bluuebunny/crossref_metadata_2025 huggingface dataset:
The aromatase inhibitor letrozole and inhibitors of insulin-like growth factor I receptor synergistically induce apoptosis in in vitro models of estrogen-dependent breast cancer
Authors: Lisztwan Joanna , Pornon Astrid , Chen Bin , Chen Shiuan , Evans Dean B
Published: July 2008

Introduction

Endocrine-dependent, estrogen receptor positive breast cancer cells proliferate in response to estrogens, synthesized by the cytochrome p450 aromatase enzyme. Letrozole is a potent nonsteroidal aromatase inhibitor that is registered for the treatment of postmenopausal women with advanced metastatic breast cancers and in the neoadjuvant, early, and extended adjuvant indications. Because crosstalk exists between estrogen receptor and insulin-like growth factor I receptor (IGF-IR), the effect of combining a selective IGF-IR inhibitor (NVP-AEW541) with letrozole was assessed in two independent in vitro models of estrogen-dependent breast cancer.

Methods

MCF7 and T47D cells stably expressing aromatase (MCF7/Aro and T47D/Aro) were used as in vitro models of aromatase-driven breast cancer. The role of the IGF-IR pathway in breast cancer cells stimulated only by 17β-estradiol or androstenedione was assessed by proliferation assays. The combination of letrozole and NVP-AEW541 was assessed for synergy in inhibiting cell proliferation using Chou-Talalay derived equations. Finally, combination or single agent effects on proliferation and apoptosis were assessed using proliferation assays, flow cytometry, and immunoblotting.

Results

Both MCF7 and T47D cells, as well as MCF7/Aro and T47D/Aro, exhibited sensitivity to inhibition of 17β-estradiol dependent proliferation by NVP-AEW541. Letrozole combined with NVP-AEW541 synergistically inhibited androstenedione-dependent proliferation in aromatase-expressing cells with combination index values of 0.6 or less. Synergistic combination effects correlated with higher levels of apoptosis as compared with cells treated with the single agent alone. Treatment with either agent also appeared to inhibit IGF-IR signalling via phosphoinositide 3-kinase. Notably, IGF-IR inhibition had limited effect on estrogen-dependent proliferation in the cell lines, but was clearly required for survival, suggesting that the combination of letrozole and IGF-IR inhibition sensitizes cells to apoptosis.

Conclusion

Inhibition of the IGF-IR pathway and aromatase was synergistic in two independent estrogen-dependent in vitro models of breast cancer. Moreover, synergism of NVP-AEW541 and letrozole correlated with induction of apoptosis, but not cell cycle arrest, in the cell lines tested. Combination of IGF-IR inhibitors and letrozole may hold promise for the treatment of patients with estrogen-dependent breast cancers.
Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view
Authors: Duffy Stephen W , Nagtegaal Iris D , Astley Susan M , Gillan Maureen GC , McGee Magnus A , Boggis Caroline RM , Wilson Mary , Beetles Ursula M , Griffiths Miriam A , Jain Anil K , Johnson Jill , Roberts Rita , Deans Heather , Duncan Karen A , Iyengar Geeta , Griffiths Pam M , Warwick Jane , Cuzick Jack , Gilbert Fiona J
Published: July 2008

Introduction

Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies.

Methods

Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years.

Results

Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67).

Conclusion

This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals.
Global Robust Fuzzy Sliding Mode Control for a Class of Non-Linear System
Authors: Zhang Jinggang , Jiang Kun , Chen Zhimei , Zhao Zhicheng
Published: July 2008

It is well known that sliding mode control can give good transient performance and system robustness. However, due to the sensitivity of the sliding mode control before reaching the sliding surface, the presence of chattering may introduce problems to the tracking control of the system. In this paper, a scheme of fuzzy time-varying sliding mode controller with global robustness is proposed for a class of non-linear system with uncertainties. Since the proper fuzzy logic control is applied to the time-varying sliding surface, the state of the control system always lies on the sliding surface from the beginning of any initial state and the reaching phase is avoided. As a consequence, the system is robust with respect to external disturbances and parameter uncertainties. Furthermore, the chattering phenomenon, which is inherent to a conventional sliding mode control, is avoided by proper fuzzy tuning of the controller. The effectiveness of proposed controller is demonstrated through comparative simulations for a second-order non-linear uncertain system.
A New Algorithm Based on Support Vectors and Penalty Strategy for Identifying Key Genes Related with Cancer
Authors: Wang Hong-Qiang , Li Kang
Published: July 2008

This paper proposes a new gene selection algorithm based on support vectors and penalty strategy (SVPS). In detail, cross-validation procedures are performed on training datasets, and in each validation sub-procedure, support vector machines (SVMs) are trained and tested. For each SVM, the support vectors are weighted and combined to form the initial correlation degrees of genes with the class distinction. A penalty strategy is then used to penalize these initial degrees, and the penalized degrees are finally used to produce a criterion for gene selection. The application to the leukaemia dataset shows that the proposed algorithm can identify the key genes related to the class distinction and is competitive to the existing methods.
On the origin of the Basic Variety
Authors: Comrie Bernard
Published: July 2008

