bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of a Mandatory Declination Form in a Program for Influenza Vaccination of Healthcare Workers
Authors: Ribner Bruce S. , Hall Cynthia , Steinberg James P. , Bornstein William A. , Chakkalakal Rosette , Emamifar Amir , Eichel Irving , Lee Peter C. , Castellano Penny Z. , Grossman Gilbert D.
Published: February 2008

Objective.

To evaluate the utility and impact of using a declination form in the context of an influenza immunization program for healthcare workers.

Methods.

A combined form for documentation of vaccination consent, medical contraindication(s) for vaccination, or vaccination declination was used during the 2006-2007 influenza season in a healthcare system employing approximately 9,200 nonphysician employees in 3 hospitals; a skilled nursing care facility; a large, multisite, faculty-practice plan; and an administrative building. Responses were entered into a database that contained files from human resources departments, which allowed correlation with job category and work location.

Results.

The overall levels of influenza vaccination coverage of employees increased from 43% (3,892 of 9,050) during the 2005-2006 season to 66.5% (6,123 of 9,214) during the 2006-2007 season. Of 9,214 employees, 1,898 (20.6%) signed the declination statement. Among the occupation groups, nurses had the lowest rate of declining vaccination (13.2% [393 of 2,970]; P < .0001), followed by pharmacy personnel (18.1% [40 of 221]), ancillary personnel with frequent patient contact (21.9% [169 of 771), and all others (24.7% [1,296 of 5,252]). Among the employees who declined vaccination, nurses were the least likely to select the reasons “afraid of needles” (3.8% [15 of 393], vs. 9.1% [137 of 1,505] for all other groups; P < .001) and “fear of getting influenza from the vaccine” (13.5% [53 of 393], vs. 20.5% [309 of 1,505]; P = .002). Seven pregnant nurses had been advised by their obstetricians to avoid vaccination. When declination of influenza vaccination was analyzed by age, 16% of personnel (797 of 4,980) 50 years of age and older declined to be vaccinated, compared with 26% of personnel (1,101 of 4,234) younger than 50 years of age {P < .0001).

Conclusions.

Implementing use of the declination form during the 2006-2007 influenza season was one of several measures that led to a 55% increase in the acceptance of influenza vaccination by healthcare workers in our healthcare system. Although we cannot determine to what degree use of the declination form contributed to the increased rate of vaccination, use of this form helped the vaccination program assess the reasons for declination and will help to focus future vaccination campaigns.
Multiplexed Dendritic Targeting of α Calcium Calmodulin-dependent Protein Kinase II, Neurogranin, and Activity-regulated Cytoskeleton-associated Protein RNAs by the A2 Pathway
Authors: Gao Yuanzheng , Tatavarty Vedakumar , Korza George , Levin Mikhail K. , Carson John H.
Published: February 2008

In neurons, many different RNAs are targeted to dendrites where local expression of the encoded proteins mediates synaptic plasticity during learning and memory. It is not known whether each RNA follows a separate trafficking pathway or whether multiple RNAs are targeted to dendrites by the same pathway. Here, we show that RNAs encoding α calcium calmodulin-dependent protein kinase II, neurogranin, and activity-regulated cytoskeleton-associated protein are coassembled into the same RNA granules and targeted to dendrites by the same cis/trans-determinants (heterogeneous nuclear ribonucleoprotein [hnRNP] A2 response element and hnRNP A2) that mediate dendritic targeting of myelin basic protein RNA by the A2 pathway in oligodendrocytes. Multiplexed dendritic targeting of different RNAs by the same pathway represents a new organizing principle for coordinating gene expression at the synapse.
Genome-wide Expression Profiling, In Vivo DNA Binding Analysis, and Probabilistic Motif Prediction Reveal Novel Abf1 Target Genes during Fermentation, Respiration, and Sporulation in Yeast
Authors: Schlecht Ulrich , Erb Ionas , Demougin Philippe , Robine Nicolas , Borde Valérie , Nimwegen Erik van , Nicolas Alain , Primig Michael
Published: February 2008

The autonomously replicating sequence binding factor 1 (Abf1) was initially identified as an essential DNA replication factor and later shown to be a component of the regulatory network controlling mitotic and meiotic cell cycle progression in budding yeast. The protein is thought to exert its functions via specific interaction with its target site as part of distinct protein complexes, but its roles during mitotic growth and meiotic development are only partially understood. Here, we report a comprehensive approach aiming at the identification of direct Abf1-target genes expressed during fermentation, respiration, and sporulation. Computational prediction of the protein's target sites was integrated with a genome-wide DNA binding assay in growing and sporulating cells. The resulting data were combined with the output of expression profiling studies using wild-type versus temperature-sensitive alleles. This work identified 434 protein-coding loci as being transcriptionally dependent on Abf1. More than 60% of their putative promoter regions contained a computationally predicted Abf1 binding site and/or were bound by Abf1 in vivo, identifying them as direct targets. The present study revealed numerous loci previously unknown to be under Abf1 control, and it yielded evidence for the protein's variable DNA binding pattern during mitotic growth and meiotic development.
Traditional Chinese Medicine for Chronic Fatigue Syndrome
Authors: Chen Rui , Moriya Junji , Yamakawa Jun-ichi , Takahashi Takashi , Kanda Tsugiyasu
Published: February 2008

