bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular rearrangement of hsp90‐binding immunophilins accompanies neuronal differentiation and neurite outgrowth
Authors: Quintá Héctor R. , Maschi Darío , Gomez‐Sanchez Celso , Piwien‐Pilipuk Graciela , Galigniana Mario D. 
Published: August 2010

J. Neurochem.(2010)115, 716–734.AbstractFKBP51 and FKBP52 (FK506‐binding protein 51 and 52) are tetratricopeptide repeat‐domain immunophilins belonging to the tetratricopeptide‐protein•hsp90•hsp70•p23 heterocomplex bound to steroid receptors. Immunophilins are related to receptor folding, subcellular localization, and hormone‐dependent transcription. Also, they bind the immunosuppressant macrolide FK506, which shows neuroregenerative and neuroprotective actions by a still unknown mechanism. In this study, we demonstrate that in both, undifferentiated neuroblastoma cells and embryonic hippocampal neurons, the FKBP52•hsp90•p23 heterocomplex concentrates in a perinuclear structure. Upon cell stimulation with FK506, this structure disassembles and this perinuclear area becomes transcriptionally active. The acquisition of a neuronal phenotype is accompanied by increased expression of βIII‐tubulin, Map‐2, Tau‐1, but also hsp90, hsp70, p23, and FKBP52. During the early differentiation steps, the perinuclear heterocomplex redistributes along the cytoplasm and nascent neurites, p23 binds to intermediate filaments and microtubules acquired higher filamentary organization. While FKBP52 moves towards neurites and concentrates in arborization bodies and terminal axons, FKBP51, whose expression remains constant, replaces FKBP52 in the perinuclear structure. Importantly, neurite outgrowth is favored by FKBP52 over‐expression or FKBP51 knock‐down, and is impaired by FKBP52 knock‐down or FKBP51 over‐expression, indicating that the balance between these FK506‐binding proteins plays a key role during the early mechanism of neuronal differentiation.
The E3‐ubiquitin ligase TRIM2 regulates neuronal polarization
Authors: Khazaei Mohammad R. , Bunk Eva C. , Hillje Anna‐Lena , Jahn Hannah M. , Riegler Eva M. , Knoblich Jürgen A. , Young Peter , Schwamborn Jens C. 
Published: August 2010

J. Neurochem. (2011) 117, 29–37.AbstractThe establishment of a polarized morphology with a single axon and multiple dendrites is an essential step during neuronal differentiation. This cellular polarization is largely depending on changes in the dynamics of the neuronal cytoskeleton. Here, we show that the tripartite motif (TRIM)‐NHL protein TRIM2 is regulating axon specification in cultured mouse hippocampal neurons, where one of several initially indistinguishable neurites is selected to become the axon. Suppression of TRIM2 by RNA interference results in the loss of neuronal polarity while over‐expression of TRIM2 induces the specification of multiple axons. TRIM2 conducts its function during neuronal polarization by ubiquitination of the neurofilament light chain. Together, our results imply an important function of TRIM2 for axon outgrowth during development.
Burnout as an existential deficiency – lived experiences of burnout sufferers
Authors: Arman Maria , Hammarqvist Anne‐Sofie , Rehnsfeldt Arne 
Published: August 2010

Scand J Caring Sci; 2011; 25; 294–302

Burnout as an existential deficiency – lived experiences of burnout sufferers Aiming at a deeper and existential understanding of burnout, by looking especially at the patterns of health, suffering and expressions of understanding of life in a longitudinal perspective, qualitative data from 18 Swedish women and men were analysed. Burnout as an illness has been subject to constant questioning during its incidence in western societies. Yet it is generally agreed that people afflicted by burnout experience huge problems and suffering. Data from interviews face to face, telephone follow‐up interviewing during 1 year and e‐mail interview dialogues were collected. With a nursing science perspective in which health and suffering are basic concepts, an interpretive analysis revealed signs of existential deficiencies in the lived experience of the people afflicted. The images of the patterns of lived experience elucidated reveal a discord between the people and their work, a blindness towards their own actions, bodily illness as signs of burnout, experiencing a collapse as a ‘crossroad’, secondary suffering related to the social system and a struggle towards a way out. Our interpretation reveals assumptions concerning three levels of life: actions, values and universal existence, which is somewhat different from previous studies. Unless a person is in contact with these three dimensions, he/she seems to find it difficult to maintain health in his/her encounters with life. Implications for health care are existential interest on the part of caregivers and understanding of life as signs of universal values. Patients’‘shut off’ and restrained longings understood as signs of ‘darkness’ in their understanding of life may induce caring acts on the part of caregivers that offer patients an opening and a glimpse of what it might be like to find health in the midst of their suffering. The caregivers’ own natural light of understanding of life can then work as a caring component.
Analysis of the actions of the novel dopamine receptor‐directed compounds (S)‐OSU6162 and ACR16 at the D2dopamine receptor
Authors: Kara Elodie , Lin Hong , Svensson Kjell , Johansson Anette M , Strange Philip G 
Published: August 2010

