bluuebunny/crossref_metadata_2025 huggingface dataset:
The implications of a growing evidence base for drug use in elderly patients. Part 1. Statins for primary and secondary cardiovascular prevention
Authors: Mangoni A. A. , Jackson S. H. D.
Published: March 2006

Although elderly patients represent a rapidly growing population often requiring multiple drug treatment, the evidence of effectiveness is limited for many interventions and therapies in this age group. Only during the last 30 years has a requirement to incorporate evidence into the treatment of older subjects become part of the pre‐ and postmarketing regulatory process in Europe and the United States. Recently, elderly patients have been shown to benefit comparably from several treatments. These studies have supported the validity of an increasingly interventional approach to disorders common in late life. However, an important issue is the applicability of the growing body of clinical trials to ‘real life’ patients. This is particularly true in very old (i.e. >80 years) patients and those with significant comorbidities. We review the current evidence and controversies related to the effectiveness and safety of several therapeutic strategies in cardiovascular disease (i.e. statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, β‐adrenoceptor blockers, and thrombolytic agents) and bone health (i.e. vitamin D and bisphosphonates).
The implications of a growing evidence base for drug use in elderly patients Part 2 − ACE inhibitors and angiotensin receptor blockers in heart failure and high cardiovascular risk patients
Authors: Mangoni A. A. , Jackson S. H. D.
Published: March 2006

Traditionally, angiotensin converting enzyme (ACE) inhibitors have been used for the management of patients with congestive cardiac failure. Studies performed over the last decade have demonstrated that (1) angiotensin receptor blockers (ARBs) are as effective as ACE inhibitors in reducing morbidity and mortality in cardiac failure; and (2) inhibition of the renin‐angiotensin system provides beneficial effects in patients at high cardiovascular risk without cardiac failure. This review focuses on the applicability of the results of the main trials with ACE inhibitors and ARBs to the elderly population.
The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis
Authors: Dhesi J. K. , Allain T. J. , Mangoni A. A. , Jackson S. H. D.
Published: March 2006

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age‐related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients.
Access to emergency hormonal contraception from community pharmacies and family planning clinics
Authors: Lewington Gaye , Marshall Kay
Published: March 2006

Aims To evaluate differences in the time taken to access progestogen‐only emergency hormonal contraception (EHC) by young women from family planning (FP) or community pharmacy settings.

Methods An observational study of 203 women requesting EHC from FP clinics and community pharmacies in South‐west Kent Primary Care Trust (PCT) from December 2002 to October 2003.

Results Access to EHC from community pharmacy was significantly faster than from FP clinics (16 h vs. 41 h, P < 0.001). Older teenagers tended to seek EHC more quickly and were more likely to have had a contraceptive failure rather than have used no contraception at all.

Conclusion The results provide further support for pharmacist involvement in the supply of EHC.
Paroxetine: population pharmacokinetic analysis in late‐life depression using sparse concentration sampling
Authors: Feng Yan , Pollock Bruce G. , Ferrell Robert E. , Kimak Mark A. , Iii Charles F. Reynolds , Bies Robert R.
Published: March 2006

Aim

To develop a population pharmacokinetic (PK) model using sparse sampling of long‐term treatment with paroxetine in elderly depressed subjects, incorporating CYP2D6 genotype as well as other covariates.

Methods

Elderly subjects (age ≥ 70 years) with nonpsychotic, nonbipolar major depressive disorder from the inpatient and outpatient clinic were treated with paroxetine in a 5‐year clinical trial investigating ‘Maintenance Therapies in Late‐Life Depression’ (MTLD‐2). Plasma concentrations were collected during regular visits. CYP2D6 genotype was determined using polymerase chain reaction (PCR) for each individual. A nonlinear mixed‐effects model was developed with NONMEM® for these subjects who received 10–40 mg day−1 of paroxetine during treatment. One‐ and two‐compartment models with linear and nonlinear elimination (Michaelis–Menten) were evaluated. PK parameters as well as interindividual and residual variability were estimated. The effects of age, weight, sex, race and CYP2D6 genotypes on the pharmacokinetics of paroxetine were evaluated.

Results

One hundred and seventy‐one subjects with a mean age of 77 years (range 69–95) and a mean weight of 72.0 kg (range 32.9–137.0) were enrolled in the MTLD‐2 clinical trial. A total of 1970 paroxetine concentrations were available for population PK analyses. Approximately 10 samples were taken per subject. A two‐compartment nonlinear PK model with additive and proportional error provided the best base model for description of the data. Weight and CYP2D6 polymorphisms were found to have a significant effect on maximal velocity (Vm), whereas sex had an effect on volume of distribution of the central compartment. The Vm estimates in each of the CYP2D6 phenotypic groups were: 125 µg h−1 in poor metabolizer (n = 1), 182 µg h−1 in intermediate metabolizers (n = 28), 454 µg h−1 in extensive metabolizers (n = 36) and 3670 µg h−1 in ultra‐rapid metabolizers (n = 5).

