bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo therapeutic efficacy of the PPAR‐γ agonist troglitazone in combination with cisplatin against malignant pleural mesothelioma cell growth
Authors: Hamaguchi Naohiko , Hamada Hironobu , Miyoshi Seigo , Irifune Kazunori , Ito Ryoji , Miyazaki Tatsuhiko , Higaki Jitsuo
Published: May 2010

Malignant pleural mesothelioma (MPM), an aggressive and refractory tumor type, is increasing in frequency throughout the world. Peroxisome proliferator activated receptor‐γ (PPAR‐γ) agonists have anticancer activity against several cancer cell lines in vitro and in vivo. However, there have been no reports that PPAR‐γ agonists induce growth inhibition of MPM cell lines. In this study, we investigated the inhibitory effect of a PPAR‐γ agonist in combination with an anticancer agent on MPM cell growth in vitro and in vivo. We examined the therapeutic efficacy of the PPAR‐γ agonist troglitazone (TGZ) in combination with cisplatin against a human MPM cell line, both in vitro and orthotopically inoculated into severe combined immunodeficient (SCID) mice. Troglitazone (TGZ) alone inhibited MPM cell growth in vitro in a dose‐dependent manner via induction of G1 cell cycle arrest and apoptosis. The combination of TGZ and cisplatin showed an additive inhibitory effect on MPM cell growth compared to treatment with either individual drug. Treatment with 500 mg/kg or 1000 mg/kg TGZ effectively inhibited the production of thoracic tumors and pleural effusion in EHMES‐10 cell‐bearing SCID mice. Moreover, treatment with 500 mg/kg TGZ in combination with 3 mg/kg cisplatin more effectively prolonged survival compared to treatment with either individual drug. These results suggest that TGZ in combination with cisplatin may become a novel therapy for MPM. (Cancer Sci 2010)
Enhanced adherence to HCV therapy with higher dose ribavirin formulation: final analyses from the ADHERE registry
Authors: Alam I. , Stainbrook T. , Cecil B. , Kistler K. D.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 535–542

Background  Poor adherence to Hepatitis C virus (HCV) treatment is an important cause of treatment failure. Traditional ribavirin 200 mg (RBV) treatment is associated with a significant daily pill burden. RibaPak (RBP), available as 400 mg and 600 mg ribavirin tablets, offers simplified dosing at two pills daily.

Aim  To examine whether improved adherence was associated with RBP vs. RBV.

Methods  Accurate Dosing in Hepatitis C: Examining the RibaPak Experience (ADHERE) was a U.S., multi‐centre, prospective registry capturing data on adherence with RBP vs. RBV in adults with HCV. Adherence was measured by the proportion of subjects remaining on treatment at weeks 4, 12 and 24; by pill counts; and by the proportion of subjects who took ≥80% of their prescribed dose.

Results A total of 503 patients (RBP = 346, RBV = 157) from 33 sites were included. A greater proportion of RBV vs. RBP subjects prematurely discontinued treatment. At 12 and 24 weeks, a greater proportion of RBP vs. RBV subjects took ≥80% of their prescribed doses (P < 0.05). For patients who remained on treatment, the mean milligrams missed per day was significantly greater for RBV vs. RBP at 24 weeks.

Conclusions  First line treatment with RBP may offer the best prospect for less discontinuation and improved treatment adherence.
Effectiveness of antibiotics for acute sinusitis in real‐life medical practice
Authors: Blin Patrick , Blazejewski Sylvie , Lignot Séverine , Lassalle Régis , Bernard Marie‐Agnès , Jayles Delphine , Théophile Hélène , Bénichou Jacques , Demeaux Jean‐Louis , Ebbo David , Franck Jacques , Moride Yola , Peyramond Dominique , Rouveix Bernard , Sturkenboom Miriam , Gehanno Paul , Droz Cécile , Moore Nicholas
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Determining bacterial aetiology of acute sinusitis is difficult without employing invasive procedures.

• Most episodes of acute sinusitis resolve spontaneously.

• Antibiotics have demonstrated efficacy for the treatment of acute bacterial sinusitis in clinical trials yet little is known of their effectiveness in real‐life treatment settings.

WHAT THIS STUDY ADDS

• Most cases of untreated acute sinusitis resolved spontaneously. Antibiotics were more effective when given within the first 10 days of treatment. This had no effect on later recurrence.

• Patients with poor oro‐dental condition or recent antibiotic use may derive the most benefit from an antibiotic prescription and this should be considered by prescribers.

• The antibiotics used were found to be equally effective.

• Existing recommendations to identify acute sinusitis with high probability of bacterial origin, such as the French recommendations, fever or duration of symptoms fail to identify patients in whom antibiotics are more effective.

AIMS

To assess the effectiveness of antibiotics in acute bacterial sinusitis.

METHODS

This was a prospective cohort study with 2 months follow‐up of 5640 patients with acute sinusitis included by a random sample from 1174 GPs and 120 ENT specialists. Main outcomes were short‐term initial success, defined as the absence of prescription of (another) antibiotic or sinus lavage within 10 days, and lack of recurrence between the 11th and 60th day, after initial success.

