bluuebunny/crossref_metadata_2025 huggingface dataset:
Maillard‐Reaction‐Induced Modification and Aggregation of Proteins and Hardening of Texture in Protein Bar Model Systems
Authors: Zhou Peng , Guo Mufan , Liu Dasong , Liu Xiaoming , Labuza Teodore P.
Published: February 2013

The hardening of high‐protein bars causes problems in their acceptability to consumers. The objective of this study was to determine the progress of the Maillard reaction in model systems of high‐protein nutritional bars containing reducing sugars, and to illustrate the influences of the Maillard reaction on the modification and aggregation of proteins and the hardening of bar matrices during storage. The progress of the Maillard reaction, glycation, and aggregation of proteins, and textural changes in bar matrices were investigated during storage at 25, 35, and 45 °C. The initial development of the Maillard reaction caused little changes in hardness; however, further storage resulted in dramatic modification of protein with formation of high‐molecular‐weight polymers, resulting in the hardening in texture. The replacement of reducing sugars with nonreducing ingredients such as sugar alcohols in the formula minimized the changes in texture.

Practical Application: The hardening of high‐protein bars causes problems in their acceptability to consumers. Maillard reaction is one of the mechanisms contributing to the hardening of bar matrix, particularly for the late stage of storage. The replacement of reducing sugars with nonreducing ingredients such as sugar alcohols in the formula will minimize the changes in texture.
Australasian brachytherapy audit: Results of the ‘end‐to‐end’ dosimetry pilot study
Authors: Haworth Annette , Wilfert Lisa , Butler Duncan , Ebert Martin A , Todd Stephen , Bucci Joseph , Duchesne Gillian M , Joseph David , Kron Tomas
Published: February 2013

Introduction

We present the results of a pilot study to test the feasibility of a brachytherapy dosimetry audit.

Methods

The feasibility study was conducted at seven sites from four Australian states in both public and private centres. A purpose‐built cylindrical water phantom was imaged using the local imaging protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of 3) thermoluminescent dosimeter (TLD) from six dwell positions.

Results

All centres completed the audit, consisting of three consecutive irradiations, within a 2‐h time period, with the exception of one centre that uses a pulsed dose rate brachytherapy unit. All TLD results were within 4.5% of the predicted value, with the exception of one subset where the dwell position step size was incorrectly applied.

Conclusions

While the limited data collected in the study demonstrated considerable heterogeneity in clinical practice, the study proved a brachytherapy dosimetry audit to be feasible. Future studies should include verification of source strength using a Standard Dosimetry Laboratory calibrated chamber, a phantom that more closely mimics the clinical situation, a more comprehensive review of safety and quality assurance (QA) procedures including source dwell time and position accuracy, and a review of patient treatment QA procedures such as applicator position verification.
An ethical analysis of proxy and waiver of consent in critical care research
Authors: BERG R. M. G. , MøLLER K. , ROSSEL P. J. H.
Published: February 2013

It is a central principle in medical ethics that vulnerable patients are entitled to a degree of protection that reflects their vulnerability. In critical care research, this protection is often established by means of so‐called proxy consent. Proxy consent for research participation constitutes a substituted judgement by a close relative or friend, based on knowledge of patient's values, preferences, and view of life. For the consent to be genuine, the proxy must be informed of and understand three fundamental aspects of research practice: (1) that participation is voluntary and the consent can be withdrawn at any time; (2) that the research is designed to benefit future patients and society as a whole, and not the individual study participant; and (3) that participation involves an incremental non‐therapeutic risk. If this is not fulfilled because the research is to be conducted under circumstances where the proxy is unavailable, adequate protection of the patient must be ensured by other means. Thus, the research must be designed specifically to benefit critically ill patients, and the incremental non‐therapeutic risk must only comprise a minimal risk.
Large chromosome deletions, duplications, and gene conversion events accumulate with age in normal human colon crypts
Authors: Hsieh John C. F. , Van Den Berg David , Kang Haeyoun , Hsieh Chih‐Lin , Lieber Michael R.
Published: February 2013

Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is difficult. We have compared colon crypts, which are putatively clonal and contain ~2000 cells each, to determine how much somatic genetic variation occurs in vivo (without ex vivo cell culturing). Using high‐density SNP microarrays, we find that chromosome deletions, duplications, and gene conversions were significantly more frequent in colons from the older individuals. These changes affected lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a single mutant stem cell to reach niche dominance over neighboring stem cells, none of the deletions appear likely to confer a selective advantage. Mutations can become fixed randomly during stem cell evolution through neutral drift in normal human crypts. The fact that chromosomal changes are detected in individual crypts with increasing age suggests that either such changes accumulate with age or single stem cell dominance increases with age, and the former is more likely. This progressive genome‐wide divergence of human somatic cells with age has implications for aging and disease in multicellular organisms.
Self‐reported alcohol abuse in HIV–HCV co‐infected patients: a better predictor of HIV virological rebound than physician's perceptions (HEPAVIH ARNS CO13 cohort)
Authors: Marcellin Fabienne , Lions Caroline , Winnock Maria , Salmon Dominique , Durant Jacques , Spire Bruno , Mora Marion , Loko Marc‐Arthur , Dabis François , Dominguez Stéphanie , Roux Perrine , Carrieri Maria Patrizia ,   ANRS CO13 HEPAVIH Study Group
Published: February 2013

Aims

Studying alcohol abuse impact, as measured by physicians' perceptions and patients' self‐reports, on HIV virological rebound among patients chronically co‐infected with HIV and hepatitis C virus (HCV).

