bluuebunny/crossref_metadata_2025 huggingface dataset:
Fourth‐line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures
Authors: Gisbert J. P. , Castro‐Fernandez M. , Perez‐Aisa A. , Cosme A. , Molina‐Infante J. , Rodrigo L. , Modolell I. , Cabriada J. L. , Gisbert J. L. , Lamas E. , Marcos E. , Calvet X.
Published: February 2012

Background

In some cases, Helicobacter pylori infection persists even after three eradication treatments.

Aim

To evaluate the efficacy of an empirical fourth‐line rescue regimen with rifabutin in patients with three eradication failures.

Methods

Design: Multicentre, prospective study. Patients: In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). Intervention: A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. Outcome: Eradication was confirmed by 13C‐urea breath test 4–8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire.

Results

One‐hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per‐protocol and intention‐to‐treat eradication rates were 52% (95% CI = 41–63%) and 50% (40–60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150 000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases.

Conclusions

Even after three previous H. pylori eradication failures, an empirical fourth‐line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin‐based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin.
The effect of short time periods of pre‐operative warming in the prevention of peri‐operative hypothermia
Authors: Horn E.‐P. , Bein B. , Böhm R. , Steinfath M. , Sahili N. , Höcker J.
Published: February 2012

The aim of our study was to evaluate the performance of different durations of active pre‐operative skin‐surface warming (pre‐warming) to prevent peri‐operative hypothermia and postoperative shivering. We randomly assigned 200 patients, scheduled for surgery of 30–90 min under general anaesthesia, to receive passive insulation or forced‐air skin surface warming for 10, 20 or 30 min. Body temperature was measured at the tympanic membrane. Shivering was graded by visual inspection. There were significant differences in changes of core temperature between the non‐pre‐warmed group and all the pre‐warmed groups (p < 0.00001), but none between the three pre‐warmed groups (p = 0.54). Without pre‐warming, 38/55 (69%) patients became hypothermic (< 36 °C) at the end of anaesthesia, whereas only 7/52 (13%), 3/43 (7%) and 3/50 (6%) patients following 10, 20 or 30 min pre‐warming, respectively, became hypothermic (p < 0.001 vs no pre‐warming). Shivering was observed in 10 patients without, and in three, three and one patients with pre‐warming in the respective groups (p = 0.02). Pre‐warming of patients for only 10 or 20 min before general anaesthesia mostly prevents hypothermia and reduces shivering.
The role of statin therapy in the prevention of atrial fibrillation: a meta‐analysis of randomized controlled trials
Authors: Fang Wen‐tong , Li Hong‐jian , Zhang Haibo , Jiang Su
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia, and AF is associated with relatively higher all‐cause mortality in both men and women.

• However, there are limited treatment options for AF.

• Statins are hypothesized to have a benefit against arrhythmias in addition to well‐established secondary prevention benefit for atherosclerotic coronary artery disease, yet the data are inconsistent

WHAT THIS STUDY ADDS

• Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF.

• The benefit of statin therapy seemed more markedly in secondary prevention than primary prevention.

• These results provided some evidence for the benefit of statins beyond their lipid‐lowering activity

AIMS The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF.

METHODS Meta‐analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed.

RESULTS Twenty studies with 23 577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37–0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18–0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40–0.74; P < 0.0001).

CONCLUSIONS Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention.
Increased prevalence of light chain monoclonal gammopathy of undetermined significance (LC‐MGUS) in first‐degree relatives of individuals with multiple myeloma
Authors: Greenberg Alexandra J. , Vincent Rajkumar S. , Larson Dirk R. , Dispenzieri Angela , Therneau Terry M. , Colby Colin L. , Phelps Tara K. , Kumar Shaji K. , Katzmann Jerry A. , Kyle Robert A. , Slager Susan L. , Vachon Celine M.
Published: February 2012

Previously, we reported increased risk of heavy‐chain (HC) monoclonal gammopathy of undetermined significance (MGUS) among first‐degree (1°) relatives of multiple myeloma (MM) or HC‐MGUS probands. This study investigated whether there was comparable risk for light‐chain (LC) MGUS among 911 relatives of the same HC‐MGUS/MM probands versus a reference population of 21 463. Seventeen 1° relatives had LC‐MGUS (adjusted prevalence = 1·7%, 95% CI = 0·9–2·6%). There was increased risk of LC‐MGUS in relatives of MM probands (RR = 3·4, 95% CI = 2·0–5·5). We saw no increased risk in relatives of HC‐MGUS probands. We conclude that the prevalence of LC‐MGUS is significantly higher among 1° relatives of MM probands compared to the reference population.
BCR‐ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia
Authors: Roy Swagata , Jørgensen Heather G. , Roy Poornima , Abed El Baky Mohamed , Melo Junia V. , Strathdee Gordon , Holyoake Tessa L. , Bartholomew Chris
Published: February 2012

MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony‐forming cells by 34% and moderately reduces BCR‐ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34+ selected cells of both CML chronic phase (CML‐CP), and non‐CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML‐CP CD34+ cells, K562 and KY01 cell lines whereas imatinib had no effect in non‐CML BCR‐ABL1 −ve CD34+ cells. Together these results suggest that BCR‐ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML‐CP progenitor cells and that the BCR‐ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML‐CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis.
Buffering and plasticity in vital rates of oldfield rodents
Authors: Reed Aaron W. , Slade Norman A.
Published: February 2012

1. Under the hypothesis of environmental buffering, populations are expected to minimize the variance of the most influential vital rates; however, this may not be a universal principle. Species with a life span <1 year may be less likely to exhibit buffering because of temporal or seasonal variability in vital rate sensitivities. Further, plasticity in vital rates may be adaptive for species in a variable environment with reliable cues.

2. We tested for environmental buffering and plasticity in vital rates using stage‐structured matrix models from long‐term data sets in four species of grassland rodents. We used periodic matrices to estimate stochastic elasticity for each vital rate and then tested for correlations with a standardized coefficient of variation for each rate.

3. We calculated stochastic elasticities for individual months to test for an association between increased reproduction and the influence of reproduction, relative to survival, on the population growth rate.

4. All species showed some evidence of buffering. The elasticity of vital rates of Peromyscus leucopus (Rafinesque, 1818), Sigmodon hispidus Say & Ord, 1825 and Microtus ochrogaster (Wagner, 1842) was negatively related to vital rate CV. Elasticity and vital rate CV were negatively related in Peromyscus maniculatus (Wagner, 1845), but the relationship was not statistically significant. Peromyscus leucopus and M. ochrogaster showed plasticity in vital rates; reproduction was higher following months where elasticity for reproduction exceeded that of survival.

5. Our results suggest that buffering is common in species with fast life histories; however, some populations that exhibit buffering are capable of responding to short‐term variability in environmental conditions through reproductive plasticity.
Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle
Authors: BERTARELLI D. , BALBO A. , CARLETTI M. , CANNIZZO T. , GIROLAMI F. , NEBBIA C.
Published: February 2012

Bertarelli, D., Balbo, A., Carletti, M., Cannizzo, T., Girolami, F., Nebbia, C. Hepatic tyrosine aminotransferase and glucocorticoid abuse in meat cattle. J. vet. Pharmacol. Therap. 35, 596–603.

Besides being extensively applied as therapeutical remedies, glucocorticoids (GCs) – most notably dexamethasone or prednisolone – are also illegally used in livestock for growth‐promoting purposes. This study was designed to assess the suitability of liver tyrosine aminotransferase (TAT), a gluconeogenic enzyme known to be induced by GCs, to act as a reliable candidate biomarker to screen for GC abuse in cattle. Enzyme activity was measured spectrophotometrically in liver cytosols or in cell extracts, and TAT gene expression was determined by real‐time PCR. Compared with untreated veal calves, a notable scatter (20‐fold) and much higher median values (3‐fold) characterized TAT specific activity in liver samples from commercially farmed veal calves. A time‐related increase in both enzyme activity and gene expression was detected in rat hepatoma cell lines treated with dexamethasone concentrations (10−8 or 10−9 m) in the range of those recorded in noncompliant samples from EU official controls. In experimental studies in which finishing bulls were administered GCs at growth‐promoting dosages, however, no such changes were recorded in dexamethasone‐treated animals; a statistically significant rise in liver TAT activity (+95%) only occurred in prednisolone‐treated bulls. Although further research is needed to characterize the GC‐mediated response in cattle liver, TAT does not appear to be a specific and sensitive biomarker of GC abuse in the bovine species.
A homologue of the human STRIPAK complex controls sexual development in fungi
Authors: Bloemendal Sandra , Bernhards Yasmine , Bartho Kathrin , Dettmann Anne , Voigt Oliver , Teichert Ines , Seiler Stephan , Wolters Dirk A. , Pöggeler Stefanie , Kück Ulrich
Published: February 2012

