bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic alterations in chemokine gradients induce transendothelial shuttling of human T cells under physiologic shear conditions
Authors: Lee Jack Y , Buzney Catherine D , Poznansky Mark C , Sackstein Robert
Published: October 2009

Findings support a novel paradigm by which temporospatial modulations in subendothelial chemokine display drive cell migration from interstitial compartments into the bloodstream.

The active movement of cells from subendothelial compartments into the bloodstream (intravasation) has been recognized for several decades by histologic and physiologic studies, yet the molecular effectors of this process are relatively uncharacterized. For extravasation, studies based predominantly on static transwell assays support a general model, whereby transendothelial migration (TEM) occurs via chemoattraction toward increasing chemokine concentrations. However, this model of chemotaxis cannot readily reconcile how chemokines influence intravasation, as shear forces of blood flow would likely abrogate luminal chemokine gradient(s). Thus, to analyze how T cells integrate perivascular chemokine signals under physiologic flow, we developed a novel transwell-based flow chamber allowing for real-time modulation of chemokine levels above (luminal/apical compartment) and below (abluminal/subendothelial compartment) HUVEC monolayers. We routinely observed human T cell TEM across HUVEC monolayers with the combination of luminal CXCL12 and abluminal CCL5. With increasing concentrations of CXCL12 in the luminal compartment, transmigrated T cells did not undergo retrograde transendothelial migration (retro-TEM). However, when exposed to abluminal CXCL12, transmigrated T cells underwent striking retro-TEM and re-entered the flow stream. This CXCL12 fugetactic (chemorepellant) effect was concentration-dependent, augmented by apical flow, blocked by antibodies to integrins, and reduced by AMD3100 in a dose-dependent manner. Moreover, CXCL12-induced retro-TEM was inhibited by PI3K antagonism and cAMP agonism. These findings broaden our understanding of chemokine biology and support a novel paradigm by which temporospatial modulations in subendothelial chemokine display drive cell migration from interstitial compartments into the bloodstream.
Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity
Authors: Biburger Markus , Theiner Gabi , Schädle Mirjam , Schuler Gerold , Tiegs Gisa
Published: October 2009

HO-1 induction in human T cells inhibits their proliferation, HO-1 suppression in Tregs increases their proliferation, but neither treatment fundamentally changes their respective suppressive capacity.

HO-1 is the only inducible one of three isoenzymes that catalyzes the oxidative degradation of heme. HO-1 is inducible by various cellular stress factors and exerts cytoprotective and immunomodulatory effects. Recent publications demonstrated that HO-1 is constitutively expressed by CD4+CD25+ Tregs and induced in CD4+CD25− T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human Tregs to exert immunosuppression in vitro. PGJ2 induced pronounced expression of HO-1 in CD4+CD25− T cells without accompanying FoxP3 induction. Treatment of CD4+CD25− T cells with PGJ2 decreased their proliferation, whereas the HO-1 inhibitor SnPP enhanced the proliferation of HO-1-expressing Tregs, suggesting that HO-1 may modulate the proliferative capacity of T lymphocytes. HO-1 modulation by SnPP treatment of Tregs or PGJ2 treatment of CD4+CD25− T cells neither suppressed nor induced immune-modulatory function in these cells, respectively, as measured by responder-cell proliferation and/or IL-2 production. In summary, these data suggest that HO-1 expression by Tregs might contribute to their typical reluctance to proliferate but does not account independently for their suppressive functions.
Transcriptional Profiling of the Hormone-Responsive Stages of Spermatogenesis Reveals Cell-, Stage-, and Hormone-Specific Events
Authors: O'Donnell Liza , Pratis Kyriakos , Wagenfeld Andrea , Gottwald Ulrich , Müller Jörg , Leder Gabriele , McLachlan Robert I. , Stanton Peter G.
Published: October 2009

Spermatogenesis occurs within the highly complex seminiferous epithelium. This cyclic process is accompanied by dynamic stage-specific transcriptional changes and is driven by androgens and FSH by mechanisms that are unclear. Here we report the impact of acute androgen and FSH suppression on the transcriptional dynamics of the seminiferous epithelium. We used transcriptional profiling to compare the most hormone-sensitive seminiferous epithelial stages (VII and VIII) from control and hormone-suppressed adult rats, together with publicly available datasets to delineate stage- and cell-specific transcriptional changes. The analyses reveal that, in these stages, there was a hormone-responsive down-regulation of spermatogonial and Sertoli cell transcripts maximally expressed in the earlier spermatogenic stages (I–VI). Transcripts expressed in Sertoli cells from stage VII and beyond were both up- and down-regulated by hormone suppression, with lysosome function, immune system-related genes, and lipid metabolism predicted to be hormone responsive. Hormone-responsive genes with putative roles in integrin-mediated cell adhesion were also identified. In pachytene spermatocytes, there was an initiation of transcription likely important for the completion of meiosis. A transcriptional switch in round spermatids was observed, from a hormone-responsive down-regulation of transcripts expressed in steps 1–7 spermatids to a hormone-independent up-regulation of transcripts expressed in steps 8–11 and likely involved in spermatid differentiation and DNA compaction. This study points to the existence of hormone-responsive global transcriptional repressors in Sertoli cells, spermatogonia, and spermatids and reveals novel and diverse cell-specific responses of the seminiferous epithelium to hormone suppression.
Male-Specific Hepatic Bcl6: Growth Hormone-Induced Block of Transcription Elongation in Females and Binding to Target Genes Inversely Coordinated with STAT5
Authors: Meyer Rosana D. , Laz Ekaterina V. , Su Ting , Waxman David J.
Published: October 2009