More and more patients have been diagnosed as having chronic fatigue syndrome (CFS) in recent years. Western drug use for this syndrome is often associated with many side‐effects and little clinical benefit. As an alternative medicine, traditional Chinese medicine (TCM) has provided some evidences based upon ancient texts and recent studies, not only to offer clinical benefit but also offer insights into their mechanisms of action. It has perceived advantages such as being natural, effective and safe to ameliorate symptoms of CFS such as fatigue, disordered sleep, cognitive handicaps and other complex complaints, although there are some limitations regarding the diagnostic standards and methodology in related clinical or experimental studies. Modern mechanisms of TCM on CFS mainly focus on adjusting immune dysfunction, regulating abnormal activity in the hypothalamic‐pituitary‐adrenal (HPA) axis and serving as an antioxidant. It is vitally important for the further development to establish standards for ‘zheng’ of CFS, i.e. the different types of CFS pathogenesis in TCM, to perform randomized and controlled trials of TCM on CFS and to make full use of the latest biological, biochemical, molecular and immunological approaches in the experimental design.
Cu(II) organizes β‐2‐microglobulin oligomers but is released upon amyloid formation
Authors: Antwi Kwasi , Mahar Maura , Srikanth Rapole , Olbris Mark R. , Tyson Julian F. , Vachet Richard W.
Published: February 2008

β‐2‐Microglobulin (β2m) is deposited as amyloid fibrils in the bones and joints of patients undergoing long‐term dialysis treatment as a result of kidney failure. Previous work has shown that biologically relevant amounts of Cu(II) can cause β2m to be converted to amyloid fibrils under physiological conditions in vitro. In this work, dynamic light scattering, mass spectrometry, and size‐exclusion chromatography are used to characterize the role that Cu plays in the formation of oligomeric intermediates that precede fibril formation. Cu(II) is found to be necessary for the stability of the dimer and an initial form of the tetramer. The initially formed tetramer then undergoes a structural change to a state that no longer binds Cu(II) before progressing to a hexameric state. Based on these results, we propose that the lag phase associated with β2m fibril formation is partially accounted for by the structural transition of the tetramer that results in Cu(II) loss. Consistent with this observation is the determination that the mature β2m amyloid fibrils do not contain Cu. Thus, Cu(II) appears to play a catalytic role by enabling the organization of the necessary oligomeric intermediates that precede β2m amyloid formation.
Structural and thermodynamic effects of ANS binding to human interleukin‐1 receptor antagonist
Authors: Latypov Ramil F. , Liu Dingjiang , Gunasekaran Kannan , Harvey Timothy S. , Razinkov Vladimir I. , Raibekas Andrei A.
Published: February 2008

Although 8‐anilinonaphthalene‐1‐sulfonic acid (ANS) is frequently used in protein folding studies, the structural and thermodynamic effects of its binding to proteins are not well understood. Using high‐resolution two‐dimensional NMR and human interleukin‐1 receptor antagonist (IL‐1ra) as a model protein, we obtained detailed information on ANS–protein interactions in the absence and presence of urea. The effects of ambient to elevated temperatures on the affinity and specificity of ANS binding were assessed from experiments performed at 25°C and 37°C. Overall, the affinity of ANS was lower at 37°C compared to 25°C, but no significant change in the site specificity of binding was observed from the chemical shift perturbation data. The same site‐specific binding was evident in the presence of 5.2 M urea, well within the unfolding transition region, and resulted in selective stabilization of the folded state. Based on the two‐state denaturation mechanism, ANS‐dependent changes in the protein stability were estimated from relative intensities of two amide resonances specific to the folded and unfolded states of IL‐1ra. No evidence was found for any ANS‐induced partially denatured or aggregated forms of IL‐1ra throughout the experimental conditions, consistent with a cooperative and reversible denaturation process. The NMR results support earlier observations on the tendency of ANS to interact with solvent‐exposed positively charged sites on proteins. Under denaturing conditions, ANS binding appears to be selective to structured states rather than unfolded conformations. Interestingly, the binding occurs within a previously identified aggregation‐critical region in IL‐1ra, thus providing an insight into ligand‐dependent protein aggregation.
Nonspecific base recognition mediated by water bridges and hydrophobic stacking in ribonuclease I from Escherichia coli
Authors: Rodriguez Sergio Martinez , Panjikar Santosh , Van Belle Karolien , Wyns Lode , Messens Joris , Loris Remy
Published: February 2008

The crystal structure of Escherichia coli ribonuclease I (EcRNase I) reveals an RNase T2‐type fold consisting of a conserved core of six β‐strands and three α‐helices. The overall architecture of the catalytic residues is very similar to the plant and fungal RNase T2 family members, but the perimeter surrounding the active site is characterized by structural elements specific for E. coli. In the structure of EcRNase I in complex with a substrate‐mimicking decadeoxynucleotide d(CGCGATCGCG), we observe a cytosine bound in the B2 base binding site and mixed binding of thymine and guanine in the B1 base binding site. The active site residues His55, His133, and Glu129 interact with the phosphodiester linkage only through a set of water molecules. Residues forming the B2 base recognition site are well conserved among bacterial homologs and may generate limited base specificity. On the other hand, the B1 binding cleft acquires true base aspecificity by combining hydrophobic van der Waals contacts at its sides with a water‐mediated hydrogen‐bonding network at the bottom. This B1 base recognition site is highly variable among bacterial sequences and the observed interactions are unique to EcRNaseI and a few close relatives.
Characterization of β‐Silicon Carbide Powders Synthesized by the Carbothermal Reduction of Silicon Carbide Precursors
Authors: Huang Daxiang , Ikuhara Yuichi , Narisawa Masaki , Okamura Kiyohito
Published: February 2008

