bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive escape: annual plant responds to butterfly eggs by accelerating seed production
Authors: Lucas‐Barbosa Dani , van Loon Joop J. A. , Gols Rieta , van Beek Teris A. , Dicke Marcel
Published: November 2012

Plants respond to insect herbivores with changes in physical and chemical traits, both locally and systemically, in leaves and flowers. Such phenotypic changes may influence the behaviour of every community member that interacts with the plant. Here, we address effects of plant responses to eggs and subsequent herbivory by caterpillars on plant‐mediated interactions with pollinators and consequences for plant fitness.

Using a common garden set‐up, we have investigated responses ofBrassica nigraplants to herbivore exposure from egg deposition onwards throughout larval development. We quantified effects of infestation by the specialistPieris brassicaeon: 1. behaviour of pollinators; 2. volatile emission and 3. timing and number of seeds produced.

Egg deposition and folivory did not influence visitation by pollinators to plots of infested or control plants. Effects of herbivore infestation on both pollinator visitation and volatile emission were observed only at a later stage, when caterpillars were feeding on the flowers.

Remarkably, before eggs had hatched, infested plants accelerated seed production. The caterpillars that developed from the eggs fed on flowers but not on seeds and thus seed production prior to herbivory on flowers safeguarded reproductive output.

The results of this study show that early plant investments in reproduction can successfully prevent consumption of expensive reproductive tissues. By accelerating seed production, plants prevented consumption of flowers and effectively defended themselves against the herbivores.
The size‐number trade‐off in clonal broods of a parasitic wasp: responses to the amount and timing of resource availability
Authors: Saeki Yoriko , Crowley Philip H.
Published: November 2012

Life‐history traits that shift in response to environmental conditions are well studied; however, allocation patterns of traits in the context of a trade‐off shifting with the environment are hardly examined.

Using a polyembryonic parasitoid wasp system, we revealed features of the plasticity in allocation by observing the trade‐off outcome between individual body mass and the number of offspring in a wasp brood in response to different host conditions.

We manipulated food availability to the host caterpillar at two different phases of development: early host instars during wasp embryo division and late host instars after completion of wasp embryo division. The food manipulation allowed us to shift the rate of development and the total mass of the wasp brood both separately and together through altered host development time and final size.

With greater host mass, the trade‐off relationship between wasp body mass and brood size shifted, to the same extent for both sexes, towards higher wasp brood size and individual body mass. On the other hand, with faster host development, the trait combinations shifted towards greater wasp body mass but smaller brood size along the same trade‐off relationship.

These shifts indicate a reduction of wasp brood size when resource level is reduced late in host development. This adjustment yields wasp brood size and body mass in rough proportion to each other and positively related to resource availability late in development.

Our demonstration of simultaneous shifts in traits under the trade‐off relationship indicates that wasp broods respond differently to the different environmental conditions by altering body mass and the number of wasp individuals, suggesting that the plastic response in the trade‐off allocation pattern may be adaptive.
Personality and the pace‐of‐life syndrome: variation and selection on exploration, metabolism and locomotor performances
Authors: Le Galliard Jean‐François , Paquet Matthieu , Cisel Matthieu , Montes‐Poloni Laetitia
Published: November 2012

Consistent individual differences in behaviour are seen in numerous animals and could be maintained by life‐history trade‐offs and integrated within a pace‐of‐life syndrome involving physiological and locomotor traits.

Lizard species are characterized by inter‐specific variation in activity and foraging behaviours associated with differences in locomotor performances and metabolic rates. Similar syndromes could exist within species, but have not been investigated so far.

We scored the exploratory behaviour of newborn common lizards (Zootoca vivipara) using a neutral arena test and measured concomitantly resting metabolic rate (RMR), maximal sprint speed (MSS) and endurance capacity. Animals were released in outdoor enclosures exposed to avian predation and measured again for the same traits 1 year later.

Common lizards displayed consistent individual differences over a week for an exploration score associated with high activity in the neutral arena. Individual differences in three activity scores were also consistent over the first year of life.

Correlations among behavioural, metabolic and locomotor traits were weak, except for a marginally significant, positive correlation between exploration score and MSS and endurance at the age of 1 year.

Correlational survival selection was found for RMR and exploration score such that newborns with low exploration score and high RMR and newborns with high exploration score and low RMR survived better. Correlational growth selection was also found with faster growth in newborns with low exploration score and high RMR.

