bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of drop‐out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia
Authors: Hutton P. , Morrison A. P. , Yung A. R. , Taylor P. J. , French P. , Dunn G.
Published: April 2012

Hutton P, Morrison AP, Yung AR, Taylor PJ, French P, Dunn G. Effects of drop‐out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia.

Objective:  Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second‐generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop‐out in placebo‐controlled trials.

Method:  We examined the following: (i) whether reviews included data from studies with a level of drop‐out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop‐out.

Results:  All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low‐attrition studies because of missing standard deviations.

Conclusion:  Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high‐attrition studies was difficult to quantify because of the exclusion of relevant low‐attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow‐up data from people who leave the double‐blind process early.
Yoga in schizophrenia: a systematic review of randomised controlled trials
Authors: Vancampfort D. , Vansteelandt K. , Scheewe T. , Probst M. , Knapen J. , De Herdt A. , De Hert M.
Published: April 2012

Vancampfort D, Vansteelandt K, Scheewe T, Probst M, Knapen J, De Herdt A, De Hert M. Yoga in schizophrenia: a systematic review of randomised controlled trials.

Objective:  The objective of this systematic review was to assess the effectiveness of yoga as a complementary treatment on general psychopathology, positive and negative symptoms and health‐related quality of life (HRQL) for people with schizophrenia.

Method:  Randomised controlled trials (RCTs) were considered whether they investigated a yoga intervention in patients with schizophrenia. The selection of studies, data extraction and quality assessment were performed independently by two reviewers.

Results:  Only three RCTs met the inclusion criteria. Lower Positive and Negative Syndrome Scale (PANSS) total scores and subscale scores for positive and negative symptoms were obtained after yoga compared with exercise or waiting list control conditions. In the same way, the physical, psychological, social and environmental HRQL as measured with the abbreviated version of the World Health Organization Quality of Life questionnaire (WHOQOL‐BREF) increased more significantly after yoga than after exercise or waiting list control conditions. None of the RCTS encountered adverse events. Dose–response relationships could, however, not be determined.

Conclusion:  Although the number of RCTs included in this review was limited, results indicated that yoga therapy can be an useful add‐on treatment to reduce general psychopathology and positive and negative symptoms. In the same way, HRQL improved in those antipsychotic‐stabilised patients with schizophrenia following yoga.
Occupational food‐related hand dermatoses seen over a 10‐year period
Authors: Vester Lotte , Thyssen Jacob P. , Menné Torkil , Johansen Jeanne Duus
Published: April 2012

Background. Protein contact dermatitis was originally defined in 1976 by Hjorth and Roed‐Petersen as a distinct kind of dermatitis seen in patients with occupational food contact. Even though occupational skin diseases are frequent in Denmark, little attention has been paid to protein contact dermatitis, and the frequency is unknown.

Objectives. To evaluate the frequency of occupational food‐related hand dermatoses and test results in patients occupationally exposed to foods.

Materials and Methods. This was a retrospective study based on examinations, including skin prick testing and patch testing, performed at the Department of Dermato‐Allergology, Gentofte University Hospital, Denmark between 2001 and 2010.

Results. Of all patients (n = 372), 57.0% had irritant contact dermatitis, 22.0% had protein contact dermatitis, 2.4% had contact urticaria, and 1.8% had allergic contact dermatitis. A suggestion for diagnostic criteria is presented. Frequent risk occupations were cooking in restaurants, baking, and kitchen work. Substantially more patients reacted in skin prick testing with fresh foods than with food extracts.

Conclusion. Protein contact dermatitis is a frequent disorder among patients who professionally handle foods, and should be considered to be a distinct clinical entity. When diagnosing protein contact dermatitis and in other food‐related skin prick testing procedures, it is important to include fresh foods.
Sesquiterpene lactone mix as a diagnostic tool for Asteraceae allergic contact dermatitis: chemical explanation for its poor performance and Sesquiterpene lactone mix II as a proposed improvement
Authors: Jacob Mathias , Brinkmann Jürgen , Schmidt Thomas J.
Published: April 2012

Background. Two preparations are currently in use for the diagnosis of allergic contact dermatitis caused by Asteraceae: (i) Sesquiterpene lactone (SL) mix [three pure sesquiterpene lactones (STLs)], whose use has been questioned, owing to an insufficient rate of true‐positive results; and (ii) Compositae mix, consisting of five Asteraceae extracts, which is problematic because of lack of standardization and questionable reproducibility.

Objectives. To analyse the reasons for the narrow sensitivity of SL mix from a chemoinformatic point of view, and to propose a solution by rational selection of alternative constituents for a new SL mix II covering a broader cohort of allergic patients.

Materials/methods. Structural and biological information on allergenic STLs was retrieved from databases and the literature, and molecular modelling and chemoinformatic computations were performed.

Results. An explanation for the insufficient hit rate of SL mix is that the three constituents possess extremely similar molecular structures/properties and do not represent well the structural diversity of allergenic STLs. STLs that are known as constituents of Compositae mix plants show much a wider diversity, which explains the higher positive rate.

