bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition Rate Effect of Alq3 Thin Film Growth: A Kinetic Monte Carlo Study
Authors: Lin Yih-Jiun , Chang Jian-Chuang , Tai Chin-Kuen , Wang Bo-Cheng , Li Feng-Yin
Published: August 2008

This paper is the winner of the Young Scientist Award at the Asian Chemical Congress in Kuala Lumpur, 2007. Applying the Kinetic Monte Carlo (KMC) technique, we successfully investigated the effect of deposition rate on the growth pattern of an Alq3 thin film. In good agreement with experimental results, our simulation results indicate that there exists a transition growth in terms of the deposition rate that corresponds to the transition between the island growth and random deposition growth. In the regions of island growth (where the deposition rate is lower than 1.1 Å s–1) and random deposition growth (where the deposition rate is higher than 3 Å s–1), the surface morphology is not suitable for luminant devices because of a high roughness, a larger inner vacancy ratio at higher deposition rate, and low homogeneity at lower deposition rate conditions. Within the transition growth region (deposition rate is between 1.1 and 3.0 Å s–1), the homogeneity of the film surface improves as the deposition rate increases. Not only does the pattern of the island structures become blurred, but the inner vacancy ratio and surface roughness also remain low as the deposition rate increases. From our results, there may exist a deposition rate to optimize the Alq3 film with a suitable surface morphology for luminant devices.
Photocycloaddition of 5-Methoxyoxazoles to Aldehydes and ?-Keto Esters: A Comprehensive View on Stereoselectivity, Triplet Biradical Conformations, and Synthetic Applications of Paternò–Büchi Adducts
Authors: Griesbeck Axel G. , Bondock Samir
Published: August 2008

The photocycloaddition of carbonyl compounds (aldehydes and keto esters, respectively) with 5-methoxyoxazoles bearing substituents at C2 and C4 is described with respect to regio- and diastereoselectivity. In all cases the reactions proceed with excellent regioselectivity and with high to moderate (exo) diastereoselectivity independent of the nature of the excited carbonyl compound. The products can be easily ring-opened to give α-amino, β-hydroxy carboxylic acid derivatives.
Photochemistry of Anthracene-Appended Cobalt(III) Cyclam Complexes
Authors: Boyd Simon , Ghiggino Kenneth P. , McFadyen W. David
Published: August 2008

The photochemistry of two anthracene-appended cobalt(iii) cyclam complexes is explored with a view to demonstrate a photoactivated ligand release process. The ligand exchange processes that occur in the complexes cis-[CoL(NO2)(ONO)]+ and trans-[CoL(NO2)(ONO)]+ in which L = 6-(anthracen-9-ylmethyl)-1,4,8,11-tetraazacyclotetradecane were monitored upon illumination of the anthracenyl chromophore at 360 nm in the presence of a large excess of thiocyanate. The trans-[CoL(NO2)(ONO)]+ complex underwent a ligand exchange reaction in the absence of light and displayed an enhancement of the reaction upon illumination. In contrast the cis-[CoL(NO2)(ONO)]+ complex was stable in the dark but displayed a significant quantum yield of photoactivated ligand release (Φ = 0.19). It is proposed that in cis-[CoL(NO2)(ONO)]+ the photoexcited anthracenyl chromophore undergoes efficient energy transfer to the cobalt(iii) cyclam before ligand exchange. Complexes based on the anthracenylcyclam–cobalt(iii) framework may be potentially useful candidates as photoactivated ligand release systems.
Male dominance rarely skews the frequency distribution of Y chromosome haplotypes in human populations
Authors: Lansing J. Stephen , Watkins Joseph C. , Hallmark Brian , Cox Murray P. , Karafet Tatiana M. , Sudoyo Herawati , Hammer Michael F.
Published: August 2008

A central tenet of evolutionary social science holds that behaviors, such as those associated with social dominance, produce fitness effects that are subject to cultural selection. However, evidence for such selection is inconclusive because it is based on short-term statistical associations between behavior and fertility. Here, we show that the evolutionary effects of dominance at the population level can be detected using noncoding regions of DNA. Highly variable polymorphisms on the nonrecombining portion of the Y chromosome can be used to trace lines of descent from a common male ancestor. Thus, it is possible to test for the persistence of differential fertility among patrilines. We examine haplotype distributions defined by 12 short tandem repeats in a sample of 1269 men from 41 Indonesian communities and test for departures from neutral mutation-drift equilibrium based on the Ewens sampling formula. Our tests reject the neutral model in only 5 communities. Analysis and simulations show that we have sufficient power to detect such departures under varying demographic conditions, including founder effects, bottlenecks, and migration, and at varying levels of social dominance. We conclude that patrilines seldom are dominant for more than a few generations, and thus traits or behaviors that are strictly paternally inherited are unlikely to be under strong cultural selection.
Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease
Authors: Jiang Hong , Schiffer Eric , Song Zhangfa , Wang Jianwei , Zürbig Petra , Thedieck Kathrin , Moes Suzette , Bantel Heike , Saal Nadja , Jantos Justyna , Brecht Meiken , Jenö Paul , Hall Michael N. , Hager Klaus , Manns Michael P. , Hecker Hartmut , Ganser Arnold , Döhner Konstanze , Bartke Andrzej , Meissner Christoph , Mischak Harald , Ju Zhenyu , Rudolph K. Lenhard
Published: August 2008

Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1α, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc
−/−
). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc
−/−
mice but not in aging mice with long telomere reserves. Orthologs of these proteins are up-regulated in late-passage presenescent human fibroblasts and in early passage human cells in response to γ-irradiation. The study shows that the expression level of these marker proteins increases in the blood plasma of aging humans and shows a further increase in geriatric patients with aging-associated diseases. Moreover, there was a significant increase in the expression of the biomarkers in the blood plasma of patients with chronic diseases that are associated with increased rates of cell turnover and telomere shortening, such as cirrhosis and myelodysplastic syndromes (MDS). Analysis of blinded test samples validated the effectiveness of the biomarkers to discriminate between young and old, and between disease groups (MDS, cirrhosis) and healthy controls. These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease.
A model of the differentation and relative incidence of glandular versus squamous cell neoplasia of the uterine cervix: Connection between incidence and etiology
Authors: LEPPÄLUOTO PENTTI A.
Published: August 2008

It has remained unclear why cervical adenocarcinoma, as observed in consecutive screening, has rapidly increased during the past decades, while at the same time both that of squamous cell carcinoma (SCC) and the combined toll of adeno‐ and SCC have consistently decreased. Here it is argued that this might be ascribed to coitus‐related changes in the cervicovaginal milieu, where the target cells become infected through a coital act. Frequent alterations in vaginal acidity and changing sexual habits in the era after the oral contraceptive pills and even after the introduction of erectile dysfunction medication, contribute to the pathogenetic scene.
IVF pregnancies: Neonatal outcomes after the new Italian law on assisted reproduction technology (law 40/2004)
Authors: CASERTA DONATELLA , MARCI ROBERTO , TATONE CARLA , SCHIMBERNI MAURO , VAQUERO ELENA , LAZZARIN NATALIA , FAZI ALESSANDRA , MOSCARINI MASSIMO
Published: August 2008

Objective. To compare maternal and neonatal outcome of pregnancies achieved by assisted reproduction technique (ART) according to the guidelines of the newly established Italian ART law 40/2004, with that of naturally conceived. Design. Three hundred and sixty‐four ART pregnancies and 304 naturally conceived pregnancies were analyzed in terms of the incidence of obstetric complications and perinatal outcome. Control group was enrolled prospectively after being matched for an extensive number of maternal characteristics. Results. Among singletons, ART pregnancies when compared to naturally conceived pregnancies showed a higher incidence of pregnancy loss (23.4% versus 10.5%) and a lower mean birth weight. A higher but not significant incidence of small for gestational age fetuses was observed in ART pregnancies, compared to those from normally conceived pregnancies (7.2% versus 2.7%). Moreover, the ART pregnancies showed a slightly, but nonetheless significantly shorter mean gestational age (38.6 versus 39.3 weeks) and more frequent preterm deliveries (11%) than the control group (2.7%). No difference was found in terms of other obstetric complications such as pregnancy‐induced hypertension, gestational diabetes and placental abruption. Neonatal outcome was similar in both groups. Conclusion. Although the obstetric outcome among singleton ART pregnancies was good, these patients should be considered obstetric risk cases. The different frequency of complications is not related to maternal age or parity and could be the consequence of infertility or the procedures by which these women conceived. The reasons are, however, unclear and further studies are necessary.
Association between lactate concentration in amniotic fluid and dysfunctional labor
Authors: WIBERG‐ITZEL EVA , PETTERSSON HANS , CNATTINGIUS SVEN , NORDSTRÖM LENNART
Published: August 2008

Objectives. To assess whether there is an association between high lactate concentration in amniotic fluid (AF) and labor dystocia. Design. Prospective observational study. Setting. Labor ward at General South Hospital, Stockholm, Sweden. Population and methods. Women in active labor attending labor ward, having at least two consecutive measurements of lactate concentration in AF, measured 60 minutes apart. Main outcome measure. Dysfunctional labor, defined as instrumental or operative delivery due to dystocia. Results. Among women with spontaneous vaginal deliveries (n =23) the mean lactate concentration in AF during labor was 8.9 mmol/l (range 6.6–10.8), and among women with operative delivery due to labor dystocia (n =31) the corresponding value was 10.9 mmol/l (range 8.0–16.1) (p<0.001). Of 29 women with a high lactate concentration (≥10.1 mmol/l) in at least two consecutive measures collected at least 60 minutes apart, 25 (86%) were delivered instrumentally/operatively due to dystocia. Using this definition of a positive test, the diagnostic accuracy to predict operative delivery due to dystocia was: sensitivity 81% (25/31), specificity 83% (19/23), positive predictive value 86% (25/29), and negative predictive value 76% (19/25). The likelihood ratio was 5.0 for a positive test and 0.2 for a negative test. Conclusions. High lactate concentration (≥10.1mmol/l) in at least two consecutive samples of AF collected during labor 60 minutes apart is strongly associated with dystocia. This method might be useful in clinical management to identify labor dystocia at an early stage of labor.
When Seve Met Bregović: Folklore, Turbofolk and the Boundaries of Croatian Musical Identity
Authors: Baker Catherine
Published: August 2008