Conclusions

The population PK model adequately described paroxetine data in this elderly depressed population. The data indicate that female and male subjects with different CYP2D6 polymorphisms have different elimination rates and therefore may need to be dosed differently based on metabolizer genotype.
Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother‐infant pairs
Authors: Gardiner Sharon J. , Gearry Richard B. , Roberts Rebecca L. , Zhang Mei , Barclay Murray L. , Begg Evan J.
Published: March 2006

Aims

To determine infant exposure to 6‐thioguanine and 6‐methylmercaptopurine nucleotides (6‐TGN and 6‐MMPN, respectively) during maternal use of azathioprine in breastfeeding.

Methods

Mother‐infant pairs provided blood for determination of 6‐TGN and 6‐MMPN concentrations, and TPMT genotype.

Results

Four women taking azathioprine 1.2–2.1 mg kg−1 day−1 and their infants were studied. All had the wild‐type TPMT genotype. Maternal 6‐TGN and 6‐MMPN concentrations ranged from 234 to 291 and 284 to 1178 pmol per 8 × 108 red blood cells, respectively, and were consistent with those associated with improved therapeutic outcomes. Neither 6‐TGN nor 6‐MMPN was detected in any of the infants, despite a sensitive assay.

Conclusions

The data suggest that azathioprine may be ‘safe’ during breastfeeding in patients with the wild‐type TPMT genotype (∼90% of caucasian patients) taking ‘normal’ doses.
A polymorphism of MS4A2 (−109T>C) encoding the β‐chain of the high‐affinity immunoglobulin E receptor (FcɛR1β) is associated with a susceptibility to aspirin‐intolerant asthma
Authors: Kim S. ‐H. , Bae J. ‐S. , Holloway J. W. , Lee J. ‐T. , Suh C. ‐H. , Nahm D. ‐H. , Park H. ‐S.
Published: March 2006

Background and objective
The MS4A2 gene, the β chain of the high‐affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The β‐chain of FcɛR1 enhances receptor maturation and signal transduction capacity, leading to the release of proinflammatory mediators and cytokines that can exacerbate the symptom of asthma. This study was performed to evaluate whether two genetic polymorphisms of the FcɛR1β gene (FcɛR1β−109T>C and FcɛR1β E237G) are associated with aspirin‐intolerant asthma (AIA).

Methods
The MS4A2 gene polymorphisms (FcɛR1β−109T>C and FcɛR1β E237G) were determined by SNP‐IT™ assays in patients with AIA (N=164), aspirin‐tolerant asthma (ATA, N=144) and normal controls (NC, N=264) recruited from a Korean population.

Results
The genotype frequencies of FcɛR1β−109T>C and E237G polymorphisms were not significantly associated with the pathogenesis of AIA. However, FcɛR1β−109T>C polymorphism was significantly associated with the presence of specific IgE to Staphylococcal enterotoxin B (SEB); the number of subjects carrying both homozygous TT genotype of FcɛR1β−109T>C and specific IgE to SEB was significantly higher in the AIA group when compared with the other control groups (P=0.01, odds ratio (OR)=7.723, 95% confidence interval (CI)=1.327–39.860 for AIA vs. ATA; P=0.02, OR=6.364, 95% CI=1.149∼35.229 for AIA vs. NC). In addition, luciferase reporter assays also showed that the FcɛR1β−109T allele was associated with higher promoter activity of MS4A2 in both RBL‐2H3 and A549 cell lines.

Conclusion
FcɛR1β−109T>C polymorphism may increase expression of MS4A2 by mast cells, leading to enhanced release of proinflammatory mediators in the asthmatic airway, contributing to increased susceptibility to AIA.
The DnaA homolog of the hyperthermophilic eubacterium Thermotoga maritima forms an open complex with a minimal 149‐bp origin region in an ATP‐dependent manner
Authors: Ozaki Shogo , Fujimitsu Kazuyuki , Kurumizaka Hitoshi , Katayama Tsutomu
Published: February 2006

In Escherichia coli, ATP‐DnaA, but not ADP‐DnaA, forms an initiation complex that undergoes site‐specific duplex DNA unwinding, open complex formation. However, it remains unclear how highly the ATP‐dependent activation of the initiation factor is conserved in evolution. The hyperthermophile Thermotoga maritima is one of the most ancient eubacteria in evolution. Here, we show that the DnaA homolog (tmaDnaA) of this bacterium forms open complexes with the predicted origin region (tma‐oriC) in vitro. TmaDnaA has a strong and specific affinity for ATP/ADP as well as for 12‐mer repeating sequences within the tma‐oriC. Unlike ADP‐tmaDnaA, ATP‐tmaDnaA is highly cooperative in DNA binding and forms open complexes in a manner that depends on temperature and the superhelical tension of the tma‐oriC‐bearing plasmid. The minimal tma‐oriC required for unwinding is a 149‐bp region containing five repeats of the 12‐mer sequence and two AT‐rich 9‐mer repeats. TmaDnaA‐binding to the 12‐mer motif provokes DNA bending. The 9‐mer region is the duplex‐unwinding site. The tmaDnaA‐binding and unwinding motifs of tma‐oriC share sequence homology with corresponding archaeal and eukaryotic sequences. These findings suggest that the ATP‐dependent molecular switch of the initiator and the mechanisms in the replication initiation complex are highly conserved in eubacterial evolution.
TFII‐I down‐regulates a subset of estrogen‐responsive genes through its interaction with an initiator element and estrogen receptor α
Authors: Ogura Yuji , Azuma Motoki , Tsuboi Yasunori , Kabe Yasuaki , Yamaguchi Yuki , Wada Tadashi , Watanabe Hajime , Handa Hiroshi
Published: February 2006