Three of the points made in Klein and Perdue's paper are addressed. The presence of the basic word order Agent-Verb-Patient in the Basic Variety may simply reflect the salience of this basic word order in the target language, as is also suggested by some comparable data from creoles. Complexity can indeed arise as a language tries to pay heed to competing, if not conflicting, demands, although it can also arise as a historical accretion of changes that are in themselves simple and natural.While the Basic Variety may serve the communicative functions of true languages, it remains to be shown that it can fulfil their cognitive function.
Dose-dependent thiol and immune responses to ovalbumin challenge in Brown Norway rats
Authors: Al-Humadi Nabil H , Ma Joseph KH , Lewis Daniel M , Ma Jane YC , Barger Mark W , Siegel Paul D
Published: July 2008

Dose-dependent specific antibody production, antigen-dependent pulmonary inflammation, and thiol changes in the lung and associated lymph nodes were examined in a Brown Norway rat model of pulmonary sensitization. Cysteine (CYSH), glutathione (GSH), and markers of inflammation in bronchoalveolar lavage fluid (BALF) were measured following ovalbumin (OVA) inhalation challenge. Alveolar macrophages (AM) and pulmonary-associated lymph node cells (LNC) were isolated and intracellular CYSH and GSH assessed. OVA-specific IgE and IgG antibodies were quantified from sera. A dose-dependent biphasic response was noted with respect to OVA-specific IgE. OVA-specific IgG concentrations were maximal at 68 mg (OVA)/m3. OVA challenge to sensitized rats induced increases in BALF albumin, total protein, lactate dehydrogenase, CYSH and GSH that were independent of serum antibody concentrations. AM thiols were modestly elevated at low OVA challenge doses, but sharply reduced at the higher OVA challenge doses. In contrast, both thiols were dose dependently elevated in BALF. CYSH, but not GSH, was elevated in LNC of OVA challenged rats. In summary, antigen exposure caused a dose-dependent alteration of inflammatory, thiol and immune parameters in OVA sensitized and challenged rats. Changes in thiol levels did not correlate with antibody responses. While the results of the present study do not support a functional role for thiols in the immune response, it is important to note the dose-dependent dramatic alteration seen in thiols following sensitization and challenge.
Aluminum as a toxicant
Authors: Becaria A , Campbell A , Bondy SC
Published: July 2008

Although aluminum is the most abundant metal in nature, it has no known biological function. However, it is known that there is a causal role for aluminum in dialysis encephalopathy, microcytic anemia, and osteomalacia. Aluminum has also been proposed to play a role in the pathogenesis of Alzheimer’s disease (AD) even though this issue is controversial. The exact mechanism of aluminum toxicity is not known but accumulating evidence suggests that the metal can potentiate oxidative and inflammatory events, eventually leading to tissue damage. This review encompasses the general toxicology of aluminum with emphasis on the potential mechanisms by which it may accelerate the progression of chronic age-related neurodegenerative disorders.
Quantitative risk assessment for lung cancer after exposure to bitumen fume
Authors: Hooiveld Mariëtte , Burstyn Igor , Kromhout Hans , Heederik Dick
Published: July 2008

An international cohort of asphalt workers was assembled to study cancer risk after bitumen exposure. This article describes the combination of the exposure assessment with the exposure-response for a quantitative risk assessment for lung cancer mortality within the Dutch component of the study. We identified a retrospective cohort of 3,709 workers with at least one season of employment. Semi-quantitative exposure to bitumen fume was estimated by a job-exposure matrix. Exposure-response relations were fitted by Poisson regression, and excess lifetime risks through age 75 were calculated by a life table method. Working lifetime cumulative exposure to bitumen fume was calculated under different scenarios, representing past and future exposures. For workers with exposures accumulated in the past, excess risks for lung cancer varied from 7.8 to 14.3%. Calculations for future exposures resulted in considerably lower excess risks ranging from 0.6 to 2.6%. The calculated excess risks for lung cancer mortality after working lifetime exposure to bitumen fume depend strongly on when exposure was experienced and to some extent on the exposure-response model chosen, while confounding by smoking cannot be ruled out. Nevertheless, the excess lifetime risk for lung cancer in this Dutch cohort of asphalt workers is above benchmark risks as applied by the Dutch Health Council. Current exposure levels have decreased this risk considerably, but further exposure control may be required.
Tissue-specific patterns of neurokinin-1 receptor (NK-1R) gene expression in mice exposed to sidestream cigarette smoke
Authors: Wong Simon S , Sun Nina N , Lantz R Clark , Witten Mark L
Published: July 2008