RESULTS

Initial success was found in 88.7% (95% CI 85.1, 91.4%) of patients without antibiotic prescription at inclusion and 96.2% (95% CI 95.7, 96.7%) of patients prescribed antibiotics. The 10 day adjusted hazard ratio (HR) for treatment failure (new antibiotic prescription or sinus drainage) with initial antibiotics compared with no antibiotics was 0.30 (95% CI 0.21, 0.42) with no difference between antibiotics. Antibiotics were more effective in patients with poor oro‐dental condition (HR 0.04, 95% CI 0.01, 0.20) and in patients who had already used antibiotics during the previous 2 months (HR 0.09, 95% CI 0.03, 0.28). For patients without failure at 10 days, recurrence between the 11th and 60th day was similar whether or not they had initially been prescribed an antibiotic, 94.1% (95% CI 93.4, 94.7%) and 93.4% (95%CI 90.3, 95.5%), respectively.

CONCLUSION

Most acute sinusitis cases not prescribed antibiotics resolve spontaneously. Antibiotics reduced by 3.3‐fold the risk of failure within 10 days, without impact on later recurrence. The greatest benefit of antibiotics was found for patients with poor oro‐dental condition or with antibiotic use within the previous 2 months.
Emerging treatment options for type 2 diabetes
Authors: Piya Milan K. , Tahrani Abd A. , Barnett Anthony H.
Published: May 2010

Type 2 diabetes mellitus (T2DM) is rapidly increasing in prevalence and is a major public health problem. It is a progressive disease which commonly requires multiple pharmacotherapy. Current options for treatment may have undesirable side effects (particularly weight gain and hypoglycaemia) and contraindications, and little effect on disease progression. Incretin based therapy is one of several newer therapies to improve glycaemia and is available in two different forms, dipeptidyl peptidase‐4 (DPP‐4) inhibitors and glucagon‐like peptide‐1 (GLP‐1) agonists. Use of these agents results in a ‘glucose‐dependant’ increase in insulin secretion and glucagon suppression resulting in improved glycaemia with low incidence of hypoglycaemia. DPP‐4 inhibitors are oral drugs which are weight neutral, while GLP‐1 agonists are injected subcutaneously and help promote weight loss while improving glycaemia. GLP‐1 agonists have also been shown to increase beta cell mass in rat models. Bariatric surgery is another option for the obese patient with T2DM, with blood glucose normalizing in over half of the patients following surgery. Other therapies in development for the treatment of T2DM include sodium‐glucose transporter 2 (SGLT‐2) inhibitors, glucagon receptor antagonists, glucokinase activators and sirtuins. In this article, we will review the various existing and emerging treatment options for T2DM.
Perceived adverse drug reactions among non‐institutionalized children and adolescents in Germany
Authors: Knopf Hildtraud , Du Yong
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Drug safety in paediatric medication is a public health concern. According to previous studies, the incidence of adverse drug reactions (ADRs) varies greatly from 0.7% to 2.7% among paediatric outpatients and from 2.6% to 18.1% among paediatric inpatients. Little has been reported on the risks of drug use in the general child population.

WHAT THIS STUDY ADDS

Our study showed that the prevalence of perceived ADRs in Germany was 0.9% among non‐institutionalized children in general and 1.7% among children who had used at least one medicine within the 7 days before the medical interview. Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and for identifying risk factors among non‐institutionalized children. They should be taken into account together with other pharmacovigilance systems.

AIMS

Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non‐institutionalized children in Germany.

METHODS

All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0–17 years who participated in the 2003–06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children's parents and confirmed by trained medical professionals during the medical interview.

RESULTS

One hundred and fifty‐seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders. Perceived ADRs were most frequently reported in relation to drugs acting on the nervous system (25.8%), followed by systemic anti‐infectives (18.7%) and drugs acting on the respiratory system (16.2%). Risk factors for perceived ADRs included older age groups, polypharmacy (≥2) and a poor health status.

CONCLUSION

Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and identifying risk factors among non‐institutionalized children. They should be taken into account together with other pharmacovigilance systems.
Estimates of asthma heritability in a large twin sample
Authors: Thomsen S. F. , Van Der Sluis S. , Kyvik K. O. , Skytthe A. , Backer V.
Published: May 2010

Background
Asthma is a complex disease characterized by symptoms of wheezing, shortness of breath, chest tightness, and cough.

Objective
To study the relative contribution of genetic and environmental factors in the liability to asthma in a large sample of twins.

Methods
Data on asthma in 21 135 twin pairs, 3–71 years of age, from the Danish Twin Registry were collected via a multidisciplinary questionnaire survey. Heritability estimates were calculated using variance components models.

Results
A monozygotic twin had an approximately sixfold increased risk of asthma whereas a dizygotic twin only had an approximately threefold increased risk relative to the general population if his or her co‐twin was affected. The difference was more pronounced among males. Familial aggregation of asthma in children and adolescents was explained mainly by additive genetic factors, but common environment was also important. The heritability of asthma was also substantial in adults aged 20–49 years. In older adults (aged 50–71 years), additive genetic factors did not significantly influence the disease risk.

