bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboprophylaxis in patients with lower limb immobilisation – review of current status
Authors: Nokes Timothy J. C. , Keenan Jonathan
Published: June 2009

The risk for venous thromboembolism (VTE) associated with lower limb immobilisation is unclear, owing to of a lack of evidence from studies in this patient group. However, six small, randomised control trials (RCTs), totalling 1536 patients, compared low molecular weight heparin (LMWH) with controls and showed a significant reduction in asymptomatic deep vein thrombosis (DVT) from 17·1% to 9·8%, with very low bleeding rates. This is likely to be an underestimate of the real risk reduction as most trials excluded high‐risk patients from randomisation. There have been no other controlled trials in cast‐immobilised patients using alternative prophylactic measures. Together with the RCTs, other cohort studies have identified risk factors that increase the risk for VTE in lower limb immobilisation. In summary, patients in lower limb cast (or brace) immobilisation should be risk assessed and those deemed high risk for VTE should receive prophylactic LMWH for at least the duration of cast immobilisation.
Phase II study of a TLR‐9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma
Authors: Friedberg Jonathan W. , Kelly Jennifer L. , Neuberg Donna , Peterson Derick R. , Kutok Jeffery L. , Salloum Rabih , Brenn Thomas , Fisher David C. , Ronan Elizabeth , Dalton Virginia , Rich Lynn , Marquis Diana , Sims Paul , Rothberg Paul G. , Liesveld Jane , Fisher Richard I. , Coffman Robert , Mosmann Tim , Freedman Arnold S.
Published: June 2009

Toll‐like receptor‐9 (TLR‐9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody‐dependent cell‐mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR‐9 agonist (1018 ISS, 0·2 mg/kg sc weekly × 4 beginning day 8) with standard rituximab (375 mg/m2 weekly × 4) in patients (n = 23) with relapsed/refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was well‐tolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progression‐free survival was 9 months. Biologically relevant increases in ADCC and circulating CD‐3 positive T cells were observed in 35% and 39% of patients, respectively. Forty‐five percent of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post‐therapy. Pre‐ and post‐biopsies of tumour tissue demonstrated an infiltration of CD8+ T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma.
Impaired activation of Stat1 and c-Jun as a possible defect in macrophages of patients with active tuberculosis
Authors: Esquivel-Solís H , Quiñones-Falconi F , Zarain-Herzberg A , Amieva-Fernández R I , López-Vidal Y
Published: June 2009

Studies of patients with active tuberculosis (TB) and infected healthy individuals have shown that interferon (IFN)-γ is present in sites of Mycobacterium tuberculosis infection in comparable levels. This suggests that there is a deficiency in the macrophage response to IFN-γ in TB patients. We used recombinant human IFN-γ to stimulate adherent monocyte-derived macrophages from three groups of people: patients with active tuberculosis (TBP), their healthy household contacts (HHC) and healthy uninfected controls from the community (CC). We then evaluated the ability of the macrophages to inhibit the growth of M. tuberculosis H37Rv as well as their cytokine profile at early in infection (48 h). After IFN-γ treatment, macrophages of healthy individuals (HHC and CC) controlled M. tuberculosis growth and produced mainly nitric oxide (NO) and interleukin (IL)-12p70, whereas TBP macrophages did not kill M. tuberculosis. Additionally, TBP macrophages produced low levels of NO and IL-12p70 and high levels of tumour necrosis factor (TNF)-α and IL-10. Transforming growth factor (TGF)-β levels were similar among all three groups. M. tuberculosis infection had little effect on the cytokine response after IFN-γ stimulus, but infection alone induced more IL-10 and TGF-β in TBP macrophages. There were no differences in Stat1 nuclear translocation and DNA binding between the groups. However, the phosphorylated Stat1 and c-Jun (AP-1) in nuclear protein extracts was diminished in TBP macrophages compared to macrophages of healthy individuals. These results indicate an impairment of Stat1-dependent and Stat1-independent IFN-γ signalling in macrophages of people with active tuberculosis, suggesting a different molecular regulation that could impact macrophage functionality and disease outcome.
Spring 2007 warmth and frost: phenology, damage and refoliation in a temperate deciduous forest
Authors: Augspurger Carol K.
Published: June 2009

1. Climate change is predicted to bring earlier bud break and perhaps a greater risk of frost damage to developing leaves and flowers. Given the rarity and unpredictability of major frost events and limited community‐level phenological observations, comparisons among deciduous forest species experiencing frost damage and refoliation are rare.

2. This study used phenological observations ongoing at the time of a hard freeze to compare leaf and flower development, frost damage and leaf refoliation of 20 deciduous woody species in Trelease Woods, Champaign Co., IL, USA. Freezing temperatures from 5 to 9 April 2007 followed 22 days after very warm temperatures began in March.