The results are discussed against recent hypotheses to explain the maintenance of animal temperaments.
Catabolite repression in Pseudomonas aeruginosa PAO1 regulates the uptake of C4‐dicarboxylates depending on succinate concentration
Authors: Valentini Martina , Lapouge Karine
Published: November 2012

In Pseudomonas aeruginosa carbon catabolite repression (CCR) is exerted by the CbrA/B‐CrcZ‐Crc global regulatory system. Crc is a translational repressor that, in the presence of preferred carbon sources, such as C4‐dicarboxylates, impairs the utilization of less preferred substrates. When non‐preferred substrates are present, the CrcZ sRNA levels increase leading to Crc capture, thereby allowing growth of the bacterium at the expense of the non‐preferred substrates. The C4‐dicarboxylate transport (Dct) system in P. aeruginosa is composed of two main transporters: DctA, more efficient at mM succinate concentrations, and DctPQM, more important at μM. In this study, we demonstrate that the Dct transporters are differentially regulated by Crc, depending on the concentration of succinate. At high concentrations, Crc positively regulates the expression of the dctA transporter gene and negatively regulates dctPQM post‐transcriptionally. The activation of dctA is explained by a Crc‐mediated repression of dctR, encoding a transcriptional repressor of dctA. At low succinate concentrations, Crc regulation is impaired. In this condition, CrcZ levels are higher and therefore more Crc proteins are sequestered, decreasing the amount of Crc available to perform CCR on dctR and dctPQM. As a result, expression of dctA is reduced and that of dctPQM is increased.
Intraoperative post‐conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study
Authors: Torné A , Fusté P , Rodríguez‐Carunchio L , Alonso I , del Pino M , Nonell R , Cardona M , Rodríguez A , Castillo P , Pahisa J , Balasch J , Ramírez J , Ordi J
Published: November 2012

Objective

To evaluate the feasibility and utility of intraoperative post‐conisation human papillomavirus (IOP‐HPV) testing and cytology to detect treatment failure in patients with cervical intraepithelial neoplasia grades 2–3 (CIN2–3).

Design

Prospective observational pilot study.

Setting

Barcelona, Spain.

Population

A cohort of 132 women treated for CIN2–3 by loop electrosurgical conisation.

Methods

An endocervical sample was obtained intraoperatively with a cytobrush from the cervix remaining after the conisation. The material was kept in PreservCyt medium and processed for Hybrid Capture 2 and cytology. Patients were followed‐up for 24 months. The performance of IOP‐HPV testing and IOP cytology was compared with conventional indicators of recurrence (cone margin, endocervical curettage, and HPV testing and cytology at 6 months).

Main outcome measure

Treatment failure (i.e. recurrent CIN2–3 during follow‐up).

Results

Treatment failure was identified in 12 women (9.1%). IOP‐HPV testing for sensitivity, specificity, and positive and negative predictive values for treatment failure were 91.7, 78.3, 62.2, and 96.0%, respectively, which are similar to the figures for conventional HPV testing at 6 months (91.7, 76.0, 64.0, and 95.1%, respectively), and are better than the values of other conventional predictive factors (cone margin, endocervical curettage, and cytology intraoperative at 6 months). IOP‐HPV was strongly associated with treatment failure in the multivariate analysis (OR 15.40, 95% CI 1.58–150.42).

Conclusion

IOP‐HPV testing is feasible, and accurately predicts treatment failure in patients with CIN2–3. This new approach may allow an early identification of patients with treatment failure, thereby facilitating the scheduling of an attenuated follow‐up for negative patients who are at very low risk of persistent disease.
Childbirth after pelvic floor surgery: analysis of Hospital Episode Statistics in England, 2002–2008
Authors: Pradhan A , Tincello DG , Kearney R
Published: November 2012

Objective

To report the numbers of patients having childbirth after pelvic floor surgery in England.

Design

Retrospective analysis of Hospital Episode Statistics data.

Setting

Hospital Episode Statistics database.

Population

Women, aged 20–44 years, undergoing childbirth after pelvic floor surgery between the years 2002 and 2008.

Methods

Analysis of the Hospital Episode Statistics database using Office of Population, Censuses and Surveys: Classification of Interventions and Procedures, 4th Revision (OPCS‐4) code at the four‐character level for pelvic floor surgery and delivery, in women aged 20–44 years, between the years 2002 and 2008.

Main outcome measures

Numbers of women having delivery episodes after previous pelvic floor surgery, and numbers having further pelvic floor surgery after delivery.

Results

Six hundred and three women had a delivery episode after previous pelvic floor surgery in the time period 2002–2008. In this group of 603 women, 42 had a further pelvic floor surgery episode following delivery in the same time period. The incidence of repeat surgery episode following delivery was higher in the group delivered vaginally than in those delivered by caesarean (13.6 versus 4.4%; odds ratio, 3.38; 95% confidence interval, 1.87–6.10).

