bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Dementia. Part II: Clinical, Functional, Neuropsychological and Social Issues
Authors: McLeanm Steve
Published: January 2011

Comprehensive assessment of the dementing person entails looking beyond syndromal diagnosis to broader aspects of the individual's functioning and circumstances. Systematic attempts are being made to conceptualise the stage, severity and sub-type of dementia and these may prove useful in daily practice. Clinical aspects of a broader assessment include attention to possible coexisting psychiatric syndromes and the disruptive behavioural changes common in dementia. In addition, alternative perspectives to the medical model can contribute valuable information for future planning. Functional assessment can delineate lost abilities that limit the person's adaptive capacity and indicate retained skills necessary for independent living. The neuropsychological approach can identify spared abilities and specific impairments, as well as quantifying changes over time. Attention to social issues can clarify the strengths and deficiencies of the support network and define the burdens of caring. A general approach, which emphasises the need for dementia assessment to be comprehensive, multidisciplinary, naturalistic, intervention oriented, practical and longitudinal, is proposed. This assessment approach is closely linked to the most important role of the clinician, that of continuing care and management.
Depot Neuroleptic Medication and Serum Levels by Radioreceptor Assay: Prolactin Concentration, Electrocardiogram Abnormalities and Six-Month Outcome
Authors: Turbott John , Villiger John , Hunter Lynley
Published: January 2011

Twenty-six chronic schizophrenic patients on well-established depot neuroleptic regimes with stable doses (16 on fluphenazine decanoate, 10 on flupenthixol decanoate) had serum neuroleptic levels measured by radioreceptor assay (RRA) and were followed for six months. The serum prolactin (PRL) concentration and resting electrocardiogram (ECG) were also taken at the beginning of the study period. Correlations had previously been noted between RRA measured neuroleptic levels and outcome in both acute and chronic patients on oral medication. However, in this study of depot medication no significant correlations were found between serum neuroleptic concentration, serum prolactin concentration and the clinical state or outcome. The prevalence (33%) and type of ECG abnormality observed was similar to that previously reported.
Psychiatric Research Series Editor: Wayne Hall: A Critical Survey of Scientific Methods in Two Psychiatry Journals
Authors: Davies John
Published: January 2011

In a critical review of 29 analytical papers from the 1985 Australian and New Zealand Journal of Psychiatry and the American Journal of Psychiatry, examples of 10 methodological errors were found. Twenty-three papers contained at least one error. The commonest error in design was the failure to assess outcome independently of knowledge of the subjects' groups. The most frequent error in analysis was the failure to control for the increased type I error rate when multiple comparisons were made. The high frequency of statistical errors in published articles indicates a need for research methodology to be included in postgraduate psychiatry training. The limitations of statistical designs highlight the importance of alternative investigative models in psychiatric research.
A Study of Women Who Refused to Participate in a Community Survey of Psychiatric Disorder
Authors: Romans-Clarkson Sarah E. , Walton Valerie A. , Herbison G. Peter , Mullen Paul E.
Published: January 2011

The bias resulting from nonresponse causes problems for all epidemiological research. This study investigated the characteristics of those who refused to participate in a community survey of female psychiatric disorder. The demographic characteristics of refusers were similar to those previously reported. When compared to responders, those who refused tended to be older, never married and not widowed, of lower socioeconomic status and urban dwellers. No differences in physical illness requiring hospitalization or inpatient and outpatient psychiatric illness, as assessed through hospital records, were discerned between refusers and responders. Reasons for refusal are discussed. The bias problem may get worse as changing community attitudes to privacy and patients' rights lead to greater refusal rates.
The Gravely Inadequate Definition of a “Mentally Ill Person” in the Mental Health Act (New South Wales) 1983
Authors: Durham James
Published: January 2011

The definition, given in Section 5 of the new Act, of a “mentally ill person” is examined. It is argued that this “definition” is cumbersome, logically incoherent, and impractical. It is predicted that if given effect it will have very unwelcome consequences. Various sources of inherent misunderstanding and uncertainty are noted. Arguments are presented for allowing severe mental illness itself rather than its consequences to be the ground for involuntary hospitalization in certain circumstances. Various suggestions are proposed for the Section's amendment. These fall into two categories, depending upon alternative assumptions: (1) minor improvements, upon the pessimistic assumption that the main structure and content of the definition will be retained; (2) more radical amendment, involving the abandonment of the entire present structure of the section, and the adoption of a working definition of “mental illness” with clear safeguards against error and abuse. The nature and requirements of such a definition are discussed.
The Social and Family Context of Aboriginal Self-Harmful Behaviour in Remote Australia
Authors: Hunter Ernest M.
Published: January 2011

In the preceding paper information was presented on a series of recent Aboriginal suicides in the Kimberley region of Western Australia. In this paper the author proceeds to an examination of the social and historical context of these events, which have occurred in conjunction with increases in other violent behaviours. Drawing from information generated by a survey of a stratified random sample of Aborigines from across the region, the rapidly changing environment of childhood is discussed, with particular attention to the structural and functional changes in caretaking roles. The inter-cultural context of these, as yet, largely intra-cultural manifestations of disadvantage, are emphasised.
Borderline Disorder and Post-Traumatic Stress Disorder: An Equivalence?
Authors: Lonie Isla
Published: January 2011