Conclusions. On the basis of their positions in chemical property space, a new collection of STLs that more evenly cover the overall structural diversity spectrum is proposed. SL mix II is likely to detect a larger number of patients sensitized to Asteraceae.
C957T polymorphism of the dopamine D2 receptor gene is associated with motor learning and heart rate
Authors: Huertas E. , Bühler K.‐M. , Echeverry‐Alzate V. , Giménez T. , López‐Moreno J. A.
Published: April 2012

Genetic variants that are related to the dopaminergic system have been frequently found to be associated with various neurological and mental disorders. Here, we studied the relationships between some of these genetic variants and some cognitive and psychophysiological processes that are implicated in such disorders. Two single nucleotide polymorphisms were chosen: one in the dopamine D2 receptor gene (rs6277‐C957T) and one in the catechol‐O‐methyltransferase gene (rs4680‐Val158Met), which is involved in the metabolic degradation of dopamine. The performance of participants on two long‐term memory tasks was assessed: free recall (declarative memory) and mirror drawing (procedural motor learning). Heart rate (HR) was also monitored during the initial trials of the mirror‐drawing task, which is considered to be a laboratory middle‐stress generator (moderate stress), and during a rest period (low stress). Data were collected from 213 healthy Caucasian university students. The C957T C homozygous participants showed more rapid learning than the T allele carriers in the procedural motor learning task and smaller differences in HR between the moderate‐ and the low‐stress conditions. These results provide useful information regarding phenotypic variance in both healthy individuals and patients.
Use of acronyms in the patient dental record
Authors: Pepper K , Robinson FG
Published: April 2012

To cite this article:   Int J Dent Hygiene  DOI: 10.1111/j.1601‐5037.2012.00547.x  Pepper K, Robinson FG. Use of acronyms in the patient dental record.

The patient dental record is a legal document that captures the history of patient care for a particular patient. This article references the American Dental Association's listing of common dental abbreviations, symbols and acronyms, which aid in establishing uniformity for clinicians.
Comparison of canine core bone marrow biopsies from multiple sites using different techniques and needles
Authors: Abrams‐Ogg Anthony C.G. , Defarges Alice , Foster Robert A. , Bienzle Dorothee
Published: April 2012

Background

Commonly used 11 or 13ga needles are relatively large for collection of bone marrow (BM) biopsies from small dogs.

Objectives

The aims of this study were to assess ease of BM collection and quality of specimens obtained from small dogs using 13 and 15ga needles and to determine if specimen encasement would improve quality.

Methods

Humeral and iliac biopsies obtained from 17 Beagle dogs with a 15ga needle and a power driver were compared with humeral biopsies obtained with a 13ga Jamshidi needle. Ease of collection (scored as 1 [very difficult] to 5 [very easy] for 3 components of collection with scores summed), section quality (scored as 1 [poor] to 5 [good]), and lesions at collection sites were scored. Quality of additional humeral biopsies obtained with a 15ga needle and wrapped in tissue paper prior to fixation was assessed.

Results

Use of a 15ga needle to obtain a humeral BM biopsy was significantly easier (mean score ± SD = 13.6 ± 1.7) than obtaining humeral BM using a 13ga needle (11.4 ± 1.6; P < .001) or obtaining iliac BM using a 15ga needle (10.9 ± 2.0, P < .001). Quality of humeral biopsies obtained with a 13ga needle (3.9 ± 1.2) was better than for biopsies of the humerus (1.9 ± 1.3, P < .001) or ilium (1.4 ± 0.6, P < .001) using a 15ga needle. Only sites sampled with a 13ga needle were identifiable grossly after the procedure. In most biopsies, cell density and cellularity were lower when a 15ga needle was used. Paper‐wrapping of biopsies did not improve quality.

Conclusions

In small dogs, collection of humeral BM biopsies using a 15g needle is feasible and more easily accomplished than collection using a 13ga needle. Hematopoiesis may be underestimated in specimens collected using the smaller needle.
A Reverse Genetics Approach To Study Feline Infectious Peritonitis
Authors: Tekes Gergely , Spies Danica , Bank-Wolf Barbara , Thiel Volker , Thiel Heinz-Jürgen
Published: April 2012

Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).
Pathogenicity and Transmission in Pigs of the Novel A(H3N2)v Influenza Virus Isolated from Humans and Characterization of Swine H3N2 Viruses Isolated in 2010-2011
Authors: Kitikoon Pravina , Vincent Amy L. , Gauger Phillip C. , Schlink Sarah N. , Bayles Darrell O. , Gramer Marie R. , Darnell Daniel , Webby Richard J. , Lager Kelly M. , Swenson Sabrina L. , Klimov Alexander
Published: April 2012

