological HBV testing of nurses and residents receiving fingerstick blood glucose monitoring.

RESULTS: At Facility A, five confirmed acute, two probable acute, and one probable chronic HBV infections were identified in the 109 residents tested. All of the eight identified residents with HBV infection had diabetes mellitus. HBV deoxyribonucleic acid (DNA) sequences from the chronic and acute cases were identical. Transmission of HBV was associated with fingerstick blood glucose monitoring (relative risk (RR)=28.5, 95% confidence interval (CI)=1.6–498; P<.001) and insulin injections (RR=7.4, 95% CI=1.3–40.8; P=.03). At Facility B, seven of 21 residents (33.3%) receiving fingerstick blood glucose monitoring had evidence of recent HBV infection.

CONCLUSION: Nurses probably transmitted HBV infection from resident to resident during fingerstick blood glucose monitoring in two separate ALFs, causing outbreaks. Awareness of the high risk for HBV transmission during procedures for the care of diabetes mellitus was limited. Following established infection control measures is critical to prevent spread of this highly contagious virus.
Lean Mass Index: A Better Predictor of Mortality than Body Mass Index in Elderly Asians
Authors: Han Seung Seok , Kim Ki Woong , Kim Kwang‐Il , Na Ki Young , Chae Dong‐Wan , Kim Suhnggwon , Chin Ho Jun
Published: January 2010

OBJECTIVES: To evaluate the correlation between body mass index (BMI), body composition, and all‐cause mortality in an elderly Asian population.

DESIGN: A prospective observational cohort study with 3.5‐year follow‐up.

SETTING: The Korean Longitudinal Study on Health and Aging Project for elderly residents in Seongnam City, Korea.

PARTICIPANTS: Eight hundred seventy‐seven subjects aged 65 and older for whom baseline body composition data was available.

MEASUREMENTS: BMI, waist circumference, and body composition of each subject was evaluated. Body composition was examined using bioelectrical impedance analyses of measures, including lean mass (kg), fat mass (kg), and fat proportion (%). In addition, lean mass index (LMI, kg/m2) was calculated by dividing lean mass by the square of height. Participants were divided into three groups: Group 1 (<25th percentile), Group 2 (25–75th percentiles), and Group 3 (≥75th percentile) for BMI, waist circumference, body composition, and LMI.

RESULTS: In the fully adjusted Cox proportional hazard model, BMI, waist circumference, and fat composition were not correlated with mortality, but higher lean mass and LMI were considered predictors of lower mortality when comparing Group 3 and Group 1 (in lean mass, relative risk reduction of 84%, 95% confidence interval (CI)=45–96%, P=.004; in LMI, relative risk reduction of 69%, 95% CI=12–89%, P=.03).

CONCLUSION: The present study indicates that the recommendation of low BMI as a means of obtaining a survival advantage in the elderly is not supported. Instead, higher lean mass and higher LMI are associated with better survival in the elderly Asian population.
Efficacy and Safety of a Once‐Yearly Intravenous Zoledronic Acid 5 mg for Fracture Prevention in Elderly Postmenopausal Women with Osteoporosis Aged 75 and Older
Authors: Boonen Steven , Black Dennis M. , Colón‐Emeric Cathleen S. , Eastell Richard , Magaziner Jay S. , Eriksen Erik Fink , Mesenbrink Peter , Haentjens Patrick , Lyles Kenneth W.
Published: January 2010

OBJECTIVES: To determine the efficacy of once‐yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women.

DESIGN: A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial.

SETTING: Multicenter, randomized, double‐blind, placebo‐controlled trials.

PARTICIPANTS: Postmenopausal women (aged ≥75) with documented osteoporosis (T‐score ≤−2.5 at femoral neck or ≥1 prevalent vertebral or hip fracture) or a recent hip fracture.

INTERVENTION: Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months.

MEASUREMENTS: Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment.

RESULTS: At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54–0.78, P<.001; HR=0.34, 95% CI=0.21–0.55, P<.001; and HR=0.73, 95% CI=0.60–0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups.

CONCLUSION: Once‐yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis.
Guided tissue regeneration combined with a deproteinized bovine bone mineral (Bio‐Oss®) in the treatment of intrabony periodontal defects: 6‐year results from a randomized‐controlled clinical trial
Authors: Stavropoulos Andreas , Karring Thorkild
Published: January 2010

Stavropoulos A, Karring T. Guided tissue regeneration combined with a deproteinized bovine bone mineral (Bio‐Oss®) in the treatment of intrabony periodontal defects: 6‐year results from a randomized‐controlled clinical trial. J Clin Periodontol 2010; 37: 200–210. doi: 10.1111/j.1600‐051X.2009.01520.x.

Aim: To present the 6‐year results of a randomized‐controlled clinical trial evaluating guided tissue regeneration (GTR) combined with or without deproteinized bovine bone mineral (DBBM) in intrabony defects.