This paper draws attention to various similarities between Borderline Personality Disorder and Post-traumatic Stress Disorder. It is argued that the former may be considered to be an equivalent of the latter, with the difference that the trauma has either undergone repression or, having been suffered before the establishment of speech, has not been registered in verbal form. The criteria for Borderline Personality Disorder are presented in terms of symptoms of failed attachment consistent with early trauma, and various research papers linking these concepts are considered. Other research in infant attachment suggests intergenerational links between disorganised attachment patterns in infancy and parents with unresolved problems with their own parents. Research concerning the biochemical underpinning of emotional responses is quoted to link these conditions more securely, and may offer conceptual framework in which to understand the need of these patients for therapeutic milieu in which early developmental needs may be understood.
Parental Evaluation of Treatment Outcome and Satisfaction with an Inpatient Program for Eating Disorders
Authors: Kopec-Schrader E. M. , Marden K. , Rey J. M. , Touyz S. W. , Beumont P. J. V.
Published: January 2011

This study is concerned with the service provided to adolescent patients with eating disorders admitted to private hospital. The patients' parents were asked to evaluate the service. Parental satisfaction was assessed by means of questionnaire devised for this purpose and comments were elicited as to how the service could be improved. Parents of consecutive series of 56 patients were asked to complete the questionnaire 6 months after admission; 82% (N=46) responded. Most parents were pleased with the service provided but nevertheless many made some criticisms (35%) or suggestions for improvement (37%). The parental responses were discussed with the staff involved in treatment, resulting in changes to the service.
Are Oppositional and Conduct Disorders of Adolescents Separate Conditions?
Authors: Rey Joseph M. , Morris-Yates Allen
Published: January 2011

This study explores the factor structure of behaviours that correspond to symptoms of DSM-III-R oppositional defiant (OD) and conduct disorder (CD). It also seeks to clarify how those hypothetical factors may relate to diagnoses of OD and CD. Using exploratory factor analysis and cluster analysis of parent questionnaire data from group of referred adolescents (N=528) diagnosed according to DSM-III criteria the authors extracted four factors. One of them corresponded closely to DSM-III-R OD, while the others comprised different aspects of the CD construct. The findings suggest there are subtypes of conduct problems in adolescents, and give some support to the distinction between conduct and oppositional disorders.
Estimating the Proportion of Healthcare-Associated Infections That Are Reasonably Preventable and the Related Mortality and Costs
Authors: Umscheid Craig A. , Mitchell Matthew D. , Doshi Jalpa A. , Agarwal Rajender , Williams Kendal , Brennan Patrick J.
Published: January 2011

Objective.

To estimate the proportion of healthcare-associated infections (HAIs) in US hospitals that are “reasonably preventable,” along with their related mortality and costs.

Methods.

To estimate preventability of catheter-associated bloodstream infections (CABSIs), catheter-associated urinary tract infections (CAUTIs), surgical site infections (SSIs), and ventilator-associated pneumonia (VAP), we used a federally sponsored systematic review of interventions to reduce HAIs. Ranges of preventability included the lowest and highest risk reductions reported by US studies of “moderate” to “good” quality published in the last 10 years. We used the most recently published national data to determine the annual incidence of HAIs and associated mortality. To estimate incremental cost of HAIs, we performed a systematic review, which included costs from studies in general US patient populations. To calculate ranges for the annual number of preventable infections and deaths and annual costs, we multiplied our infection, mortality, and cost figures with our ranges of preventability for each HAI.

Results.

AS many as 65%–70% of cases of CABSI and CAUTI and 55% of cases of VAP and SSI may be preventable with current evidence-based strategies. CAUTI may be the most preventable HAI. CABSI has the highest number of preventable deaths, followed by VAP. CABSI also has the highest cost impact; costs due to preventable cases of VAP, CAUTI, and SSI are likely less.

Conclusions.

Our findings suggest that 100% prevention of HAIs may not be attainable with current evidence-based prevention strategies; however, comprehensive implementation of such strategies could prevent hundreds of thousands of HAIs and save tens of thousands of lives and billions of dollars.
Validity of ICD-9-CM Coding for Identifying Incident Methicillin-Resistant Staphylococcus aureus (MRSA) Infections: Is MRSA Infection Coded as a Chronic Disease?
Authors: Schweizer Marin L. , Eber Michael R. , Laxminarayan Ramanan , Furuno Jon P. , Popovich Kyle J. , Hota Bala , Rubin Michael A. , Perencevich Eli N.
Published: January 2011

Background and Objective.

Investigators and medical decision makers frequently rely on administrative databases to assess methicillin-resistant Staphylococcus aureus (MRSA) infection rates and outcomes. The validity of this approach remains unclear. We sought to assess the validity of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for infection with drug-resistant microorganisms (V09) for identifying culture-proven MRSA infection.