Conclusions

There were 603 women having childbirth after pelvic floor surgery in the time period 2002–2008. The incidence of further pelvic floor surgery after childbirth was lower after caesarean delivery than after vaginal delivery, and this may indicate a protective effect of abdominal delivery.
Plantar pressures in diabetes with no known neuropathy (无神经病变的糖尿病患者的足底压力)
Authors: Syed Nafeez , Maiya Arun G. , Hanifa Nazia , Goud Sandeep
Published: November 2012

Background

The aim of the present study was to investigate associations of arch type and gender with plantar pressure distribution in non‐diabetic subjects and subjects with type 2 diabetes mellitus (T2DM) without peripheral neuropathy (PN).

Methods

Plantar pressures were recorded in 62 subjects with T2DM but without PN (mean [±SD] age 63.6 ± 7.6 years, body mass index [BMI] 24.3 ± 2.9 kg/m2, and duration of diabetes 7.0 ± 3.0 years) and in 63 non‐diabetic adults (62.5 ± 8.5 years of age; BMI 22.4 ± 2.5 kg/m2) in static stance using a foot analyzer. Data were collected from both feet and were analyzed for their association with disease, arch type, and gender using the Mann–Whitney U‐test and Chi‐squared test, respectively.

Results

There were significant differences in plantar pressures between the left and right feet in T2DM subjects, regardless of gender, and their metatarsal heads were overloaded. There were poor correlations between the overloaded plantar pressures and both foot arch and gender for all diabetic subjects. However, there were no differences in pressures at different zones between the diabetic and non‐diabetic subjects.

Conclusions

There were no differences in plantar pressures between non‐diabetic and T2DM subjects without PN. Furthermore, there were no significant correlations between plantar pressures in diabetic subjects and either arch type or gender. However, there were significant differences in plantar pressures between the right and left feet.
Kakkalide ameliorates endothelial insulin resistance by suppressing reactive oxygen species‐associated inflammation (葛花苷通过抑制活性氧相关的炎症改善内皮细胞胰岛素抵抗)
Authors: Zhang Dongyan , Gao Xuejiao , Wang Qi , Qin Minjian , Liu Kang , Huang Fang , Liu Baolin
Published: November 2012

Background

Kakkalide is the predominant isoflavone derived from the flowers of Pueraria lobata (Willd.) Ohwi. The aim of the present study was to investigate the effects of kakkalide on insulin resistance in the endothelium.

Methods

Human umbilical vein endothelial cells (HUVEC) were stimulated with 100 μmol/L palmitate (PA) for 30 min and the effects of 30 min pretreatment with 0.1–10 μmol/L kakkalide on reactive oxygen species (ROS)‐associated inflammation in cells were evaluated by western blot analysis and reverse transcription–polymerase chain reaction. Furthermore, we investigated the biomodulation of insulin signaling by kakkalide along the insulin receptor substrate (IRS)‐1/Akt/endothelial nitric oxide synthase (eNOS) pathway. We also determined the effects of 30 min pretreatment with 0.1–10 μmol/L kakkalide on insulin‐mediated endothelium‐dependent vasodilation of rat aorta in vitro following stimulation with 100 μmol/L PA.

Results

Kakkalide inhibited ROS overproduction and effectively restored mitochondrial membrane potential, demonstrating its chemoprotection of mitochondrial function. In addition, kakkalide inhibited ROS‐associated inflammation in the endothelium by inhibiting tumor necrosis factor‐α and interleukin‐6 production and gene expression, as well as suppressing the phosphorylation of c‐Jun N‐terminal kinase and IκB kinase β/nuclear factor‐κB. Inflammation impaired insulin phosphatidylinositol 3‐kinase (PI3K) signaling and reduced insulin‐mediated NO production in endothelial cells. Kakkalide facilitated PI3K signaling by positively regulating serine/tyrosine phosphorylation of IRS‐1.

Conclusions

Kakkalide inhibited ROS‐associated inflammation and ameliorated insulin‐resistant endothelial dysfunction by beneficial effects on IRS‐1 function.
The Clermont Escherichia coli phylo‐typing method revisited: improvement of specificity and detection of new phylo‐groups
Authors: Clermont Olivier , Christenson Julia K. , Denamur Erick , Gordon David M.
Published: November 2012