Neurokinin-1 receptor (NK-1R), a high-affinity plasma membrane-bound receptor for neurokinin substance P, plays important roles in the onset of the pathophysiological responses. To test whether the transcript levels of gene encoding NK-1R in organs are affected by sidestream cigarette smoke (SSCS) exposure, the C57BL/6 mice were randomly assigned to five groups (six/group) in a study of the dose-effect relationship. The mice were exposed to 0 (filtered room air), 2, 4, 8 and 16 mg total particulate matter (TPM) of SSCS/exposure/day, respectively, for seven days through a nose-only exposure chamber (IN-TOX, Albuquerque, NM, USA). The levels of NK-1R mRNA in the lung, heart, liver, kidney and spleen tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) techniques and normalized against GAPDH expression. NK-1R mRNA in heart tissue showed SSCS-induced dose-dependent downregulation, with minimum expression at a dose of 8.0 mg TPM. Whereas, the levels of NK-1R mRNA in the liver were upregulated to 2.86 and 5.13- fold after exposure to 2.0 and 4.0 mg TPM of SSCS respectively, then returned to 4.19 and 3.93-fold at the exposure doses of 8.0 and 16.0 mg TPM, respectively, when compared to that of the control. In the kidney, SSCS exposure at a dose of 2.0 TPM, but not higher than that level, induced significant elevation of NK-1R mRNA expression. These findings suggest that there are the paracrine and/or autocrine signalling mechanisms through receptor -ligand interactions. No alteration of NK-1R gene expression was observed in the lungs and spleen tissues in this study. The tissue-specific patterns by which SSCS affect NK-1R gene expression in these organs may partially explain dissimilarity of NK-1R activation and the associated toxicity caused by environmental tobacco smoke.
A nonparametric changepoint model for stratifying continuous variables under order restrictions and binary outcome
Authors: Salanti Georgia , Ulm Kurt
Published: July 2008

Modelling using monotonic regression can be a useful alternative to parametric approaches when optimal stratification for continuous predictors is of interest. This method is described here in the context of binary response. Within this framework we aim to address two points. First, we propose a method to enhance the parsimony of the model, by applying a reducing procedure based on a sequence of Fisher exact tests and a bootstrap method to select between full monotonic and reduced model. Secondly, we discuss the case of multiple predictors: an iterative algorithm (an extension of the Pool Adjacent Violators Algorithm) can be applied when more than one predictor variable is taken into account. The resulting model is a monotonic surface and can be applied alternatively to the additive monotonic models as described by Morton-Jones and colleagues when the explanatory variables are assumed to interact. The monotonic-surface model provides also a multivariate extension of the monotonic likelihood ratio test. This test is discussed here and an approach based on permutations to assess the p-value is proposed. Finally, we combine both ideas (reduced monotonic regression and monotonic-surface estimation) to a simple and easy to interpret model, which leads to a combination of the predictors in a few constant risk groups. Despite the fact that the proposed approach becomes somewhat cumbersome due to the lack of asymptotic methods to infer, it is attractive because of its simplicity and stability. An application will outline the benefit of using bivariate step functions in modelling.
Pancreatic trauma
Authors: Brooks A , Shukla A , Beckingham I
Published: July 2008

Pancreatic trauma is relatively uncommon and although the surgical management is in many cases comparatively simple, occasionally complex technical surgery is required. Early diagnosis is paramount, although this remains difficult. The challenge of pancreatic trauma is compounded by a high incidence of associated injuries to adjoining organs and major vascular structures that may require damage control surgery and delayed definitive repair and add to the high frequency of postoperative complications, morbidity and mortality.
Pathophysiology and management of bowel and mesenteric injuries due to blunt trauma
Authors: Abbasakoor F , Vaizey C
Published: July 2008

Injuries to the bowel and mesentery are uncommon in blunt trauma and rarely occur in isolation. Delay to diagnosis has a significant impact on morbidity and mortality. The literature tends to focus on the diagnosis of hollow viscus and mesenteric injury, with little written on its management. Studies are usually retrospective with a paucity of comparative trials. The use of computerized tomography (CT) scanning in blunt abdominal trauma has overshadowed other reports. Early-generation scanners had a relatively poor sensitivity in detecting bowel-related injuries, but the CT scan is now the primary modality for imaging stable patients. However radiological signs can be subtle and should be regarded as complementary to meticulous clinical assessment.
Diffuse axonal injury in adults
Authors: Smith Martin
Published: July 2008

Diffuse axonal injury is a frequent component of traumatic brain injury that contributes significantly to morbidity and mortality. It encompasses a spectrum of injury from mild concussion to deep coma and death. There have been advances in our understanding of the pathophysiological processes that occur after diffuse axonal injury and ionic, immunological and genetic factors all play a role. Improvements in imaging techniques will allow more accurate diagnosis of diffuse injury in the acute phase and greater understanding of the complex pathophysiology might assist in the development of rational and specific therapies. Identification of genetic factors might also allow identification of high-risk patients who would benefit from targeted neuroprotective strategies.
High-beam headlamp usage on unlighted rural roadways
Authors: Sullivan JM , Adachi G , Mefford ML , Flannagan MJ
Published: July 2008