3. Bud break was the earliest in 17 years. Frost caused damage to leaf buds, developing shoots and/or expanding leaves of canopy trees of six species and saplings of two species. Undamaged species were inactive, or in bud break or shoot expansion. Among damaged species, 11–100% of individuals exhibited some frost damage. Mean damage level per individual ranged from 20% to 100% among species.

4. Refoliation from dormant buds led to mean final canopy fullness that ranged from 46% to 99% among damaged species, but time of full leaf expansion was extended by 16–34 days for refoliating species.

5. Frost damaged flowers, but not flower buds or developing fruit, of five of eight species that flowered during the frost period.

6. The extent of frost damage in 2007 was unusual; damage was greater than any of the other 4 years with frost damage from 1993 to 2009 because record‐breaking March temperatures in 2007 caused more species to be at later vulnerable stages with the advent of subfreezing temperatures in April.

7. Differences among individuals and species in frost damage and ability to refoliate caused strong selection on individuals and differences in carbon gain that could, in the long‐term, affect species’ abundances. The frost also reduced fruit/seed abundance for insects and mammals.
Pharmacokinetic allometric scaling of coagulation factors and tissue‐type plasminogen activators
Authors: MAHMOOD I.
Published: June 2009

Summary.  The objective of this study was to evaluate the predictive performance of pharmacokinetic interspecies scaling of coagulation factors and tissue‐type plasminogen activators to predict clearance, volume of distribution at steady‐state and half‐life in humans from animal data. The human pharmacokinetic parameters were predicted using one, two or at least three animal species. The results of the study indicated that the pharmacokinetic parameters of coagulation factors and tissue‐type plasminogen activators can be predicted with reasonable accuracy in humans when three or more animal species are available. Two‐species scaling can also be performed, but the accuracy of predicted parameters is less than three‐species scaling.
Floristic heterogeneity between forested sites in Kibale National Park, Uganda: insights into the fine‐scale determinants of density in a large‐bodied frugivorous primate
Authors: Potts Kevin B. , Chapman Colin A. , Lwanga Jeremiah S.
Published: June 2009

1. Despite a long history of research on the influence of fruit availability on the population density of large‐bodied vertebrate frugivores, operational understanding of the factors regulating density in these taxa remains elusive. We propose that fruit resources can be distinguished from one another on the basis of their functional role for the animals in question, and that such a classification system can aid in identifying the most influential determinants of frugivore density.

2. We compared the availability of several resource classes between two sites in Kibale National Park, Uganda separated by only 12 km yet differing threefold in density of chimpanzees (Pan troglodytes).

3. We categorized plant species used for fruit by chimpanzees according to their availability relative to habitat‐wide fruit productivity, and by their tendency towards inter‐individual fruiting synchrony. We predicted that the site of high chimpanzee density would support a higher density of food plant species tending to produce crops during periods of high habitat‐wide productivity [high fruit abundance (HFA foods)] and of those tending to fruit synchronously among individuals during times of low habitat‐wide availability (sLFA foods). The first food class should provide chimpanzees with a high nutrient density (and thus promote population growth), whereas the second should provide stable subsistence during lean periods and thus a temporally consistent resource base.

4. Counter to our prediction, only sLFA resources were more abundant at the site of high chimpanzee density than at the site of low density. We suggest that sLFA resources are most important in influencing density of large‐bodied frugivores.
Impacts of forest fragmentation on species richness: a hierarchical approach to community modelling
Authors: Zipkin Elise F. , DeWan Amielle , Andrew Royle J.
Published: June 2009

1. Species richness is often used as a tool for prioritizing conservation action. One method for predicting richness and other summaries of community structure is to develop species‐specific models of occurrence probability based on habitat or landscape characteristics. However, this approach can be challenging for rare or elusive species for which survey data are often sparse.

2. Recent developments have allowed for improved inference about community structure based on species‐specific models of occurrence probability, integrated within a hierarchical modelling framework. This framework offers advantages to inference about species richness over typical approaches by accounting for both species‐level effects and the aggregated effects of landscape composition on a community as a whole, thus leading to increased precision in estimates of species richness by improving occupancy estimates for all species, including those that were observed infrequently.

3. We developed a hierarchical model to assess the community response of breeding birds in the Hudson River Valley, New York, to habitat fragmentation and analysed the model using a Bayesian approach.

4. The model was designed to estimate species‐specific occurrence and the effects of fragment area and edge (as measured through the perimeter and the perimeter/area ratio, P/A), while accounting for imperfect detection of species.

5. We used the fitted model to make predictions of species richness within forest fragments of variable morphology. The model revealed that species richness of the observed bird community was maximized in small forest fragments with a high P/A. However, the number of forest interior species, a subset of the community with high conservation value, was maximized in large fragments with low P/A.