There is extensive genetic substructure within the species Escherichia coli. In 2000 a simple triplex PCR method was described by Clermont and colleagues that enables an E. coli isolate to be assigned to one of the phylo‐groups A, B1, B2 or D. The growing body of multi‐locus sequence data and genome data for E. coli has refined our understanding of E. coli's phylo‐group structure and eight phylo‐groups are now recognized: seven (A, B1, B2, C, D, E, F) belong to E. coli sensu stricto, whereas the eighth is the Escherichia cryptic clade I. Here a new PCR‐based method is developed that enables an E. coli isolate to be assigned to one of the eight phylo‐groups and which allows isolates that are members of the other cryptic clades (II to V) of Escherichia to be identified. The development of the method is described and the method is validated. Over 95% of E. coli isolates can be correctly assigned to a phylo‐group. Two collections of human faecal isolates were screened using the new phylo‐group assignment method demonstrating that about 13% of E. coli isolates belong to the newly described phylo‐groups C, E, F and clade I.
Is Typhoid Mary a good role model?
Authors: Hough‐Goldstein J. A.
Published: November 2012

Read the Feature Paper: Typhoid Mary in the frogpond: can we use native frogs to disseminate a lungworm biocontrol for invasive cane toads?

Other Commentaries on this paper: Benefits and costs of using a lungworm parasite to control invasive toads in Australia

Response from the authors: New methods in the battle against cane toads: when should we move from research to implementation?
Transition of children with epilepsies to adult care
Authors: Khan Arif , Baheerathan Aravindhan , Hussain Nahin , Whitehouse William
Published: November 2012

Young people aged between 10 and 20 years will account for nearly 23% of the UK's total population by the end of 2012. This fact, coupled with an increasing number of children with chronic illness surviving into adulthood, means that the transition of children with chronic illness into adult care is becoming an increasingly important issue. Epilepsies are pervasive disorders that consist not only of recurrent epileptic seizures that can change over time, but also of evolving behavioural, academic and social difficulties. Many of these young individuals feel ‘dumped’ or ‘left in the dark’ once they are ‘transferred’ to adult care.

Conclusion

Therefore, it is essential to acknowledge that ‘transition of care’ in children with epilepsies is not a ‘step’ but a ‘process’. It is a very challenging time with increased stress and anxiety, for both the individual and their families. This article will discuss the various factors associated with the complex topic and aim to establish a framework for the successful transition of children with epilepsy into adult care.
Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn's disease
Authors: Wilson A. , Patel V. , Chande N. , Ponich T. , Urquhart B. , Asher L. , Choi Y. , Tirona R. , Kim R. B. , Gregor J. C.
Published: November 2012

Background

Methotrexate (MTX) is administered subcutaneously to Crohn's Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80–125% of the bioavailability of the standard (US Food and Drug Administration ‐ FDA).

Aim

To compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD patients to determine the bioequivalence of these two routes.

Methods

Eleven patients received a PO and an SC MTX dose (25 mg) separated by one week over a two‐week interval. Blood samples were collected at specified times over a 24‐h period for each patient on two separate days. MTX plasma levels were obtained using sensitive mass spectrometry. Areas under the curve (AUC) were compared between the two routes.

Results

The mean AUC values were 3375 ng/mL × h (PO MTX) and 3985 ng/mL × h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62–1.08). This correlates with a relative PO bioavailability of 86% in comparison to SC. The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). There were no adverse events.

Conclusions

The mean MTX AUC (PO/SC) in these patients falls outside the 90% confidence interval for the bioequivalence limit. SC MTX is more bioavailable than PO MTX; however, the mean relative MTX bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX could be proposed in responders who would prefer this route.
Review article: the management of acute gastroenteritis in children
Authors: Pieścik‐Lech M. , Shamir R. , Guarino A. , Szajewska H.
Published: November 2012

Background

In 2008, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society of Paediatric Infectious Disease (ESPID) developed evidence‐based guidelines for the management of acute gastroenteritis (AGE) in children in Europe.

Aim

To summarise data published subsequently to the ESPGHAN/ESPID guidelines.

Methods

MEDLINE and The Cochrane Library were searched in August 2012 for randomised controlled trials (RCTs) or their meta‐analyses published after 2008.

Results

Efforts to improve the taste and/or efficacy of oral rehydration solution (ORS) continue, and some interventions are promising. While standard (over 24 h) nasogastric rehydration is still being used, new evidence confirms that rapid (over 4 h) rehydration is also effective. For intravenous rehydration, new evidence is available regarding rapid or ultrarapid and large‐volume vs. standard‐volume rehydration; as the new evidence is not consistent, until more data are available, the administration of 20 mL/kg seems appropriate. Convincing evidence has accumulated showing that ondansetron reduces the risk for vomiting; however, a clearance on safety in children is needed. New evidence has reconfirmed that in Europe, where zinc deficiency is rare, there is no benefit from the use of zinc. New data, although mainly from outside of Europe, have reconfirmed that either smectite or racecadotril is an effective adjunctive therapy to oral rehydration. There is a clear effect of using certain probiotics, such as Lactobacillus GG or S. boulardii.