The transcriptional repressor Bcl6 is a male-specific rat liver gene product and one of 24 early GH-response genes encoding DNA-binding proteins. Presently, the sex specificity of Bcl6 was shown to emerge at puberty, when hepatic Bcl6 mRNA was induced in males and repressed in females by the female plasma GH profile. Hepatic Bcl6 mRNA was increased to near-normal male levels in hypophysectomized females and was extinguished in intact males given a continuous GH infusion (female-like GH pattern). Bcl6 was also repressed in adult male somatostatin-deficient mice, where plasma GH profiles are female like. Hepatic Bcl6 RNA was rapidly down-regulated by GH pulse treatment, both in hypophysectomized male rats and in primary rat hepatocytes. Bcl6 was substantially induced in female mice deficient in hepatic signal transducer and activator of transcription (STAT)5a/STAT5b, suggesting that these STAT transcriptional mediators of GH signaling repress Bcl6. Indeed, STAT5 was bound to Bcl6 STAT5-binding region-B, previously associated with Bcl6 repression, in both male and female liver chromatin. STAT5 also bound to Bcl6 region-A in male chromatin but only during a plasma GH pulse. Analysis of primary transcripts (heterogenous nuclear RNA) across the Bcl6 gene revealed a novel mechanism of GH-dependent sex specificity, with two apparent blocks in Bcl6 transcription elongation seen in female liver and in continuous GH-treated male liver, one early in intron 4 and one in exon 5, which together reduced transcription beyond exon 5 more than 300-fold. Finally, Bcl6 was bound to a subset of STAT5-binding sites in male liver chromatin, including a Socs2 STAT5-binding site where Bcl6 binding increased substantially between plasma GH pulses, i.e. when STAT5 binding was low. Bcl6 and STAT5 binding are thus inversely coordinated by the endogenous pulses of pituitary GH release, suggesting this male-specific transcriptional repressor modulates hepatic GH signaling to select STAT5 target genes.
A method to assess capacity utilization in short cycle functional layouts
Authors: Klarin M , Milanovic D D , Misita M , Spasojevic-Brkic V , Jovovic A
Published: October 2009

The aim of this article is to indicate that methods of monitoring capacity utilization applied in the processing industry such as cement production can be used in the metalworking industry that has a high level of capacity utilization. The process approach to establishing the level of capacity utilization can be employed in conditions of balanced line production, or when there are components of large-scale production, as well as short production cycles. The results of the analysis indicate that when the level of capacity utilization is high, this variable can be observed per day as stochastic, while, per machine, it can be a random variable. In the metalworking industry it is possible to monitor a larger number of factors related to operating and not operating machines, whereas in the processing industry the factor of work is generally only a single-machining time and factors of not operating are connected only to breakdowns or regular maintenance. To monitor capacity utilization in the processing industry, it is possible to apply a work-sampling method as well as the continual streaming method. The possibility common for both industries is to represent the monitoring of capacity utilization over time and to test the mastering of that stochastic function via control limits that are optimal when defined by 2SD.
Fuzzy modelling approach to magnetorheological dampers: Forward and inverse model
Authors: Won J-S , Sunwoo M
Published: October 2009

This paper proposes a new approach to the design of a control-oriented model for magnetorheological dampers for vibration control systems using a fuzzy modelling scheme. First, a forward fuzzy model that exhibits non-linear behaviour, such as hysteretic and field-dependent characteristics, and which produces a force for given operating conditions and control voltage, is devised and described. Second, using the notion of a mathematical involution, inverse fuzzy models for control analysis are continuously derived from the proposed forward fuzzy model. A simulation study is conducted for the proposed fuzzy models and performance results are analysed to evaluate their viabilities as a possible solution as well as a framework for control analysis.
Dynamic fuzzy-neural fluctuation smoothing rule for jobs scheduling in a wafer fabrication factory
Authors: Chen T
Published: October 2009

