bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Alcohol Abuse on Protein Expression of Midkine and Excitatory Amino Acid Transporter 1 in the Human Prefrontal Cortex
Authors: Flatscher‐Bader Traute , Wilce Peter A. 
Published: July 2008

Background: Alcoholism is associated with shrinkage of brain tissue and reduction in the number of neurons and dendritic arbors particularly in the prefrontal cortex. These changes correlate with the cognitive defects common in alcoholics. A recent study investigated the mRNA expression of selected genes in the prefrontal cortex and found that the levels of mRNA encoding the neurotrophic factor, midkine (MDK), and the excitatory amino acid transporter 1 (EAAT1) were significantly higher in alcoholics compared with nonalcoholic controls. This study aimed to investigate, whether the transcriptional changes observed result in alterations to protein expression. Additionally, the study aimed to expand our understanding of MDK and EAAT1 action by localizing their expression within morphologically and functionally distinct layers of this brain region.Methods: Quantitative changes in protein levels of MDK and EAAT1 were investigated in alcoholic and control cases using Western blots. Immunohistochemistry was utilized to localize proteins expression in formalin‐fixed sagittal sections of the prefrontal cortex.Results: A marked increase was revealed in protein expression of both genes in the prefrontal cortex of chronic alcoholics. MDK‐like immunofluorescence in alcoholic and control cases was present in nuclei throughout the prefrontal cortex and was particularly apparent in cell bodies of astrocytes in cortical layer II. Immunolabeling of the EAAT1 was densest in cortical layer II in control cases and induced in deeper layers in alcoholic cases.Conclusion: Midkine promotes neuronal outgrowth and survival. The up‐regulation of MDK protein expression may indicate the induction of reparative processes. The amino acid transporter is vital for the removal of glutamate from the synaptic cleft. At alcohol withdrawal, extracellular glutamate is thought to reach excitotoxic concentrations. Up‐regulation of EAAT1 throughout the cortical layers may indicate an attempt to combat elevated glutamate concentrations. The predominant expression of the two proteins in layer II of the cortex implies a region‐specific role of astrocytes.
Differences in Acute Alcohol‐Induced Behavioral Responses Among Zebrafish Populations
Authors: Gerlai Robert , Ahmad Fahad , Prajapati Sonal 
Published: July 2008

Background: With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research.Methods: Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory‐bred populations using automated as well as observation based behavioral quantification methods.Results: Alcohol treatment resulted in significant dose‐dependent behavioral changes but the dose–response trajectories differed among zebrafish populations.Conclusions: The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found.
Ethanol‐Induced Behavioral Sensitization in Adolescent and Adult Mice: Role of the nNOS Gene
Authors: Itzhak Yossef , Anderson Karen L. 
Published: July 2008

Background: In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in synaptic plasticity. Recent evidence suggests the role of NO in a variety of effects produced by alcohol in the central nervous system. The current study investigated the role of the nNOS gene in the development of behavioral sensitization to ethanol in adolescent and adult mice.Methods: Adolescent and adult wild type (WT; B6;129SF2) and nNOS knockout (KO; B6;129S4‐Nos1) mice of both sexes received saline or ethanol (1.5 g/kg; intraperitoneally) for 5 consecutive days, and locomotor activity was recorded daily. The locomotor response to challenge ethanol and saline injections was investigated at various time points following withdrawal from ethanol.Results: Adolescent WT but not nNOS KO mice developed a long‐lasting sensitized response to ethanol as well as context‐dependent hyperlocomotion (in response to saline) from adolescence through adulthood; sex‐dependent differences were not observed. Compared to adolescent WT mice, adult WT males developed a short‐term sensitized response to ethanol and context‐dependent hyperlocomotion; adult WT females showed only short‐term context‐dependent hyperlocomotion. Adult nNOS KO males (like their adolescent counterparts) did not develop behavioral sensitization; no significant differences between adult nNOS KO and WT females were observed. Blood ethanol concentrations did not show genotype‐ or sex‐dependent differences.Conclusions: (1) The nNOS gene is required for the development of behavioral sensitization to ethanol in adolescent male and female mice. (2) Adolescent exposure to ethanol results in long‐lasting behavioral sensitization through adulthood, while adult exposure to ethanol results in a shorter behavioral sensitization. (3) Sex‐dependent differences are observed when ethanol exposure begins in adulthood but not in adolescence. (4) Ethanol‐induced behavioral sensitization in adulthood is nNOS‐dependent in males but not in females. Taken together, results suggest genotype‐, ontogeny‐, and sex‐dependent differences in the development of behavioral sensitization to ethanol.
Lack of Effectiveness of a Multidisciplinary Fall‐Prevention Program in Elderly People at Risk: A Randomized, Controlled Trial
Authors: Hendriks Marike R. C. , Bleijlevens Michel H. C. , Van Haastregt Jolanda C. M. , Crebolder Harry F. J. M. , Diederiks Joseph P. M. , Evers Silvia M. A. A. , Mulder Wubbo J. , Kempen Gertrudis I. J. M. , Van Rossum Erik , Ruijgrok Joop M. , Stalenhoef Paul A. , Van Eijk Jacques Th. M. 
Published: July 2008