In 2006 the Croatian singer Severina Vučković attempted to represent Croatia at the Eurovision Song Contest with a song arranged by Goran Bregović, the ex-Yugoslav musician from Sarajevo. Before the song “Moja štikla” [My Stiletto] had even been released, the Croatian (and Serbian) mass media had questioned its “Croatianness” in an escalating sequence of claims and counter-claims to authenticity. Its use of musical elements based on folk song and dance left it open to allegations that it had compromised folk music's authenticity; those elements’ regional associations (especiallygangaandrerasinging from Lika and Herzegovina) connoted spaces which had been marginalized as “eastern” or “Balkan” in comparison to privileged inland and coastal traditions; the involvement of Bregović (represented as Serbian throughout the Croatian mass media) enabled suggestions that the song presented “Serbian folklore” or belonged to the Serbian genre of “turbofolk”—and all this in the particularly sensitive context of a competition which was supposed to symbolize Croatia's full European membership.
Ramzan Kadyrov: The Indigenous Key to Success in Putin's Chechenization Strategy?
Authors: Russell John
Published: August 2008

On 15 February 2007 Vladimir Putin accepted the resignation of Alu Alkhanov as President of Chechnya and nominated the Chechen prime minister—Ramzan Kadyrov—to act as his successor. This appointment, duly rubber-stamped by Chechnya's parliament, brought to an end to more than four months of speculation since 5 October 2006, when Kadyrov attained the age of 30 and thus became eligible for the post of Chechnya's head of state. Kadyrov's elevation to de jure rather than de facto supremacy in Chechen society not only completed the final stage of the remarkably rapid transformation of this one-time rebel, juvenile thug and politicalingénuebut also put Putin's policy of Chechenization firmly back on track, which had been effectively derailed since the assassination of Chechnya's first pro-Russian president—Akhmad Kadyrov—Ramzan's father, in May 2004.
From the Cradle of the Nation to the Most Expensive Serbian Word: Changes in Serbian Public Language in the Last Decade of the Twentieth Century
Authors: Šajkaš Marija
Published: August 2008

We cannot educate our children in the spirit of cosmopolitism, but instruct them to love their homeland instead. We have to put the big ideology in their little heads.

Danilo Ž. Marković, Serbian Minister of Education in a speech to school managers of the Banat district, Daily Borba, 19 March 1993

The words people use reflect their view of the world. In totalitarian societies the primary goal of a regime's language is to influence public opinion. A closer inspection of the most exploited phrases in Serbian public discourse in the period of the late 1980s until 2000 reveals a strong presence of propagandistic language. Thus, it can be argued that the consequences of Slobodan Milošević's politics are visible not only in the devastation of the people and the country but also in the sphere of Serbian public discourse. It is not only that his politics influenced the language. Rather, it is precisely because of the rich and diversified propaganda language of the regime that Slobodan Milošević's was able to maintain his firm grip on power in Serbia for 13 years.
Over‐the‐counter nicotine replacement therapy: a methodological review of the evidence supporting its effectiveness
Authors: WALSH RAOUL A.
Published: August 2008

Despite optimistic predictions when nicotine replacement therapy (NRT) was switched to over‐the‐counter (OTC) availability, population surveys have failed to demonstrate a positive impact on long‐term smoking cessation. This review examined the strength of the evidence from randomised trials and comparison group studies supporting the effectiveness of OTCNRT. Twelve eligible studies were identified: OTCNRT was compared with placebo in four studies and with health professional‐delivered NRT in four studies, and four studies involved community‐based minimal intervention NRT. These studies were assessed systematically to determine their methodological quality and generalisibility to ‘real‐world’ conditions of NRT use. The review found a number of issues, including provision of free NRT, heavy cigarette intakes (average 25 daily), high levels of personal interactions (7.6 per subject), lack of blindness assessment and failure of most studies to actively follow‐up all subjects seriously limit the degree to which studies' results can be applied to non‐research OTCNRT users. In addition, several important limitations affecting the meta‐analyses of OTCNRT by Hughes et al. were highlighted. The review concluded that the superiority of OTCNRT over unaided smoking cessation has not been demonstrated convincingly. Future directions for research involve more innovative, rigorous controlled trials and prospective cohort studies where nicotine dependence is assessed adequately.
Mechatronics and Bioinspiration in Actuator Design and Control
Authors: Pons J. L. , Forner-Cordero A. , Rocon E. , Moreno J. C.
Published: August 2008

Actuators are components of motion control systems in which mechatronics plays a crucial role. They can be regarded as a paradigmatic case in which this mechatronic approach is required. Furthermore, actuator technologies can get new sources of inspiration from nature (bioinspiration). Biological systems are the result of an evolutionary process and show excellent levels of performance. In this paper, we analyse the actuator as a bioinspired mechatronic system through analogies between mechatronics and biological actuating mechanisms that include hierarchical control of actuators, switched control of power flow and some transduction principles. Firstly, some biological models are introduced as a source of inspiration for setting up both actuation principles and control technologies. Secondly, a particular actuator technology, the travelling wave ultrasonic motor, is taken to illustrate this approach. Eventually, the last section draws some conclusions and points out future directions.
Graphical methods for quantifying macromolecules through bright field imaging
Authors: Chang Hang , DeFilippis Rosa Anna , Tlsty Thea D. , Parvin Bahram
Published: August 2008

