bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of age on cardiac excitation–contraction coupling
Authors: Fares Elias , Howlett Susan E
Published: August 2009

1. Cardiovascular diseases most commonly occur in the elderly and are a frequent cause of disability or death. However, the effect of age itself on cardiac function is not well understood.

2. Studies in both human and animal hearts indicate that contractile function is unaffected by age while at rest. However, the ability to increase cardiac contractile force during strenuous activities, such as exercise, declines with age.

3. Similar findings have been observed in individual ventricular myocytes isolated from aged hearts. When myocytes are stimulated with β‐adrenoceptor agonists or rapid pacing frequencies, aged cells show a much smaller increase in peak contractions and Ca2+ transients than young adult cells. In addition, contractions and Ca2+ transients are prolonged in aged cells compared with younger cells under these conditions.

4. These observations suggest that the age‐related decline in cardiac contractile function originates at the cellular level and may reflect modifications in processes involved in excitation–contraction (EC) coupling.

5. Biochemical studies have shown that there are age‐related modifications in the expression, regulation and function of a number of proteins essential to EC coupling in the heart.

6. Functional studies indicate that these changes in EC coupling proteins disrupt Ca2+ homeostasis and contribute to decrease in peak contraction and prolongation of contraction duration observed in myocytes from aged hearts.

7. The present review describes modifications in cardiac contractile function that occur in the ageing heart and evaluates underlying alterations in the EC coupling pathway that may be responsible for this decline in contractile function in ageing.
Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia
Authors: Tsukamoto Taiji , Endo Yukihiro , Narita Michiro
Published: August 2009

Objectives: To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH).

Methods: This was a randomized, double‐blind, placebo‐controlled, parallel‐group study. A total of 378 subjects with clinical BPH having an International Prostate Symptom Score (IPSS) of 8 points or greater, a prostate volume of 30 mL or greater, and a maximal urinary flow rate (Qmax) of 15 mL/s or less were randomized to receive placebo or dutasteride once daily for 52 weeks. Subjects were stratified according to tamsulosin use at baseline. The numbers of subjects with and without tamsulosin use were 242 and 136, respectively. IPSS, Qmax, prostate volume and drug safety were evaluated.

Results: Continued improvement in IPSS was noted in the dutasteride group, and dutasteride significantly decreased IPSS compared with placebo. At week 52, dutasteride significantly improved Qmax and prostate volume compared with placebo. Drug‐related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting.

Conclusions: Dutasteride improves urinary symptoms and flow rate and reduces prostate volume. In Japanese men with BPH, it is effective and generally well tolerated during the one‐year treatment period.
Near Infrared Spectroscopy study of the central nervous activity during artificial changes in bladder sensation in men
Authors: Matsumoto Shinya , Ishikawa Akira , Kume Haruki , Takeuchi Takumi , Homma Yukio
Published: August 2009

Objectives:  To investigate the regional specificity of multi‐channel near infrared spectroscopy (NIRS) on the detection of urination‐related cortical activation in healthy men.

Methods:  Frontal lobe blood flow was measured non‐invasively in 20 resting subjects using NIRS before and after micturition. The relative concentrations of oxyhemoglobin were recorded over the frontal lobe during artificial changes in bladder sensation with a 52‐channel NIRS machine. An increase in oxyhemoglobin represented locally increased blood flow. In artificially induced bladder sensation (desire to void), the lower abdomen of each participant was pressed by the examiner's hand to keep each participant feeling the desire to void for 5 s. Each participant received this series of tasks three times before and after urination. Activated concentrations calculated by contrast of subtracting the two different conditions were designed to disclose the brain areas that are involved during artificial changes in bladder sensation. The measurements were repeatedly carried out for each subject on different days to reveal the reproducibility and intra‐individual variability of the results.

Results:  Cerebral responses during artificial changes in bladder sensation were bilaterally associated with increased levels of oxyhemoglobin in the frontal area. Oxyhemoglobin increases during the compression maneuver were significantly larger than those during an empty bladder in several bilateral frontal channels (P < 0.05).

