bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subjective Response to Alcohol as a Research Domain Criterion
Authors: Ray Lara A. , Bujarski Spencer , Roche Daniel J. O. 
Published: January 2016

BackgroundIndividual differences in the subjective experience of the pharmacological effects of alcohol have long been implicated in the likelihood that one will drink heavily and develop alcoholism. The theme of this conceptual review and perspective article is to synthesize the literature on subjective responses to alcohol and to set an agenda for the next generation of research in the area. Specifically, we contend that in order for subjective response to alcohol to play a prominent role in alcoholism research, it is critical that it be studied as a multimodal phenotype.MethodsFirst, we review the human research on subjective response to alcohol measured under controlled laboratory conditions and draw recommendations for the application of these findings to understanding alcoholism neurobiology in humans. Second, we highlight multimodal approaches, including studies of the genetic and neural substrates of individual differences in subjective response to alcohol. Third, we review treatment implications with a focus on subjective response to alcohol as an intervention target. Upon review of the research on subjective response to alcohol across levels of analyses, we provide recommendations for leveraging these phenotypes in a systematic and methodologically rigorous fashion that can address central questions about alcoholism etiology, disease progression, and personalized treatment.DiscussionThe approach recommended herein is largely consistent with the Research Domain Criteria (RDoC) initiative across the National Institute of Mental Health. The defining feature of such domains is that they inform behavior yet be amenable to examination through multiple units of analysis, such as molecular, genetic, circuit‐level, and behavioral measurements. To that end, we contend that subjective response to alcohol represents a behaviorally and biologically plausible phenotype upon which to build using the RDoC framework for understanding alcohol use disorder.
GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations
Authors: Enoch Mary‐Anne , Hodgkinson Colin A. , Shen Pei‐Hong , Gorodetsky Elena , Marietta Cheryl A. , Roy Alec , Goldman David 
Published: January 2016

BackgroundAnimal and human studies indicate that GABBR1, encoding the GABAB1 receptor subunit, and SLC6A1, encoding the neuronal gamma‐aminobutyric acid (GABA) transporter GAT1, play a role in addiction by modulating synaptic GABA. Therefore, variants in these genes might predict risk/resilience for alcoholism.MethodsThis study included 3 populations that differed by ethnicity and alcoholism phenotype: African American (AA) men: 401 treatment‐seeking inpatients with single/comorbid diagnoses of alcohol and drug dependence, 193 controls; Finnish Caucasian men: 159 incarcerated alcoholics, half with comorbid antisocial personality disorder, 181 controls; and a community sample of Plains Indian (PI) men and women: 239 alcoholics, 178 controls. Seven GABBR1 tag single nucleotide polymorphisms were genotyped in the AA and Finnish samples; rs29220 was genotyped in the PI for replication. Also, a uniquely African, functional SLC6A1 insertion promoter polymorphism (IND) was genotyped in the AAs.ResultsWe found a significant and congruent association between GABBR1 rs29220 and alcoholism in all 3 populations. The major genotype (heterozygotes in AAs, Finns) and the major allele in PIs were significantly more common in alcoholics. Moreover, SLC6A1 IND was more abundant in controls, that is, the major genotype predicted alcoholism. An analysis of combined GABBR1 rs29220 and SLC6A1 IND genotypes showed that rs29220 heterozygotes, irrespective of their IND status, had an increased risk for alcoholism, whereas carriers of the IND allele and either rs29220 homozygote were more resilient.ConclusionsOur results show that with both GABBR1 and SLC6A1, the minor genotypes/alleles were protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist.
Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings
Authors: Donald Kirsten A. , Ipser Jonathan C. , Howells Fleur M. , Roos Annerine , Fouche Jean‐Paul , Riley Edward P. , Koen Nastassja , Woods Roger P. , Biswal Bharat , Zar Heather J. , Narr Katherine L. , Stein Dan J. 
Published: January 2016

