bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifetime alcohol use, abuse and dependence among university students in Lebanon: exploring the role of religiosity in different religious faiths
Authors: Ghandour Lilian A. , Karam Elie G. , Maalouf Wadih E. 
Published: May 2009

ABSTRACTAims  To examine alcohol consumption and the role of religiosity in alcohol use disorders in Christian, Druze and Muslim youth in Lebanon, given their distinct religious doctrines and social norms.Methods  Using a self‐completed anonymous questionnaire, data were collected on 1837 students, selected randomly from two large private universities in Beirut. Life‐time abuse and dependence were measured as per the Diagnostic and Statistical Manual version IV.Findings  Alcohol use was more common in Christians, who started drinking younger and were twice as likely to be diagnosed with abuse and dependence. However, among ever drinkers, the odds of alcohol use disorders were comparable across religious groups. Believing in God and practising one's faith were related inversely to alcohol abuse and dependence in all religious groups, even among ever drinkers (belief in God only). The associations were sometimes stronger for Muslims, suggesting that religiosity may play a larger role in a more proscriptive religion, as postulated by‘reference group theory’.Conclusions  Students belonging to conservative religious groups may be shielded from the opportunity to try alcohol. Once an ever drinker, however, religion is not related to the odds of an alcohol use disorder. Religiosity (i.e. belief in God and religious practice) is, nevertheless, related inversely to alcohol‐related problems, even among drinkers. Findings from this culturally and religiously diverse Arab country corroborate the international literature on religion, religiosity and alcohol use, highlighting potential differences between Christians and Muslims.
A cohort study to examine whether time and risk preference is related to smoking cessation success
Authors: Goto Rei , Takahashi Yuko , Nishimura Shuzo , Ida Takanori 
Published: May 2009

ABSTRACTAim  To identify whether time and risk preference predicts relapse among smokers trying to quit.Design  A cohort study of smokers who had recently started to quit. Time and risk preference parameters were estimated using a discrete choice experiment (DCE).Participants  A total of 689 smokers who began quitting smoking within the previous month.Measurements  Time discount rate, coefficient of risk‐aversion measured at study entry and duration of smoking cessation measured for 6 months.Findings  In the unadjusted model, Cox's proportional hazard regression showed that those with a high time discount rate were more likely to relapse [hazard ratio: 1.18, 95% confidence interval (CI): 1.11–1.25]. A high coefficient of risk‐aversion reduced the hazard of relapse (0.96, 0.96–0.97). When adjusted for other predictors of relapse (age, gender, self‐efficacy of quitting, health status, mood variation, past quitting experience, the use of nicotine replacement therapy, nicotine dependence), the hazard ratios of time discount rate and the coefficient of risk‐aversion is 1.17 (95% CI: 1.10–1.24) and 0.98 (95% CI: 0.97–0.99), respectively.Conclusions  Those who emphasize future rewards (time–patient preference) and those who give more importance to rewards that are certain (higher risk‐aversion) were significantly more likely to continue to abstain from smoking.
Recognition of Phytophthora infestans Avr4 by potato R4 is triggered by C‐terminal domains comprising W motifs
Authors: VAN POPPEL PIETER M. J. A. , JIANG RAYS H. Y. , ŚLIWKA JADWIGA , GOVERS FRANCINE 
Published: May 2009

SUMMARYOomycete RXLR‐dEER effector proteins are rapidly evolving proteins with the selective pressure targeted predominantly at their C‐terminal ends. The majority of RXLR‐dEER proteins have recognizable motifs of 21–30 amino acids in the C‐terminal domain that are named after conserved amino acid residues at fixed positions within the respective motifs. In this article, it is reported that the Phytophthora infestans RXLR‐dEER protein Avr4 contains three W motifs and one Y motif in its C‐terminal domain. Agroinfection assays using constructs encoding modified forms of PiAvr4 have shown that the region containing the W2 motif, in combination with either the W1 or W3 motif, triggers a necrotic response in potato plants carrying the resistance gene R4. By mining the superfamily of avirulence homologues (Avh) deduced from three sequenced Phytophthora genomes, several Avh proteins were identified as homologues of PiAvr4: six in P. infestans, one in P. ramorum and seven in P. sojae. One very close homologue of PiAvr4 was cloned from the sibling species, P. mirabilis. This species is not pathogenic on potato but, similar to PiAvr4, PmirAvh4 triggered a necrotic response on potato clones carrying R4, but not on clones lacking R4. Genes encoding RXLR‐dEER effectors are often located in regions showing genome rearrangements. Alignment of the genomic region harbouring PiAvr4 with syntenic regions in P. sojae and P. ramorum revealed that PiAvr4 is located on a 100‐kb indel block and is surrounded by transposable elements.
Specialty care and education associated with greater disease‐specific knowledge but not satisfaction with care for chronic hepatitis C
Authors: BESTE L. A. , STRAITS‐TROSTER K. , ZICKMUND S. , LARSON M. , CHAPKO M. , DOMINITZ J. A. 
Published: May 2009

