bluuebunny/crossref_metadata_2025_split huggingface dataset:
Operational implications of varying ambient light levels and time‐of‐day effects on saccadic velocity and pupillary light reflex
Authors: Yu Minzhong , Kautz Mary A. , Thomas Maria L. , Johnson Dagny , Hotchkiss Edwin R. , Russo Michael B. 
Published: February 2007

AbstractChanges in maximal saccadic velocity (SV), initial pupil diameter (IPD), constriction latency (CL) and constriction amplitude (CA) determined by the pupillary light reflex have been found to be sensitive indicators of impairment as a result of drugs, sleepiness, and/or fatigue. Ambient illuminance and time of day are controlled when these indices are applied as repeated measures in fitness‐for‐duty determinations. The application of oculometrics in unrestricted operational environments, where ambient illuminance and time‐of‐day testing are not constant, requires understanding of, and potential compensation for, the effects of, and interactions among, these multiple uncontrolled variables. SV, IPD, CL, and CA were evaluated in the morning and evening on two consecutive days following adequate nightly sleep under one baseline ambient illuminance and seven test ambient illuminances. Sixteen healthy volunteers (21–38 years, eight females/eight males) participated. Within and across days, SV was unaffected by decreasing ambient light or time‐of‐day effects. With the increase of ambient light from 670 to 3300 lx, CL decreased by 1%, while IPD and CA decreased by 17% and 20%, respectively. IPD increased with time of day by 1–10% (IPD was smaller in the morning). The results show that SV and CL are essentially resistant to changes in ambient light and time‐of‐day effects, simplifying their application in uncontrolled operational environments.
Eye and head movement alterations in naïve progressive addition lens wearers
Authors: Hutchings Natalie , Irving Elizabeth L. , Jung Nadine , Dowling Lisa M. , Wells Kelly A. 
Published: February 2007

AbstractAims:  To examine adaptation to progressive addition lenses (PALs) by investigating eye and head movement strategies of individuals naïve to PAL wear; to determine whether adaptation is a short‐term change in strategy or is maintained with continued PAL wear; to determine if adaptation strategies are different between PAL designs.Methods:  Ten presbyopic individuals participated in a double‐blind crossover study. Participants wore one PAL design for ≤4 weeks, had approximately 1 week without PAL wear and then wore the second PAL for ≤4 weeks. Eye and head movements were recorded at the beginning and end of each period of PAL wear in response to several visual tasks. Visual tasks were a flash discrimination task at 2 m and 40 cm, and reading text aloud. Quantitative analysis was undertaken for eye and head movement dynamics (latency, duration, peak velocity, etc.). Categorical analysis used eye and head movement metrics to classify participants as eye‐movers, head‐movers or mixed at each visit.Results:  There was significant between‐participant variability. A number of eye/head movement parameters exhibited carry‐over effects. The number of vertical head movements for the distance task showed a significant increase between the first and second visit (F1,9 = 5.578; p = 0.042), irrespective of lens design. Categorical analysis showed that participants employed task dependent strategies for all tasks. Participants that altered their strategy tended to include more head movements. Seven of the 10 participants preferred the second PAL worn.Conclusions:  Participants recruited more head movements for flash discrimination tasks and for reading text during adaptation to PAL wear. The many and various eye and head movement parameters analysed were unable to discriminate differences dependent on PAL design.
Regression analysis of ranked segment parameters for optic nerve head classification: a pilot study
Authors: Cubbidge Robert P. , Hosking Sarah L. , Hilton Emma J. , Gibson Jonathan M. 
Published: February 2007