6. 
Synthesis and applications. Our results demonstrate the importance of understanding the responses of both individual, and groups of species, to environmental heterogeneity while illustrating the utility of hierarchical models for inference about species richness for conservation. This framework can be used to investigate the impacts of land‐use change and fragmentation on species or assemblage richness, and to further understand trade‐offs in species‐specific occupancy probabilities associated with landscape variability.
Self‐injurious behaviour in Cornelia de Lange syndrome: 1. Prevalence and phenomenology
Authors: Oliver C. , Sloneem J. , Hall S. , Arron K.
Published: June 2009

Background  Self‐injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case‐control study of the prevalence and phenomenology of self‐injurious behaviour (SIB) in CdLS.

Methods  A total of 54 participants with CdLS were compared with 46 individuals who were comparable on key variables including age, degree of intellectual disability and wheelchair use, using questionnaire and observational measures.

Results  Clinically significant self‐injury was not more prevalent in the CdLS group (55.6%), nor was it different in presentation from that seen in the comparison group. Hyperactivity, stereotyped and compulsive behaviours predicted clinically significant self‐injury in all participants. Hand directed, mild self‐injury was more prevalent in CdLS.

Conclusions  The results show that clinically significant self‐injury may not be part of the behavioural phenotype of CdLS but a specific body target for proto‐SIB is more common.
Self‐injurious behaviour in Cornelia de Lange syndrome: 2. association with environmental events
Authors: Sloneem J. , Arron K. , Hall S. S. , Oliver C.
Published: June 2009

Background  Self‐injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self‐injury in CdLS and whether environmental factors influence the behaviour.

Methods  We observed the self‐injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched for age, gender, level of intellectual disability and mobility. Descriptive analyses were used to determine the extent to which environmental events were associated with self‐injury.

Results  Lag sequential analysis of the association between self‐injurious behaviour and environmental events revealed no differences between the two groups in terms of either the number or degree of environmental associations.

Conclusions  The results suggest that the associations between the environment and self‐injury in CdLS do not differ from those seen in the broader population of people with intellectual disability. By implication the social reinforcement hypothesis is equally applicable to both groups.
Simultaneous analysis of the behavioural phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome
Authors: Wulffaert J. , van Berckelaer‐Onnes I. , Kroonenberg P. , Scholte E. , Bhuiyan Z. , Hennekam R.
Published: June 2009

Background Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical principal component analysis. The characteristics of the CdLS phenotype measured were also analysed in relation to parenting stress.

Method Data for 37 children and adults with CdLS were collected. The type of gene mutation and relevant medical characteristics were measured. Information on adaptive functioning, behavioural problems, the presence of the autistic disorder and parenting stress were obtained through questionnaires and semi‐structured interviews with the parents. Chronological age and gender were also included in the analysis.

Results All characteristics measured, except gender, were highly interrelated and there was much variability in the CdLS phenotype. Parents perceived more stress when their children were older, were lower functioning, had more behavioural problems, and if the autistic disorder was present. A new perspective was acquired on the relation between the gene mutation type and medical and behavioural characteristics. In contrast with earlier research the severity of medical characteristics did not appear a strong prognostic factor for the level of development.

Conclusion Categorical principal component analysis proved particularly valuable for the description of this small group of participants given the large number of variables with different measurement levels. The success of the technique in the present study suggests that a similar approach to the characterisation of other rare genetic syndromes could prove extremely valuable. Given the high variability and interrelatedness of characteristics in CdLS persons, parents should be informed about this differentiated perspective.
Cardioprotection with beta‐blockers: myths, facts and Pascal’s wager
Authors: Messerli F. H. , Bangalore S. , Yao S. S. , Steinberg J. S.
Published: June 2009

Beta‐blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta‐blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta‐blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta‐blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta‐blockers increase all‐cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta‐blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta‐blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta‐blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta‐blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta‐blockers but attest to their usefulness for specific cardiovascular indications.
Circulating high molecular weight adiponectin isoform is heritable and shares a common genetic background with insulin resistance in nondiabetic White Caucasians from Italy: evidence from a family‐based study
Authors: Menzaghi C. , Salvemini L. , Paroni G. , De Bonis C. , Mangiacotti D. , Fini G. , Doria A. , Di Paola R. , Trischitta V.
Published: June 2009

Abstract.  Menzaghi C, Salvemini L, Paroni G, De Bonis C, Mangiacotti D, Fini G, Doria A, Di Paola R, Trischitta V (IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (FG), Italy, Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA, “Sapienza” University; IRCCS Casa Sollievo della Sofferenza‐Mendel Institute, Rome, Italy). Circulating HMW adiponectin isoform is heritable and shares a common genetic background with insulin resistance in nondiabetic White Caucasians from Italy: evidence from a family‐based study. J Intern Med 2010; 267: 287–294.

Objective.  Reduced circulating adiponectin levels contribute to the aetiology of insulin resistance. Adiponectin circulates in three different isoforms: high molecular weight (HMW), medium molecular weight (MMW) and low molecular weight (LMW) isoforms. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance‐related traits.