TFII‐I was initially identified as the general transcription factor that binds to initiator (Inr) elements in vitro. Subsequent studies have shown that TFII‐I activates transcription of various genes either through Inr elements or through other upstream elements in vivo. Since, however, most studies so far on TFII‐I have been limited to over‐expression and reporter gene assays, we reevaluated the role of TFII‐I in vivo by using stable knockdown with siRNA and by examining the expression of endogenous genes. Contrary to the widely accepted view, here we show that TFII‐I is not important for cell viability in general but rather inhibits the growth of MCF‐7 human breast cancer cells. MCF‐7 cells are known to proliferate in an estrogen‐dependent manner. Through analysis of TFII‐I's cell‐type specific growth inhibitory effect, we show evidence that TFII‐I down‐regulates a subset of estrogen‐responsive genes, only those containing Inr elements, by recruiting estrogen receptor (ER) α and corepressors to these promoters. Thus, this study has revealed an unexpected new role of TFII‐I as a negative regulator of transcription and cell proliferation
The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila
Authors: Brun Sylvain , Vidal Sheila , Spellman Paul , Takahashi Kuniaki , Tricoire Hervé , Lemaitre Bruno
Published: February 2006

Septic injury triggers a rapid and widespread response in Drosophila adults that involves the up‐regulation of many genes required to combat infection and for wound healing. Genome‐wide expression profiling has already demonstrated that this response is controlled by signaling through the Toll, Imd, JAK‐STAT and JNK pathways. Using oligonucleotide microarrays, we now demonstrate that the MAPKKK Mekk1 regulates a small subset of genes induced by septic injury including Turandot (Tot) stress genes. Our analysis indicates that Tot genes show a complex regulation pattern including signals from both the JAK‐STAT and Imd pathways and Mekk1. Interestingly, Mekk1 flies are resistant to microbial infection but susceptible to paraquat, an inducer of oxidative stress. These results point to a role of Mekk1 in the protection against tissue damage and/or protein degradation and indicate complex interactions between stress and immune pathways in Drosophila.
Human scribble, a novel tumor suppressor identified as a target of high‐risk HPV E6 for ubiquitin‐mediated degradation, interacts with adenomatous polyposis coli
Authors: Takizawa Shin , Nagasaka Kazunori , Nakagawa Shunsuke , Yano Tetsu , Nakagawa Keiichi , Yasugi Toshiharu , Takeuchi Takamasa , Kanda Tadahito , Huibregtse Jon M. , Akiyama Tetsu , Taketani Yuji
Published: February 2006

Recently, we have identified human scribble (hScrib), human homolog of the Drosophila tumor suppressor Scribble, as a substrate of human papillomavirus E6 oncoproteins for ubiquitin‐mediated degradation dependent on ubiquitin‐protein ligase E6AP. Human Scribble, classified as a LAP protein containing leucine‐rich repeats and PDZ domains, interacts with E6 through its PDZ domains and C‐terminal PDZ domain‐binding motif of E6 protein. Interaction between human Discs Large (hDlg), which is a substrate of E6 for the ubiquitin‐mediated degradation, and adenomatous polyposis coli (APC) has been shown. Here, we investigated whether hScrib and APC interact with each other in vitro and in vivo. Interaction between hScrib and APC is mediated by the PDZ domains 1 and 4 of hScrib and C‐terminal PDZ domain‐binding motif of APC. Human Scribble co‐localized with APC at the synaptic sites of hippocampal neuron and at the tip of membrane protrusion in the epithelial cell line. Interference of the interaction between hScrib and APC caused disruption of adherens junction. Knockdown of hScrib expression by RNAi disrupts localization of APC at the adherens junction. These data suggest that hScrib may participate in the hDlg‐APC complex through its PDZ domains and regulate cell cycle and neural function by associating with APC.
Fibrosis in heart disease: understanding the role of transforming growth factor‐β1 in cardiomyopathy, valvular disease and arrhythmia
Authors: Khan Razi , Sheppard Richard
Published: March 2006

The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor‐β1 (TGF‐β1), a potent stimulator of collagen‐producing cardiac fibroblasts. Previously, TGF‐β1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF‐β1. In fact, the pathogenic effects of TGF‐β1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF‐β1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF‐β1 not only in the post‐ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF‐β1 is an appropriate target for therapy in a variety of cardiovascular diseases.
Oestradiol potentiates the suppressive function of human CD4+ CD25+ regulatory T cells by promoting their proliferation
Authors: Prieto G. Aleph , Rosenstein Yvonne
Published: March 2006