Design

Cohort study.

Setting

Seventeen French hospitals.

Participants

Five hundred and twelve patients receiving antiretroviral therapy (ART) with an undetectable initial HIV viral load and at least two viral load measures during follow‐up.

Measurements

Medical records and self‐administered questionnaires. HIV virological rebound defined as HIV viral load above the limit of detection of the given hospital's laboratory test. Alcohol abuse defined as reporting to have drunk regularly at least 4 (for men) or 3 (for women) alcohol units per day during the previous 6 months. Correlates of time to HIV virological rebound identified using Cox proportional hazards models.

Findings

At enrolment, 9% of patients reported alcohol abuse. Physicians considered 14.8% of all participants as alcohol abusers. Self‐reported alcohol abuse was associated independently with HIV virological rebound [hazard ratio (95% confidence interval): 2.04 (1.13–3.67); P = 0.02], after adjustment for CD4 count, time since ART initiation and hospital HIV caseload. No significant relationship was observed between physician‐reported alcohol abuse and virological rebound (P = 0.87).

Conclusions

In France, the assessment of alcohol abuse in patients co‐infected with HIV and hepatitis C virus should be based on patients' self‐reports, rather than physicians' perceptions. Baseline screening of self‐reported alcohol abuse may help identify co‐infected patients at risk of subsequent HIV virological rebound.
Clinical usefulness of portal venous stent in hepatobiliary pancreatic cancers
Authors: Zhou Zun Qiang , Lee Jae Hoon , Song Ki Byung , Hwang Ji Woong , Kim Song Cheol , Lee Young‐Joo , Park Kwang‐Min
Published: February 2013

Background

Treatment options for patients with portal vein (PV) stenosis or occlusion after surgery are limited. The purpose of this study was to investigate the efficacy and safety of PV stent placement in patients with portal vein occlusion or stenosis after radical operation for hepatobiliary pancreatic malignant tumour.

Methods

We retrospectively reviewed the records of 59 patients who underwent portal venous stent placement at the Asan Medical Center, Seoul, Korea, for PV stenosis or occlusion between February 2008 and February 2012.

Results

Stents were placed in the portal venous system across stenotic (n = 47) and occlusive (n = 12) lesions after percutaneous transhepatic portography. Reasons for stent placement were tumour recurrence (n = 30), portal vein resection and anastomosis (n = 18) and post‐operative inflammatory changes (n = 11). Pressure gradients (superior mesenteric vein, main PV) decreased immediately after stent placement, from 10.5 mm Hg ± 4.4 (standard deviation) to 2.5 mm Hg ± 2.6 (P < 0.0001). Liver function was improved post‐stenting (P < 0.05). The median time between the original surgery and stent placement was 16 (1–137) days in the vascular‐orientated group and 306 (13–3703) days in the tumour recurrence group (P < 0.0001). Transient fever developed in 11 patients, but resolved in 2–5 days. Stents were occluded in 15 of the 59 patients (25.4%).

Conclusion

PV stent placement is a safe choice, has an acceptable success rate and provides marked relief from portal hypertension due to portal vein occlusion or stenosis after hepatobiliary pancreatic surgery. Liver function data are also improved after portal venous stent placement.
Economics of childbirth
Authors: Fahy Michael , Doyle Orla , Denny Kevin , Mcauliffe Fionnuala M. , Robson Michael
Published: February 2013

Background

Increasing birth rates have raised questions for policy makers and hospital management about the economic costs of childbirth.

Objective

The purpose of this article is to identify and review all existing scientific studies in relation to the economic costs of alternative modes of childbirth delivery and to highlight deficiencies in the existing scientific research.

Method

We searched Cochrane, Centre for Reviews and Dissemination, EconLit, the Excerpta Medica Database, the Health Economic Evaluations Database, MEDLINE and PubMed.

Results

Thirty articles are included in this review. The main findings suggest that there is no internationally acceptable childbirth cost and clinical outcome classification system that allows for comparisons across different delivery modes.

Conclusion

This review demonstrates that a better understanding and classification of the costs and associated clinical outcomes of childbirth is required to allow for valid comparisons between maternity units, and to inform policy makers and hospital management.
Meta‐analysis: oral or enteral nutritional supplementation in cirrhosis
Authors: Ney M. , Vandermeer B. , van Zanten S. J. V. , Ma M. M. , Gramlich L. , Tandon P.
Published: February 2013

Background

Malnutrition is a common and clinically significant problem in patients with cirrhosis. The impact of nutritional therapy remains unclear.