OBJECTIVES: To assess whether a pragmatic multidisciplinary fall‐prevention program was more effective than usual care in preventing new falls and functional decline in elderly people.DESIGN: A two‐group, randomized, controlled trial with 12 months of follow‐up.SETTING: University hospital and home‐based intervention, the Netherlands.PARTICIPANTS: Three hundred thirty‐three community‐dwelling Dutch people aged 65 and over who were seen in an emergency department after a fall.INTERVENTION: Participants in the intervention group underwent a detailed medical and occupational‐therapy assessment to evaluate and address risk factors for recurrent falls, followed by recommendations and referral if indicated. People in the control group received usual care.MEASUREMENTS: Number of people sustaining a fall (fall calendar) and daily functioning (Frenchay Activity Index).RESULTS: Results showed no statistically significantly favorable effects on falls (odds ratio=0.86, 95% confidence interval (CI)=0.50–1.49) or daily functioning (regression coefficient=0.37, CI=−0.90 to 1.63) after 12 months of follow‐up.CONCLUSION: The multidisciplinary fall‐prevention program was not effective in preventing falls and functional decline in this Dutch healthcare setting. Implementing the program in its present form in the Netherlands is not recommended. This trial shows that there can be considerable discrepancy between the “ideal” (experimental) version of a program and the implemented version of the same program. The importance of implementation research in assessing feasibility and effectiveness of such a program in a specific healthcare setting is therefore stressed.
Obesity, Physical Function, and Mortality in Older Adults
Authors: Lang Iain A. , Llewellyn David J. , Alexander Kirsty , Melzer David 
Published: July 2008

OBJECTIVES: To estimate the effects of excess body weight on objective and subjective physical function and mortality risks in noninstitutionalized older adults.DESIGN: Population‐based cohort study.SETTING: The English Longitudinal Study of Ageing (ELSA).PARTICIPANTS: Three thousand seven hundred ninety‐three participants in the ELSA aged 65 and older followed up for 5 years.MEASUREMENTS: Analyses compared the risks of impaired physical function and mortality for subjects who were at the recommended weight (body mass index (BMI)=20.0–24.9) with those who were overweight (BMI=25.0–29.9), obese (BMI=30.0–34.9) or severely obese (BMI≥35.0). Outcome measures were difficulties with activities of daily living (ADLs), score on the Short Physical Performance Battery, and mortality.RESULTS: Participants in higher BMI categories had greater risk of impaired physical function at follow‐up but little or no greater risk of mortality. For example, compared with men of recommended weight, obese men (BMI=30.0–34.9) had relative risk ratios of difficulties with ADLs of 1.99 (95% confidence interval (CI)=1.42–2.78), of measured functional impairment of 1.51 (95% CI=1.05–2.16), and of mortality of 0.99 (95% CI=0.60–1.61). Findings were robust when excluding those who lost weight, smoked, or had poor self‐rated health.CONCLUSION: Excess body weight in people aged 65 and older is associated with greater risk of impaired physical function but not with greater mortality risk. Societies with growing numbers of overweight and obese older people are likely to face increasing burdens of disability‐associated health and social care costs.
Two‐Year Progression from Mild Cognitive Impairment to Dementia: To What Extent Do Different Definitions Agree?
Authors: Matthews Fiona E. , Stephan Blossom C. M. , McKeith Ian G. , Bond John , Brayne Carol ,   the Medical Research Council Cognitive Function and Ageing Study
Published: July 2008