SummaryBackground  Little is known about differences among hepatitis C virus (HCV) patients managed by generalists vs. specialists with respect to patient‐centred outcomes, such as disease‐specific knowledge, health‐related quality of life (HRQoL) and satisfaction with care.Aim  To examine selected patient‐centred outcomes of HCV‐related care provided in primary care, specialty care or both.Methods  A total of 629 chronic HCV patients completed a survey including an HCV knowledge assessment and validated instruments for satisfaction and HRQoL. Multivariable linear regression was used to compare outcomes between groups.Results  Adjusted total HCV knowledge score was lower among patients who did not attend specialty care (P < 0.01). Primary care and specialty patients did not differ in adjusted general HRQoL or satisfaction. Sixty percent of specialty patients underwent formal HCV education, which was associated with 5% higher knowledge score (P = 0.01). General HRQoL and patient satisfaction did not differ between primary care and specialty groups. Disease‐specific knowledge and care satisfaction were independent of mental illness, substance abuse, socio‐economic variables, history of antiviral treatment, formal HCV education and duration of time between last visit and survey completion.Conclusions  Primary care patients with chronic HCV have lower adjusted disease‐specific knowledge than specialty patients, but no difference in general HRQoL or patient satisfaction.
Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections
Authors: SCHNEEWEISS S. , KORZENIK J. , SOLOMON D. H. , CANNING C. , LEE J. , BRESSLER B. 
Published: May 2009