Conclusions

The update of current ESPGHAN/ESPID recommendations is warranted.
Exploring early self‐referential memory effects through ownership
Authors: Cunningham Sheila J. , Vergunst Francis , Macrae C. Neil , Turk David J.
Published: November 2012

The self‐reference effect (SRE) is the reliable memory advantage for information encoded about self over material encoded about other people. The developmental pathway of the SRE has proved difficult to chart, because the standard SRE task is unsuitable for young children. The current inquiry was designed to address this issue using an ownership paradigm, as encoding objects in the context of self‐ownership have been shown to elicit self‐referential memory advantages in adults. Pairs of 4‐ to 6‐year‐old children (n = 64) sorted toy pictures into self‐ and other‐owned sets. A surprise recognition memory test revealed a significant advantage for toys owned by self, which decreased with age. Neither verbal ability nor theory of mind attainment predicted the size of the memory advantage for self‐owned items. This finding suggests that contrary to some previous reports, memory in early childhood can be shaped by the same self‐referential biases that pervade adult cognition.
Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro‐coagulant vesicles
Authors: Burger Patrick , Kostova Elena , Bloem Esther , Hilarius‐Stokman Petra , Meijer Alexander B. , van den Berg Timo K. , Verhoeven Arthur J. , de Korte Dirk , van Bruggen Robin
Published: November 2012

During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37°C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long‐term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS‐negative state by shedding parts of their membrane as PS‐containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well‐known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post‐transfusion function and side effects of stored erythrocytes.
Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists
Authors: Sanger G J , Wang Y , Hobson A , Broad J
Published: November 2012

The gastrointestinal hormone motilin has been known about for >40 years, but after identification of its receptor and subsequent development of new tools and methods, a reappraisal of its actions is required. Firstly, it is important to note that motilin and ghrelin receptors are members of the same family (similar genomic organization, gastrointestinal distribution and abilities to stimulate gastrointestinal motility), yet each fails to recognize the ligand of the other; and whereas ghrelin and ghrelin receptors are widespread outside the gastrointestinal tract, motilin and its receptors are largely restricted to the gastrointestinal tract. Secondly, although some studies suggest motilin has activity in rodents, most do not, and receptor pseudogenes exist in rodents. Thirdly, motilin preferentially operates by facilitating enteric cholinergic activity rather than directly contracting the muscle, despite the relatively high expression of receptor immunoreactivity in muscle. This activity is ligand‐dependent, with short‐lasting actions of motilin contrasting with longer‐lasting actions of the non‐selective and selective motilin receptor agonists erythromycin and GSK962040. Finally, the use of erythromycin (also an antibiotic drug) to treat patients requiring acceleration of gastric emptying has led to concerns over safety and potential exacerbation of antibiotic resistance. Replacement motilin receptor agonists derived from erythromycin (motilides) have been unsuccessful. New, non‐motilide, small molecule receptor agonists, designed to minimize self‐desensitization, are now entering clinical trials for treating patients undergoing enteral feeding or with diabetic gastroparesis. Thus, for the translational pharmacologist, the study of motilin illustrates the need to avoid overreliance on artificial systems, on structural information and on animal studies.

Linked Articles

This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue‐7
The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin
Authors: Broad John , Sanger Gareth J
Published: November 2012

Background and Purpose

The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin.

Experimental Approach

[125I]‐motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves.

Key Results

Azithromycin (1–100 μM) and erythromycin (3–30 μM) concentration‐dependently displaced [125I]‐motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration‐dependently caused short‐lived increases in intracellular [Ca2+] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30–300 μM each) facilitated these contractions (apparent Emax values of 2007 ± 396 and 1924 ± 1375%, n = 3–4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short‐lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug.

Conclusions and Implications

Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long‐lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin.
Dealing With Missing Data in Developmental Research
Authors: Enders Craig K.
Published: November 2012

Approaches to handling missing data have improved dramatically in recent years and researchers can now choose from a variety of sophisticated analysis options. The methodological literature favors maximum likelihood and multiple imputation because these approaches offer substantial improvements over older approaches, including a strong theoretical foundation, less restrictive assumptions, and the potential for bias reduction and greater power. These benefits are especially important for developmental research where attrition is a pervasive problem. This article provides a brief introduction to modern methods for handling missing data and their application to developmental research.
Intracellular RNA recognition pathway activates strong anti-viral response in human mast cells
Authors: Lappalainen J , Rintahaka J , Kovanen P T , Matikainen S , Eklund K K
Published: November 2012

