bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen receptor alpha is required in GABAergic, but not glutamatergic, neurons to masculinize the brain
Authors: Wu Melody V. , Tollkuhn Jessica 
Published: March 2017

AbstractMasculinization of the rodent brain is driven by estrogen signaling during a perinatal critical period. Genetic deletion of estrogen receptor alpha (Esr1/ERα) results in altered hypothalamic-pituitary-gonadal (HPG) axis signaling and a dramatic reduction of male sexual and territorial behaviors. However, the requirement of ERα function in masculinizing distinct classes of neurons, and if these populations mediate components of male-typical behavior, remains unexplored. We deleted ERα in excitatory or inhibitory neurons using either aVglut2orVgatdriver and assessed male behaviors. We find thatVglut2-Cre;Esr1lox/loxmutant males lack ERa in the ventrolateral region of the ventromedial hypothalamus (VMHvl) and posterior ventral portion of the medial amygdala (MePV). These mutants recapitulate the increased serum testosterone levels seen with constitutive ERα deletion, but have none of the behavioral deficits. In contrast,Vgat-Cre;Esr1lox/loxmales with substantial ERα deletion in inhibitory neurons, including those of the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr), posterior dorsal MeA (MePD), and medial preoptic area (MPOA) have normal testosterone levels, but display alterations in mating and territorial behaviors. These mutants also show demasculinized expression of androgen receptor (AR) and estrogen receptor beta (Esr2). Our results demonstrate that ERα masculinizes GABAergic neurons that gate the display of male-typical behaviors.
Consumer characteristics as drivers of online information searches
Authors: Gallant Isabelle , Arcand Manon 
Published: March 2017

Purpose
The purpose of this study is to investigate consumer characteristics (gender, subjective knowledge of product category, susceptibility to social influence, attitude to internet shopping and internet use) having a bearing on the proportion of online information searches conducted using personal and impersonal information sources, and to explore which of these factors impact the use of electronic word-of-mouth (eWOM).

Design/methodology/approach
A real-time longitudinal design is used to survey 274 consumers about their information searches when shopping for high involvement goods.

Findings
Susceptibility to normative social influence and internet use prove the main drivers of the inclination to resort to the internet to conduct searches using personal information sources. Subjective knowledge also positively impacts the proportion of time spent online conducting searches using personal information sources. Men and consumers with a positive attitude to internet shopping use a greater proportion of impersonal online information sources. Complementary analyses show that the use of eWOM is driven by almost all consumer characteristics (except gender) investigated.

Originality/value
By using a real-time longitudinal approach, this study directly addresses calls for more research into information searches by investigating multi-channel source use in actual purchase situations and minimizing bias relating to forgotten information, while facilitating the collection of more valid data on consumer information search behaviour. The paper also ranks as one of the first to revisit the drivers of the proportion of online information sources in personal and impersonal sources in the era of Web 2.0.
Metformin attenuates renal fibrosis in both AMPKα2‐dependent and independent manners
Authors: Feng Yenan , Wang Shuaixing , Zhang Youyi , Xiao Han 
Published: March 2017

SummaryMetformin is a well‐known AMP‐activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild‐type (WT) and AMPKα2 knockout (AMPKα2−/−) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO. In WT mice, metformin significantly inhibited UUO‐induced renal fibrosis. In AMPKα2−/− mice, metformin also tended to inhibit UUO‐induced renal fibrosis. Specifically, metformin significantly reduced UUO‐induced transforming growth factor β1 (TGFβ1) mRNA and protein expression in WT mice but not in AMPKα2−/− mice. In contrast, metformin reduced UUO‐induced TGFβ1 downstream Smad3 phosphorylation in both WT and AMPKα2−/− mice, suggesting that this regulation occurs in an AMPKα2‐independent manner. In conclusion, the underlying mechanisms for the protective effects of metformin against renal fibrosis include AMPKα2‐dependent targeting of TGFβ1 production and AMPKα2‐independent targeting of TGFβ1 downstream signalling. In this regard, metformin has an advantage over other AMPK activators for the treatment of renal fibrosis.
An indirect legitimacy argument for a directly elected European Parliament
Authors: LORD CHRISTOPHER 
Published: March 2017