In a survey conducted over 34 years ago, researchers found that drivers in the United States underuse their high beams in circumstances in which their use is prudent and advisable. High-beam use was also found to be inversely related to traffic density. Since that time, changes in beam pattern design, dimming controls, and perhaps driver awareness of the hazards of limited visibility may have sufficiently altered the driver behaviour to warrant a follow-up investigation. A survey of high-beam headlamp use was conducted on three unlit local roadways in the Ann Arbor area. Observers judged whether vehicles that were clear of both oncoming and preceding traffic, had their high or low beams turned on. Illuminance measures at approximate beam pattern locations were also recorded to support beam judgments. In addition, traffic density was estimated over 15-min intervals so that the relationship between beam use and traffic density could be examined. The results suggest that the pattern of high-beam underuse is similar to that observed in the late 1960s.
Enhancement of axonal regeneration by in vitro conditioning and its inhibition by cyclopentenone prostaglandins
Authors: Tonge David , Chan Kevin , Zhu Ning , Panjwani Aliza , Arno Mathew , Lynham Steven , Ward Malcolm , Snape Alison , Pizzey John
Published: July 2008

Axonal regeneration is enhanced by the prior `conditioning' of peripheral nerve lesions. Here we show that Xenopus dorsal root ganglia (DRG) with attached peripheral nerves (PN-DRG) can be conditioned in vitro, thereafter showing enhanced neurotrophin-induced axonal growth similar to preparations conditioned by axotomy in vivo. Actinomycin D inhibits axonal outgrowth from freshly dissected PN-DRG, but not from conditioned preparations. Synthesis of mRNAs that encode proteins necessary for axonal elongation might therefore occur during the conditioning period, a suggestion that was confirmed by oligonucleotide microarray analysis. Culturing PN-DRG in a compartmentalized system showed that inhibition of protein synthesis (but not RNA synthesis) in the distal nerve impaired the conditioning response, suggesting that changes in gene expression in cultured DRG depend on the synthesis and retrograde transport of protein(s) in peripheral nerves. The culture system was also used to demonstrate retrograde axonal transport of several proteins, including thioredoxin (Trx). Cyclopentenone prostaglandins, which react with Trx, blocked the in vitro conditioning effect, whereas inhibition of other signalling pathways thought to be involved in axonal regeneration did not. This suggests that Trx and/or other targets of these electrophilic prostaglandins regulate axonal regeneration. Consistent with this hypothesis, morpholino-induced suppression of Trx expression in dissociated DRG neurons was associated with reduced neurite outgrowth.
Fabrication and optical characterization of nano-hole arrays in gold and gold/palladium films on glass
Authors: Piciu O M , Docter M W , van der Krogt M C , Garini Y , Young I T , Sarro P M , Bossche A
Published: July 2008

This paper reports on the improved fabrication process and the optical characterization of different nano-hole arrays in thin metal films that are to be integrated into a novel atto-litre titre plate device for high-speed molecular analysis, such as DNA hybridizations and protein immunoassays. The optical detection is based on the enhanced optical transmission that was recently discovered when light passes through periodically distributed sub-wavelength apertures in optically thick metal films. The transmitted light has also small angular diffraction and well-defined spectral features. Using electron-beam (e-beam) lithography (EBL) and lift-off technique, various array structures with hole diameters ranging between 100 nm and 200 nm and different pitches were fabricated in a 200-nm thick layer of gold (Au), palladium (Pd), and gold/palladium (Au/Pd = 60/40) alloy on glass. Introducing Pd to Au, the grain size of the material is decreased, getting a more well-defined shape of the holes. The transmitted spectrum was measured through periodically and randomly distributed nano-holes in Au. Transmitted spectra were compared as well through similar subwavelength hole arrays in Au, Pd, and Au/Pd alloy. Moreover, the fluorescence of Rhodamine G6 (0.05 µM) was measured when using the transmitted light through periodical cavities in Au as the illumination source. It reveals a nine-fold increase in the fluorescent signal.
Analysis of a porous inclined slider bearing lubricated with a magnetic fluid considering slip velocity
Authors: Ahmad N , Singh J P
Published: July 2008

A theoretical model of a magnetic-fluid-based porous inclined slider bearing has been considered to study the slip velocity effect on the load capacity of the bearing. The expression for load capacity has been obtained in terms of the slip parameter and the permeability parameter. The dependence of load on the magnetic parameter, the permeability parameter, and the slip parameter has been studied graphically. Minimization of the slip parameter and the permeability parameter have been discussed for the possible increase in load capacity.
Synthesis of High-silica CHA Zeolite from FAU Zeolite in the Presence of Benzyltrimethylammonium Hydroxide
Authors: Itakura Masaya , Inoue Takayuki , Takahashi Atsushi , Fujitani Tadahiro , Oumi Yasunori , Sano Tsuneji
Published: July 2008

A highly crystalline and pure high-silica chabazite zeolite with a Si/Al ratio of ca. 17 was obtained by the hydrothermal conversion of FAU zeolite used as a crystalline Si/Al source in benzyltrimethylammonium hydroxide media.
Photoresponsive Fluorescence Color Change Derived from TICT in an Organogel System
Authors: Kitahara Tatsuya , Fujita Norifumi , Shinkai Seiji
Published: July 2008