Conclusion
Genetic influences on asthma are substantial throughout the life span but the proportion of the disease liability explained by genetic factors is decreased in older adults.

Cite this as: S. F. Thomsen, S. van der Sluis, K. O. Kyvik, A. Skytthe, V. Backer, Clinical & Experimental Allergy, 2010 (40) 1054–1061.
Effects of soil‐surface microbial community phenotype upon physical and hydrological properties of an arable soil: a microcosm study
Authors: Jeffery S. , Harris J. A. , Rickson R. J. , Ritz K.
Published: May 2010

The nature of the first few millimetres of the soil surface strongly affects water infiltration rates, generation of run‐off, soil detachment and sediment transport. We hypothesized that the phenotypic community structure of the soil‐surface microbiota affects the physical and hydrological properties of an arable soil. A range of contrasting microbial community phenotypes were established in microcosms by manipulating the wavelength of light reaching the soil surface, with the microcosms being incubated in the field for approximately 6 months. Phenotypes were characterized by phospholipid fatty acid (PLFA), ergosterol and chlorophyll analysis. The microcosms were then subjected to simulated rainfall at an intensity of 60 mm hour−1 for 20 minutes at a slope gradient of 9°. Water infiltration rates, run‐off generation, soil loss (including a particle‐size analysis of the sediment) and soil‐surface shear strength were quantified.

Distinct microbial phenotypes developed on the soil surfaces with UV‐A and restricted‐UV treatments when compared with subsurface layers. There was significantly greater fungal biomass in the no‐light treatment when compared with all other treatments, with approximately 4.5 times more ergosterol being extracted from the subsurface layer of the no‐light treatment when compared with other treatments. The no‐light treatment produced the greatest amount of run‐off, which was approximately 15% greater than the restricted photosynthetically‐active radiation (PAR) treatment. Significant differences between treatments were also found in shear strengths, with increasing strength being correlated with increasing ergosterol concentration. Water infiltration, erosion and the sediment concentrations in run‐off were not significantly different between treatments. This work demonstrates that the quality of light reaching the soil surface affects the microbial phenotype, in turn producing functional consequences with regard to the physical and hydrological properties of arable soil surfaces.
Longevity cost of remaining unmated under dietary restriction
Authors: Stoltz Jeffrey A. , Hanna Ramez , Andrade Maydianne C.B.
Published: May 2010

1. Increases in longevity from dietary restriction (DR) have been linked to the evolution of physiological strategies for maintaining lifetime reproductive output despite periods of nutritional deficiency. If this is the case, then reproductive life history and mating status should determine whether or not dietary restriction increases longevity.

2. We investigate the effects of DR and mating status (mated or unmated) on longevity and lifetime reproductive output and explore mechanisms underlying these patterns by measuring resting energetic rates and changes in mass over time. We study iteroparous female Australian redback spiders (Latrodectus hasselti), which are known to tolerate periods of starvation (ecologically relevant DR) in nature.

3. Mated DR females had the highest longevity of any experimental group, in strong contrast to results for semelparous males of this species [M.M. Kasumovic, M.C.B. Andrade & R.C. Brooks (2009), Biology Letters,5, 636]. Most strikingly, mated females (whether DR or not) had higher longevity than unmated females.

4. Mated females rapidly decreased their resting energetic rates and stopped egg production under DR. Once feeding returned to normal, resting energetic rates of mated females increased immediately, egg sac production continued and there was no net decrease in lifetime reproductive output relative to mated females without DR.

5. This shows DR increases longevity for mated females, but there is a longevity cost of remaining unmated, which may arise because unmated females (regardless of diet) maintained high energetic rates. This may be an evolved pattern of physiological support for reproductive readiness which exerts a fitness cost when mating is delayed. Taken together, these results suggest positive effects of DR on longevity critically depend on reproductive life history (iteroparity or semelparity) and individual mating status.
Characterization of the testis‐specific promoter region in the human pituitary adenylate cyclase‐activating polypeptide (PACAP) gene
Authors: Tominaga Aiko , Sugawara Hideki , Futagawa Toshitaka , Inoue Kazuhiko , Sasaki Kazuki , Minamino Naoto , Hatakeyama Mamoru , Handa Hiroshi , Miyata Atsuro
Published: May 2010

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a pleiotropic neuropeptide localized in the testis at concentration comparable to that found in the brain, suggesting involvement in spermatogenesis. In this study, we identified the human PACAP testis‐specific exon (TSE) 10.9 kb upstream from the translational start site and found that the testis‐specific transcript of the human PACAP gene was found to be spliced from the TSE into a region of intron 2 without a frameshift. The resulting PACAP precursor has no signal peptide, suggesting that PACAP functions physiologically in an intracrine manner in the testis. The 5′‐flanking region of the TSE contains an 80‐bp fragment with potent promoter activity in testicular F9 cell. Electrophoresis mobility shift assays showed that proteins from the F9 nuclear extract interacted specifically with the 80‐bp fragment. DNA affinity chromatography allowed isolation of the specific proteins bound to the 80‐bp fragment, two of which were identified as Poly (ADP‐ribose) polymerase‐1 (PARP‐1) and TIA‐1‐related protein (TIAR) by mass spectrometry. By using their siRNAs, the depletion of their proteins in F9 cells affected the potent promoter activity of the 80‐bp fragment, suggesting that they might be involved in the testis‐specific gene expression of PACAP.
Future active layer dynamics and carbon dioxide production from thawing permafrost layers in Northeast Greenland
Authors: HOLLESEN J. , ELBERLING B. , JANSSON P. E.
Published: May 2010