Bright field imaging of biological samples stained with antibodies and/or special stains provides a rapid protocol for visualizing various macromolecules. However, this method of sample staining and imaging is rarely employed for direct quantitative analysis due to variations in sample fixations, ambiguities introduced by color composition and the limited dynamic range of imaging instruments. We demonstrate that, through the decomposition of color signals, staining can be scored on a cell-by-cell basis. We have applied our method to fibroblasts grown from histologically normal breast tissue biopsies obtained from two distinct populations. Initially, nuclear regions are segmented through conversion of color images into gray scale, and detection of dark elliptic features. Subsequently, the strength of staining is quantified by a color decomposition model that is optimized by a graph cut algorithm. In rare cases where nuclear signal is significantly altered as a result of sample preparation, nuclear segmentation can be validated and corrected. Finally, segmented stained patterns are associated with each nuclear region following region-based tessellation. Compared to classical non-negative matrix factorization, proposed method: (i) improves color decomposition, (ii) has a better noise immunity, (iii) is more invariant to initial conditions and (iv) has a superior computing performance.

contact:  hchang@lbl.gov
A novel CHHC Zn-finger domain found in spliceosomal proteins and tRNA modifying enzymes
Authors: Andreeva Antonina , Tidow Henning
Published: August 2008

Summary: We report a previously uncharacterized CHHC Zn-finger domain identified in spliceosomal U11-48K proteins, tRNA methyl-transferases TRM13 and gametocyte specific factors. We show that this domain behaves as an independent folding unit and that it stoichiometrically binds zinc in a one-to-one ratio. Based on the conserved sequence features we predict that this domain may function as a RNA recognition and binding module.

Contact:  tony@mrc-lmb.cam.ac.uk

Supplementary information:  Supplementary data are available on Bioinformatics online.
Physicochemical Properties, Pharmacokinetics, and Pharmacodynamics of a Reformulated Microemulsion Propofol in Rats
Authors: Lee Eun-Ho , Lee Soo-Han , Park Do-Yang , Ki Kyoung-Ho , Lee Eun-Kyung , Lee Dong-Ho , Noh Gyu-Jeong
Published: August 2008

Background

A newly developed microemulsion propofol consisted of 10% purified poloxamer 188 and 0.7% polyethylene glycol 660 hydroxystearate. The authors studied the physicochemical properties, aqueous free propofol concentration, and plasma bradykinin generation. Pharmacokinetics and pharmacodynamics were also evaluated in rats.

Methods

The pH, particle size, and osmolarity of microemulsion propofol were measured using a pH meter, particle size analyzer, and cryoscopic osmometer, respectively. The aqueous free propofol and plasma bradykinin were measured by a dialysis method and radioimmunoassay, respectively. Microemulsion propofol was administered by zero-order infusion of 0.5, 1.0, and 1.5 mg . kg . min for 20 min in 30 rats. The electroencephalographic approximate entropy was used as a surrogate measure of propofol effect.

Results

The pH, osmolarity, and particle size of microemulsion propofol are 7.5, 280 mOsm/l, and 67.0 +/- 28.5 nm, respectively. The aqueous free propofol concentration in microemulsion propofol was 63.3 +/- 1.2 mug/ml. When mixed with human blood, microemulsion propofol did not generate bradykinin in plasma. Although microemulsion propofol had nonlinear pharmacokinetics, a two-compartment model with linear pharmacokinetics best described the time course of the propofol concentration as follows: V1 = 0.143 l/kg, k10 = 0.175 min, k12 = 0.126 min, k21 = 0.043 min. The pharmacodynamic parameters in a sigmoid Emax model were as follows: E0 = 1.18, Emax = 0.636, Ce50 = 1.87 mug/ml, gamma = 1.28, ke0 = 1.02 min.

Conclusions

Microemulsion propofol produced a high concentration of free propofol in the aqueous phase. For the applied dose range, microemulsion propofol showed nonlinear pharmacokinetics.
Observations on Surgical Demand Time Series
Authors: Moore Ian C. , Strum David P. , Vargas Luis G. , Thomson David J.
Published: August 2008

Background

Surgical scheduling is complicated by both naturally occurring and human-induced variability in the demand for surgical services. Surgical demand time series are decomposed into periodic, lagged, and linear trends with frequent occurrences of nonconstant variations in mean and variance. The authors used time series methods to model surgical demand time series in order to improve the scheduling of scarce surgical resources.

Methods

With institutional approval, the authors studied 47,752 surgeries undertaken at a large academic medical center. They initially extracted periodic information from the time series using two frequency domain techniques: the harmonic F test and the multitaper test. They subsequently extracted lagged (correlated) behavior using a seasonal autoregressive integrated moving average model. Finally, they used moving variance filters on the residuals to identify variance in the time series that coincided with major US holidays.

Results

Linear terms such as periodic cycles, trends, and daily and weekly lags explained 80% of the variance in the raw time series. In the residuals, the authors used moving variance filters to detect nonlinear variance artifacts that correlated with surgical activities on specific US holidays.

Conclusions

After extracting linear terms, the remaining variance was attributable to a combination of nonlinear and unexplained random events. The authors used the term holiday variance to describe a specific nonlinear disturbance in surgical demand attributable to statutory US holidays. Resolving these holiday variances may assist in management and scheduling of scarce surgical personnel and resources.
Guidance of Block Needle Insertion by Electrical Nerve Stimulation
Authors: Rigaud Marcel , Filip Patrick , Lirk Philipp , Fuchs Andreas , Gemes Geza , Hogan Quinn
Published: August 2008

Background

Little is known regarding the final needle tip location when various intensities of nerve stimulation are used to guide block needle insertion. Therefore, in control and hyperglycemic dogs, the authors examined whether lower-intensity stimulation results in injection closer to the sciatic nerve than higher-threshold stimulation.