The present paper proposes a dynamic fuzzy-neural fluctuation smoothing rule to improve the performance of scheduling jobs in a wafer fabrication factory. The rule is modified from the well-known fluctuation smoothing rules with some innovative treatments. First, two non-linear forms of the fluctuation smoothing rule are obtained. To consider two performance measures (the average cycle time and cycle time variation) simultaneously, the two non-linear fluctuation smoothing rules are merged into a bi-criteria rule. Second, to tailor the content of the bi-criteria rule for a specific wafer fabrication factory, a dynamic factor is designed which facilitates the gradual transition between rules. Third, the remaining cycle time of a job to be scheduled is estimated by applying the fuzzy c-means (FCM)-back-propagation network (BPN) approach to improve the estimation accuracy. To evaluate the effectiveness of the proposed methodology, production simulation is also applied in this study. According to experimental results, the proposed methodology outperforms some existing approaches in reducing the average cycle time and cycle time variation at the same time. Moreover, experimental results also reveal that with the dynamic rule it is possible to improve one performance measure without raising the expense of another performance measure.
Optimum simple ramp test for the log-logistic distribution with censoring
Authors: Srivastava P W , Shukla R
Published: October 2009

This paper presents an optimum simple ramp accelerated life test with two different linearly increasing stresses for the log-logistic distribution under type I censoring. The log-logistic life distribution has been found appropriate for high-reliability components. The inverse power law and a cumulative exposure model are assumed. The higher of the two stress rates is specified and the low stress rate and proportion of test units allocated to the low stress mode are found by minimizing the asymptotic variance of the maximum likelihood estimates of the quantile of the cumulative distribution function at design stress. For some selected values of the parameters, the effect of the incorrect pre-estimates of the design parameters has been studied in terms of the percentage of the variance increase. Confidence intervals involving design parameters have also been obtained.
Orthotopic Neobladder versus Ileal Conduit Urinary Diversion after Cystectomy – A Quality-of-Life Based Comparison
Authors: Philip Joe , Manikandan Ramaswamy , Venugopal Suresh , Desouza John , Javlé Pradip M
Published: October 2009

INTRODUCTION

Radical cystectomy remains the gold standard in treatment of muscle invasive bladder cancer. Evolution of pathological guidelines has empowered centres to offer orthotopic substitution (OBS) to patients undergoing radical cystectomy. We compared health-related quality of life (HRQoL) between patients who underwent OBS or ileal conduit urinary diversion (ICD) following radical cystectomy.

PATIENTS AND METHODS

A total of 57 patients who underwent cystectomy were assessed pre-operatively using Karnofsky performance scale (KPS). Of these, 52 patients (28 OBS and 24 ICD) who responded to a postal questionnaire consisting of SF-36 and a functional index questionnaire were included.

RESULTS

Median age of patients was 70 years. Pre-operative KPS scores were similar. All eight HRQoL scales were favourable in both groups. OBS patients had significantly better physical functioning. In the cohort, 42% of men with OBS and 25% of diversions could maintain an erection to varying degrees. Of the OBS patients, 85% were continent with two patients reporting reduced QoL with pad usage. Of ICD patients, 63% felt less complete and 42% were embarrassed due to the stoma, with 58% apprehensive of stomal leakage. Of OBS patients, 96% had significant relationships and a more active life-style.

CONCLUSIONS

In a similar age-group population, there was no significant difference in most QoL indices but body image issues persist in ICD patients. OBS patients had significantly better physical function, continuing to have a more active life-style. They attained urethral voiding with good continence. A detailed discussion of long-term functional outcome would engender a realistic expectation allowing better adaptation.
The Evolution of a Hand Day-Surgery Unit
Authors: Dillon CK , Chester DL , Nightingale Peter , Titley OG
Published: October 2009

INTRODUCTION

Following the merger of two major units to form a regional centre for plastic surgery in the West Midlands, acute hand surgery referrals reached overwhelming proportions. This study describes audits performed at three time points. The first highlighted the extent of in-patient delay and was instrumental in the subsequent development of a dedicated hand trauma day-case unit.

PATIENTS AND METHODS

Data were collected on 77 patients in June 2002, 109 patients in November 2003 and 90 patients in November 2004. The day-case unit opened on 1 November 2003.

RESULTS

The number of bed-days per patient fell from 2.63 to 1.34 (P < 0.001) over the study period. In November 2004, 51% of patients received a day-case procedure. Importantly, if admission was required at initial presentation, the delay to theatre reduced from 1.5 bed-days per patient in June 2002 to 0.6 in November 2004. Overall, the in-patient delay was significantly reduced (P < 0.001) but time from presentation to theatre was not significantly affected (P = 0.119).

CONCLUSIONS

This series of audits confirmed that a significant number of acute hand injuries are suitable for day-case procedures and that simple audit can lead to a significant change in service provision. Improvements were demonstrated in reduced in-patient delay and total stay. We hope that other units find our experience useful given that it may be possible to apply this approach to other forms of ambulatory trauma.
Introduction of a Day-Case Laparoscopic Cholecystectomy Service in the UK: A Critical Analysis of Factors Influencing Same-Day Discharge and Contact with Primary Care Providers
Authors: Briggs CD , Irving GB , Mann CD , Cresswell A , Englert L , Peterson M , Cameron IC
Published: October 2009

INTRODUCTION

The objective of this study was to determine the safety and acceptability of the implementation of a day-case laparoscopic cholecystectomy (LC) service in a large UK teaching hospital, and analyse factors influencing contact with primary care providers. Wide-spread introduction of day-case LC in the UK is a major target of healthcare providers. However, few centres have reported their experience. In the US, out-patient surgery for LC has been reported, though many groups have utilised 24-h observation units to facilitate discharge. Concerns remain amongst surgeons regarding the feasibility and acceptability of the introduction of day-case LC in the UK.

