bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis
Authors: Anty Rodolphe , Canivet Clémence M. , Patouraux Stéphanie , Ferrari‐Panaia Patricia , Saint‐Paul Marie Christine , Huet Pierre‐Michel , Lebeaupin Cynthia , Iannelli Antonio , Gual Philippe , Tran Albert 
Published: May 2015

BackgroundAmong its pleiotropic effects, vitamin D may protect the liver from fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology in hepatitis C remains unclear, and very few studies including alcoholic patients with liver pathologies have been performed. Here we compared the levels of 25‐OH vitamin D in the blood of alcoholic patients with the occurrence of alcoholic steatohepatitis (ASH) or bridging fibrosis.MethodsOne hundred and one alcoholic patients were included. All the patients received a liver biopsy, and the levels of 25‐OH vitamin D were evaluated with the Liaison 25‐OH vitamin D assay. Logistic regression analyses were performed to obtain predictive factors of liver histology.ResultsAmong alcoholic patients, 40.6% presented ASH and 39.6% presented bridging fibrosis. A severe deficiency in 25‐OH vitamin D (<10 ng/ml) was seen in 60.4% of patients. This deficiency was frequent in patients with ASH (85.4%) and in those with bridging fibrosis (80%) but was independently associated only with ASH (odds ratio = 8.46 [95% confidence interval 2.05 to 34.89], p = 0.003).ConclusionsIn alcoholic patients, a severe deficiency in 25‐OH vitamin D was independently associated with the occurrence of ASH.
Adolescent Alcohol Use Before and After the High School Transition
Authors: Burdzovic Andreas Jasmina , Jackson Kristina M. 
Published: May 2015

BackgroundAn important question is whether the high school (HS) entry is a critical developmental event associated with escalation of alcohol use. This study examined trajectories of adolescent alcohol use as a function of a normative developmental event—the HS entry. In addition, given that at‐risk youth may be particularly vulnerable to the stress associated with this transition, we examined how these alcohol use trajectories may be shaped by a measure of early behavioral risk, early adolescent delinquency.MethodsParticipants included 891 twelve‐year‐olds from the prospective National Longitudinal Survey of Youth 1997 for whom relevant longitudinal school data were available (51.2% boys; 61.4% White).ResultsAlcohol use after HS entry increased at a significantly greater rate than did use during the middle school years, even after accounting for students' age at transition. In addition, early delinquency emerged as a risk factor such that differences in alcohol use existed prior to the transition. That is, children with early delinquency characteristics displayed more rapid progression in alcohol use, but this effect was evident only during middle school.ConclusionsHS entry appears to be a critical developmental event associated with increased social risk for greater alcohol use that goes beyond the simple maturational (i.e., aging) factors. Youth with behavioral problems appears to be at greater risk in middle school, in contrast to lower risk youth for whom HS entry may be a more critical event, in part because HS may be a less restrictive environment and/or because alcohol use becomes more normative at that time. Adolescent substance use may be described as a series of distinct developmental stages that closely correspond to school transitions and suggest a critical period for targeted intervention that may differ as a function of preexisting risk.
Validation of the ASSIST for Detecting Unhealthy Alcohol Use and Alcohol Use Disorders in Urgent Care Patients
Authors: Johnson J. Aaron , Bembry Whitney , Peterson Justin , Lee Anna , Seale J. Paul 
Published: May 2015