BACKGROUND AND PURPOSEThe two phenylpiperidines, OSU6162 and ACR16, have been proposed as novel drugs for the treatment of brain disorders, including schizophrenia and Huntington's disease, because of their putative dopamine stabilizing effects. Here we evaluated the activities of these compounds in a range of assays for the D2dopamine receptorin vitro.EXPERIMENTAL APPROACHThe affinities of these compounds for the D2dopamine receptor were evaluated in competition with [3H]spiperone and [3H]NPA. Agonist activity of these compounds was evaluated in terms of their ability to stimulate [35S]GTPγS binding.KEY RESULTSBoth compounds had low affinities for inhibition of [3H]spiperone binding (pKivs. [3H]spiperone, ACR16: <5, OSU6162: 5.36). Neither compound was able to stimulate [35S]GTPγS binding when assayed in the presence of Na+ions, but if the Na+ions were removed, both compounds were low‐affinity, partial agonists (Emaxrelative to dopamine: ACR16: 10.2%, OSU6162:54.3%). Schild analysis of the effects of OSU6162 to inhibit dopamine‐stimulated [35S]GTPγS binding indicated Schild slopes of ∼0.9, suggesting little deviation from competitive inhibition. OSU6162 was, however, able to accelerate [3H]NPA dissociation from D2dopamine receptors, indicating some allosteric effects of this compound.CONCLUSIONS AND IMPLICATIONSThe two phenylpiperidines were low‐affinity, low‐efficacy partial agonists at the D2dopamine receptorin vitro, possibly exhibiting some allosteric effects. Comparing theirin vitroandin vivoeffects, thein vitroaffinities were a reasonable guide to potenciesin vivo. However, the lack ofin vitro–in vivocorrelation for agonist efficacy needs to be further addressed.LINKED ARTICLESThis article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2010.161.issue‐6
Study of Metamemory in Patients With Chronic Alcoholism Using a Feeling‐of‐Knowing Episodic Memory Task
Authors: Le Berre Anne‐Pascale , Pinon Karine , Vabret François , Pitel Anne‐Lise , Allain Philippe , Eustache Francis , Beaunieux Hélène 
Published: August 2010

Background:  Alcoholism affects various cognitive processes, including components of memory. Metamemory, though of particular interest for patient treatment, has not yet been extensively investigated.Methods:  A feeling‐of‐knowing (FOK) measure of metamemory was administered to 28 alcoholic patients and 28 healthy controls during an episodic memory task including the learning of 20 pairs of items, followed by a 20‐minute delayed recall and a recognition task. Prior to recognition, participants rated their ability to recognize each nonrecalled word among 4 items. This episodic FOK measure served to compare predictions of future recognition performance and actual recognition performance. Furthermore, a subjective measure of metamemory, the Metamemory In Adulthood (MIA) questionnaire, was completed by patients and controls. This assessment of alcoholic patients’ metamemory profile was accompanied by an evaluation of episodic memory and executive functioning.Results:  FOK results revealed deficits in accuracy, with the alcoholic patients providing overestimations. There were also links between FOK inaccuracy, executive decline, and episodic memory impairment in patients. MIA results showed that although alcoholics did display memory difficulties, they did not differ from controls on questions about memory capacity.Conclusions:  Chronic alcoholism affects both episodic memory and metamemory for novel information. Patients were relatively unaware of their memory deficits and believed that their memory was as good as that of the healthy controls. The monitoring measure (FOK) and the subjective measure of metamemory (MIA) showed that patients with chronic alcoholism overestimated their memory capacities. Episodic memory deficit and executive dysfunction would explain metamemory decline in this clinical population.
Reduced Expression of Circadian Clock Genes in Male Alcoholic Patients
Authors: Huang Ming‐Chyi , Ho Chia‐Wei , Chen Chun‐Hsin , Liu Shing‐Cheng , Chen Chiao‐Chicy , Leu Sy‐Jye 
Published: August 2010