PATIENTS AND METHODS

Comprehensive care and operative data were prospectively collected on the first 106 consecutive day-case procedures in our hospital. Postoperative recovery was monitored by telephone questionnaire on days 2, 5 and 14, including complications, satisfaction and general practitioner consultation.

RESULTS

A total of 106 patients were admitted for day-case LC, of whom 84% were discharged on the day of surgery. Patient satisfaction rate was 94% in both the successful day-case and the admitted patients. Mean operation time was 62 min, with an average total stay on the day-care unit of 426 min. Training-grade surgeons performed 31% of operations. Both the re-admission rate after surgery and rate of conversion to open surgery were 2%. Advice from primary healthcare providers was sought by 33% of patients within the first 14 postoperative days.

CONCLUSIONS

Introduction of day-case LC in the UK is feasible and acceptable to patients. The potential burden to primary care providers needs further study.
Operative Mortality, Blood Loss and the Use of Pringle Manoeuvres in 526 Consecutive Liver Resections
Authors: Lordan Jeffrey T , Worthington Tim R , Quiney Nial , Fawcett William J , Karanjia Nariman D
Published: October 2009

INTRODUCTION

Centres with high volumes of high-risk surgery have significantly better outcomes than low-volume centres for pancreatic resection, oesophagectomy and pelvic exenteration. However, this has not to date been conclusively demonstrated for hepatic resection. With increased experience, operative practice can change. The use of the Pringle manoeuvre reduced substantially over a 12-year period in a single centre as it was felt anecdotally that its use increased the incidence of hepatic insufficiency and operative mortality. This study was designed to review 12 years of experience in a single hepatobiliary centre

PATIENTS AND METHODS

Data regarding 526 consecutive liver resections were prospectively recorded and retrospectively analysed in a high-volume referral unit over a 12-year period. Patients' demographics, operative mortality and morbidity were analysed on an annual basis.

RESULTS

Overall peri-operative mortality was 1.9%. Operative mortality in the first 6 years compared to the latter 6 years was 4.1% and 1.2%, respectively (P = 0.13). The morbidity rate was 26.8% and 20.3% in the first and second halves of the study, respectively (P = 0.15). With increased experience, intra-operative blood loss and patients receiving blood transfusions decreased (P = 0.047 and 0.03, respectively) while the number of intra-operative Pringle manoeuvres also decreased (P < 0.0001). Hospital stay decreased significantly over the 12 years (P = 0.049).

CONCLUSIONS

High-volume centres are the safest environment for hepatic resection. With increased experience, it may be possible to reduce the intra-operative use of the Pringle manoeuvre without increasing the intra-operative blood loss. This may be associated with a decrease in hepatic insufficiency and peri-operative mortality.
Penetrating Missile Injuries During the Iraqi Insurgency
Authors: Ramasamy A , Harrisson SE , Stewart MPM , Midwinter M
Published: October 2009

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.
Laparoscopic Colorectal Surgery: Summary of the Current Evidence
Authors: Aly Emad H
Published: October 2009

INTRODUCTION

Laparoscopic colectomy has not been accepted as quickly as laparoscopic cholecystectomy. This is because of its steep learning curve, concerns with oncological outcomes, lack of randomised controlled trials (RCTs) and initial reports on port-site recurrence after curative resection. The aim of this review is to summarise current evidence on laparoscopic colorectal surgery.

PATIENTS AND METHODS

Review of literature following Medline search using key words ‘laparoscopic’, ‘colorectal’ and ‘surgery’.

CONCLUSIONS

Laparoscopic colorectal surgery proved to be safe, cost-effective and with improved short-term outcomes. However, further studies are needed to assess the role of laparoscopic rectal cancer surgery and the value of enhanced recovery protocols in patients undergoing laparoscopic colorectal resections.
Open access publication of scientific research: facts and myths
Authors: Kumar M
Published: October 2009

The publishing industry influences the way in which scientific knowledge is disseminated. In the knowledge 'industry' neither the producer nor the consumer has control over the economics and marketing of knowledge. The researcher gives away research data free to the journals, which retain the copyright. The peer reviewers are also not usually paid. Journal subscription rates of scientific, technical and medical (STM) journals in North America have increased 200% over ten years and this is six times more than the inflation rate during that period.
College research: raising awareness
Authors: Jary Louise
Published: October 2009

The cutting-edge research conducted by College fellows, which is the focus of this issue of the Bulletin, would not be possible without legacies and donations. In this article Louise Jary highlights the role of presentations given nationally by the College to promote its surgical research and to raise awareness of its activities.
GMC consults on important research guidance
Authors: O'Brien Jane
Published: October 2009