BackgroundScreening and brief intervention (SBI) is effective in reducing alcohol use, particularly among moderate risk patients. Results of SBI are inconsistent among patients with alcohol use disorders (AUDs). The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) is used as a screening tool in many existing SBI programs. ASSIST validation studies have identified risk level cutoff scores using criteria for AUD and have not included a criterion measure for at‐risk drinking (ARD), the group for whom SBI is most effective. This study examines the ability of the ASSIST to identify unhealthy alcohol use (ARD or AUD) and AUD in patients presenting to urgent care.MethodsData were obtained from interviews with 442 adult drinkers presenting to 1 of 3 urgent care clinics. Subjects completed the ASSIST, a 90‐day timeline follow‐back interview to detect ARD, and a modified Diagnostic Interview Schedule to identify AUD. Validity measures compared the specificity and sensitivity of cutoff scores for the ASSIST in detecting unhealthy alcohol use and AUDs.ResultsThe optimal ASSIST score for detecting unhealthy alcohol use is 6+ for males (sensitivity and specificity 68 and 66%, respectively) and 5+ for females (62%/70%). Sensitivity, specificity, and receiver operating characteristic values were lower than those previously reported for the Alcohol Use Disorders Identification Test (AUDIT). For AUD, the optimal ASSIST cutoff scores are 10+ for males (63%/85%) and 9+ for females (63%/85%). While higher scores provided increased specificity, thereby reducing the percentage of false positives, sensitivity dropped sharply as scores increased.ConclusionsOptimal ASSIST cutoff scores for unhealthy alcohol use are lower than those commonly used in many SBI programs. Use of lower ASSIST cutoff scores may increase detection of unhealthy alcohol use and increase the numbers served by SBI programs.
MoCA as a Screening Tool of Neuropsychological Deficits in Alcohol‐Dependent Patients
Authors: Alarcon Régis , Nalpas Bertrand , Pelletier Stéphanie , Perney Pascal 
Published: May 2015

BackgroundAlcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation.MethodsConsecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members.ResultsA total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (<26). Age was negatively and education was positively associated with the MoCA score. Significant cognitive deficits concerned visuospatial capacity, attention, fluency, abstraction, and delayed recall. Neither age nor sex was significantly related to the MoCA score, while having a high education level (>12 years) significantly increased the likelihood of having a high MoCA score.ConclusionsOwing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.
Association Between Three Different Cognitive Behavioral Alcohol Treatment Programs and Recidivism Rates Among Male Offenders: Findings from the United Kingdom
Authors: Needham Marie , Gummerum Michaela , Mandeville‐Norden Rebecca , Rakestrow‐Dickens Janine , Mewse Avril , Barnes Andrew , Hanoch Yaniv 
Published: May 2015

BackgroundCognitive behavioral therapy‐based alcohol treatment programs have been widely used to break the link between alcohol and crime. While evidence exists on the connection between alcohol and crime, there is little data that demonstrate the effectiveness of different alcohol treatment programs in reducing criminal behavior. We tested whether male offenders who participate in alcohol treatment programs show lower rates of recidivism than a matched offender group who did not participate in an alcohol prevention program.MethodsThis is an observational matched case–control study. Participants were 564 male offenders with an alcohol problem related to offending. Participants were assigned by the courts to 1 of 3 alcohol treatment programs (141 offenders per treatment): Low Intensity Alcohol Program (LIAP), Alcohol Specified Activity Requirement, and Addressing Substance‐Related Offending. A fourth matched group (n = 141) was not assigned to a program and served as a control group. Survival analysis was used to calculate participants' charged and reconviction rates over 4 time periods (0 to 3, 4 to 6, 7 to 9, and 10 to 12 months after completion of program or order).ResultsOffenders who did not participate in a program were more than twice as likely to be charged compared to offenders who participated in a program. Furthermore, offenders who did not participate in a program were over 2.5 times more likely to be reconvicted. Among the 3 alcohol treatment programs evaluated, the LIAP was the most cost‐effective.ConclusionsOffenders enrolled in an alcohol treatment program showed a significant reduction in being charged with or reconvicted of a crime. With costs of keeping offenders in prison per year reaching close to £40,000 per offender per year (Mulheirn et al., 2010, www.smf.co.uk), assigning offenders to alcohol preventive programs—such as LIAP—are a promising way to reduce recidivism and reduce cost.
Pollen‐derived adenosine is a necessary cofactor for ragweed allergy
Authors: Wimmer M. , Alessandrini F. , Gilles S. , Frank U. , Oeder S. , Hauser M. , Ring J. , Ferreira F. , Ernst D. , Winkler J. B. , Schmitt‐Kopplin P. , Ohnmacht C. , Behrendt H. , Schmidt‐Weber C. , Traidl‐Hoffmann C. , Gutermuth J. 
Published: May 2015

AbstractBackgroundRagweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation.MethodsAqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1–11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen‐derived adenosine was removed from the extract enzymatically to analyze its role in ragweed‐induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed‐stimulated bronchial epithelial cells was analyzed.ResultsInstillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1, pulmonary infiltration with inflammatory cells, a Th2‐associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed‐induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present.ConclusionsPollen‐derived adenosine is a critical factor in ragweed‐pollen‐induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen‐independent pathways.
Psychological wellbeing in 20‐year‐old adults receiving repeated lifestyle counselling since infancy
Authors: Kaseva Kaisa , Pulkki‐Råback Laura , Elovainio Marko , Pahkala Katja , Keltikangas‐Järvinen Liisa , Hintsanen Mirka , Hakulinen Christian , Lagström Hanna , Jula Antti , Niinikoski Harri , Rönnemaa Tapani , Viikari Jorma , Simell Olli , Raitakari Olli 
Published: May 2015

AbstractAimThis study examined whether there was an association between a repeated dietary and lifestyle intervention that began in infancy and participants' psychological wellbeing at the age of 20.MethodsWe examined the psychological wellbeing of 457 young adults participating in the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomised controlled trial conducted in Finland between 1989 and 2011. We assessed potential differences in psychological wellbeing between the intervention and control groups by examining participants' satisfaction with life, how they rated their health, their experiences of stress and the consequences of experiencing stress and symptoms of depression at the age of 20. We also assessed socio‐economic status during childhood as a potential confounding factor.ResultsWe found no association between the long‐term dietary and lifestyle intervention and participants' psychological wellbeing in adulthood. Adjusting for sex and childhood socio‐economic status did not affect the results and socio‐economic status did not moderate the association between the intervention and psychological wellbeing.ConclusionOur findings showed no association between intensive dietary and lifestyle counselling that was initiated in infancy with psychological wellbeing in adulthood and the initiative did not appear to pose any psychological risks.
Interindividual epigenetic variation in ABCB1 promoter and its relationship with ABCB1 expression and function in healthy Chinese subjects
Authors: Wu Lan‐Xiang , Wen Chun‐Jie , Li Ying , Zhang Xue , Shao Ying‐Ying , Yang Zhu , Zhou Hong‐Hao 
Published: May 2015

AimInterindividual epigenetic variation is likely to be an important mechanism contributing to the interindividual variability in the expression and function of ATP‐binding cassette, sub‐family B, member 1 (ABCB1). The aim of the present study was to explore the effect of interindividual epigenetic variability in the ABCB1 promoter on ABCB1 expression and function in healthy Chinese subjects.MethodsUsing bisulfite sequencing polymerase chain reaction (PCR) and chromatin immunoprecipitation assays, the DNA methylation and histone acetylation status of the ABCB1 promoter in stool DNA and exfoliated colonic epithelial cells of 157 healthy Chinese male volunteers was analysed. ABCB1 mRNA levels in colonic epithelial cells were detected by real‐time PCR. The digoxin pharmacokinetics in subjects with different epigenetic profiles was investigated after a single oral administration of digoxin (0.5 mg).ResultsThe methylation levels of ABCB1 promoter in stool DNA showed a significant interindividual variation, from 0.84% to 18.05%. A high methylation level of the ABCB1 promoter was closely related to the low levels of acetylated histone H3 and ABCB1 mRNA expression. In the high methylation group, the area under the concentration–time curves (AUC(0–4 h) and AUC(0–10 h)) of digoxin was increased by 19% [95% confidence interval (CI) 10%, 31%; P = 0.024] and 13% (95% CI 8%, 26%; P = 0.026), respectively, and the peak concentration (Cmax) of digoxin was increased by 30% (95% CI 12%, 41%; P = 0.021) compared with the low methylation group.ConclusionsThe epigenetic modifications of the ABCB1 promoter show high interindividual variability in healthy Chinese subjects, and are closely related to the interindividual variation in ABCB1 mRNA expression and digoxin 0–4 h plasma concentrations in vivo.
Pharmacokinetics and pharmacodynamics of PF‐05231023, a novel long‐acting FGF21 mimetic, in a first‐in‐human study
Authors: Dong Jennifer Q. , Rossulek Michelle , Somayaji Veena R. , Baltrukonis Daniel , Liang Yali , Hudson Krischan , Hernandez‐Illas Martha , Calle Roberto A. 
Published: May 2015