AbstractPurpose:  To determine whether curve‐fitting analysis of the ranked segment distributions of topographic optic nerve head (ONH) parameters, derived using the Heidelberg Retina Tomograph (HRT), provide a more effective statistical descriptor to differentiate the normal from the glaucomatous ONH.Methods:  The sample comprised of 22 normal control subjects (mean age 66.9 years; S.D. 7.8) and 22 glaucoma patients (mean age 72.1 years; S.D. 6.9) confirmed by reproducible visual field defects on the Humphrey Field Analyser. Three 10°‐images of the ONH were obtained using the HRT. The mean topography image was determined and the HRT software was used to calculate the rim volume, rim area to disc area ratio, normalised rim area to disc area ratio and retinal nerve fibre cross‐sectional area for each patient at 10°‐sectoral intervals. The values were ranked in descending order, and each ranked‐segment curve of ordered values was fitted using the least squares method.Results:  There was no difference in disc area between the groups. The group mean cup–disc area ratio was significantly lower in the normal group (0.204 ± 0.16) compared with the glaucoma group (0.533 ± 0.083) (p < 0.001). The visual field indices, mean deviation and corrected pattern S.D., were significantly greater (p < 0.001) in the glaucoma group (−9.09 dB ± 3.3 and 7.91 ± 3.4, respectively) compared with the normal group (−0.15 dB ± 0.9 and 0.95 dB ± 0.8, respectively). Univariate linear regression provided the best overall fit to the ranked segment data. The equation parameters of the regression line manually applied to the normalised rim area–disc area and the rim area–disc area ratio data, correctly classified 100% of normal subjects and glaucoma patients. In this study sample, the regression analysis of ranked segment parameters method was more effective than conventional ranked segment analysis, in which glaucoma patients were misclassified in approximately 50% of cases. Further investigation in larger samples will enable the calculation of confidence intervals for normality. These reference standards will then need to be investigated for an independent sample to fully validate the technique.Conclusions:  Using a curve‐fitting approach to fit ranked segment curves retains information relating to the topographic nature of neural loss. Such methodology appears to overcome some of the deficiencies of conventional ranked segment analysis, and subject to validation in larger scale studies, may potentially be of clinical utility for detecting and monitoring glaucomatous damage.
Development of a Humanized In Vitro Blood–Brain Barrier Model to Screen for Brain Penetration of Antiepileptic Drugs
Authors: Cucullo Luca , Hossain Mohammed , Rapp Ed , Manders Toby , Marchi Nicola , Janigro Damir 
Published: February 2007

Summary: Purpose:A biotechnologic breakthrough for the study of drug permeability across the blood–brain barrier (BBB) would be the use of a reproducible in vitro model that recapitulates the functional, structural, and pathologic properties of the BBB in situ. We developed a humanized dynamic in vitro BBB model (DIV‐BBB) based on cocultures of human microvascular endothelial cells (HBMECs) from “normal” and drug‐resistant epileptic brain tissue with human brain astrocytes (HAs) from epilepsy patients or controls.Methods:HBMECs and HAs were cocultured for 28 days in polypropylene capillaries. HBMECs were exposed to physiologic levels of shear stress generated by intraluminal flow. Permeability to [3H]sucrose, [14C]phenytoin, and [14C]diazepam was measured in control and drug‐resistant DIV‐BBB with and without pretreatment with the MDR1 inhibitor XR9576. BBB integrity was monitored by transendothelial electrical resistance measurements (TEERs). Cell growth and viability were assessed by measurement of glucose consumption and lactate production.Results:PSucroseand TEER values did not depend on the origin of the endothelium used (epileptic or normal). PPhenytoinwas 10‐fold less (1.54 × 10−6cm/s) in drug‐resistant BBB models than in controls (1.74 × 10−5cm/s). MDR1 blockade with XR9576 was effective (3.5‐fold increase) only in drug‐resistant cultures. PDiazepamin control and drug‐resistant DIV‐BBB was not affected by XR9576 and did not depend on the epileptic or control origin of endothelia. The overall contribution of epileptic glia to pharmacoresistance was negligible.Conclusions:These results show that, for the substances used, the humanized DIV‐BBB recapitulates the physiologic permeability properties of the BBB in vivo and is also capable of mimicking a drug‐resistant BBB phenotype.
Voltage‐dependent Calcium Channel Abnormalities in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats
Authors: Yan Hai‐Dun , Ishihara Kumatoshi , Hanaya Ryosuke , Kurisu Kaoru , Serikawa Tadao , Sasa Masashi 
Published: February 2007

