bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation of proteobacterial magnetosome genes and structures in an uncultivated member of the deep-branchingNitrospiraphylum
Authors: Jogler Christian , Wanner Gerhard , Kolinko Sebastian , Niebler Martina , Amann Rudolf , Petersen Nikolai , Kube Michael , Reinhardt Richard , Schüler Dirk
Published: December 2010

Magnetotactic bacteria (MTB) are a phylogenetically diverse group which uses intracellular membrane-enclosed magnetite crystals called magnetosomes for navigation in their aquatic habitats. Although synthesis of these prokaryotic organelles is of broad interdisciplinary interest, its genetic analysis has been restricted to a few closely related members of theProteobacteria, in which essential functions required for magnetosome formation are encoded within a large genomic magnetosome island. However, because of the lack of cultivated representatives from other phyla, it is unknown whether the evolutionary origin of magnetotaxis is monophyletic, and it has been questioned whether homologous mechanisms and structures are present in unrelated MTB. Here, we present the analysis of the uncultivated “CandidatusMagnetobacterium bavaricum” from the deep branchingNitrospiraphylum by combining micromanipulation and whole genome amplification (WGA) with metagenomics. Target-specific sequences obtained by WGA of cells, which were magnetically collected and individually sorted from sediment samples, were used for PCR screening of metagenomic libraries. This led to the identification of a genomic cluster containing several putative magnetosome genes with homology to those inProteobacteria.A variety of advanced electron microscopic imaging tools revealed a complex cell envelope and an intricate magnetosome architecture. The presence of magnetosome membranes as well as cytoskeletal magnetosome filaments suggests a similar mechanism of magnetosome formation in“Cand.M. bavaricum” as inProteobacteria. Altogether, our findings suggest a monophyletic origin of magnetotaxis, and relevant genes were likely transferred horizontally betweenProteobacteriaand representatives of theNitrospiraphylum.
The second variational formula for the functional ∫𝑣⁽⁶⁾(𝑔)𝑑𝑉_{𝑔}
Authors: Guo Bin , Li Haizhong
Published: December 2010

In this paper, we compute the second variational formula for the functional

∫
M

v

(
6
)

(
g
)
d

v
g

\int _M v^{(6)}(g)dv_g

, which was introduced by Graham-Juhl; the first variational formula was obtained by Chang-Fang. We also prove that an Einstein manifold (with dimension

≥
7

\ge 7

) is a strict local maximum within its conformal class unless the manifold is isometric to a round sphere with the standard metric up to a multiple of a constant.
Influence of ventilatory mode on target concentrations required for anaesthesia using a ‘Diprifusor’ TCI system
Authors: Richards A. L. , Orton J. K. , Gregory M. J.
Published: December 2010

This study examined the influence of mode of ventilation (spontaneous or controlled) on the target blood concentrations required to maintain anaesthesia with ‘Diprifusor’ (a target controlled infusion system for propofol) in 40 healthy, unpremedicated, adult patients undergoing knee arthroscopy. All patients were given alfentanil (10 μgkg−1) and ketorolac (10 mg) immediately before induction and all received a 2:1 mixture of nitrous oxide:oxygen. An initial target blood concentration of propofol of 6.0 μgml−1 was used in most patients to induce anaesthesia. The blood target concentration required to produce acceptable anaesthetic conditions was not significantly influenced by the mode of ventilation. The mean maintenance target concentration for propofol was 3.9 (SD 0.83) μgml−1 in the ventilated group and 3.5 (SD 0.82) μgml−1 in the group of patients breathing spontaneously.
Evaluation of the predictive performance of a ‘Diprifusor’ TCI system
Authors: Swinhoe C. F. , Peacock J. E. , Glen J. B. , Reilly C. S.
Published: December 2010

The predictive performance of a ‘Diprifusor’ target controlled infusion system for propofol was examined in 46 patients undergoing major surgery, divided into three age groups (18–40, 41–55 and 56–80 years). Measured arterial propofol concentrations were compared with values calculated (predicted) by the target controlled infusion system. Performance indices (median performance error and median absolute performance error) were similar in the three age groups, with study medians of 16.2% and 24.1%, respectively. Mean values for ‘divergence’ and ‘wobble’ were −7.6%.h−1 and 21.9%, respectively. Measured concentrations tended to be higher than calculated concentrations, particularly following induction or an increase in target concentration. The mean (SD) propofol target concentration of 3.5 (0.7) μgml−1 during maintenance was lower in older patients, compared with higher target concentrations of 4.2 (0.6) and 4.3 (0.7) μgml−1 in the two younger age groups, respectively. The control of depth of anaesthesia was good in all patients and the predictive performance of the ‘Diprifusor’ target controlled infusion system was considered acceptable for clinical purposes.
‘Diprifusor’ for neurosurgical procedures
Authors: Huggins N. J.
Published: December 2010