SummaryBackground There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD).Aim To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD.Methods We assembled a cohort study of patients with IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, includingClostridium difficile.Results Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person‐years (95% confidence interval 2.1–6.2) for other immunosuppressive agents to 7.4 (3.3–19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47–4.24).Clostridium difficileinfections occurred in 0/1000 (0–5.4) among 521 infliximab initiations and 14/1000 (10.6–18.2) for corticosteroids. Corticosteroid initiation tripled the risk ofC. difficileinfections (RR = 3.4; 1.9–6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose‐dependent nor duration‐dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events).Conclusions In a population‐based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk forC. difficileinfections in these patients.
Gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy
Authors: Luo Jiing‐Chyuan , Chang Full‐Young , Chen Tseng‐Shing , Ng Yee‐Yung , Lin Han‐Chieh , Lu Ching‐Liang , Chen Chih‐Yen , Lin Hsiao‐Yi , Lee Shou‐Dong 
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Whether glucocorticoids induce gastric mucosal injury remains uncertain, and Helicobacter pylori infection in steroid users has not been well evaluated in the past.• Pulse methylprednisolone therapy with the very high dose of steroid that is 100 times larger than the physiological dose will be a special model to evaluate whether glucocorticoids induce gastric mucosal injury. WHAT THIS STUDY ADDS • Use of nonsteroidal anti‐inflammatory drugs/aspirin, but not H. pylori infection, increases gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy.• Very high‐dose steroids de novo seem not to induce gastric mucosal injury in these patients.• However, a larger, case‐controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury.AIMSWhether glucocorticoids induce gastric mucosal injury remains uncertain. We investigated whether very high‐dose steroids caused gastric mucosal injury in systemic lupus erythematous (SLE) patients and evaluated the possible risk factors for mucosal injury.METHODSIn this prospective paired study, 67 SLE patients who had received pulse methylprednisolone therapy were enrolled. Each patient underwent endoscopic examination and tissue and blood sampling before and after pulse steroid therapy. Mucosal injury was diagnosed if the follow‐up injury scale was higher than the initial scale. Examined parameters included Helicobacter pylori infection, cyclooxygenase (COX)‐1 and COX‐2 activity, and current nonsteroidal anti‐inflammatory drug (NSAID) usage including aspirin.RESULTSEleven (16.4%) of 67 cases who developed gastric mucosal injury after pulse therapy had significantly higher rates of peptic ulcer history, NSAID/aspirin use, lower gastric thromboxane B2 and prostaglandin E2 levels when compared with cases without gastric mucosal injury (P < 0.05). Infection by H. pylori was not a risk factor for gastric mucosal injury. Multivariate logistic regression analysis showed that NSAID/aspirin use was the only risk factor for gastric mucosal injury in these patients (odds ratio 26.99, 95% confidence interval 4.91, 148.57, P < 0.0001). Pulse steroid therapy alone did not induce gastric mucosal injury in fifty SLE patients without taking any NSAID/aspirin.CONCLUSIONSUse of NSAIDs/aspirin, but not H. pylori infection, increases gastric mucosal injury in SLE patients receiving pulse methylprednisolone therapy. Very high‐dose steroids de novo seem not to induce gastric mucosal injury in these patients. A larger case‐controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury.
The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine
Authors: Gjerden Pål , Slørdal Lars , Bramness Jørgen G. 
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Extrapyramidal side‐effects induced by antipsychotic agents are treated with dose reduction, switching of antipsychotic medication or the addition of anticholinergic antiparkinson drugs. WHAT THIS STUDY ADDS • The use of anticholinergic antiparkinson drugs appears to be superfluous in a large number of patients.AIMSExtrapyramidal side‐effects induced by antipsychotic drugs are treated with dose reduction or substitution with another antipsychotic drug or by the addition of anticholinergic antiparkinson agents. The withdrawal of orphenadrine from the Norwegian market provided a possibility to investigate to what degree these alternative measures were taken in clinical practice.METHODSData were drawn from the Norwegian Prescription Database on the sales of antipsychotics and one of the two anticholinergic antiparkinson agents marketed in 2004, orphenadrine and biperiden, to a total of 39 758 outpatients. The patients were reinvestigated in 2007. The consequences of the withdrawal of orphenadrine from the Norwegian market in 2005 regarding dosing, switching and cessation of antipsychotics and use of anticholinergics were assessed for orphenadrine users compared with biperiden users.RESULTSOf the patients originally using orphenadrine, 28.4% stopped using the drug without reducing the antipsychotic dose or replacing orphenadrine with another anticholinergic agent. The corresponding number for biperiden users was 19.3%. Only 11.8% of patients switched to another antipsychotic drug, but they used significantly lower antipsychotic doses than those who stayed on the same drug.CONCLUSIONThe use of anticholinergic antiparkinson agents could be seen as superfluous for at least one‐third of patients.
Prospective observational study of adverse drug reactions to diclofenac in children
Authors: Standing Joseph F. , Ooi Kuan , Keady Simon , Howard Richard F. , Savage Imogen , Wong Ian C. K. 
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Diclofenac is frequently used off‐label in children for acute pain, but little information is available on diclofenac adverse drug reactions in this population. WHAT THIS STUDY ADDS • The common adverse drug reactions of diclofenac for acute pain in children are of a similar type to those seen in adults.• Serious adverse reactions occur in <0.8% of children and the incidence of diclofenac‐induced bronchospasm in asthmatic children is <2.7%.AIMThe aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain.METHODSA prospective observational study was undertaken on paediatric surgical patents aged ≤12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel.RESULTSChildren prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is <0.8%.CONCLUSIONChildren given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%.
Tolerability and safety of GS‐101 eye drops, an antisense oligonucleotide to insulin receptor substrate‐1: a ‘first in man’ Phase I investigation
Authors: Kain Hermann , Goldblum David , Geudelin Bernard , Thorin Eric , Beglinger Christoph 
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Corneal proliferative angiogenesis is an orphan disease leading to cornea loss.• Today's therapeutic approach is not clearly established, although essentially based on topical corticosteroids.• There is therefore a need for new therapeutic alternatives specifically targeting angiogenesis. WHAT THIS PAPER ADDS • Preclinical data demonstrated the efficacy of GS‐101, an antisense oligonucleotide inhibiting insulin receptor substrate‐1 expression, at inhibiting experimental corneal angiogenesis.• This study demonstrates the excellent safety and tolerability profile of GS‐101 applied as eye drops three times daily in this ‘first‐in‐man’ study.• Upon validation in human of its immediate benefit, GS‐101 would offer an alternative to antivascular endothelial growth factor therapies in the treatment of corneal angiogenesis.AIMSGS‐101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate‐1 (IRS‐1). Inhibition of IRS‐1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS‐101 eye drops.METHODSThis was a Phase I open‐label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS‐101 in one eye for 14 days.RESULTSThe 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS‐101 from 43 to 430 µg per day. Other than itching, experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed.CONCLUSIONSThe tolerability profile obtained from this study suggests that GS‐101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization‐related orphan indications of corneal graft rejection, retinopathy of pre‐maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results.
Plasminogen activator inhibitor‐1 and asthma: role in the pathogenesis and molecular regulation
Authors: Ma Z. , Paek D. , Oh C. K. 
Published: May 2009