Summary:  Purpose: Hippocampal CA3 neurons of spontaneously epileptic rats (SER; zi/zi, tm/tm), which show both absence‐like seizures and tonic convulsions, exhibit a long‐lasting depolarization shift with repetitive firing with a single stimulation of mossy fibers. Therefore a whole‐cell patch‐clamp study using temporarily dissociated hippocampal CA3 neurons from SER was performed to elucidate whether such abnormal excitability was due to abnormalities in voltage‐dependent Ca2+ channels (VDCCs). Methods: Hippocampal CA3 neurons were temporarily dissociated with enzymatic and mechanical treatments. In a voltage‐clamp mode with whole‐cell recording, depolarizing step pulses were applied to induce Ca2+ currents in the presence of tetrodotoxin and tetraethylammonium. Results: The threshold level of the Ca2+ current induced by depolarizing pulses was found to be lower in hippocampal CA3 neurons of SER compared with those of control Wistar rats. In addition, the Ca2+ current peak amplitude was greater, and decay of the current was weaker in CA3 neurons of SER than in those of normal Wistar rats. Conclusions: These findings suggest that enhancements of Ca2+ influx into hippocampal CA3 neurons due to the easier activation properties of VDCCs, as well as a decrease in decay, are involved in SER epileptic seizures.
Diagnostic Values of Surface‐Enhanced Laser Desorption/Ionization Technology for Screening of Habitual Drinkers
Authors: Sogawa Kazuyuki , Itoga Sakae , Tomonaga Takeshi , Nomura Fumio 
Published: February 2007

Background: The currently available biological markers are limited in sensitivity and specificity for screening of excessive alcohol drinkers. We recently purified and identified 3 potential markers for alcoholism (5.9 and 7.8 kDa peptides and 28 kDa protein) by using surface‐enhanced laser desorption/ionization (SELDI‐TOF MS) technology. In the present study, we determined the diagnostic values of these novel markers in screening habitual drinkers with moderate alcohol consumption (hereafter habitual drinkers) in the general population as compared with 2 conventional markers: γ‐glutamyltransferase (GGT) and carbohydrate‐deficient transferrin (CDT).Methods: Serum samples obtained from a total of 128 Japanese who sought regular medical checkup were analyzed by SELDI‐TOF MS.Results: The relative intensities of the 5.9 and the 28 kDa peak of habitual drinkers were significantly different from those in nondrinkers even in GGT nonresponders. The sensitivity and specificity were the highest in 5.9 kDa. When 5.9, 28 kDa, and GGT were combined, 96.8% of the habitual drinkers were successfully screened with a specificity of 60.9%.Conclusion: The results of this study clearly indicate that the 5.9 kDa peak is a promising novel biological marker for moderate alcohol consumption.
Role of the Genetic Polymorphisms in the 5′‐Flanking Region for Transcriptional Regulation of the Human CYP2E1 Gene
Authors: Uchimoto Takayuki , Itoga Sakae , Nezu Masahiko , Sunaga Masahiko , Tomonaga Takeshi , Nomura Fumio 
Published: February 2007

Background: The human cytochrome P‐4502E1 (CYP2E1) has been known to be that are associated with alcohol‐related diseases and various cancers. Difference in susceptibility in enzyme induction of the CYP2E1 by environmental factors such as ethanol may be associated with the risk of these diseases. In the 5′‐flanking region of the human CYP2E1 gene, there were tandem repeat polymorphism (CYP2E1*1C*,1D) and RsaI polymorphism (CYP2E1*5A*,5B), which have been reported to be related to these diseases. Thus, we focused relationship between these polymorphisms and transcriptional regulation. The aim of this study was to determine the role of these polymorphisms for the transcriptional regulation of the human CYP2E1 gene in general transcription and during enzyme induction.Methods: To determine the role of these polymorphisms, various constructs of the 5′‐flanking region of the human CYP2E1 gene were prepared and transfected into HeLa cells and HepG2 cells treated or not with pyrazine, a well‐known CYP2E1 inducer.Results: The transcriptional activity of CYP2E1*1D was higher than that of CYP2E1*1C in HeLa cells. The −1,306 base pairs (bp) construct (−1,306 to +9) increased transcriptional activity compared with the 2.5 kb full‐length construct. The suppressive effect of transcriptional activity by deletion of the region including CYP2E1*1C was greater than that by CYP2E1*1D in HeLa cells. The −580 bp construct (−580 to +9) decreased transcriptional activity compared with the −1,306 bp construct. The −1,306 bp construct also showed a similar tendency during pyrazine treatment.Conclusions: The region including the tandem repeat polymorphism was suggested to regulate transcription suppressively. Besides, it was speculated that the transcriptional activity of CYP2E1*1D was higher than that of CYP2E1*1C because transcriptional suppression of CYP2E1*1D was weaker than that of CYP2E1*1C. Also, it was confirmed that the region including RsaI polymorphism was associated with the promotion of transcription.
Mutation of Mitochondrial DNA in Livers From Patients With Alcoholic Hepatitis and Nonalcoholic Steatohepatitis
Authors: Kawahara Hiromu , Fukura Masayuki , Tsuchishima Mutsumi , Takase Shujiro 
Published: February 2007