Sexual development in fungi is a complex process involving the generation of new cell types and tissues – an essential step for all eukaryotic life. The characterization of sterile mutants in the ascomycete Sordaria macrospora has led to a number of proteins involved in sexual development, but a link between these proteins is still missing. Using a combined tandem‐affinity purification/mass spectrometry approach, we showed in vivo association of developmental protein PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding subunit of protein phosphatase 2A. Further experiments extended the protein network to the putative kinase activator SmMOB3, known to be involved in sexual development. Extensive yeast two‐hybrid studies allowed us to pinpoint functional domains involved in protein–protein interaction. We show for the first time that a number of already known factors together with new components associate in vivo to form a highly conserved multi‐subunit complex. Strikingly, a similar complex has been described in humans, but the function of this so‐called striatin interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S. macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual development and cell fusion, indicating a role for the fungal STRIPAK complex in both processes.
The impact of sirolimus on sex hormones in male adolescent kidney recipients
Authors: Cavanaugh Teresa M. , Schoenemen Heather , Goebel Jens
Published: February 2012

Cavanaugh TM, Schoenemen H, Goebel J. The impact of sirolimus on sex hormones in male adolescent kidney recipients.

Abstract: While it is known that sirolimus affects sex hormones in adult kidney transplant patients, there is a scarcity of data on its effects on sex hormone levels in adolescent kidney recipients. The objective of this study is to describe the impact of sirolimus on the sex hormones in this patient population. This is a retrospective review of male adolescent renal transplant patients transitioned to sirolimus. Baseline and subsequent annual testosterone levels were collected. Linear regression was undertaken to determine the predictors of testosterone levels. Four African Americans and 11 Caucasians, median age of 15 yr (11–18) in 2008, were included. Mean time post‐transplant was 81 ± 37 months. Mean testosterone values were the following: 336 ± 135 ng/dL (n = 8) at baseline, 349 ± 130 ng/dL (n = 15) one yr later, and 360 ± 132 ng/dL (n = 13) two yr later (normal range for adult males: 350–970 ng/dL). Seven (47%) patients experienced a decrease in testosterone levels. Time on sirolimus was associated with decreased testosterone (r = 0.643, p = 0.010). Testosterone levels in pubertal male kidney transplant recipients on sirolimus may be suppressed, especially if they have been treated with sirolimus for several years. These data need to be confirmed in a larger study.
Tacrolimus as a risk factor for tuberculosis and outcome of treatment with rifampicin in solid organ transplant recipients
Authors: Ha Y.E. , Joo E.J. , Park S.Y. , Wi Y.M. , Kang C.I. , Chung D.R. , Joh J.W. , Lee S.K. , Song J.H. , Peck K.R.
Published: February 2012

Background

The purpose of this study was to investigate the incidence, risk factors, and treatment outcome of tuberculosis (TB) in solid organ transplant (SOT) recipients treated with rifampicin.

Methods

The incidence density of TB was calculated by a retrospective cohort study. Risk factors for TB were analyzed by a nested case–control study. Treatment outcome and effects of anti‐TB drugs on immunosuppressants and allograft were compared between patients whose initial 2‐month intensive regimen included rifampicin and those whose intensive regimen did not.

Results

Among the 2144 SOT recipients over 16 years, 40 cases of TB were found (1.7%). The incidence density was 372 cases per 105 patient years (95% confidence interval [CI], 270–503), which was 4 times higher than for the general Korean population (90 cases per 105 person years). The median time to the development of TB was 234 days (range, 33–3940 days). The use of tacrolimus (odds ratio [OR] 4.90; 95% CI, 1.74–13.80; P = 0.003) and cytomegalovirus (CMV) infection within the prior 3 months (OR 4.62; 95% CI, 1.44–14.87; P = 0.01) were found to be risk factors for TB. Patients whose intensive regimen included rifampicin were more likely to have an increased dose of calcineurin inhibitors than patients whose intensive regimen did not include rifampicin (13/15 [86.7%] vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ between the 2 groups.

Conclusions

Use of tacrolimus and CMV infection were major risk factors for TB in SOT recipients. The graft outcome and mortality did not differ whether rifampicin was used or not during the first 2‐month intensive phase.
Epibiotic traits of the invasive red seaweed Acanthophora spicifera in La Paz Bay, South Baja California (Eastern Pacific)
Authors: Ávila Enrique , Méndez‐Trejo María del Carmen , Riosmena‐Rodríguez Rafael , López‐Vivas Juan M. , Sentíes Abel
Published: February 2012