Background:  There are clear interactions between chronic alcohol consumption and circadian rhythmicity that is regulated by several circadian clock genes. The altered expressions of these genes have been mainly described in animals. The mammalian master clock in the suprachiasmatic nuclei orchestrates the biological rhythms in peripheral tissues. As peripheral blood mononuclear cells (PBMCs) are the most accessible tissue clinically, we assessed the mRNA levels of these genes in patients with alcohol dependence (AD) undergoing alcohol‐withdrawal (AW) treatment.Methods:  Twenty‐two male patients fulfilled the DSM‐IV diagnostic criteria of AD, and 12 comparison healthy control subjects were recruited. The patients with AD were further divided by the presence of delirium tremens (DTs), the most severe form of AW syndrome, into DT group and non‐DT group. All the participants received blood withdrawal at 9 am, while the patients with AD had blood collection twice: on the next morning of admission (baseline) and on the seventh day. PBMCs were isolated from whole blood, and the mRNA expression profiles of hClock1, hBmal1, hPer1, hPer2, hCry1, and hCry2 were determined by quantitative real‐time PCR.Results:  The baseline mRNA levels of the target circadian clock genes were markedly lower in patients with AD than in control subjects. After 1 week of alcohol detoxification, there were very limited restorations of discrete circadian gene expressions. DT group did not differ in the expression patterns of circadian clock genes from non‐DT group.Conclusions:  This is the first study demonstrating the overall lowering of circadian clock genes among patients with AD. The expression pattern is comparable between patients with and without DTs. Although preliminary with data at only one single time point, the observation of strikingly reduced mRNA levels supports the association between circadian clock gene dysregulation and chronic alcohol intake.
Late‐Life Alcohol Consumption and 20‐Year Mortality
Authors: Holahan Charles J. , Schutte Kathleen K. , Brennan Penny L. , Holahan Carole K. , Moos Bernice S. , Moos Rudolf H. 
Published: August 2010

Background:  Growing epidemiological evidence indicates that moderate alcohol consumption is associated with reduced total mortality among middle‐aged and older adults. However, the salutary effect of moderate drinking may be overestimated owing to confounding factors. Abstainers may include former problem drinkers with existing health problems and may be atypical compared to drinkers in terms of sociodemographic and social‐behavioral factors. The purpose of this study was to examine the association between alcohol consumption and all‐cause mortality over 20 years among 1,824 older adults, controlling for a wide range of potential confounding factors associated with abstention.Methods:  The sample at baseline included 1,824 individuals between the ages of 55 and 65. The database at baseline included information on daily alcohol consumption, sociodemographic factors, former problem drinking status, health factors, and social‐behavioral factors. Abstention was defined as abstaining from alcohol at baseline. Death across a 20‐year follow‐up period was confirmed primarily by death certificate.Results:  Controlling only for age and gender, compared to moderate drinkers, abstainers had a more than 2 times increased mortality risk, heavy drinkers had 70% increased risk, and light drinkers had 23% increased risk. A model controlling for former problem drinking status, existing health problems, and key sociodemographic and social‐behavioral factors, as well as for age and gender, substantially reduced the mortality effect for abstainers compared to moderate drinkers. However, even after adjusting for all covariates, abstainers and heavy drinkers continued to show increased mortality risks of 51 and 45%, respectively, compared to moderate drinkers.Conclusions:  Findings are consistent with an interpretation that the survival effect for moderate drinking compared to abstention among older adults reflects 2 processes. First, the effect of confounding factors associated with alcohol abstention is considerable. However, even after taking account of traditional and nontraditional covariates, moderate alcohol consumption continued to show a beneficial effect in predicting mortality risk.
Increased Risk of Esophageal Varices, Liver Cancer, and Death in Patients With Alcoholic Liver Disease
Authors: Stokkeland Knut , Ebrahim Fereshte , Ekbom Anders 
Published: August 2010