Research involving people directly or indirectly is vital in improving care and reducing uncertainty for patients now and in the future, and improving the health of the population as a whole.
National clinical audit: lessons from cardiac surgery
Authors: Bridgewater Ben
Published: October 2009

Cardiac surgery has a long history of collecting and analysing clinical outcomes data. Initial systems for benchmarking mortality against pooled national data started in the 1970s. The initiative was given impetus by the Bristol Pubic Inquiry Report and the introduction of the Freedom of Information Act in 2005. Over recent years national data collection has been supported by funding from the National Clinical Audit Support Programme. All NHS hospitals in the UK now submit data to the national database. The Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS) in conjunction with Dendrite Clinical Systems have recently produced a major report, Demonstrating quality, the sixth national database report, which received significant national press coverage because it reported marked improvement in the quality of care for patients undergoing cardiac surgery over the last decade.
College pump-primes urological research
Authors: Cornick Ed
Published: October 2009

Marcus Drake, a consultant surgeon at Bristol Urological Institute (BUI) at Southmead Hospital, believes that undertaking research into surgical problems is increasingly challenging: 'The decline in numbers of medical academics has particularly affected the surgical specialties. "Own account" research has become harder and funding is now directed to researchers with a track record so it is ever harder to get started.' His experiences exemplify the challenges that have to be faced and how it is still possible to overcome them, even outside an academic setting.
The differential effect of team members' trust on team performance: The mediation role of team cohesion
Authors: Mach Merce , Dolan Simon , Tzafrir Shay
Published: October 2009

This study examines team performance as affected by various trusting relationships: trust between team members and the team's trust in their direct manager and in top management. Data for the study were collected from a survey of 690 professional elite athletes (belonging to 59 different sports clubs) playing in the regular, top professional Spanish leagues. The model was tested at the team level. Findings reveal that team member trust with respect to the different foci has both a direct and indirect effect on team performance, and that team player trust and cohesion play a mediating role. This study illustrates the dynamic relationship within teams, and, as such, trust among teammates mediates the relationship between trust in the coach as well as team cohesion in determining team performance. The implications for managing teams in other contexts are also evaluated.
Increasing the probability of finding an interaction in work stress research: A two‐wave longitudinal test of the triple‐match principle
Authors: Chrisopoulos Sergio , Dollard Maureen F. , Winefield Anthony H. , Dormann Christian
Published: October 2009

Research into work stress has attempted to identify job resources that can moderate the effects of job demands on strain. The recently developed triple‐match principle (TMP) proposes that job demands, resources, and strain can be conceptualized as being composed of cognitive, emotional, and physical dimensions. When a psychological imbalance is induced by job demands, individuals activate corresponding resources to reduce the effects of the demands. A closer match occurs when the resources are processed in the same psychological domain as the demands. The further away from a match, the less likely an interactive effect will become. Put simply, the likelihood of finding an interactive effect between job demands and job resources is greatest when demands, resources, and strain are based on qualitatively similar dimensions (i.e. cognitive, emotional, and physical). For example, emotional support from colleagues is likely to buffer the effects of emotional demands on emotional exhaustion. The TMP was tested in a sample of 179 Australian police officers in a two‐wave longitudinal study. The likelihood of finding an interactive effect was related to the degree of match between job demands, job resources, and strain with 33.3% of triple‐match interactions significant, 22.2% when there was a double‐match, and 0.0% when there was no match. These findings lend support to the TMP as a guiding framework, for research, to explore possible interactive effects in work stress research, and for practice, to inform interventions matching resources to occupational demands, to offset strain.
Microsystem for Isolation of Fetal DNA from Maternal Plasma by Preparative Size Separation
Authors: Hahn Thomas , Drese Klaus S , O'Sullivan Ciara K
Published: October 2009

Background: Routine prenatal diagnosis of chromosomal anomalies is based on invasive procedures, which carry a risk of approximately 1%–2% for loss of pregnancy. An alternative to these inherently invasive techniques is to isolate fetal DNA circulating in the pregnant mother’s plasma. Free fetal DNA circulates in maternal plasma primarily as fragments of lengths <500 bp, with a majority being <300 bp. Separating these fragments by size facilitates an increase in the ratio of fetal to maternal DNA.

Methods: We describe our development of a microsystem for the enrichment and isolation of cell-free fetal DNA from maternal plasma. The first step involves a high-volume extraction from large samples of maternal plasma. The resulting 80-μL eluate is introduced into a polymeric microsystem within which DNA is trapped and preconcentrated. This step is followed by a transient isotachophoresis step in which the sample stacks within a neighboring channel for subsequent size separation and is recovered via an outlet at the end of the channel.

Results: Recovered fractions of fetal DNA were concentrated 4–8 times over those in preconcentration samples. With plasma samples from pregnant women, we detected the fetal SRY gene (sex determining region Y) exclusively in the fragment fraction of <500 bp, whereas a LEP gene (leptin) fragment was detected in both the shorter and longer recovery fractions.