Methods

During anesthesia, the sciatic nerve was approached with an insulated nerve block needle emitting either 1 mA (high-current group, n = 9) or 0.5 mA (low-current group, n = 9 in control dogs and n = 6 in hyperglycemic dogs). After positioning to obtain a distal motor response, the lowest current producing a response was identified, and ink (0.5 ml) was injected. Frozen sections of the tissue revealed whether the ink was in contact with the epineurium of the nerve, distant to it, or within it.

Results

In control dogs, the patterns of distribution using high-threshold (final current 0.99 +/- 0.03 mA, mean +/- SD) and low-threshold (final current 0.33 +/- 0.08 mA) stimulation equally showed ink that was in contact with the epineurium or distant to it. One needle placement in the high-threshold group resulted in intraneural injection. In hyperglycemic dogs, all needle insertions used a low-threshold technique (n = 6, final threshold 0.35 +/- 0.08 mA), and all resulted in intraneural injections.

Conclusions

In normal dogs, current stimulation levels in the range of 0.33-1.0 mA result in needle placement comparably close to the sciatic nerve but do not correlate with distance from the target nerve. In this experimental design, low-threshold electrical stimulation does not offer satisfactory protection against intraneural injection in the presence of hyperglycemia.
A118G Single Nucleotide Polymorphism of Human μ-Opioid Receptor Gene Influences Pain Perception and Patient-controlled Intravenous Morphine Consumption after Intrathecal Morphine for Postcesarean Analgesia
Authors: Sia Alex T. , Lim Yvonne , Lim Eileen C. P. , Goh Rachelle W. C. , Law Hai Yang , Landau Ruth , Teo Yik-ying , Tan Ene Choo
Published: August 2008

Background

Previous studies have shown that genetic variability at position 118 of the human mu-opioid receptor gene altered patients' response to intravenous morphine. The purpose of this study was to investigate whether this polymorphism contributes to the variability in response to morphine for postcesarean analgesia.

Methods

After investigators obtained informed consent, 588 healthy women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their blood samples were genotyped for the A118G polymorphism-A118 homozygous (AA), heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity of nausea and vomiting, the incidence of pruritus, and the total self-administered intravenous morphine were recorded for the first 24 postoperative hours.

Results

Two hundred seventy women (46%) were AA, 234 (40%) were AG, and 82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1-6.8) versus the AG (8.0; 6.9-9.1) and GG groups (9.4; 7.3-11.5). Pain scores were lowest in the AA group and highest in the GG group, with a statistically significant difference detected between AA, AG, and GG (P = 0.049). Total morphine consumption was also influenced by patients' age and paying status. AA group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P = 0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and GG, respectively).

Conclusion

Genetic variation at position 118 of the mu-opioid receptor is associated with interindividual differences in pain scores, self-administered intravenous morphine, and the incidence of nausea postoperatively.
Intraoperative Acceleromyographic Monitoring Reduces the Risk of Residual Neuromuscular Blockade and Adverse Respiratory Events in the Postanesthesia Care Unit
Authors: Murphy Glenn S. , Szokol Joseph W. , Marymont Jesse H. , Greenberg Steven B. , Avram Michael J. , Vender Jeffery S. , Nisman Margarita
Published: August 2008

Background

Incomplete recovery from neuromuscular blockade in the postanesthesia care unit (PACU) may contribute to adverse postoperative respiratory events. This study determined the incidence and degree of residual neuromuscular blockade in patients randomized to conventional qualitative train-of-four (TOF) monitoring or quantitative acceleromyographic monitoring. The incidence of adverse respiratory events in the PACU was also evaluated.

Methods

One hundred eighty-five patients were randomized to intraoperative acceleromyographic monitoring (acceleromyography group) or qualitative TOF monitoring (TOF group). Anesthetic management was standardized. TOF patients were extubated when standard criteria were met and no fade was observed during TOF stimulation. Acceleromyography patients had a TOF ratio of greater than 0.80 as an additional extubation criterion. Upon arrival in the PACU, TOF ratios of both groups were measured with acceleromyography. Adverse respiratory events during transport to the PACU and during the first 30 min of PACU admission were also recorded.

Results

A lower frequency of residual neuromuscular blockade in the PACU (TOF ratio < or = 0.9) was observed in the acceleromyography group (4.5%) compared with the conventional TOF group (30.0%; P < 0.0001). During transport to the PACU, fewer acceleromyography patients developed arterial oxygen saturation values, measured by pulse oximetry, of less than 90% (0%) or airway obstruction (0%) compared with TOF patients (21.1% and 11.1%, respectively; P < 0.002). The incidence, severity, and duration of hypoxemic events during the first 30 min of PACU admission were less in the acceleromyography group (all P < 0.0001).

Conclusions

Incomplete neuromuscular recovery can be minimized with acceleromyographic monitoring. The risk of adverse respiratory events during early recovery from anesthesia can be reduced by intraoperative acceleromyography use.
Electrical Impedance to Distinguish Intraneural from Extraneural Needle Placement in Porcine Nerves during Direct Exposure and Ultrasound Guidance
Authors: Tsui Ban C. H. , Pillay Jennifer J. , Chu Kinny T. , Dillane Derek
Published: August 2008

Background

Intraneural injection during peripheral nerve blockade can cause neurologic injury. Current approaches to prevent or detect intraneural injection lack reliability and consistency, or only signal intraneural injection upon the event. A change in electrical impedance (EI) could be indicative of intraneural needle placement before injection.