CD4+ CD25+ regulatory T (Treg) cells play an important role in the control of the immune system by suppressing the proliferation of effector cells, thereby preventing autoreactive, unnecessary or inconvenient responses. Recently, it has been shown that the number of Treg cells increases during pregnancy, a period with high serum levels of female sex hormones. Oestrogen replacement therapy has been reported to alleviate the symptoms of autoimmune diseases, yet the cellular and molecular mechanisms involved are not fully understood. Here, we show that physiological doses of oestradiol (E2) found during pregnancy, combined with activation through CD3/CD28 engagement, promoted the proliferation of Treg cells without altering their suppressive phenotype. Enhanced suppression was detected when Treg cells were pretreated with the hormone as well as when both cell subpopulations (Treg and T effector) were exposed to E2 throughout the experiment. Together, these data suggest that when combined with an activating stimulus, E2 can modulate the function of human Treg cells by regulating their numbers, and highlight a potential use of E2, or its analogs, to manipulate Treg function.
Waiting in line for online services: a qualitative study of the user's perspective
Authors: Ryan Gerard , Valverde Mireia
Published: March 2006

Abstract. This manuscript is conceptually based in the areas of e‐consumer behaviour and e‐services marketing. Specifically, it examines the phenomenon of waiting in terms of the role it plays in the functionality of service delivery over the internet and the effect waiting has on how consumers behave online. A number of previous studies have identified a link between the ‘quickness’ of web sites and the site's overall functionality. The existing knowledge on consumer waiting behaviour in the general context of traditional or ‘off‐line’ services and in the specific context of online services is reviewed. A qualitative empirical study of consumer behaviour in online waiting situations is undertaken. The factors that determine how e‐consumers behave when faced with online waiting situations are identified and explored.
Failure mechanism of ProTaper Ni–Ti rotary instruments during clinical use: fractographic analysis
Authors: Spanaki‐Voreadi A. P. , Kerezoudis N. P. , Zinelis S.
Published: February 2006

Aim  To evaluate the failure mechanism of ProTaper Ni–Ti rotary instruments fractured under clinical conditions.

Methodology  A total of 46 ProTaper instruments that failed (fractured and/or plastically deformed) during the clinical use were collected from various dental clinics, whereas a new set of ProTaper instruments served as control. After inspection under stereomicroscopy the instruments were classified into three categories: (i) plastically deformed but not fractured, (ii) fractured with plastic deformation and (iii) fractured without plastic deformation. Three instruments from each group were analysed with computerized X‐ray microtomography (micro‐XCT) to detect surface and internal defects, whilst all the fracture surfaces were investigated under SEM.

Results  Stereomicroscopic inspection showed that 17.4% of the discarded instruments were only plastically deformed, 8.7% were fractured with plastic deformation and 73.9% were fractured without plastic deformation. Micro‐XCT revealed instruments without any surface or bulk defects along with a few files with crack development below the fracture surface. No defects were identified in the unused instruments. SEM examination of fractured surfaces demonstrated the presence of dimples and cones, a typical pattern of dimple rupture developed because of ductile failure.

Conclusions  The results suggest that a single overloading event causing ductile fracture of ProTaper instruments is the most common fracture mechanism encountered under the clinical conditions.
Co‐production of vascular endothelial cadherin and inducible nitric oxide synthase by endothelial cells in periapical granuloma
Authors: Hama S. , Takeichi O. , Hayashi M. , Komiyama K. , Ito K.
Published: February 2006

Aim  To clarify the mechanisms of inflammatory cell migration in human periapical granulomas by examining vascular endothelial (VE) cadherin and inducible nitric oxide synthase (iNOS)‐producing cells.

Methodology  Periapical tissues were obtained from patients during endodontic surgery and were divided into two portions. After fixing the tissues with acetone or 4% paraformaldehyde in phosphate‐buffered saline, 5‐μm‐thick paraffin or cryostat sections were prepared, respectively. The paraffin sections of the inflamed tissues were evaluated histologically with haematoxylin–eosin stains. Cryostat sections of the tissue, diagnosed as periapical granulomas, were then examined by either immunohistochemistry using anti‐human VE‐cadherin or iNOS antibodies (Abs) for the characterization of infiltrating cells. In addition, co‐localization of VE‐cadherin and iNOS production was also analysed by two‐colour immunofluorescence image analysis.

Results  Endothelial cells were strongly stained with iNOS Abs. Macrophages, lymphocytes, polymorphonuclear leucocytes and fibroblasts also exhibited iNOS production. These iNOS‐positive cells accumulated around the blood vessels. On the other hand, VE‐cadherin production was exhibited in only endothelial cells. Two‐colour immunofluorescence image analysis using VE‐cadherin and iNOS Abs demonstrated that iNOS‐producing endothelial cells also showed VE‐cadherin production.

Conclusions  Vascular endothelial‐cadherin produced by endothelial cells could be regulated by iNOS‐producing cells in periapical granulomas and might play a pivotal role in vascular permeability.
The effect of German chamomile (Marticaria recutita L.) extract and tea tree (Melaleuca alternifolia L.) oil used as irrigants on removal of smear layer: a scanning electron microscopy study
Authors: Sadr Lahijani M. S. , Raoof Kateb H. R. , Heady R. , Yazdani D.
Published: February 2006

Aim  To compare the cleaning effectiveness of chamomile hydroalcoholic extract and tea tree oil to 2.5% sodium hypochlorite (NaOCl) solution as an intracanal irrigant for the removal of the smear layer.