SummaryPlasminogen activator inhibitor (PAI)‐1 is a major inhibitor of the fibrinolytic system. PAI‐1 levels are markedly increased in asthmatic airways, and mast cells (MCs), a pivotal cell type in the pathogenesis of asthma, are one of the main sources of PAI‐1 production. Recent studies suggest that PAI‐1 may promote the development of asthma by regulating airway remodelling, airway hyperresponsiveness (AHR), and allergic inflammation. The single guanosine nucleotide deletion/insertion polymorphism (4G/5G) at −675 bp of the PAI‐1 gene is the major genetic determinant of PAI‐1 expression. Plasma PAI‐1 level is higher in people with the 4G/4G genotype than in those with the 5G/5G genotype. A strong association between the 4G/5G polymorphism and the risk and the severity of asthma has been suggested. Levels of plasma IgE and PAI‐1 and severity of AHR are greater in asthmatic patients with the 4G/4G genotype than in those with the 5G/5G genotype. The PAI‐1 promoter with the 4G allele renders higher transcription activity than the PAI‐1 promoter with the 5G allele in stimulated MCs. The molecular mechanism for the 4G allele‐mediated higher PAI‐1 expression is associated with greater binding of upstream stimulatory factor‐1 to the E‐box adjacent to the 4G site (E‐4G) than to the E‐5G. In summary, PAI‐1 may play an important role in the pathogenesis of asthma. Further studies evaluating the mechanisms of PAI‐1 action and regulation may lead to the development of a novel prognostic factor and therapeutic target for the treatment and prevention of asthma and other PAI‐1‐associated diseases.
Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis
Authors: Sidhu M , Griffiths M M , Bradley D S 
Published: May 2009

SummaryImmature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6αβ8αβ transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6αβ8αβ transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5·5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3·5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.
The skin homing receptor cutaneous leucocyte-associated antigen (CLA) is up-regulated byLeishmaniaantigens in T lymphocytes during active cutaneous leishmaniasis
Authors: Mendes-Aguiar C de O , Gomes-Silva A , Nunes Jr E , Pereira-Carvalho R , Nogueira R S , Oliveira-Neto M de P , Bertho A L , Da-Cruz A M 
Published: May 2009

SummaryThe cutaneous leucocyte-associated antigen receptor (CLA) can direct Leishmania-specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte-associated antigen 1 (LFA-1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A-CL) presented lower levels of T lymphocytes expressing the CLA+ phenotype (T CD4+ = 10·4% ± 7·5% and T CD8+ = 5·8% ± 3·4%) than did healthy subjects (HS) (T CD4+ = 19·3% ±  13·1% and T CD8+ = 21·6% ± 8·8%), notably in T CD8+ (P &lt; 0·001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up-regulated CLA in T cells (CLA+ in T CD4+ =  33·3% ± 14·1%; CLA+ in T CD8+ = 22·4% ± 9·4%) from A-CL but not from HS. An enrichment of CLA+ cells was observed in lesions (CLA+ in T CD4+ = 45·9% ± 22·5%; CLA+ in T CD8+ = 46·4% ± 16·1%) in comparison with blood (CLA+ in T CD4+ = 10·4% ± 7·5%; CLA+ in T CD8+ = 5·8% ±  3·4%). Conversely, LFA-1 was highly expressed in CD8+ T cells and augmented in CD4+ T from peripheral blood of A-CL patients. In contrast, CD62L was not affected. These results suggest that Leishmania antigens can modulate molecules responsible for migration to skin lesions, potentially influencing the cell composition of inflammatory infiltrate of leishmaniasis or even the severity of the disease.