A novel gelator containing 9-(9′-acridyl)carbazole (TICT probe) and azobenzene within a molecule was synthesized and the photoresponsive gel properties were investigated by spectroscopic analyses; it showed an interesting photoinduced fluorescence wavelength change, which leads to a potential development toward a new type of optical information materials.
Silicon-containing Bilayer Resist Based on a Single Component Nonchemically Amplified Resist System
Authors: Park Ji Young , Kim Jin-Baek
Published: July 2008

A photobleachable bilayer resist material based on a nonchemically amplified resist system was synthesized by copolymerization of 3-methacryloxypropyl trimethoxysilane, 2-(2-diazo-3-oxobutyryloxy)ethyl methacrylate, and γ-butyrolactonyl methacrylate. Upon UV irradiation, the resist film in the exposed region become insoluble in organic solvent by the reaction of methoxysilanes with carboxylic acids generated by photoinduced reaction of diazoketo groups. The initial lithographic evaluation of the resist showed the potential of this system for the next generation resist.
Magnetically Retrievable Palladium/Maghemite Nanocomposite Catalysts Prepared by Sonochemical Reduction Method
Authors: Mizukoshi Yoshiteru , Sato Kazuhisa , Konno Toyohiko J , Masahashi Naoya , Tanabe Shuji
Published: July 2008

Nanocomposite catalysts, consisting of Pd and magnetic maghemite, prepared by sonochemical reduction method showed high catalytic activities for the reduction of nitrobenzene. The used catalysts could be readily retrieved by magnets and be employed for further repetitive tests and verified the durability of the catalytic performance.
The case for social marketing in gonorrhoea prevention: insights from sexual lifestyles in Glasgow genitourinary medicine clinic attendees
Authors: Scoular Anne , Abu-Rajab Kirsty , Winter Andy , Connell Judith , Hart Graham
Published: July 2008

We conducted a matched case-control study to investigate social factors associated with gonorrhoea acquisition among genitourinary (GU) medicine clinic attendees, designed to inform appropriate prevention strategies. Detailed social and behavioural data were elicited using a self-completed questionnaire. The effect sizes of these characteristics were quantified using univariate and multivariable conditional logistic regression in 53 cases and 106 matched controls. Homo-bisexual orientation was the strongest independent predictor of gonorrhoea acquisition (Adjusted odds ratio 31.1 (95% confidence intervals, 3.09-312.92). Other independent predictors were not currently being in a relationship and concordant residential characteristics. Three principal implications for sexual health policy were identified; social marketing approaches to gonorrhoea prevention should focus on gay men and individuals not in established relationships; gonorrhoea prevention should be more closely integrated with wider social inclusion policies; finally, more proactive, systematic and theory-based approaches should capitalize on opportunities for sexual health promotion in GU medicine clinic settings.
Physical activity uptake in patients with HIV: who does how much?
Authors: Fillipas S , Bowtell-Harris C A , Oldmeadow L B , Cicuttini F , Holland A E , Cherry C L
Published: July 2008

Regular physical activity is recommended for patients with human immunodeficiency virus (HIV) to help manage their disease. However, to date, little is known about levels of uptake of this advice. This study describes daily physical activity in HIV antibody-positive patients attending a public hospital infectious diseases clinic, compares them with those of patients attending the clinic for general infectious diseases and investigates compliance with the recommendations of the Centres for Disease Control and Prevention and American College of Sports Medicine physical activity guidelines. During April 2006, 261 patients completed the International Physical Activity Questionnaire short form. One hundred and ninety-one reported being HIV antibody-positive. Results showed that 1:4 HIV antibody-positive and 1:3 HIV antibody-negative respondents failed to meet the recommended guidelines. These findings are of concern, given the evidence-based benefits of regular physical activity. Further work is needed to identify barriers to participation and interventions that can improve uptake.
Evaluation of a home-delivery service for HIV-infected patients attending an inner London HIV treatment centre
Authors: Harte D , Hamill M , Edwards S G , Copas A J , Minton J , Jones V L , Allason-Jones E , Williams I G , Miller R F
Published: July 2008

Home delivery (HD) of medication is a goal of the Department of Health's Pharmacy in the Future; Implementing the NHS Plan. We evaluated the safety and effectiveness of an HD service for antiretroviral therapy (ART). Patients on ART with stable viral load (VL) <50 were identified. Comparison was made between patients using HD and those using the clinic-based pharmacy (CP). The primary endpoint was HIV virological failure (VF) (HIV VL >400 copies/mL on two consecutive occasions). Secondary endpoints included frequency of outpatient attendances (OPA) and an incidence of adverse events. Cumulative incidences (Culmln) for each outcome event were calculated. Incidence-rate ratios (IRR) were obtained using Poisson regression. Of 1663 patients identified; 450 received HD and 1213 used CP. Culmln of VF was =4% in those using HD and =7% in those using CP (IRR [95% confidence intervals, CI] =0.53, 0.32-0.90). HD patients had fewer OPA, less frequent blood test monitoring and less frequent abnormal liver function results (IRR [95% Cl]= 0.63 [0.59-0.67] and 0.59 [0.53-0.67], 0.68 [0.65-0.71] and 0.64 [0.53-0.78], respectively). Patients deemed stable enough on social, psychological and medical grounds to receive HD of ART had a lower risk of VF, fewer OPA and no increase in adverse events when compared with patients using CP.
High plasma activity of endogenous antioxidants protect CD4+ T-cells in HIV-serodiscordant heterosexual partners in a Nigerian population
Authors: O Ibeh Bartholomew , Obidoa Onyechi , Uzoegwu Peter N
Published: July 2008

