bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐components of evoked‐brain potentials in deficit and nondeficit schizophrenia
Authors: Li Zhe , Zheng Bo , Deng Wei , Liu Xiang , Zheng Zhong , Li Tao
Published: March 2013

Introduction

The present study aims to detect the specific and common impairment index relative to evoked brain potentials (EBPS) in deficit schizophrenia (DS) and nondeficit schizophrenia (NDS), and investigates the relationship between EBPs and clinical variables.

Methods

The study used EBPs in 21 patients with DS, 38 patients with NDS, and 50 healthy controls (HCs) to investigate P300 waves, mismatch negative (MMN), sensory gating (SG) P50 and contingent negative variation (CNV). A comparison of three groups and the relationship between EBPs and clinical variables were performed using general linear model analyses and partial correlation, respectively.

Results

Compared with HCs, both groups of patients showed delayed N1, N2, and P3a latency, and reduced N1 and N2 amplitude. The MMN showed delayed latency. The P50 ratios and the inhibited ratios were impaired, whereas SG loss ratios increased. CNV amplitude was reduced. Compared with HCs, NDS showed delayed latency of S2′‐C in CNV, whereas DS showed shortened latency. Only NDS, when compared with HCs, showed delayed latency of P3b, Also, only DS, when compared with HCs, showed delayed latency of point A in CNV. Latency of point A in CNV of DS, correlated with a poorer Global Assessment of Functioning Scale (6 weeks) and was independent of clinical characteristics.

Discussion

Schizophrenia represents a clinical syndrome with shared impairments in brain function, whereas DS is a relatively homogeneous subgroup of schizophrenia with unique pathophysiological changes.
Randomized controlled trials of antibiotics for neonatal infections: a systematic review
Authors: Kaguelidou Florentia , Turner Mark A. , Choonara Imti , van Anker John , Manzoni Paolo , Alberti Corinne , Langhendries Jean‐Paul , Jacqz‐Aigrain Evelyne
Published: March 2013

Aims

Antibiotics are a key resource for the management of infectious diseases in neonatology and their evaluation is particularly challenging. We reviewed medical literature to assess the characteristics and quality of randomized controlled trials on antibiotics in neonatal infections.

Methods

We performed a systematic search of PubMed, Embase and the Cochrane Library from January 1995 to March 2010. Bibliographies of relevant articles were also hand‐searched. We included all randomized controlled trials that involved neonates and evaluated the use of an antibiotic agent in the context of a neonatal infectious disease. Methodological quality was evaluated using the Jadad scale and the Cochrane Risk of Bias Tool. Two reviewers independently assessed studies for inclusion and evaluated methodological quality.

Results

A total of 35 randomized controlled trials were evaluated. The majority were conducted in a single hospital institution, without funding. Median sample size was 63 (34–103) participants. The most frequently evaluated antibiotic was gentamicin. Respectively, 18 (51%) and 17 (49%) trials evaluated the therapeutic or prophylactic use of antibiotics in various neonatal infections. Overall, the methodological quality was poor and did not improve over the years. Risk of bias was high in 66% of the trials.

Conclusions

Design and reporting of randomized controlled trials of antibacterial agents in neonates should be improved. Nevertheless, the necessity of implementing such trials when antibacterial efficacy has already been established in other age groups may be questioned and different methods of evaluation should be further developed.
Effects of Ethanolic Extract and Naphthoquinones Obtained from the Bulbs of Cipura paludosa on Short‐Term and Long‐Term Memory: Involvement of Adenosine A1 and A2A Receptors
Authors: Lucena Greice M. R. S. , Matheus Filipe C. , Ferreira Vania M. , Tessele Priscila B. , Azevedo Mariangela S. , Cechinel‐Filho Valdir , Prediger Rui D.
Published: March 2013

Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti‐nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short‐ and long‐term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre‐training oral administration of the ethanolic extract improved the short‐term social memory in rats as well as facilitated the step‐down inhibitory avoidance short‐ and long‐term memory in mice. Moreover, the co‐administration of ‘non‐effective’ doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non‐selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co‐administration of sub‐effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short‐ and long‐term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short‐ and long‐term memory in mice. These results demonstrate for the first time the cognitive‐enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects.
Drug and Therapeutics Committees in Danish Hospitals: A Survey of Organization, Activities and Drug Selection Procedures
Authors: Plet Hanne T. , Hallas Jesper , Nielsen Gitte S. , Kjeldsen Lene J.
Published: March 2013