AimsThe aim of the present study was to evaluate the pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerability of single intravenous (IV) doses of PF‐05231023, a long acting fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of type 2 diabetes mellitus (T2DM).MethodsT2DM subjects (glycosylated haemoglobin: 7.0–10.5%; on stable metformin therapy and/or diet and exercise) were randomized to receive a single dose of placebo or PF‐05231023 (0.5–200 mg). Safety evaluations were performed up to 14 days after dosing. PK and PD endpoints were measured and a PK/PD model was developed for triglyceride – an early marker of drug activity.ResultsNo antidrug antibody or serious adverse events (AEs) were observed. The most frequent AEs were gastrointestinal but were generally mild. Plasma PF‐05231023 levels peaked immediately post‐IV dosing, with mean terminal half‐lives of 6.5–7.7 h and 66.5– 96.6 h for intact C‐ and N‐termini, respectively. Intact C‐terminus exposures increased proportionally with increasing dose, whereas N‐terminus exposures appeared to trend higher than dose‐proportionally. Although no apparent effect on plasma glucose was seen, dose‐dependent decreases in triglyceride were observed, with a maximum reduction of 48.5 ± 10.0% (mean ± standard deviation) for the 200 mg dose compared with a reduction of 19.1 ± 26.4% for placebo, demonstrating proof of pharmacology. Moreover, a reduction in total cholesterol and low‐density lipoprotein cholesterol and an increase in high‐density lipoprotein cholesterol were observed in the high‐dose groups.ConclusionsSingle IV doses of PF‐05231023 up to 200 mg were generally safe and well tolerated by subjects with T2DM. The observed early sign of pharmacology supports further clinical testing of PF‐05231023 upon repeated administration.
Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
Authors: Lanchote Vera Lucia , Almeida Roque , Barral Aldina , Barral‐Netto Manoel , Marques Maria Paula , Moraes Natália V. , da Silva Angela M. , Souza Tania M. V. , Suarez‐Kurtz Guilherme 
Published: May 2015

AimsThe aim of the present study was to investigate the impact of human visceral leishmaniasis (VL) and curative chemotherapy on the activity of cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 in patients from an endemic region in Brazil.MethodsAdult patients with parasitologically confirmed VL were given a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan, immediately before (Study phase 1), 2–3 days (phase 2) and 3–6 months (phase 3) after curative VL chemotherapy. CYP activity was assessed by the apparent clearance of midazolam (CYP3A), omeprazole/5‐hydroxyomeprazol ratio in plasma (CYP2C19) and losartan/E3174 ratio in urine (CYP2C9).ResultsMean values (95% confidence interval) in phases 1, 2 and 3 were, respectively: log apparent midazolam clearance, 1.21 (1.10–1.31), 1.45 (1.32–1.57) and 1.35 (1.26–1.44) ml min–1 kg–1; omeprazole/5‐hydroxyomeprazole ratio, 0.78 (0.61–0.94), 0.45 (0.27–0.63) and 0.37 (0.20‐0.55); losartan/E3174 ratio, 0.66 (0.39–0.92), 0.35 (0.20–0.50) and 0.35 (0.16–0.53). Analysis of variance revealed significant differences in CYP3A (P = 0.018) and CYP2C19 (P = 0.008), but not CYP2C9 (P = 0.11) phenotypic activity, across the three study phases.ConclusionThe phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during acute VL compared with post‐chemotherapy. We propose that increased plasma concentrations of proinflammatory cytokines during active disease account for the suppression of CYP activity. The failure to detect significant changes in CYP2C9 activity in the overall cohort may reflect differential effects of the inflammatory process on the expression of CYP isoforms, although the possibility of insufficient statistical power cannot be dismissed.
Mammary tissue microenvironment determines T cell‐dependent breast cancer‐associated inflammation
Authors: Takahashi Kei , Nagai Nao , Ogura Keisuke , Tsuneyama Koichi , Saiki Ikuo , Irimura Tatsuro , Hayakawa Yoshihiro 
Published: May 2015