Methodology  Forty extracted, single‐rooted, mature, permanent, human teeth were allocated at random into one of three experimental groups of ten teeth and two control groups of five teeth. For each tooth, the pulp chamber was accessed and the canal prepared using K‐type files and Gates‐Glidden burs, using a step‐back technique; the apical stop was prepared to a size 30. Each canal was subsequently irrigated with one of the following solutions: distilled water (as a negative control), 2.5% NaOCl + 17% ethylenediamine tetraacetic acid (EDTA) (as a positive control), chamomile or tea tree oil or 2.5% NaOCl. Each tooth was split longitudinally and prepared for examination by scanning electron microscopy (SEM). The quantity of smear layer remaining on the three levels of each canal (coronal, middle and apical) was examined using magnifications of 2000 and 5000×. The data were analysed using nonparametric Kruskal–Wallis and Mann–Whitney U‐tests.

Results  The most effective removal of smear layer occurred with the use of NaOCl with a final rinse of 17% EDTA (negative control) followed by the use of a chamomile extract. Chamomile extract was found to be significantly more effective than distilled water and tea tree oil (P < 0.008).The use of a 2.5% NaOCl solution alone, without EDTA and that of tea tree oil, was found to have only minor effects. There was no statistical difference between distilled water, 2.5% NaOCl and tea tree oil.

Conclusions  The efficacy of chamomile to remove smear layer was superior to NaOCl alone but less than NaOCl combined with EDTA.
Comparative study on the shaping ability and cleaning efficiency of rotary Mtwo instruments. Part 1. Shaping ability in simulated curved canals
Authors: Schäfer E. , Erler M. , Dammaschke T.
Published: February 2006

Aim  To compare the shaping ability of Mtwo instruments with K3 and RaCe instruments. Part 1 of this two‐part report describes the efficacy of these nickel–titanium instruments in simulated curved root canals.

Methodology  Simulated canals with 28° and 35° curves in resin blocks were prepared with Mtwo instruments using a single length technique and with K3 and RaCe instruments using a crowndown preparation technique (n = 20 canals in each case). Pre‐ and post‐instrumentation images were recorded and assessment of canal shape was completed with a computer image analysis program. Material removal was measured at 20 measuring points, beginning 1 mm from the endpoint of preparation. Incidence of canal aberrations, preparation time, changes of working length and instrument failures were also recorded. The data were analysed statistically using anova and Student–Newman–Keuls test.

Results  On an average, canals prepared with Mtwo instruments remained better centred compared with those enlarged with K3 or RaCe instruments. Six RaCe instruments, four K3 files and none of the Mtwo instruments fractured during preparation (P > 0.05). In both of the canal types, Mtwo was significantly faster (P < 0.001). It was possible with all types of instruments to control working length as well.

Conclusions  Mtwo instruments prepared curved canals rapidly, respected original canal curvature well and were safe to use.
X‐ray diffraction analysis of mineral trioxide aggregate and Portland cement
Authors: Islam I. , Chng H. K. , Yap A. U. J.
Published: February 2006

Aim  To compare the major constituents present in ProRoot mineral trioxide aggregate (MTA), ProRoot MTA (tooth coloured formula), ordinary Portland cement and white Portland cement using powder X‐ray diffractometery.

Methodology  X‐ray diffractometery of the four materials was carried out with the divergence and scatter slits set at 1° and the receiving slit at 0.10 mm. The scan range was set at 5–70° and continuous scans for the θ–2θ range were run with a scan speed of 2° min−1. The patterns obtained were then compared with the Powder Diffraction Files (PDF) found in the International Centre for Diffraction Data database. The three strongest peaks were used for the identification of the constituents. The relative intensities were plotted against the angle 2θ and compared with the plots in the PDF.

Results  The main constituents were found to be tricalcium silicate, tricalcium aluminate, calcium silicate, and tetracalcium aluminoferrite in all the four cements with the additional presence of Bi2O3 in ProRoot MTA and ProRoot MTA (tooth coloured formula).

Conclusions  The four cements had similar major constituents. Data on Portland cement may be used for the further development or modification of ProRoot MTA in order to improve its physical characteristics and expand its scope of clinical applications.
How does canal taper affect root stresses?
Authors: Rundquist B. D. , Versluis A.
Published: February 2006

Aim  To examine the effect of specific tapers on root stresses and thus vertical root fracture.

Methodology  The effect of taper on root stresses was calculated during simulated warm vertical compaction of gutta‐percha in a straight rooted premolar for three tapers (0.04, 0.06 and 0.12 mm mm−1) using finite element analysis. Stresses in the dentine were observed whilst the root was filled with three subsequent gutta‐percha increments. Each increment was compacted at 10 or 15 N and the gutta‐percha cooled down to 37 °C. After filling, composite was polymerized in the access space. A functional occlusal load of 50 N was then applied on the buccal cusp incline. The stress distribution in the root during the occlusal loading was compared with the stresses during filling.

Results  During filling, the highest stresses were found: (a) at the canal surface; (b) using the smallest taper; (c) in the apical third; and (d) during the first gutta‐percha increment. The root stress distribution changed when the functional post‐filling load was applied. It generated the highest stresses at the external root surface, with a tensile stress concentration at the lingual surface of the cervical third. Since the stresses during simulated masticatory loading concentrated on the external surface, an increased taper size caused only slightly higher root stress levels.