Conclusions: The microdevice we have described has the potential to open new perspectives in noninvasive prenatal diagnosis by facilitating the isolation of fetal DNA from maternal plasma in an integrated, inexpensive, and easy-to-use microsystem.
Utility of Urine Myoglobin for the Prediction of Acute Renal Failure in Patients with Suspected Rhabdomyolysis: A Systematic Review
Authors: Rodríguez-Capote Karina , Balion Cynthia M , Hill Stephen A , Cleve Richard , Yang Lufang , El Sharif Adell
Published: October 2009

Background: Urine myoglobin continues to be used as a marker of rhabdomyolysis, particularly to assess risk of developing acute renal failure and evaluate treatment success. We sought to determine the predictive validity of urine myoglobin (uMb) for acute renal failure (ARF) in patients with suspected rhabdomyolysis.

Methods: We performed a broad systemic review of the literature from January 1980 to December 2006 using the search terms myoglobin$ AND (renal OR ARF OR kidney). Only primary studies published in English where uMb measurement was related to ARF were included.

Results: Of 1602 studies screened, 52 met all selection criteria. The studies covered a wide spectrum of etiologies for rhabdomyolysis, dissimilar diagnostic criteria for ARF and rhabdomyolysis, and various methods of uMb measurement and were mostly case series (n = 32). There was poor reporting on the uMb method, and 17 studies failed to provide any information about the method. The reporting of clinical criteria for ARF with respect to timing, description, performance, and interpretation also lacked adequate detail for replication. Eight studies (total 295 patients) had data for 2-by-2 tables. Sensitivity of the uMb test was 100% in 5 of the 8 studies, specificity varied widely (15% to 88%), and CIs around these measures were high. Pooling of data was not possible because of study heterogeneity.

Conclusions: There is inadequate evidence evaluating the use of uMb as a predictor of ARF in patients with suspected rhabdomyolysis.
Healthy Individuals Carrying the PCSK9 p.R46L Variant and Familial Hypercholesterolemia Patients Carrying PCSK9 p.D374Y Exhibit Lower Plasma Concentrations of PCSK9
Authors: Humphries Steve E , Neely R Dermot G , Whittall Roslyn A , Troutt Jason S , Konrad Robert J , Scartezini Marileia , Li Ka Wah , Cooper Jackie A , Acharya Jayshree , Neil Andrew
Published: October 2009

Background: We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p.R46L), in statin-treated patients with a clinical diagnosis of familial hypercholesterolemia (FH) and carrying a PCSK9 gain-of-function mutation (p.D374Y), and in statin-treated patients with FH due to different genetic causes.

Methods: PCSK9 was measured with a previously described ELISA.

Results: In 81 healthy middle-aged Caucasian men, the PCSK9 concentration was significantly associated with the concentrations of total cholesterol (r = 0.42; P < 0.0001), LDL cholesterol (r = 0.34; P = 0.01), and triglycerides (r = 0.25; P = 0.02). In p.R46L carriers, mean (SD) concentrations of PCSK9 were 15% lower than in RR individuals [65.5 μg/L (21.6 μg/L) vs 77.5 μg/L (18.2 μg/L); P = 0.03]. In patients with the p.D374Y variant (n = 7), the mean PCSK9 concentration was significantly lower than in the combined group of patients with an LDLR (low density lipoprotein receptor) mutation (n = 25), an APOB [apolipoprotein B (including Ag(x) antigen)] variant encoding p.R3527Q (n = 6), or no detectable mutation (n = 14) [96.4 μg/L (42.5 μg/L) vs 151.6 μg/L (69.6 μg/L); P = 0.02]. Two of the 14 patients with no mutation had PCSK9 concentrations below the mean for p.D374Y carriers; sequencing of the PCSK9 gene and promoter revealed no mutations. Among 409 FH patients, we identified 6 carriers of the promoter variant −287G>A (1.5%), a frequency similar to that (1.0%) previously reported for 2772 healthy men in the UK. In neither group was the −287G>A variant associated with differences in lipid traits.

Conclusions: The loss-of-function p.R46L variant is associated with the expected lower concentrations of circulating PCSK9; the gain-of-function p.D374Y mutation is also associated with lower concentrations, presumably because of the higher affinity of this variant for the LDL receptor and its more rapid clearance. In treated FH patients, a low plasma PCSK9 concentration does not appear to be a useful screening tool for identifying novel PCSK9 mutations.
The sensory-motor theory of semantics: Evidence from functional imaging
Authors: Noppeney Uta
Published: October 2009

This review discusses the contributions of functional imaging (fMRI/PET) to our understanding of how semantic concepts are represented and processed in the human brain. The sensory-motor theory of semantic memory suggests that semantic processing relies on reactivation of sensory-motor representations that were involved in perception and action. More specifically, it attributes an apparent category-specific (e.g. tool vs. animals) organization of semantics to anatomical segregation for different semantic features (e.g. action vs. visual). Within this framework, we will review functional imaging evidence that semantic processing of tools and actions may rely on activations within the visuo-motor system.
Technical details influence the diagnostic accuracy of the 1 μg ACTH stimulation test
Authors: Wade Matthew , Baid Smita , Calis Karim , Raff Hershel , Sinaii Ninet , Nieman Lynnette
Published: October 2009

Objective

To examine the factors causing inadequate cortisol responses to the 1 μg ACTH stimulation test.