Boron‐doped and nondoped ultrafine β‐silicon carbide (β‐SiC) powders were synthesized via the carbothermal reduction of SiC precursors at temperatures of 1773–1973 K. Although the reaction rate of carbothermal reduction was generally higher when a boron‐doped precursor was used, the reaction rate for the boron‐doped precursor was reduced considerably at 1873 K. For boron‐doped and nondoped precursors, the reaction rates were almost the same. Powder characterization via transmission electron microscopy indicated that the suppression of the reaction rate for boron‐doped precursor at 1873 K was due to the formation of a special coexistent system with two types of particle agglomerates. As expected, boron doping inhibited the particle growth in the synthesis of SiC powder.
Sintering Model for Mixed‐Oxide‐Derived Lead Zirconate Titanate Ceramics
Authors: Hammer Marianne , Hoffmann Michael J.
Published: February 2008

The properties of lead zirconate titanate (PZT) ceramics are determined by the microstructure and chemical homogeneity of Zr, Ti, and dopants within the grains as well as the presence of secondary grain boundary phases. Stoichiometric 53/47 PZT and compositions with 3 mol% PbO excess were prepared by the mixed‐oxide process, and were densified by pressureless sintering in oxygen. The influence of PbO content and different La concentrations on the densification behavior was analyzed by dilatometric measurements. Quantitative image analysis showed a different relative density and grain size dependence for samples containing >0.5 mol% additives compared to samples with <0.5 mol% La. On the basis of a model experiment and by using different analytical methods (microprobe analysis, HRTEM, STEM, and Auger spectroscopy) three types of inhomogeneities could be detected in conventionally prepared PZT ceramics: the existence of Ti and La enrichment in the core of PZT grains, and PbO‐rich secondary phases in triple junctions as well as in grain boundary films. The results of the microstructural characterization and the analysis of the densification behavior were finally combined to deduce a sintering model based on a Pb‐vacancy concentration gradient within the PZT grains.
Subsolidus Phase Relations in the Ga2O3‐In2O3‐SnO2 System
Authors: Edwards Doreen D. , Mason Thomas O.
Published: February 2008

Subsolidus phase relationships in the Ga2O3–In2O3–SnO2 system were studied by X‐ray diffraction over the temperature range 1250–1400°C. At 1250°C, several phases are stable in the ternary system, including Ga2O3(ss), In2O3(ss), SnO2, Ga3−xIn5+xSn2O16, and several intergrowth phases that can be expressed as Ga4−4xIn4xSnn−4O2n−2 where n is an integer. An In2O3–SnO2 phase and Ga4SnO8 form at 1375°C but are not stable at 1250°C. GaInO3 did not form over the temperature range 1000–1400°C.
Calculation of the Theoretical Energy Requirement for Melting Technical Silicate Glasses
Authors: Madivate Carvalho M. de O.
Published: February 2008

The theoretical energy requirement (TER) for the fusion of batch samples of flat and container glasses was determined by using the drop‐mixing method. The TER values obtained from this study have been compared to values derived from other models; a deviation of up to 8% was observed. This comparison suggested no significant difference between the experimental results and those derived from the different models. A new procedure for the TER determination was developed. The TER value obtained from this procedure showed deviations of <2%.
Low‐Temperature Preparation of Nanocrystalline Lead Zirconate Titanate and Lead Lanthanum Zirconate Titanate Powders Using Triethanolamine
Authors: Das Rabindra N. , Pathak Amita , Pramanik Panchanan
Published: February 2008

Nanocrystalline lead zirconate titanate (PZT) powders, with a Zr:Ti ratio of 60:40, have been prepared from a solution of triethanolamine (TEA) and Ti4+, Zr4+, and Pb2+ ions. The metal ions were in solution through complex formation with TEA. The soluble metal‐ion–TEA complex formed the precursor material when it was completely dehydrated. Heat treatment of the precursor at 450°C resulted in single‐phase PZT powders. The precursor and the heat‐treated powders have been characterized by using thermal analysis and X‐ray diffractometry (XRD) studies. The average particle size, as measured from X‐ray line broadening and transmission electron microscopy studies, was ∼20 nm. PZT powders modified with 3 mol% of lanthanum (PLZT) also were prepared through this route and were investigated via XRD studies. The dielectric constants of the PZT and PLZT powders were 12475 and 11262, and their corresponding Curie temperatures were 362° and 315°C, respectively.
The human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y‐box‐binding protein‐1 overexpressing tumor cells
Authors: Guay David , Garand Chantal , Reddy Shanti , Schmutte Chris , Lebel Michel
Published: February 2008