Aim

To provide an up‐to‐date systematic review and meta‐analysis of RCTs of oral or enteral nutritional supplementation (ONS or ENS) on nutritional and clinical outcomes in adult patients with cirrhosis.

Methods

The primary outcome measure was survival. Included: full‐text English language RCTs investigating ONS or ENS vs. a standard nonsupplemented diet in patients with cirrhosis. Excluded: parenteral or branched chain amino acids intervention; treatment duration ≤7 days, exclusive evaluation of posttransplant, postsurgical or quality of life outcomes.

Results

Six trials (4 ONS/2 ENS) and 470 patients were included with 71% males and median age 53 years. When all studies were combined, there was no reduction in mortality [Relative risk (RR): 0.75 (0.42, 1.32), P = 0.31]. Subgroup analysis of 3 of the 4 ONS studies did demonstrate a mortality reduction [RR: 0.40 (0.18, 0.90), P = 0.03]. Of the 2 ENS studies, one included the sickest patients in the meta‐analysis (82% Child Pugh C) and the other had the shortest mean intervention duration (8.6 days), possibly impacting the potential for benefit. Study quality was suboptimal (median Jadad = 2).

Conclusions

Although there is insufficient evidence to definitively state that oro‐enteral nutritional supplementation impacts clinical outcomes, on the basis of this analysis, one can be cautiously optimistic that there is the potential for benefit without an increase in adverse events. Adequately powered, Child Pugh stratified studies of at least 1 month in duration are needed to clarify the impact on relevant clinical outcomes.
CGRP in the trigeminovascular system: a role for CGRP, adrenomedullin and amylin receptors?
Authors: Walker C S , Hay D L
Published: February 2013

The neuropeptide calcitonin gene‐related peptide (CGRP) is reported to play an important role in migraine. It is expressed throughout the trigeminovascular system. Antagonists targeting the CGRP receptor have been developed and have shown efficacy in clinical trials for migraine. However, no CGRP antagonist is yet approved for treating this condition. The molecular composition of the CGRP receptor is unusual because it comprises two subunits; one is a GPCR, the calcitonin receptor‐like receptor (CLR). This associates with receptor activity‐modifying protein (RAMP) 1 to yield a functional receptor for CGRP. However, RAMP1 also associates with the calcitonin receptor, creating a receptor for the related peptide amylin but this also has high affinity for CGRP. Other combinations of CLR or the calcitonin receptor with RAMPs can also generate receptors that are responsive to CGRP. CGRP potentially modulates an array of signal transduction pathways downstream of activation of these receptors, in a cell type‐dependent manner. The physiological significance of these signalling processes remains unclear but may be a potential avenue for refining drug design. This complexity has prompted us to review the signalling and expression of CGRP and related receptors in the trigeminovascular system. This reveals that more than one CGRP responsive receptor may be expressed in key parts of this system and that further work is required to determine their contribution to CGRP physiology and pathophysiology.

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
Molecular mechanisms underlying the anti‐proliferative and anti‐migratory effects of folate on homocysteine‐challenged rat aortic smooth muscle cells
Authors: Chou Ying , Lin Hui‐Chen , Chen Kuan‐Chou , Chang Chi‐Cheng , Lee Wen‐Sen , Juan Shu‐Hui
Published: February 2013

Background and Purpose

Homocysteine is an intermediate product formed during the metabolism of methionine, and is increased in cells with folate deficiency. Patients with hyperhomocysteinemia tend to develop cardiovascular disease. Here, we have examined the molecular mechanisms underlying the anti‐proliferative and anti‐migratory effects of folate on homocysteine‐challenged rat aortic smooth muscle cells (RASMCs).

Experimental Approach

Cultures of RASMC were challenged with homocysteine and then incubated with folate added. Changes in p21/p27, AKT and RhoA were followed by RT‐PCR, Western blotting and immunocytochemistry. Transfection and anti‐sense techniques were also used. Cell viability, growth and migration were measured.

Key Results

Folate up‐regulated p21/p27 through a Src/ERK‐dependent mechanism that accounted for its anti‐proliferative effects on RASMC. Folate protected RASMC from the effects of homocysteine by reducing AKT1, focal adhesion kinase (FAK), paxillin, and p190RhoGAP activation/phosphorylation, along with cytosolic levels of p21 and p27, and increasing RhoA activation. Overexpression of AKT1, but not of AKT2, induced p21/p27 phosphorylation and increased cytosolic p21/p27 levels, as did homocysteine treatment. By contrast, and similarly to folate treatment, transfection with dominant negative (DN) AKT1 counteracted these effects. Additionally, AKT was shown to be an upstream target of FAK activation. In RASMC overexpressing constitutively active RhoA, activation of RhoA mediated the anti‐migratory effects of folate. Addition of Y27632 (a RhoA inhibitor) and DNRhoA counteracted the anti‐migratory effects, confirming RhoA involvement.