Swine influenza virus (SIV) H3N2 with triple reassorted internal genes (TRIG) has been enzootic in Unites States since 1998. Transmission of the 2009 pandemic H1N1 (pH1N1) virus to pigs in the United States was followed by reassortment with endemic SIV, resulting in reassorted viruses that include novel H3N2 genotypes (rH3N2p). Between July and December 2011, 12 cases of human infections with swine-lineage H3N2 viruses containing the pandemic matrix (pM) gene [A(H3N2)v] were detected. Whole-genome analysis of H3N2 viruses isolated from pigs from 2009 to 2011 sequenced in this study and other available H3N2 sequences showed six different rH3N2p genotypes present in the U.S. swine population since 2009. The presence of the pM gene was a common feature among all rH3N2p genotypes, but no specific genotype appeared to predominate in the swine population. We compared the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2)v isolate and two swine H3N2 isolates, H3N2-TRIG and rH3N2p. Our
in vivo
study detected no increased virulence in A(H3N2)v or rH3N2p viruses compared to endemic H3N2-TRIG virus. Antibodies to cluster IV H3N2-TRIG and rH3N2p viruses had reduced cross-reactivity to A(H3N2)v compared to other cluster IV H3N2-TRIG and rH3N2p viruses. Genetic analysis of the hemagglutinin gene indicated that although rH3N2p and A(H3N2)v are related to cluster IV of H3N2-TRIG, some recent rH3N2p isolates appeared to be forming a separate cluster along with the human isolates of A(H3N2)v. Continued monitoring of these H3N2 viruses is necessary to evaluate the evolution and potential loss of population immunity in swine and humans.
Oct4
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Stem/Progenitor Swine Lung Epithelial Cells Are Targets for Influenza Virus Replication
Authors: Khatri Mahesh , Goyal Sagar M. , Saif Yehia M.
Published: April 2012

We isolated stem/progenitor epithelial cells from the lungs of 4- to 6-week-old pigs. The epithelial progenitor colony cells were surrounded by mesenchymal stromal cells. The progenitor epithelial colony cells expressed stem cell markers such as octamer binding transcription factor 4 (Oct4) and stage-specific embryonic antigen 1 (SSEA-1), as well as the epithelial markers pancytokeratin, cytokeratin-18, and occludin, but not mesenchymal (CD44, CD29, and CD90) and hematopoietic (CD45) markers. The colony cells had extensive self-renewal potential and had the capacity to undergo differentiation to alveolar type I- and type II-like pneumocytes. Additionally, these cells expressed sialic acid receptors and supported the active replication of influenza virus, which was accompanied by cell lysis. The lysis of progenitor epithelial cells by influenza virus may cause a marked reduction in the potential of progenitor cells for self renewal and for their ability to differentiate into specialized cells of the lung. These observations suggest the possible involvement of lung stem/progenitor cells in influenza virus infection.
Role for TBC1D20 and Rab1 in Hepatitis C Virus Replication via Interaction with Lipid Droplet-Bound Nonstructural Protein 5A
Authors: Nevo-Yassaf Inbar , Yaffe Yakey , Asher Meital , Ravid Orly , Eizenberg Sharon , Henis Yoav I. , Nahmias Yaakov , Hirschberg Koret , Sklan Ella H.
Published: April 2012

Replication and assembly of hepatitis C virus (HCV) depend on the host's secretory and lipid-biosynthetic machinery. Viral replication occurs on endoplasmic reticulum (ER)-derived modified membranes, while viral assembly is thought to occur on lipid droplets (LDs). A physical association and coordination between the viral replication and assembly complexes are prerequisites for efficient viral production. Nonstructural protein 5A (NS5A), which localizes both to the ER and LDs, is an ideal candidate for this function. Here, the interaction of NS5A with host cell membranes and binding partners was characterized in living cells. The binding of NS5A to LDs is apparently irreversible, both in HCV-infected cells and when ectopically expressed. In HCV-infected cells, NS5A fluorescence was observed around the LDs and in perinuclear structures that were incorporated into a highly immobile platform superimposed over the ER membrane. Moreover, TBC1D20 and its cognate GTPase Rab1 are recruited by NS5A to LDs. The NS5A-TBC1D20 interaction was shown to be essential for the viral life cycle. In cells, expression of the Rab1 dominant negative (Rab1DN) GTPase mutant abolished steady-state LDs. In infected cells, Rab1DN induced the elimination of NS5A from viral replication sites. Our results demonstrate the significance of the localization of NS5A to LDs and support a model whereby its interaction with TBC1D20 and Rab1 affects lipid droplet metabolism to promote the viral life cycle.
CD44 Participates in IP-10 Induction in Cells in Which Hepatitis C Virus RNA Is Replicating, through an Interaction with Toll-Like Receptor 2 and Hyaluronan
Authors: Abe Takayuki , Fukuhara Takasuke , Wen Xiauyu , Ninomiya Akinori , Moriishi Kohji , Maehara Yoshihiko , Takeuchi Osamu , Kawai Taro , Akira Shizuo , Matsuura Yoshiharu
Published: April 2012

The mechanisms of induction of liver injury during chronic infection with hepatitis C virus (HCV) are not well understood. Gamma interferon (IFN-γ)-inducible protein 10 (IP-10), a member of the CXC chemokine family, is expressed in the liver of chronic hepatitis C (CHC) patients and selectively recruits activated T cells to the sites of inflammation. Recently, it was shown that a low plasma concentration of IP-10 in CHC patients was closely associated with the outcome of antiviral therapy. In this study, we examined the role of the Toll-like receptor (TLR) pathway on IP-10 production in cells replicating HCV. Among the CXC chemokines, the expression of IP-10 was specifically increased in cells replicating HCV upon stimulation with conventional TLR2 ligands. The enhancement of IP-10 production upon stimulation with TLR2 ligands in cells replicating HCV induced CD44 expression. CD44 is a broadly distributed type I transmembrane glycoprotein and a receptor for the glycosaminoglycan hyaluronan (HA). In CHC patients, the expression of HA in serum has been shown to increase in accord with the progression of liver fibrosis, and HA also works as a ligand for TLR2. In the present study, IP-10 production upon HA stimulation was dependent on the expression of TLR2 and CD44, and a direct association between TLR2 and CD44 was observed. These results suggest that endogenous expression of HA in hepatocytes in CHC patients participates in IP-10 production through an engagement of TLR2 and CD44.
Association of Major Histocompatibility Complex Class I Haplotypes with Disease Progression after Simian Immunodeficiency Virus Challenge in Burmese Rhesus Macaques
Authors: Nomura Takushi , Yamamoto Hiroyuki , Shiino Teiichiro , Takahashi Naofumi , Nakane Taku , Iwamoto Nami , Ishii Hiroshi , Tsukamoto Tetsuo , Kawada Miki , Matsuoka Saori , Takeda Akiko , Terahara Kazutaka , Tsunetsugu-Yokota Yasuko , Iwata-Yoshikawa Naoko , Hasegawa Hideki , Sata Tetsutaro , Naruse Taeko K. , Kimura Akinori , Matano Tetsuro
Published: April 2012