Antioxidants significantly inhibit oxidative processes. The study seeks to determine the activity of endogenous antioxidants and CD4+ T-cell expression in HIV-serodiscordant-heterosexual partners. The case-control study had the following groups; A- (13 serodiscordant-seronegative subjects), B- (13 serodiscordant-seropositive subjects) and C/control- (13 healthy volunteers). CD4+ T-cell expression was determined using a FACScan (fluorescent activated cell sorting) flow cytometer. CAT (catalase), superoxide dismutase, glutathione peroxidase (GHPX) and glutathione S-transferase (GST) activities were assayed using spectrophotometer. The activities of SOD, GHPX, GST and CAT were significantly ( P < 0.05) increased by 164.7% (0.090 ± 0.032), 126% (662 + 96), 355.2% (22.023 ± 1.4) and 119.1 % (2.76 ± 0.10), respectively, in group A when compared with B. The mean CD4+ T-cell (1348 ± 142) showed a significant ( P < 0.05) increase by 237% when compared with group B (400 ± 182). Conversely, group B revealed a significant ( P < 0.05) decrease in activity by 86.5% (CAT), 76.5% (SOD), 106.8% (GHPX) and 81.8% (GST) when compared with C. CD4+ T-cells in groups A and C (1390 ± 190) did not show any significant decrease (3.11 %). The antioxidant activity showed a positive correlation ( P < 0.01, r = 0.89) with their respective CD4+ T-cells in groups A and C. Group B showed same positive correlation ( P < 0.01, r = 0.76). These results show that high activity of endogenous antioxidants may have a protective role on CD4+ T-cells, which limits HIV infection.
Unusual transmission route of Lymphogranuloma venereum; following sexual contact with a female donkey
Authors: Khorvash Farzin , Keshteli Ammar H , Salehi Hassan , Szeredi Levente , MorrÉ Servaas A
Published: July 2008

Here, we present a 20-year-old man who presented with painful inguinal and femoral masses. He gave a history of sexual contact with a mare 14 days before his recent illness. He was diagnosed with lymphogranuloma venereum based on the histopathological findings and a high titre of IgG (1:1400).
Monocusp – novel common femoral vein monocusp surgery uncorrectable chronic venous insufficiency with aplastic/dysplastic valves
Authors: Opie J C , Izdebski T , Payne D N , Opie S R
Published: July 2008

Objective

Previous reparative valvular surgical options directed at reconstructing damaged common femoral vein (CFV) valves associated with pathological chronic venous insufficiency (CVI) have not succeeded in reliably managing CVI. In consequence, venous valvuloplasty is rare and most patients are managed conservatively. As a result, monocusp surgery was identified as an optional surgical solution for this large underserved patient group.

Methods

Ulcer patients appear at wound clinics and often experience disappointing results. Monocusp valves were constructed utilizing viable vein wall in 14 operations on 11 patients. These patients were observed for four years to see if such an autogenous vein wall valve might control aggressive symptomatic CVI when faced with unusable valves.

Results

Long-term follow-up showed that the monocusp valves remained competent at four years. Symptomatic failures have not appeared at this time. Pain, swelling, ulcers and leg congestion were reliably reversed. VEnous INsufficiency Epidemiologic and Economic Study (VEINES) classification (see Abenhaim L, Krux X, VIENES Study collaborators. Angiology 1997;48:59 and Kurz X, Kahn SR, Abenhaim L, et al. Int Angiol 1999;18:83–102) improved over four years from 2.7 ± 0.9 to 0 ( P < 0.001); CEAP classifications (see Kistner RL, Eklof B, Masuda EM. Mayo Clin Proc 1996;71:338–45) improved from grade 4–6 to 0–1 (CEAP is not generally a postoperative grading system, but it can be used to develop some form of qualitative analyses as to intervention effectiveness, i.e. what existed preoperatively no longer exists postoperatively. Its postsurgery use is limited by (C5) classification – history of ulcer, which by definition cannot go below that with a history of ulcer even if the ulcer has been cured). Mean venous reflux scores decreased from 3.8 ± 0.4 to 0.3 ± 0.5 ( P < 0.001).