Y‐box‐binding protein‐1 (YB‐1) is a multifunctional protein involved in the regulation of transcription, translation, and mRNA splicing. In recent years, several laboratories have demonstrated that YB‐1 is directly involved in the cellular response to genotoxic stress. Importantly, YB‐1 is increased in tumor cell lines resistant to cisplatin, and the level of nuclear expression of YB‐1 is predictive of drug resistance and patient outcome in breast tumors, ovarian cancers, and synovial sarcomas. YB‐1 binds to several DNA repair enzymes in vitro including human endonuclease III (hNTH1). Human NTH1 is a bifunctional DNA glycosylase/apurinic/apyrimidinic lyase involved in base excision repair. In this study, we show that YB‐1 binds specifically to the auto‐inhibitory domain of hNTH1, providing a mechanism by which YB‐1 stimulates hNTH1 activity. Indeed, YB‐1 strongly stimulates in vitro the activity of hNTH1 toward DNA duplex probes containing oxidized bases, lesions prone to be present in cisplatin treated cells. We also observed an increase in YB‐1/hNTH1 complex formation in the mammary adenocarcinoma MCF7 cell line treated with UV light and cisplatin. Such an increase was not observed with mitomycin C or the topoisomerase I inhibitor camptothecin. Accordingly, antisense RNAs against either YB‐1 or hNTH1 increased cellular sensitivity to UV and cisplatin but not to mitomycin C. An antisense RNA against YB‐1 increased camptothecin sensitivity. In contrast, an antisense against hNTH1 did not. Finally, siRNA against hNTH1 re‐established cytotoxicity in otherwise cisplatin‐resistant YB‐1 overexpressing MCF7 cells. These data indicate that hNTH1 is a relevant target to potentiate cisplatin cytotoxicity in YB‐1 overexpressing tumor cells. (Cancer Sci 2008; 99: 762–769)
Quantitative trait loci for white blood cell numbers in swine
Authors: Reiner G. , Fischer R. , Hepp S. , Berge T. , Köhler F. , Willems H.
Published: February 2008

Differential white blood cell counts are essential diagnostic parameters in veterinary practice but knowledge on the genetic architecture controlling variability of leucocyte numbers and relationships is sparse, especially in swine. Total leucocyte numbers (Leu) and the differential leucocyte counts, i.e. the fractions of lymphocytes (Lym), polymorphonuclear leucocytes [neutrophils (Neu), eosinophils (Eos) and basophils (Bas)] and monocytes (Mon) were measured in 139 F2 pigs from a Meishan/Pietrain family, before and after challenge with the protozoan pathogen Sarcocystis miescheriana for genome‐wide quantitative trait loci (QTL) analysis. After infection, the pigs passed through three stages representing acute disease, reconvalescence and chronic disease. Nine genome‐wide significant and 29 putative, single QTL controlling leucocyte traits were identified on 15 chromosomes. Because leucocyte traits varied with health and disease status, QTL influencing the leucocyte phenotypes showed specific health/disease patterns. Regions on SSC1, 8 and 12 contained QTL for baseline leucocyte traits. Other QTL regions reached control on leucocyte traits only at distinct stages of the disease model. Two‐thirds of the QTL have not been described before. Single QTL explained up to 19% of the phenotypic variance in the F2 animals. Related traits were partly under common genetic influence. Our analysis confirms that leucocyte trait variation is associated with multiple chromosomal regions.
A novel and sensitive ELISA reveals that the soluble form of IL‐13R‐α2 is not expressed in plasma of healthy or asthmatic subjects
Authors: O'Toole M. , Legault H. , Ramsey R. , Wynn T. A. , Kasaian M. T.
Published: February 2008

Background
IL‐13 plays a key regulatory role in asthmatic responses and immunity to parasitic infection. In vivo, IL‐13R‐α2 is a critical modulator of IL‐13 bioactivity. When inducibly expressed on the surface of fibroblasts and other cell types under inflammatory conditions, IL‐13R‐α2 contributes to resolution of IL‐13 responses. A soluble form of IL‐13R‐α2 (sIL‐13R‐α2) can be detected in murine circulation, and functions as a regulator of IL‐13 bioactivity. In humans, sIL‐13R‐α2 has been more difficult to detect. Recently, novel assay systems have been described to quantitate sIL‐13R‐α2 in human circulation, and revealed unexpectedly high levels of sIL‐13R‐α2 in healthy subjects.

Objective
To verify sIL‐13R‐α2 quantitation in human plasma samples under stringent conditions of signal verification and false‐positive detection.

Methods
A standard ELISA protocol was evaluated for specificity using false‐positive detection reagents. A more stringent ELISA protocol was developed by optimizing the composition of blocking and dilution buffers.

Results
Using the stringent assay protocol, endogenous sIL‐13R‐α2 was undetectable in plasma samples from a total of 120 asthmatics and 20 healthy subjects, and in bronchoalveolar lavage fluid from 10 asthmatics and eight healthy subjects undergoing allergen challenge.