Methods.  In a family‐based sample of 640 nondiabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test the association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance‐related traits.

Results.  All isoforms were highly heritable (h2 = 0.60–0.80, P = 1.0 × 10−13–1.0 × 10−23). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2–9%, P = 1.0 × 10−3–1.0 × 10−5). In a multiple‐SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (P = 3.0 × 10−4 and 2.0 × 10−2). Significant genetic correlations (P = 1.0 × 10−2–1.0 × 10−5) were observed between HMW adiponectin and fasting insulin, homeostasis model assessment of insulin resistance, HDL cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations.

Conclusion.  Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance‐related traits and involves, but is not limited to, the ADIPOQ locus.
Consistency of blood pressure and impact on cardiovascular structure over 20 years in young men
Authors: Ridderstråle W. , Saluveer O. , Johansson M. C. , Bergbrant A. , Jern S. , Hrafnkelsdóttir T. J.
Published: June 2009

Abstract.  Ridderstråle W, Saluveer O, Johansson MC, Bergbrant A, Jern S, Hrafnkelsdóttir TJ (Sahlgrenska University Hospital Östra, Gothenburg; AstraZeneca, Mölndal, Sweden, Landspítali University Hospital, Reykjavík, Iceland). Consistency of blood pressure and impact on cardiovascular structure over 20 years in young men. J Intern Med 2010; 267: 295–304.

Objective.  To identify, in a prospective study, how blood pressure levels at the age of twenty predict hypertension and cardiovascular remodelling 20 years later.

Methods.  Twenty‐year‐old men with blood pressure (BP) elevation [systolic blood pressure (SBP) 140–160 and/or diastolic blood pressure (DBP) 85–95 mmHg; blood pressure elevation (BPE) group] or normal BP [SBP 110–130 and DBP 60–80 mmHg; normal controls (NC) group] entered the study in 1987. In 2007, follow‐up was conducted including ambulatory BP, echocardiography, anthropometric and intima media thickness (IMT) measurements.

Results.  Assessed with 24‐h ambulatory BP, the prevalence of hypertension was 35/47 (74.5%) and 1/17 (5.9%) in the BPE and NC group at follow‐up respectively. Twenty‐four hour mean arterial pressure (MAP) increased from 86.6 (0.8) to 97.2 (1.2) (P < 0.0001), and from 83.1 (1.5) to 88.1 (1.2) mmHg (P < 0.01) from baseline to follow‐up in the BPE and NC group respectively. At follow‐up, left ventricular mass index (LVMI) was 122 (4) and 106 (4) g m−1 in the BPE and NC group (unpaired t‐test; P < 0.01) respectively, whilst IMT was 0.61 (0.01) and 0.57 (0.01) mm in the BPE and NC group (P < 0.05) respectively. In a logistic regression model, prevalence of hypertension was best explained by office MAP and 24‐h DBP at baseline (R2 0.333; P < 0.05). A combined model of office MAP, body mass index and insulin levels at baseline explained 56% of LVMI at follow‐up.

Conclusions.  BP elevation in young age predicts hypertension and adverse cardiovascular remodelling at the age of 40 years. Baseline office MAP is the best predictor of hypertension, 24‐h MAP and LVMI.
A 2‐log drop in viral load at 1 month is the best predictor of sustained response in HCV patients with normal ALT: a kinetic prospective study
Authors: Deltenre P. , Canva V. , Nady M. El , François C. , Castelain S. , Dharancy S. , Louvet A. , Bocket L. , Lazrek M. , Hollebecque A. , Wartel F. , Henrion J. , Duverlie G. , Mathurin P.
Published: June 2009

Summary.  The most reliable predictor of a sustained virological response in patients with persistently normal ALT has not been identified. We analysed 17 patients with genotype 1 chronic HCV who underwent therapy with pegylated interferon alfa 2b and ribavirin for 48 weeks. Two patients discontinued therapy within 28 days because of side effects and the remaining 15 patients were analysed in detail. An analysis of on treatment virological response using area under the receiver operating characteristic analyses showed that a 2 log drop in HCV RNA at day 28 was the best predictor of a sustained virological response and a failure to reduce viral load by 2 logs correctly identified patients with a low (<15%) probability of achieving a sustained virological response. Introduction of this early discontinuation rule in patients with normal ALT would allow nearly half of the patients to discontinue futile therapy at an early stage.
Acidianus, Sulfolobus and Metallosphaera surface layers: structure, composition and gene expression
Authors: Veith Andreas , Klingl Andreas , Zolghadr Behnam , Lauber Karin , Mentele Reinhard , Lottspeich Friedrich , Rachel Reinhard , Albers Sonja‐Verena , Kletzin Arnulf
Published: June 2009