Conclusions:  Frontal regions were activated during artificial changes in bladder sensation before micturition using a 52‐channel NIRS machine.
Regent Honeyeater Habitat Restoration Project Lurg Hills, Victoria
Authors: Thomas Ray
Published: July 2009

Summary  The Regent Honeyeater Habitat Restoration Project is a landscape scale community effort to protect and restore all significant remnants of native woodland habitat in the agricultural district of the Lurg hills, Victoria. While focus is placed on the Regent Honeyeater, many other declining birds and mammals also benefit from the restoration project. Over 14 years of sustained effort, the project has involved 115 local landholders (approximately 95% of local farms) and about 17 000 volunteers. Together, they have protected relatively healthy remnants by fencing, planted or direct seeded depleted understoreys and replanted open areas that had been cleared for agriculture. Other restoration activities include ecological thinning of ‘pole forests’, mistletoe removal, environmental weeding, feral animal control, kangaroo reduction, systematic monitoring of a range of threatened and declining woodland birds, and nest box placement for hollow‐dependent mammals. The works have achieved the rapid closing of some high‐priority gaps in the local landscape, connecting the Lurg hills project area to other major regional habitats nearby. The oldest tree plantings are now 12 yrs old and 6‐m high and the first Ironbarks flowered in 2006. While the Regent Honeyeater has not yet returned in numbers (because the trees have not yet reached optimum flowering age), surveys and nest box monitoring reveal a range of threatened birds and mammals are already using this project’s regenerated and reconstructed habitats.
Effect of bevacizumab on corneal neovascularization in experimental rabbit model
Authors: Ahmed Abdulgani , Berati Hasanreisoglu , Nalan Akyurek , Aylin Sepici
Published: August 2009

Abstract

Purpose:  To investigate the effect of bevacizumab in an experimental rabbit model of corneal neovascularization.

Methods:  The right eyes of 24 white New Zealand rabbits were included in a corneal neovascularization model using alkaline burn. They were divided into four groups. Topical bevacizumab was installed three times daily in group 1, 5 mg bevacizumab subconjunctivally every 2 days in group 2, 10 mg bevacizumab subconjunctivally every 2 days in group 3 and 0.2 cc of normal saline in the same way in group 4 (control group). All eyes were treated for 7 days. Then the animals were killed and corneal specimens sent for histopathological analysis. Tear film and aqueous humour samples were obtained to assess vascular endothelial growth factor (VEGF) levels.

Results:  Seven days after topical bevacizumab treatment the neovascular index in group 1 was lower than that in the control group (P = 0.028). In groups 2 and 3 the neovascular index was lower 2 days after subconjunctival bevacizumab treatment than that in control group (P = 0.009 and P = 0.009, respectively). In the control group the VEGF level in aqueous humour increased by 66% from day 7 to 14. In groups 1–3 it decreased by 49.80%, 70.20% and 76.44%, respectively (P = 0.043). The VEGF level in tear film of the control group increased by 35.23% from day 7 to 14, which was not significant (P = 0.893), while in groups 1–3 it decreased by 57.26%, 34.59% and 67.97%, respectively, which was only significant in groups 1 and 3 (P = 0.043).

Conclusions:  Subconjunctival 5 mg/mL bevacizumab is effective in reducing corneal neovascularization in animal models and in reducing VEGF levels. Further research is needed to assess the potential side effects and minimal effective dose.
Optic perineuritis secondary to Wegener's granulomatosis
Authors: Purvin Valerie , Kawasaki Aki
Published: August 2009

Abstract

Background:  Optic perineuritis (OPN) is an inflammatory condition involving the optic nerve sheath because of a variety of causes. We describe three patients in whom OPN was secondary to Wegener's granulomatosis (WG) and compare the clinical findings in these cases with those of idiopathic OPN.