Mast cells have been implicated in the first line of defence against parasites and bacteria, but less is known about their role in anti-viral responses. Allergic diseases often exacerbate during viral infection, suggesting an increased activation of mast cells in the process. In this study we investigated human mast cell response to double-stranded RNA and viral infection. Cultured human mast cells were incubated with poly(I:C), a synthetic RNA analogue and live Sendai virus as a model of RNA parainfluenza virus infection, and analysed for their anti-viral response. Mast cells responded to intracellular poly(I:C) by inducing type 1 and type 3 interferons and TNF-α. In contrast, extracellular Toll-like receptor 3 (TLR)-3-activating poly(I:C) failed to induce such response. Infection of mast cells with live Sendai virus induced an anti-viral response similar to that of intracellular poly(I:C). Type 1, but not type 3 interferons, up-regulated the expression of melanoma differentiation–associated gene 5 (MDA-5) and retinoic acid-inducible gene-1 (RIG-1), and TLR-3, demonstrating that human mast cells do not express functional receptors for type 3 interferons. Furthermore, virus infection induced the anti-viral proteins MxA and IFIT3 in human mast cells. In conclusion, our results support the notion that mast cells can recognize an invading virus through intracellular virus sensors and produce high amounts of type 1 and type 3 interferons and the anti-viral proteins human myxovirus resistance gene A (MxA) and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in response to the virus infection.
Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls
Authors: Bradley A S , Ford B , Bansal A S
Published: November 2012

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity. To date, defects in B cell numbers or function have not been shown in the literature. However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping. We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age- and gender-matched healthy controls (HC). CFS patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.
Emerging trends in the diagnosis and treatment of acromegaly in Canada
Authors: Vallette Sophie , Ezzat Shereen , Chik Constance , Ur Ehud , Imran Syed Ali , Van Uum Stan , Rivera Juan , Caspar‐Bell Gudrun , Serri Omar
Published: November 2012

Objective

To evaluate demographic data and quality of care of patients with acromegaly in Canada and their evolution over time and secondly, to evaluate predictors of co‐morbidities and treatment outcomes.

Design and patients

Retrospective analyses of clinical, biochemical and treatment outcome data of 649 patients with acromegaly (males: 50·7%) followed from 1980 to 2010 (mean 10·2 years, SD 13·7) in eight tertiary care centres from six Canadian provinces.

Results

In comparison to 1980–1994, the number of patients referred with acromegaly in the last 15 years was higher with female preponderance (52·8% vs 41·4%, P = 0·01) and an older age at diagnosis (46·4 ± 14 vs 41·3 ± 12 years, P < 0·0001). Diabetes was present in 28%, hypertension in 37% and sleep apnoea in 33% of cases. Pretreatment IGF‐1 levels, but not GH levels were significant predictors of diabetes (P = 0·0002) and hypertension (P < 0·0001). Eighty‐nine per cent of patients underwent pituitary surgery, 64·5% had medical therapy and 22% received radiotherapy. Radiotherapy was less utilized in the past 15 years (16% vs 45%, P < 0·0001). Multimodal therapy achieved remission or control of acromegaly in 70% of patients. Patients in remission or disease control had lower initial random GH (P = 0·04) and IGF‐1 levels (P < 0·0001). Hypopituitarism was present in 23% of patients and cancer in 8·5%.

Conclusions

There was an increase over time of referral for acromegaly management with female predilection. Initial higher IGF‐1, but not GH levels, were predictive of co‐morbidities and persistent active disease after treatment. Disease remission or control was attained in 70% of patients utilizing multimodal therapy.
Current level of glycaemic control and its associated factors in patients with type 2 diabetes across Europe: data from the PANORAMA study
Authors: de Pablos‐Velasco Pedro , Parhofer Klaus G , Bradley Clare , Eschwège Eveline , Gönder-Frederick Linda , Maheux Pierre , Wood Ian , Simon Dominique
Published: November 2012

Abstract

Objective

To provide an update on glycaemic control in European patients with type 2 diabetes based on data from the nine‐country, cross‐sectional PANORAMA study (NCT00916513).

Design

Post‐hoc analysis to report the number of patients achieving/not achieving glycaemic goal (HbA1c <7%).

Patients

Patients were randomly or consecutively selected from physician practices in nine countries. Eligible patients were aged ≥40 years, diagnosed with type 2 diabetes >1 year prior to study entry, and had an available medical record of >1 year.

Measurements

All data were collected at a single visit, including HbA1c measurement using a common device (A1CNow®). Bivariate and multivariate analyses were used to investigate factors associated with not reaching glycaemic goal.