The aim of this study was to analyze the interaction of a non‐native macroalga (Acanthophora spicifera) with native macroalgae (Sargassum spp.) and sponge assemblages in a subtropical embayment of the Mexican Pacific. The intensity of A. spicifera epiphytism on the native seaweed Sargassum varied significantly over time and was inversely related to the Sargassum density and size. The higher intensity (up to 28 individuals per host plant) occurred when Sargassum was smaller and was lower in density (senescence period). The lower intensity was recorded during the growth period of Sargassum and the subsequent increase in intensity was attributed to a high fragmentation period of A. spicifera, which was evidenced by a decrease in its average size and biomass and by the presence of larger free‐floating accumulations on the subtidal zone. The facultative interaction between A. spicifera and Sargassum appears to be neutral, as no negative or positive effects were found for epiphytic or basibiont seaweeds. However, this invasive seaweed characteristically monopolizes almost all types of hard substrate, and its effects on other algae and benthic organisms should be investigated. Moreover, A. spicifera was often epizoic on epilithic sponges. This invasive seaweed was found anchored on the sponge tissue by rhizome‐like structures. In addition, free‐floating fronds of A. spicifera were frequently found carrying small pieces of the basibiont sponge in its basis (60% of them with eggs and embryos), which suggests a novel facilitation mechanism for some sponge species, as the A. spicifera epizoism could favor fragmentation, dispersal and recruitment of these invertebrates. This study shows that A. spicifera is not only a species that adapts rapidly to the new conditions of the receiving environment but, due to its epibiotic traits, it can directly interact with and influence the life histories of some native species.
Blinded Continuous Monitoring of Nuisance Parameters in Clinical Trials
Authors: Friede Tim , Miller Frank
Published: February 2012

Determination of a clinical trial's size is an important task in the planning of any trial because of the direct implications of the sample size on feasibility, costs and timelines. However, sample size calculations are often subject to substantial uncertainty due to limited prior information on the size of nuisance parameters such as variances or event rates. Continuous monitoring of the nuisance parameter in clinical trials has been proposed as a tool to size trials appropriately. With this approach, the nuisance parameter is continuously monitored during the trial. The trial is stopped when the actual estimate for the nuisance parameter and sample size fulfil a stopping criterion. Continuous monitoring can therefore be viewed as a stochastic process with stopping time. We describe the bias that occurs with unblinded continuous monitoring of the variance in clinical trials by means of a simulation study. Then we propose a procedure for blinded continuous monitoring that does not require breaking the treatment code during the on-going study and show that the procedure does not suffer from the same biases as observed in unblinded monitoring. Results on the performance properties of such designs are given and the designs are compared with blinded re-estimation procedures with a single data look. By means of asymptotic theoretical arguments and finite sample size simulations we find that the variability in sample size is smaller with blinded continuous monitoring than with blinded sample size re-estimation whenever the power for both designs is close to the target value. Repeated sample size re-estimation is in between continuous monitoring and sample size re-estimation in this respect. Furthermore, we present a hypertension trial where blinded sample size re-estimation with a single data look was applied and we investigate the properties of blinded continuous monitoring in this setting. Finally we close with a brief discussion.
GROWTH, UNEMPLOYMENT AND ENDOGENOUS TECHNICAL PROGRESS: A HICKSIAN RESOLUTION OF HARROD'S KNIFE‐EDGE
Authors: Palley Thomas I.
Published: February 2012

This paper presents a neo‐Kaleckian growth model with unemployment, endogenous technical progress, and a steady‐state requirement of balanced labor demand and supply growth. There are two key innovations: first, a Marx–Hicks unemployment rate–profit rate channel affecting labor‐saving technical progress; second, a Keynesian unemployment rate channel affecting saving and investment. Changes in the unemployment rate change the profit rate, rebalancing effective labor supply and employment growth. This provides a Hicksian resolution of Harrod's knife‐edge. The Keynesian unemployment rate channel strengthens the growth benefits of a lower unemployment rate, potentially obviating any growth–unemployment trade‐off.
The determinants of competitive success in the interwar British radio industry1
Authors: Scott Peter
Published: February 2012

This article discusses the sources of competitive advantage in the interwar British radio industry. Specifically, it examines why sections of the industry that reaped substantial monopoly rents from the downstream value chain failed to dominate the industry. During the 1920s Marconi (which controlled the fundamental UK patents) had a key cost advantage, as had other members of the ‘Big Six’ electrical engineering firms which formed the BBC and were granted preferential royalties. Meanwhile the valve manufacturers' cartel was also able to extract high rents from set manufacturers. The vertical integration literature suggests that input monopolists have incentives to control downstream production. Yet—in contrast to the gramophone industry, which became concentrated into two huge companies following market saturation in the 1930s—radio retained a much more competitive structure. The Big Six failed to capitalize fully on their initial cost advantages owing to logistical weaknesses in supplying markets subject to rapid technical and design obsolescence. Subsequently, during the 1930s, marketing innovations are shown to have played a key role in allowing several independents to establish successful brands. This gave them sufficient scale to provide strong bargaining positions with input suppliers, negating most of their initial cost disadvantage.
‘Some Good Clean Fun’: Humour, Control and Subversion in an Advertising Agency
Authors: Kenny Kate , Euchler Gordon
Published: February 2012