AbstractCan a directly elected European Parliament help deliver standards by which the European Union can be indirectly legitimated through its component national democracies? This article argues that the Union can be indirectly legitimate where it helps member state democracies meet their own obligations to their own publics. The Union can do just that by managing externalities in ways needed to secure core values of justice, democracy and freedom from arbitrary domination within member states. Yet that poses a predicament: for if any one member state has an interest in imposing negative externalities or in freeriding on positive externalities provided by another, then so may its voters and democratic institutions. The article argues a directly elected European Parliament can help manage that predicament both by identifying externalities and by ensuring their regulation meets standards of public control, political equality and justification owed to individual national democracies.
Correlation between Antimicrobial, Antioxidant Activity, and Polyphenols of Alkalized/Nonalkalized Cocoa Powders
Authors: Todorovic Vanja , Milenkovic Marina , Vidovic Bojana , Todorovic Zoran , Sobajic Sladjana 
Published: March 2017

AbstractMany factors can influence antioxidative and antimicrobial characteristics of plant materials. The quality of cocoa as functional food ingredient is influenced through its processing. The main aim of this study was to test if there is difference in polyphenol content, antioxidant capacity, and antimicrobial activity between nonalkalized and alkalized cocoa powders. To estimate polyphenol and flavonoid content in cocoa samples the spectrophotometric microassays were used. Flavan‐3ols were determined with reversed‐phase high‐performance liquid chromatography (RP‐HPLC). Antimicrobial activity against 3 Gram positive bacteria, 4 Gram negative bacteria and 1 strain of yeast was determined using broth microdilution method. Total polyphenol content was 1.8 times lower in alkalized cocoa samples than in natural ones. Epicatechin/catechin ratio was changed due to the process of alkalization in favor of catechin (2.21 in natural and 1.45 in alkalized cocoa powders). Combined results of 3 antioxidative tests (DPPH, FRAP, ABTS) were used for calculation of RACI (Relative Antioxidant Capacity Index) and GAS (Global Antioxidant Score) values that were consistently higher in natural than in alkalized cocoa extracts. Obtained results have shown significant correlations between these values and phenolic content (0.929 ≤ r ≤ 0.957, P < 0.01). Antimicrobial activity varied from 5.0 to 25.0 mg/ml (MICs), while Candida albicans was the most sensitive tested microorganism. Cocoa powders subjected to alkalization had significantly reduced content of total and specific phenolic compounds and reduced antioxidant capacity (P < 0.05), but their antimicrobial activity was equal for Gram‐positive bacteria or even significantly enhanced for Gram‐negative bacteria.
In Vitro Starch Digestibility of Commercial Gluten‐Free Pasta: The Role of Ingredients and Origin
Authors: Marti Alessandra , Abbasi Parizad Parisa , Marengo Mauro , Erba Daniela , Pagani Maria Ambrogina , Casiraghi Maria Cristina 
Published: March 2017

AbstractGluten replacement in gluten‐free (GF) products presents major challenges for the food industry in terms of sensorial, technological and nutritional characteristics. The absence of gluten reportedly affects starch digestibility, thus increasing the postprandial glycaemic response. However, the role of ingredients and processing conditions has been addressed only seldom. We investigated the in vitro starch digestibility of 9 commercial GF products (5 Italian pasta and 4 Oriental noodles) differing in formulation and processing conditions. Content of rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) were assessed and combined with information on starch pasting properties and on the overall protein organization. Oriental noodles presented higher relative levels of RS and RDS than Western‐style pasta, that often had SDS levels compatible with low rates of starch digestion. As regard formulation, presence of multiple ingredients seems to likely increase the RDS level, as did the different protein organization in the various samples.
Affect lability predicts occurrence of suicidal ideation in bipolar patients: a two‐year prospective study
Authors: Ducasse D. , Jaussent I. , Guillaume S. , Azorin J. M. , Bellivier F. , Belzeaux R. , Bougerol T. , Etain B. , Gard S. , Henry C. , Kahn J. P. , Leboyer M. , Loftus J. , Passerieux C. ,   FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE‐BD) Collaborators, Olié E. , Courtet P. 
Published: March 2017

ObjectiveThe aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2‐year follow‐up, and which subtype of affect lability was associated with suicidal ideation.MethodA total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2‐year follow‐up. Affect lability was assessed by the French version of the Affect Lability Scale.ResultsBipolar patients with high affect lability were more likely to report suicidal ideation during follow‐up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15–5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation.ConclusionReducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.
No cognitive‐enhancing effect of GLP‐1 receptor agonism in antipsychotic‐treated, obese patients with schizophrenia
Authors: Ishøy P. L. , Fagerlund B. , Broberg B. V. , Bak N. , Knop F. K. , Glenthøj B. Y. , Ebdrup B. H. 
Published: March 2017

ObjectiveSchizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive‐enhancing effects. In this investigator‐initiated, double‐blind, randomized, placebo‐controlled trial, we tested non‐metabolic effects of exenatide once‐weekly (Bydureon™) in obese, antipsychotic‐treated patients with schizohrenia spectrum disorder.MethodBefore and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey–Osterreith complex figure test (REY), Short‐Form Health Survey (SF‐36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS). We used BACS composite score as the main outcome measure.ResultsRepeated measures analysis of variance on BACS composite score showed significant effect of ‘Time’ (P < 0.001), no effect of ‘Group’ (P = 0.64) and no ‘Time*Group’ interaction (P = 0.77). For REY, SF‐36, PSP and PANSS, only significant ‘Time’ effects were found.ConclusionThe non‐significant results of this first clinical trial exploring non‐metabolic effects of a long‐acting GLP‐1RA in patients with schizophrenia could reflect a general problem of translating cognitive‐enhancing effects of GLP‐1RAs from animals to humans or be explained by factors specifically related to schizophrenia spectrum patients with obesity such as antipsychotic treatment.
Clinical high risk for psychosis: the association between momentary stress, affective and psychotic symptoms
Authors: van der Steen Y. , Gimpel‐Drees J. , Lataster T. , Viechtbauer W. , Simons C. J. P. , Lardinois M. , Michel T. M. , Janssen B. , Bechdolf A. , Wagner M. , Myin‐Germeys I. 
Published: March 2017

ObjectiveThe aim of this study was to assess associations between momentary stress and both affective and psychotic symptoms in everyday life of individuals at clinical high risk (CHR), compared to chronic psychotic patients and healthy controls, in search for evidence of early stress sensitization. It also assessed whether psychotic experiences were experienced as stressful.MethodThe experience sampling method was used to measure affective and psychotic reactivity to everyday stressful activities, events and social situations in 22 CHR patients, 24 patients with a psychotic disorder and 26 healthy controls.ResultsMultilevel models showed significantly larger associations between negative affect (NA) and activity‐related stress for CHR patients than for psychotic patients (P = 0.008) and for CHR compared to controls (P < 0.001). Similarly, the association between activity‐related stress and psychotic symptoms was larger in CHR than in patients (P = 0.02). Finally, the association between NA and symptoms (P < 0.001) was larger in CHR than in patients.ConclusionStress sensitization seems to play a role particularly in the early phase of psychosis development as results suggest that CHR patients are more sensitive to daily life stressors than psychotic patients. In this early phase, psychotic experiences also contributed to the experience of stress.
Questionable diagnostic benefit of the commercially available panel of bee venom components
Authors: Arzt L. , Bokanovic D. , Schrautzer C. , Schwarz I. , Laipold K. , Aberer W. , Sturm G. J. 
Published: March 2017

AbstractFor many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV‐allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double‐sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross‐reacting allergens.
Sevoflurane‐induced isoelectricEEGand burst suppression: differential and antagonistic effect of added nitrous oxide
Authors: Niu B. , Xiao J. Y. , Fang Y. , Zhou B. Y. , Li J. , Cao F. , Tian Y. K. , Mei W. 
Published: March 2017

SummaryThe objective of this study was to investigate whether nitrous oxide influenced theED50 of sevoflurane for induction of isoelectric electroencephalogram (ED50isoelectric) differently from its influence on theED50 of sevoflurane for electroencephalogram burst suppression (ED50burst). In a prospective, randomised, double‐blind, parallel group, up–down sequential allocation study, 77ASAphysical status 1 and 2 patients received sevoflurane induction and, after tracheal intubation, were randomly allocated to receive sevoflurane with either 40% oxygen in air (control group) or 60% nitrous oxide in oxygen mixture (nitrous group). TheED50isoelectricin the two groups was determined using Dixon's up and down method, starting at 2.5% with 0.2% step size of end‐tidal sevoflurane. The electroencephalogram was considered as isoelectric when a burst suppression ratio of 100% lasted > 1 min. The subsequent concentrations of sevoflurane administered were determined by the presence or absence of isoelectric electroencephalogram in the previous patient in the same group. TheED50isoelectricin the nitrous group 4.08 (95%CI, 3.95–4.38)% was significantly higher than that in the control group 3.68 (95%CI, 3.50–3.78)% (p < 0.0001). The values forED50burstwere 3.05 (95%CI, 2.66–3.90)% and 3.02 (95%CI, 3.00–3.05)% in nitrous group and control group, respectively (p = 0.52). The addition of 60% nitrous oxide increasesED50isoelectric, but not theED50burstof sevoflurane. Neither result indicates an additive effect of anaesthetic agents, as might be expected, and possible reasons for this are discussed.
Plasma long‐chain omega‐3 polyunsaturated fatty acids and macular pigment in subjects with family history of age‐related macular degeneration: the Limpia Study
Authors: Merle Bénédicte M. J. , Buaud Benjamin , Korobelnik Jean‐François , Bron Alain , Delyfer Marie‐Noëlle , Rougier Marie‐Bénédicte , Savel Hélène , Vaysse Carole , Creuzot‐Garcher Catherine , Delcourt Cécile 
Published: March 2017