Thawing permafrost and the resulting mineralization of previously frozen organic carbon (C) is considered an important future feedback from terrestrial ecosystems to the atmosphere. Here, we use a dynamic process oriented permafrost model, the CoupModel, to link surface and subsurface temperatures from a moist permafrost soil in High‐Arctic Greenland with observed heat production and carbon dioxide (CO2) release rates from decomposition of previously frozen organic matter. Observations show that the maximum thickness of the active layer at the end of the summer has increased 1 cm yr−1 since 1996. The model is successfully adjusted and applied for the study area and shown to be able to simulate active layer dynamics. Subsequently, the model is used to predict the active layer thickness under future warming scenarios. The model predicts an increase of maximum active layer thickness from today 70 to 80–105 cm as a result of a 2–6 °C warming. An additional increase in the maximum active layer thickness of a few centimetres may be expected due to heat production from decomposition of organic matter. Simulated future soil temperatures and water contents are subsequently used with measured basal soil respiration rates in a respiration model to predict the corresponding depth‐integrated CO2 production from permafrost layers between 0.7 and 2 m below the surface. Results show an increase from present values of <40 g C m−2 yr−1 to between 120 and 213 g C m−2 yr−1 depending on the magnitude of predicted warming. These rates are more than 50% of the present soil CO2 efflux measured at the soil surface. Future modelling accounting for snow, vegetation and internal biological heat feedbacks are of interest in order to test the robustness of the above predictions and to describe the entire ecosystem response.
Climate change predicted to cause severe increase of organic carbon in lakes
Authors: LARSEN SØREN , ANDERSEN TOM , HESSEN DAG O.
Published: May 2010

Riverine transport of organic carbon (OC) to the ocean is a significant component in the global carbon (C) cycle and the concentration of total organic carbon (TOC) in rivers and lakes is vital for ecosystem properties and water quality for human use. By use of a large dataset comprising chemical variables and detailed catchment information in ∼1000 Norwegian pristine lakes covering a wide climatic range, we were able to predict TOC concentrations with high accuracy. We further predict, using a ‘space‐for‐time’ approach and a downscaled, moderate, climate change scenario, that northern, boreal regions likely will experience strong increases in OC export from catchments to surface waters. Median concentrations of OC in these lakes will increase by 65%, from the current median of 2.0–3.3 mg C L−1. This is a long‐term effect, primarily mediated by increased terrestrial vegetation cover in response to climate change. This increase OC will have severe impacts on food‐webs, productivity and human use. Given the robustness of the estimates and the general applicability of the parameters, we suggest that these findings would be relevant to boreal areas in general.
Nitrous oxide fluxes from a grain–legume crop (narrow‐leafed lupin) grown in a semiarid climate
Authors: BARTON LOUISE , BUTTERBACH‐BAHL KLAUS , KIESE RALF , MURPHY DANIEL V.
Published: May 2010

Understanding nitrous oxide (N2O) fluxes from grain–legume crops in semiarid and arid regions is necessary if we are to improve our knowledge of global terrestrial N2O losses resulting from biological N2 fixation. N2O fluxes were measured from a rain‐fed soil, cropped to a grain–legume in a semiarid region of southwestern Australia for 1 year on a subdaily basis. The site included plots planted to narrow‐leafed lupin (Lupinus angustifolius; ‘lupin’) and plots left bare (no lupin). Fluxes were measured using soil chambers connected to a fully automated system that measured N2O by gas chromatography. Daily N2O fluxes were low (−0.5 to 24 g N2O‐N ha−1 day−1) and not different between treatments, culminating in an annual loss of 127 g N2O‐N ha−1. Greatest daily N2O fluxes occurred from both treatments in the postharvest period, and following a series of summer and autumn rainfall events. At this time of the year, soil conditions were conducive to soil microbial N2O production: elevated soil water contents, increased inorganic nitrogen (N) and dissolved organic carbon concentrations, and soil temperatures generally > 25 °C; furthermore, there was no active plant growth to compete for mineralized N. N2O emissions from the decomposition of legume crop residue were low, and approximately half that predicted using the currently recommended IPCC methodology. Furthermore, the contribution of the biological N2 fixation process to N2O emissions appeared negligible in the present study, supporting its omission as a source of N2O from the IPCC methodology for preparing national greenhouse gas inventories.
Fungal endophytes reduce regrowth and affect competitiveness of meadow fescue in early succession of pastures
Authors: Saari S. , Helander M. , Lehtonen P. , Wallius E. , Saikkonen K.
Published: May 2010