Material & Methods: In each of 45 patients, one defect was treated with GTR combined with DBBM hydrated in saline (DBBM−) or gentamicin sulphate (DBBM+) or with GTR alone. Clinical parameters were recorded pre‐surgery, at 1 and 6 years postsurgery.

Results: Thirty‐six patients/33 teeth were available for the 6‐year control. Statistically significant clinical improvements were observed for all treatments. Clinical attachment level (CAL) gain averaged 2.5 mm (DBBM−), 4.1 mm (DBBM+), and 3.0 mm (GTR) at 1 year postsurgery, and remained stable over 5 additional years (2.3, 4.1, and 2.7 mm, respectively). Treatment did not appear to influence residual probing depths (PDs) or CAL gains at 6 years postsurgery, or the extent of PD and CAL change from 1 to 6 years, and did not associate with sites losing CAL during follow‐up. No association of grafting with sites showing CAL gain 4 mm at the 1‐ or 6‐year control was observed.

Conclusion: The improvements in periodontal conditions obtained after GTR treatment with or without the adjunct use of DBBM can be preserved on a long‐term basis.
The bioactive dipeptide anserine is transported by human proton‐coupled peptide transporters
Authors: Geissler Stefanie , Zwarg Madlen , Knütter Ilka , Markwardt Fritz , Brandsch Matthias
Published: January 2010

The bioactive dipeptide derivative anserine (β‐alanyl‐1‐N‐methyl‐l‐histidine) is absorbed from the human diet in intact form at the intestinal epithelium. The purpose of this study was to investigate whether anserine is a substrate of the H+/peptide cotransporters 1 and 2 (PEPT1 and PEPT2). We first assessed the effects of anserine on [14C]glycylsarcosine ([14C]Gly‐Sar) uptake into Caco‐2 cells expressing human PEPT1 and into spontaneous hypertensive rat kidney proximal tubule (SKPT) cells expressing rat PEPT2. Anserine inhibited [14C]Gly‐Sar uptake with Ki values of 1.55 mm (Caco‐2) and 0.033 mm (SKPT). In HeLa cells transfected with pcDNA3‐hPEPT1 or pcDNA3‐hPEPT2, Ki values of 0.65 mm (hPEPT1) and 0.18 mm (hPEPT2) were obtained. We conclude from these data that anserine is recognized by PEPT1 and PEPT2. Carnosine also inhibited [14C]Gly‐Sar uptake. Using the two‐electrode, voltage‐clamp technique at Xenopus laevis oocytes, strong hPEPT1‐specific inward transport currents were recorded for Gly‐Sar, anserine and carnosine, but not for glycine. We conclude that anserine and carnosine interact with the human intestinal peptide transporter and are transported by hPEPT1 in an active, electrogenic H+ symport. As PEPT1 is the predominant transport system for di‐ and tripeptides at the intestinal epithelium, this transporter is most probably responsible for the intestinal absorption of anserine after food intake. In addition, anserine might be useful for the design of new substrates of peptide transporters, such as prodrugs, that can be administered orally.
The role of the Fe‐S cluster in the sensory domain of nitrogenase transcriptional activator VnfA from Azotobacter vinelandii
Authors: Nakajima Hiroshi , Takatani Nobuyuki , Yoshimitsu Kyohei , Itoh Mitsuko , Aono Shigetoshi , Takahashi Yasuhiro , Watanabe Yoshihito
Published: January 2010

Transcriptional activator VnfA is required for the expression of a second nitrogenase system encoded in the vnfH and vnfDGK operons in Azotobacter vinelandii. In the present study, we have purified full‐length VnfA produced in E. coli as recombinant proteins (Strep‐tag attached and tag‐less proteins), enabling detailed characterization of VnfA for the first time. The EPR spectra of whole cells producing tag‐less VnfA (VnfA) show distinctive signals assignable to a 3Fe‐4S cluster in the oxidized form ([Fe3S4]+). Although aerobically purified VnfA shows no vestiges of any Fe‐S clusters, enzymatic reconstitution under anaerobic conditions reproduced [Fe3S4]+ dominantly in the protein. Additional spectroscopic evidence of [Fe3S4]+in vitro is provided by anaerobically purified Strep‐tag attached VnfA. Thus, spectroscopic studies both in vivo and in vitro indicate the involvement of [Fe3S4]+ as a prosthetic group in VnfA. Molecular mass analyses reveal that VnfA is a tetramer both in the presence and absence of the Fe‐S cluster. Quantitative data of iron and acid‐labile sulfur in reconstituted VnfA are fitted with four 3Fe‐4S clusters per a tetramer, suggesting that one subunit bears one cluster. In vivoβ‐gal assays reveal that the Fe‐S cluster which is presumably anchored in the GAF domain by the N‐terminal cysteine residues is essential for VnfA to exert its transcription activity on the target nitrogenase genes. Unlike the NifAL system of A. vinelandii, O2 shows no effect on the transcriptional activity of VnfA but reactive oxygen species is reactive to cause disassembly of the Fe‐S cluster and turns active VnfA inactive.