This article explores the relation between humour and control, drawing on participant observation in an organization in which humour was central to daily life. Keys is a leading advertising agency whose staff spent an unusually large amount of time sending humorous e‐mails. Examining these e‐mails in some depth, we unpack the role of humour in subverting various forms of control, including gender norms and managerial authority. We find the relation between humour, control and subversion to be ambiguous. Building upon current debates in organization studies, we develop the concept of humour based on our observations at Keys. Specifically, we argue that humour is always in excess of both control and subversion, a ‘nicely impossible’ object that cannot be captured. This article thus contributes to theoretical approaches on organizational humour, conceptualizing the concept of ‘newness’ through Judith Butler's re‐reading of Derridean différance and the Lacanian Real. In addition, we contribute a novel empirical account of the study of e‐mail list humour in a contemporary advertising firm.
Economic Distress, Labor Market Reforms, and Dualism in Japan and Korea
Authors: SONG JIYEOUN
Published: February 2012

This article seeks to examine the rapid rise of labor market dualism and inequality in Japan and Korea. It argues that the path‐dependent trajectories of labor market and social protection reforms biased in favor of labor market insiders explain recent institutional developments in the two countries. In Japan, political coalitions between conservative policymakers, large firms, and core regular workers in reform politics consolidated labor market dualism and inequality during its protracted recession. Meanwhile, the organizational capacity of largechaebolunions deepened the inequality and the segmentation of the dualistic labor market in Korea. By examining three key institutional domains of the labor market—labor market reform, wage bargaining, and social protection—this article analyzes the ways in which Japan and Korea have reinforced dualism and inequality over the past two decades.
Home range and shelter site selection in the greater hedgehog tenrec in the dry deciduous forest of Western Madagascar
Authors: Levesque D. L. , Rakotondravony D. , Lovegrove B. G.
Published: February 2012

Information on the spatial distribution and habitat use of the Tenrecidae (Supraorder: Afrotheria) of Madagascar are severely lacking. Here, we present the first data available on home range size, as well as further data on population distribution and rest site selection of a large tenrec, the greater hedgehog tenrec (Setifer setosus). Data were collected over two rainy seasons in the dry deciduous woodland of Western Madagascar, in Ankarafantsika National Park. Home ranges were surprisingly large for a 200–300‐g animal: males had an average home range (95% minimum convex polygon) of 13.7 ± 4.9 ha (n = 5), and females of 6.7 ± 2.0 ha (n = 5). A high overlap between multiple individuals of the opposite sex supports a promiscuous mating system for this species. Daytime shelter sites proved to be highly variable and differed between sex and reproductive status.
Metformin reduces vascular production of vasoconstrictor prostanoids in fructose overloaded rats
Authors: Puyó A. M. , Borroni J. S. , Boudou S. , Santander Y. , Carranza A. , Donoso A. S. , Peredo H. A.
Published: February 2012

1 Metformin is a hypoglycaemic drug currently used to increase insulin sensitivity in the treatment of type 2 diabetes and metabolic syndrome. Its main mechanism of action is through activation of AMP‐activated protein kinase, an enzyme that regulates cellular and whole organ metabolism.

2 The fructose‐overloaded rat is an experimental model with features that resemble human metabolic syndrome. We have previously reported alterations in vascular prostanoids (PR) in this model.

3 The aim of this study was to analyse the effects of metformin treatment on blood pressure, metabolic parameters and PR production in aorta and mesenteric vascular bed (MVB) from fructose‐overloaded animals. Four groups of male Sprague–Dawley rats were used: control, fructose overloaded (10% w/v fructose), metformin treated (50 mg kg−1 day−1) and fructose‐overloaded treated with metformin.

4 Rats with fructose overload had significantly elevated systolic blood pressure, glycaemia, triglyceridaemia, cholesterolaemia and insulinaemia compared with controls. Except for insulinaemia, metformin limited all these increases in fructose‐overloaded animals.

5 Fructose overload reduced prostacyclin levels in aorta and MVB, but prostaglandin E2 levels were only reduced in MVB. Metformin treatment reduced the levels of the vasoconstrictor prostaglandins, PGF2α and thromboxane, in both vascular preparations from fructose‐overloaded rats. PGF2α levels were significantly reduced by metformin in controls.