Systemic‐ and seed‐transmitted fungal endophytes are suggested to enhance competitive dominance of agronomic grasses by increasing plant growth and defence against herbivores. We studied whether Neotyphodium uncinatum endophyte infection frequencies of meadow fescue (Schedonorus pratensis) and botanical composition of pastures are affected by 4, 5, 7 and 21 years of grazing by dairy cattle. We then examined with one greenhouse and two field experiments, whether endophyte infection and clipping affect regrowth of young or mature plants relative to nutrient availability in soil. The frequencies of infected plants and the number of plant species were less in grazed parts of the pastures. Endophytes significantly reduced relative regrowth and dry biomass of regrowth of the grass irrespective of nutrient levels in a 1‐year‐old field (on an average 18% in 2 months) and under high nutrient conditions in the greenhouse experiment (on an average 3% in 3 months) respectively. However, effects of endophytes were not detected in 5‐year‐old fields and under low nutrient conditions in the greenhouse. In contrast to past studies, our results demonstrate that grazing may negatively affect endophyte–grass symbiosis and number of plant species of successional pastures, and suggest that the effects of endophytes may be linked to the ontogeny of the host.
Von Willebrand factor – two sides and the edge of a coin
Authors: RANGARAJAN S.
Published: May 2010

Summary.  Von Willebrand factor (VWF) has multiple functions in coagulation. It is a clotting protein and its deficiency causes a primary haemostatic bleeding disorder. Excess VWF, particularly high molecular weight multimers can cause thrombosis. There is also a debatable function of protecting factor VIII (FVIII) in circulation with the prevention of development of FVIII inhibitors. This commentary addresses these functions.
Major histocompatibility complex class I binding predictions as a tool in epitope discovery
Authors: Lundegaard Claus , Lund Ole , Buus Søren , Nielsen Morten
Published: May 2010

Over the last decade, in silico models of the major histocompatibility complex (MHC) class I pathway have developed significantly. Before, peptide binding could only be reliably modelled for a few major human or mouse histocompatibility molecules; now, high‐accuracy predictions are available for any human leucocyte antigen (HLA) ‐A or ‐B molecule with known protein sequence. Furthermore, peptide binding to MHC molecules from several non‐human primates, mouse strains and other mammals can now be predicted. In this review, a number of different prediction methods are briefly explained, highlighting the most useful and historically important. Selected case stories, where these ‘reverse immunology’ systems have been used in actual epitope discovery, are briefly reviewed. We conclude that this new generation of epitope discovery systems has become a highly efficient tool for epitope discovery, and recommend that the less accurate prediction systems of the past be abandoned, as these are obsolete.
Macrophages express membrane bound form of APRIL that can generate immunomodulatory signals
Authors: Lee Sang‐Min , Jeon Sung‐Tak , Suk Kyoungho , Lee Won‐Ha
Published: May 2010

Members of the tumour necrosis factor superfamily play an essential role in inducing various biological responses including proliferation, differentiation, survival and cell death. A proliferation‐inducing ligand (APRIL), first identified as a stimulant of tumour proliferation, is now known as a regulator of B‐cell‐mediated immune responses through the modulation of B‐cell survival and activation. However, the role of APRIL in macrophage function has not been explored. High level expression of APRIL was detected on the surface of cells of the monocytic lineage including the human macrophage‐like cell line, THP‐1. To identify the role of APRIL in macrophage functions, THP‐1 cells were stimulated with either its counterpart (TACI : Fc fusion protein) or a monoclonal antibody that is specific to APRIL. Stimulation of APRIL resulted in the expression of pro‐inflammatory mediators such as interleukin‐8 and matrix metalloproteinase‐9 through the activation of mitogen‐activated protein kinase and nuclear factor‐κB. In contrast, stimulation of APRIL had an inhibitory effect on processes that require cytoskeletal movement such as phagocytosis of opsonized zymosan and chemotaxis through an inhibition of phosphatidylinositol 3‐kinase activity. These observations demonstrate that macrophages express a membrane‐bound form of APRIL which, upon stimulation, modulates the activities of macrophages through stimulation or inhibition of processes associated with inflammation.
Stromal cells differentially regulate neutrophil and lymphocyte recruitment through the endothelium
Authors: McGettrick Helen M. , Buckley Christopher D. , Filer Andrew , Ed Rainger G. , Nash Gerard B.
Published: May 2010