Structured digital abstract

MINT‐7311946: VnfA (uniprotkb:C1DI41) and VnfA (uniprotkb:C1DI41) bind (MI:0407) by molecular sieving (MI:0071)

MINT‐7311931: VnfA (uniprotkb:C1DI41) and VnfA (uniprotkb:C1DI41) bind (MI:0407) by blue native page (MI:0276)
imProving Outcomes after STroke Clinical Pilot Trial Protocol
Authors: Hackett M. L. , Carter G. , Crimmins D. , Clarke T. , Maddock K. , Sturm J.W.
Published: January 2010

Rationale

One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated.

Aims

POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score ≥8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score ≥8) and improved health-related quality of life in patients with a recent stroke.

Design

A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups.

Study outcomes and sample size

For the primary end-point the POST trial will have 80% power to detect a relative risk of 0·4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up.

Discussion

Evidence of efficacy will determine whether a multi-centre, international trial is warranted.
Interleukin-6 as an Early Predictor for One-Year Survival following an Ischaemic Stroke/Transient Ischaemic Attack
Authors: Shenhar-Tsarfaty S. , Assayag E. Ben , Bova I. , Shopin L. , Fried M. , Berliner S. , Shapira I. , Bornstein N. M.
Published: January 2010

Background

Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis.

Aims

This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality.

Methods

Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality.

Results

Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6·47pg/ml, χ2 (I, N = 250) = 20·5, P<0·001. Interleukin-6 above 6·47 pg/ml during the acute phase predicted subsequent non-survival ( P = 0·006, odds ratio 8·0).

Conclusions

This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions.
Dual Antiplatelet Therapy is not Optimal for Stroke Prevention in Patients with Atrial Fibrillation
Authors: Chamorro Á.
Published: January 2010

The superior efficacy of oral anticoagulation over aspirin for prevention of recurrent stroke in patients with atrial fibrillation is widely acknowledged. However, oral anticoagulation therapy is notorious for having a narrow therapeutic index, numerous drug and dietary interactions, and a significant risk of serious bleeding. The value of dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation has been assessed in the ACTIVE A trial. In this study, the relative risk of primary events was significantly decreased in patients allocated clopidogrel and aspirin compared with patients receiving aspirin alone. However, the relative risk of major bleeding was also significantly increased. This article analyses critically the role of dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation.
Neurochemistry of drug action
Authors: Licata Stephanie C. , Renshaw Perry F.
Published: January 2010

Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive imaging technique that permits measurement of particular compounds or metabolites within the tissue of interest. In the brain,1H MRS provides a snapshot of the neurochemical environment within a defined volume of interest. A search of the literature demonstrates the widespread utility of this technique for characterizing tumors, tracking the progress of neurodegenerative disease, and for understanding the neurobiological basis of psychiatric disorders. As of relatively recently,1H MRS has found its way into substance abuse research, and it is beginning to become recognized as a valuable complement in the brain imaging toolbox that also contains positron emission tomography, single‐photon‐emission computed tomography, and functional magnetic resonance imaging. Drug abuse studies using1H MRS have identified several biochemical changes in the brain. The most consistent alterations across drug class were reductions inN‐acetylaspartate and elevations inmyo‐inositol, whereas changes in choline, creatine, and amino acid transmitters also were abundant. Together, the studies discussed herein provide evidence that drugs of abuse may have a profound effect on neuronal health, energy metabolism and maintenance, inflammatory processes, cell membrane turnover, and neurotransmission, and these biochemical changes may underlie the neuropathology within brain tissue that subsequently gives rise to the cognitive and behavioral impairments associated with drug addiction.
Agonist‐like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies
Authors: Herin David V. , Rush Craig. R. , Grabowski John
Published: January 2010

A variety of natural and synthetic agents have long been used for stimulant properties, with nontherapeutic use producing multiple waves of stimulant abuse and dependence. The multitude of effects of stimulants exist on continua, and accordingly, here we characterize stimulant abuse/dependence and candidate pharmacotherapies in this manner. Behavioral therapy and medications have been investigated for treatment of stimulant abuse/dependence. Effectiveness of some behavioral interventions has been demonstrated. Most medications studied have been found to lack efficacy. However, an expanding literature supports use of agonist‐like medications to treat stimulant abuse/dependence, a strategy effective for nicotine and opiate dependence. The agonist‐like conceptualization for stimulant dependence posits that medications with properties similar to that of the abused drug, but possessing lesser abuse liability, will normalize neurochemistry and stabilize behavior, thus reducing drug use. Data suggest use of a range of medications, froml‐dopa/carbidopa to amphetamine preparations, depending on the severity of use. This report reviews preclinical, human laboratory, and clinical trial data supporting the agonist‐like approach, including risks and benefits. Future directions for development of agonist‐like medications are also discussed.