Conclusion

Monocusp implantation reliably resolved patient symptoms when unusable CFV valves were encountered. Postoperative CFV reflux is usually undetectable. The monocusp valve exhibits minimal thrombogenicity related to its viability with attendant antithrombotic hormone production capacity and has markedly improved the patient's quality of life. Full thickness monocusp surgery could become widespread with the difficult dysplastic/aplastic CVI patient subset because of its simplicity, repeatability, durability, low complication rate, effectiveness, persistent availability and viability providing nitric oxide synthase and thymomodulin hormone production capacity. The full thickness of vein wall has distinct advantages over other partial thickness valve creation methods because of its long-term vitality. Postoperative coumadin is recommended for six months to minimize risks of deep vein thrombosis and/or pulmonary embolism.
A new regulatory circuit in ribosomal protein operons: S2-mediated control of the rpsB-tsf expression in vivo
Authors: Aseev Leonid V. , Levandovskaya Alexandrina A. , Tchufistova Ludmila S. , Scaptsova Nadezda V. , Boni Irina V.
Published: July 2008

Autogenous regulation is a general strategy of balancing ribosomal protein synthesis in bacteria. Control mechanisms have been studied in detail for most of ribosomal protein operons, except for rpsB-tsf encoding essential r-protein S2 and elongation factor Ts, where even the promoter has remained unknown. By using single-copy translational fusions with the chromosomal lacZ gene and Western-blot analysis, we demonstrate here that S2 serves as a negative regulator of both rpsB and tsf expression in vivo, acting at a single target within the rpsB 5′-untranslated region (5′-UTR). As determined by primer extension, transcription of the Escherichia coli rpsB-tsf operon starts 162 nucleotides upstream of the rpsB initiation codon at a single promoter TGTGGTATAAA belonging to the extended −10 promoter class. Both the promoter signature and the 5′-UTR structure of the rpsB gene appear to be highly conserved in γ-proteobacteria. Deletion analysis of the rpsB 5′-UTR within rpsB′-′lacZ fusions has revealed that an operator region involved in the S2 autoregulation comprises conserved structural elements located upstream of the rpsB ribosome binding site. The S2-mediated autogenous control is impaired in rpsB mutants and, more surprisingly, in the rpsA mutant producing decreased amounts of truncated r-protein S1 (rpsA∷IS10), indicating that S2 might act as a repressor in cooperation with S1.
Cyber Bullying: Overview and Strategies for School Counsellors, Guidance Officers, and All School Personnel
Authors: Bhat Christine Suniti
Published: July 2008

Cyber bullying or bullying via information and communications technology tools such as the internet and mobile phones is a problem of growing concern with school-aged students. Cyber bullying actions may not take place on school premises, but detrimental effects are experienced by victims of cyber bullying in schools. Tools used by cyber bullies are presented and the impact on victims is discussed. Intervention strategies for school counsellors, guidance officers, and school personnel to adopt with students and parents are presented.
Dynamic Interaction between P-Bodies and Transport Ribonucleoprotein Particles in Dendrites of Mature Hippocampal Neurons
Authors: Zeitelhofer Manuel , Karra Daniela , Macchi Paolo , Tolino Marco , Thomas Sabine , Schwarz Martina , Kiebler Michael , Dahm Ralf
Published: July 2008

The dendritic localization of mRNAs and their subsequent translation at stimulated synapses contributes to the experience-dependent remodeling of synapses and thereby to the establishment of long-term memory. Localized mRNAs are transported in a translationally silent manner to distal dendrites in specific ribonucleoprotein particles (RNPs), termed transport RNPs. A recent study suggested that processing bodies (P-bodies), which have recently been identified as sites of RNA degradation and translational control in eukaryotic cells, may participate in the translational control of dendritically localized mRNAs inDrosophilaneurons. This study raised the interesting question of whether dendritic transport RNPs are distinct from P-bodies or whether those structures share significant overlap in their molecular composition in mammalian neurons. Here, we show that P-body and transport RNP markers do not colocalize and are not transported together in the same particles in dendrites of mammalian neurons. Detailed time-lapse videomicroscopy analyses reveal, however, that both P-bodies and transport RNPs can interact in a dynamic manner via docking. Docking is a frequent event involving as much as 50% of all dendritic P-bodies. Chemically induced neuronal activity results in a 60% decrease in the number of P-bodies in dendrites, suggesting that P-bodies disassemble after synaptic stimulation. Our data lend support to the exciting hypothesis that dendritically localized mRNAs might be stored in P-bodies and be released and possibly translated when synapses become activated.
Neuroinflammation and Oxidation/Nitration of α-Synuclein Linked to Dopaminergic Neurodegeneration
Authors: Gao Hui-Ming , Kotzbauer Paul T. , Uryu Kunihiro , Leight Susan , Trojanowski John Q. , Lee Virginia M.-Y.
Published: July 2008