Conclusions  With increasing taper, root stresses decreased during root filling but tended to increase for masticatory loading. Root fracture originating at the apical third is likely initiated during filling, whilst fracture originating in the cervical portion is likely caused by occlusal loads.
The resistance of packed beds of moth gram (Vigna aconitifolius) to airflow
Authors: Nimkar Prabhakar M. , Khobragade Bhagyoday V.
Published: February 2006

The resistance of packed beds of clean moth gram (Vigna aconitifolius) to airflow was studied at moisture contents varying from 5.64 to 19.42% dry basis (d.b.) and at superficial air velocities ranging between 0.0104 and 0.8321 m s−1 with bed depths of 0.2–0.6 m and bulk densities ranging from 745 to 875 kg m−3. The airflow resistance of moth gram increased with increase in airflow rate and bulk density and decreased with moisture content. Results indicated that a 13.78% increase in moisture content decreased the pressure drop by 26.58% whereas, a 7.7% increase in bulk density increased the pressure drop by 43%. The modified Shedd's equation and Hukill and Ives equation were evaluated to see if they predicted pressure drop accurately. Airflow resistance was accurately described by the modified Shedd's equation. The statistical model that related airflow rate and bulk density could fit pressure drop data reasonably well. For loose fill beds an increase in grain moisture content increased the minimum fluidization velocity value from 1.1009 to 1.2391 m s−1 whereas, for grain beds with 12.47% moisture content, the increase in bulk density decreased the minimum fluidization velocity value from 1.1152 to 1.0306 m s−1.
Studies on the stability of an edible film and its use for the preservation of carrot (Daucus carota)
Authors: Jagannath Jambur H. , Nanjappa Chindalaga , Gupta Dilipkumar Das , Bawa Amarinder S.
Published: February 2006

An edible coating was formed by blending turmeric (Curcuma longa) and casein in equal proportions at 95 °C for 12 h. Small quantities of polyvinyl alcohol and propylene glycol were added to encourage film formation and plasticizing respectively. The blend was removed from the reaction vessel and homogenized using Tween‐80 as emulsifier. The homogenized blend was sampled at 2‐h intervals for stability by means of the ‘keeping property’ and ‘accelerated stability’ tests. Stability was also determined by differential scanning calorimetry in which a singlet endotherm indicated molecular mixing (miscibility window) of the components. All three tests indicated that the emulsion was stable after 12 h of blending. Colour, carotenoid content, texture retention and antimicrobial properties remained satisfactory for 10 days in the stable emulsion‐coated carrot whereas the control spoiled after 3 days. Thus turmeric and casein based‐emulsion coating could extend the shelf‐life of carrots by 7 days.
Effect of continuous (intermittent) use on the power output of domestic microwave ovens
Authors: Swain Mark J. , Ferron Stéphanie , Coelho Andrea Isabel Pinto , Swain M. Veronica L.
Published: February 2006

The power output of five recent domestic microwave ovens (on the market 2003/2004) was measured using a standard 1000 g water load during 30 min of continuous use. The power output of the ovens declined significantly (P ≤ 0.05) in the first 5 min of use, ranging from a minimum of 7.0% to a maximum of 19.7%. Further but not always significant declines (P ≤ 0.05) were measured after 20 min of continuous use. No significant reductions were measured between 20 and 30 min. Overall, the mean reduction in power output after 30 min of continuous use was 17.3% for these five ovens compared with 13.5% for five ovens in a previous study. Based on trials carried out approximately a decade apart, there has not been any improvement in the performance of domestic microwave ovens in terms of the decline in power output after continuous or prolonged use. The authors believe that many users, including consumers, caterers and those using domestic microwave ovens for research purposes, would benefit from a greater awareness and understanding of how the rapid reduction in power output in the first 5–20 min of use is likely to affect the expected heating performance.
Effectiveness of treatment programmes for depression among adults with mild/moderate intellectual disability
Authors: McCabe M. P. , McGillivray J. A. , Newton D. C.
Published: February 2006

Background  The current study describes the development and evaluation of group treatment programme for people with mild/moderate intellectual disability (ID).

Methods  A total of 34 participants (16 males, 18 females) completed the treatment programme and 15 participants (six males, nine females) comprised a control group.

Results  Compared to the control group, the intervention group showed an improvement in levels of depression, positive feelings about the self, and lower levels of automatic negative thoughts after the intervention. These changes were maintained at 3‐month follow‐up.

Conclusions  These results demonstrate that intervention programmes are effective for the treatment of depression among people with ID.
A prospective analysis of life events, problem behaviours and depression in adults with intellectual disability
Authors: Esbensen A. J. , Benson B. A.
Published: February 2006

Background  Life events have consistently been found to be associated with behaviour problems and depression among individuals with intellectual disability (ID). However, prior findings have typically been based on correlational or retrospective analyses of case files. The current study attempted to replicate prior findings from life events with concurrent data and extend them to the prospective prediction of behaviour problems and depression. The influence of impact ratings of life events was also explored.