AbstractPurposeIn numerous epidemiological studies, omega‐3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age‐related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega‐3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega‐3 PUFAs in subjects with family history of AMD.MethodsThe Limpia study is a double‐blind, placebo‐controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40–70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega‐3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega‐3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high‐density lipoprotein (HDL) cholesterol and lutein+zeaxanthin.ResultsAfter multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD.ConclusionIn the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega‐3 DPA.
Transformation of hepatitis C antiviral treatment in a national healthcare system following the introduction of direct antiviral agents
Authors: Moon A. M. , Green P. K. , Berry K. , Ioannou G. N. 
Published: March 2017

SummaryBackgroundHighly effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were introduced recently. Their utilisation has been limited by high cost and low access to care.AimTo describe the effect of DAAs on HCV treatment and cure rates in the United States Veterans Affairs (VA) national healthcare system.MethodsWe identified all HCV antiviral treatment regimens initiated from 1 January 1999 to 31 December 2015 (n = 105 369) in the VA national healthcare system, and determined if they resulted in sustained virological response (SVR).ResultsHCV antiviral treatment rates were low (1981–6679 treatments/year) in the interferon era (1999–2010). The introduction of simeprevir and sofosbuvir in 2013 and ledipasvir/sofosbuvir and paritaprevir/ombitasvir/ritonavir/dasabuvir in 2014 were followed by increases in annual treatment rates to 9180 in 2014 and 31 028 in 2015. The number of patients achieving SVR was 1313 in 2010, the last year of the interferon era, and increased 5.6‐fold to 7377 in 2014 and 21‐fold to 28 084 in 2015. The proportion of treated patients who achieved SVR increased from 19.2% in 1999 and 36.0% in 2010 to 90.5% in 2015. Within 2015, monthly treatment rates ranged from 727 in July to 6868 in September correlating with the availability of funds for DAAs.ConclusionsDAAs resulted in a 21‐fold increase in the number of patients achieving HCV cure. Treatment rates in 2015 were limited primarily by the availability of funds. Further increases in funding and cost reductions of DAAs in 2016 suggest that the VA could cure the majority of HCV‐infected Veterans in VA care within the next few years.
Associations of CYP2C9 and CYP2A6 Polymorphisms with the Concentrations of Valproate and its Hepatotoxin Metabolites and Valproate‐Induced Hepatotoxicity
Authors: Zhao Mingming , Zhang Ti , Li Guofei , Qiu Feng , Sun Yaxin , Zhao Limei 
Published: March 2017

AbstractThe aim of this study was to compare genetic polymorphisms and concentrations of hepatotoxic metabolites in patients with epilepsy and liver injury and those with normal liver function receiving valproate monotherapy to identify risk factors for VPA‐induced hepatotoxicity. A total of 279 Chinese patients with epilepsy were divided into an abnormal liver function (ANLFT) group (n = 79) and a normal liver function (NLFT) group (n = 200). Polymerase chain reaction–restriction fragment length polymorphism PCR‐RFLP and nested PCR were applied to identify the frequency of two SNPs in candidate genes. Serum concentrations of VPA and its major metabolites were determined by Ultra‐Performance Liquid Chromatography–tandem mass spectrometry UPLC‐MS/MS. Significant differences were found in genotype distributions of CYP2A6 and CYP2C9 between the two groups. The values of 4‐ene‐VPA and 2,4‐diene‐VPA in the ANLFT group were significantly higher than in the NLFT group. Only CYP2A6 polymorphisms had associations with the concentrations of 4‐ene‐VPA and 2,4‐diene‐VPA. CYP2A6*1/*4 and CYP2A6*4/*4 variant carriers had higher CDR4‐ene‐VPA and CDR2,4‐diene‐VPA values than CYP2A6*1/*1 carriers. The logistic regression analysis showed that CYP2C9 and CYP2A6 were significant risk factors for hepatotoxicity by increasing the risk by 7.50 and 5.13 times, respectively. These findings provide preliminary evidence that CYP2A6 and CYP2C9 are associated with hepatotoxicity. However, only the CYP2A6 polymorphism was found to be associated with concentrations of 4‐ene‐VPA and 2,4‐diene‐VPA. Potential important risk factors include mutated genotypes of CYP2C9 and CYP2A6 and higher concentrations of VPA, 4‐ene‐VPA and 2,4‐diene‐VPA.