bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of SLC6A12 variants with aspirin‐intolerant asthma in a Korean population
Authors: Pasaje Charisse Flerida A. , Kim Jeong‐Hyun , Park Byung‐Lae , Cheong Hyun Sub , Chun Ji‐Yong , Park Tae‐Joon , Lee Jin‐Sol , Kim Yongha , Bae Joon Seol , Park Jong Sook , Yoon Sang‐Hyuk , Uh Soo‐Taek , Choi Jae‐Sung , Kim Yong‐Hoon , Kim Mi‐Kyeong , Choi Inseon S. , Cho Sang Heon , Choi Byoung Whui , Park Choon‐Sik , Shin Hyoung Doo 
Published: June 2010

SummaryAspirin‐intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin‐intolerant asthma (AIA) and 429 aspirin‐tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P= 0.005; Pcorr= 0.03), rs557881 (non‐synonymous C10R, P= 0.007; Pcorr= 0.04), and SLC6A12_BL1_ht1 (P= 0.009; Pcorr= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV1 by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.
Elucidation of CYP2D6 Genetic Diversity in a Unique African Population: Implications for the Future Application of Pharmacogenetics in the Xhosa Population
Authors: Wright Galen E. B. , Niehaus Dana J. H. , Drögemöller Britt I. , Koen Liezl , Gaedigk Andrea , Warnich Louise 
Published: June 2010

SummaryGenetic variation of the CYP2D6 gene has been associated with altered drug metabolism; however, limited studies have investigated CYP2D6 sequence diversity in African populations. We devised a CYP2D6 genotyping strategy to analyse the South African Xhosa population and genotype a Xhosa schizophrenia cohort, as CYP2D6 metabolises many antipsychotics and antidepressants.The entire CYP2D6 gene locus was sequenced in 15 Xhosa control individuals and the data generated were used to design a comprehensive genotyping strategy. Over 25 CYP2D6 alleles were genotyped in Xhosa controls and Xhosa schizophrenia patients using long‐range PCR, DNA sequencing and single nucleotide primer extension analysis. Bioinformatic algorithms were used to predict the functional consequences of relevant mutations and samples were assigned CYP2D6 activity scores.A unique allele distribution was revealed and two rare novel alleles, CYP2D6*73 and CYP2D6*74, were identified. No significant differences in allele frequencies were detected between Xhosa controls and schizophrenia patients. This study provides i) comprehensive data on a poorly characterised population, ii) a valuable CYP2D6 genotyping strategy and iii) due to their unique genetic profile, provides the basis for pharmacogenetic intervention for Xhosa individuals.
Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes
Authors: Fernandes Samantha P. , Dringen Ralf , Lawen Alfons , Robinson Stephen R. 
Published: June 2010

J. Neurochem. (2010) 114, 1527–1536.AbstractGlutamine synthetase (GS) forms glutamine by catalyzing the ATP‐dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer’s disease and cell culture, GS has been detected in neurones. The present study demonstrates the expression of functional GS in cultured cerebellar granule cells and investigates conditions required to reduce this expression. Cerebellar granule cells from neonatal rats were grown in the absence of glutamine. Immunostaining revealed that the majority of neurones contained GS in their somata and dendrites. Treatment of neuronal cultures with glutamine greatly reduced the enzymatic activity of GS and also reduced the intensity of GS immunolabelling in dendrites. GS activity was reduced by 32% in neurones that had been transiently co‐cultured with astrocytes, wherreas GS immunoreactivity was largely abolished from neurones that had been directly seeded onto astrocytic monolayers. These results imply that GS expression in neurones occurs in response to a reduced availability of glutamine from astrocytes, and that neuronal GS expression represents a default phenotype which is normally suppressed via direct contacts with astrocytes. The aberrant expression of GS in sporadic neurones in Alzheimer’s disease may indicate an impairment of such interactions.
Comparative pharmacology of chemically distinct NADPH oxidase inhibitors
Authors: Wind S , Beuerlein K , Eucker T , Müller H , Scheurer P , Armitage ME , Ho H , Schmidt HHHW , Wingler K 
Published: June 2010