Conclusion
These results underscore the necessity to perform rigorous assay controls in the biological matrix to be tested. Because the soluble form could not be demonstrated, our findings question a role for sIL‐13R‐α2 in the regulation of IL‐13 bioactivity, and highlight the potentially important contribution of the membrane‐bound form of IL‐13R‐α2 in humans.
Identification and management of undiagnosed and undertreated allergic rhinitis in adults and children
Authors: Stewart M. G.
Published: February 2008

Allergic rhinitis (AR) is a common health problem that affects adults, adolescents and children and is often undiagnosed or inadequately treated. Because AR is not a life‐threatening disease, many patients do not seek medical treatment for their symptoms, and others self‐medicate with over‐the‐counter medications, often sedating antihistamines. However, untreated or inadequately treated AR can substantially impair overall quality of life (QOL) by causing fatigue, headache, cognitive impairment and other problems. The risk for comorbid conditions, such as asthma, otitis media, and lymphoid hypertrophy with obstructive sleep apnea, can increase, and the symptoms of AR can worsen if AR is not adequately treated. Among the symptoms of AR, nasal congestion has been described by patients as the most bothersome because it disrupts sleep, resulting in diminished daytime performance. A new congestion screening tool, the Congestion Quantifier, has been developed to aid in the diagnosis and treatment of AR and to help guide treatment decisions. Intranasal corticosteroids (INSs) are recommended as effective pharmaceutical treatments for controlling the symptoms of AR. Randomized, controlled trials in children and adults have demonstrated that INSs relieve rhinitis symptoms, thereby improving QOL in individuals with seasonal or perennial AR. Most INSs are approved for use in children 6 years of age, but mometasone furoate and fluticasone furoate are approved for use in children as young as 2 years of age and fluticasone propionate for children 4 years old. Long‐term benefits have also been seen with the use of immunotherapy, although some patients, especially children, resist the injections used in subcutaneous immunotherapy. Recent studies with sublingual immunotherapy have indicated that it might be an effective and well‐tolerated alternative to immunotherapy injections.
Efficacy of ProTaper Universal rotary retreatment system for gutta‐percha removal from root canals
Authors: Gu L.‐S. , Ling J.‐Q , Wei X. , Huang X.‐Y.
Published: February 2008

Aim  To evaluate the efficacy of the ProTaper Universal rotary retreatment system for gutta‐percha (GP) removal from root canals.

Methodology  Root canals of 60 extracted human maxillary anterior teeth were prepared and filled with laterally condensed GP and AH Plus sealer. Teeth were divided into three groups: group A – GP removal completed with the ProTaper Universal rotary retreatment system and with further canal repreparation accomplished with ProTaper Universal rotary instruments; group B – GP removal was completed using Gates Glidden drills and Hedström files with chloroform as a solvent, followed with further canal repreparation with ProTaper Universal rotary instruments; group C – the same as group B for GP removal with further canal preparation with stainless steel K‐flex files (Kerr). The operating time was recorded. Teeth were rendered transparent for the evaluation of the area of remaining GP/sealer in bucco‐lingual and mesial–distal directions. Statistical analysis was performed by using repeated measures analysis of variance and anova.

Results  The ProTaper Universal technique (group A) resulted in a smaller percentage of canal area covered by residual GP/sealer than in groups B and C, with a significant difference between groups A and C (P < 0.05). Mean operating time for group A was 6.73 min, which was significantly shorter (P < 0.05) than group B (10.86 min) and group C (13.52 min).

Conclusions  In this laboratory study all test techniques left GP/sealer remnants within the root canal. The ProTaper Universal rotary retreatment system proved to be an efficient method of removing GP and sealer from maxillary anterior teeth.
Low‐dose doxycycline inhibits bone resorption associated with apical periodontitis
Authors: Metzger Z. , Belkin D. , Kariv N. , Dotan M. , Kfir A.
Published: February 2008

Aim  To test the effect of low‐dose doxycycline on bone resorption associated with apical periodontitis.

Methodology  Apical periodontitis was induced by occlusal pulp exposure in the mandibular first molars of 36 rats. Animals were divided into three groups of 12: group A received doxycycline in drinking water at a dose of 5.85 mg day−1; group B received a dose of 1.48 mg day−1 (one‐quarter of the original dose); and group C received no medicament and served as the control. A bioassay determined the doxycycline serum levels. After 21 days, the mandibles were removed, radiographed and the radiographs scanned to generate digital images. These images were analysed morphometrically and the total area of the periapical bone resorption of the mesial and distal roots of each tooth was determined and used to compare the groups. Statistical analysis was completed using anova with repeated measures.

Results  The mean doxycycline serum level in group A was 0.22(±0.03) μg mL−1 and in group B below the detection level of the assay (<0.062 μg mL−1). The mean area of the periapical bone resorption in the control group C was 2.91(±0.61) mm2. In animals treated with a low‐dose doxycycline, the mean size of the bone resorption was significantly smaller at 1.59(±0.59) mm2 (group A) and 1.72(±0.85) mm2 (group B) (P = 0.001). No significant difference was found in the area of the bone resorption between these two groups A and B.

Conclusions  Low‐dose doxycycline reduced the area of bone resorption associated with apical periodontitis in the mandibular first molar teeth of rats.
Predicting population responses to restoration of breeding habitat in Atlantic salmon
Authors: Einum Sigurd , Nislow Keith H. , Reynolds John D. , Sutherland William J.
Published: February 2008

Habitat degradation is seriously threatening stream biodiversity and productivity world‐wide. For salmonid fish, restoration projects in disturbed systems commonly aim at increasing the availability of suitable breeding habitats, but expectations of effects on population abundance based on explicit models are lacking.

We used a spatial population model to predict how breeder dispersion may influence population dynamics of salmonids. Simulations involved changing the relative abundance of habitat suitable for two juvenile size classes (small fry and larger parr), the type of density‐dependent regulation (effects on survival only vs. effects on survival and growth) and intercohort competitive mechanisms.