OBJECTIVES: To determine the 2‐year outcome from 16 different current classifications of mild cognitive impairment (MCI) in a population‐based sample.DESIGN: Prospective cohort study: baseline and 2‐year follow‐up phases.SETTING: Large‐scale multicenter study, United Kingdom.PARTICIPANTS:: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study. From this, a subsample of 2,640 individuals was selected and completed a more‐detailed cognitive assessment. Individuals who underwent further assessment were asked to complete annual or 2‐year follow‐ups.MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment and functional ability were collected using a structured interview. Individuals were classified according to 16 different definitions of MCI. These were applied retrospectively.RESULTS: The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality. Progression to dementia was variable and generally poor. Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains. Predictability was age dependent in some but not all classifications.CONCLUSION: Current classifications of MCI have variable outcomes in population‐based samples. Progression to dementia is relatively rare and is dependent on age and definition. Selection criteria developed for the clinic are based on a “high risk” approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available. A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population‐based studies.
Staphylococcus aureus Bloodstream Infections: The Association Between Age and Mortality and Functional Status
Authors: Malani Preeti N. , Rana Meenakshi M. , Banerjee Mousumi , Bradley Suzanne F. 
Published: July 2008

OBJECTIVES: To assess the association between Staphylococcus aureus (S. aureus) blood stream infections (BSIs) and morbidity and mortality in older adults.DESIGN: Retrospective review.SETTING: Veterans Affairs Ann Arbor Healthcare System.PARTICIPANTS: All patients with S. aureus BSI during 2004/05.MEASUREMENTS: Outcomes included in‐hospital and 6‐month mortality, as well as need for subacute care.RESULTS: Sixty‐eight patients with S. aureus BSI were identified (mean age 63.5±13.0). Outcomes of interest included in‐hospital mortality (19.1%), 6‐month mortality (33.8%), and need for subacute care (65.4%). Univariate analysis identified several predictors of death, including older age, chronic renal insufficiency, catheter‐related infection, Charlson weighted index of comorbidity score, and infection with methicillin‐resistant S. aureus (MRSA). Multivariable analysis demonstrated that older age (odds ratio (OR)=1.1, P<.01), chronic renal insufficiency (OR=16.6, P=.01), and MRSA infection (OR=5.1, P=.03) were independently associated with 6‐month mortality. These results suggest that, for every decade increase in age, the odds of death within 6 months of S. aureus BSI doubles (OR=1.1). Chronic renal insufficiency was also independently associated with in‐hospital mortality. Of the previously community‐dwelling patients (n=50), 41 survived hospitalization, of whom 22 (53.7%) required subacute care after discharge.CONCLUSION: Better understanding of the epidemiology of S. aureus BSI in older patients and validation of risk factors for poor functional outcomes and death should be the focus of future prospective studies.
Cognition in Older Women: The Importance of Daytime Movement
Authors: Barnes Deborah E. , Blackwell Terri , Stone Katie L. , Goldman Suzanne E. , Hillier Teresa , Yaffe Kristine ,   for the Study of Osteoporotic Fractures
Published: July 2008