6 In conclusion, one of the mechanisms by which metformin reduced blood pressure in this model is by decreasing vasoconstrictor prostaglandin production.
Tramadol inhibits the contractility of isolated caprine detrusor muscle
Authors: Kumar A. , Prabha R. , Paul T. , Margaret Shanthi F. X. , George J. , Peedicayil J. , Ernest K.
Published: February 2012

1 The atypical opioid analgesic tramadol has been shown to provide beneficial clinical and urodynamic effects in patients with detrusor overactivity. The effect of tramadol on isolated detrusor muscle has not been studied. This study investigated the ability of tramadol to inhibit acetylcholine (ACh)‐induced contractility of the isolated caprine (goat) detrusor muscle. The effect of three concentrations (30, 100 and 300 μm) of tramadol on 10 caprine detrusor strips contracted by the addition of 100, 200 or 400 μm ACh was studied. The sensitivity of tramadol‐induced inhibition of ACh responses to treatment with the β‐adrenoceptor antagonist propranolol (1 μm) and the opioid receptor antagonist naloxone (100 μμ) was also studied.

2 Tramadol caused a concentration‐dependent inhibition of ACh‐induced detrusor contraction that was reversed by raising the concentration of ACh. Propranolol, but not naloxone, reversed the tramadol‐induced inhibition of contractions to ACh in the detrusor.

3 These results suggest that tramadol inhibits ACh‐induced contractility of the isolated detrusor. They also suggest that tramadol does so by an indirect anticholinergic mechanism involving the stimulation of β‐adrenoceptors. Tramadol may be useful in managing clinical conditions requiring relaxation of the detrusor muscle. Although the concentrations of tramadol needed to relax the detrusor were relatively high, these could be clinically attained via intravesical administration.
Impact of Deductibles on Initiation and Continuation of Psychotherapy for Treatment of Depression
Authors: Fishman Paul A. , Ding Victoria , Hubbard Rebecca , Ludman Evette J. , Pabiniak Chester , Stewart Christine , Morales Leo , Simon Gregory E.
Published: February 2012

Objective

To estimate the impact of deductibles on the initiation and continuation of psychotherapy for depression.

Data Sources/Study Setting

Data from health care encounters and claims from Group Health Cooperative, a large integrated health care system in Washington State, was merged with information from a centralized behavioral health triage call center to conduct study analyses.

Study Design

A retrospective observational design using a hierarchical logistic regression model was used to estimate initiation and continuation probabilities for use of psychotherapy, adjusting for key sociodemographic/economic factors and prior use of behavioral health services relevant to individual decisions to seek mental health care.

Data Collection/Extraction Methods

Analyses were based on merged datasets on patient enrollment, insurance benefits, use of mental health and general medical services and information collected by a triage specialist at a centralized behavioral health call center.

Principal Findings

Among individuals with unmet deductibles between $100 and $500, we found a statistically significant lower likelihood of making an initial visit, but there was no statistically significant effect on making an initial or subsequent visit among individuals that had met their deductible.

Conclusions

Unmet deductibles appear to influence the likelihood of initiating psychotherapy for treating depression.
Identifying the Latent Failures Underpinning Medication Administration Errors: An Exploratory Study
Authors: Lawton Rebecca , Carruthers Sam , Gardner Peter , Wright John , McEachan Rosie R. C.
Published: February 2012

Objectives

The primary aim of this article was to identify the latent failures that are perceived to underpin medication errors.

Study Setting

The study was conducted within three medical wards in a hospital in the United Kingdom.

Study Design

The study employed a cross‐sectional qualitative design.

Data Collection Methods

Interviews were conducted with 12 nurses and eight managers. Interviews were transcribed and subject to thematic content analysis. A two‐step inter‐rater comparison tested the reliability of the themes.

Principal Findings

Ten latent failures were identified based on the analysis of the interviews. These were ward climate, local working environment, workload, human resources, team communication, routine procedures, bed management, written policies and procedures, supervision and leadership, and training. The discussion focuses on ward climate, the most prevalent theme, which is conceptualized here as interacting with failures in the nine other organizational structures and processes.

Conclusions

This study is the first of its kind to identify the latent failures perceived to underpin medication errors in a systematic way. The findings can be used as a platform for researchers to test the impact of organization‐level patient safety interventions and to design proactive error management tools and incident reporting systems in hospitals.
Ambulatory Subspecialty Visits in a Large Pediatric Primary Care Network
Authors: Vernacchio Louis , Muto Jennifer M. , Young Gregory , Risko Wanessa
Published: February 2012

Objective

To determine patterns of subspecialty utilization within a pediatric primary care network.

Data Sources/Study Setting

Paid claims from a large not‐for‐profit health plan for patients of The Pediatric Physicians' Organization at Children's, a network of private pediatric practices affiliated with Children's Hospital Boston.

Principal Findings

The subspecialty visit rate was 1.01 visits per subject‐year. In 2007, 56.8 percent of subjects had no subspecialty visits, whereas 4.2 percent had ≥5 visits; the corresponding figures in 2008 were 54.1 and 4.5 percent, respectively. The most frequently visited subspecialties were Ophthalmology, Orthopedics, Dermatology, Otorhinolaryngology, and Allergy/Immunology. Visit rates varied sevenfold by practice.