Nonhuman primate AIDS models are essential for the analysis of AIDS pathogenesis and the evaluation of vaccine efficacy. Multiple studies on human immunodeficiency virus and simian immunodeficiency virus (SIV) infection have indicated the association of major histocompatibility complex class I (MHC-I) genotypes with rapid or slow AIDS progression. The accumulation of macaque groups that share not only a single MHC-I allele but also an MHC-I haplotype consisting of multiple polymorphic MHC-I loci would greatly contribute to the progress of AIDS research. Here, we investigated SIVmac239 infections in four groups of Burmese rhesus macaques sharing individual MHC-I haplotypes, referred to as A, E, B, and J. Out of 20 macaques belonging to A+(n= 6), E+(n= 6), B+(n= 4), and J+(n= 4) groups, 18 showed persistent viremia. Fifteen of them developed AIDS in 0.5 to 4 years, with the remaining three at 1 or 2 years under observation. A+animals, including two controllers, showed slower disease progression, whereas J+animals exhibited rapid progression. E+and B+animals showed intermediate plasma viral loads and survival periods. Gag-specific CD8+T-cell responses were efficiently induced in A+animals, while Nef-specific CD8+T-cell responses were in A+, E+, and B+animals. Multiple comparisons among these groups revealed significant differences in survival periods, peripheral CD4+T-cell decline, and SIV-specific CD4+T-cell polyfunctionality in the chronic phase. This study indicates the association of MHC-I haplotypes with AIDS progression and presents an AIDS model facilitating the analysis of virus-host immune interaction.
Suppression of Antigen-Specific T Cell Responses by the Kaposi's Sarcoma-Associated Herpesvirus Viral OX2 Protein and Its Cellular Orthologue, CD200
Authors: Misstear Karen , Chanas Simon A. , Rezaee S. A. Rahim , Colman Rachel , Quinn Laura L. , Long Heather M. , Goodyear Oliver , Lord Janet M. , Hislop Andrew D. , Blackbourn David J.
Published: April 2012

Regulating appropriate activation of the immune response in the healthy host despite continual immune surveillance dictates that immune responses must be either self-limiting and therefore negatively regulated following their activation or prevented from developing inappropriately. In the case of antigen-specific T cells, their response is attenuated by several mechanisms, including ligation of CTLA-4 and PD-1. Through the study of the viral OX2 (vOX2) immunoregulator encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), we have identified a T cell-attenuating role both for this protein and for CD200, a cellular orthologue of the viral vOX2 protein.In vitro, antigen-presenting cells (APC) expressing either native vOX2 or CD200 suppressed two functions of cognate antigen-specific T cell clones: gamma interferon (IFN-γ) production and mobilization of CD107a, a cytolytic granule component and measure of target cell killing ability. Mechanistically, vOX2 and CD200 expression on APC suppressed the phosphorylation of ERK1/2 mitogen-activated protein kinase in responding T cells. These data provide the first evidence for a role of both KSHV vOX2 and cellular CD200 in the negative regulation of antigen-specific T cell responses. They suggest that KSHV has evolved to harness the host CD200-based mechanism of attenuation of T cell responses to facilitate virus persistence and dissemination within the infected individual. Moreover, our studies define a new paradigm in immune modulation by viruses: the provision of a negative costimulatory signal to T cells by a virus-encoded orthologue of CD200.
Thirty-day mortality after elective and emergency total colectomy in Danish patients with inflammatory bowel disease: a population-based nationwide cohort study
Authors: Tøttrup Anders , Erichsen Rune , Sværke Claus , Laurberg Søren , Srensen Henrik Toft
Published: April 2012

Objectives

The purpose of this investigation was to assess 30-day mortality among Danish inflammatory bowel diseases (IBD) patients and to examine the prognostic impact of hospital total colectomy volume, age, gender and comorbidity.

Design

Cohort study.

Setting

The authors compared 30-day survival over the period 1996–2010 among 2889 IBD patients with total colectomy identified in the Danish National Registry of Patients. This registry covers all hospitals in Denmark. Postoperative survival patterns for patients with ulcerative colitis and Crohn's disease were compared, using proportional hazard regression. The regression model accounted for the timing of surgery, hospital total colectomy volume, age, gender and comorbidity.