BACKGROUND AND PURPOSE Oxidative stress [i.e. increased levels of reactive oxygen species (ROS)] has been suggested as a pathomechanism of different diseases, although the disease‐relevant sources of ROS remain to be identified. One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re‐interpreted.EXPERIMENTAL APPROACH We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4‐(2‐amino‐ethyl)‐benzolsulphonyl‐fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947. We used several assays for detecting cellular and tissue ROS, as none of them is specific and artefact free.KEY RESULTS DPI abolished NADPH oxidase‐mediated ROS formation, but also inhibited other flavo‐enzymes such as NO synthase (NOS) and xanthine oxidase (XOD). Apocynin interfered with ROS detection and varied considerably in efficacy and potency, as did AEBSF. Conversely, the novel NADPH oxidase inhibitor, VAS3947, consistently inhibited NADPH oxidase activity in low micromolar concentrations, and interfered neither with ROS detection nor with XOD or eNOS activities. VAS3947 attenuated ROS formation in aortas of spontaneously hypertensive rats (SHRs), where NOS or XOD inhibitors were without effect.CONCLUSIONS AND IMPLICATIONS Our data suggest that triazolo pyrimidines such as VAS3947 are specific NADPH oxidase inhibitors, while DPI and apocynin can no longer be recommended. Based on the effects of VAS3947, NADPH oxidases appear to be a major source of ROS in aortas of SHRs.
The roles and mechanisms of PAR4 and P2Y12/phosphatidylinositol 3‐kinase pathway in maintaining thrombin‐induced platelet aggregation
Authors: Wu Chin‐Chung , Wu Shih‐Yun , Liao Chieh‐Yu , Teng Che‐Ming , Wu Yang‐Chang , Kuo Sheng‐Chu 
Published: June 2010

BACKGROUND AND PURPOSE Activation of human platelets by thrombin is mediated predominately through two proteinase‐activated receptors (PARs), PAR1 and PAR4. Phosphatidylinositol 3‐kinase (PI3K) inhibition leads to reversible PAR1‐mediated platelet aggregation, but has no effect on the stability of platelet aggregation induced by thrombin. In the present study, the molecular mechanisms underlying this difference were investigated.EXPERIMENTAL APPROACH The functions of PI3K and PAR4 were assessed using specific inhibitors and aggregometry. The duration of platelet glycoprotein (GP) IIb/IIIa exposure was determined by flow cytometry with the antibody PAC‐1. Western blotting and fluo‐3 was used to evaluate the activation of Akt and protein kinase C (PKC) and intracellular Ca2+ mobilization respectively.KEY RESULTS When PAR4 function was inhibited either by the PAR4 antagonist YD‐3 [1‐benzyl‐3‐(ethoxycarbonylphenyl)‐indazole] or by receptor desensitization, the PI3K inhibitor wortmannin turned thrombin‐elicited platelet aggregation from an irreversible event to a reversible event. Moreover, wortmannin plus YD‐3 markedly accelerated the inactivation of GPIIb/IIIa in thrombin‐stimulated platelets. The aggregation‐reversing activity mainly resulted from inhibition of both PI3K‐dependent PKC activation and PAR4‐mediated sustained intracellular Ca2+ rises. Blockade of ADP P2Y12 receptor with 2‐methylthioadenosine 5′‐monophosphate triethylammonium salt mimicked the inhibitory effect of wortmannin on PI3K‐dependent PKC activation and its ability to reverse PAR1‐activating peptide‐induced platelet aggregation. Co‐administration of 2‐methylthioadenosine 5′‐monophosphate triethylammonium salt with YD‐3 also decreased the stability of thrombin‐induced platelet aggregation.CONCLUSIONS AND IMPLICATIONS These results suggest that PAR4 acts in parallel with the P2Y12/PI3K pathway to stabilize platelet aggregates, and provide new insights into the mechanisms of thrombus stabilization and potential applications for antithrombotic therapy.
Differential Effect of Biventricular and Right Ventricular DDD Pacing on Coronary Flow Reserve in Patients With Ischemic Cardiomyopathy
Authors: DEFTEREOS SPYRIDON , GIANNOPOULOS GEORGIOS , KOSSYVAKIS CHARALAMPOS , RAISAKIS KONSTANTINOS , KAOUKIS ANDREAS , DRIVA METAXIA , PANAGOPOULOU VASILIKI , NTZOUVARA OLGA , THEODORAKIS ANDREAS , TOUTOUZAS KONSTANTINOS , PYRGAKIS VLASIOS , STEFANADIS CHRISTODOULOS 
Published: June 2010