Design

Random test assignment (by age and gender) at 0800 or 1600 h.

Methods

We recruited 20 healthy adults to each of the three age groups (<40 years, 40–55 years, and >55 years; half females in each group). ACTH stimulation tests were performed in an outpatient clinic at the NIH Clinical Research Center. Plasma cortisol was measured just before, and 30 and 60 min after the administration of 1 μg ACTH (1–24). The ACTH concentration in diluted and administered solutions was measured.

Results

Twenty-five volunteers (19 at 1600 h) had a subnormal cortisol response (peak cortisol 10.4–17.5 μg/dl), using a criterion <18 μg/dl (497 nmol/l), for a specificity of 58% (confidence interval (CI) 45–71%). Afternoon testing had a significant impact on failure rates (odds ratio 6.98, CI 2.17–22.43), while gender and age did not. The stock solution contained 1 μg ACTH, but after administration through tubing it contained only 0.5–0.8 μg.

Conclusions

The high rate of abnormal results, especially in the afternoon, and loss of ACTH through tubing suggest that morning testing and minimal tubing should be adopted to avoid an inappropriate diagnosis of adrenal insufficiency. Earlier time points and standardized protocols would facilitate comparison of studies.
Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?
Authors: Eller-Vainicher Cristina , Morelli Valentina , Salcuni Antonio Stefano , Torlontano Massimo , Coletti Francesca , Iorio Laura , Cuttitta Antonello , Ambrosio Angelo , Vicentini Leonardo , Carnevale Vincenzo , Beck-Peccoz Paolo , Arosio Maura , Ambrosi Bruno , Scillitani Alfredo , Chiodini Iacopo
Published: October 2009

Objective

Few data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic–pituitary–adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism.

Aim

This study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function.

Design

Prospective, multicenter.

Methods

A total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 μg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 μg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 μg/dl.

Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated.

Results

The presence of >2 alterations among 1 mg-DST>5.0 μg/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54–42.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters.

Conclusion

Post-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma.
Excretion and binding of tritium-labelled oestradiol in mice (Mus musculus): implications for the Bruce effect
Authors: Guzzo Adam C , Berger Robert G , deCatanzaro Denys
Published: October 2009

Male mouse urine contains 17β-oestradiol (E2) and other steroids. Given that males actively direct urine at proximate females and intrauterine implantation of blastocysts is vulnerable to minute amounts of exogenous oestrogens, males' capacity to disrupt early pregnancy could be mediated by steroids in their urine. When male mice were implanted with osmotic pumps containing tritium-labelled E2(3H-E2) or injected i.p. with3H-E2, radioactivity was reliably detected in their urine. Following intranasal administration of3H-E2to inseminated females, radioactivity was detected in diverse tissue samples, with there being significantly more in reproductive tissues than in brain tissues. When urine was taken from males injected with3H-E2, and then intranasally administered to inseminated females, radioactivity was detected in the uterus, olfactory bulbs, and mesencephalon and diencephalon (MC+DC). When inseminated and ovariectomised females were perfused at the point of killing to remove blood from tissues, more radioactivity was detected in the uterus than in muscle, olfactory bulbs, MC+DC and cerebral cortex. Pre-treatment with unlabelled E2significantly reduced the uptake of3H-E2in the uterus. Taken with evidence that males deliver their urine to the nasal area of females, these results indicate that male urinary E2arrives in tissues, including the uterus, where it could lead to the disruption of blastocyst implantation.
Estudos anatômicos e histológicos sôbre a subfamília Triatominae (Heteroptera, Reduviidae): VIII parte: observações sôbre a superfície dos ovos das espécies mais importantes
Authors: Barth Rudolf , Muth Hans
Published: October 2009

Nesta comunicação analisa-se a formação do cório e a amostra da sua superfícies do ovo maduro. As amostras superficiais do cório, apresentadas em esquemas, são características para cada espécie examinada, de maneira que estas estruturas servem para a classificação das espécies.
Caracteres anatômicos de duas espécies de trapoeraba e a eficiência do glyphosate
Authors: Santos I.C. , Meira R.M.S.A. , Ferreira F.A. , Santos L.D.T. , Miranda G.V.
Published: October 2009