The pharmacokinetic profile of propofol is an advantage in neurosurgery, where the rapid return of cognitive function is essential for an early postoperative assessment of neurological status. Administration of propofol by ‘Diprifusor’ target controlled infusion allows induction of anaesthesia in neurosurgical patients without significant reduction of mean arterial pressure or occurrence of apnoeic episodes. This short paper describes our experience of ‘Diprifusor’ target controlled infusion for neuroanaesthesia in a series of 20 patients undergoing craniotomy for excision of epileptic foci. The results have been compared with ten similar operations where propofol infusion was controlled manually.
TCI compared with manually controlled infusion of propofol: a multicentre study
Authors: Servin F. S.
Published: December 2010

This prospective, randomised multicentre study was designed to determine the clinical profile of ‘Diprifusor’ target controlled infusion compared with manually controlled infusion of propofol in 562 patients, aged 18–85 years, in a range of surgical procedures in 29 centres. The dose of propofol required for loss of consciousness was statistically significantly lower in the target controlled infusion group [1.69 (0.50) vs. 2.31 (0.75) mg.kg−1, p < 0.001] but the overall rate of propofol administration was slightly, but significantly, higher [12.1 (5.1) vs. 11.0 (6.0) mg.kg−1.h−1, p < 0.05]. The target concentration (CT) required for induction decreased with increasing age and ASA class, with premedication and with the administration of an opioid before induction. However, the amount of opioid given did not influence the CT required for induction, but enhanced the haemodynamic effects of propofol induction in both groups. Most investigators expressed an overall preference for target controlled infusion (93%) and found it easier to use (76%). Despite the lack of experience of most investigators in using target controlled infusion, the clinical profiles of both propofol administrations were similar. Data suggest that the clinical profile of target controlled infusion may be improved with experience, for example by more active titration of CT to effect. Target controlled infusion may well become the preferred choice for anaesthetists.
Use of ‘Diprifusor’ in anaesthesia for ophthalmic surgery
Authors: Sutcliffe N. P. , Hyde R. , Martay K.
Published: December 2010

A technique of balanced anaesthesia involving propofol infusions and a rapidly metabolised opioid offers advantages over traditional anaesthetic techniques for eye surgery. The most appropriate mode of delivery of propofol is by a ‘Diprifusor’ target controlled infusion system. This paper discusses the use of a ‘Diprifusor’ target controlled infusion system for eye surgery. Published data are reviewed and the results of a retrospective analysis of 138 successive eye surgery patients are presented.
Future applications for TCI systems
Authors: Milne S. E. , Kenny G. N. C.
Published: December 2010

Infusion pumps incorporating ‘Diprifusor’ for the administration of propofol by target controlled infusion are now commercially available and are becoming more widely used. This paper considers possible future applications of target controlled infusion and summarises results obtained using prototype systems as a component of other control techniques and with other drugs. These include studies with patient‐controlled systems for the administration of analgesia or sedation and a closed loop control system for the administration of propofol. Among currently available analgesic drugs, alfentanil and remifentanil are considered to be the most suitable for administration by target controlled infusion, but commercial systems for these agents are not yet available.
Intravenous anaesthesia: manual infusion schemes versus TCI systems
Authors: Russell D.
Published: December 2010

Propofol was first used to induce and maintain anaesthesia in the early 1980s. Several infusion regimens were described, some based on pharmacokinetic predictions. Advances in computing technology subsequently have allowed the development of portable target controlled infusion devices, with drugs delivered to achieve specific predicted target blood propofol concentrations. Assessments of propofol target controlled infusion systems in clinical practice and comparisons of ‘Diprifusor’ target controlled infusion systems with manual infusion are reviewed here.
The development of ‘Diprifusor’: a TCI system for propofol
Authors: Glen J. B.
Published: December 2010

The ‘Diprifusor’ target controlled infusion system has been developed as a standardised infusion system for the administration of propofol by target controlled infusion. A preferred set of pharmacokinetic parameters for propofol was selected using computer simulation of a known infusion scheme with pharmacokinetic parameters described in published literature. The selected model was included in a ‘Diprifusor’ module that was interfaced with, and later incorporated into, a computer‐compatible infusion pump. Clinical trials with such systems led to guidance on appropriate target concentrations for the administration of propofol by ‘Diprifusor’ target controlled infusion for inclusion in drug prescribing information. Standardisation of the delivery performance (± 5%) of commercial systems has been achieved with a laboratory performance specification. Clinical studies indicate that the actual blood concentrations achieved were about 16% greater than the calculated values displayed by the system. In an individual patient, titration of the target concentration is required in the same manner as an anaesthetic vapouriser is adjusted to obtain a specific pharmacodynamic effect.
Genomic regions associated with antibody response to sheep red blood cells in the chicken
Authors: Dorshorst B. J. , Siegel P. B. , Ashwell C. M.
Published: December 2010