Methods  Seventy‐four informants rated 104 adults with ID on measures of life events, behaviour problems and depressive symptoms. Life events were rated as having either a positive, negative or no impact on the life of the individual with ID. Measures were completed twice, at a 4‐month interval.

Results  Behaviour problems were both correlated with and predicted by frequency counts of life events and life events perceived as negative. However, the predictive ability depended on which measure of problem behaviour was selected. Positive life events were not associated with concurrent behaviour problems. Depressive symptoms were correlated with all life changes, but only predicted by frequency counts of life events and life events perceived as negative. Again, the predictive ability depended on which measure of depression was selected. Findings were corroborated with a group of individuals with clinical diagnoses of major depression.

Conclusions  Frequency counts of all life events and life events perceived as negative play a role in the development of behaviour problems and depressive symptoms among adults with ID. The results have implications for interventions for behaviour problems following a life event, and for reducing depressive symptoms for adults with mild ID.
Protein–protein interactions of tandem affinity purification‐tagged protein kinases in rice
Authors: Rohila Jai S. , Chen Mei , Chen Shuo , Chen Johann , Cerny Ronald , Dardick Chris , Canlas Patrick , Xu Xia , Gribskov Michael , Kanrar Siddhartha , Zhu Jian‐Kang , Ronald Pamela , Fromm Michael E.
Published: February 2006

Forty‐one rice cDNAs encoding protein kinases were fused to the tandem affinity purification (TAP) tag and expressed in transgenic rice plants. The TAP‐tagged kinases and interacting proteins were purified from the T1 progeny of the transgenic rice plants and identified by mass spectrometry. Ninety‐five percent of the TAP‐tagged kinases were recovered. Fifty‐six percent of the TAP‐tagged kinases were found to interact with other rice proteins. A number of these interactions were consistent with known protein complexes found in other species, validating the TAP‐tag method in rice plants. Phosphorylation sites were identified on four of the kinases that interacted with either 14‐3‐3 proteins or cyclins.
Type III effectors orchestrate a complex interplay between transcriptional networks to modify basal defence responses during pathogenesis and resistance
Authors: Truman William , de Zabala Marta Torres , Grant Murray
Published: February 2006

To successfully infect a plant, bacterial pathogens inject a collection of Type III effector proteins (TTEs) directly into the plant cell that function to overcome basal defences and redirect host metabolism for nutrition and growth. We examined (i) the transcriptional dynamics of basal defence responses between Arabidopsis thaliana and Pseudomonas syringae and (ii) how basal defence is subsequently modulated by virulence factors during compatible interactions. A set of 96 genes displaying an early, sustained induction during basal defence was identified. These were also universally co‐regulated following other bacterial basal resistance and non‐host responses or following elicitor challenges. Eight hundred and eighty genes were conservatively identified as being modulated by TTEs within 12 h post‐inoculation (hpi), 20% of which represented transcripts previously induced by the bacteria at 2 hpi. Significant over‐representation of co‐regulated transcripts encoding leucine rich repeat receptor proteins and protein phosphatases were, respectively, suppressed and induced 12 hpi. These data support a model in which the pathogen avoids detection through diminution of extracellular receptors and attenuation of kinase signalling pathways. Transcripts associated with several metabolic pathways, particularly plastid based primary carbon metabolism, pigment biosynthesis and aromatic amino acid metabolism, were significantly modified by the bacterial challenge at 12 hpi. Superimposed upon this basal response, virulence factors (most likely TTEs) targeted genes involved in phenylpropanoid biosynthesis, consistent with the abrogation of lignin deposition and other wall modifications likely to restrict the passage of nutrients and water to the invading bacteria. In contrast, some pathways associated with stress tolerance are transcriptionally induced at 12 hpi by TTEs.
Activation of an alfalfa cyclin‐dependent kinase inhibitor by calmodulin‐like domain protein kinase
Authors: Pettkó‐Szandtner Aladár , Mészáros Tamás , Horváth Gábor V. , Bakó László , Csordás‐Tóth Éva , Blastyák András , Zhiponova Miroslava , Miskolczi Pál , Dudits Dénes
Published: February 2006

Kip‐related proteins (KRPs) play a central role in the regulation of the cell cycle and differentiation through modulation of cyclin‐dependent kinase (CDK) functions. We have identified a CDK inhibitor gene from Medicago truncatula (Mt) by a yeast two‐hybrid screen. The KRPMt gene was expressed in all plant organs and cultured cells, and its transcripts accumulated after abscisic acid and NaCl treatment. The KRPMt protein exhibits seven conserved sequence domains and a PEST motif that is also detected in various Arabidopsis KRPs. In the yeast two‐hybrid test, the KRPMt protein interacted with CDK (Medsa;CDKA;1) and D‐type cyclins. However, in the pull‐down assays, B‐type CDK complexes were also detectable. Recombinant KRPMt differentially inhibited various alfalfa CDK complexes in phosphorylation assays. The immunoprecipitated Medsa;CDKA;1/A;2 complex was strongly inhibited, whereas the mitotic Medsa;CDKB2;1 complex was the most sensitive to inhibition. Function of Medsa;CDKB1;1 complex was not inhibited by the KRPMt protein. The mitotic Medsa;CYCB2 and Medsa;CYCA2;1 complexes responded weakly to this inhibitor protein. Kinase complexes from G2/M cells showed increased sensitivity towards the inhibitor compared with those isolated from G1/S‐phase cells. In vitro phosphorylation of Medicago retinoblastoma‐related protein was also reduced in the presence of KRPMt. Phosphorylation of this inhibitor protein by the recombinant calmodulin‐like domain protein kinase (MsCPK3) resulted in enhanced inhibition of CDK function. The data presented emphasize the selective sensitivity of various cyclin‐dependent kinase complexes to this inhibitor protein, and suggest a role for CDK inhibitors and CPKs in cross‐talk between Ca2+ signalling and regulation of cell‐cycle progression in plants.
Genetic knowledge and moral responsibility: ambiguity at the interface of genetic research and clinical practice
Authors: Pullman D. , Hodgkinson K.
Published: March 2006