BackgroundChildren exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school‐age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored.MethodsSixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol‐exposed (PAE) and 14 age‐matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed‐based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit.ResultsAlcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance.ConclusionsAlthough results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting‐state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.
The Ability of Functional Magnetic Resonance Imaging to Predict Heavy Drinking and Alcohol Problems 5 Years Later
Authors: Schuckit Marc A. , Smith Tom L. , Paulus Martin P. , Tapert Susan F. , Simmons Alan N. , Tolentino Neil J. , Shafir Alexandra 
Published: January 2016

BackgroundLow levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR‐related blood oxygen level‐dependent (BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes (Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (fMRI) patterns.MethodsOf 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline fMRI patterns and alcohol‐related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes.ResultsBaseline fMRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections.ConclusionsThe data suggest that fMRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether fMRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates.
Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity
Authors: Rao P. S. S. , Kumar Santosh 
Published: January 2016

BackgroundOur recent study has shown that acute treatment with ethanol (EtOH) increases oxidative stress and cytotoxicity through cytochrome P450 2E1 (CYP2E1)‐mediated pathway in U937 monocytic cells. U937 cells are derived from blood monocytes and are considered as the model system for HIV‐related study. Since the prevalence of alcohol use in HIV‐infected population is high, and HIV+ patients are on antiretroviral therapy (ART) soon after they are diagnosed, it is important to study the interactions between EtOH and ART in monocytes.MethodsThis study examined the chronic effects of EtOH and ART (darunavir/ritonavir), alone and in combination, on expression/levels of cytochrome P450 enzymes (CYPs), antioxidant enzymes (AOEs), reactive oxygen species (ROS), and cytotoxicity in U937 cells. The mRNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. ROS and cytotoxicity were measured using flow cytometry and cell viability assay, respectively.ResultsWhile chronic ART treatment increased CYP2E1 protein expression by 2‐fold, EtOH and EtOH+ART increased CYP2E1 by ~5‐fold. In contrast, ART and EtOH treatments decreased CYP3A4 protein expression by 38 ± 17% and 74 ± 15%, respectively, and the combination additively decreased CYP3A4 level by 90 ± 8%. Expressions of superoxide dismutase 1 (SOD1) and peroxiredoxin (PRDX6) were decreased by both EtOH and ART, however, the expressions of SOD2 and catalase were unaltered. These results suggested increased EtOH metabolism, increased ART accumulation, and decreased defense against ROS. Therefore, we determined the effects of EtOH and ART on ROS and cytotoxicity. While ART showed a slight increase, EtOH and EtOH+ART displayed significant increase in ROS and cytotoxicity. Moreover, the combination showed additive effects on ROS and cytotoxicity.ConclusionsThese results suggest that chronic EtOH, in the absence and presence of ART, increases ROS and cytotoxicity in monocytes, perhaps via CYP‐ and AOE‐mediated pathways. This study has clinical implications in HIV+ alcohol users who are on ART.
Worldwide Prevalence of Fetal Alcohol Spectrum Disorders: A Systematic Literature Review Including Meta‐Analysis
Authors: Roozen Sylvia , Peters Gjalt‐Jorn Y. , Kok Gerjo , Townend David , Nijhuis Jan , Curfs Leopold 
Published: January 2016