Background: In alcoholic hepatitis (Al‐Hep) and nonalcoholic steatohepatitis (NASH), triglycerides accumulate in hepatocytes. We examined the hypothesis that mutations in mitochondrial DNA may take place by mitochondrial overwork, resulting in dysfunction of mitochondria.Subjects and Methods: Subjects of this research were 8 cases each of Al‐Hep, NASH, and fatty liver (FL). Total DNA was extracted from the biopsied liver samples. DNA fragments were amplified by PCR and DNA sequences determined in the control and coding regions of mitochondrion.Results: When the numbers of mutations per 1,000 bases of mitochondrial DNA were compared between each group, no significant differences were found among D‐loop, HV1, and HV2 mitochondrial DNA regions. However, there were significantly more mutations in ND1 and COII of Al‐Hep and NASH than in FL, and mutations were comparatively at random. Neither a region in which mutations were focused nor differences among the groups were recognized. When details of the base mutation in a control region were investigated by group, the transition type of mutation between T:A≪–≫C:G occurred in at least 70%. Also, a transition‐type mutation was found mostly in a coding region, which was similar to the mutation pattern in the control region, except for the ND1 and COII regions where there were hardly any mutations.Conclusions: As gene mutations of mitochondrial DNA appeared frequently in Al‐Hep, and also in NASH, mitochondrial dysfunction caused by mutation in mitochondrial DNA may be involved in the pathogenesis of both diseases.
Concurrent and Predictive Validity of Drug Use and Psychiatric Diagnosis Among First‐Time DWI Offenders
Authors: Palmer Rebekka S. , Ball Samuel A. , Rounsaville Bruce J. , O'Malley Stephanie S. 
Published: February 2007

Background: Previous studies have found that driving while intoxicated (DWI) offenders report high rates of substance dependence and other psychiatric disorders.Method: The current study evaluated the prevalence, clinical correlates at program admission, and prognostic significance over a 1‐year follow‐up of 2 diagnostic subgroup variables (drug abuse or dependence; mood or anxiety disorder) among 290 first‐time DWI offenders receiving group counseling interventions.Results: A lifetime diagnosis of drug abuse or dependence (42% of sample) was associated with higher levels of alcohol consumption, lower coping confidence, greater readiness to change, increased alcohol, drug, and legal problems, and more alcohol‐related negative consequences at the initiation of DWI intervention. Significant decreases in drinking were noted at intervention termination for the drug diagnoses subgroup, but were not sustained at 1‐year follow‐up. The presence of a lifetime diagnosis of anxiety or mood disorder (30% of sample) was associated with lower coping confidence, greater readiness to change, and with greater and more enduring negative consequences of drinking during the DWI intervention and 1‐year follow‐up period.Conclusions: Results suggest that a psychiatric diagnosis might guide the intervention and aftercare planning for DWI offenders to reduce recidivism and drinking.
Predictors of a Suicide Attempt One Year After Entry Into Substance Use Disorder Treatment
Authors: Ilgen Mark A. , Harris Alex H. S. , Moos Rudolf H. , Tiet Quyen Q. 
Published: February 2007