OBJECTIVES: To determine whether an objective measure of daytime movement is associated with better cognitive function in women in their 80s.DESIGN: Cross‐sectional.SETTING: A study of health and aging.PARTICIPANTS: Two thousand seven hundred thirty‐six older women without evidence of dementia.MEASUREMENTS: Daytime movement was assessed using actigraphy, which involved wearing a watch‐like device that objectively quantified accelerometer motion over a mean of 3.0±0.8 days. Cognitive function was measured using the Trail‐Making Test, Part B (Trails B) and the Mini‐Mental State Examination (MMSE). Cognitive impairment was defined as performing 1.5 standard deviations (SDs) worse than the mean on a given test.RESULTS: Participants had a mean age of 83±4; 10% were African American. After adjustment for age, race, and education, women in the highest movement quartiles had better mean cognitive test scores (20±0.3 seconds faster on Trails B and 0.3±0.2 points higher on MMSE, both P<.001) than those in the lowest quartile and were less likely to be cognitively impaired (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.41–0.92 for Trails B; OR=0.68, 95% CI=0.44–1.07 for MMSE). Associations were similar in different subgroups and were independent of self‐reported walking, medical comorbidities, physical function, and other health‐related behaviors.CONCLUSION: Daytime movement as measured objectively using actigraphy was associated with better cognitive function and lower odds of cognitive impairment in women in their 80s. Additional studies are needed to clarify the direction of the association and to explore potential mechanisms.
Platelet transfusions in heparin‐induced thrombocytopenia: a report of four cases and review of the literature
Authors: Hopkins Courtney K. , Goldfinger Dennis 
Published: July 2008

BACKGROUND: Heparin‐induced thrombocytopenia (HIT) is a complication of heparin therapy associated with thrombocytopenia and thrombosis. The diagnosis of HIT is based on clinical criteria and laboratory tests, including the serotonin release assay (SRA). Because HIT patients are thrombocytopenic, platelet (PLT) transfusions may be contemplated; however, many published reviews have concluded that PLT transfusions are contraindicated in HIT because they may precipitate thrombotic events. This study reports four patients with clinically suspected HIT who received PLT transfusions without complications, and the literature regarding this subject has been reviewed.STUDY DESIGN AND METHODS: Patients with a SRA ordered for suspected HIT were retrospectively identified. Charts of patients with positive SRAs who received a PLT transfusion when HIT was clinically suspected were reviewed for evidence of PLT transfusion safety and efficacy. A comprehensive search of the published literature regarding PLT transfusions in patients with HIT was conducted.RESULTS: A SRA was performed on 189 patients with suspected HIT. Thirteen patients tested positive and 4 of these received a PLT transfusion. No patient developed a thrombotic complication. All 4 patients had adequate posttransfusion PLT increments. Two of the 3 patients with active bleeding had cessation of bleeding after transfusion. Review of the literature revealed no case of a complication clearly attributable to PLT transfusion.CONCLUSION: Four patients with clinically suspected HIT and a positive SRA were transfused PLTs both efficaciously and safely. These outcomes, combined with the results of the literature review, suggest that PLT transfusions should not be withheld when clinically indicated in patients with HIT.
Plasma fibrinogen level, bleeding, and transfusion after on‐pump coronary artery bypass grafting surgery: a prospective observational study
Authors: Karlsson Martin , Ternström Lisa , Hyllner Monica , Baghaei Fariba , Nilsson Staffan , Jeppsson Anders 
Published: July 2008