Design.

Retrospective cohort study.

Methods.

All adults admitted to 3 geographically distinct hospitals between January 1, 2001, and December 31, 2007, were assessed for presence of incident MRSA infection, defined as an MRSA-positive clinical culture obtained during the index hospitalization, and presence of the V09 ICD-9-CM code. The k statistic was calculated to measure the agreement between presence of MRSA infection and assignment of the V09 code. Sensitivities, specificities, positive predictive values, and negative predictive values were calculated.

Results.

There were 466,819 patients discharged during the study period. Of the 4,506 discharged patients (1.0%) who had the V09 code assigned, 31% had an incident MRSA infection, 20% had prior history of MRSA colonization or infection but did not have an incident MRSA infection, and 49% had no record of MRSA infection during the index hospitalization or the previous hospitalization. The V09 code identified MRSA infection with a sensitivity of 24% (range, 21%–34%) and positive predictive value of 31% (range, 22%–53%). The agreement between assignment of the V09 code and presence of MRSA infection had a k coefficient of 0.26 (95% confidence interval, 0.25–0.27).

Conclusions.

In its current state, the ICD-9-CM code V09 is not an accurate predictor of MRSA infection and should not be used to measure rates of MRSA infection.
Multicenter, Prospective Surveillance Study of Staphylococcus aureus Nasal Colonization in 28 Italian Intensive Care Units: The ISABEL Study
Authors: Viale Pierluigi , Gesu Giovanni , Privitera Gaetano , Allaria Biagio , Petrosillo Nicola , Zamparini Eleonora , Scudeller Luigia ,   ISABEL Study Group
Published: January 2011

The role of methicillin-resistant Staphylococcus aureus (MRSA) colonization as a predictor of invasive disease in intensive care unit (ICU) patients was established many years ago. The role of mefhicillin-susceptible Staphylococcus aureus (MSSA) colonization is more debated, although in a recent report patients who were carriers of MRSA or MSSA at ICU admission were found to be at increased risk. Whether carriage at ICU admission involves a higher risk of invasive infection than carriage acquired during an ICU stay has not been established. We report the results of a study aimed at estimating the frequency of S. aureus (MRSA and MSSA) colonization at admission and at discharge in patients admitted to several ICUs in Italy and at estimating the relationship between colonization status and infection by S. aureus.
Effect of Accounting for Multiple Concurrent Catheters on Central Line–Associated Bloodstream Infection Rates: Practical Data Supporting a Theoretical Concern
Authors: Aslakson Rebecca A. , Romig Mark , Galvagno Samuel M. , Colantuoni Elizabeth , Cosgrove Sara E. , Perl Trish M. , Pronovost Peter J.
Published: January 2011

Background.

Central line-associated bloodstream infection (CLABSI) rates are gaining importance as they become publicly reported metrics and potential pay-for-performance indicators. However, the current conventional method by which they are calculated may be misleading and unfairly penalize high-acuity care settings, where patients often have multiple consurrent central venous catheters (CVCs).

Objective.

We compared the conventional method of calculating CLABSI rates, in which the number of catheter-days is used (1 patient with n catheters for 1 day has 1 catheter-day), with a new method that accounts for multiple concurrent catheters (1 patient with n catheters for 1 day has n catheter-days), to determine whether the difference appreciably changes the estimated CLABSI rate.

Design.

Cross-sectional survey.

Setting.

Academic, tertiary care hospital.

Patients.

Adult patients who were consecutively admitted from June 10 through July 9, 2009, to a cardiac-surgical intensive care unit and a surgical intensive and surgical intermediate care unit.

Results.

Using the conventional method, we counted 485 catheter-days throughout the study period, with a daily mean of 18.6 catheter-days (95% confidence interval, 17.2-20.0 catheter-days) in the 2 intensive care units. In contrast, the new method identified 745 catheter-days, with a daily mean of 27.5 catheter-days (95% confidence interval, 25.6-30.3) in the 2 intensive care units. The difference was statistically significant (P < .001). The new method that accounted for multiple concurrent CVCs resulted in a 53.6% increase in the number of catheter-days; this increased denominator decreases the calculated CLABSI rate by 36%.

Conclusions.

The undercounting of catheter-days for patients with multiple concurrent CVCs that occurs when the conventional method of calculating CLABSI rates is used inflates the CLABSI rate for care settings that have a high CVC burden and may not adjust for underlying medical illness. Additional research is needed to validate and generalize our findings.
Peripherally Inserted Central Venous Catheter–Associated Bloodstream Infections in Hospitalized Adult Patients
Authors: Ajenjo M. Cristina , Morley James C. , Russo Anthony J. , McMullen Kathleen M. , Robinson Catherine , Williams Robert C. , Warren David K.
Published: January 2011

Background.

Limited data on the risk of peripherally inserted central venous catheter-associated bloodstream infections (PICC BSIs) in hospitalized patients are available. In 2007, dedicated intravenous therapy nurses were no longer available to place difficult peripheral intravenous catheters or provide PICC care Barnes-Jewish Hospital.

Objectives.