To implement rational pharmacotherapy in hospitals, it is important to develop, implement and evaluate hospital drug formularies (HDFs). A report from Denmark recommended standardizing activities of the drug and therapeutics committees (DTCs) in Denmark, but little is known about their current organization. The aim of the study was to describe the organization of DTCs in Denmark, how HDFs are developed and implemented, and to what extent policies that support the use of HDFs exist. A questionnaire was developed based on previous research and guidelines and contained 20 questions, which were divided into the following subjects: structure, activities, drug selection and implementation. The questionnaire was sent to the chairmen of the nine DTCs in Denmark. The response rate was 100% (9/9). The DTCs varied in structure and activities; meetings were held between 2 and 6 times annually, and the duration of the meetings lasted between 1 and 2.5 hr. Eight (89%) DTCs developed HDFs, policies and guidelines (P&Gs) that supported the use of HDFs. Eight (89%) had established criteria for inclusion of drugs on the HDFs, and seven had developed criteria for generic substitution and therapeutic interchange. The number of trade names on the HDFs varied between 116 and 1195. The nine DTCs in Denmark varied considerably regarding structure and activity. The main activity was to develop formularies, and most of the committees developed policies that supported medication use.
Silymarin Inhibits Cell Cycle Progression and mTOR Activity in Activated Human T Cells: Therapeutic Implications for Autoimmune Diseases
Authors: Gharagozloo Marjan , Javid Elahe N. , Rezaei Abbas , Mousavizadeh Kazem
Published: March 2013

Silymarin, a complex flavonolignan from the ‘milk thistle’ (Silybum marianum) plant, exhibits anticarcinogenic, anti‐inflammatory and cytoprotective effects. Several reports have demonstrated immunosuppressive activity of silymarin; however, the molecular mechanisms involved in immunomodulatory activities of silymarin are not fully understood yet. In this study, the effect of silymarin on cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and activated with anti‐CD3 (5 μg/ml) and anti‐CD28 (2 μg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with 10, 50 and 100 μM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24–96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was determined in activated T cells after 72‐hr incubation with silymarin or DMSO. A significant G1 arrest in cell cycle of activated T lymphocytes was found after 96‐hr incubation with 100 μM silymarin without causing cell death. Silymarin also significantly inhibited the level of phospho‐S6 ribosomal protein and mTOR activity in cell lysates of activated T cells after 72‐hr incubation in comparison with DMSO. This study shows that silymarin inhibits cell proliferation through G1 cell cycle arrest and also through the suppression of the mTOR signalling pathway in human activated T lymphocytes in vitro. Characterizing molecular mechanism of such immunomodulatory effects may have a great potential in future practical application of silymarin in transplantation and auoimmunity.
Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers
Authors: Wang Liqing , Hu Zheyi , Deng Xun , Wang Yong , Zhang Zhongyi , Cheng Ze‐Neng
Published: March 2013

This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G‐3860A), G‐3113A, CYP1A2*1F (C‐163A) and CYP1A2*1B (C‐5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200‐mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7‐dimethylxanthine/caffeine ratios (17X/137X) after administration of 100‐mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high‐performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the ‐3113 AA genotype compared with those with the ‐3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the ‐3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with ‐3860G/‐3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.
Intimate Partner Violence and the Association with Very Preterm Birth
Authors: Watson Lyndsey F. , Taft Angela J.
Published: March 2013

Background

Intimate partner violence is a major public health problem. It occurs commonly in pregnancy, resulting in adverse events for women and their fetus or children. The objective of this study was to examine the association between intimate partner violence and very preterm birth.

Methods

This population‐based, case‐control study was conducted in Victoria, Australia, from 2002 to 2004. Interviews were conducted with 603 women who had a singleton very preterm birth (20–31 weeks' gestation), 770 women who had a singleton term birth (37 or more completed weeks' gestation), 139 women who had a very preterm twin birth, and 214 women who had a term twin birth. Intimate partner violence was measured using the Composite Abuse Scale, and questions were also asked about fear of partners and violence from others.

Results

Prevalence of intimate partner violence in the past 12 months was 14.9 percent in singleton case women, 11.7 percent in singleton control women, 9.5 percent in twin case women, and 14.7 percent in twin control women. Fear of a previous partner and reporting similar violence experience with someone else were more likely in singleton births (AOR = 1.36; 95% CI 1.03, 1.79) and (AOR = 1.44; 95% CI 1.12, 1.86), respectively. No differences between twin case women and twin control women were observed. When the precipitating cause of very preterm birth was investigated, antepartum hemorrhage was significantly associated with intimate partner violence and all its subscales.

Conclusions

The heterogeneity of causes of very preterm birth may explain the lack of association found with intimate partner violence in pregnancy. Pregnant women have a significant risk of intimate partner violence, which should be a serious concern for all care providers. (BIRTH 40:1 March 2013)
Perceptions of Barriers to Paternal Presence and Contribution During Childbirth: An Exploratory Study from Syria
Authors: Abushaikha Lubna , Massah Rana
Published: March 2013

Background

The barriers that face fathers during childbirth are an understudied phenomenon. The objective of our study was to explore Syrian parents' perceptions of barriers to paternal presence and contribution during childbirth.

Methods

A descriptive phenomenological qualitative approach based on Colaizzi's method was used with a purposive sample of 23 mothers and 14 fathers recruited from a major public maternity hospital in Syria.

Results

In our study, four themes on barriers to paternal presence and contribution during childbirth were found: 1) sociocultural influences and rigidity; 2) being unprepared; 3) unsupportive policies and attitudes; and 4) unfavorable reactions and circumstances.