F
1 and F2 populations were generated by crossing two lines of chickens divergently selected from a common founder population for 32 generations for either high or low antibody response 5 days post‐injection of a non‐pathogenic antigen, sheep red blood cells (SRBCs). The number of loci with major effects on day 5 SRBC titers was estimated to be more than 7 in this population. There was a significant association between MHC haplotype and day 5 antibody titers as well as body weight at sexual maturity. A significant difference between reciprocal F2 crosses for both 5‐ and 12‐day antibody titers suggests that sex chromosome and/or parent of origin effects on autosomal loci have an important role in immune response. A single marker‐trait association analysis on 1024 genetic markers and 128 F2 individuals detected 11 genomic regions associated with antibody response traits and 17 regions associated with body weight gain. Several of the genomic regions identified as being associated with antibody response have been described previously, while novel regions associated with antibody response were identified on chromosomes 11 and 24. Based on the lack of overlap of the regions associated with body weight and antibody response, we conclude that while these phenotypes are inversely correlated in the selected lines, they are controlled by distinct genetic loci and may be reflective of intense selection pressure on loci affecting the partitioning of nutrients between the immune system and growth pathways.
Reversible posterior leucoencephalopathy syndrome in an elderly male on sunitinib therapy
Authors: Padhy Biswa M. , Shanmugam Saravana P. , Gupta Yogendra K. , Goyal Aman
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Agents inhibiting vascular endothelial growth factor can lead to development of reversible posterior leucoencephalopathy syndrome (RPLS).

• Few cases of sunitinib‐induced RPLS have been reported previously.

WHAT THIS STUDY ADDS

• A case of sunitinib‐induced RPLS in an elderly man is described in this study.

• Elevated blood pressure at presentation occurs in most cases of sunitinib‐induced RPLS.

AIMS Reversible posterior leucoencephalopathy syndrome (RPLS) has been reported following the use of anti‐vascular endothelial growth factor (VEGF) agents such as bevacizumab, sorafinib and sunitinib. In this report we present a case of RPLS that occurred in an elderly male on sunitinib therapy.

METHODS Other case reports of sunitinib‐induced RPLS were reviewed and causality assessment was carried out using the World Health Organization‐Uppsala Monitoring Centre criteria and the Naranjo algorithm.

RESULTS Only a few cases of sunitinib‐induced RPLS had been reported previously and elevated blood pressure at presentation was common in most of the patients. Our case was clinically similar to the earlier reports and the adverse reaction had a ‘probable’ relationship with sunitinib intake.

CONCLUSIONS Physicians should monitor and manage elevated blood pressure in patients with sunitinib‐induced RPLS.
Statin adherence and the risk of major coronary events in patients with diabetes: a nested case–control study
Authors: Ruokoniemi Päivi , Korhonen Maarit J. , Helin‐Salmivaara Arja , Lavikainen Piia , Jula Antti , Junnila Seppo Y. T. , Kettunen Raimo , Huupponen Risto
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Statin therapy is recommended in diabetes to lower the risk of coronary events. However, large randomized trials of statins performed specifically among diabetic patients have produced conflicting results. No long‐term follow‐up studies are available on the incidence of major coronary events and adherence to statin therapy in real‐life patients with diabetes.

WHAT THIS STUDY ADDS

• The study results demonstrate that good adherence to statins is associated with a reduced risk of major coronary events in patients with diabetes, irrespective of the presence of coronary heart disease at statin initiation. This study provides further justification for maintenance statin therapy in diabetes.

AIMS To evaluate whether good statin adherence is associated with a reduced incidence of major coronary events (MCEs) among diabetic patients with and without coronary heart disease (CHD).

METHODS Using data derived by linkage of nationwide health databases in Finland, we conducted a nested case–control analysis of 3513 cases with an MCE, a composite of acute myocardial infarction and/or coronary revascularization, and 20 090 matched controls identified from a cohort of 60 677 statin initiators with diabetes. Cases and controls were matched according to gender, time of cohort entry and duration of follow‐up and further classified to two risk groups according to the presence of CHD at statin initiation. The incidence of MCEs was compared between patients with good statin adherence (the proportion of days covered ≥80%) and patients with poor statin adherence (<80%). Odds ratios (OR) for MCEs were estimated by conditional logistic regression adjusting for several covariables.

RESULTS Good statin adherence was associated with a reduced incidence of MCEs in those with prior CHD [OR 0.84 (95% CI 0.74–0.95)] and in those without it [OR 0.86 (95% CI 0.78–0.95)]. The association persisted among those followed up for 5 years or longer [OR 0.77 (95% CI 0.58–1.02) and OR 0.79 (95% CI 0.66–0.94) respectively]. In sensitivity analyses, a reduced MCE incidence was observed also in those without any documented cardiovascular disease (CVD) at statin initiation [OR 0.87 (95% CI 0.78–0.96) overall and OR 0.80 (95% CI 0.66–0.97) for those followed up 5 years or longer].