To determine the hospital-wide incidence of PICC BSIs and to assess the effect of discontinuing intravenous therapy service on PICC use and PICC BSI rates.

Setting.

A 1,252-bed tertiary care teaching hospital.

Methods.

A 31-month retrospective cohort study was performed. PICC BSIs were defined using National Healthcare Safety Network criteria.

Results.

In total, 163 PICC BSIs were identified (3.13 BSIs per 1,000 catheter-days). PICC use was higher in intensive care units (ICUs) than non-ICU areas (PICC utilization ratio, 0.109 vs 0.059 catheter-days per patient-day for ICU vs non-ICU; rate ratio [RR], 1.84 [95% confidence interval {CI}, 1.78-1.91]). PICC BSI rates were higher in ICUs (4.79 vs 2.79 episodes per 1,000 catheter-days; RR, 1.7 [95% CI, 1.10-2.61]). PICC use increased hospital-wide after the intravenous therapy service was discontinued (0.049 vs 0.097 catheter-days per patient-day; P = .01), but PICC BSI rates did not change (2.68 vs 3.63 episodes per 1,000 catheter-days; P = .06). Of PICC BSIs, 73% occurred in non-ICU patients.

Conclusions.

PICC use and PICC BSI rates were higher in ICUs; however, most of the PICC BSIs occurred in non-ICU areas. Reduction in intravenous therapy services was associated with increased PICC use across the hospital, but PICC BSI rates did not increase.
Is Continuous Subglottic Suctioning Cost-Effective for the Prevention of Ventilator-Associated Pneumonia?
Authors: Hallais Corinne , Merle Véronique , Guitard Pierre-Gildas , Moreau Anne , Josset Valérie , Thillard Denis , Haghighat Suzanne , Veber Benoit , Czernichow Pierre
Published: January 2011

Objective.

To establish whether continuous subglottic suctioning (CSS) could be cost-effective.

Design.

Cost-benefit analysis, based on a hypothetical replacement of conventional ventilation (CV) with CSS.

Setting.

A surgical intensive care unit (SICU) of a tertiary care university hospital in France.

Patients.

All consecutive patients receiving ventilation in the SICU in 2006.

Methods.

Efficacy data for CSS were obtained from the literature and applied to the SICU of our hospital. Costs for CV and CSS were provided by the hospital pharmacy; costs for ventilator-associated pneumonia (VAP) were obtained from the literature. The cost per averted VAP episode was calculated, and a sensitivity analysis was performed on VAP incidence and on the number of tubes required for each patient.

Results.

At our SICU in 2006, 416 patients received mechanical ventilation for 3,487 ventilation-days, and 32 VAP episodes were observed (7.9 episodes per 100 ventilated patients; incidence density, 9.2 episodes per 10,000 ventilation-days). Based on the hypothesis of a 29% reduction in the risk of VAP with CSS than CV, 9 VAP episodes could have been averted. The additional cost of CSS for 2006 was estimated to be €10,585.34. The cost per averted VAP episode was €1,176.15. Assuming a VAP cost of €4,387, a total of 3 averted VAP episodes would neutralize the additional cost. For a low VAP incidence of 6.6%, the cost per averted VAP would be €1,323. If each patient required 2 tubes during ventilation, the cost would be €1,383.69 per averted VAP episode.

Conclusion.

Replacement of CV with CSS was cost-effective even when assuming the most pessimistic scenario of VAP incidence and costs.
Effect of Patterns of Transferring Patients among Healthcare Institutions on Rates of Nosocomial Methicillin-ResistantStaphylococcus aureusTransmission: A Monte Carlo Simulation
Authors: Lesosky Maia , McGeer Allison , Simor Andrew , Green Karen , Low Don E. , Raboud Janet
Published: January 2011

Objective.

To determine the effect of the rate and pattern of patient transfers among institutions within a single metropolitan area on the rates of methicillin-resistantStaphylococcus aureus(MRSA) transmission among patients in hospitals and nursing homes.

Methods.

A stochastic, discrete-time, Monte Carlo simulation was used to model the rate and spread of MRSA transmission among patients in medical institutions within a single metropolitan area. Admission, discharges, transfers, and nosocomial transmission were simulated with respect to different interinstitutional transfer strategies and various situational scenarios, such as outlier institutions with high transmission rates.

Results.

The simulation results indicated that transfer patterns and transfer rate changes do not affect nosocomial MRSA transmission. Outlier institutions with high transmission rates affect the systemwide rate of nosocomial infections differently, depending on institution type.

Conclusion.