Stromal fibroblasts modify the initial recruitment of leucocytes by endothelial cells (EC), but their effects on subsequent transendothelial migration remain unclear. Here, EC and dermal or synovial fibroblasts were cultured on opposite surfaces of 3‐μm pore filters and incorporated in static or flow‐based migration assays. Fibroblasts had little effect on tumour necrosis factor‐α‐induced transendothelial migration of neutrophils, but tended to increase the efficiency of migration away from the endothelium. Surprisingly, similar close contact between EC and fibroblasts strongly reduced lymphocyte migration in static assays, and nearly abolished stable lymphocyte adhesion from flow. Fibroblasts did not alter endothelial surface expression of adhesion molecules or messenger RNA for chemokines. Inhibition of attachment did not occur when EC‐fibroblast contact was restricted by using 0·4‐μm pore filters, but under these conditions pre‐treatment with heparinase partially inhibited adhesion. In the 3‐μm pore co‐cultures, inhibition of metalloproteinase activity partially recovered lymphocyte adhesion, but addition of CXCL12 (SDF‐1α) to the endothelial surface did not. Hence, the ability of EC to present activating chemokines for lymphocytes may have been enzymatically inhibited by direct contact with fibroblasts. To avoid contact, we cultured EC and fibroblasts on separate 3‐μm pore filters one above the other. Here, fibroblasts promoted the transendothelial migration of lymphocytes. Fibroblasts generate CXCL12, but blockade of CXCL12 receptor had no effect on lymphocyte migration. While stromal cells can provide signal(s) promoting leucocyte migration away from the sub‐endothelial space, direct cell contact (which might occur in damaged tissue) may cause disruption of chemokine signalling, specifically inhibiting lymphocyte rather than neutrophil recruitment.
LAMP‐2‐deficient human B cells exhibit altered MHC class II presentation of exogenous antigens
Authors: Crotzer Victoria L. , Glosson Nicole , Zhou Delu , Nishino Ichizo , Blum Janice S.
Published: May 2010

Major histocompatibility complex (MHC) class II molecules present antigenic peptides derived from engulfed exogenous proteins to CD4+ T cells. Exogenous antigens are processed in mature endosomes and lysosomes where acidic proteases reside and peptide‐binding to class II alleles is favoured. Hence, maintenance of the microenvironment within these organelles is probably central to efficient MHC class II‐mediated antigen presentation. Lysosome‐associated membrane proteins such as LAMP‐2 reside in mature endosomes and lysosomes, yet their role in exogenous antigen presentation pathways remains untested. In this study, human B cells lacking LAMP‐2 were examined for changes in MHC class II‐restricted antigen presentation. MHC class II presentation of exogenous antigen and peptides to CD4+ T cells was impaired in the LAMP‐2‐deficient B cells. Peptide‐binding to MHC class II on LAMP‐2‐deficient B cells was reduced at physiological pH compared with wild‐type cells. However, peptide‐binding and class II‐restricted antigen presentation were restored by incubation of LAMP‐2‐negative B cells at acidic pH, suggesting that efficient loading of exogenous epitopes by MHC class II molecules is dependent upon LAMP‐2 expression in B cells. Interestingly, class II presentation of an epitope derived from an endogenous transmembrane protein was detected using LAMP‐2‐deficient B cells. Consequently, LAMP‐2 may control the repertoire of peptides displayed by MHC class II molecules on B cells and influence the balance between endogenous and exogenous antigen presentation.
The nuclear question: rethinking species importance in multi‐species animal groups
Authors: Srinivasan Umesh , Raza Rashid Hasnain , Quader Suhel
Published: May 2010

1. Animals group for various benefits, and may form either simple single‐species groups, or more complex multi‐species associations. Multi‐species groups are thought to provide anti‐predator and foraging benefits to participant individuals.

2. Despite detailed studies on multi‐species animal groups, the importance of species in group initiation and maintenance is still rated qualitatively as ‘nuclear’ (maintaining groups) or ‘attendant’ (species following nuclear species) based on species‐specific traits. This overly simplifies and limits understanding of inherently complex associations, and is biologically unrealistic, because species roles in multi‐species groups are: (i) likely to be context‐specific and not simply a fixed species property, and (ii) much more variable than this dichotomy indicates.

3. We propose a new view of species importance (measured as number of inter‐species associations), along a continuum from ‘most nuclear’ to ‘least nuclear’. Using mixed‐species bird flocks from a tropical rainforest in India as an example, we derive inter‐species association measures from randomizations on bird species abundance data (which takes into account species ‘availability’) and data on 86 mixed‐species flocks from two different flock types. Our results show that the number and average strength of inter‐species associations covary positively, and we argue that species with many, strong associations are the most nuclear.

4. From our data, group size and foraging method are ecological and behavioural traits of species that best explain nuclearity in mixed‐species bird flocks. Parallels have been observed in multi‐species fish shoals, in which group size and foraging method, as well as diet, have been shown to correlate with nuclearity. Further, the context in which multi‐species groups occur, in conjunction with species‐specific traits, influences the role played by a species in a multi‐species group, and this highlights the importance of extrinsic factors in shaping species importance.

5. Our view of nuclearity provides predictive power in examining species roles in a variety of situations (e.g. predicting leadership in differently composed communities), and can be applied to examine a broad range of ecological and evolutionary questions pertinent to multi‐species groups in general.
Implementing bedside handover: strategies for change management
Authors: McMurray Anne , Chaboyer Wendy , Wallis Marianne , Fetherston Cathy
Published: May 2010

Aims and objectives.  To identify factors influencing change in two hospitals that moved from taped and verbal nursing handover to bedside handover.

Background.  Bedside handover is based on patient‐centred care, where patients participate in communicating relevant and timely information for care planning. Patient input reduces care fragmentation, miscommunication‐related adverse events, readmissions, duplication of services and enhances satisfaction and continuity of care.

Design.  Analysing change management was a component of a study aimed at developing a standard operating protocol for bedside handover communication. The research was undertaken in two regional acute care hospitals in two different states of Australia.