Conclusions

Common and current sociocultural norms in Syria do not encourage fathers to be present or contribute during childbirth. Therefore, establishing culturally sensitive supportive policies and practices is a vital step toward overcoming these barriers. (BIRTH 40:1 March 2013)
Does the CenteringPregnancy Group Prenatal Care Program Reduce Preterm Birth? The Conclusions Are Premature
Authors: Devitt Neal F.
Published: March 2013

Prenatal care is promoted as a means to a healthy pregnancy outcome. In the United States great resources have been spent to expand the availability of a program of prenatal care, but without evidence for its effectiveness in the general population. Despite greater access to prenatal care over the last several decades, there has been no improvement in obstetric outcomes, such as preterm delivery. The CenteringPregnancy program of group prenatal visits is a novel form of prenatal care that, according to several studies, has been said to improve satisfaction with prenatal visits and with pregnancy outcomes. A careful reading of the studies shows that those goals are yet to be achieved. Innovation is welcome and essential, but larger studies are needed to achieve statistical significance to demonstrate improved outcome. (BIRTH 40:1 March 2013)
Accuracy of post‐radiotherapy biopsy before salvage radical prostatectomy
Authors: Meeks Joshua J. , Walker Marc , Bernstein Melanie , Kent Matthew , Eastham James A.
Published: March 2013

Objective

To determine whether post‐radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer.

Patients and Methods

SRP was performed between 1998 and 2011 on 198 patients.

All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external‐beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%).

Results

Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8.

Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%.

Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade.

The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid‐gland.

Conclusions

Radiation‐recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours.

More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP.
Stimulated release of a hyperpolarizing factor (ADHF) from mesenteric artery perivascular adipose tissue: involvement of myocyte BKCa channels and adiponectin
Authors: Weston A H , Egner I , Dong Y , Porter E L , Heagerty A M , Edwards G
Published: March 2013

Background and Purpose

Perivascular adipose tissue (PVAT) releases adipocyte‐derived hyperpolarizing factors (ADHFs) that may partly act by opening myocyte K+ channels. The present study in rat and mouse mesenteric arteries aimed to identify the myocyte K+ channel activated by PVAT and to determine whether adiponectin contributed to the hyperpolarizing effects of PVAT.

Experimental Approach

Myocyte membrane potential was recorded from de‐endothelialized, non‐contracted rat and mouse mesenteric arteries in the presence and absence of PVAT.

Key Results

The β3‐adrenoceptor agonist, CL‐316,243 (10 μM), generated PVAT‐dependent, iberiotoxin‐sensitive myocyte hyperpolarizations resulting from BKCa channel opening and which were partially blocked by L‐NMMA (100 μM). Adiponectin (5 μg·mL−1) also produced iberiotoxin‐sensitive hyperpolarizations in PVAT‐denuded arterioles. Activation of myocyte AMP‐activated protein kinase (AMPK) using 5 μM A‐769662 also induced BKCa‐mediated hyperpolarizations. Dorsomorphin abolished hyperpolarizations to CL‐316,243, adiponectin and A‐769662. In vessels from Adipo−/− mice, hyperpolarizations to CL‐316,243 were absent whereas those to A‐769662 and adiponectin were normal. In rat vessels, adipocyte‐dependent hyperpolarizations were blocked by glibenclamide and clotrimazole but those to NS1619 (33 μM) were unaltered.

Conclusions and Implications

Under basal, non‐contracted conditions, β3‐adrenoceptor stimulation of PVAT releases an ADHF, which is probably adiponectin. This activates AMPK to open myocyte BKCa channels indirectly and additionally liberates NO, which also contributes to the observed PVAT‐dependent myocyte hyperpolarizations. Clotrimazole and glibenclamide each reversed hyperpolarizations to adiponectin and A‐769662, suggesting the involvement of myocyte TRPM4 channels in the ADHF‐induced myocyte electrical changes mediated via the opening of BKCa channels.
ACE2, angiotensin‐(1‐7) and Mas receptor axis in inflammation and fibrosis
Authors: Simões e Silva AC , Silveira KD , Ferreira AJ , Teixeira MM
Published: March 2013

Recent advances have improved our understanding of the renin‐angiotensin system (RAS). These have included the recognition that angiotensin (Ang)‐(1‐7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang‐(1‐7) from Ang II, and the GPCR Mas as an Ang‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang‐(1‐7). Most available evidence supports a counter‐regulatory role for Ang‐(1‐7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang‐(1‐7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang‐(1‐7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang‐(1‐7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
Histamine is required for H3 receptor‐mediated alcohol reward inhibition, but not for alcohol consumption or stimulation
Authors: Vanhanen J , Nuutinen S , Lintunen M , Mäki T , Rämö J , Karlstedt K , Panula P
Published: March 2013

Background and Purpose

Conflicting data have been published on whether histamine is inhibitory to the rewarding effects of abused drugs. The purpose of this study was to clarify the role of neuronal histamine and, in particular, H3 receptors in alcohol dependence‐related behaviours, which represent the addictive effects of alcohol.