It is worth effort to understanding disease-transmission dynamics and interinstitutional transfer patterns for the management of recently introduced diseases or strains. Once endemic in a system, other strategies for transmission control need to be implemented.
Martin’s maximum and weak square
Authors: Cummings James , Magidor Menachem
Published: January 2011

We analyse the influence of the forcing axiom Martin’s Maximum on the existence of square sequences, with a focus on the weak square principle◻λ,μ\square _{\lambda , \mu }.
Estimates of nuclear DNA content in 98 species of brown algae (Phaeophyta)
Authors: Phillips Naomi , Kapraun Donald F. , Gómez Garreta Amelia , Ribera Siguan M. Antonia , Rull Jorde L. , Salvador Soler Noemi , Lewis Raymond , Kawai Hiroshi
Published: January 2011

Background and aims

Brown algae are critical components of marine ecosystems around the world. However, the genome of only one species of the class has so far been sequenced. This contrasts with numerous sequences available for model organisms such as higher plants, flies or worms. The present communication expands our coverage of DNA content information to 98 species of brown algae with a view to facilitating further genomic investigations of the class.

Methodology

The DNA-localizing fluorochrome DAPI (4′,6-diamidino-2-phenylindole) and the red blood cell (chicken erythrocyte) standard were used to estimate 2C values by static microspectrophotometry.

Principal results

2C DNA contents are reported for 98 species of brown algae, almost doubling the number of estimates available for the class. The present results also expand the reported DNA content range to 0.2–3.6 pg, with several species of Fucales and Laminariales containing apparent polyploid genomes with 2C = 1.8–3.6 pg.

Conclusions

The data provide DNA content values for 12 of the 19 recognized orders of brown algae spanning the breadth of the class. Despite earlier contentions concerning DNA content and the presence of oogamy, the present results do not support a correlation between phylogenetic placement and genome size. The closest sister groups to the brown algae have genome sizes on the order of 0.3 pg (e.g. Schizocladiophyceae), suggesting that this may be the ancestral genome size. However, DNA content ranges widely across the class.
Succinct data structures for assembling large genomes
Authors: Conway Thomas C. , Bromage Andrew J.
Published: January 2011

Motivation: Second-generation sequencing technology makes it feasible for many researches to obtain enough sequence reads to attempt the de novo assembly of higher eukaryotes (including mammals). De novo assembly not only provides a tool for understanding wide scale biological variation, but within human biomedicine, it offers a direct way of observing both large-scale structural variation and fine-scale sequence variation. Unfortunately, improvements in the computational feasibility for de novo assembly have not matched the improvements in the gathering of sequence data. This is for two reasons: the inherent computational complexity of the problem and the in-practice memory requirements of tools.

Results: In this article, we use entropy compressed or succinct data structures to create a practical representation of the de Bruijn assembly graph, which requires at least a factor of 10 less storage than the kinds of structures used by deployed methods. Moreover, because our representation is entropy compressed, in the presence of sequencing errors it has better scaling behaviour asymptotically than conventional approaches. We present results of a proof-of-concept assembly of a human genome performed on a modest commodity server.

Availability: Binaries of programs for constructing and traversing the de Bruijn assembly graph are available from http://www.genomics.csse.unimelb.edu.au/succinctAssembly.

Contact:  tom.conway@nicta.com.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
S (+)-Ketamine Suppresses Desensitization of γ-Aminobutyric Acid Type B Receptor-mediated Signaling by Inhibition of the Interaction of γ-Aminobutyric Acid Type B Receptors with G Protein–coupled Receptor Kinase 4 or 5
Authors: Ando Yuko , Hojo Minoru , Kanaide Masato , Takada Masafumi , Sudo Yuka , Shiraishi Seiji , Sumikawa Koji , Uezono Yasuhito
Published: January 2011

Background

Intrathecal baclofen therapy is an established treatment for severe spasticity. However, long-term management occasionally results in the development of tolerance. One of the mechanisms of tolerance is desensitization of γ-aminobutyric acid type B receptor (GABABR) because of the complex formation of the GABAB2 subunit (GB2R) and G protein-coupled receptor kinase (GRK) 4 or 5. The current study focused on S(+)-ketamine, which reduces the development of morphine tolerance. This study was designed to investigate whether S(+)-ketamine affects the GABABR desensitization processes by baclofen.

Methods

The G protein-activated inwardly rectifying K channel currents induced by baclofen were recorded using Xenopus oocytes coexpressing G protein-activated inwardly rectifying K channel 1/2, GABAB1a receptor subunit, GB2R, and GRK. Translocation of GRKs 4 and 5 and protein complex formation of GB2R with GRKs were analyzed by confocal microscopy and fluorescence resonance energy transfer analysis in baby hamster kidney cells coexpressing GABAB1a receptor subunit, fluorescent protein-tagged GB2R, and GRKs. The formation of protein complexes of GB2R with GRKs was also determined by coimmunoprecipitation and Western blot analysis.

Results

Desensitization of GABABR-mediated signaling was suppressed by S(+)-ketamine in a concentration-dependent manner in the electrophysiologic assay. Confocal microscopy revealed that S(+)-ketamine inhibited translocation of GRKs 4 and 5 to the plasma membranes and protein complex formation of GB2R with the GRKs. Western blot analysis also showed that S(+)-ketamine inhibited the protein complex formation of GB2R with the GRKs.