Conclusion and implications

Folate was anti‐proliferative and anti‐migratory in homocysteine‐challenged RASMC. Mechanisms underlying folate‐mediated protection against the proatherosclerotic effects of homocysteine have been delineated.
The macrocyclic tetrapeptide [D‐Trp]CJ‐15,208 produces short‐acting κ opioid receptor antagonism in the CNS after oral administration
Authors: Eans Shainnel O , Ganno Michelle L , Reilley Kate J , Patkar Kshitij A , Senadheera Sanjeewa N , Aldrich Jane V , McLaughlin Jay P
Published: February 2013

Background and Purpose

Cyclic peptides are resistant to proteolytic cleavage, therefore potentially exhibiting activity after systemic administration. We hypothesized that the macrocyclic κ opioid receptor (KOR)‐selective antagonist [D‐Trp]CJ‐15,208 would demonstrate antagonist activity after systemic, that is, s.c. and oral (per os, p. o.), administration.

Experimental Approach

C57BL/6J mice were pretreated with [D‐Trp]CJ‐15,208 s.c. or p.o. before administration of the KOR‐selective agonist U50,488 and the determination of antinociception in the warm‐water tail‐withdrawal assay. The locomotor activity of mice treated with [D‐Trp]CJ‐15,208 was determined by rotorod testing. Additional mice demonstrating cocaine conditioned place preference and subsequent extinction were pretreated daily with vehicle or [D‐Trp]CJ‐15,208 and then exposed to repeated forced swim stress or a single additional session of cocaine place conditioning before redetermining place preference.

Key Results

Pretreatment with [D‐Trp]CJ‐15,208 administered s.c. or p.o. dose‐dependently antagonized the antinociception induced by i.p. administration of U50,488 in mice tested in the warm‐water tail‐withdrawal assay for less than 12 and 6 h respectively. [D‐Trp]CJ‐15,208 also produced limited (<25%), short‐duration antinociception mediated through KOR agonism. Orally administered [D‐Trp]CJ‐15,208 dose‐dependently antagonized centrally administered U50,488‐induced antinociception, and prevented stress‐, but not cocaine‐induced, reinstatement of extinguished cocaine‐seeking behaviour, consistent with its KOR antagonist activity, without affecting locomotor activity.

Conclusions and Implications

The macrocyclic tetrapeptide [D‐Trp]CJ‐15,208 is a short‐duration KOR antagonist with weak KOR agonist activity that is active after oral administration and demonstrates blood–brain barrier permeability. These data validate the use of systemically active peptides such as [D‐Trp]CJ‐15,208 as potentially useful therapeutics.
Farnesyl Diphosphate Synthase Inhibitors fromIn SilicoScreening
Authors: Lindert Steffen , Zhu Wei , Liu Yi‐Liang , Pang Ran , Oldfield Eric , McCammon J. Andrew
Published: February 2013

The relaxed complex scheme is anin silicodrug screening method that accounts for receptor flexibility using molecular dynamics simulations. Here, we used this approach combined with similarity searches and experimental inhibition assays to identify several low micromolar, non‐bisphosphonate inhibitors, bisamidines, of farnesyl diphosphate synthase (FPPS), an enzyme targeted by some anticancer and antimicrobial agents and for the treatment of bone resorption diseases. This novel class of farnesyl diphosphate synthase inhibitors have more drug‐like properties than existing bisphosphonate inhibitors, making them interesting pharmaceutical leads.
Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3− T cells in complete DiGeorge anomaly
Authors: Chinn I K , Milner J D , Scheinberg P , Douek D C , Markert M L
Published: February 2013

The development of T cells with a regulatory phenotype after thymus transplantation has not been examined previously in complete DiGeorge anomaly (cDGA). Seven athymic infants with cDGA and non-maternal pretransplantation T cell clones were assessed. Pretransplantation forkhead box protein 3 (Foxp3)+ T cells were detected in five of the subjects. Two subjects were studied in greater depth. T cell receptor variable β chain (TCR-Vβ) expression was assessed by flow cytometry. In both subjects, pretransplantation FoxP3+ and total CD4+ T cells showed restricted TCR-Vβ expression. The development of naive T cells and diverse CD4+ TCR-Vβ repertoires following thymic transplantation indicated successful thymopoiesis from the thymic tissue grafts. Infants with atypical cDGA develop rashes and autoimmune phenomena before transplantation, requiring treatment with immunosuppression, which was discontinued successfully subsequent to the observed thymopoiesis. Post-transplantation, diverse TCR-Vβ family expression was also observed in FoxP3+ CD4+ T cells. Interestingly, the percentages of each of the TCR-Vβ families expressed on FoxP3+ and total CD4+ T cells differed significantly between these T lymphocyte subpopulations before transplantation. By 16 months post-transplantation, however, the percentages of expression of each TCR-Vβ family became significantly similar between FoxP3+ and total CD4+ T cells. Sequencing of TCRBV DNA confirmed the presence of clonally amplified pretransplantation FoxP3+ and FoxP3− T cells. After thymus transplantation, increased polyclonality was observed for both FoxP3+ and FoxP3− cells, and pretransplantation FoxP3+ and FoxP3− clonotypes essentially disappeared. Thus, post-transplantation thymic function was associated with the development of a diverse repertoire of FoxP3+ T cells in cDGA, corresponding with immunological and clinical recovery.
Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1
Authors: Ingram R J , Harris A , Ascough S , Metan G , Doganay M , Ballie L , Williamson E D , Dyson H , Robinson J H , Sriskandan S , Altmann D M
Published: February 2013