Experimental Approach

Alcohol‐induced conditioned place preference (alcohol‐CPP) was used to measure alcohol reward. Alcohol‐induced locomotor stimulation, alcohol consumption and kinetics were also assessed. mRNA levels were quantified using radioactive in situ hybridization.

Key Results

Low doses of H3 receptor antagonists, JNJ‐10181457 and JNJ‐39220675, inhibited alcohol reward in wild‐type (WT) mice. However, these H3 receptor antagonists did not inhibit alcohol reward in histidine decarboxylase knock‐out (HDC KO) mice and a lack of histamine did not alter alcohol consumption. Thus H3 receptor antagonists inhibited alcohol reward in a histamine‐dependent manner. Furthermore, WT and HDC KO mice were similarly stimulated by alcohol. The expression levels of dopamine D1 and D2 receptors, STEP61 and DARPP‐32 mRNA in striatal subregions were unaltered in HDC KO mice. No differences were seen in alcohol kinetics in HDC KO compared to WT control animals. In addition, JNJ‐39220675 had no effect on alcohol kinetics in WT mice.

Conclusions and Implications

These data suggest that histamine is required for the H3 receptor‐mediated inhibition of alcohol‐CPP and support the hypothesis that the brain histaminergic system has an inhibitory role in alcohol reward. Increasing neuronal histamine release via H3 receptor blockade could therefore be a novel way of treating alcohol dependence.

Linked Articles

This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Expression of histamine receptor genes Hrh3 and Hrh4 in rat brain endothelial cells
Authors: Karlstedt K , Jin C , Panula P
Published: March 2013

Background and Purpose

Brain vascular endothelial cells express histamine H1 and H2 receptors, which regulate brain capillary permeability. We investigated whether H3 and H4 receptors are also expressed in these cells and may thus play a role in permeability regulation.

Experimental Approach

An immortalized rat brain endothelial cell line RBE4 was used to assess the presence of H3 and H4 receptors. Reverse transcription‐PCR (RT‐PCR) and sequencing were used to identify the receptor mRNAs. The receptors were stimulated with histamine and immepip, and specific inverse agonists/antagonists ciproxifan and JNJ 7777120 were used to block H3 and H4 receptors, respectively.

Key Results

RT‐PCR of mRNA extracted from cultured immortalized RBE4 cells revealed two rat H4 receptor gene (Hrh4) transcripts, one full‐length (coding sequence 1173 bp), and one with a 164 bp deletion. Also, two rat H3 receptor gene (Hrh3) isoform mRNAs were expressed in RBE4 cells, and sequencing showed they were the full‐length H3 receptor and the 144 bp deletion form. Both histamine and immepip (H3 and H4 receptor agonists) activated the Erk1/2 MAPK pathway in the RBE4 cells and in vivo in brain blood vessels by activating H4 receptors, as the H4 receptor‐specific inverse agonists/antagonist JNJ 7777120, but not ciproxifan, H3 receptor antagonist, dose‐dependently blocked this effect in RBE4 cells.

Conclusions and Implications

Both Hrh3 and Hrh4 receptors are expressed in rat brain endothelial cells, and activation of the histamine H4 receptor activates the Erk1/2 cascade. H3 and H4 receptors in endothelial cells are potentially important for regulation of blood–brain barrier permeability, including trafficking of immunocompetent cells.

Linked Articles

This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease
Authors: Iborra M , Bernuzzi F , Correale C , Vetrano S , Fiorino G , Beltrán B , Marabita F , Locati M , Spinelli A , Nos P , Invernizzi P , Danese S
Published: March 2013

The altered expression of micro-RNA (miRNA) has been associated with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to establish specific miRNA expression patterns in the serum and mucosa of inflammatory bowel disease (IBD) patients (UC and CD with colonic involvement) at different stages of the disease. Serum and biopsies from nine active CD (aCD), nine inactive CD (iCD), nine active UC (aUC) and nine inactive UC (iUC) and serum from 33 healthy subjects were collected. Up to 700 miRNAs were evaluated by the TaqMan® human miRNA array. The ΔCt values were obtained using the mean expression values of all expressed miRNAs in a given sample as a normalization factor for miRNA real-time quantitative polymerase chain reaction data. The levels of serum miRNAs in CD and UC patients were different to healthy subjects. Thirteen serum miRNAs were expressed commonly in CD and UC patients. Two miRNAs were higher and four miRNAs were lower in the serum of aCD than iCD. No serum miRNA was regulated exclusively in aUC compared with iUC patients. Four miRNAs were higher and three miRNAs were lower in the mucosa of aCD than iCD. Two miRNAs were higher and three miRNAs were lower in the mucosa of aUC than iUC. No serum miRNAs coincided with tissue miRNAs in aCD and aUC patients. Our results suggest the existence of specific miRNA expression patterns associated with IBD and their different stages and support the utility of miRNA as possible biomarkers. This pilot study needs to be validated in a large prospective cohort.
Phylogenetic relationships of Hamadryas (Nymphalidae: Biblidinae) based on the combined analysis of morphological and molecular data
Authors: Garzón‐Orduña Ivonne J. , Marini‐Filho Onildo , Johnson Steve G. , Penz Carla M.
Published: March 2013