Conclusion

S(+)-Ketamine suppressed the desensitization of GABABR-mediated signaling at least in part through inhibition of formation of protein complexes of GB2R with GRK 4 or 5.
Midazolam Suppresses Maturation of Murine Dendritic Cells and Priming of Lipopolysaccharide-induced T Helper 1-type Immune Response
Authors: Ohta Noriyuki , Ohashi Yoshifumi , Takayama Chihiro , Mashimo Takashi , Fujino Yuji
Published: January 2011

Background

Dendritic cells (DCs), as antigen-presenting cells, play a key role in the induction and regulation of adaptive immune response. Midazolam is reported to have immunomodulatory properties that affect immune cells. However, the effect of midazolam on DCs has not been characterized. We examined the immunomodulatory properties of midazolam on DC-mediated immune response.

Methods

After allowing murine bone marrow-derived DCs induced by granulocyte macrophage colony stimulating factor to mature, we analyzed their expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class II molecules, and the secretion of interleukin-12 p40. In vitro, we evaluated the effect of midazolam on maturing DCs in mixed cell cultures containing DCs and T cells. In vivo, we investigated the contact-hypersensitivity response.

Results

Midazolam suppressed the expression of CD80, CD86, and major histocompatibility complex class II molecules from murine DCs. Treated with midazolam, DCs also secreted less interleukin-12 p40. In mixed cell cultures with CD3-positive T cells, midazolam-treated DCs showed less propensity to stimulate the proliferation of CD3-positive T cells and the secretion of interferon-γ from CD4-positive T cells. Midazolam-treated DCs impaired the induction of contact-hypersensitivity response. Treatment with ligands for peripheral benzodiazepine receptor inhibited the up-regulation of CD80 during DC maturation.

Conclusion

Midazolam inhibits the functional maturation of murine DCs and interferes with DC induction of T helper 1 immunity in the whole mouse. In addition, it appears that the immunomodulatory effect of midazolam is mediated via the action of midazolam on the peripheral benzodiazepine receptor.
Flexing the abdominals: do bigger muscles make better fighters?
Authors: Mowles Sophie L. , Cotton Peter A. , Briffa Mark
Published: January 2011

Animal contests often involve the use of repeated signals, which are assumed to advertise stamina, and hence fighting ability. While an individual may be predicted to give up once it has crossed an energetic threshold, costs inflicted by its opponent may also contribute to the giving-up decision. Therefore, physical strength should be of key importance in contests, allowing high signal magnitude as well as potentially inflicting costs. We investigated this using hermit crab shell fights, which employ a ‘hybrid signal’ of shell rapping, which advertises stamina but also imposes potentially deleterious consequences for the receiver. We examined the links between contest outcomes and two proxies for strength; the protein content and relative mass of hermit crab abdominal muscles, the main muscle group used in shell rapping. Our results indicate that there was no difference in muscle protein between winners and losers, whereas winners had significantly greater muscle mass : body mass ratios. Thus, while stamina has been assumed by theory to be an important determinant of agonistic success, the present results demonstrate the importance of muscle size and thereby strength.
Patterns of variability in early-life traits of fishes depend on spatial scale of analysis
Authors: Di Franco Antonio , Guidetti Paolo
Published: January 2011

Estimates of early-life traits of fishes (e.g. pelagic larval duration (PLD) and spawning date) are essential for investigating and assessing patterns of population connectivity. Such estimates are available for a large number of both tropical and temperate fish species, but few studies have assessed their variability in space, especially across multiple scales. The present study, where a Mediterranean fish (i.e. the white seabream
Diplodus sargus sargus
) was used as a model, shows that spawning date and PLD are spatially more variable at a scale of kilometres than at a scale of tens to hundreds of kilometres. This study indicates the importance of considering spatial variability of early-life traits of fishes in order to properly delineate connectivity patterns at larval stages (e.g. by means of Lagrangian simulations), thus providing strategically useful information on connectivity and relevant management goals (e.g. the creation of networks of marine reserves).
Oxidative damage to DNA related to survivorship and carotenoid-based sexual ornamentation in the common yellowthroat
Authors: Freeman-Gallant Corey R. , Amidon Joel , Berdy Brittany , Wein Stephanie , Taff Conor C. , Haussmann Mark F.
Published: January 2011

Carotenoid-based sexual ornaments are hypothesized to be reliable signals of male quality, based on an allocation trade-off between the use of carotenoids as pigments and their use in antioxidant defence against reactive oxygen species. Carotenoids appear to be poor antioxidants
in vivo
, however, and it is not clear whether variation in ornament expression is correlated with measures of oxidative stress (OXS) under natural conditions. We used single-cell gel electrophoresis to assay oxidative damage to erythrocyte DNA in the common yellowthroat (
Geothlypis trichas
), a sexually dichromatic warbler in which sexual selection favours components of the males' yellow ‘bib’. We found that the level of DNA damage sustained by males predicted their overwinter survivorship and was reflected in the quality of their plumage. Males with brighter yellow bibs showed lower levels of DNA damage, both during the year the plumage was sampled (such that yellow brightness signalled current OXS) and during the previous year (such that yellow brightness signalled past OXS). We suggest that carotenoid-based ornaments can convey information about OXS to prospective mates and that further work exploring the proximate mechanism(s) linking OXS to coloration is warranted.
Multiplexed protein analysis using encoded antibody-conjugated microbeads
Authors: Theilacker Nora , Roller Eric E. , Barbee Kristopher D. , Franzreb Matthias , Huang Xiaohua
Published: January 2011