Conclusions

Wide practice variability in pediatric subspecialty utilization suggests an opportunity for reducing unnecessary visits. Better integration between primary care and the most commonly used subspecialties will be needed to meaningfully reduce unnecessary visits and enhance value.
ET‐1 actions in the kidney: evidence for sex differences
Authors: Kittikulsuth W , Sullivan JC , Pollock DM
Published: February 2012

Hypertension and chronic kidney disease are more common in men than in premenopausal women at the same age. In animal models, females are relatively protected against genetic or pharmacological procedures that produce high blood pressure and renal injury. Overactivation or dysfunction of the endothelin (ET) system modulates the progression of hypertension or kidney diseases with the ETA receptor primarily mediating vasoconstriction, injury and anti‐natriuresis, and ETB receptors having opposite effects. The purpose of this review is to examine the role of the ET system in the kidney with a focus on the inequality between the sexes associated with the susceptibility to and progression of hypertension and kidney diseases. In most animal models, males have higher renal ET‐1 mRNA expression, greater ETA‐mediated responses, including renal medullary vasoconstriction, and increased renal injury. These differences are reduced following gonadectomy suggesting a role for sex hormones, mainly testosterone. In contrast, females are relatively protected from high blood pressure and kidney damage via increased ETB versus ETA receptor function. Furthermore, ETA receptors may have a favourable effect on sodium excretion and reducing renal damage in females. In human studies, the genetic polymorphisms of the ET system are more associated with hypertension and renal injury in women. However, the knowledge of sex differences in the efficacy or adverse events of ETA antagonists in the treatment of hypertension and kidney disease is poorly described. Increased understanding how the ET system acts differently in the kidneys between sexes, especially with regard to receptor subtype function, could lead to better treatments for hypertension and renal disease.

LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-2
The Role of the MTHFR Gene in Migraine
Authors: Stuart Shani , Cox Hannah C. , Lea Rod A. , Griffiths Lyn R.
Published: February 2012

Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the methylenetetrahydrofolate reductase (MTHFR) gene and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the MTHFR gene in migraine and also discuss the use of a genetic isolate to investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of MTHFR in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.
Update on the Genetics of Migraine
Authors: Merikangas Kathleen Ries
Published: February 2012

Genetics and Headache: The Role of the MTHFR Gene in Migraine

Stuart S, Cox H, Lea R, Griffiths L.

Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the methylenetetrahydrofolate reductase gene (MTHFR) and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the MTHFR gene in migraine and also discuss the use of a genetic isolate to investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of MTHFR in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.
The Presence of p47phox in Liver Parenchymal Cells is a Key Mediator in the Pathogenesis of Alcoholic Liver Steatosis
Authors: Levin Ivan , Petrasek Jan , Szabo Gyongyi
Published: February 2012

Background

Reactive oxygen species contribute to steatosis and inflammation in alcoholic liver disease (ALD). Here, we evaluated the selective contribution of p47phox, a critical subunit of nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase complex, in liver parenchymal cells and in bone marrow (BM)‐derived cells.

Methods

Female C57Bl/6 wild type [WT], total body p47phox‐deficient knockout [KO] or p47phox chimera mice generated by BM transplantation of p47phox‐KO‐BM into irradiated WT mice (WT/p47phox‐KO‐BM mice) received 5% Lieber–DeCarli alcohol or control (pair feeding) diet for 4 weeks.

Results

Alcohol‐induced liver steatosis as measured by Oil Red O staining and serum triglyceride up‐regulation were prevented in p47phox‐KO mice but not in WT/p47phox‐KO‐BM chimeras compared to WT controls. Serum alanine aminotransferase (ALT) was significantly increased in alcohol‐fed WT mice but not in p47phox‐KO mice compared to pair‐fed controls. There was no protection from alcohol‐induced increase in ALT and liver damage in the WT/p47phox‐KO‐BM mice. Alcohol‐induced liver steatosis was accompanied by up‐regulation of the lipid droplet–stabilizing protein, adipocyte differentiation–related protein (ADRP), and the fatty acid synthesis–associated genes, fatty acid synthase (FASN) and acetyl‐CoA carboxylase (ACACA). Total body deficiency in p47phox but not selective absence of p47phox in BM‐derived cells prevented alcohol‐induced up‐regulation of ADRP, FASN, and ACACA in the liver. Finally, alcohol‐induced activation and DNA binding of nuclear factor κB (NF‐κB), a master regulator of inflammation, were significantly increased after alcohol feeding in WT but not in p47phox‐KO mice. Selective deficiency of p47phox in BM‐derived cells (WT/p47phox‐KO‐BM chimera) failed to prevent NF‐κB induction after alcohol feeding.