A new phylogenetic hypothesis for the Neotropical butterfly genus Hamadryas, based on the combination of a morphological matrix, one mitochondrial (COI) and four nuclear markers (CAD, RpS5, EF1a, and Wingless), is presented. Results from analyses of the molecular evidence are compared with a previously published morphological phylogeny. Molecular data and the analysis of the complete dataset support the monophyly of Hamadryas and most sister groups suggested by morphological data alone. The addition of DNA sequences to the morphological matrix helped define species groups for which no morphological synapomorphies were found. Partitioned Bremer support indicates that COI, CAD, and morphology were consistently in agreement with the combined evidence tree. In contrast, signal from the nuclear markers Rps5, EF1a, and Wingless showed indifference at most levels of the tree, and minor conflict at nodes solving the relationships between species groups. Though resolved, the combined evidence tree shows low resample values, particularly among species groups whose relationships were characterized by short internodes. A reassessment about the pattern of character change for sound production is presented and discussed.
M9, A Novel Region of Amino‐Nogo‐A, Attenuates Cerebral Ischemic Injury by Inhibiting NADPH Oxidase‐Derived Superoxide Production in Mice
Authors: Guo Fan , Jin Wei‐Lin , Li Li‐Ya , Song Wen‐Ying , Wang Hui‐Wen , Gou Xing‐Chun , Mi Ya‐Jing , Wang Qiang , Xiong Lize
Published: March 2013

Aims

In acute stroke, neurological damage is due to oxidative stress and neuronal apoptotic death. This study investigated whether Nogo‐A 290‐562 residues region (M9), fused to the transduction domain of the HIV trans‐activator (TAT) protein, is neuroprotective against cerebral ischemia and the mechanisms.

Methods

Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in male C57BL/6J mice. TAT‐M9, its mutation or vehicle was applied via intraperitoneal injection at the onset of reperfusion. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the ratio of Bax/Bcl‐2 were evaluated. Malondialdehyde (MDA), reactive oxygen species (ROS) levels, and NADPH oxidase activation were measured in the presence or absence of the NADPH oxidase inhibitor apocynin or activator tetrabromocinnamic acid (TBCA).

Results

Immunofluorescence results confirmed that TAT‐M9 was transduced into brain parenchyma, and it significantly improved neurological behavior, reduced infarct volumes, protected neuronal cells from apoptosis, inhibited activation of NADPH oxidase, and decreased MDA and ROS contents. Furthermore, apocynin imitated the beneficial effects of TAT‐M9, while TBCA abolished them.

Conclusions

Our results demonstrate that TAT‐M9 administration attenuates cerebral ischemia by inhibiting NADPH oxidase‐mediated oxidative damage and neuronal apoptosis in mice. TAT‐M9 may be a potential treatment for cerebrovascular disease.
Stenting as first‐line management for all patients with nonperforating left‐sided obstructing colorectal cancer
Authors: Warden C. , Stupart D. , Goldberg P.
Published: March 2013

Aim

Since 2005, we have used self‐expanding metal stents (SEMS) as primary treatment for all patients with left‐sided obstructing colorectal cancer without evidence of perforation. The purpose of this study was to assess the safety and efficacy of this treatment.

Method

This was a prospective study of consecutive patients with left‐sided obstructing colorectal cancer without perforation or peritonitis treated between January 2005 and June 2009. SEMS placement was attempted in all cases. Emergency surgery was reserved for patients in whom a stent placement failed. After successful decompression, surgery was offered to patients with potentially curable disease.

Results

Seventy‐seven patients were included, with successful SEMS placement in 60/77 (78%) patients, 25 as a bridge to surgery and 35 for palliation. Immediate complications occurred in two (3%) cases. There was no mortality. Of 35 patients in whom SEMS was for palliation, 32 (91%) avoided surgery altogether. A stoma was fashioned in 5 (8.3%) of the 60 patients who were successfully stented, and in 12 (71%) of the 17 patients in whom stenting failed (P = 0.0001).

Conclusion

A SEMS‐based management protocol for patients with large bowel obstruction due to colorectal cancer is safe and effective.
Factors predictive of inaccurate determination of horizontal extent of intestinal‐type early gastric cancers during endoscopic submucosal dissection: A retrospective analysis
Authors: Asada‐Hirayama Itsuko , Kodashima Shinya , Goto Osamu , Yamamichi Nobutake , Ono Satoshi , Niimi Keiko , Mochizuki Satoshi , Konno‐Shimizu Maki , Mikami‐Matsuda Rie , Minatsuki Chihiro , Takahashi Yu , Matsusaka Keisuke , Ushiku Tetsuo , Fukayama Masashi , Fujishiro Mitsuhiro , Koike Kazuhiko
Published: March 2013

Background

Certain tumor characteristics may pose challenges when endoscopically determining the horizontal extent of early gastric cancers (EGC). In the present study, clinicopathological features related to inaccurate endoscopic evaluation of horizontal extent of intestinal‐type EGC were analyzed.