Although the importance of the host tissue microenvironment in cancer progression and metastasis has been established, the spatiotemporal process establishing a cancer metastasis‐prone tissue microenvironment remains unknown. In this study, we aim to understand the immunological character of a metastasis‐prone microenvironment in a murine 4T1 breast tumor model, by using the activation of nuclear factor‐κb (NF‐κB) in cancer cells as a sensor of inflammatory status and by monitoring its activity by bioluminescence imaging. By using a 4T1 breast cancer cell line stably expressing an NF‐κB/Luc2 reporter gene (4T1 NF‐κB cells), we observed significantly increased bioluminescence approximately 7 days after metastasis‐prone orthotopic mammary fat‐pad inoculation but not ectopic s.c. inoculation of 4T1 NF‐κB cells. Such in vivo NF‐κB activation within the fat‐pad 4T1 tumor was diminished in immune‐deficient SCID or nude mice, or T cell‐depleted mice, suggesting the requirement of host T cell‐mediated immune responses. Given the fat‐pad 4T1 tumor expressed higher inflammatory mediators in a T cell‐dependent mechanism compared to the s.c. tumor, our results imply the importance of the surrounding tissue microenvironment for inflaming tumors by collaborating with T cells to instigate metastatic spread of 4T1 breast cancer cells.
Synergistic antiproliferative effect of imatinib and adriamycin in platelet‐derived growth factor receptor‐expressing osteosarcoma cells
Authors: Yamaguchi Sayaka I. , Ueki Arisa , Sugihara Eiji , Onishi Nobuyuki , Yaguchi Tomonori , Kawakami Yutaka , Horiuchi Keisuke , Morioka Hideo , Matsumoto Morio , Nakamura Masaya , Muto Akihiro , Toyama Yoshiaki , Saya Hideyuki , Shimizu Takatsune 
Published: May 2015

Osteosarcoma (OS) is the most frequent primary solid malignant tumor of bone. Its prognosis remains poor in the substantial proportion of patients who do not respond to chemotherapy and novel therapeutic options are therefore needed. We previously established a mouse model that mimics the aggressive behavior of human OS. Enzyme‐linked immunosorbent assay‐based screening of such mouse tumor lysates identified platelet‐derived growth factor–BB (PDGF‐BB) as an abundant soluble factor, the gene for which was expressed dominantly in surrounding non‐malignant cells of the tumor, whereas that for the cognate receptor (PDGF receptor β) was highly expressed in OS cells. Platelet‐derived growth factor‐BB induced activation of both MEK–ERK and phosphatidylinositol 3‐kinase–protein kinase B signaling pathways and promoted survival in OS cells deprived of serum, and these effects were blocked by the PDGF receptor inhibitor imatinib. However, these actions of PDGF‐BB and imatinib were mostly masked in the presence of serum. Whereas imatinib alone did not manifest an antitumor effect in mice harboring OS tumors, combined treatment with imatinib and adriamycin exerted a synergistic antiproliferative effect on OS cells in vivo. These results suggest that treatment of OS with imatinib is effective only when cell survival is dependent on PDGF signaling or when imatinib is combined with another therapeutic intervention that renders the tumor cells susceptible to imatinib action, such as by inducing cellular stress.