Methods

After animal care committee approval, eight pigs were anesthetized and kept spontaneously breathing. In four pigs (part 1), the sciatic nerves were exposed bilaterally for direct needle placement; in a further four pigs (part 2), the tissue was kept intact for ultrasound-guided needle placement. An insulated needle (Sprotte 24 gauge; Pajunk GmbH Medizintechnologie, Geisingen, Germany), attached to a nerve stimulator displaying EI (Braun Stimuplex HNS 12; B. Braun Medical, Bethlehem, PA), was placed extraneurally and then advanced to puncture the nerve sheath. Five punctures within approximately a 1-cm length of each nerve were performed. For each Part, overall EI at each compartment and EI after individual punctures were compared using a general linear model, with post hoc analysis using the Duncan multiple range test.

Results

The EI was lower extraneurally compared with intraneurally during open dissection (12.1 +/- 1.8 vs. 23.2 +/- 4.4 kOmega; P < 0.0001; n = 8) and when using ultrasound guidance (10.8 +/- 2.9 vs. 18.2 +/- 6.1 kOmega; P < 0.0001; n = 7 nerves were visualized adequately). The EI difference was maintained despite performing five sequential punctures.

Conclusions

With further study, EI could prove to be a quantifiable warning signal to alert clinicians to intraneural needle placement, preventing local anesthetic injection and subsequent nerve injury.
Antiinflammatory Effect of Peripheral Nerve Blocks after Knee Surgery
Authors: Martin Frédéric , Martinez Valéria , Mazoit Jean Xavier , Bouhassira Didier , Cherif Kamel , Gentili Marc Edouard , Piriou Philippe , Chauvin Marcel , Fletcher Dominique
Published: August 2008

Background

Nerve blocks provide analgesia after surgery. The authors tested whether nerve blocks have antiinflammatory effects.

Methods

Patients had combined sciatic (single-shot) and continuous femoral block (48 h) (block group) or morphine patient-controlled analgesia after total knee arthroplasty. Pain at rest and upon movement was monitored at 1 (D1), 4 (D4), and 7 days (D7) and 1 (M1) and 3 months (M3) after surgery. Knee inflammation was evaluated (skin temperature, knee circumference) before surgery and at D1, D4, D7, M1, and M3. Plasma cytokine concentrations (interleukin [IL]-6, IL-1beta, tumor necrosis factor [TNF], IL-10, soluble receptor 1 of TNF [sTNF-R1]) were measured before surgery and at 4 h, D1, D4, and D7 after surgery. Capsule and synovial membrane cytokines were measured (IL-6, TNF, IL-1, IL-10). Knee flexion was evaluated before surgery and at D1, D4, D7, M1, and M3. Morphine use and recovery time to autonomy were monitored.

Results

Pain at rest and upon movement was lower in the block group than in patient-controlled analgesia patients between D1 and D7 (analysis of variance, P < 0.005). Knee flexion was improved in the block group for D1 to M1 (analysis of variance, P < 0.0001). Block group patients recovered nonassisted mobilization (t test, P = 0.04) and toilet use (t test, P = 0.03) more rapidly. Knee circumference and skin temperature were lower in the block group between D1 and D7 (analysis of variance, P < 0.05). Synovial membrane IL-1 (P < 0.05) and IL-10 (P < 0.01) increased, and plasma IL-6 and sTNF-R1 peaked at 24 h, with no difference between groups.

Conclusion

Nerve blocks inhibited clinical inflammation after total knee arthroplasty, with no change in tissue and plasma cytokine concentrations.
Transmission of Pathogenic Bacterial Organisms in the Anesthesia Work Area
Authors: Loftus Randy W. , Koff Matthew D. , Burchman Corey C. , Schwartzman Joseph D. , Thorum Valerie , Read Megan E. , Wood Tammara A. , Beach Michael L.
Published: August 2008

Background

The current prevalence of hospital-acquired infections and evolving amplification of bacterial resistance are major public health concerns. A heightened awareness of intraoperative transmission of potentially pathogenic bacterial organisms may lead to implementation of effective preventative measures.

Methods

Sixty-one operative suites were randomly selected for analysis. Sterile intravenous stopcock sets and two sites on the anesthesia machine were decontaminated and cultured aseptically at baseline and at case completion. The primary outcome was the presence of a positive culture on the previously sterile patient stopcock set. Secondary outcomes were the number of colonies per surface area sampled on the anesthesia machine, species identification, and antibiotic susceptibility of isolated organisms.

Results

Bacterial contamination of the anesthesia work area increased significantly at the case conclusion, with a mean difference of 115 colonies per surface area sampled (95% confidence interval [CI], 62-169; P < 0.001). Transmission of bacterial organisms, including vancomycin-resistant enterococcus, to intravenous stopcock sets occurred in 32% (95% CI, 20.6-44.9%) of cases. Highly contaminated work areas increased the odds of stopcock contamination by 4.7 (95% CI, 1.42-15.42; P = 0.011). Contaminated intravenous tubing was associated with a trend toward increased nosocomial infection rates (odds ratio, 3.08; 95% CI, 0.56-17.5; P = 0.11) and with an increase in mortality (95% CI odds ratio, 1.11-infinity; P = 0.0395).