BackgroundAlthough fetal alcohol spectrum disorders (FASD) affect communities worldwide, little is known about its prevalence. The objective of this study was to provide an overview of the global FASD prevalence.MethodsWe performed a search in multiple electronic bibliographic databases up to August 2015, supplemented with the ascendancy and descendancy approach. Studies were considered when published in English, included human participants, and reported empirical data on prevalence or incidence estimates of FASD. Raw prevalence estimates were transformed using the Freeman–Tukey double arcsine transformation so that the data followed an approximately normal distribution. Once the pooled prevalence estimates, 95% confidence intervals and prediction intervals were calculated based on multiple meta‐analyses with transformed proportions using random effects models, these estimates were transformed back to regular prevalence rates. Heterogeneity was tested using Cochran's Q and described using the I2 statistic.ResultsAmong studies that estimated prevalence in general population samples, considerable differences in prevalence rates between countries were found and therefore separate meta‐analyses for country were conducted. Particularly high‐prevalence rates were observed in South Africa for fetal alcohol syndrome (55.42 per 1,000), for alcohol‐related neurodevelopmental disorder (20.25 per 1,000), and FASD (113.22 per 1,000), For partial fetal alcohol syndrome high rates were found in Croatia (43.01 per 1,000), Italy (36.89 per 1,000), and South Africa (28.29 per 1,000). In the case of alcohol‐related birth defects, a prevalence of 10.82 per 1,000 was found in Australia. However, studies into FASD exhibited substantial heterogeneity, which could only partly be explained by moderators, most notably geography and descent, in meta‐regressions. In addition, the moderators were confounded, making conclusions as to each moderator's relevance tentative at best.ConclusionsThe worldwide pooled prevalence estimates are higher than assumed so far, but this was largely explained by geography and descent. Furthermore, prevalence studies varied considerably in terms of used methodology and methodological quality. The pooled estimates must therefore be interpreted with caution and for future research it is highly recommended to report methodology in a more comprehensive way. Finally, clear guidelines on assessing FASD prevalence are urgently needed, and a first step toward these guidelines is presented.
Clinical features, impulsivity, temperament and functioning and their role in suicidality in patients with bipolar disorder
Authors: Jiménez E. , Arias B. , Mitjans M. , Goikolea J. M. , Ruíz V. , Brat M. , Sáiz P. A. , García‐Portilla M. P. , Burón P. , Bobes J. , Oquendo M. A. , Vieta E. , Benabarre A. 
Published: January 2016

ObjectiveOur aim was to analyse sociodemographic and clinical differences between non‐suicidal (NS) bipolar patients (BP), BP reporting only suicidal ideation (SI) and BP suicide attempters according to Columbia–Suicide Severity Rating Scale (C‐SRSS) criteria. Secondarily, we also investigated whether the C‐SRSS Intensity Scale was associated with emergence of suicidal behaviour (SB).MethodA total of 215 euthymic bipolar out‐patients were recruited. Semistructured interviews including the C‐SRSS were used to assess sociodemographic and clinical data. Patients were grouped according to C‐SRSS criteria: patients who scored ≤1 on the Severity Scale were classified as NS. The remaining patients were grouped into two groups: ‘patients with history of SI’ and ‘patients with history of SI and SB’ according to whether they did or did not have a past actual suicide attempt respectively.ResultsPatients from the three groups differed in illness onset, diagnosis, number of episodes and admissions, family history, comorbidities, rapid cycling and medication, as well as level of education, functioning, impulsivity and temperamental profile.ConclusionOur results suggest that increased impulsivity, higher rates of psychiatric admissions and a reported poor controllability of SI significantly increased the risk for suicidal acts among patients presenting SI.
Heat shock protein‐70 and hypoxia inducible factor‐1α in type 2 diabetes mellitus patients complicated with retinopathy
Authors: Sayed Khulood M. , Mahmoud Aida A. 
Published: January 2016

AbstractPurposeTo elucidate the role of heat shock protein‐70 (HSP70) and hypoxia inducible factor‐1α (HIF‐1α) in diabetic retinopathy (DR) patients.Design and methodsA comparative study was done on the serum level of both HSP70 and HIF‐1α in 50 patients with type 2 diabetes mellitus (T2DM) without DR, 50 patients with T2DM and DR and 70 healthy control subjects.ResultsHSP70 and HIF‐1α were significantly increased in T2DM patients compared to controls and increased in patients with T2DM & DR compared to T2DM patients without DR (p < 0.0001). HSP70 did not differ among the patients with different stages of DR, while HIF‐1α increased significantly in grades 3 and 4 DR patients compared to grades 1 and 2 DR patients. A strong correlation was found between HIF‐1α and the development of DR (r = 0.835, p = 0.00) but not with HSP70. HIF‐1α can be used as a predictor for development of DR but not HSP70.ConclusionsOur study was the first that investigated both HSP70 and HIF‐1α in humans and was the first that measured their levels in serum of patients with DR. The study suggested that HSP70 might have a protective function in T2DM patients rather than a therapeutic function. HIF‐1α had an upper hand in the development and progression of DR. Induction of HSP70 and blockage of HIF‐1α could lead to the development of novel prophylactic and therapeutic strategies for DR and potentially other diabetic complications.
Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer
Authors: Walsh Christopher , Bonner Jennifer J. , Johnson Trevor N. , Neuhoff Sibylle , Ghazaly Essam A. , Gribben John G. , Boddy Alan V. , Veal Gareth J. 
Published: January 2016