We describe a method for multiplexed analysis of proteins using fluorescently encoded microbeads. The sensitivity of our method is comparable to the sensitivity obtained by enzyme-linked immunosorbent assay while only 5 µl sample volumes are needed. Streptavidin-coated, 1 µm beads are encoded with a combination of fluorophores at different intensity levels. As a proof of concept, we demonstrate that 27 microbead populations can be readily encoded by affinity conjugation using three intensity levels for each of three different biotinylated fluorescent dyes. Four populations of encoded microbeads are further conjugated with biotinylated capture antibodies and then combined and immobilized in a microfluidic flow cell for multiplexed protein analysis. Using four uniquely encoded microbead populations, we show that a cancer biomarker and three cytokine proteins can be analysed quantitatively in the picogram per millilitre range by fluorescence microscopy in a single assay. Our method will allow for the fabrication of high density, bead-based antibody arrays for multiplexed protein analysis using integrated microfluidic devices and automated sample processing.
Antibacterial burst-release from minimal Ag-containing plasma polymer coatings
Authors: Lischer Stefanie , Körner Enrico , Balazs Dawn J. , Shen Dakang , Wick Peter , Grieder Kathrin , Haas Dieter , Heuberger Manfred , Hegemann Dirk
Published: January 2011

Biomaterials releasing silver (Ag) are of interest because of their ability to inhibit pathogenic bacteria including antibiotic-resistant strains. In order to investigate the potential of nanometre-thick Ag polymer (Ag/amino-hydrocarbon) nanocomposite plasma coatings, we studied a comprehensive range of factors such as the plasma deposition process and Ag cation release as well as the antibacterial and cytocompatible properties. The nanocomposite coatings released most bound Ag within the first day of immersion in water yielding an antibacterial burst. The release kinetics correlated with the inhibitory effects on the pathogens
Pseudomonas aeruginosa
or
Staphylococcus aureus
and on animal cells that were in contact with these coatings. We identified a unique range of Ag content that provided an effective antibacterial peak release, followed by cytocompatible conditions soon thereafter. The control of the
in situ
growth conditions for Ag nanoparticles in the polymer matrix offers the possibility to produce customized coatings that initially release sufficient quantities of Ag ions to produce a strong adjacent antibacterial effect, and at the same time exhibit a rapidly decaying Ag content to provide surface cytocompatibility within hours/days. This approach seems to be favourable with respect to implant surfaces and possible Ag-resistance/tolerance built-up.
Determination of surface-induced platelet activation by applying time-dependency dissipation factor versus frequency using quartz crystal microbalance with dissipation
Authors: Fatisson Julien , Mansouri Sania , Yacoub Daniel , Merhi Yahye , Tabrizian Maryam
Published: January 2011

Platelet adhesion and activation rates are frequently used to assess the thrombogenicity of biomaterials, which is a crucial step for the development of blood-contacting devices. Until now, electron and confocal microscopes have been used to investigate platelet activation but they failed to characterize this activation quantitatively and in real time. In order to overcome these limitations, quartz crystal microbalance with dissipation (QCM-D) was employed and an explicit time scale introduced in the dissipation versus frequency plots (Df–t) provided us with quantitative data at different stages of platelet activation. The QCM-D chips were coated with thrombogenic and non-thrombogenic model proteins to develop the methodology, further extended to investigate polymer thrombogenicity. Electron microscopy and immunofluorescence labelling were used to validate the QCM-D data and confirmed the relevance ofDf–tplots to discriminate the activation rate among protein-modified surfaces. The responses showed the predominant role of surface hydrophobicity and roughness towards platelet activation and thereby towards polymer thrombogenicity. Modelling experimental data obtained with QCM-D with a Matlab code allowed us to define the rate at which mass change occurs (A/B), to obtain anA/Bvalue for each polymer and correlate this value with polymer thrombogenicity.
Probing neural circuitry and function with electrical microstimulation
Authors: Clark Kelsey L. , Armstrong Katherine M. , Moore Tirin
Published: January 2011

Since the discovery of the nervous system's electrical excitability more than 200 years ago, neuroscientists have used electrical stimulation to manipulate brain activity in order to study its function. Microstimulation has been a valuable technique for probing neural circuitry and identifying networks of neurons that underlie perception, movement and cognition. In this review, we focus on the use of stimulation in behaving primates, an experimental system that permits causal inferences to be made about the effect of stimulation-induced activity on the resulting behaviour or neural signals elsewhere in the brain.
Hormone levels predict individual differences in reproductive success in a passerine bird
Authors: Ouyang Jenny Q. , Sharp Peter J. , Dawson Alistair , Quetting Michael , Hau Michaela
Published: January 2011