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either ‘low’ or ‘high’ expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.
Indoleamine 2,3 dioxygenase contributes to transferable tolerance in rat red blood cell inducible model of experimental autoimmune haemolytic anaemia
Authors: Dahal L N , Hall L S , Barker R N , Ward F J
Published: February 2013

Autoimmune haemolytic anaemia (AIHA) is caused by autoantibodies against red blood cell (RBC) surface antigens that render RBC susceptible to Fc-mediated phagocytosis and complement-mediated lysis. Experimental AIHA can be induced by injection of rat RBC to naive mice, but a lymphocyte-mediated regulatory mechanism eventually suppresses the production of autoantibodies specific for mouse RBC. Critically, this tolerogenic response can be transferred to naive mice by splenocytes from the rat RBC-immunized mouse. Here we investigate whether indoleamine 2,3 dioxygenase (IDO) or the initiators of IDO cascade, including the cytotoxic T lymphocyte antigen (CTLA)-4 receptor and its soluble isoform, contribute to this tolerogenic mechanism. Splenocytes from experimental AIHA mice were transferred adoptively to naive mice under the cover of anti-CTLA-4, anti-soluble CTLA-4 antibodies or IDO inhibitor 1-methyl tryptophan (1-MT). Recipient mice were immunized with rat RBC and levels of antibody against self-RBC and rat-RBC were monitored. Our results indicate that transfer of tolerance to naive recipients is dependent upon IDO-mediated immunosuppression, as mice receiving previously tolerized splenocytes under the cover of 1-MT were refractory to tolerance and developed haemolytic disease upon further challenge with rat RBC. Initiators of IDO activity, CTLA-4 or soluble CTLA-4 did not mediate this tolerogenic process but, on their blockade, boosted antigen-specific effector immune responses.
Polymorphism −116C/Gof HumanX‐box‐Binding Protein 1 Promoter is Associated with Risk ofAlzheimer's Disease
Authors: Liu Sheng‐Yuan , Wang Wei , Cai Zhi‐You , Yao Li‐Fen , Chen Zhong‐Wei , Wang Chang‐Yi , Zhao Bin , Li Ke‐Shen
Published: February 2013

Aim

Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum (ER) stress response. In the response, the regulator factor humanX‐box‐binding protein 1 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid‐beta (Aβ) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the −116C/Gpolymorphism ofXBP1and the risk ofAD.

Methods

The association between −116C/Gpolymorphism ofXBP1promoter and possible risk ofADwas assessed among 276 patients withADand 254 matched healthy individuals in a case–control study.

Results

Overall, there was a significantly statistical difference in genotype (P = 0.0354) and allele frequencies (P = 0.0150,OR = 1.3642, 95%CI = 1.0618–1.7528) between theADsubjects and control subjects, showing that the −116C/Gpolymorphism ofXBP1might lead to increased susceptibility forADin aChineseHan population. In addition, the −116CGand −116GGgenotypes were significantly associated with increasedADrisk in female (P = 0.0217) and in subjects withAPOEє4 (−) (P = 0.0070) in stratified analyses, and the −116CCgenotype was significantly associated with fast cognitive deterioration in theADpatients (P = 0.0270).

Conclusion

The study supports a role for the −116C/G polymorphism ofXBP1gene in the pathogenesis ofAD, and further studies with a larger sample size and detailed data should be performed in other populations.
Once weekly exenatide: efficacy, tolerability and place in therapy
Authors: Wysham C. , Grimm M. , Chen S.
Published: February 2013

Exenatide once weekly is the first glucose‐lowering agent available to patients with type 2 diabetes mellitus (T2DM) which is administered once per week. This long‐acting formulation contains the same active ingredient as exenatide twice daily, except that the exenatide is encapsulated in dissolvable microspheres. Following subcutaneous injection, exenatide once weekly microspheres remain in place under the skin and slowly degrade, releasing active exenatide continuously into circulation. In randomized clinical trials, exenatide once weekly was associated with significant glycaemic improvement and moderate weight loss in patients with T2DM when administered as monotherapy or in combination with a variety of oral antidiabetic agents. Exenatide once weekly also lowered blood glucose more effectively than titrated basal insulin in patients on metformin or metformin plus sulphonylurea background therapy. Gastrointestinal side effects (nausea, vomiting and diarrhoea) were the most common tolerability issues associated with exenatide once weekly administration, but they occurred at lower rates than in patients on other glucagon‐like peptide receptor agonists (i.e., exenatide twice daily or liraglutide). Issues regarding the place of exenatide once weekly in T2DM pharmacotherapy are discussed.
Gender dimorphic increase in RBP‐4 and NGAL in children born after IVF: an epigenetic phenomenon?
Authors: Sakka Sophia D. , Margeli Alexandra , Loutradis Dimitrios , Chrousos George P. , Papassotiriou Ioannis , Kanaka‐Gantenbein Christina
Published: February 2013

Background

In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children's metabolic profile compared with controls. The recently reported lipocalins retinol‐binding protein 4 (RBP‐4) and neutrophil gelatinase‐associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP‐4 and NGAL as well as visfatin in children born after IVF.