AimsUse of the anti‐tumour antibiotic actinomycin D is associated with development of hepatotoxicity, particularly in young children. A paucity of actinomycin D pharmacokinetic data make it challenging to develop a sound rationale for defining dosing regimens in younger patients. The study aim was to develop a physiologically based pharmacokinetic (PBPK) model using a combination of data from the literature and generated from experimental analyses.MethodsAssays to determine actinomycin D Log P, blood:plasma partition ratio and ABCB1 kinetics were conducted. These data were combined with physiochemical properties sourced from the literature to generate a compound file for use within the modelling‐simulation software Simcyp (version 14 release 1). For simulation, information was taken from two datasets, one from 117 patients under the age of 21 and one from 20 patients aged 16–48.ResultsThe final model incorporated clinical renal and biliary clearance data and an additional systemic clearance value. The mean AUC0‐26h of simulated subjects was within 1.25‐fold of the observed AUC0‐26h (84 ng h ml−1 simulated vs. 93 ng h ml−1 observed). For the younger age ranges, AUC predictions were within two‐fold of observed values, with simulated data from six of the eight age/dose ranges falling within 15% of observed data. Simulated values for actinomycin D AUC0‐26h and clearance in infants aged 0–12 months ranged from 104 to 115 ng h ml−1 and 3.5–3.8 l h−1, respectively.ConclusionsThe model has potential utility for prediction of actinomycin D exposure in younger patients and may help guide future dosing. However, additional independent data from neonates and infants is needed for further validation. Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models.
Effects of perceived school well‐being and negative emotionality on students' attentional bias for academic stressors
Authors: Scrimin Sara , Moscardino Ughetta , Altoè Gianmarco , Mason Lucia 
Published: January 2016

BackgroundPrevious research indicates that children can display different attention allocation patterns in response to threat. However, data are lacking on the possible existence of an attentional bias in response to academic stressors, and whether variables related to school well‐being (SWB) and students' individual characteristics may influence such attentional patterns.AimWe aimed to investigate whether students show an attentional bias for school‐related stressors. We sought to identify groups of students who differ in their perceived SWB, and to test whether they display different attention allocation patterns. We also examined whether negative emotionality moderates the expected association between students' SWB and attentional bias.MethodsEighth‐grade students completed a dot‐probe detection task to register attentional patterns towards or away from an academic threatening word. SWB in terms of school anxiety, school‐based stress, and perceived class climate was also assessed via self‐reports. In addition, participants reported on their negative emotionality.ResultsThe results indicated that students showed an attentional bias towards words describing academic stressors. Cluster analyses allowed the identification of two groups of students with high versus low SWB. Regression analysis indicated that those with low SWB were more likely to show a greater bias and that negative emotionality moderated this relationship. Specifically, within the context of low SWB, students with high negative emotionality were more prone to biased attention towards school‐related stressors compared with students with low negative emotionality.ConclusionsThe present data indicate a perceptual bias for the detection of academic threats. Within the school practice, teachers should promote SWB and devote specific attention to students with high negative emotionality to reduce a biased allocation of attention in response to school‐related stressors.
Examining a one‐hour synchronous chat in a microblogging‐based professional development community
Authors: Gao Fei , Li Lan 
Published: January 2016

AbstractResearch on microblogging in education has suggested its potential to promote community building and collaborative learning, but little is known about the nature of interaction in such microblogging communities. More research is needed to understand how online learning communities can be designed in a way that supports effective learning. The purpose of the study is to explore how people interact in a popular microblogging‐based learning community by examining a one‐hour synchronous chat event and analyzing its network structure, levels of participation, major topics generated and types of interaction. The findings suggested that the levels of participation in the synchronous chat were largely uneven. During the chat, participants were engaged in many types of interaction and discussed a variety of issues related to the topic. Interestingly, people who were different in their levels of participation also varied on the types of topics generated, but not on the types of interaction.