α-Synuclein (SYN) is the major component of Lewy bodies, the neuropathological hallmarks of Parkinson's disease (PD). Missense mutations and multiplications of the SYN gene cause autosomal dominant inherited PD. Thus, SYN is implicated in the pathogenesis of PD. However, the mechanism whereby SYN promotes neurodegeneration remains unclear. Familial PD with SYN gene mutations are rare because the majority of PD is sporadic and emerging evidence indicates that sporadic PD may result from genetic and environmental risk factors including neuroinflammation. Hence, we examined the relationship between SYN dysfunction and neuroinflammation in mediating dopaminergic neurodegeneration in mice and dopaminergic neuronal cultures derived from wild-type SYN and mutant A53T SYN transgenic mice in a murine SYN-null (SYNKO) background (M7KO and M83KO, respectively). Stereotaxic injection of an inflammagen, lipopolysaccharide, into substantia nigra of these SYN genetically engineered mice induced similar inflammatory reactions. In M7KO and M83KO, but not in SYNKO mice, the neuroinflammation was associated with dopaminergic neuronal death and the accumulation of insoluble aggregated SYN as cytoplasmic inclusions in nigral neurons. Nitrated/oxidized SYN was detected in these inclusions and abatement of microglia-derived nitric oxide and superoxide provided significant neuroprotection in neuron–glia cultures from M7KO mice. These data suggest that nitric oxide and superoxide released by activated microglia may be mediators that link inflammation and abnormal SYN in mechanisms of PD neurodegeneration. This study advances understanding of the role of neuroinflammation and abnormal SYN in the pathogenesis of PD and opens new avenues for the discovery of more effective therapies for PD.
Satellite NG2 Progenitor Cells Share Common Glutamatergic Inputs with Associated Interneurons in the Mouse Dentate Gyrus
Authors: Mangin Jean-Marie , Kunze Albrecht , Chittajallu Ramesh , Gallo Vittorio
Published: July 2008

Several studies have provided evidence that NG2-expressing (NG2+) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2+cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2+cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2+cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2+cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2+cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2+cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 μm. The finding that NG2+cells are sensing patterns of activity arising in closely associated neurons suggests that NG2+cell function is finely regulated by the local network.
Analysis of Peripheral Nerve Expression Profiles Identifies a Novel Myelin Glycoprotein, MP11
Authors: Ryu Elizabeth J. , Yang Mao , Gustin Jason A. , Chang Li-Wei , Freimuth Robert R. , Nagarajan Rakesh , Milbrandt Jeffrey
Published: July 2008

The myelin sheath insulates axons and allows for rapid salutatory conduction in the nervous system of all vertebrates. The formation of peripheral myelin requires expression of the transcription factor Egr2, which is responsible for inducing such essential myelin-associated genes asMpz,Mbp,Pmp22, andMag. Using microarray analysis to compare gene expression patterns in peripheral nerve during development, during remyelination after nerve injury, and in a congenital hypomyelinating mouse model, we identified an evolutionarily conserved novel component of myelin called Mp11 (myelin protein of 11 kDa). The Mp11 genomic locus contains multiple conserved Egr binding sites, and Mp11 induction is regulated by the expression of Egr2. Similar to other Egr2-dependent genes, it is induced during developmental myelination and remyelination after nerve injury. Mp11 is a glycoprotein expressed preferentially in the myelin of the peripheral nervous system versus CNS and is specifically localized to the Schmidt-Lanterman incisures and paranodes of peripheral nerve. The Mp11 protein contains no identifiable similarity to other known protein domains or motifs. However, like other myelin genes, strict Mp11 expression levels are a requirement for thein vitromyelination of DRG neurons, indicating that this previously uncharacterized gene product is a critical component of peripheral nervous system myelin.
A Role for Polymodal C-Fiber Afferents in Nonhistaminergic Itch
Authors: Johanek Lisa M. , Meyer Richard A. , Friedman Robert M. , Greenquist Kenneth W. , Shim Beom , Borzan Jasenka , Hartke Tim , LaMotte Robert H. , Ringkamp Matthias
Published: July 2008

Recent psychophysical and electrophysiological studies in humans suggest the existence of two peripheral pathways for itch, one that is responsive to histamine and a second pathway that can be activated by nonhistaminergic pruritogens (e.g., cowhage spicules). To explore the peripheral neuronal pathway for nonhistaminergic itch, behavioral responses and neuronal activity in unmyelinated afferent fibers were assessed in monkey after topical application of cowhage spicules or intradermal injection of histamine and capsaicin. Cowhage and histamine, but not capsaicin, evoked scratching behavior indicating the presence of itch. In single-fiber recordings, cowhage, histamine and/or capsaicin were applied to the cutaneous receptive field of 43 mechano-heat-sensitive C-fiber (CMH) nociceptors. The majority of CMHs exhibited a prolonged response to cowhage (39 of 43) or histamine (29 of 38), but not to capsaicin (3 of 34). Seven CMHs were activated by cowhage but not histamine. The average response to cowhage was more than twice the response to histamine, and responses were not correlated. The response of the CMHs to a stepped heat stimulus (49°C, 3 s) was either quickly adapting (QC) or slowly adapting (SC). In contrast, the cowhage response was characterized by bursts of two or more action potentials (at ∼1 Hz). The total cowhage response of the QC fibers (97 action potentials/5 min) was twice that of the SC fibers (49 action potentials/5 min). A subset of QC fibers exhibited high-frequency intraburst discharges (∼30 Hz). These results suggest multiple mechanisms by which CMHs may encode itch to cowhage as well as pain to mechanical and heat stimuli.