The cell walls of Sulfolobales species consist of proteinaceous S‐layers assembled from two polypeptides, SlaA and SlaB. We isolated the large S‐layer protein of Acidianus ambivalens and both S‐layer subunits of Sulfolobus solfataricus and Metallosphaera sedula, respectively. The slaAB genes, lying adjacently in the chromosomes, are constitutively transcribed as bicistronic operons in A. ambivalens and S. solfataricus. A smaller slaA transcript appeared in Northern hybridizations of A. ambivalens RNA. PCRs experiments showed that 80–85% of the transcripts stop at an oligo‐T terminator downstream of slaA while 15–20% are read through to a second terminator downstream of slaB. The bicistronic operons including promoter and terminator regions are conserved in the Sulfolobales. While no SlaA homologue is found outside the Sulfolobales, SlaB is distantly similar to S‐layer proteins of other Crenarchaeota, e.g. the Staphylothermus marinus tetrabrachion. Molecular modelling suggests SlaBs to be composed of 2–3 consecutive beta sandwich domains, a coiled‐coil domain of 15–17 nm in length and a C‐terminal transmembrane helix. Electron microscopy shows crystalline protein arrays with triangular and hexagonal pores. We propose that the mushroom‐shaped ‘unit cells’ of the Sulfolobales' S‐layers consist of three SlaBs anchoring the complex in the membrane and six SlaAs forming the detergent‐resistant outer sacculus.
Essential role for TRPV1 in stress‐induced (mast cell‐dependent) colonic hypersensitivity in maternally separated rats
Authors: Van Den Wijngaard R. M. , Klooker T. K. , Welting O. , Stanisor O. I. , Wouters M. M. , Van Der Coelen D. , Bulmer D. C. , Peeters P. J. , Aerssens J. , De Hoogt R. , Lee K. , De Jonge W. J. , Boeckxstaens G. E.
Published: June 2009

Abstract  Irritable bowel syndrome is in part characterized by an increased sensitivity to colonic distension. Stress is an important trigger factor for symptom generation. We hypothesized that stress induces visceral hypersensitivity via mast cell degranulation and transient receptor ion channel 1 (TRPV1) modulation. We used the rat model of neonatal maternal separation (MS) to investigate this hypothesis. The visceromotor response to colonic distention was assessed in adult MS and non‐handled (NH) rats before and after acute water avoidance (WA) stress. We evaluated the effect of the mast cell stabilizer doxantrazole, neutralizing antiserum against the mast cell mediator nerve growth factor (NGF) and two different TRPV1 antagonists; capsazepine (non‐specific) and SB‐705498 (TRPV1‐specific). Immunohistochemistry was used to assess post‐WA TRPV1 expression in dorsal root ganglia and the presence of immunocytes in proximal and distal colon. Retrograde labelled and microdissected dorsal root ganglia sensory neurons were used to evaluate TRPV1 gene transcription. Results showed that acute stress induces colonic hypersensitivity in MS but not in NH rats. Hypersensitivity was prevented by prestress administration of doxantrazole and anti‐NGF. Capsazepine inhibited and SB‐705498 reversed poststress hypersensitivity. In MS rats, acute stress induced a slight increase in colonic mast cell numbers without further signs of inflammation. Post‐WA TRPV1 transcription and expression was not higher in MS than NH rats. In conclusion, the present data on stress‐induced visceral hypersensitivity confirm earlier reports on the essential role of mast cells and NGF. Moreover, the results also suggest that TRPV1 modulation (in the absence of overt inflammation) is involved in this response. Thus, mast cells and TRPV1 are potential targets to treat stress‐induced visceral hypersensitivity.
The impact of children's emotional and behavioural difficulties on their lives and their use of mental health services
Authors: Simpson Gloria A. , Cohen Robin A. , Bloom Barbara , Blumberg Stephen J.
Published: June 2009

This paper examines the relationship between the impact of children's emotional and behavioural difficulties and the use of mental health services, using 3 years of nationally representative data from the National Health Interview Survey. Data for the years 2001, 2003 and 2004 were combined (n = 29 265) to identify a sample of 1423 children aged 4–17 years with emotional/behavioural difficulties. Multivariable logistic regression analysis was used.

About 5% of U.S. children had emotional or behavioural difficulties. Children whose difficulty was a burden on their family were almost twice as likely to have contact with a mental health professional. Younger children (aged 4–7 years), Hispanic children and non‐Hispanic black children with emotional or behavioural difficulties were less likely to use mental health services. These findings indicate that children's emotional and behavioural difficulties influence their lives and those of their families, leading parents to seek help. Racial disparities in mental health service use exist when controlling for the severity and the burden of these difficulties.
Revised classification of the family Hesperiidae (Lepidoptera: Hesperioidea) based on combined molecular and morphological data
Authors: WARREN ANDREW D. , OGAWA JOSHUA R. , BROWER ANDREW V. Z.
Published: June 2009