Conclusion

Potentially pathogenic, multidrug-resistant bacterial organisms are transmitted during the practice of general anesthesia to both the anesthesia work area and intravenous stopcock sets. Implementation of infection control measures in this area may help to reduce both the evolving problem of increasing bacterial resistance and the development of life-threatening infectious complications.
Analgesic Effects of Sazetidine-A, a New Nicotinic Cholinergic Drug
Authors: Cucchiaro Giovanni , Xiao Yingxian , Gonzalez-Sulser Alfredo , Kellar Kenneth J.
Published: August 2008

Background

The use of nicotinic agonists for analgesia is limited by their unacceptable side effects. Sazetidine-A is a new partial agonist nicotinic ligand that has very high selectivity for beta2-containing nicotinic acetylcholine receptors. It potently and selectively desensitizes alpha4beta2 nicotinic acetylcholine receptors without measurable effects on alpha3beta4 receptors. The authors investigated the analgesic effects of Sazetidine-A using the formalin model of chronic inflammatory pain.

Methods

The formalin test was conducted after rats received intraperitoneal saline, Sazetidine-A (0.125, 0.25, 0.5, 1, 2 mg/kg), or subcutaneous epibatidine (2.5-5-10 mug/kg). In other experiments, Sazetidine-A was preceded by naloxone (0.5 mg/kg) or mecamylamine (10 mg). Effects of Sazetidine-A and epibatidine on locomotor were tested in an open field, and seizure activity was measured using the Racine scale. Locus coeruleus neuron extracellular single-unit spontaneous discharge was recorded in anesthetized animals after Sazetidine-A and epibatidine.

Results

Higher doses of Sazetidine-A (0.5, 1, or 2 mg/kg) induced analgesia, with pain scores significantly lower than those seen after saline, lower doses of Sazetidine-A, and epibatidine (P < 0.001). Naloxone did not antagonize the effects of Sazetidine-A, and mecamylamine had partial, dose-dependent antagonistic effects. Epibatidine excited locus coeruleus neurons, whereas Sazetidine-A had no effect on these neurons. Epibatidine and Sazetidine-A affected animals' locomotor activity for the initial 20 min. While analgesic doses of epibatidine caused seizures, no seizure activity or other neurologic complications were seen in animals that received as much as four times the minimum analgesic dose of Sazetidine-A.

Conclusions

Sazetidine-A seems to be a potent analgesic without causing neurologic side effects.
Knut Schmidt–Nielsen. 24 September 1915 — 25 January 2007
Authors: Vogel Steven
Published: August 2008

Knut Schmidt–Nielsen, born in Trondheim, Norway, was the leading comparative physiologist of the second half of the twentieth century. He played a key role in the transformation of what, in the first half of the century, had been a well–regarded but essentially local approach to the subject begun by his mentor, August Krogh, into what is now an established, worldwide field. He was a pioneer in integratingfield and laboratory measurements and in recognizing the intimate relationship between an animal's environment and its physiological adaptations. He greatly broadened and provided perhaps the best support for Krogh's notion that mechanisms could often be best illuminated by shrewd choice of experimental material, in particular by using animals in which a particular function met an especially strong challenge. He also drew attention to the way in which the pattern of variation of some feature or function varied withsize—‘scaling’—could be used as yet another tool for elucidating function. He began work that integrated animal locomotion and physiology, recognizing that locomotion typically represented an extreme challenge for physiological systems. More than any other person, he changed the way in which physiology is taught to undergraduates in the USA and elsewhere: from a human–oriented perspective derived from its origin in medicine to a comparative outlook compatible with the rest of biology.
Regulation of apoptosis by XIAP ubiquitin-ligase activity
Authors: Schile Andrew J. , García-Fernández María , Steller Hermann
Published: August 2008

Inhibitor of Apoptosis Proteins (IAPs) can bind to and inhibit caspases, the key executioners of apoptosis. Because IAPs are frequently overexpressed in human tumors, they have become major pharmacological targets for developing new cancer therapeutics. However, the precise physiological function of individual mammalian IAPs and their role as E3 ubiquitin-ligases in situ remain largely obscure. Here, we investigated the function of XIAP ubiquitin-ligase activity by inactivating the RING motif via gene targeting in the mouse. Removing the RING stabilized XIAP in apoptotic thymocytes, demonstrating that XIAP ubiquitin-ligase activity is a major determinant of XIAP protein stability. Surprisingly, the increased amounts of “XIAP-BIR-only” protein did not lead to attenuated but rather increased caspase activity and apoptosis. ΔRING embryonic stem cells and fibroblasts had elevated caspase-3 enzyme activity, and XIAP ΔRING embryonic fibroblasts were strongly sensitized to TNF-α-induced apoptosis. Similar results were obtained with XIAP deficient mice. Furthermore, deletion of the RING also improved the survival of mice in the Eμ-Myc lymphoma model. This demonstrates a physiological requirement of XIAP ubiquitin-ligase activity for the inhibition of caspases and for tumor suppression in vivo.
Recognition of misfolded proteins by Lon, a AAA+ protease
Authors: Gur Eyal , Sauer Robert T.
Published: August 2008