CONCLUSIONS In patients with diabetes, good adherence to statins predicts reduced incidence of MCEs irrespective of the presence of CHD at statin initiation.
Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice
Authors: Franchini Massimo , Mannucci Pier Mannuccio
Published: December 2010

The management of patients with congenital haemophilia who develop alloantibodies against factors of the propagation phase of blood coagulation, commonly known as inhibitors, is the most important challenge facing haemophilia caregivers at present, as this complication not only compromises the efficacy of replacement therapy but also consumes an enormous amount of economic resources. Development of inhibitors further complicates the clinical course of severe haemophilia, with a prevalence of up to 30% in patients with haemophilia A (factor VIII deficiency) and up to 5% in those with haemophilia B (factor IX deficiency) and haemophilia C (factor XI deficiency). While the short‐term goal of treatment of patients who develop alloantibodies is the control of bleeding, the eradication of the inhibitor is the main long‐term goal. The management of severe bleeding episodes and the eradication of the autoantibody are also the mainstays of treatment of patients with acquired haemophilia, a rare but life‐threatening haemorrhagic condition characterized by the development of inhibitory autoantibodies against coagulation factor VIII. The most recent options available for treating patients with congenital haemophilia complicated by inhibitors and acquired haemophilia because of autoantibodies against factor VIII are summarized in this review article.
Genetics of type 2 diabetes: pathophysiologic and clinical relevance
Authors: Herder Christian , Roden Michael
Published: December 2010

Eur J Clin Invest 2011; 41 (6): 679–692

Background  Recent genome‐wide association studies enlarged our knowledge about the genetic background of type 2 diabetes.

Aims  This review provides an overview of the role of these novel genetic findings for the pathophysiology, prediction and treatment of type 2 diabetes.

Results  The genetic susceptibility to type 2 diabetes appears to be determined by many common variants in multiple gene loci with low effect sizes. Although at least 36 diabetes‐associated genes were identified, only about 10% of the heritability of type 2 diabetes can be explained. Most of the discovered gene variants have been linked to beta‐cell dysfunction rather than insulin resistance, which might challenge established thinking of type 2 diabetes as a predominant disorder of insulin action. Genetic data can lead to statistically significant, but not to clinically relevant contributions to risk prediction for type 2 diabetes. Nevertheless, preliminary evidence suggests interactions between genotypes and response to lifestyle changes or drug treatment.

Conclusions  Future studies need to target the issue of hidden heritability and to detect the causal gene variants within the identified gene loci. Improved understanding of the genetic contribution to type 2 diabetes may then help addressing the questions whether genotyping is useful to predict individual diabetes risk, identifies individual responsiveness to preventive and therapeutic interventions or at least allows for breaking down type 2 diabetes into smaller, clinically meaningful subtypes.
Bat habitat use in logged jarrah eucalypt forests of south‐western Australia
Authors: Webala Paul W. , Craig Michael D. , Law Bradley S. , Armstrong Kyle N. , Wayne Adrian F. , Bradley J. Stuart
Published: December 2010

1. Ecologically sustainable forest management is being implemented to address the competing demands of timber production and conservation, but its effectiveness is poorly understood. Bats play key roles in forest ecosystems and are sensitive to timber harvesting, so are potential indicators of whether management is successfully achieving biodiversity conservation in production forests.

2. We evaluated logging impacts in jarrah eucalypt forests of south‐western Australia by examining insectivorous bat activity, feeding buzzes and insect biomass at four sites in each of recently logged forest, young regrowth and old regrowth.

3. Forest tracks supported higher overall activity and higher feeding activity than off‐track sites, but activity was similar on‐track irrespective of logging history. However, off‐track activity in old regrowth was significantly higher than in either young regrowth or recently logged forest.

4. Vespadelus regulus and Nyctophilus spp. were more active in old regrowth than other logging histories. Similarly, V. regulus, Nyctophilus spp., Chalinolobus gouldii, Chalinolobus morio and Falsistrellus mackenziei activity was significantly greater on‐ than off‐tracks, but activity was similar on‐track across logging histories.

5. Increased understorey clutter was the strongest predictor of reduced bat activity in off‐track sites. Reduced clutter and roost availability most probably explained greater activity in old regrowth forest. Neither insect biomass nor interactive effects of clutter and insect biomass significantly affected bat activity.

6. Synthesis and applications. Tracks provided internal linear edges within cluttered forests allowing bat species to use such areas for foraging. However, our results suggest that the retention of unlogged areas within logged forests is likely to be the most effective strategy in many forest ecosystems for conserving bat populations and achieving ecologically sustainable forest management for this group.
Development of a protocol for the quantitative determination of HBeAg using the Elecsys® HBeAg immunoassay
Authors: Wursthorn K. , Zacher B. J. , Jaroszewicz J. , Darnedde M. , Manns M. , Wedemeyer H.
Published: December 2010

Summary.  Loss of hepatitis ‘e’ antigen (HBeAg) in patients with HBeAg‐positive chronic hepatitis B is associated with improved long‐term clinical outcome and is defined as a goal of antiviral treatment by clinical practice guidelines. Recent studies suggest that baseline levels and on‐treatment monitoring of HBeAg levels may identify patients most likely to respond to therapy. The aim of this study was the development of a protocol for the quantitative determination of HBeAg using the Elecsys® HBeAg immunoassay. The linear range of the Elecsys® HBeAg immunoassay was established using recombinant HBeAg and five different diluents. The assay was validated against the Paul Ehrlich Institute (PEI) international standard serum. Linearity was demonstrated up to a cut‐off index (COI) of 1000, independent of the diluent used. Optimal linearity was obtained using the Elecsys® Universal Diluent. Using the PEI reference standard, conversion factors were established as 4.50 COI for 1 PEIU/mL corresponding to 0.222 PEIU/mL for a COI of 1. Based on the results from these analyses, a simple algorithm for the quantitative measurement of HBeAg using the Elecsys® HBeAg immunoassay was developed. Using a simple algorithm with an initial 1:40 dilution, the Elecsys® HBeAg assay provides robust quantification of serum HBeAg in an easy‐to‐use and rapid system. The use of a commercially available, standardized diluent improves comparability between laboratories.
Influence of the 5‐HT3 receptor antagonist ondansetron on gastric sensorimotor function and nutrient tolerance in healthy volunteers
Authors: Janssen P. , Vos R. , Van Oudenhove L. , Tack J.
Published: December 2010