BACKGROUND: Early identification of patients with increased risk of excessive bleeding and transfusion after cardiac surgery offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade and thus a potential biomarker for bleeding. We investigated the relationship between preoperative fibrinogen plasma concentration and postoperative bleeding and transfusion after coronary artery bypass grafting (CABG).STUDY DESIGN AND METHODS: A total of 170 patients (mean age, 67 ± 9 years; 75% men) undergoing isolated CABG were included in a prospective observational study. Patient variables (age, sex, operation time, anticoagulation therapy), preoperative laboratory variables (platelet [PLT] count, activated partial thromboplastin time, prothrombin time, and fibrinogen), postoperative bleeding volume, and transfusions during hospital stay were registered. Independent predictors of bleeding volume and transfusion were identified with multiple regression models.RESULTS: Postoperative bleeding volume correlated univariately with preoperative fibrinogen concentration (r = −0.53, p < 0.001) and PLT count (r = −0.26, p = 0.001) but only preoperative fibrinogen concentration was an independent predictor of postoperative bleeding volume. Twenty‐nine of the 170 patients (17%) received transfusions with blood products. Independent predictors of transfusion were preoperative fibrinogen concentration (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1‐3.7 per 1‐unit decrease; p = 0.027), female sex (OR, 5.0; 95% CI, 1.8‐14.7; p = 0.002), and aortic cross‐clamp time (OR, 1.03; 95% CI, 1.01‐1.06 per minute; p = 0.013).CONCLUSION: The results indicate that preoperative fibrinogen concentration (even within the normal range) is a limiting factor for postoperative hemostasis. Preoperative measurement of fibrinogen concentration provides information about bleeding volume and transfusion requirements after CABG.
Good manufacturing practice–grade fibrin gel is useful as a scaffold for human mesenchymal stromal cells and supports in vitro osteogenic differentiation
Authors: Trombi Luisa , D'Alessandro Delfo , Pacini Simone , Fiorentino Bruno , Scarpellini Manuela , Fazzi Rita , Galimberti Sara , Guazzini Stefano , Petrini Mario 
Published: July 2008

BACKGROUND: Recently, there has been an increased interest in using mesenchymal stromal cells (MSCs) in bone tissue engineering coupled with a suitable scaffold of both biological and synthetic origin. The cells and these constructs can be combined in vitro or directly in vivo to enhance tissue repair. MSCs are spindle‐shaped cells capable of self‐renewal and can be induced to differentiate mainly into osteo‐, chondro‐, and adipogenic‐progeny types. Several biomaterials are currently available and, among them, fibrin‐based constructs seem to be suitable for guiding the cells during tissue repair or regeneration due to their biocompatibility and biodegradability.STUDY DESIGN AND METHODS: Here, this study describes a simple in vitro system using human mesenchymal stromal cells (hMSCs) and fibrin scaffold prepared at different concentrations in fibrinogen (1.5%‐3% and 6%) to evaluate cell proliferation and viability inside these constructs.RESULTS: The data demonstrate that the constructs with 3 percent in fibrinogen resulted in the best scaffolds, because within them the cells were able to proliferate and were uniformly distributed. Finally, analyzing the capability of the clots to support osteogenic differentiation of MSCs, we observed that they differentiated into osteoblasts.CONCLUSION: These results suggest that fibrin gel could be useful as a delivery system for hMSCs.
Psychometric properties of the Blood Donation Reactions Inventory: a subjective measure of presyncopal reactions to blood donation
Authors: France Christopher R. , Ditto Blaine , France Janis L. , Himawan Lina K. 
Published: July 2008

BACKGROUND: Presyncopal reactions are among the most common systemic reactions experienced by blood donors, occur most frequently in novice donors, and can serve as a deterrent to future donation regardless of donation experience. This report describes the validation of a presyncopal reactions scale that can be used to standardize assessment of the donor's subjective experience.STUDY DESIGN AND METHODS: A psychometric analysis of the Blood Donation Reactions Inventory (BDRI), a measure of presyncopal reactions, was conducted using data obtained from two independent samples of volunteer blood donors. Based on these analyses, a new, brief version of the BDRI is proposed, and psychometric data regarding the reliability and construct validity of this instrument are presented.RESULTS: Results of confirmatory factor analyses indicate that a 4‐item version of the BDRI can be used to assess subjective perception of mild, prefaint symptoms. Additional analyses indicate that the BDRI has good internal consistency and demonstrates concurrent validity relative to other indices of donor reactions (e.g., donor chair reclines and loss of consciousness). Construct validity is supported by factor analyses, expected score differences in different donor groups, and convergent validation against measures of donor satisfaction and likelihood of repeat donation.CONCLUSION: The BDRI provides an assessment of subjective ratings of presyncopal symptoms that is brief, easily understood by donors, and quick to administer and score. The BDRI yields important information about the donor's experience that can be used to predict satisfaction and likelihood of repeat donation.