Increased breeding dispersion could alter patterns of density‐dependent mortality and increase equilibrium adult abundance and maximum sustainable yield (MSY). However, there was a strong interaction between stage‐specific habitat abundance and breeding dispersion. The most pronounced effects of breeding dispersion were observed under intermediate levels of fry habitat abundance.

When fry habitat was abundant, density‐dependent mortality was most intense during the parr stage, and increased breeding dispersion did not increase adult abundance or MSY. In fact, when populations were regulated in the parr stage, increased breeding dispersion could cause decreased adult abundance because of the effects of intercohort competition. This negative effect only occurred, however, when competition among juveniles was symmetric (no age or size advantage).

Synthesis and applications.The population effects of restoring breeding habitat can differ among environments, and we have demonstrated how these differences can be understood in the light of stage‐specific density dependence. Increasing spatial dispersion of breeders may often be an efficient measure for conserving threatened populations and increasing yields in fished populations. However, if direct evidence or habitat considerations suggest that fish populations experience density‐dependent mortality during the parr stage, attempts to increase abundance through increased breeding distribution or artificial stocking should be avoided, as these are likely to be ineffective or even detrimental. The difference between fishing rates providing maximum sustainable yield and extinction is particularly small for such populations, suggesting that fish managers should adopt a conservative and flexible regulation regime.
The epidemiology of obesity: the size of the problem
Authors: James W. P. T.
Published: February 2008

The epidemic of obesity took off from about 1980 and in almost all countries has been rising inexorably ever since. Only in 1997 did WHO accept that this was a major public health problem and, even then, there was no accepted method for monitoring the problem in children. It was soon evident, however, that the optimum population body mass index is about 21 and this is particularly true in Asia and Latin America where the populations are very prone to developing abdominal obesity, type 2 diabetes and hypertension. These features are now being increasingly linked to epigenetic programming of gene expression and body composition in utero and early childhood, both in terms of fat/lean tissue ratios and also in terms of organ size and metabolic pathway regulation. New Indian evidence suggests that insulin resistance at birth seems linked to low birth weight and a higher proportion of body fat with selective B12 deficiency and abnormalities of one carbon pool metabolism potentially responsible and affecting 75% of Indians and many populations in the developing world. Biologically there are also adaptive biological mechanisms which limit weight loss after weight gain and thereby in part account for the continuing epidemic despite the widespread desire to slim. Logically, the burden of disease induced by inappropriate diets and widespread physical inactivity can be addressed by increasing physical activity (PA), but simply advocating more leisure time activity is unrealistic. Substantial changes in urban planning and diet are needed to counter the removal of any every day need for PA and the decades of misdirected food policies which with free market forces have induced our current ‘toxic environment’. Counteracting this requires unusual policy initiatives.
Automated assessment of keratocyte density in clinical confocal microscopy of the corneal stroma
Authors: McLAREN J. W. , PATEL S. V. , NAU C. B. , BOURNE W. M.
Published: February 2008

Cell density in the corneal stroma is typically determined by counting the number of bright objects, presumably keratocyte nuclei, in images from clinical confocal microscopy. We present a program that identifies bright objects and counts those that most likely represent cells. Selection variables were determined from 125 normal corneas with cell densities that had been assessed manually. The program was tested on 17 corneas of patients before and at several intervals to 5 years after laser in situ keratomileusis (LASIK) surgery. In these corneas, which showed a decrease in cell density after surgery, the program identified cells as well as human observers did.
Raster image correlation spectroscopy (RICS) for measuring fast protein dynamics and concentrations with a commercial laser scanning confocal microscope
Authors: BROWN C. M. , DALAL R. B. , HEBERT B. , DIGMAN M. A. , HORWITZ A. R. , GRATTON E.
Published: February 2008

Raster image correlation spectroscopy (RICS) is a new and novel technique for measuring molecular dynamics and concentrations from fluorescence confocal images. The RICS technique extracts information about molecular dynamics and concentrations from images of living cells taken on commercial confocal systems. Here we develop guidelines for performing the RICS analysis on an analogue commercial laser scanning confocal microscope. Guidelines for typical instrument settings, image acquisition settings and analogue detector characterization are presented. Using appropriate instrument/acquisition parameters, diffusion coefficients and concentrations can be determined, even for highly dynamic dye molecules in solution. Standard curves presented herein demonstrate the ability to detect protein concentrations as low as ∼ 2 nM. Additionally, cellular measurements give accurate values for the diffusion of paxillin‐enhanced‐green fluorescent protein (EGFP), an adhesion adaptor molecule, in the cytosol of the cell and also show slower paxillin dynamics near adhesions where paxillin interacts with immobile adhesion components. Methods are presented to account for bright immobile structures within the cell that dominate spatial correlation functions; allowing the extraction of fast protein dynamics within and near these structures. A running average algorithm is also presented to address slow cellular movement or movement of cellular features such as adhesions. Finally, methods to determine protein concentration in the presence of immobile structures within the cell are presented. A table is presented giving guidelines for instrument and imaging setting when performing RICS on the Olympus FV300 confocal and these guidelines are a starting point for performing the analysis on other commercial confocal systems.
Nurses' accounts of locked ward doors: ghosts of the asylum or acute care in the 21st century?
Authors: ASHMORE R.
Published: February 2008