Despite a rapidly expanding literature on the issue of duty to warn at‐risk relatives in the context of clinical genetic testing, little has been written on parallel issues with regard to the management of genetic research results. Some might view this lack as an indication that there is little to discuss in this regard. That is, standard practice is that data obtained through medical research should not be treated as though they are clinically relevant, and this standard should hold for genetic research as well. This paper challenges this conclusion and its underlying assumptions. We argue that the line between genetic research and clinical practice is often ambiguous. In some cases, research data gathered from a very small number of subjects could have immediate clinical implications. Hence, it is unethical for genetic researchers to absolve themselves of clinical responsibilities for research subjects and/or their families, on the grounds that the data were obtained for research purposes. Indeed, we argue that it could well be unethical to embark on some forms of genetic research unless advance arrangements have been made for genetic counseling and clinical follow‐up. Furthermore, in some cases, it might be unethical to enroll subjects in studies if the subjects are unwilling to receive their individual results.
Molecular genetic analysis of 1053 Danish individuals with clinical signs of familial hypercholesterolemia
Authors: Brusgaard K , Jordan P , Hansen H , Hansen AB , Hørder M
Published: March 2006

The lipid disorder familial hypercholesterolemia (FH) predisposes to cardiovascular disease. With a prevalence of approximately one in 500 in the general Caucasian population, FH is one of the most frequent single‐gene disorders. As the mutational spectra vary between populations, it is crucial to identify the mutations in a given population in order to implement a molecular genetic screening strategy. A total of 1053 referred individuals with clinical signs of FH were investigated, and mutations were identified in 425 individuals. Fifty‐four different mutations were identified, of which 13 are novel. The five most frequent mutations accounted for 56.3% of all disease‐causing mutations. The majority of the remaining mutations were of a private nature only encountered in single families. In this study, a reliable molecular genetic screening protocol was established, and the relevance of performing presymptomatic genetic analysis as part of a preventive strategy was documented. We have acquired knowledge of the mutational spectra in the Danish population and thus will be able to trace mutations in their relatives through our index cases.
Elements for Legislation in User Countries to Meet the Fair and Equitable Benefit‐Sharing Commitment
Authors: Tvedt Morten Walløe
Published: February 2006

The third objective of the Convention on the Biological Diversity, the fair and equitable benifit sharing of the use of genetic resources, is lagging behind at the implementation phase. Very few countries have taken effective measures to promote sharing of benefits arising from the use of genetic resources. This article offers some suggestions as to why this is the case and poses a number of questions that need to be dealt with before such a system can be in place. It develops the concept ofgenetic resourcesand suggests that the focus need to be at the successful end uses of genetic material rather than at the point in time when genetic material is found in the nature.
The Intellectual Property Provisions of the United States–Jordan Free Trade Agreement: Template or Not Template
Authors: Malkawi Bashar H.
Published: February 2006

The objective of this article is to examine the implications of the intellectual property provisions in the US–Jordan Free Trade Agreement (US–JO FTA) and whether they serve as a template for other Arab countries who will be concluding free trade agreements with the USA. My claim in this article is that the intellectual property part of the US–JO FTA goes beyond the World Trade Organization Agreement and cannot form the right template for the proposed US–Middle East FTA of 2013. The first section provides a brief introduction to the US–JO FTA. The second section provides a critical analysis of the FTA's protection of trademarks, copyright and patents. The third and fourth sections discuss enforcement and implementation of the intellectual property provisions of the FTA. The final section provides a conclusion regarding the intellectual property provisions of the US–JO FTA and highlights an alternative template for the proposed US–Middle East FTA.
How to Cope with China's (Alleged) Failure to Implement the TRIPS Obligations on Enforcement
Authors: Bender Tobias
Published: February 2006

This article deals with the enforcement of intellectual property rights (IPRs) in China. First, it describes pirating and counterfeiting of IPR‐protected goods as a global problem, highlighting the role of China in this activity. It then looks at concrete enforcement deficits and assesses the extent to which this practice collides with China's Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS) obligations on enforcement. After giving reasons for the current situation of IPR enforcement, various reform efforts are presented and their TRIPS conformity is appraised. Against this background, the article discusses the options at the disposal both of private enterprises doing business in China and governments in coping with and influencing the current environment of IPR enforcement in China.