CRT and Coronary Flow Reserve. Background: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy. Methods and Results: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non‐responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07–0.23, P = 0.001). When comparing responders to non‐responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13–0.39; P = 0.002), while in non‐responders the difference was 0.04 ± 0.03 (95% confidence interval −0.02 to 0.10; P = 0.168). Conclusion: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT‐responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1233‐1239, November 2010)
Recurrent Pregnancy Loss and Apolipoprotein E Gene Polymorphisms: A Case–Control Study from North India
Authors: Agarwal Meenal , Parveen Farah , Faridi Rehan Mujeeb , Phadke Shubha R. , Das Vinita , Agrawal Suraksha 
Published: June 2010

Citation Agarwal M, Parveen F, Faridi RM, Phadke SR, Das V, Agrawal S. Recurrent pregnancy loss and apolipoprotein E gene polymorphisms: a case–control study from North India. Am J Reprod Immunol 2010; 64: 172–178Problem  The role of apolipoprotein E gene polymorphisms in the etiology of recurrent pregnancy loss (RPL) is not clearly understood. We evaluated this polymorphism in unexplained pregnancy losses among North Indian women.Method of study  In a retrospective case–control study, 200 well‐characterized RPL cases were examined for their APO‐E genotypes based on restriction fragment length polymorphism analysis of PCR‐amplified fragments including amino acid positions 112 and 158. The observed genotypes were compared with those obtained from an equal number of ethnically matched negative controls.Results  We found similar APO‐E genotypes and E2, E3, and E4 allele frequency distribution among RPL patients and controls. The allele frequencies obtained in patients and controls respectively were as follows: E2 = 7.5% and 9.0% (P = 0.52; OR = 0.81; 95%CI = 0.49–1.35), E3 = 89.7% and 90% (P = 1.00; OR = 0.97; 95%CI = 0.61–1.54), and E4 = 2.8% and 1% (P = 0.12; OR = 2.79; 95%CI = 0.88–8.86).Conclusions  Our data did not support the association of APO‐E gene polymorphisms with recurrent pregnancy loss as reported by some of the previous studies. We endorse adequate characterization of RPL cases, inclusion of appropriate negative controls, and adequate sample size prior to addressing such studies.
Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis
Authors: Ohlin Andreas , Björkqvist Maria , Montgomery Scott M , Schollin Jens 
Published: June 2010

AbstractAim:  To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age.Methods:  Among 401 newborn infants <28 days of age with suspected sepsis, nine signs of sepsis and C‐reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex.Results:  Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures.Conclusion:  In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.
Sexual Desire and the Female Sexual Function Index (FSFI): A Sexual Desire Cutpoint for Clinical Interpretation of the FSFI in Women with and without Hypoactive Sexual Desire Disorder
Authors: Gerstenberger Eric P. , Rosen Raymond C. , Brewer Jessica V. , Meston Cindy M. , Brotto Lori A. , Wiegel Markus , Sand Michael 
Published: June 2010

ABSTRACT

Introduction
A validated cutpoint for the total Female Sexual Function Index scale score exists to classify women with and without sexual dysfunction. However, there is no sexual desire (SD) domain-specific cutpoint for assessing the presence of diminished desire in women with or without a sexual desire problem.

Aims
This article defines and validates a specific cutpoint on the SD domain for differentiating women with and without hypoactive sexual desire disorder (HSDD).

Methods
Eight datasets (618 women) were included in the development dataset. Four independent datasets (892 women) were used in the validation portion of the study.

Main Outcome Measures
Diagnosis of HSDD was clinician-derived. Receiver-operator characteristic (ROC) curves were used to develop the cutpoint, which was confirmed in the validation dataset.

Results
The use of a diagnostic cutpoint for classifying women with SD scores of 5 or less on the SD domain as having HSDD and those with SD scores of 6 or more as not having HSDD maximized diagnostic sensitivity and specificity. In the development sample, the sensitivity and specificity for predicting HSDD (with or without other conditions) were 75% and 84%, respectively, and the corresponding sensitivity and specificity in the validation sample were 92% and 89%, respectively.