Subjects and methods

A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 4–14 year, were studied cross‐sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP‐4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated.

Results

Children born after IVF had significantly higher RBP‐4 (P = 0·009) and NGAL (P = 0·028) levels than controls. When divided by gender, RBP‐4 remained higher in IVF girls (P = 0·002), whereas NGAL was higher in IVF boys (P = 0·021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se.

Conclusions

In our study, IVF children had significantly higher RBP‐4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile.
COMTrs4680 Met is not always the ‘smart allele’: Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese
Authors: Wang Y. , Li J. , Chen C. , Chen C. , Zhu B. , Moysis R. K. , Lei X. , Li H. , Liu Q. , Xiu D. , Liu B. , Chen W. , Xue G. , Dong Q.
Published: February 2013

Catechol‐O‐methyltransferase (COMT)Val158Met(rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lowerCOMTactivity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important forWM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related toWMin Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association ofCOMT Val158Metgenotype with behavioral data on a two‐backWMtask (n= 443,189M/254F) andT1 MRIdata (n = 320,134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus:β= −0.118,t= −2.367,P= 0.019, and the left hippocampus:β= −0.099,t= −1.949,P= 0.052) and betterWMperformance (β= −0.110,t= −2.315,P= 0.021). These results add to the growing literature on differentiated effects ofCOMTrs4680 polymorphism onWMacross populations and offer a brain structural mechanism for such population‐specific genetic effects.
Niche conservatism in non‐native birds in Europe: niche unfilling rather than niche expansion
Authors: Strubbe Diederik , Broennimann Olivier , Chiron François , Matthysen Erik
Published: February 2013

Aim

Niche conservatism, or the extent to which niches are conserved across space and time, is of special concern for the study of non‐native species as it underlies predictions of invasion risk. Based on the occurrence of 28 non‐native birds in Europe, we assess to what extent Grinnellian realized niches are conserved during invasion, formulate hypotheses to explain the variation in observed niche changes and test how well species distribution models can predict non‐native bird occurrence in Europe.

Location

Europe.

Methods

To quantify niche changes, a recent method that applies kernel smoothers to densities of species occurrence in a gridded environmental space was used. This corrects for differences in the availability of environments between study areas and allows discrimination between ‘niche expansion’ into environments new to the species and ‘niche unfilling’, whereby the species only partially fills its niche in the invaded range. Predictions of non‐native bird distribution in Europe were generated using several distribution modelling techniques.

Results

Niche overlap between native and non‐native bird populations is low, but niche changes are smaller for species having a higher propagule pressure and that were introduced longer ago. Non‐native birds in Europe occupy a subset of the environments they inhabit in their native ranges. Niche expansion into novel environments is rare for most species, allowing species distribution models to accurately predict invasion risk.

Main conclusions

Because of the recent nature of most bird introductions, species occupy only part of the suitable environments available in the invaded range. This signals that apart from purely ecological factors, patterns of niche conservatism may also be contingent on population‐specific historical factors. These results also suggest that many claims of niche differences may be due to a partial filling of the native niche in the invaded range and thus do not represent true niche changes.
Histological features in western patients with idiopathic non‐cirrhotic portal hypertension
Authors: Verheij Joanne , Schouten Jeoffrey N L , Komuta Mina , Nevens Frederik , Hansen Bettina E , Janssen Harry L A , Roskams Tania
Published: February 2013

Aims

In the western world, idiopathic non‐cirrhotic portal hypertension (INCPH) is a rare disease. This study aimed to investigate the histopathological features in western INCPH patients and to assess pathological differences between liver specimens of INCPH with and without HIV.

Methods and results

Biopsies of 70 INCPH patients (of which 15 were HIV‐infected) were compared to 23 patients with non‐cirrhotic portal vein thrombosis (PVT), which served as a control group for non‐cirrhotic portal hypertension. Phlebosclerosis, nodular regeneration (NR), sinusoidal dilatation, paraportal shunting vessels, perisinusoidal fibrosis and portal tract remnants were the most prevalent morphological features of INCPH. There were significant (P < 0.01) morphological differences between INCPH and PVT liver specimens with regard to portal tract remnants (46% versus 0%), phlebosclerosis (95% versus 65%), portal vein dilatation (34% versus 78%) and NR (56% versus 22%). The degree of NR correlated with the severity of phlebosclerosis (P < 0.01). NR was seen more frequently in the HIV–INCPH group, compared to the non‐HIV‐infected patients (P < 0.001).