The practice of locking acute ward doors in the UK to manage patient care has been reported with increasing frequency in a number of recent official documents; however, there is little research examining the practice. This study explores the perceptions and experiences of mental health nurses working on acute wards where the doors are locked for all or part of a shift. Audio‐taped, semi‐structured interviews were undertaken with 11 qualified mental health nurses and analysed using content analysis. Six broad categories were identified: policies and documentation, locking and unlocking the doors, communicating the decision, reasons for locking the doors, benefits and concerns. The findings suggest that there is a need for mental health nurses to reflect on the reasons for, and wider implications of locking ward doors before their wholesale implementation is considered in the UK.
A review of the literature on the historical development of community mental health services in the United Kingdom
Authors: WRIGHT N. , BARTLETT P. , CALLAGHAN P.
Published: February 2008

Community mental health encompasses a diverse range of statutory, voluntary and informal care services. However, little has been written about how changes in policy, legislation and philosophies throughout time impact on the service user experience of mental health care today. The purpose of this paper was to review the literature using systematic approaches and address the question: ‘How have historical factors influenced the development of community mental health care in the United Kingdom?’ Following a comprehensive literature search, we included 70 texts. Owing to the difficulties of classifying historical texts numerically, two themes were identified: (1) changing perspectives towards mental illness and the mentally ill; and (2) the complexities of mental health care provision. We structured the review around these themes. A narrative approach was used to illustrate the diversity within the identified texts. In response to the review question, an exploration of the historical literature demonstrates that some form of community care has always been evident. It also suggests that over time different philosophical ideas have influenced mental health policy and service structure. These have in turn shaped the care a service user receives when they come into contact with mental health professionals.
Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation
Authors: Tessarz Peter , Mogk Axel , Bukau Bernd
Published: February 2008

The oligomeric AAA+ chaperone Hsp104 is essential for thermotolerance development and prion propagation in yeast. Thermotolerance relies on the ability of Hsp104 to cooperate with the Hsp70 chaperone system in the reactivation of heat‐aggregated proteins. Prion propagation requires the Hsp104‐dependent fragmentation of prion fibrils to create infectious seeds. It remained elusive whether both processes rely on common or different activities of Hsp104. Specifically, protein reactivation has been suggested to require a substrate threading activity of Hsp104 whereas fibril fragmentation may be mediated by a crowbar activity. Here we engineered an Hsp104 variant, HAP, which cooperates with the bacterial peptidase ClpP to form a novel proteolytic system. HAP threads aggregated model substrates as well as the yeast prion Sup35 through its central pore into associated ClpP. HAP variants that harbour a reduced threading activity were affected in both protein disaggregation and prion propagation, demonstrating that substrate threading represents the common mechanism for the processing of both substrate classes.
Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB‐oprM genes
Authors: Pamp Sünje Johanna , Gjermansen Morten , Johansen Helle Krogh , Tolker‐Nielsen Tim
Published: February 2008

Bacteria living as biofilm are frequently reported to exhibit inherent tolerance to antimicrobial compounds, and might therefore contribute to the persistence of infections. Antimicrobial peptides are attracting increasing interest as new potential antimicrobial therapeutics; however, little is known about potential mechanisms, which might contribute to resistance or tolerance development towards these compounds in biofilms. Here we provide evidence that a spatially distinct subpopulation of metabolically active cells in Pseudomonas aeruginosa biofilms is able to develop tolerance to the antimicrobial peptide colistin. On the contrary, biofilm cells exhibiting low metabolic activity were killed by colistin. We demonstrate that the subpopulation of metabolically active cells is able to adapt to colistin by inducing a specific adaptation mechanism mediated by the pmr operon, as well as an unspecific adaptation mechanism mediated by the mexAB‐oprM genes. Mutants defective in either pmr‐mediated lipopolysaccharide modification or in mexAB‐oprM‐mediated antimicrobial efflux were not able to develop a tolerant subpopulation in biofilms. In contrast to the observed pattern of colistin‐mediated killing in biofilms, conventional antimicrobial compounds such as ciprofloxacin and tetracycline were found to specifically kill the subpopulation of metabolically active biofilm cells, whereas the subpopulation exhibiting low metabolic activity survived the treatment. Consequently, targeting the two physiologically distinct subpopulations by combined antimicrobial treatment with either ciprofloxacin and colistin or tetracycline and colistin almost completely eradicated all biofilm cells.
The d‐alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum‐mediated protection from visceral pain perception in a rat colorectal distension model
Authors: Duncker S. C. , Wang L. , Hols P. , Bienenstock J.
Published: February 2008