Abstract We propose a revised higher classification for the genera of Hesperiidae (skipper butterflies) of the world. We have augmented our published DNA data matrix with 49 morphological characters in order to infer relationships for taxa not sampled in the molecular study. We use the results of a combined analysis to identify morphological synapomorphies of the suprageneric clades of Hesperiidae, and to hypothesize a phylogenetic classification of the world’s genera of Hesperiidae, the first of its kind for this diverse group. Monophyly of the family Hesperiidae is strongly supported, as are some of the traditionally recognized subfamilies. The results presented here largely corroborate those of our molecular study, but differ in several details. The Australian endemic Euschemon rafflesia is given subfamily status, as is Eudaminae. We recognize seven subfamilies of Hesperiidae: Coeliadinae, Euschemoninae (confirmed status), Eudaminae (new status), Pyrginae, Heteropterinae (confirmed status), Trapezitinae and Hesperiinae. We treat Pyrrhopygini, Tagiadini, Celaenorrhinini, Carcharodini, Achlyodidini, Erynnini and Pyrgini as tribes of Pyrginae. Circumscriptions of Achlyodidini and Pyrgini require further elucidation. Tribes of Hesperiinae include Aeromachini, Baorini, Taractrocerini, Thymelicini, Calpodini (reinstated status), Anthoptini (new tribe), Moncini and Hesperiini. The tribal placement of many Old World hesperiine genera remains ambiguous.
Phylogeny of the bee family Melittidae (Hymenoptera: Anthophila) based on combined molecular and morphological data
Authors: MICHEZ DENIS , PATINY SÉBASTIEN , DANFORTH BRYAN N.
Published: June 2009

The bee family Melittidae comprises a small, but biologically fascinating, group of mostly oligolectic bees, some of which are oil collecting. Phylogenetic relationships within this family are poorly understood and some genera cannot be placed with confidence at the subfamily level. We analysed melittid phylogeny using a combined dataset of five nuclear genes [28S, elongation factor‐1α (EF‐1α, F2 copy), long‐wavelength rhodopsin, Na‐K ATPase and RNA polymerase II] spanning 4842 bp plus 68 adult morphological characters. Our study included 25% of the species‐level diversity and 81% of the generic‐level diversity and included all previously recognized tribes and subfamilies. We analysed the dataset using parsimony, maximum likelihood and Bayesian methods. All methods yielded congruent results. All topologies recovered the three previously recognized subfamilies (Dasypodainae, Melittinae, Meganomiinae), but two genera (Afrodasypoda and Promelitta) are transferred from Dasypodainae to Melittinae. On the basis of our tree topologies we identify four tribes (Dasypodaini comb.n., Hesperapini stat.n., Macropidini comb.n. and Melittini), only one of which (Melittini) matches a widely used classification. Lastly, we discuss the evolution of host‐plant association in the light of our new phylogenetic hypothesis. Our results strongly support multiple independent origins of oil‐collecting behaviour in the Melittinae.
A short history of HLA
Authors: Thorsby E.
Published: June 2009

In 1958, just a little more than 50 years ago, an alloantigen present on human leucocytes was detected, which was to become the ‘first’ human leucocyte antigen (HLA); HLA‐A2. Since then, we have seen a tremendous development of the HLA field, which has moved from histocompatibility to become one of the most central fields in basic and clinical immunology. This development is briefly reviewed in this article, focusing on some highlights of the history of HLA class I and II molecules and their role in immune responses. It is emphasized that the quick and extensive development of the HLA field is the result not only of excellent individual contributions by outstanding pioneers in the field, but also of an extensive international collaboration, in particular through the many international histocompatibility workshops. Admitting that it is too late to change the name now, it is concluded that instead of calling the HLA complex and similar complexes in other species the major histocompatibility complex, these gene complexes should better have been named the major immune response complex, the MIRC.
The effect of coil phenotypes and genotypes on the fecundity and viability of Partula suturalis and Lymnaea stagnalis: implications for the evolution of sinistral snails
Authors: DAVISON A. , BARTON N. H. , CLARKE B.
Published: June 2009

Why are sinistral snails so rare? Two main hypotheses are that selection acts against the establishment of new coiling morphs, because dextral and sinistral snails have trouble mating, or else a developmental constraint prevents the establishment of sinistrals. We therefore used an isolate of the snail Lymnaea stagnalis, in which sinistrals are rare, and populations of Partula suturalis, in which sinistrals are common, as well as a mathematical model, to understand the circumstances by which new morphs evolve. The main finding is that the sinistral genotype is associated with reduced egg viability in L. stagnalis, but in P. suturalis individuals of sinistral and dextral genotype appear equally fecund, implying a lack of a constraint. As positive frequency‐dependent selection against the rare chiral morph in P. suturalis also operates over a narrow range (< 3%), the results suggest a model for chiral evolution in snails in which weak positive frequency‐dependent selection may be overcome by a negative frequency‐dependent selection, such as reproductive character displacement. In snails, there is not always a developmental constraint. As the direction of cleavage, and thus the directional asymmetry of the entire body, does not generally vary in other Spiralia (annelids, echiurans, vestimentiferans, sipunculids and nemerteans), it remains an open question as to whether this is because of a constraint and/or because most taxa do not have a conspicuous external asymmetry (like a shell) upon which selection can act.
Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia–reperfusion‐induced acute kidney injury
Authors: NAKAZAWA JUN , ISSHIKI KEIJI , SUGIMOTO TOSHIRO , ARAKI SHIN‐ICHI , KUME SHINJI , YOKOMAKU YUKIYO , CHIN‐KANASAKI MASAMI , SAKAGUCHI MASAYOSHI , KOYA DAISUKE , HANEDA MASAKAZU , KASHIWAGI ATSUNORI , UZU TAKASHI
Published: June 2009