Background  Serotonin is believed to be involved in the regulation of the gastric accommodation reflex in man however which receptor subtype(s) are involved remains to be elucidated.

Methods  Eleven healthy subjects (nine men, age 19–30) underwent a gastric barostat and a drinking test after treatment with either placebo or ondansetron (8 mg intravenously). During the barostat protocol an intragastric flaccid bag was stepwise distended (2 mmHg increments 2 min) to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure +2 mmHg while volume was followed before and after administration of a liquid meal (200 mL; 300 kcal). During the drink test volunteers drank at a rate of 15 mL min−1 until maximal satiation. Results (mean ± SEM) were compared using t‐tests and mixed model analysis.

Key Results  Gastric compliance was not significantly altered by ondansetron (51.5 ± 5.6 vs 49.2 ± 5.2 mL mmHg−1), neither were the pressure thresholds for first perception or discomfort. Ondansetron treatment did not affect basal gastric tone (173 ± 14 vs 156 ± 12 mL), neither did it affect the amplitude of the meal‐induced relaxation (160 ± 52 vs 131 ± 43 mL) or the maximum volume increase after the meal (264 ± 54 mL vs 234 ± 51 mL). During the drinking test the amount of liquid meal ingested at maximum satiation was significantly increased by ondansetron (784 ± 74 vs 907 ± 64 mL, P < 0.05).

Conclusions & Inferences  These data suggest that 5‐HT acting at 5‐HT3 receptors is not involved in the control of gastric sensorimotor function, but contributes to the regulation of hunger and satiation in man.
Effects of tripeptides and lactogenic hormones on oligopeptide transporter 2 in bovine mammary gland
Authors: Zhou M. M. , Wu Y. M. , Liu H. Y. , Zhao K. , Liu J. X.
Published: December 2010

This study was conducted to investigate the expression of oligopeptide transporter 2 (PepT2) and its potential function in bovine mammary gland. First, the PepT2 mRNA and protein were determined in cultured mammary epithelial cells. Then the effects of lactogenic hormones (prolactin, hydrocortisone or insulin) and substrate (threonyl‐phenylalanyl‐phenylalanine) on PepT2 were investigated. The PepT2 mRNA and protein were successfully detected in bovine mammary epithelial cells. PepT2 gene expression was enhanced by the addition of 50, 500 and 5000 ng/ml prolactin, 10 and 100 ng/ml hydrocortisone, and 50, 500, 5000 and 50 000 ng/ml insulin. PepT2 mRNA abundance was increased when 5, 10 and 15% of threonyl‐phenylalanyl‐phenylalanine was included. Responses of PepT2 to lactogenic hormones and oligopeptide inferred that it may play an important role in bovine mammary gland.
The impact of perinatal urinoma formation on renal function: our experience and review of the literature
Authors: Adorisio Ottavio , Silveri Massimiliano , Colajacomo Mauro , Bassani Francesca , Rivosecchi Massimo
Published: December 2010

Introduction:  A urinoma is a fluid mass consisting of extravasated urine in the perirenal space. Its impact on renal function was analysed.

Methods:  All cases of prenatal and neonatal urinoma reported in the literature were analysed as well as two cases recently observed in our department.

Results:  A review of all prenatally diagnosed urinomas revealed 25 cases, for a total of 30 renal units. The cause of obstruction was: lower urinary tract (LUT) obstruction in 16 cases (62.5%), upper urinary tract (UUT) obstruction in seven cases (29.5%) and unknown in two cases (8%). A preserved renal function was found in only 30% of all cases. Furthermore, prognosis for renal function was better in posterior urethral valve (PUV) patients than in uretero‐pelvic junction obstruction (UPJO) patients.

In addition, we analysed 35 published cases of urinoma with a neonatal onset, without prenatal diagnosis, and secondary to LUT obstruction in 27 cases (77%), UUT obstruction in seven cases (20%), while the underlying cause was unknown in one cases (3%). A preserved renal function was observed in 84% of cases with UUT obstruction and in 80% of cases presenting a LUT obstruction.