Abstract  The mechanisms leading to positive effects of probiotics in irritable bowel syndrome and inflammatory bowel disease have not been clarified, but the possible involvement of cell wall components is widely discussed. Reduction of the d‐alanine content of lipoteichoic acid (LTA) in Lactobacillus plantarum (Dlt− mutant) enhanced its anti‐inflammatory properties in a mouse colitis model. Another lactobacillus species inhibited visceral pain perception in response to colorectal distension (CRD) in rats. Therefore, we investigated if LTA modification influences the constitutive intestinal pain perception in addition to modulation of cytokine release. Male Sprague‐Dawley rats were gavaged with L. plantarum, L. plantarum Dlt− mutant or buffer control, respectively and the responses to CRD were tested in this non‐inflammatory model. Tumour necrosis factor (TNF), interferon (IFN)‐gamma and interleukin (IL)‐10 release were measured in colon tissue homogenates and upon anti‐CD3/CD28 activation of isolated splenocytes and mesenteric lymphocytes. Control animals showed significant bradycardia following noxious CRD, whereas only the L. plantarum Dlt− mutant inhibited the response. The mutant also decreased the activation‐induced release of TNF and IFN‐gamma from mesenteric T cells and the IL‐10 concentration in colonic tissue, while increasing the activation‐induced secretion of IL‐10 in splenocytes and mesenteric lymphocytes and the baseline IL‐10 release of splenocytes. In conclusion, d‐alanine depletion of LTA in L. plantarum inhibited visceral pain perception in healthy, non‐inflamed rats. Regardless of the non‐inflammatory nature of the model decreased visceral pain perception was seen in parallel with anti‐inflammatory properties.
Right atrial thrombosis complicating renal transplantation in a child
Authors: Bilginer Yelda , Ozaltin Fatih , Duzova Ali , Erdogan Ilkay , Aki Tuncay Fazil , Demircin Metin , Bakkaloglu Mehmet , Bakkaloglu Aysin
Published: February 2008

Abstract:  Nephrotic syndrome represents a form of acquired thrombophilia thereby causing increased risk of thrombosis. In patients with nephrotic syndrome both venous and arterial thrombosis can occur; however, intracardiac thrombus is among the rarest reported in the literature. In this case report, we present a 10.5‐yr‐old boy with right atrial thrombosis and an acute rejection episode after renal transplantation due to end stage renal disease caused by focal segmental glomerulosclerosis manifested by nephrotic syndrome. The clinical course was successfully managed with surgical removal of thrombus, institution of anticoagulant as well as antirejection therapy. This report draws attention to the risks that could be associated with thrombosis in renal recipients with congenital or acquired thrombophilias and emphasizes the importance of identifying risk factors for thrombosis in these patients.
Cellular mechanisms of potassium transport in plants
Authors: Britto Dev T. , Kronzucker Herbert J.
Published: February 2008

Potassium (K+) is the most abundant ion in the plant cell and is required for a wide array of functions, ranging from the maintenance of electrical potential gradients across cell membranes, to the generation of turgor, to the activation of numerous enzymes. The majority of these functions depend more or less directly upon the activities and regulation of membrane‐bound K+transport proteins, operating over a wide range of K+concentrations. Here, we review the physiological aspects of potassium transport systems in the plasma membrane, re‐examining fundamental problems in the field such as the distinctions between high‐ and low‐affinity transport systems, the interactions between K+and other ions such as NH4+and Na+, the regulation of cellular K+pools, the generation of electrical potentials and the problems involved in measurement of unidirectional K+fluxes. We place these discussions in the context of recent discoveries in the molecular biology of K+acquisition and produce an overview of gene families encoding K+transporters.
Exploring the reasons why adolescents participate in physical activity and identifying strategies that facilitate their involvement in such activity
Authors: Ketteridge Asha , Boshoff Kobie
Published: February 2008

Background:  Prompted by the dramatic rise in obesity and the decline in physical activity of adolescents aged 11–15 years, this study explored, from the participants’ viewpoints, the influences contributing to the engagement of adolescents in physical activities and the strategies facilitating their participation in physical activities.

Methods:  An interpretive qualitative methodology was used involving 13 adolescents in three separate activity‐based focus groups.

Results:  The findings describe the personal abilities of the participants and the health benefits, psychological, emotional and environmental factors influencing participation in physical activity. Findings endorse the use of supportive, enjoyable and skill‐appropriate approaches to physical activity intervention.

Conclusions:  Implications for occupational therapy include promoting physical activities as aspects of occupations to improve the health and well‐being of adolescents through engagement in such activities.
MECHANICAL AND CIRCULATING BIOMARKERS IN ISOLATED CLINIC HYPERTENSION
Authors: Martin Catherine , Cameron James , McGrath Barry
Published: February 2008

This review examines the current evidence for altered mechanical and circulating biomarkers in isolated clinic hypertension and their potential significance.

Arterial stiffness, as assessed by central pulse wave velocity, is influenced by multiple cardiovascular risk factors; however, an independent association with isolated clinic hypertension (ICHT) has not been convincingly shown in four small studies.

Endothelial dysfunction, as assessed by brachial artery flow‐mediated vasodilation, circulating levels of endothelial markers (e.g. nitrite/nitrate, von Willebrand factor, endothelin‐1) and/or circulating levels of inhibitors of vascular nitric oxide (plasma asymmetric dimethylarginine, homocysteine), has been shown to be present in established hypertension and to a variable and inconsistent extent in subjects with ICHT.

Evidence of increased oxidative stress in ICHT versus normotensive subjects was found in two of three studies.

Circulating inflammatory markers C‐reactive protein and plasminogen activator inhibitor‐1 were significantly increased in two of three and two of two studies, respectively, in ICHT compared with normotensive subjects.

Urinary albumin excretion is a marker of both arterial and renal disease. The consensus from seven studies in patients with ICHT is that albuminuria is not an independent marker for ICHT.

Studies to date assessing biomarkers in ICHT have been small and cross‐sectional. Larger, long‐term longitudinal studies of arterial functional and circulating biomarkers are required to assess the potential vascular impact of ICHT.