Aim:  Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non‐haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes‐related acceleration of renal damage after ischaemia–reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non‐haematopoietic erythropoietin derivative, against ischaemia–reperfusion‐induced acute kidney injury in diabetic mice.

Methods:  C57BL/6J mice with and without streptozotocin‐induced diabetes were subjected to 30 min unilateral renal ischaemia–reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non‐diabetic plus ischaemia–reperfusion injury; (ii) non‐diabetic plus ischaemia–reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia–reperfusion injury; and (iv) diabetic plus ischemia–reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia–reperfusion injury.

Results:  Ischaemia–reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl‐2, an anti‐apoptotic molecule, and bone morphogenetic protein‐7 (BMP‐7), an anti‐fibrotic and pro‐regenerative factor, compared with non‐diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non‐diabetic kidney. Treatment with asialoerythropoietin induced bcl‐2 and BMP‐7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation.

Conclusion:  Reduced induction bcl‐2 and BMP‐7 may play a role in the acceleration of renal damage after ischaemia–reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute kidney injury may be mediated through the induction of bcl‐2 and BMP‐7.
Changes in serum lactate dehydrogenase activity in children with atopic dermatitis
Authors: Morishima Yasuyuki , Kawashima Hisashi , Takekuma Kouji , Hoshika Akinori
Published: June 2009

Background:  In recent years an increase has been seen in the number of patients with severe atopic dermatitis (AD) accompanied with generalized typical eruptions. Some markers indicating the severity of the disease and symptom changes are very useful, and therefore the purpose of the present study was to investigate serum lactate dehydrogenase (LDH) as such a marker.

Methods:  A total of 58 children with AD were enrolled. The severity of the disease was graded on the basis of the extent of eruptions and the severity of atopic symptoms. The fraction of serum LDH, number of eosinocytes in the peripheral blood, and serum IgE levels were also determined.

Results and Conclusion:  There was a close correlation between the severity of cutaneous symptoms and serum LDH activity, and between severity and eosinocyte count, but no relationship was seen between serum IgE levels and severity of the disease. The aforementioned factors were determined in a time‐related way. As the patients' condition improved, serum LDH activity tended to decline, but there were no consistent changes in eosinocyte count in the peripheral blood or serum IgE level. On LDH isozyme the levels of LDH4 and LDH5 were high. Tissue showed high LDH activity, especially in epidermides. These results suggest that serum LDH activity is a useful marker.
Manual expression and electric breast pumping in the first 48 h after delivery
Authors: Ohyama Makiko , Watabe Harumi , Hayasaka Yumiko
Published: June 2009

Background:  Early feeding for preterm infants via the mother's own milk is crucial for lowering morbidity and mortality. Obtaining the mother's milk in the first few days is sometimes difficult; an effective way of mediating this problem has not yet been established. The aim of the present study was therefore to investigate whether breast pumping using a hospital‐grade electric pump was more effective in maximizing the available milk volume and more comfortable than manual expression in the first 48 h after birth.

Methods:  A sequential cross‐over study was performed in a maternity ward, in a tertiary perinatal center, Japan. Eleven women whose infants were admitted to the neonatal intensive care unit were sequentially allocated to either manual or electric breast expression (Symphony) for their first expression after 6 h following birth. The women then used the other method for the next expression, and continued to alternate between methods until seven sessions had been completed for each method. The time interval between expressions was 3 h. Main outcome measures were volume of milk expressed per session and pain assessment at each expression using the Wong and Baker face‐scale.

Results:  Net milk yield per woman was 2 mL manually (median; range: 0–12.6 mL) and 0.6 mL (0–7.2 mL) by electric expression (P < 0.05). The frequency of women stating no pain was higher for electric pumping than manual expression (90% vs 36%, respectively; P < 0.05).