Patients and Methods

We analyzed 431 lesions with intestinal‐type EGC treated by endoscopic submucosal dissection (ESD) at our hospital. We focused on whether pretreatment demarcation was accurate by comparing positional relationships between marking dots and tumor edges in resected specimens, and factors related to inaccurate evaluation were analyzed. Gender, age, tumor size, location, circumference, depth, ulceration, macroscopic type, presence of a flat (0‐IIb) component, predominant histological type, mixture of diffuse‐type adenocarcinoma, mixed histology, and use of magnification endoscopy with narrow band imaging were analyzed. Reasons for inaccurate evaluation were also investigated by re‐examining endoscopic images and prepared histological slides.

Results

Rate of inaccurate evaluation of horizontal extent was 7.4% (32/431 lesions). Multivariate analysis revealed the following significant independent variables contributing to inaccurate endoscopic evaluation: presence of a flat component, large size, and predominant histological findings of moderately differentiated adenocarcinoma. Re‐examination of prepared histological slides of inaccurately evaluated cases revealed a marginal flat spreading area in 28 of the 32 lesions (87.5%). In 14 of the 32 lesions (43.8%), tumor margins were composed of moderately differentiated adenocarcinoma.

Conclusions

For lesions with a flat component, large lesions, and moderately differentiated adenocarcinoma, determination of the horizontal extent can be challenging in EGC indicated for ESD, even with the best available endoscopic tools.
Proper stratification of survival curves by level of gross motor function
Authors: Day Steven M
Published: March 2013

This commentary is on the original article by Touyama et al on pages 459–463 of this issue.
The use of U‐500 regular insulin in the management of patients with obesity and insulin resistance
Authors: Jones P. , Idris I.
Published: March 2013

The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin. This article reviews the published literature on the properties of U‐500 insulin and its use in clinical practice. U‐500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U‐100 insulin. Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U‐500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control. To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U‐500 insulin who are admitted to hospital.
Baseline HbA1c predicts attainment of 7.0% HbA1c target with structured titration of insulin glargine in type 2 diabetes: a patient‐level analysis of 12 studies
Authors: Riddle M. C. , Vlajnic A. , Zhou R. , Rosenstock J.
Published: March 2013

Aims

To determine whether baseline characteristics, especially haemoglobin A1c (HbA1c), predict the likelihood of reaching HbA1c ≤ 7.0% or the risk of experiencing hypoglycaemia after the addition of insulin glargine to oral therapy in type 2 diabetes.

Methods

Pooled patient‐level data from 12 prospective, randomized, controlled studies that used insulin glargine in a treat‐to‐target titration regimen seeking fasting glucose levels ≤5.5 mmol/l (100 mg/dl) were analysed. Baseline characteristics were evaluated by logistic regression models as predictors of reaching a target HbA1c ≤ 7.0% or experiencing confirmed hypoglycaemia. The effect of prior glycaemic control was further explored by analysis of categorical ranges of baseline HbA1c.

Results

Of 2312 participants, 95% completed 24 weeks of treatment. Lower HbA1c at baseline was independently associated with reaching HbA1c target [adjusted odds ratio (OR) for 1% difference: 0.538, p < 0.0001] and also with likelihood of experiencing confirmed hypoglycaemic events (adjusted OR: 0.835, p < 0.0001) at week 24. In an unadjusted analysis by baseline HbA1c range, the strong association between baseline control and attaining target HbA1c was confirmed (75% with baseline HbA1c < 8.0%, 60% with baseline HbA1c ≥ 8.0 and <9.0% and 38% with baseline HbA1c ≥ 9.0% attained HbA1c ≤ 7.0%). The incidence of hypoglycaemia confirmed <3.9 mmol/l (70 mg/dl) was higher in the lower baseline HbA1c ranges but severe hypoglycaemia was infrequent at all baseline HbA1c levels.

Conclusions

Systematically titrated insulin glargine, added to oral agents, was effective over a wide range of baseline HbA1c. Lower baseline HbA1c was the best clinical predictor of achieving HbA1c ≤ 7.0% and also associated with higher risk of glucose‐confirmed hypoglycaemia. Severe hypoglycaemia was infrequent using this treatment approach.
Superior glycaemic control with once‐daily insulin degludec/insulin aspart versus insulin glargine in Japanese adults with type 2 diabetes inadequately controlled with oral drugs: a randomized, controlled phase 3 trial
Authors: Onishi Y. , Ono Y. , Rabøl R. , Endahl L. , Nakamura S.
Published: March 2013

Aims

This phase 3, 26‐week, open‐label, treat‐to‐target trial investigated the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in insulin‐naïve Japanese adults with type 2 diabetes.