Background:The present study examined the patient intake and treatment‐related risk factors associated with a suicide attempt in the 30 days before a 1‐year posttreatment assessment.Methods:A national sample of 8,807 patients presenting for treatment of substance use disorders (SUDs) in the Department of Veterans Affairs healthcare system were assessed at treatment intake and follow‐up. Using the MacArthur Model, the risk and protective factors for suicide attempt were identified at baseline and during treatment.Results:At follow‐up, 4% (314/8,807) of the patients reported a suicide attempt within the past 30 days. Baseline predictors of a suicide attempt before follow‐up included elevated suicidal/psychiatric symptoms, more recent problematic alcohol use, and longer duration of cocaine use. Contact with the criminal justice system was a protective factor that reduced the likelihood of a future suicide attempt. Greater engagement in SUD treatment was also associated with a reduction in suicide risk.Conclusions:More involvement in SUD treatment reduced the likelihood of a future suicide attempt in high‐risk patients. Substance use disorder treatment providers interested in reducing future suicidal behavior may want to concentrate their efforts on identifying at‐risk individuals and actively engaging these patients in longer treatment episodes.
Attention‐Deficit/Hyperactivity Disorder Risk for Heavy Drinking and Alcohol Use Disorder Is Age Specific
Authors: Molina Brooke S.G. , Pelham William E. , Gnagy Elizabeth M. , Thompson Amanda L. , Marshal Michael P. 
Published: February 2007

Background: This study was designed to assess age specificity in the risk for heavy drinking and alcohol use disorder (AUD) among adolescents and young adults with Attention‐Deficit/Hyperactivity Disorder (ADHD) diagnosed in childhood.Method: Children diagnosed with ADHD (n=364 probands) were interviewed an average of 8 years later in the Pittsburgh ADHD Longitudinal Study, either as adolescents (11–17 years old) or as young adults (18–28 years of age). Demographically similar age‐matched participants without ADHD were recruited as adolescents (n=120) or as adults (n=120) for comparison with the probands. Alcohol involvement was assessed comprehensively to include measures of heavy drinking that are standard in alcoholism research and prognostic of later alcohol‐related problems.Results: Results revealed age specificity in the association such that episodic heavy drinking (measured as 5+ drinks per occasion), drunkenness, DSM‐IV AUD symptoms, and DSM‐IV AUD were elevated among 15‐ to 17‐year‐old probands, but not among younger adolescents. Among young adults, drinking quantity and AUD were elevated among probands with antisocial personality disorder. Childhood predictors indexing antisocial behavior were also examined.Conclusions: The age‐ specificity of these findings helps to explain prior inconsistencies across previous studies regarding risk for alcohol‐related outcomes among children with ADHD.
Embryonic Cerebral Cortical Progenitors Are Resistant to Apoptosis, but Increase Expression of Suicide Receptor DISC‐Complex Genes and Suppress Autophagy Following Ethanol Exposure
Authors: Prock Terasa L. , Miranda Rajesh C. 
Published: February 2007

Background: In utero exposure to ethanol can result in severe fetal brain defects. Previous studies showed that ethanol induces apoptosis in differentiated cortical neurons. However, we know little about ethanol's effects on proliferating embryonic cortical progenitors. This study investigated the impact of ethanol exposure on the Fas/Apo‐1/CD95 suicide receptor pathway, and on the survival of proliferating cortical neuroepithelial progenitors.Methods: Murine embryonic‐derived primary cortical neuroepithelial cells were maintained as neurosphere cultures and exposed to a dose range of ethanol for periods ranging from 1 to 5 days. Programmed cell death was measured by 4 independent means (Annexin‐V staining, caspase activation, DNA fragmentation, and autophagic vacuole formation). Surface Fas/Apo‐1 suicide receptor expression was measured by flow cytometry. Expression of Fas/Apo‐1‐associated DISC‐complex genes was measured by quantitative polymerase chain reaction.Results: Ethanol exposure did not substantially increase apoptosis, necrosis, or surface Fas/Apo‐1 expression. Moreover, ethanol significantly decreased caspase activation and autophagic activity. Finally, ethanol exposure induced mRNA expression of genes that constitute the death receptor complex.Conclusions: This study provides surprising evidence that ethanol does not induce either programmed cell death or necrosis of immature progenitors during neurogenesis, although ethanol may render neural progenitors susceptible to future apoptotic insults. Furthermore, our novel observation that ethanol suppresses autophagy is consistent with a hypothesis that ethanol promotes premature neural progenitor maturation. Taken together with our previous data regarding the role of the Fas/Apo‐1 receptor in neural development, we conclude that ethanol disrupts basic proliferation and differentiation machinery rather than initiating cell death per se.