Participants

Patients were enrolled in the study if they had a hospital registry diagnosis of IBD, with accompanying procedure codes for total colectomy (see codes in online appendix table 1). Hospitalisations were described as elective or emergency, and patients were categorised as having Crohn's disease, ulcerative colitis or as a mixed group.

Outcome measures

Primary outcome measure was 30-day mortality.

Results

Among 2889 IBD patients with total colectomy, 1439 (50%) underwent surgery during an emergency hospitalisation. Thirty-day mortality was 5.3% (76/1439) among emergency cases compared with 1% (14/1450) among elective cases. The highest mortality (8.1%; 11 of 136) was observed among Crohn's patients undergoing emergency surgery. The mortality of patients with ulcerative colitis undergoing emergency surgery was 5.2% (55/1056). After elective surgery, the 30-day mortality was 0.9% (8/938) among patients with ulcerative colitis and 1.5% (3/201) among Crohn's disease patients. Low hospital total colectomy volume, comorbidity and high age were associated with increased 30-day mortality in ulcerative colitis patients undergoing emergency surgery.

Conclusion

Emergency total colectomy among patients with ulcerative colitis and particularly Crohn's disease is associated with substantial 30-day mortality.
How does a history of psychiatric hospital care influence access to coronary care: a cohort study
Authors: Manderbacka Kristiina , Arffman Martti , Sund Reijo , Haukka Jari , Keskimäki Ilmo , Wahlbeck Kristian
Published: April 2012

Objectives

Equity in physical health of patients with severe mental disorders is a major public health concern. The aim of this cohort study was to examine equity in access to coronary care among persons with a history of severe mental disorder in 1998–2009.

Design

Nationwide register linkage cohort study.

Setting

Hospital care in the Finnish healthcare system.

Population

The study population consisted of all residents in Finland aged 40 years or older. All hospital discharges in 1998–2009 with a diagnosis of coronary heart disease or severe mental disorder were obtained from the Care Register.

Primary outcome measures

Data on deaths, hospitalisations and coronary revascularisations were linked to the data set using unique personal identifiers.

Results

Patients with severe mental disorders had increased likelihood of hospital care due to coronary heart disease (RR between 1.22, 95% CI 1.18 to 1.25 and 1.93, 1.84 to 2.03 in different age groups) and in 40–49-year-olds also increased likelihood of revascularisation (1.26, 1.16 to 1.38) compared with persons without mental disorders. Access to revascularisation was poorer among older persons with severe mental disorders in relation to need suggested by increased coronary mortality. In spite of excess coronary mortality (ranging from 0.95, 0.89 to 1.01 to 3.16, 2.82 to 3.54), worst off were people with a history of psychosis, who did not have increased use of hospital care and had lower likelihood of receiving revascularisations (ranging from 0.44, 0.37 to 0.51 to 0.74, 0.59 to 0.93) compared with persons without mental disorders.

Conclusions

Selective mechanisms seem to be at work in access to care and revascularisations among people with severe mental disorders. Healthcare professionals need to be aware of the need for targeted measures to address challenges in provision of somatic care among people with severe mental health problems, especially among people with psychoses and old people.
The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT
Authors: Rozé Jean-Christophe , Darmaun Dominique , Boquien Clair-Yves , Flamant Cyril , Picaud Jean-Charles , Savagner Christophe , Claris Olivier , Lapillonne Alexandre , Mitanchez Delphine , Branger Bernard , Simeoni Umberto , Kaminski Monique , Ancel Pierre-Yves
Published: April 2012

Context

Supplementation of breast milk is difficult once infants suckle the breast and is often discontinued at end of hospitalisation and after discharge. Thus, breastfed preterm infants are exposed to an increased risk of nutritional deficit with a possible consequence on neurodevelopmental outcome.

Objective

To assess the relationship between breast feeding at time of discharge, weight gain during hospitalisation and neurodevelopmental outcome.

Design

Observational cohort study.

Setting

Two large, independent population-based cohorts of very preterm infants: the Loire Infant Follow-up Team (LIFT) and the EPIPAGE cohorts.

Patients

2925 very preterm infants alive at discharge.

Main outcome measure

Suboptimal neurodevelopmental outcome, defined as a score in the lower tercile, using Age and Stages Questionnaire at 2 years in LIFT and Kaufman Assessment Battery for Children Test at 5 years in EPIPAGE. Two propensity scores for breast feeding at discharge, one for each cohort, were used to reduce bias.

Results

Breast feeding at time of discharge concerned only 278/1733 (16%) infants in LIFT and 409/2163 (19%) infants in EPIPAGE cohort. Breast feeding is significantly associated with an increased risk of losing one weight Z-score during hospitalisation (LIFT: n=1463, adjusted odd ratio (aOR)=2.51 (95% CI 1.87 to 3.36); EPIPAGE: n=1417, aOR=1.55 (95% CI 1.14 to 2.12)) and with a decreased risk for a suboptimal neurodevelopmental assessment (LIFT: n=1463, aOR=0.63 (95% CI 0.45 to 0.87); EPIPAGE: n=1441, aOR=0.65 (95% CI 0.47 to 0.89) and an increased chance of having a head circumference Z-score higher than 0.5 at 2 years in LIFT cohort (n=1276, aOR=1.43 (95% CI 1.02 to 2.02)) and at 5 years in EPIPAGE cohort (n=1412, aOR=1.47 (95% CI 1.10 to 1.95)).