Methods

Subjects were randomized to once‐daily injections of IDegAsp (n = 147) or insulin glargine (IGlar) (n = 149), both ±≤2 oral antidiabetic treatments. IDegAsp was given before the largest meal at the discretion of each subject (and maintained throughout the trial); IGlar was dosed according to label. Both insulins were titrated to a target prebreakfast self‐measured plasma glucose of 3.9 to <5.0 mmol/l.

Results

After 26 weeks, mean HbA1c was 7% with IDegAsp and 7.3% with IGlar; superiority of IDegAsp to IGlar was shown (estimated treatment difference, ETD; IDegAsp–IGlar: –0.28% points [−0.46; –0.10]95% CI, p < 0.01). At end‐of‐trial, mean fasting plasma glucose (FPG) was similar for IDegAsp and IGlar (5.7 vs. 5.6 mmol/l; ETD IDegAsp–IGlar: 0.15 mmol/l [−0.29; 0.60]95% CI, p = NS). IDegAsp was associated with numerically lower rates of overall confirmed (27%) and nocturnal confirmed hypoglycaemia (25%) versus IGlar (estimated rate ratio IDegAsp/IGlar: 0.73 [0.50; 1.08]95% CI, p = NS, and 0.75 [0.34; 1.64]95% CI, p = NS, respectively). Mean daily insulin doses were similar between groups at end‐of‐trial (both: 0.41 U/kg) as were the increases in body weight from baseline (both: 0.7 kg). Adverse event profiles were similar between groups.

Conclusions

IDegAsp provided superior long‐term glycaemic control compared to IGlar, with similar FPG and doses and numerically lower rates of overall and nocturnal hypoglycaemia (p = NS).
Reduced Right Ventricular Myocardial Strain in the Elite Athlete May Not Be a Consequence of Myocardial Damage. “Cream Masquerades as Skimmed Milk”
Authors: King Gerard , Almuntaser Ibrahim , Murphy Ross T , La Gerche Andre , Mahoney Nick , Bennet Kathleen , Clarke John , Brown Angela
Published: March 2013

Background

Latest research shows that the lower resting values of right ventricular (RV) myocardial % strain may represent a physiologic change rather than subclinical myocardial damage. Therefore, we assessed load‐independent changes to the RV as a consequence of high intensity training by measuring the Isovolumic acceleration (IVA) of the free wall of the RV in conjunction with NT pro‐BNP measured by an electrochemiluminescence assay.

Methods

Seventeen controls (mean age 27 ± 4), 24 soccer footballers (mean age 24 ± 4), and 18 elite rowers (mean age 22 ± 4) were studied. Left ventricular (LV) and RV % strain were measured using two‐dimensional (2D) speckle based automated functional imaging (AFI) software. RV free wall IVA was measured using pulsed‐wave tissue Doppler at the lateral tricuspid annulus. Standard 2D echo were used to measured RV parameters including the Tei index (systolic and diastolic function) and the total annular plane systolic excursion (TAPSE) of the RV annulus. NT pro‐BNP was measured by an electrochemiluminescence assay.

Results

The RV diameter was increased in the footballers and elite rowers compared with controls (P < 0.001). RV wall size was greater in the elite rowers compared with controls and footballers (P = 0.002). The peak IVA of the RV was higher in the rowers, compared with the footballers and to controls (P < 0.001). The mean LV and RV % myocardial strain were lower in the elite athletes and the footballers compared with controls (P < 0.001). There was no difference in RV Tei index, levels of BNP, and TAPSE across all subjects.

Conclusions

This study showed a significant increase in IVA of the RV of athletes despite reduced myocardial % strain and normal levels in NT‐proBNP. This suggests that the decrease in % strain is not a consequence of myocardial damage, but may represents a part of the physiological response to endurance exercise. Therefore, a reduced IVA in a remodeled RV could herald a pathological response.
The Role of Three‐Dimensional Echocardiography in Interventricular Mass Evaluation
Authors: Miglioranza Marcelo Haertel , Leiria Tiago Luiz Luz , Haertel José Carlos , Winkler Maristela , Fernández‐Golfin Covadonga , Zamorano José Luis
Published: March 2013

A young patient underwent a screening electrocardiogram (EKG) that suggested apical hypertrophic cardiomyopathy. Serial investigation with echocardiography showed a well‐defined hyperechogenic mass involving the interventricular septal. To better define the lesion extension three‐dimensional (3D) echocardiography was done and it demonstrated a mass invading the septal myocardium, involving the major part of the muscular portion. The findings were highly suggestive of a cardiac fibroma. A cardiac magetic resonance image (MRI) was also compatible with this diagnosis. In our case, 3D echo showed a high accuracy, proving to be a useful tool to determine the anatomy of the lesion, complementary to MRI, guiding best management strategy.
Primary Cardiac Angiosarcoma with Spontaneous Ruptures of the Right Atrium and Right Coronary Artery
Authors: Tang Kui , Shang Quan‐Liang , Zhou Qi‐Chang , Zhou Jia‐Wei , She Xiao‐Lin , Zhang Ming
Published: March 2013