Conclusions:  Prognosis concerning renal function seems to be mainly related to two factors: age at presentation and underlying diagnosis. Decompression of the urinary tract by urine extravasation produces the best results in terms of preservation of the renal function in LUT obstruction (75% in prenatal and 84% in postnatal cases); UUT obstruction however is associated with a good prognosis in the neonatal period (80% of preserved renal function) but with a severe impairment (only 20% of preserved renal function) in prenatally detected cases.
Children of substance‐using mothers: child health engagement and child protection outcomes
Authors: Callaghan Tamara , Crimmins Jennifer , Schweitzer Robert D
Published: December 2010

Aim:  Maternal substance use has been associated with a range of child risk factors. The study investigated the relationship between engagement with child health services and child protection outcomes for children of substance‐using mothers.

Methods:  The sample comprised 119 children of mothers who disclosed opiate, amphetamine or methadone use during a maternity admission between 2000 and 2003. Statutory child protection agency and child health engagement information for the first 2 years of life was obtained. The relationship between type of maternal substance use, child health engagement and child protection outcomes was examined.

Results:  Of study group infants, 72% were engaged with child health services during the first 2 years of life. Chi‐squared analysis showed no significant relationship between child health engagement and child protection reports. Child health engagement was associated with decreased substantiated child protection notifications for children of methadone using mothers, but not for children of illicit substance users.

Conclusions:  Almost a quarter of identified children of substance‐using mothers are not accessing standard child health services in their first 2 years of life. This study provides support for increased attention to the provision of child health services for children of methadone using mothers. Further research into effective intervention strategies for children of illicit substance‐using mothers is indicated.
Intrapleural urokinase versus surgical management of childhood empyema
Authors: van Loo Anouk , van Loo Eva , Selvadurai Hiran , Cooper Peter , Van Asperen Peter , Fitzgerald Dominic A
Published: December 2010

Aim:  Empyema can be managed conservatively with intravenous antibiotics or invasively with a drain inserted under image guidance or via surgical evacuation. Both approaches are successful but comparisons of the method of drainage are few. This study compared clinical outcomes for empyema in previously well children from a single centre over a 12 year period.

Methods:  A retrospective analysis of cases over 12 years from the Children's Hospital at Westmead in Sydney was undertaken. Ethics committee approval was obtained.

Results:  Seventy two cases were identified from medical records, 12 cases were excluded and 60 cases remained. The mean age was 4.7 ± 4.3 years and there was a slight male preponderance. Treatment was divided into surgical management with a large bore drain alone [n = 25] and minimally invasive management with the use of a “pigtail catheter” and intrapleural fibrinolytic [“Urkoinase”][n = 35]. At presentation the mean heart rate and respiratory rate were not statistically different. The median (range) number of doses of urokinase was 5.66 doses (1–12). More fluid was drained with the use of urokinase [594 ml (25–4575 ml) vs. 195 ml (10–1426 ml); p = 0.006], but this did not influence the rate of resolution of fever or the length of hospital stay. A pathogen was isolated in 42.9% of the urokinase group and 68% of the surgical group which approached statistical significance [p = 0.054].

Conclusions:  Both large bore surgical drains and “pigtail catheter” drains with the instillation of urokinase lead to similarly favourable treatment outcomes. Either treatment could be recommended depending on local expertise and preferences.
Cardiac cirrhosis and hepatocellular carcinoma in a 13‐year‐old treated with doxorubicin microbead transarterial chemoembolization
Authors: Rosenbaum Jeremy , Vrazas John , Lane Geoffrey K , Hardikar Winita
Published: December 2010

Increasing numbers of children are surviving into adulthood following surgery to correct or palliate congenital heart disease. This surgery can occasionally result in long‐standing elevated right heart pressures and chronic hepatic venous congestion leading to cardiac cirrhosis. We report the first paediatric case of hepatocellular carcinoma in the setting of cardiac cirrhosis. A 13‐year‐old girl developed inoperable hepatocellular carcinoma and was treated with transarterial embolization with lipiodol and doxorubicin eluting microbeads. Promoting awareness of this association, even in younger patients, will hopefully result in better surveillance and screening of hepatic complications in survivors of complex cardiac surgery.
Intolerance to food additives – does it exist?
Authors: Turner Paul J , Kemp Andrew S
Published: December 2010

‘Food intolerance’ is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. ‘Food intolerance’ is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non‐allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non‐allergic food hypersensitivity on testing.
Vascular catheter‐related complications in newborns
Authors: Wu Jinlin , Mu Dezhi
Published: December 2010

Babies in Neonatal Intensive Care Unit have more frequent invasive procedures such as heel prick samples for gases, bilirubin levels or if ventilated suction down the endotracheal tube is more frequent and still invasive. Central and peripheral vascular catheters are essential to serve many important functions for sick neonates. However, there is growing recognition of potential risks, such as infection, thrombosis, vasospasm, phlebitis, infiltration and so on, associated with their use. Based on current evidence, this paper reviews the common complications of vascular catheters and their corresponding preventive or treatment approaches in newborns.
Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo
Authors: KUO Curtis , LIM Sam , KING Nicholas J.C. , BARTLETT Nathan W. , WALTON Ross P. , ZHU Jie , GLANVILLE Nicholas , ANISCENKO Julia , JOHNSTON Sebastian L. , BURGESS Janette K. , BLACK Judith L. , OLIVER Brian G.
Published: December 2010

Background and objective:  A hallmark of asthma is airway remodelling, which includes increased deposition of extracellular matrix (ECM) protein. Viral infections may promote the development of asthma and are the most common causes of asthma exacerbations. We evaluated whether rhinovirus (RV) infection induces airway remodelling, as assessed by ECM deposition.

Methods:  Primary human bronchial epithelial cells and lung parenchymal fibroblasts were infected with RV‐2 or RV‐16, or treated with RV‐16 RNA, imiquimod (Toll‐like receptor (TLR) 7/8 agonist) or polyinosinic : polycytidylic acid (poly I : C) (activator of TLR 3, retinoic‐acid‐inducible protein I and melanoma‐differentiated‐associated gene 5). Changes in ECM proteins and their transcription were measured by ELISA and quantitative real‐time PCR. In addition, gene expression for ECM proteins was assessed in a mouse model of RV infection.

Results:  RV infection increased deposition of the ECM protein, perlecan, by human bronchial epithelial cells, and collagen V and matrix‐bound vascular endothelial growth factor were increased in both human bronchial epithelial cell and fibroblast cultures. Purified RV‐16 RNA, poly I : C and imiquimod induced similar increases in ECM deposition to those observed with RV‐infected fibroblasts. However, only poly I : C induced ECM deposition by bronchial epithelial cells, suggesting that RV‐induced ECM deposition is mediated through TLR. Furthermore, gene expression for fibronectin and collagen I was increased in lung homogenates of mice infected with RV‐1b.

Conclusions:  RV infection and TLR ligands promote ECM deposition in isolated cell systems and RV induces ECM gene expression in vivo, thus demonstrating that RV has the potential to contribute to remodelling of the airways through induction of ECM deposition.
Cigarette smoke modulates PGE2 and host defence against Moraxella catarrhalis infection in human airway epithelial cells
Authors: ZHANG WEIYUN , CASE STEPHANIE , BOWLER RUSSELL P. , MARTIN RICHARD J. , JIANG DI , CHU HONG WEI
Published: December 2010

Background and objective:  Airway bacterial infections pose a significant challenge to the management of COPD, a disease mainly caused by cigarette smoking. However, the mechanisms of impaired airway mucosal innate immunity against bacteria in COPD remain unclear. We examined the effect of cigarette smoke on prostaglandin E2 (PGE2) and downstream epithelial host defence mechanisms including the antimicrobial substance human β‐defensin‐2 (hBD‐2).

Methods:  Brushed bronchial epithelial cells were obtained from healthy smokers and individuals with COPD, and cultured under air–liquid interface conditions with or without exposure to whole cigarette smoke (WCS) or Moraxella catarrhalis (Mc) infection. Bacterial load, hBD‐2 (a molecule known to kill Mc) and PGE2 were measured.

Results:  WCS decreased Mc‐induced hBD‐2 expression and increased Mc load on bronchial epithelial cells from healthy smokers and COPD patients. Moreover, WCS inhibited PGE2 induction following Mc. PGE2 was shown to increase hBD‐2 production in bronchial epithelial cells from healthy smokers, but not from COPD patients.

Conclusions:  The results suggest that in well‐differentiated human bronchial epithelial cells, WCS may impair host defence against Mc in part through inhibiting PGE2 production.
Phylogeny of macrophagous leeches (Hirudinea, Clitellata) based on molecular data and evaluation of the barcoding locus
Authors: Oceguera‐Figueroa Alejandro , Phillips Anna J. , Pacheco‐Chaves Bernald , Reeves Will K. , Siddall Mark E.
Published: December 2010

Oceguera‐Figueroa, A., Phillips, A. J., Pacheco‐Chaves, B., Reeves, W. K. & Siddall, M. E. (2010). Phylogeny of macrophagous leeches (Hirudinea, Clitellata) based on molecular data and evaluation of the barcoding locus. —Zoologica Scripta,40, 194–203.

The phylogenetic relationships of macrophagous leech species are studied using two mitochondrial [cytochromecoxidase subunit I (COI) and 12S rDNA] and two nuclear (28S rDNA and 18S rDNA) markers. The complete dataset analysed in this study included 49 terminals and 5540 aligned characters. Phylogenetic analyses were performed under two optimality criteria: Maximum Parsimony and Maximum Likelihood. The monophyly of the two currently recognized families (i.e. Erpobdellidae and Salifidae) is confirmed and well supported. The phylogenetic position of Gastrostomobdellidea is studied for the first time and found to be sister to family Salifidae nested well within Erpobdelliformes. Previously recognized taxonomic arrangements were evaluated and discarded through successive constraint analyses. Correlation between morphology and phylogeny was notable in Salifidae but not in Erpobdellidae. Variability of COI, the barcoding locus, was examined across species leading to the recognition of the invasiveBarbronia weberiin Mexico, Costa Rica, Germany, South Africa and Taiwan.
THE IMPACT OF TRADE AND INVESTMENT AGREEMENTS ON AUSTRALIA'S INWARD FDI FLOWS
Authors: CROTTI SIMON , CAVOLI TONY , WILSON JOHN K.
Published: December 2010