Method.  Data collection included 532 semi‐structured observations in six wards in the two hospitals and 34 in‐depth interviews conducted with a purposive sample of nursing staff involved in the handovers. Observation and interview data were analysed separately then combined to generate thematic analysis of factors influencing the change process in the transition to bedside handover.

Results and conclusion.  Themes included embedding the change as part of the big picture, the need to link the project to standardisation initiatives, providing reassurance on safety and quality, smoothing out logistical difficulties and learning to listen. We conclude that change is more likely to be successful when it is part of a broader initiative such as a quality improvement strategy.

Relevance to clinical practice.  Nurses are generally supportive of quality improvement initiatives, particularly those aimed at standardising care. For successful implementation, change managers should be mindful of clinicians’ attitudes, motivation and concerns and their need for reassurance when changing their practice. This is particularly important when change is dramatic, as in moving from verbal handover, conducted in the safety of the nursing office, to bedside handover where there is greater transparency and accountability for the accuracy and appropriateness of communication content and processes.
Evaluation of nursing and medical students’ attitudes towards people with disabilities
Authors: Sahin Hatice , Akyol Asiye D
Published: May 2010

Aims and objectives.  The aim of this study is to assess the attitudes of students towards disabled people and provide suggestions to make necessary changes in the curricula.

Background.  Disabled people suffer from rejection, exclusion and discrimination. The undergraduate education of future health professionals should include processes of critical thinking towards and analysis of the disabled.

Design.  Cross‐sectional design was used.

Methods.  All the preclinical medical and nursing students in our institution were included in study. Data were collected using the Turkish Attitudes towards Disabled Person Scale (TATDP) and demographical variables. TATDP Scale was scored according to five‐point Likert Scale.

Results.  Students’ mean attitude score is 120·57 (SD 15·24). Subscale mean scores are 53·61 (SD 7·25) for compassion (CP), 50·47 (SDS 7·26) for social value (SV) and 16·49 (SD 2·89) for resource distribution (RD). Whilst nursing students had less contact with the disabled, medical students had a closer contact with them. Medical students acquired more prior knowledge about attitudes towards the disabled. Total attitude scores of female students were above the students’ mean attitude score when compared to those of male students.

Conclusion.  Only if early contact is established with patients and the disabled, practical educational strategies are adopted, and the students are provided with information on attitudes about the disabled, will a social model of disability be introduced into the curriculum.

Relevance to clinical practice.  This study results were presented to curriculum planning committees of nursing and medical schools, so that they should use them as needs assessment data in developing a disability awareness curriculum. The curriculum will be implemented in cooperation with not only schools but also other social institutions. For instance, clerkship applications will be accomplished by cooperating with nursing homes and organisations of disabled people.
Health‐related beliefs and consumer knowledge as determinants of fish consumption
Authors: Pieniak Z. , Verbeke W. , Scholderer J.
Published: May 2010

Background: Despite scientific evidence on the positive effects of seafood consumption on human health, the consumption of fish remains below the recommended intake levels for the majority of Europeans. The present study aimed to explore cultural differences in potential determinants of fish consumption: consumers’ knowledge and health‐related beliefs, as well as the relationship between those variables, socio‐demographics and fish consumption frequency, using data from five European countries.

Methods: A cross‐sectional consumer survey was carried out in 2004 with representative household samples from Belgium, the Netherlands, Denmark, Poland and Spain. The sample consisted of 4786 respondents, aged 18–84 years, who were responsible for food purchasing and cooking in the household.

Results: European consumers had a very strong belief that eating fish is healthy. Consumers’ belief that eating fish is healthy, their interest in healthy eating and objective fish‐related nutrition knowledge, positively, but only weakly, influenced fish consumption frequency. Subjective knowledge was found to be a stronger predictor of fish consumption than the previously noted factors. Age and education contributed, both directly and indirectly through knowledge, to explain fish consumption behaviour. However, the path coefficients in the estimated model were relatively low, which indicates that fish consumption frequency was also determined by factors other than health‐related beliefs and consumers’ knowledge.

Conclusions: The findings of the present study suggest that communication should focus on health‐related benefits other than fish consumption alone. Communicating that eating fish is healthy and stressing the health benefits of fish alone, as is still commonly performed (e.g. in generic promotion and other types of public information campaigns) will be insufficient to achieve higher levels of compliance with fish consumption recommendations.
Evaluation and standardisation of different matrices used for double‐blind placebo‐controlled food challenges to fish
Authors: Vassilopoulou E. , Douladiris N. , Sakellariou A. , Cortes S. V. , Sinaniotis A. , Rivas M. F. , Papadopoulos N. G.
Published: May 2010

Background:  Fish allergens represent one of the most common causes of adverse reactions to food worldwide. Double‐blind placebo‐controlled food challenges (DBPCFC) are the gold standard for food allergy diagnosis. However, no standardised recipes are available for common food allergens such as fish, and a well trained dietitian is essential for creating and standardising them. The present study aimed to create and standardise recipes for use in DBPCFCs to fish.