Conclusions
These analyses support the diagnostic accuracy of the SD domain for use in future observational studies and clinical trials of HSDD.
Characteristics of Vibrator Use by Gay and Bisexually Identified Men in the United States
Authors: Reece Michael , Rosenberger Joshua G. , Schick Vanessa , Herbenick Debby , Dodge Brian , Novak David S. 
Published: June 2010

ABSTRACT

Introduction
Recent reports indicate that vibrator use during solo and partnered sexual activities is common among heterosexual men and women in the United States. However, little research has comprehensively assessed vibrator use among gay and bisexually identified men.

Aims
This study sought to document the extent to which gay and bisexually identified men report using vibrators, the sexual and relational situations within which they use them, and how men use vibrators on their own and their partners’ bodies.

Methods
Data were collected from 25,294 gay and bisexually identified men from 50 U.S. states and from the District of Columbia via an internet-based survey.

Main Outcome Measure
Measures included sociodemographics, health-related indicators, sexual behaviors, and those related to recent and past use of vibrators during solo and partnered sexual interactions with other men.

Results
Approximately half (49.8%) of gay and bisexually identified men reported having used vibrators. Most men who had used a vibrator in the past reported use during masturbation (86.2%). When used during partnered interactions, vibrators were incorporated into foreplay (65.9%) and intercourse (59.4%). Men reported frequent insertion of vibrators into the anus or rectum when using them during masturbation (87.3%), which was also common during partnered interactions (~60%), but varied slightly for casual and relationship sex partners. For both masturbation and partnered interactions, men overwhelmingly endorsed the extent to which vibrator use contributed to sexual arousal, orgasm, and pleasure.

Conclusions
Vibrator use during both solo and partnered sexual acts was common among the gay and bisexually identified men in this sample and was described by men as adding to the quality of their sexual experiences.
Time course of vasovagal syncope with whole blood donation
Authors: Tomasulo P. , Bravo M. , Kamel H. 
Published: June 2010

Background  Improving the safety of the donation experience will reduce donor injuries and increase donations, donation frequency and donor satisfaction. Understanding the physiology of donor reactions supports selection of effective interventions to reduce risk.Aims  The examination of the time course of donor vasovagal syncopal reactions (VVS) to determine when most reactions occur supports the development of appropriate theories about cause of the majority of the reactions and the application of interventions to reduce the risk of a significant number of reactions.Materials and Methods  A database of more than 900 000 donor registrations and more than 500 000 whole blood donation events was examined for the time course of VVS reactions by reviewing the onset time of the reactions. The donor experience was divided into three periods based on the theory that the risk of reaction depends on different factors in each of the periods. The time course was analyzed using frequency distribution counts stratified by donation status and separately by gender.Results  There were 956 766 registrations, 554 513 attempted whole blood donations, 536 907 complete donations and 17 606 incomplete donations. The mean draw time of a complete donation was 8.21 (95% CI, 8.2–8.21) min and for an incomplete donation was 8.91 (95% CI, 8.8–9.01) min. The reaction rate for Period 1 (before venipuncture) was 0.045/1000 registrations; for Period 2 (venipuncture to 4 min post‐venipuncture) and Period 3 (4 min post venipuncture to last reported VVS reaction ‐265 min), the reaction rate was 3.5/1000 for women and 1.5/1000 for men. There was a steady increase in the reaction rate during phlebotomy and the rate peaked at the time of needle removal. After needle removal there were peaks in the VVS rate at 5 and 9 min. The reaction rate declined steadily thereafter.Discussion  The peak reaction rates occur within a time period of 10 min beginning 1 min before needle removal. The reactions which have the most significant risk of donor injury occur later than this and often occur after the donor leaves the donation site. Approximately 10% of VVS reactions in male donors and 25% of VVS reactions in female donors occur more than 15 min after the needle is removed. The latest VVS reaction was reported to have begun at about 4.5 h after needle withdrawal.Conclusion  It is our thought that preventive interventions for reactions which occur during phlebotomy might be slightly different from the preventive measure aimed at reducing risk to donors after assuming upright posture. Once the donor stands up, relative hypovolemia plays a greater role and interventions should be aimed at preventing changes in blood pressure due to hypovolemia during this period.