Conclusions

The observed better neurodevelopment in spite of suboptimal initial weight gain could be termed the ‘apparent breastfeeding paradox’ in very preterm infants. Regardless of the mechanisms involved, the current data provide encouragement for the use of breast feeding in preterm infants.
Insulin resistance in patients with cirrhosis and portal hypertension
Authors: Erice Eva , Llop Elba , Berzigotti Annalisa , Abraldes Juan G. , Conget Ignacio , Seijo Susana , Reverter Enric , Albillos Agustin , Bosch Jaume , García-Pagán Juan Carlos
Published: April 2012

Insulin resistance (IR) is involved in the pathogenesis of endothelial dysfunction and is also present in patients with cirrhosis. Intrahepatic endothelial dysfunction plays a major role, increasing hepatic vascular resistance and promoting portal hypertension (PH). In addition, β-adrenergic agonists and insulin share several intracellular signaling pathways. Thus IR may influence the response to β-blockers. This study aimed at evaluating the relationship between IR and hepatic hemodynamics in patients with cirrhosis and with the portal pressure response to acute β-blockade. Forty-nine patients with cirrhosis and PH were included. Hepatic and systemic hemodynamics were measured, and IR was estimated by using the updated homeostasis model assessment (HOMA)-2 index. Patients with HOMA-2 > 2.4 were considered IR. In patients with hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) [clinically significant PH (CSPH)], hemodynamic measurements were performed again 20 min after intravenous propranolol. Mean HOMA-2 index was 3 ± 1.4. Fifty-seven percent of patients had IR. A weak correlation between HOMA-2 index and HVPG was observed. Eighty-six percent of patients had CSPH. HOMA-2 index was an independent predictor of CSPH. However, in patients with CSPH, the correlation between HOMA-2 index and HVPG was lost. HVPG, but not IR, predicted the presence of esophageal varices. Response to propranolol was not different between patients with or without IR. In nondiabetic patients with cirrhosis, HOMA-2 index is directly associated with the presence of CSPH and indirectly with varices, but does not allow either grading HVPG or predicting its response to propranolol.
The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception
Authors: Tran Lee , Wiskur Brandt , Greenwood-Van Meerveld Beverley
Published: April 2012

Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophin-releasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNSTAL). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNSTAL. Mechanical sensitivity was quantified using electronic von Frey filaments, and colonic nociception was measured by quantifying a visceromotor response to graded colorectal distension. In situ hybridization was used to determine mRNA levels for CRF, CRF1, and CRF2 receptors in the BNSTAL. In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNSTAL to administer a CRF1 receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNSTAL, exhibited increased expression of CRF mRNA and increased CRF1-to-CRF2 receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNSTAL inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF1 receptor-dependent mechanism in the BNSTAL. The CeA through a descending pathway involving the BNSTAL plays a pivotal role in somatic and colonic nociception.
Vestibular-dependent spinal reflexes evoked by brief lateral accelerations of the heads of standing subjects
Authors: Laube Robyn , Govender Sendhil , Colebatch James G.
Published: April 2012

An impulsive acceleration stimulus, previously shown to activate vestibular afferents, was applied to the mastoid. Evoked EMG responses from the soleus muscles in healthy subjects ( n = 10) and patients with bilateral vestibular dysfunction ( n = 3) were recorded and compared with the effects of galvanic stimulation (GVS). Subjects were stimulated while having their eyes closed, head rotated, and while tonically activating their soleus muscles. Rectified EMG responses were recorded from the leg contralateral to the direction of head rotation. Responses were characterized by triphasic potentials that consisted of short-latency (SL), medium-latency (ML), and long-latency (LL) components beginning at (mean ± SD) 54.2 ± 4.8, 88.4 ± 4.7, and 121 ± 7.1 ms, respectively. Mean amplitudes for the optimum stimulus rise times were 9.05 ± 3.44% for the SL interval, 16.70 ± 4.41% for the ML interval, and 9.75 ± 4.89% for the LL interval compared with prestimulus values. Stimulus rise times of 14 and 20 ms evoked the largest ML amplitudes. GVS evoked biphasic responses (SL and ML) with similar latencies. Like GVS, the polarity of the initial interval was determined by the polarity of the stimulus and the evoked EMG response was attenuated when subjects were seated. There was no significant EMG response evoked when subjects were stimulated using 500-Hz vibration or in patients with bilateral vestibular dysfunction. Our study demonstrates that a brief lateral acceleration, likely to activate the utricle, can evoke spinal responses with properties similar to those previously shown for vestibular activation by GVS. The triphasic nature of the responses may allow the nervous system to respond differently to short compared with long-duration linear accelerations, consistent with their differing significance.
Prothrombolytic action of normobaric oxygen given alone or in combination with recombinant tissue-plasminogen activator in a rat model of thromboembolic stroke
Authors: David H. N. , Haelewyn B. , Degoulet M. , Colomb D. G. , Risso J. J. , Abraini J. H.
Published: April 2012