International trade and investment agreements are one of the primary instruments of global financial liberalisation. They are enacted to enhance the flows of foreign direct investment (FDI) between signatories by reducing regulatory barriers to investment; promoting stable host investment environments; and guaranteeing investors against non‐commercial risk. As a net capital importer, Australia has sought to attract FDI through participation in such accords since the early 1980s. This paper examines the determinants of Australia's inward FDI flows—focussing specifically on the effects of trade and investment agreements. Using panel data, we find that both bilateral trade and bilateral and multilateral investment agreements attract FDI flows into Australia, thereby indicating that the policy of enticing FDI through participation in these accords is quite possibly effective.
STRATEGIC DELEGATION UNDER UNIONISED DUOPOLY: WHO WILL BARGAIN WITH UNIONS?
Authors: LIAO PEI‐CHENG
Published: December 2010

This paper investigates the choice of a firm's delegate (either the owner or the manager) bargaining wages and employment with a union under a unionised duopoly. We show that if an owner delegates the task of bargaining to a manager, the owner always compensates the manager for profits by penalising sales, regardless of whether the rival owner delegates or not. Moreover, we show that an owner's decision to delegate the task of bargaining to a manager depends on the incremental benefit of delegating and the cost of hiring a manager. The asymmetric outcome (wherein one owner delegates but the other does not) can occur if there is a sufficiently large disparity of hiring costs between the owners. Finally, we show that the union in an owner‐managed firm always earns more than the union in a managerial firm.
Fiscal Activism Under Inflation Targeting and Non‐atomistic Wage Setting
Authors: LARSSON ANNA
Published: December 2010

This paper presents a game between a fiscal authority, an independent central bank and non‐atomistic wage setters. The effects of fiscal activism and inflation targeting on labour market outcomes are analysed. The results suggest that inflation targeting provides incentive for wage restraint. Moreover, real wages are increasing in the degree of fiscal activism as wage setters exploit the response of a fiscal authority seeking to promote employment. Numerical results suggest that the benefits of targeting inflation are larger when the government pursues an activist policy and therefore that there is some substitutability between fiscal and monetary rules.
Tangeretin and its metabolite 4′‐hydroxytetramethoxyflavone attenuate EGF‐stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K
Authors: Cheng Z , Surichan S , Ruparelia K , Arroo R , Boarder MR
Published: December 2010

BACKGROUND AND PURPOSE The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′‐hydroxy‐5,6,7,8‐tetramethoxyflavone (4′‐OH‐TMF) in this effect.

EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)‐stimulated rat hepatocytes, with [3H]‐thymidine incorporation into DNA as an index of progression to S‐phase of the cell cycle, and Western blots for phospho‐proteins involved in the cell signalling cascade.

KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′‐OH‐TMF. Low micromolar concentrations of tangeretin or 4′‐OH‐TMF gave a concentration‐dependent inhibition of EGF‐stimulated progression to S‐phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre‐incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF‐stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′‐OH‐TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR.

CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′‐OH‐TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′‐OH‐TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid‐rich diet.
The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL‐10 expression in cutaneous T‐cell lymphoma cells
Authors: Tiffon CE , Adams JE , van der Fits L , Wen S , Townsend PA , Ganesan A , Hodges E , Vermeer MH , Packham G
Published: December 2010

BACKGROUND AND PURPOSE

Vorinostat and romidepsin are histone deacetylase inhibitors (HDI), approved for the treatment of cutaneous T‐cell lymphoma (CTCL). However, the mechanism(s) by which these drugs exert their anti‐cancer effects are not fully understood. Since CTCL is associated with immune dysregulation, we investigated whether these HDI modulated cytokine expression in CTCL cells.

EXPERIMENTAL APPROACH

CTCL cell lines and primary CTCL cells were treated in vitro with vorinostat or romidepsin, or with STAT3 pathway inhibitors. Cell cycle parameters and apoptosis were analysed by propidium iodide and annexin V/propidium iodide staining respectively. Cytokine expression was analysed using QRT‐PCR and elisa assays. STAT3 expression/phosphorylation and transcriptional activity were analysed using immunoblotting and transfection/reporter assays respectively.

KEY RESULTS

Vorinostat and romidepsin strongly down‐regulated expression of the immunosuppressive cytokine, interleukin (IL)‐10, frequently overexpressed in CTCL, at both the RNA and protein level in CTCL cell lines and at the RNA level in primary CTCL cells. Vorinostat and romidepsin also increased expression of IFNG RNA and decreased expression of IL‐2 and IL‐4 RNA, although to a lesser extent compared to IL‐10. Transient exposure to vorinostat was sufficient to suppress IL‐10 secretion but was not sufficient to irreversibly commit cells to undergo cell death. STAT3 pathway inhibitors decreased production of IL‐10 and vorinostat/romidepsin partially decreased STAT3‐dependent transcription without effects on STAT3 expression or phosphorylation.

CONCLUSIONS AND IMPLICATIONS

These results demonstrate that HDI modulate cytokine expression in CTCL cells, potentially via effects on STAT3. Immunomodulation may contribute to the clinical activity of HDI in this disease.