Conclusion

Portal tract remnants, phlebosclerosis and nodular regeneration are typical features of INCPH. Sinusoidal dilatation, paraportal shunting vessels and increased portal and parenchymal vessels might represent pressure‐related morphological signs of portal hypertension. Finally, more nodular regeneration was observed in HIV‐associated INCPH.
Skin cell targeting with self‐assembled ligand addressed nanoemulsion droplets
Authors: Atrux‐Tallau N. , Delmas T. , Han S.‐H. , Kim J.‐W. , Bibette J.
Published: February 2013

Synopsis

Dermo‐pharmacy and cosmetic industries have utilized nanotechnologies for two decades. Initially proposed as vector systems for encapsulation of actives, they gained interest in increasing cutaneous bioavailability. Here, we assay the benefits of self‐assembled nanoemulsions bearing ligands for targeting specific skin cells. Nanoemulsions, small droplets ranging typically from 20 nm to 150 nm, possess key properties for further use in cosmetics: long‐term stability, optical transparency, extended range of textures and versatility. We investigated this nanoemulsion system and show ability to encapsulate a range of cosmetic actives with various physicochemical properties. Furthermore, this nanoemulsion presents a low cytotoxicity and is capable of directly targeting skin cells through simple addition of specific ligand in a one‐step production protocol. This is of interest for increasing bioavailability of actives encapsulated into nanoemulsion droplets which may have penetrated the skin barrier to specific skin cell. Taken together, these chemical and in vitro observations suggest follow‐up with in vivo models.
Coverage of urethroplasty in pediatric hypospadias: Randomized comparison between different flaps
Authors: Cimador Marcello , Pensabene Marco , Sergio Maria , Catalano Pieralba , de Grazia Enrico
Published: February 2013

Objectives

The use of covering urethroplasty with flaps in hypospadias surgery has been well recommended. Various techniques have been described for flap harvesting. The aim of the present study was to compare the outcome and complication rate of dorsal preputial flaps and ventral dartos flaps.

Methods

A total of 130 patients were prospectively evaluated from January 2008 to December 2011. Using the tubularized incised plate urethroplasty procedure, urethroplasty was carried out by a single surgeon. Patients were randomly divided in two groups: group A (57 patients), in which a preputial flap was carried out using three different techniques; and group B (73 patients), in which a single or a double ventral dartos flap was used.

Results

A total of 41 complications occurred in 24 patients. Urethrocutaneous fistulas were observed in 14.9%, quite equally distributed between groups A and B. There was only one urethrocutaneous fistula in a patient treated with the double ventral dartos flaps. Five cases (3.8%) of glans dehiscence were observed: four after single ventral dartos flap and one after dorsal preputial flap. Six patients in group A and seven in group B experienced meatal stenosis. In three cases of iatrogenic torsion of the penis, a dorsal preputial flap was laterally transposed. Finally, a lower complication rate was observed for double ventral dartos flap versus the other techniques.

Conclusions

The use of a double ventral dartos flap should represent the first‐line technique for coverage of distal urethroplasty.
Do 12‐Month‐Old Infants Trust a Competent Adult?
Authors: Stenberg Gunilla
Published: February 2013

Why infants prefer to look at and use information provided by some informants over others was examined in four experiments. In each experiment, 52 12‐month‐old infants participated. In Experiment 1, a familiar expert and a familiar nonexpert and in Experiment 2, a novel expert and a novel nonexpert presented an ambiguous object and provided positive information. In both experiments, the infants preferred to look at the expert and regulated their behavior more in accordance with positive information provided by the expert, regardless of she was novel or more familiar. In Experiment 3, a familiar expert and a familiar nonexpert and in Experiment 4, a novel expert and a novel nonexpert presented an ambiguous object and provided negative information. In both experiments, the infants looked more at the expert and regulated their behavior more in accordance with negative information provided by the expert, regardless of she was novel or more familiar. The results support an expertise perspective of infant behavior in social‐referencing situations.
Nursing interventions in inpatient psychiatry
Authors: Frauenfelder F. , Müller‐Staub M. , Needham I. , van Achterberg T.
Published: February 2013

Accessible summary

The use of a standardized nursing language enhances nursing quality. The Nursing Interventions Classification (NIC) considers any treatment by nurses that improve patient outcomes.

The present study identifies nursing interventions in journal articles on adult psychiatric inpatient nursing care. These interventions are compared with the NIC entries to elucidate how well this classification covers the realities of nursing in inpatient psychiatric settings.

The NIC encompasses most interventions mentioned in the articles. Only a few interventions need to be added to the NIC classification or require a reorganization of the taxonomy.