Conclusions:  In the early postpartum period, the best way to obtain colostrum is by gentle manual expression. For mothers who feel pain during manual expression, use of the stimulation phase of the Symphony pump may be preferable.
Psychometric testing of the Immigrant Barriers to Health Care Scale: Hispanic Version
Authors: Keating Stacen , Carlson Beverly , Jimenez Sophia , Estrada Jaime , Gastelum Belia , Romero Tomas , Riegel Barbara
Published: June 2009

Barriers to care contribute to health inequities for immigrant populations. Although inadequate health insurance is a known barrier, other factors impact the issue. Few instruments exist to specifically measure these other barriers. The purpose of this study was to test the Immigrant Barriers to Health Care Scale – Hispanic Version. It was first pilot‐tested in southern California with a Mexican population. After refinement, the instrument was tested in a north‐eastern sample of diverse Hispanic adults. The data were analyzed using exploratory factor analysis. Factor loadings and communalities were used to assess the adequacy of the scale's items. Six items were deleted due to ambiguous factor loadings. The final 11 items loaded onto four factors and explained 54.58% of the variance. The coefficient alpha was 0.81 for the instrument. The Immigrant Barriers to Health Care Scale is a reliable and valid tool. Its further use and reporting with other socially and economically disadvantaged groups is advised.
Nursing staff shortages and job satisfaction in Iran: Issues and challenges
Authors: Zarea Kourosh , Negarandeh Reza , Dehghan‐Nayeri Nahid , Rezaei‐Adaryani Morteza
Published: June 2009

In most countries, nurses are the largest group of health‐care professionals that provide direct and indirect care to patients in a variety of health settings. The quality of care is strongly linked to their performance, and shortages of nursing staff cause suffering and diminished patient care. In 2008, it was estimated that there were 90 026 nurses in Iran, but health‐care facilities need ∼ 220 000 nurses in order to deliver optimal nursing care. This review article provides a detailed description of the nursing shortage and related factors in Iran. It is hoped that this will inform both Iranian and international policy‐makers and administrators about the current situation in this country.
Facilitation of corticospinal excitability in the tibialis anterior muscle during robot‐assisted passive stepping in humans
Authors: Kamibayashi Kiyotaka , Nakajima Tsuyoshi , Takahashi Makoto , Akai Masami , Nakazawa Kimitaka
Published: June 2009

Although phasic modulation of the corticospinal tract excitability to the lower limb muscles has been observed during normal walking, it is unclear to what extent afferent information induced by walking is related to the modulation. The purpose of this study was to test the corticospinal excitability to the lower limb muscles by using transcranial magnetic stimulation (TMS) and transcranial electrical stimulation of the motor cortex while 13 healthy subjects passively stepped in a robotic driven‐gait orthosis. Specifically, to investigate the effect of load‐related afferent inputs on the corticospinal excitability during passive stepping, motor evoked potentials (MEPs) in response to the stimulation were compared between two passive stepping conditions: 40% body weight unloading on a treadmill (ground stepping) and 100% body weight unloading in the air (air stepping). In the rectus femoris, biceps femoris and tibialis anterior (TA) muscles, electromyographic activity was not observed throughout the step cycle in either stepping condition. However, the TMS‐evoked MEPs of the TA muscle at the early‐ and late‐swing phases as well as at the early‐stance phase during ground stepping were significantly larger than those observed during air stepping. The modulation pattern of the transcranial electrical stimulation‐evoked MEPs was similar to that of the TMS‐evoked MEPs. These results suggest that corticospinal excitability to the TA is facilitated by load‐related afferent inputs. Thus, these results might be consistent with the notion that load‐related afferent inputs play a significant role during locomotor training for gait disorders.
GABAergic transmission in the rat ventral pallidum mediates a saccharin palatability shift in conditioned taste aversion
Authors: Inui Tadashi , Yamamoto Takashi , Shimura Tsuyoshi
Published: June 2009

We previously found that the blockade of γ‐aminobutyric acid (GABA)A receptors in the ventral pallidum (VP) alters the taste palatability of a conditioned stimulus (CS) from aversive to ingestive after the establishment of conditioned taste aversion (CTA). Because these results suggest that GABAergic transmission in the VP mediates decreased palatability of the taste in CTA, the present study aimed to examine the effects of taste stimulation on the extracellular release of GABA in the VP using in vivo microdialysis. Initially, rats received a paired presentation of 5 mm saccharin or 0.3 mm quinine solution with an intraperitoneal injection of 0.15 m lithium chloride (S‐CTA and Q‐CTA groups) or saline (S‐control and Q‐control groups). After conditioning, microdialysis was carried out before, during and after the presentation of the CS via an intra‐oral cannula. We measured the latency of the first aversive orofacial responses to the CS as behavioral indices. In the S‐CTA group, which rapidly rejected the CS (within 100 s), the GABA efflux was significantly increased (147%) and was maintained for 2 h. On the other hand, the S‐control group expressed no aversive responses and showed no significant alterations in GABA efflux. Although the Q‐CTA group immediately expressed aversive responses to the CS (within 30 s), GABA release was not changed by presentation of the CS, which was similar in the Q‐control group. These findings suggest that the palatability shift from ingestive to aversive in conditioned aversion to saccharin, but not quinine, is mediated by the change in GABAergic transmission in the VP.