Background and Aims:  During the last decades, a multitude of different treatments for chronic liver disease have been introduced. New surveillance programs have been established to detect esophageal varices and liver cancer. The aims of our study were to assess whether the prognosis for patients hospitalized with liver diseases between 1969 and 2006 had improved and to study the differences in mortality and complications between patients with alcoholic liver disease and nonalcoholic liver diseases.Methods:  We used the Swedish Hospital Discharge Register and Cause of Death Register at the National Board of Health and Welfare in Sweden between 1969 and 2006 to identify and follow‐up a cohort of patients with liver disease according to the International Classification of Diseases‐8, ‐9, and ‐10.Results:  There were 36,462 patients hospitalized with alcoholic and 95,842 with nonalcoholic liver diseases. The main finding was that patients hospitalized with alcoholic liver disease had an increased mortality risk, compared to patient with nonalcoholic liver disease, 1.89 (1.85 to 1.92). In addition, the patients with alcoholic liver disease had an increased risk for esophageal varices and liver cancer. There was a reduced risk for hospitalization with esophageal varices for patients with nonalcoholic liver disease up to 1998.Conclusions:  We found that the prognosis for patients hospitalized with chronic liver diseases had not improved. Patients with alcoholic liver disease have an increased risk of complications, which suggest that the disease is more aggressive and are in need of closer follow‐up than other chronic liver diseases.
The Energy and Climate Change Implications of Different Music Delivery Methods
Authors: Weber Christopher L. , Koomey Jonathan G. , Matthews H. Scott 
Published: August 2010

SummaryThe impacts of information and communications technology (ICT) on the environment have been a rich area for research in recent years. A prime example is the continuing rise of digital music delivery, which has obvious potential for reducing the energy and environmental impacts of producing and delivering music to final consumers. This study assesses the energy and carbon dioxide (CO2) emissions associated with several alternative methods for delivering one album of music to a final customer, either through traditional retail or e‐commerce sales of compact discs or through a digital download service. We analyze a set of six (three compact disc and three digital download) scenarios for the delivery of one music album from the recording stage to the consumer's home in either CD or digital form. We find that despite the increased energy and emissions associated with Internet data flows, purchasing music digitally reduces the energy and carbon dioxide (CO2) emissions associated with delivering music to customers by between 40% and 80% from the best‐case physical CD delivery, depending on whether a customer then burns the files to CD. Despite the dominance of the digital music delivery method, however, there are scenarios by which digital music performs less well, and these scenarios are explored. We suggest future areas of research, including alternative digital media services, such as subscription and streaming systems, for which Internet energy usage may be larger than for direct downloads.
Length of Stay for Older Adults Residing in Nursing Homes at the End of Life
Authors: Kelly Anne , Conell‐Price Jessamyn , Covinsky Kenneth , Cenzer Irena Stijacic , Chang Anna , Boscardin W. John , Smith Alexander K. 
Published: August 2010

OBJECTIVES: To describe lengths of stay of nursing home decedents.DESIGN: Retrospective cohort study.SETTING: The Health and Retirement Study (HRS), a nationally representative survey of U.S. adults aged 50 and older.PARTICIPANTS: One thousand eight hundred seventeen nursing home residents who died between 1992 and 2006.MEASUREMENTS: The primary outcome was length of stay, defined as the number of months between nursing home admission and date of death. Covariates were demographic, social, and clinical factors drawn from the HRS interview conducted closest to the date of nursing home admission.RESULTS: The mean age of decedents was 83.3±9.0; 59.1% were female, and 81.5% were white. Median and mean length of stay before death were 5 months (interquartile range 1–20) and 13.7±18.4 months, respectively. Fifty‐three percent died within 6 months of placement. Large differences in median length of stay were observed according to sex (men, 3 months vs women, 8 months) and net worth (highest quartile, 3 months vs lowest quartile, 9 months) (all P<.001). These differences persisted after adjustment for age, sex, marital status, net worth, geographic region, and diagnosed chronic conditions (cancer, hypertension, diabetes mellitus, lung disease, heart disease, and stroke).CONCLUSION: Nursing home lengths of stay are brief for the majority of decedents. Lengths of stay varied markedly according to factors related to social support.
Relationship Between Physical Functioning and Physical Activity in the Lifestyle Interventions and Independence for Elders Pilot
Authors: Chalé‐Rush Angela , Guralnik Jack M. , Walkup Michael P. , Miller Michael E. , Rejeski W. Jack , Katula Jeffrey A. , King Abby C. , Glynn Nancy W. , Manini Todd M. , Blair Steven N. , Fielding Roger A. 
Published: August 2010