Proteins unfold constantly in cells, especially under stress conditions. Degradation of denatured polypeptides by Lon and related ATP-dependent AAA+ proteases helps prevent toxic aggregates formation and other deleterious consequences, but how these destructive enzymatic machines distinguish between damaged and properly folded proteins is poorly understood. Here, we show that Escherichia coli Lon recognizes specific sequences—rich in aromatic residues—that are accessible in unfolded polypeptides but hidden in most native structures. Denatured polypeptides lacking such sequences are poor substrates. Lon also unfolds and degrades stably folded proteins with accessible recognition tags. Thus, protein architecture and the positioning of appropriate targeting sequences allow Lon degradation to be dependent or independent of the folding status of a protein. Our results suggest that Lon can recognize multiple signals in unfolded polypeptides synergistically, resulting in nanomolar binding and a mechanism for discriminating irreversibly damaged proteins from transiently unfolded elements of structure.
Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes
Authors: Haeusler Rebecca A. , Pratt-Hyatt Matthew , Good Paul D. , Gipson Theresa A. , Engelke David R.
Published: August 2008

The 274 tRNA genes in Saccharomyces cerevisiae are scattered throughout the linear maps of the 16 chromosomes, but the genes are clustered at the nucleolus when compacted in the nucleus. This clustering is dependent on intact nucleolar organization and contributes to tRNA gene-mediated (tgm) silencing of RNA polymerase II transcription near tRNA genes. After examination of the localization mechanism, we find that the chromosome-condensing complex, condensin, is involved in the clustering of tRNA genes. Conditionally defective mutations in all five subunits of condensin, which we confirm is bound to active tRNA genes in the yeast genome, lead to loss of both pol II transcriptional silencing near tRNA genes and nucleolar clustering of the genes. Furthermore, we show that condensin physically associates with a subcomplex of RNA polymerase III transcription factors on the tRNA genes. Clustering of tRNA genes by condensin appears to be a separate mechanism from their nucleolar localization, as microtubule disruption releases tRNA gene clusters from the nucleolus, but does not disperse the clusters. These observations suggest a widespread role for condensin in gene organization and packaging of the interphase yeast nucleus.
TBP, Mot1, and NC2 establish a regulatory circuit that controls DPE-dependent versus TATA-dependent transcription
Authors: Hsu Jer-Yuan , Juven-Gershon Tamar , Marr Michael T. , Wright Kevin J. , Tjian Robert , Kadonaga James T.
Published: August 2008

The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional module. RNAi depletion and overexpression experiments revealed a genetic circuit that controls the balance of transcription from two core promoter motifs, the TATA box and the downstream core promoter element (DPE). In this circuit, TBP activates TATA-dependent transcription and represses DPE-dependent transcription, whereas Mot1 and NC2 block TBP function and thus repress TATA-dependent transcription and activate DPE-dependent transcription. This regulatory circuit is likely to be one means by which biological networks can transmit transcriptional signals, such as those from DPE-specific and TATA-specific enhancers, via distinct pathways.
Cooperative action of NC2 and Mot1p to regulate TATA-binding protein function across the genome
Authors: van Werven Folkert J. , van Bakel Harm , van Teeffelen Hetty A.A.M. , Altelaar A.F. Maarten , Koerkamp Marian Groot , Heck Albert J.R. , Holstege Frank C.P. , Timmers H.Th. Marc
Published: August 2008

Promoter recognition by TATA-binding protein (TBP) is an essential step in the initiation of RNA polymerase II (pol II) mediated transcription. Genetic and biochemical studies in yeast have shown that Mot1p and NC2 play important roles in inhibiting TBP activity. To understand how TBP activity is regulated in a genome-wide manner, we profiled the binding of TBP, NC2, Mot1p, TFIID, SAGA, and pol II across the yeast genome using chromatin immunoprecipitation (ChIP)–chip for cells in exponential growth and during reprogramming of transcription. We find that TBP, NC2, and Mot1p colocalize at transcriptionally active pol II core promoters. Relative binding of NC2α and Mot1p is higher at TATA promoters, whereas NC2β has a preference for TATA-less promoters. In line with the ChIP–chip data, we isolated a stable TBP–NC2–Mot1p–DNA complex from chromatin extracts. ATP hydrolysis releases NC2 and DNA from the Mot1p–TBP complex. In vivo experiments indicate that promoter dissociation of TBP and NC2 is highly dynamic, which is dependent on Mot1p function. Based on these results, we propose that NC2 and Mot1p cooperate to dynamically restrict TBP activity on transcribed promoters.
tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxis
Authors: Tang Linnan , Franca-Koh Jonathan , Xiong Yuan , Chen Mei-Yu , Long Yu , Bickford Ross M. , Knecht David A. , Iglesias Pablo A. , Devreotes Peter N.
Published: August 2008

In a forward genetic screen for chemotaxis mutants in Dictyostelium discoideum, we identified a loss-of-function mutation, designated tsunami, encoding a homolog of the Fused kinase. Cells lacking tsuA function could not effectively perform chemotaxis and were unable to become polarized or correctly orient pseudopods in chemotactic gradients. While tsuA− cells were able to couple receptor occupancy to phosphatidylinositol (3,4,5) trisphosphate (PIP3) production and actin polymerization, the PIP3 response was prolonged and basal F-actin levels were increased. Interestingly, TsuA localizes to the microtubule network and puncta mainly found at the cell periphery. Analysis of the gene uncovered a novel C-terminal domain that we designated the Tsunami Homology (TH) domain. Both the kinase domain and the TH domain are required to rescue the phenotypic defects of tsuA− cells. While kinase activity is not required for localization to microtubules, the TH domain is essential. Thus, localization of kinase activity to microtubules is critical for TsuA function. We propose that functions in association with the microtubule network may underlie the divergent roles of Fused kinase proteins in different organisms.