Results

Of 5817 patients enrolled (aged 65·9 ± 10·4 years, 53·7% male), 37·4% had an HbA1c ≥7%; (range 25·9% in The Netherlands to 52·0% in Turkey). In adjusted multivariate analyses, higher individual glycaemic target, younger age, poor physician‐reported patient adherence to lifestyle/medication, longer diabetes duration, increasing treatment regimen complexity and physician‐reported patient's unwillingness to intensify treatment were associated with not achieving goal. However, bivariate analyses also found gender, socioeconomic factors, body mass index, rate of complications and hypoglycaemia to be associated with not achieving goal.

Conclusions

In PANORAMA, 37·4% of patients enrolled were not at glycaemic goal. Factors relating to patient characteristics, physician selection of individualized HbA1c target and diabetes itself (longer duration, more complex treatment) were strongly associated with not achieving goal. Further studies are warranted to explore these associations and evaluate strategies for improving glycaemic control.
Transplantation of Human Retinal Pigment Epithelium Cells in the Treatment for Parkinson Disease
Authors: Yin Feng , Tian Zeng‐Min , Liu Shuang , Zhao Quan‐Jun , Wang Rui‐Min , Shen Li , Wieman Jeffery , Yan Ying
Published: November 2012

Background and purpose

To assess the clinical effect of transplantation of human retinal pigment epithelial (hRPE) cells into the unilateral postcommissural putamen for treatment for Parkinson disease (PD).

Methods and results

Cells from postmortem human eye tissue (10–20 weeks of gestation) were cultured in vitro. Cells from ‐generation passage were implanted in PD postcommissural putamen with stereotactic operation in 12 patients with PD. All patients tolerated surgery well, and no major adverse events occurred. Eleven patients showed improvement in the primary outcome measure at 3 months post‐treatment, particularly the Unified Parkinson's Disease Rating Scale‐M score in the off state. Response reached a peak at 12 months and declined during the next 24 months. At the 36‐month endpoint, there were eight patients who felt better than at baseline. Positron emission tomography (PET) showed a trend with increased dopamine (DA) release during the first 6 months.

Conclusion

Human retinal pigment epithelial cells have the characteristics of neural progenitor cells and can be induced to differentiate into DA neurons. The results of this clinical trial suggest that the treatment of transplanted hRPE cells could improve symptoms of PD. These cells might serve as a useful source of DA neurons for neural graft in the treatment for PD.
Indolent CD8+ lymphoid proliferation of acral sites: a clinicopathologic study of six patients with some atypical features
Authors: Greenblatt Danielle , Ally Mina , Child Fiona , Scarisbrick Julia , Whittaker Sean , Morris Stephen , Calonje Eduardo , Petrella Tony , Robson Alistair
Published: November 2012

The authors report six further cases of a cutaneous lymphoid proliferation that share many of the features of a case series previously described as indolent CD8‐positive lymphoid proliferation of the ear. Previous reports of this entity have described the slow growth of cutaneous papules and nodules, with a predilection for the ear, associated with specific histopathologic and immunophenotypic features and a benign clinical course. These include the presence of a clear Grenz zone without epidermotropism, and a CD8+ granzyme B‐ immunophenotype with a low proliferative index. The current case series presents some atypical clinical features, including site of disease beyond the ear and recurrent disease. Despite this, indolent clinical evolution is apparent. Histopathologically, three of the six cases showed a moderate‐high proliferative index, while two cases had very focal epidermotropism and Pautrier collections. A single example had significant granzyme B expression. These previously unreported features add to our understanding of this rare entity, which is not currently recognized in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) classification.
Expanding the histologic findings in smallpox‐related post‐vaccinial non‐viral folliculitis
Authors: Bunick Christopher G. , Mariwalla Kavita , Ibrahim Omer , Modi Badri , Imaeda Suguru , McNiff Jennifer M.
Published: November 2012

Post‐vaccinial non‐viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to smallpox vaccination. Contrary to more serious smallpox vaccine reactions, post‐vaccinial non‐viral folliculitis has a benign course and resolves spontaneously within approximately 7 days. We describe additional histopathologic findings associated with post‐vaccinial non‐viral folliculitis, which has only been described once previously. New findings include the presence of a neutrophilic or lymphohistiocytic infiltrate that is concentrated around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind post‐vaccinial non‐viral folliculitis.
Childhood basilar artery thrombosis: reassuring outcomes in younger patients
Authors: deVeber Gabrielle
Published: November 2012