OBJECTIVES: To determine whether participation in usual moderate‐intensity or more‐vigorous physical activity (MVPA) is associated with physical function performance and to identify sociodemographic, psychosocial, and disease‐related covariates that may also compromise physical function performance.DESIGN: Cross‐sectional analysis of baseline variables of a randomized controlled intervention trial.SETTING: Four academic research centers.PARTICIPANTS: Four hundred twenty‐four older adults aged 70 to 89 at risk for mobility disability (scoring <10 on the Short Physical Performance Battery (SPPB)) and able to complete the 400‐m walk test within 15 minutes.MEASUREMENTS: Minutes of MVPA (dichotomized according to above or below 150 min/wk of MVPA) assessed according to the Community Healthy Activities Model Program for Seniors questionnaire, SPPB score, 400‐m walk test, sex, body mass index (BMI), depressive symptoms, age, and number of medications.RESULTS: The SPPB summary score was associated with minutes of MVPA (ρ=0.16, P=.001). In multiple regression analyses, age, minutes of MVPA, number of medications, and depressive symptoms were associated with performance on the composite SPPB (P<.05). There was an association between 400‐m walk time and minutes of MVPA (ρ=−0.18; P<.001). In multiple regression analyses, age, sex, minutes of MVPA, BMI, and number of medications were associated with performance on the 400‐m walk test (P<.05).CONCLUSION: Minutes of MVPA, sex, BMI, depressive symptoms, age, and number of medications are associated with physical function performance and should all be taken into consideration in the prevention of mobility disability.
Habitual Physical Activity Levels Are Associated with Performance in Measures of Physical Function and Mobility in Older Men
Authors: Morie Marina , Reid Kieran F. , Miciek Renee , Lajevardi Newsha , Choong Karen , Krasnoff Joanne B. , Storer Thomas W. , Fielding Roger A. , Bhasin Shalender , LeBrasseur Nathan K. 
Published: August 2010

OBJECTIVES: To determine whether objectively measured physical activity levels are associated with physical function and mobility in older men.DESIGN: Cross‐sectional.SETTING: Academic research center.PARTICIPANTS: Eighty‐two community‐dwelling men aged 65 and older with self‐reported mobility limitations were divided into a low‐activity and a high‐activity group based on the median average daily physical activity counts of the whole sample.MEASUREMENTS: Physical activity according to triaxial accelerometers; physical function and mobility according to the Short Physical Performance Battery (SPPB), gait speed, stair climb time, and a lift‐and‐lower task; aerobic capacity according to maximum oxygen consumption (VO2max); and leg press and chest press maximal strength and peak power.RESULTS: Older men with higher physical activity levels had a 1.4‐point higher mean SPPB score and a 0.35‐m/s faster walking speed than those with lower physical activity levels. They also climbed a standard flight of stairs 1.85 seconds faster and completed 60% more shelves in a lift‐and‐lower task (all P<.01); muscle strength and power measures were not significantly different between the low‐ and high‐activity groups. Correlation analyses and multiple linear regression models showed that physical activity is positively associated with all physical function and mobility measures, leg press strength, and VO2max.CONCLUSION: Older men with higher physical activity levels demonstrate better physical function and mobility than their less‐active peers. Moreover, physical activity levels are predictive of performance in measures of physical function and mobility in older men. Future work is needed to determine whether modifications in physical activity levels can improve or preserve physical performance in later life.