The potential benefit of 100 vol% normobaric oxygen (NBO) for the treatment of acute ischemic stroke patients is still a matter of debate. To advance this critical question, we studied the effects of intraischemic normobaric oxygen alone or in combination with recombinant tissue-plasminogen activator (rtPA) on cerebral blood flow and ischemic brain damage and swelling in a clinically relevant rat model of thromboembolic stroke. We show that NBO provides neuroprotection by achieving cerebral blood flow restoration equivalent to 0.9 mg/kg rtPA through probable direct interaction and facilitation of the fibrinolytic properties of endogenous tPA. In contrast, combined NBO and rtPA has no neuroprotective effect on ischemic brain damage despite producing cerebral blood flow restoration. These results 1) by providing a new mechanism of action of NBO highlight together with previous findings the way by which intraischemic NBO shows beneficial action; 2) suggest that NBO could be an efficient primary care therapeutic intervention for patients eligible for rtPA therapy; 3) indicate that NBO could be an interesting alternative for patients not eligible for rtPA therapy; and 4) caution the use of NBO in combination with rtPA in acute stroke patients.
Concurrent resistance and aerobic exercise stimulates both myofibrillar and mitochondrial protein synthesis in sedentary middle-aged men
Authors: Donges Cheyne E. , Burd Nicholas A. , Duffield Rob , Smith Greg C. , West Daniel W. D. , Short Michael J. , Mackenzie Richard , Plank Lindsay D. , Shepherd Peter R. , Phillips Stuart M. , Edge Johann A.
Published: April 2012

We determined myofibrillar and mitochondrial protein fractional synthesis rates (FSR), intramuscular signaling protein phosphorylation, and mRNA expression responses after isolated bouts of resistance exercise (RE), aerobic exercise (AE), or in combination [termed concurrent exercise (CE)] in sedentary middle-aged men. Eight subjects (age = 53.3 ± 1.8 yr; body mass index = 29.4 ± 1.4 kg·m2) randomly completed 8 × 8 leg extension repetitions at 70% of one repetition-maximum, 40 min of cycling at 55% peak aerobic power output (AE), or (consecutively) 50% of the RE and AE trials (CE). Biopsies were obtained (during a primed, constant infusion of l-[ ring-13C6]phenylalanine) while fasted, and at 1 and 4 h following postexercise ingestion of 20 g of protein. All trials increased mitochondrial FSR above fasted rates (RE = 1.3-fold; AE = 1.5; CE = 1.4; P < 0.05), although only CE (2.2) and RE (1.8) increased myofibrillar FSR ( P < 0.05). At 1 h postexercise, phosphorylation of Akt on Ser473 (CE = 7.7; RE = 4.6) and Thr308 (CE = 4.4; RE = 2.9), and PRAS40 on Thr246 (CE = 3.8; AE = 2.5) increased ( P < 0.05), with CE greater than AE for Akt Ser473-Thr308 and greater than RE for PRAS40 ( P < 0.05). Despite increased phosphorylation of Akt-PRAS40, phosphorylation of mammalian target of rapamycin (Ser2448) remained unchanged ( P > 0.05), while rpS6 (Ser235/236) increased only in RE (10.4) ( P < 0.05). CE and AE both resulted in increased peroxisome proliferator receptor-γ coactivator 1-α (PGC1α) expression at 1 h (CE = 2.9; AE = 2.8; P < 0.05) and 4 h (CE = 2.6; AE = 2.4) and PGC1β expression at 4 h (CE = 2.1; AE = 2.6; P < 0.05). These data suggest that CE-induced acute stimulation of myofibrillar and mitochondrial FSR, protein signaling, and mRNA expression are equivalent to either isolate mode (RE or AE). These results occurred without an interference effect on muscle protein subfractional synthesis rates, protein signaling, or mRNA expression.
Volitional control of reflex cough
Authors: Hegland Karen W. , Bolser Donald C. , Davenport Paul W.
Published: April 2012

Multiple studies suggest a role for the cerebral cortex in the generation of reflex cough in awake humans. Reflex cough is preceded by detection of an urge to cough; strokes specifically within the cerebral cortex can affect parameters of reflex cough, and reflex cough can be voluntarily suppressed. However, it is not known to what extent healthy, awake humans can volitionally modulate the cough reflex, aside from suppression. The aims of this study were to determine whether conscious humans can volitionally modify their reflexive cough and, if so, to determine what parameters of the cough waveform and corresponding muscle activity can be modified. Twenty adults (18–40 yr, 4 men) volunteered for study participation and gave verbal and written informed consent. Participants were seated and outfitted with a facemask and pneumotacograph, and two surface EMG electrodes were positioned over expiratory muscles. Capsaicin (200 μM) was delivered via dosimeter and one-way (inspiratory) valve attached to a side port between the facemask and pneumotachograph. Cough airflow and surface EMG activity were recorded across tasks including 1) baseline, 2) small cough (cough smaller or softer than normal), 3) long cough (cough longer or louder than normal), and 4) not cough (alternative behavior). All participants coughed in response to 200 μM capsaicin and were able to modify the cough. Variables exhibiting changes include those related to the peak airflow during the expiratory phase. Results demonstrate that it is possible to volitionally modify cough motor output characteristics.
In Vivo Diagnosis of Melanoma and Nonmelanoma Skin Cancer Using Oblique Incidence Diffuse Reflectance Spectrometry
Authors: Garcia-Uribe Alejandro , Zou Jun , Duvic Madeleine , Cho-Vega Jeong Hee , Prieto Victor G. , Wang Lihong V.
Published: April 2012