The successful application of theNursingInterventionsClassification (NIC) in inpatient psychiatry depends on whether the classification adequately describes nursing care in this setting. The present study aimed to identify nursing interventions mentioned in journal articles on psychiatric inpatient nursing care and to compare these with the labels, definitions and activities described in theNICto elucidate how well the classification covers these interventions. TheMedLine,PsychInfo,Cochrane andCINAHLdatabases were searched for journal articles about nursing care in the adult inpatient setting. A qualitative content analysis approach was used to indentify nursing interventions in the articles. About 84% of the statements (terms and definitions) are encompassed by the interventions listed by theNIC. Very few interventions need to be added to theNICclassification or necessitate a reorganization of the taxonomy. Nevertheless, the further development of theNICwill promote its use in the daily work of psychiatric nurses and enhance the quality of nursing care in the inpatient setting.
Telomeric gene deletion and intrachromosomal amplification in antimony‐resistant Leishmania
Authors: Mukherjee Angana , Boisvert Sébastien , Monte‐Neto Rubens Lima do , Coelho Adriano C. , Raymond Frederic , Mukhopadhyay Rita , Corbeil Jacques , Ouellette Marc
Published: February 2013

Antimonials are still the mainstay of treatment against leishmaniasis but drug resistance is increasing. We carried out short read next‐generation sequencing (NGS) and comparative genomic hybridization (CGH) of three independent Leishmania major antimony‐resistant mutants. Copy number variations were consistently detected with both NGS and CGH. A major attribute of antimony resistance was a novel terminal deletion of variable length (67 kb to 204 kb) of the polyploid chromosome 31 in the three mutants. Terminal deletions in two mutants occurred at the level of inverted repeated sequences. The AQP1 gene coding for an aquaglyceroporin was part of the deleted region and its transfection into resistant mutants reverted resistance to SbIII. We also highlighted an intrachromosomal amplification of a subtelomeric locus on chromosome 34 in one mutant. This region encoded for ascorbate‐dependent peroxidase (APX) and glucose‐6‐phosphate dehydrogenase (G6PDH). Overexpression of these genes in revertant backgrounds demonstrated resistance to SbIII and protection from reactive oxygen species (ROS). Generation of a G6PDH null mutant in one revertant exhibited SbIII sensitivity and a decreased protection of ROS. Our genomic analyses and functional validation highlighted novel genomic rearrangements, functionally important resistant loci and the implication of new genes in antimony resistance in Leishmania.
Biogeography of ectomycorrhizal fungi associated with alders (Alnus spp.) in relation to biotic and abiotic variables at the global scale
Authors: Põlme Sergei , Bahram Mohammad , Yamanaka Takashi , Nara Kazuhide , Dai Yu Cheng , Grebenc Tine , Kraigher Hojka , Toivonen Mika , Wang Pi‐Han , Matsuda Yosuke , Naadel Triin , Kennedy Peter G. , Kõljalg Urmas , Tedersoo Leho
Published: February 2013

Much of the macroecological information about microorganisms is confounded by the lack of standardized methodology, paucity of metadata and sampling effect of a particular substrate or interacting host taxa.

This study aims to disentangle the relative effects of biological, geographical and edaphic variables on the distribution of Alnus‐associated ectomycorrhizal (ECM) fungi at the global scale by using comparable sampling and analysis methods.

Ribosomal DNA sequence analysis revealed 146 taxa of ECM fungi from 22 Alnus species across 96 sites worldwide. Use of spatial and phylogenetic eigenvectors along with environmental variables in model selection indicated that phylogenetic relations among host plants and geographical links explained 43 and 10%, respectively,in ECM fungal community composition, whereas soil calcium concentration positively influenced taxonomic richness.

Intrageneric phylogenetic relations among host plants and regional processes largely account for the global biogeographic distribution of Alnus‐associated ECM fungi. The biogeography of ECM fungi is consistent with ancient host migration patterns from Eurasia to North America and from southern Europe to northern Europe after the last glacial maximum, indicating codispersal of hosts and their mycobionts.
Drought predisposes piñon–juniper woodlands to insect attacks and mortality
Authors: Gaylord Monica L. , Kolb Thomas E. , Pockman William T. , Plaut Jennifer A. , Yepez Enrico A. , Macalady Alison K. , Pangle Robert E. , McDowell Nate G.
Published: February 2013

To test the hypothesis that drought predisposes trees to insect attacks, we quantified the effects of water availability on insect attacks, tree resistance mechanisms, and mortality of mature piñon pine (Pinus edulis) and one‐seed juniper (Juniperus monosperma) using an experimental drought study in New Mexico, USA.

The study had four replicated treatments (40 × 40 m plot/replicate): removal of 45% of ambient annual precipitation (H2O−); irrigation to produce 125% of ambient annual precipitation (H2O+); a drought control (C) to quantify the impact of the drought infrastructure; and ambient precipitation (A).

Piñon began dying 1 yr after drought initiation, with higher mortality in the H2O− treatment relative to other treatments. Beetles (bark/twig) were present in 92% of dead trees. Resin duct density and area were more strongly affected by treatments and more strongly associated with piñon mortality than direct measurements of resin flow. For juniper, treatments had no effect on insect resistance or attacks, but needle browning was highest in the H2O− treatment.

Our results provide strong evidence that ≥ 1 yr of severe drought predisposes piñon to insect attacks and increases mortality, whereas 3 yr of the same drought causes partial canopy loss in juniper.