Conclusions

Total body deficiency in p47phox subunit of NADPH oxidase complex protects mice from alcohol‐induced liver steatosis via mechanisms involving ADRP, FASN, and ACACA as well as from alcohol‐induced NF‐κB activation. In contrast, selective absence of p47phox in BM‐derived cells fails to provide protection via these mechanisms. These results suggest that p47phox in parenchymal cells plays a critical role in the pathogenesis of ALD.
What Coy Smiles Say About Positive Shyness in Early Infancy
Authors: Colonnesi Cristina , Bögels Susan M. , de Vente Wieke , Majdandžić Mirjana
Published: February 2012

Positive shyness is a universal emotion with the specific social function of regulating our interactions by improving trust and liking, and showing politeness. The present study examined early infant production of coy smiles during social interactions as a measure of positive shy behavior. Eighty 4‐month‐olds were experimentally observed during three types of interactions in front of a mirror in which (1) the infant only sees him or herself, (2) the infant only sees the other person (mother, father, or stranger), and (3) the infant sees both him or herself and the other person. Infants produced more coy smiles during the interaction with a stranger than during the interactions with their mother or their father, or when they could see only themselves in front of a mirror. Infants also produced more coy smiles when they could see their self‐reflection during the interaction than when they could not. Our results support the assumption that coy smiles indicate an early emerging emotional reaction with an important adaptive function during social situations involving novel persons and when special attention is given to the child.
Intervention Technologies for Ensuring Microbiological Safety of Meat: Current and Future Trends
Authors: Chen J. H. , Ren Y. , Seow J. , Liu T. , Bang W. S. , Yuk H. G.
Published: February 2012

Abstract:  This article reviews current and future techniques that are applied in the meat industry to ensure product safety. Consumer demand for high‐quality food and raised economic standards have triggered the development of emergent technologies to replace traditional well‐established preservation processes. Some promising nonthermal and thermal technologies, such as chemical and biological interventions, high hydrostatic pressure (HHP), irradiation, active packaging, natural antimicrobials and microwave, radiofrequency, and steam pasteurization, are under consideration for the preservation of meat products. All these alternative technologies are designed to be mild, energy‐conserving, environmentally friendly, and maintaining natural appearance and flavor, while eliminating pathogens and spoilage microorganisms. Their combination, as in the hurdle theory, may improve their effectiveness for decontamination. The objective of this article is to reflect on the possibilities and especially the limitations of the previously mentioned technologies.
Bioactive Peptides: Synthesis, Properties, and Applications in the Packaging and Preservation of Food
Authors: Perez Espitia Paula Judith , de Fátima Ferreira Soares Nilda , dos Reis Coimbra Jane Sélia , de Andrade Nélio José , Souza Cruz Renato , Alves Medeiros Eber Antonio
Published: February 2012

Abstract:  Bioactive peptides are protein fragments which have a positive impact on the functions and conditions of living beings. Peptides have shown several useful properties for human health, including antimicrobial, antifungal, antiviral, and antitumor activities. These compounds are produced by almost all species of life. However, they are produced in limited quantities in nature. As a result, researchers have tried to synthesize bioactive peptides to study their properties and applications in various areas. Among their applications in food preservation, peptides have been incorporated into packaging materials. This review begins with a brief description of the methods used for the synthesis, purification, and characterization of peptides. Also, the main bioproperties and mechanisms of action of peptides are discussed. Finally, some applications of peptides are presented, especially their use in active packaging, their effects on the polymeric matrix, and peptide migration.
Phenomenology, Psychoanalysis, and Subjectivity in Java
Authors: Good Byron J.
Published: February 2012

This essay outlines the evolution of my personal thinking about phenomenology and subjectivity. In previous work, I drew heavily on cultural phenomenology for studying illness, subjective experience, and medical knowledge across cultures. Here I describe why I have become increasingly dissatisfied with this framework for understanding subjectivity and the subject and suggest alternatives I consider important for psychological anthropology. I focus in particular on questions of how to investigate that which is largely unspeakable and unspoken in everyday speech but at times erupts into awareness as complex specters haunting the present. I provide a case from my ongoing research in Java of a young man who suffered an acute psychosis, drawing implications for a theory of subjectivity and methods for psychological anthropology. I point briefly to the relation of madness and memories of political violence as sites for investigating subjectivity, suggesting the importance of a “hauntology” for psychological anthropology. Finally, I address questions about whether a method that addresses hidden aspects of psychological experience requires a stance in which ethnographers “know better than” those with whom they are interacting. [subjectivity, phenomenology, psychoanalysis, hauntology]