Primary tumors of the heart are rarely seen. Cardiac angiosarcomas are malignant tumors that almost always have a poor prognosis. Atrium rupture and coronary artery fistula are very rare complications of primary cardiac angiosarcoma. We describe a 57‐year‐old man suffering from primary cardiac angiosarcoma with spontaneous ruptures of the right atrium and right coronary artery (RCA). Theoretically, either of these ruptures invariably results in pericardial effusion and tamponade that is rare but potentially life threatening. In this instance, however, the patient might have developed fibrous adhesions resulted from previous bloody pericardial effusion. A massive pericardial effusion was localized, which consequently prevented cardiac tamponade and hemodynamic collapse. Echocardiography revealed the tumor progression leading to detectable infiltration of solid mass into the right atrial (RA) wall, which is close to RCA. And color Doppler displayed the flow into the pericardial cavity through a disrupted RA wall and perforated RCA. Echocardiography remains the primary method of choice for evaluation of cardiac masses.
Three‐Dimensional Transesophageal Echocardiography Assessment of a Successful Transcatheter Mitral Valve in Valve Implantation for Degenerated Bioprosthesis
Authors: Théron Alexis , Gariboldi Vlad , Grisoli Dominique , Maysou Laurie‐anne , Jaussaud Nicolas , Morera Pierre , Cuisset Thomas , Quilici Jacques , Thuny Franck , Riberi Alberto , Avierinos Jean‐François , Collart Frederic
Published: March 2013

Reoperation for degenerated mitral bioprosthesis is considered a high risk procedure. Transcatheter mitral valve in valve implantation has emerged as an off‐label alternative for patients contra‐indicated to surgery. We report a 46‐year‐old man, with a 29 mm mitral bioprosthesis since 2002, who was admitted for acute heart failure because of a severe intra‐prosthetic regurgitation. His recent medical history revealed a fast growing cavum carcinoma. In view of generally poor prognosis, the heart team decided to perform a transcatheter mitral valve in valve implantation by transapical approach. Live three‐dimensional TEE was used during the implantation for sizing, device positioning, and hemodynamic assessment.
Real Time Three‐Dimensional Transesophageal Echocardiography in Partial Posteromedial Papillary Muscle Rupture
Authors: Havins Jeremiah , Lick Scott , Boor Paul , Arora Harvinder , Ahmad Masood
Published: March 2013

Mini‐Abstract

A 60‐year‐old hypertensive male with non‐ST segment elevation myocardial infarction had a hyperdynamic LV with mild posterior leaflet mitral valve prolapse without significant regurgitation on transthoracic echocardiogram. Two‐dimensional (2D) TEE showed severe mitral regurgitation with prolapse of P2 and P3 scallops. Posteromedial papillary muscle rupture was suspected. Three‐dimensional (3D) TEE demonstrated severely prolapsing P2 and P3 valve scallops with a clear view of the partially ruptured posteromedial papillary muscle. Patient underwent emergency coronary bypass and mitral valve replacement. Surgical pathology of papillary muscle confirmed coagulative necrosis. 3D TEE was superior in identifying the partial posteromedial papillary muscle rupture.
The evolution of species recognition in competitive and mating contexts: the relative efficacy of alternative mechanisms of character displacement
Authors: Okamoto Kenichi W. , Grether Gregory F.
Published: March 2013

Sympatric divergence in traits affecting species recognition can result from selection against cross‐species mating (reproductive character displacement, RCD) or interspecific aggression (agonistic character displacement, ACD). When the same traits are used for species recognition in both contexts, empirically disentangling the relative contributions of RCD and ACD to observed character shifts may be impossible. Here, we develop a theoretical framework for partitioning the effects of these processes. We show that when both mate and competitor recognition depend on the same trait, RCD sets the pace of character shifts. Moreover, RCD can cause divergence in competitor recognition, but ACD cannot cause divergence in mate recognition. This asymmetry arises because males with divergent recognition traits may avoid needless interspecific conflicts, but suffer reduced attractiveness to conspecific females. Therefore, the key empirical issue is whether the same or different traits are used for mate recognition and competitor recognition.
Consequences of defaunation for a tropical tree community
Authors: Harrison Rhett D , Tan Sylvester , Plotkin Joshua B. , Slik Ferry , Detto Matteo , Brenes Tania , Itoh Akira , Davies Stuart J.
Published: March 2013

Hunting affects a considerably greater area of the tropical forest biome than deforestation and logging combined. Often even large remote protected areas are depleted of a substantial proportion of their vertebrate fauna. However, understanding of the long‐term ecological consequences of defaunation in tropical forests remains poor. Using tree census data from a large‐scale plot monitored over a 15‐year period since the approximate onset of intense hunting, we provide a comprehensive assessment of the immediate consequences of defaunation for a tropical tree community. Our data strongly suggest that over‐hunting has engendered pervasive changes in tree population spatial structure and dynamics, leading to a consistent decline in local tree diversity over time. However, we do not find any support for suggestions that over‐hunting reduces above‐ground biomass or biomass accumulation rate in this forest. To maintain critical ecosystem processes in tropical forests increased efforts are required to protect and restore wildlife populations.