Methods:  Three recipes were prepared. Employing a standardised procedure, a total of 35 panelists evaluated the different matrices using an evaluation form. A paired comparison test was used to estimate total evaluation’s outcome. Fish allergic patients were challenged with different fish species blinded with the selected matrix and evaluated the recipe using the same form.

Results:  From a base recipe and step‐by‐step modifications, a low fat recipe was selected among other recipes tested, which proved to be appropriate for fish blinding, in terms of taste, odour, appearance and blinding. Patients challenged with the final matrix found it acceptable, no matter which fish type was used.

Conclusions:  In this pilot study, a recipe with satisfactory organoleptic characteristics was developed and validated for DBPCFC to fish.
Nanomechanical characterization of skin and skin cream
Authors: BHUSHAN B. , TANG W. , GE S.
Published: May 2010

The mechanical properties of skin are an important characteristic of its resistance to damage and important indicators of pathological situations. Skin care products are the most common method to improve skin health and create a smooth, soft, and elastic perception by altering the mechanical properties of skin. It is of interest to study how skin cream affects the mechanical properties of skin. It also can help to quantify the effectiveness of cosmetic products. In this study, we present a systematic study of the mechanical properties of virgin skin and cream‐treated skin. In nanoscratch measurements, the scratch wear tracks were generated at various loads using an atomic force microscope. Hardness and elastic moduli were measured using a nanoindenter. The in situ tensile properties of virgin skin and cream‐treated skin were measured using a custom‐built tensile stage that attaches to the atomic force microscope. Compared with virgin skin, cream‐treated skin exhibits better scratch resistance up to a normal load of 15 μN. The indentation hardness and elastic modulus of cream‐treated skin are lower than that of virgin skin, indicating that the skin cream moistens and softens the skin surface. In the stretching experiments, the elastic modulus is lower and ultimate strain is higher than that of virgin skin, indicating skin cream can improve the tensile response of skin. Mechanisms for the observed trends are discussed.
Characterization of a Leishmania stage‐specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulence
Authors: Dey Ranadhir , Meneses Claudio , Salotra Poonam , Kamhawi Shaden , Nakhasi Hira L. , Duncan Robert
Published: May 2010

Leishmaniasis is caused by the dimorphic protozoan parasite Leishmania. Differentiation of the insect form, promastigotes, to the vertebrate form, amastigotes, and survival inside the vertebrate host accompanies a drastic metabolic shift. We describe a gene first identified in amastigotes that is essential for survival inside the host. Gene expression analysis identified a 27 kDa protein‐encoding gene (Ldp27) that was more abundantly expressed in amastigotes and metacyclic promastigotes than in procyclic promastigotes. Immunofluorescence and biochemical analysis revealed that Ldp27 is a mitochondrial membrane protein. Co‐immunoprecipitation using antibodies to the cytochrome c oxidase (COX) complex, present in the inner mitochondrial membrane, placed the p27 protein in the COX complex. Ldp27 gene‐deleted parasites (Ldp27−/−) showed significantly less COX activity and ATP synthesis than wild type in intracellular amastigotes. Moreover, the Ldp27−/− parasites were less virulent both in human macrophages and in BALB/c mice. These results demonstrate that Ldp27 is an important component of an active COX complex enhancing oxidative phosphorylation specifically in infectious metacyclics and amastigotes and promoting parasite survival in the host. Thus, Ldp27 can be explored as a potential drug target and parasites devoid of the p27 gene could be considered as a live attenuated vaccine candidate against visceral leishmaniasis.
Selective inactivation of SIDER2 retroposon‐mediated mRNA decay contributes to stage‐ and species‐specific gene expression in Leishmania
Authors: Müller Michaela , Padmanabhan Prasad K. , Papadopoulou Barbara
Published: May 2010

Despite their high genomic synteny, the Leishmania major and Leishmania infantum species exhibit extensive differences in mRNA expression patterns throughout the parasite's development. Yet, the underlying mechanisms for this species‐specific differential gene expression are largely unknown. Here we report that Short Interspersed DEgenerated Retroposons of the SIDER2 subfamily, shown previously to promote rapid mRNA turnover, confer differential regulation of orthologous transcripts resulting in a stage‐ and species‐specific gene expression. We demonstrate that SIDER2‐mediated decay of two L. major transcripts encoding a hypothetical protein and an aminomethyltransferase to a similar extent in promastigote and amastigote developmental forms results in a constitutive low expression of the corresponding proteins. In contrast, their L. infantum orthologs are differentially expressed due to the selective inactivation of SIDER2 in intracellular amastigotes. Inactivation of the SIDER2 function blocks the SIDER2‐mediated deadenylation‐independent decay pathway, and stabilized transcripts are degraded by a slower, deadenylation‐dependent mechanism. Sequence variations in SIDER2 retroposons between orthologous transcripts do not contribute to SIDER2 inactivation. Our data suggest that SIDER2 inactivation is 3′‐untranslated region context‐dependent and that involves possibly species‐ and stage‐specific trans‐acting factor(s). These findings further emphasize the important contribution of SIDER retroposons in the control of gene expression across the Leishmania genus.