Early detection and treatment of skin cancer can significantly improve patient outcome. However, present standards for diagnosis require biopsy and histopathologic examinations that are relatively invasive, expensive, and difficult for patients with many early-stage lesions. Here, we show an oblique incidence diffuse reflectance spectroscopic (OIDRS) system that can be used for rapid skin cancer detection in vivo. This system was tested under clinical conditions by obtaining spectra from pigmented and nonpigmented skin lesions, including melanomas, differently staged dysplastic nevi, and common nevi that were validated by standard pathohistologic criteria. For diagnosis of pigmented melanoma, the data obtained achieved 90% sensitivity and specificity for a blinded test set. In a second analysis, we showed that this spectroscopy system can also differentiate nonpigmented basal cell or squamous cell carcinomas from noncancerous skin abnormalities, such as actinic keratoses and seborrheic keratoses, achieving 92% sensitivity and specificity. Taken together, our findings establish how OIDRS can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic. Cancer Res; 72(11); 2738–45. ©2012 AACR.
Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
Authors: Xiao Changting , Bandsma Robert H. J. , Dash Satya , Szeto Linda , Lewis Gary F.
Published: April 2012

Objectives—

Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic triglyceride-rich lipoprotein production and clearance in healthy humans.

Methods and Results—

Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 μg exenatide versus placebo), 4 to 6 weeks apart, in random order, in which triglyceride-rich lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of triglyceride-rich lipoprotein-apolipoprotein B-48, but not of triglyceride-rich lipoprotein-apolipoprotein B-100.

Conclusions—

These results suggest a possible direct effect of exenatide on intestinal lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
, NCT01056549.
Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo
Authors: de Lizarrondo Sara Martínez , Roncal Carmen , Calvayrac Olivier , Rodríguez Cristina , Varo Nerea , Purroy Ana , Lorente Leonardo , Rodríguez José A. , Doeuvre Loïc , Hervás-Stubbs Sandra , Angles-Cano Eduardo , Páramo José A. , Martínez-González José , Orbe Josune
Published: April 2012

Objective—

Thrombin induces CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) under inflammatory/prothrombotic conditions. Thrombin and CD40L could modulate endothelial MMP-10 expression in vitro and in vivo.

Methods and Results—

Human endothelial cells were stimulated with thrombin (0.1–10 U/mL), CD40L (0.25–1 μg/mL), or their combination (thrombin/CD40L) to assess MMP-10 expression and microparticle generation. Thrombin/CD40L elicited higher MMP-10 mRNA (5-fold;
P
<0.001) and protein levels (4.5-fold;
P
<0.001) than either stimulus alone. This effect was mimicked by a protease-activated receptor-1 agonist and antagonized by hirudin, a-protease-activated receptor-1, α-CD40L, and α-CD40 antibodies. The synergistic effect was dependent on p38 mitogen-activated protein kinase and c-Jun
N
-terminal kinase-1 pathways. Thrombin also upregulated the expression of CD40 in endothelial cell surface increasing its availability, thereby favoring its synergistic effects with CD40L. In mice, thrombin/CD40L further increased the aortic MMP-10 expression. Septic patients with systemic inflammation and enhanced thrombin generation (n=60) exhibited increased MMP-10 and soluble CD40L levels associated with adverse clinical outcome. Endothelial and systemic activation by thrombin/CD40L and lipopolysaccharide also increased microparticles harboring MMP-10 and CD40L.

Conclusion—

Thrombin/CD40L elicited a strong synergistic effect on endothelial MMP-10 expression and microparticles containing MMP-10 in vitro and in vivo, which may represent a new link between inflammation/thrombosis with prognostic implications.
Increasing Plasma Free Fatty Acids in Healthy Subjects Induces Aortic Distensibility Changes Seen in Obesity
Authors: Rider Oliver J. , Holloway Cameron J. , Emmanuel Yaso , Bloch Edward , Clarke Kieran , Neubauer Stefan
Published: April 2012

Background—

Elevated free fatty acid (FFA) levels are known to impair aortic elastic function. In obesity, FFA levels are elevated and aortic distensibility (AD) reduced in a pattern that predominantly affects the distal aorta. Despite this, the role of FFAs in obesity-related aortic stiffness remains unclear.

Methods and Results—

Using vascular MRI, we aimed to determine if (1) FFA level correlated with AD in obesity; and (2) whether elevating FFA acutely and subacutely in normal-weight subjects reproduced the distal pattern of AD change in obesity. To do this, regional AD was recorded in 35 normal-weight and 70 obese subjects and then correlated with FFA levels. When compared with normal weight, obesity was associated with reduced AD in a pattern predominantly affecting the distal aorta (ascending aorta by −22%, proximal descending aorta by −25%, and abdominal aorta by −35%;
P
<0.001). After controlling for age, blood pressure, and body mass index, FFA levels remained negatively correlated with abdominal AD (
r
=−0.43,
P
<0.01). In 2 further normal-weight groups, AD was recorded before and after elevation of FFA levels with intralipid infusion (by +535%, n=9) and a 5-day high-fat, low-carbohydrate diet (by +48%, n=14).

Conclusions—

Both intralipid infusion and a low-carbohydrate diet resulted in reduced abdominal AD (infusion −22%, diet −28%; both
P
<0.05), reproducing the distal pattern AD reduction seen in obesity. These findings suggest that elevated FFA impair AD in obesity and provide a potential therapeutic target to improve aortic elastic function in obesity.