O gênero Commelina engloba espécies de plantas daninhas de difícil controle em diversas culturas, principalmente onde o herbicida glyphosate tem sido utilizado com elevada freqüência. Este trabalho foi conduzido com o objetivo de avaliar diferenças entre caracteres anatômicos de Commelina benghalensis e Commelina diffusa, submetidas a crescimento sob condições de sol e sombra, que pudessem influenciar a absorção e translocação deste herbicida. O complexo estomático das duas espécies é semelhante e a folha é anfiestomática. O número de estômatos na epiderme foliar foi maior em C. diffusa (38/mm²) em relação a C. benghalensis (33,66/mm²), na epiderme abaxial (54,86/mm²) em relação à adaxial (16,80/mm²) e sob sol (37,89/mm²) em relação a sombra (33,77/mm²). A epiderme abaxial apresentou maior número de estômatos sob sol. Pêlos secretores, do mesmo tipo, estão presentes nas duas espécies, mas em maior número em C. diffusa. Somente C. benghalensis apresentou pêlos tectores, que são de dois tipos: longos com extremidade afilada e curtos com extremidade curva; os pêlos longos concentram-se na epiderme abaxial e os pêlos curtos, na epiderme adaxial. Apesar de a presença de pêlos na epiderme foliar ser freqüentemente associada à maior absorção de herbicidas, acredita-se que o fator determinante da maior suscetibilidade de C. benghalensis ao glyphosate, em relação a C. diffusa, esteja relacionado à reserva de amido no caule. Enquanto C. benghalensis apresenta poucos e pequenos grãos de amido no parênquima medular, C. diffusa apresenta grandes e numerosos grãos de amido, o que, possivelmente, torna mais lenta a translocação simplástica de herbicidas, reduzindo a quantidade de herbicida acumulada nos pontos de crescimento e permitindo que ela rebrote mesmo após a perda total das folhas.
Interação de glyphosate com carfentrazone-ethyl
Authors: Werlang R.C. , Silva A.A.
Published: October 2009

Foi conduzido um experimento em condições controladas para determinar a interação do carfentrazone-ethyl em mistura no tanque com o herbicida glyphosate, no controle de seis espécies de plantas daninhas. Glyphosate aplicado isoladamente na dose de 720 g ha-1 foi eficaz no controle de Amaranthus hybridus (100%), Desmodium tortuosum (100%), Bidens pilosa (99%), Eleusine indica (96%), Digitaria horizontalis (100%) e Commelina benghalensis (93%) aos 21 DAA. Carfentrazone-ethyl aplicado isoladamente controlou eficazmente C. benghalensis. As misturas de glyphosate nas doses de 252 e 720 g ha-1 com carfentrazone-ethyl nas doses de 15 e 30 g ha¹ demonstraram efeito aditivo no controle de A. hybridus, D. tortuosum e Bidens pilosa, à exceção das misturas de glyphosate na dose de 252 g ha-1 com as doses de 15 e 30 g ha-1 de carfentrazone-ethyl, que proporcionam efeito sinergístico no controle de D. tortuosum. A adição das duas doses de carfentrazone-ethyl antagonizou o efeito de glyphosate na menor dose (252 g ha-1) no controle de E. indica, apresentando, no entanto, efeito aditivo com o glyphosate na maior dose (720 g ha-1). Já para D. horizontalis, as misturas de carfentrazone-ethyl com glyphosate na menor dose (252 g ha-1) apresentaram efeito sinergístico no controle dessa espécie, demonstrando, ainda, efeito aditivo na mistura com glyphosate na dose de 720 g ha-1. A mistura de carfentrazone-ethyl com glyphosate proporcionou efeito aditivo no controle de C. benghalensis, independentemente das combinações de doses avaliadas. Os resultados deste experimento indicam que carfentrazone-ethyl apresenta comportamento diferenciado quanto à interação com glyphosate, dependendo da espécie de planta daninha e da dose dos herbicidas utilizados na mistura em tanque, sendo complementar na mistura em tanque com glyphosate, pois demonstrou efeito antagônico em poucas das combinações estudadas, prevalecendo seu efeito aditivo na mistura com glyphosate, no controle das espécies avaliadas.
Calagem e o potencial de lixiviação de imazaquin em colunas de solo
Authors: Inoue M.H. , Marchiori Jr. O. , Oliveira Jr. R.S. , Constantin J. , Tormena C.A.
Published: October 2009

Com o objetivo de avaliar o potencial de lixiviação do herbicida imazaquin em colunas de solo, após a aplicação de diferentes níveis de calagem em amostras de Latossolo Vermelho Distrófico (LV) (arenoso) e Latossolo Roxo Distroférrico (LR) (argiloso), foram conduzidos dois ensaios em casa de vegetação, no período de março a dezembro de 1999. Os ensaios consistiram da aplicação de imazaquin (150 g ha-1) no topo das colunas, cujos solos, após receberem os diferentes níveis de calagem, apresentavam diferentes valores de pH. A seguir, simulou-se uma chuva de 30 mm (LV) ou 90 mm (LR) no topo das colunas. Três dias após, foram instalados bioensaios com pepino (LV), lentilha e sorgo (LR), distribuindo-se as sementes em sulco ao longo das colunas, para avaliar a lixiviação do imazaquin. Os resultados evidenciaram que o incremento no nível de calagem proporcionou significativo aumento do potencial de lixiviação de imazaquin nas colunas de ambos os solos. Constatou-se também que o sorgo foi mais sensível que a lentilha como bioindicador da atividade de imazaquin.