This commentary is on the original article by Goeggel Simonetti et al. on pages 65–70 of this issue
The Role of Tissue Doppler Imaging in Predicting Left Ventricular Filling Pressures in Patients Undergoing Cardiac Surgery: An Intraoperative Study
Authors: Kumar Kanwal , Nepomuceno Roman G. , Chelvanathan Anjala , Golian Mehrdad , Bohonis Sheena , Cleverley Kelby , Ravandi Amir , Mackenzie Scott , Jassal Davinder S.
Published: November 2012

Introduction: The perioperative management of patients undergoing cardiac surgery usually requires the accurate assessment of left ventricular filling pressures (LVFP). The gold standard for determining LVFP involves the use of pulmonary artery catheters (PAC). Using tissue Doppler indices (TDI) obtained by transthoracic echocardiography, the ratio of early transmitral filling velocity to the corresponding early mitral annular velocity (E/E′) has a strong correlation with pulmonary capillary wedge pressure (PCWP). Little is known, however, on whether this relationship between E/E′ and PCWP is valid intraoperatively using transesophageal echocardiography (TEE) during cardiac surgery. Objective: The objective of our study was to determine whether TDI obtained by intraoperative TEE during cardiac surgery can accurately estimate PCWP using PAC as the gold standard. Methods and Results: A total of 34 patients (26 males, mean age 64 ± 9 years) undergoing cardiac surgery were prospectively enrolled between 2010 and 2011 at a single tertiary care center. Conventional diastolic and tissue Doppler parameters were evaluated using intraoperative TEE with concurrent PAC monitoring before and after cardiopulmonary bypass (CPB) surgery. At both pre‐ and post‐CPB, there was no significant correlation between lateral, septal, and mean E/E′ obtained by TEE and PCWP. Conclusion: Intraoperative TEE was unable to accurately predict LVFP in patients undergoing cardiac surgery. PAC may continue to be the gold standard in the assessment of LVFP for this patient population.
Isolated Congenital Left Ventricular Diverticulum in an Adult
Authors: Bilgin Murat , Yildiz Serhat , Gul Ilker , Nalbantgil Sanem
Published: November 2012

An isolated congenital left ventricular diverticulum, which is characterized by the local failure of the ventricular muscle during embryologic development, is a rare cardiac abnormality that may be found in isolated form or in the accompaniment of other cardiac abnormalities. Clinically, it has been reported to follow an asymptomatic course in the majority of cases; however, it may cause heart failure, arrhythmia, or chest pain in some patients.
BDNF‐mediated regulation of ethanol consumption requires the activation of the MAP kinase pathway and protein synthesis
Authors: Jeanblanc Jerome , Logrip Marian L. , Janak Patricia H. , Ron Dorit
Published: November 2012

We previously found that the brain‐derived neurotrophic factor (BDNF) in the dorsolateral striatum (DLS) is part of a homeostatic pathway that gates ethanol self‐administration [Jeanblanc et al. (2009). J Neurosci, 29, 13494–13502)]. Specifically, we showed that moderate levels (10%) of ethanol consumption increase BDNF expression within the DLS, and that direct infusion of BDNF into the DLS decreases operant self‐administration of a 10% ethanol solution. BDNF binding to its receptor, TrkB, activates the mitogen‐activated protein kinase (MAPK), phospholipase C‐γ (PLC‐γ) and phosphatidylinositol 3‐kinase (PI3K) pathways. Thus, here, we set out to identify which of these intracellular pathway(s) plays a role in the regulation of ethanol consumption by BDNF. We found that inhibition of the MAPK, but not PLC‐γ or PI3K, activity blocks the BDNF‐mediated reduction of ethanol consumption. As activation of the MAPK pathway leads to the initiation of transcription and/or translation events, we tested whether the BDNF‐mediated reduction of ethanol self‐administration requires de novo protein synthesis. We found that the inhibitory effect of BDNF on ethanol intake is blocked by the protein synthesis inhibitor cycloheximide. Together, our results show that BDNF attenuates ethanol drinking via activation of the MAPK pathway in a protein synthesis‐dependent manner within the DLS.
Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS–EEG
Authors: Vernet Marine , Bashir Shahid , Yoo Woo‐Kyoung , Perez Jennifer M. , Najib Umer , Pascual‐Leone Alvaro
Published: November 2012

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor‐evoked potentials (MEPs) reflective of modulation of cortico‐spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta‐burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS‐induced EEG evoked potentials (TEPs), (iii) TMS‐induced EEG synchronization and (iv) eyes‐closed resting EEG. Our results show the expected cTBS‐induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes‐closed resting EEG, whereas it decreased single‐pulse TMS‐induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes‐closed resting EEG, whereas it increased single‐pulse TMS‐induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low‐frequency (theta and/or alpha) oscillators and desynchronizes high‐frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS‐induced plasticity outside of the motor cortex.