Hormones mediate major physiological and behavioural components of the reproductive phenotype of individuals. To understand basic evolutionary processes in the hormonal regulation of reproductive traits, we need to know whether, and during which reproductive phases, individual variation in hormone concentrations relates to fitness in natural populations. We related circulating concentrations of prolactin and corticosterone to parental behaviour and reproductive success during both the pre-breeding and the chick-rearing stages in both individuals of pairs of free-living house sparrows,
Passer domesticus
. Prolactin and baseline corticosterone concentrations in pre-breeding females, and prolactin concentrations in pre-breeding males, predicted total number of fledglings. When the strong effect of lay date on total fledgling number was corrected for, only pre-breeding baseline corticosterone, but not prolactin, was negatively correlated with the reproductive success of females. During the breeding season, nestling provisioning rates of both sexes were negatively correlated with stress-induced corticosterone levels. Lastly, individuals of both sexes with low baseline corticosterone before and high baseline corticosterone during breeding raised the most offspring, suggesting that either the plasticity of this trait contributes to reproductive success or that high parental effort leads to increased hormone concentrations. Thus hormone concentrations both before and during breeding, as well as their seasonal dynamics, predict reproductive success, suggesting that individual variation in absolute concentrations and in plasticity is functionally significant, and, if heritable, may be a target of selection.
Bayesian phylogeography of the Arawak expansion in lowland South America
Authors: Walker Robert S. , Ribeiro Lincoln A.
Published: January 2011

Phylogenetic inference based on language is a vital tool for tracing the dynamics of human population expansions. The timescale of agriculture-based expansions around the world provides an informative amount of linguistic change ideal for reconstructing phylogeographies. Here we investigate the expansion of Arawak, one of the most widely dispersed language families in the Americas, scattered from the Antilles to Argentina. It has been suggested that Northwest Amazonia is the Arawak homeland based on the large number of diverse languages in the region. We generate language trees by coding cognates of basic vocabulary words for 60 Arawak languages and dialects to estimate the phylogenetic relationships among Arawak societies, while simultaneously implementing a relaxed random walk model to infer phylogeographic history. Estimates of the Arawak homeland exclude Northwest Amazonia and are bi-modal, with one potential homeland on the Atlantic seaboard and another more likely origin in Western Amazonia. Bayesian phylogeography better supports a Western Amazonian origin, and consequent dispersal to the Caribbean and across the lowlands. Importantly, the Arawak expansion carried with it not only language but also a number of cultural traits that contrast Arawak societies with other lowland cultures.
Pluripotency factors regulate definitive endoderm specification through eomesodermin
Authors: Teo Adrian Kee Keong , Arnold Sebastian J. , Trotter Matthew W.B. , Brown Stephanie , Ang Lay Teng , Chng Zhenzhi , Robertson Elizabeth J. , Dunn N. Ray , Vallier Ludovic
Published: January 2011

Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective toward the development of robust methods for the differentiation of human pluripotent stem cells into clinically relevant cell types. Here, we used human embryonic stem cells and mouse epiblast stem cells to study specification of definitive endoderm in vitro. Using a combination of whole-genome expression and chromatin immunoprecipitation (ChIP) deep sequencing (ChIP-seq) analyses, we established an hierarchy of transcription factors regulating endoderm specification. Importantly, the pluripotency factors NANOG, OCT4, and SOX2 have an essential function in this network by actively directing differentiation. Indeed, these transcription factors control the expression of EOMESODERMIN (EOMES), which marks the onset of endoderm specification. In turn, EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation. Together, these results provide for the first time a comprehensive molecular model connecting the transition from pluripotency to endoderm specification during mammalian development.
Endurance factors improve hippocampal neurogenesis and spatial memory in mice
Authors: Kobilo Tali , Yuan Chunyan , van Praag Henriette
Published: January 2011

Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor δ agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects.
The Late Ordovician deglaciation sequence of the SW Murzuq Basin (Libya)
Authors: Moreau Julien
Published: January 2011

Rocks of Late Ordovician to Silurian age are well exposed on the western rim of the Murzuq Basin (Ghat‐Tikiumit area, Libya) where seismic‐scale exposures allow spectacular insights into the growth and decay of the Late Ordovician (Hirnantian) ice sheet. The final deglaciation left a complex topography with a combination of subglacial morphologies and proglacial depositional systems. This paper documents the glacial and proglacial palaeo‐topography that controls the accumulation of a postglacial transgressive depositional system and the Rhuddanian (Early Silurian) shales. The glacial relief directly contributed to an important hiatus, with the Rhuddanian deposits at the base of the remnant glacial troughs being 3 Ma older than at the top of the topographic highs. The source‐rock in the Murzuq Basin is of Early Rhuddanian age, so it is present only in the deepest part whereas geomorphic traps are formed within the highs of the relict postglacial topography. The transgressive system, recognised for its good reservoir potential, is considered to play a key‐role in the petroleum system, linking the source rock deposited in the ancient topographic lows with the reservoir rocks in the topographic highs. This study aims to demonstrate the importance of palaeo‐glaciological reconstructions for petroleum exploration of the Ordovician–Silurian in North Africa.