Methods:  This is a retrospective small case series derived from patients with OPN seen in an outpatient neuro‐ophthalmology clinic. Medical records and imaging studies of these patients were reviewed.

Results:  These patients shared clinical similarities with idiopathic OPN including age, sex, symptoms, radiographic findings and steroid responsiveness. However, recurrence of symptoms on lowering the prednisone dose below 40 mg distinguished these patients from those with idiopathic OPN.

Conclusions:  Steroid dependency in idiopathic OPN should raise suspicion of WG. Patients with OPN should be specifically questioned regarding pre‐existing upper respiratory tract disorders and rheumatic symptoms and laboratory testing should include acute phase reactants, anti‐neutrophil cytoplasmic antibodies and tests of renal function.
Training in pediatric anesthesia for registrars – UK National survey
Authors: MELARKODE KRISHNAN , ABDELAAL AMR , BASS SAM
Published: August 2009

Background:  The aim of this National survey was to review the training provided in pediatric anesthesia to all registrars across all deaneries in the United Kingdom. The Royal College of Anaesthetists (RCA) recognizes training in pediatric anesthesia as an important training module for specialist registrars in years 1 and 2 of their training and recommends that this training should be delivered in 1–3‐month blocks.

Methods:  This was a simple online survey (http://www.esurveyspro.com). We aimed to contact all registrars via the Association of Paediatric Anaesthetists of Great Britain and Ireland and the RCA.

Results:  Our survey indicated that there is wide variation in the duration of modular training across all deaneries. Three hundred and sixty‐two registrars (65.5%) thought that the implementation of the European working time directives (EWTD) would hamper training in this specialty. One hundred and sixty‐seven trainees (42.7%) spent more than 75% of their time doing pediatric anesthesia during their training module. Only 34 trainees (6.4%) had the opportunity to anesthetize children every week in District General Hospitals (DGHs), while 280 trainees (53.03%) said they did not have regular pediatric lists in DGHs.

Conclusions:  It will be necessary to increase the duration of modular training with the implementation of EWTD. Modular training in pediatric anesthesia should be provided as a dedicated and protected module. Training opportunities in DGHs are limited. There is also a need for new guidelines, as current guidelines regarding pediatric anesthesia training will be outdated with the implementation of EWTD.
Enterocoele is a marker of severe pelvic floor weakness
Authors: Jarrett M. E. D. , Wijffels N. A. T. , Slater A. , Cunningham C. , Lindsey I.
Published: August 2009

Objective  The aim was to evaluate the relationship between the presence of an enterocoele and grade of rectal prolapse (RP).

Method  Defaecating proctograms of consecutive patients presenting to the Oxford Pelvic Floor Clinic between January 2004 and November 2008 were analysed. Patients were included if they had full thickness internal (grades 1–4 prolapse) or external RP (grade 5 prolapse). All those included were analysed with regards to the presence of an enterocoele.

Results  Three hundred and seventy‐one patients [322 (87%) women and 49 (23%) men] were found to have a degree of RP. One out of eight (12.5%) patients with grade 1 RP, 10/42 (18.5%) with grade 2 RP, 34/125 (27%) with grade 3 RP, 62/135 (46%) with grade 4 RP and 23/49 (47%) with grade 5 full thickness external RP had an enterocoele present. This was a statistically significant trend (Pearson χ2 test P < 0.0002). There was a significantly higher proportion of enterocoeles in women [125/322 (39%) than in men (5/49 (10%)] (P < 0.0001) and a higher likelihood of having an enterocoele with advancing age (P < 0.0001). Within the study, there was no significant difference in the proportion of nulliparous and parous women with enterocoeles (P = 0.8); there were a significantly higher proportion of enterocoeles in hysterectomized women (P = 0.015).

Conclusions  Enterocoele is increasingly seen with advancing RP severity. This suggests that the two findings are part of the same pelvic floor process. These data support the hypothesis that enterocoele is a marker of severe pelvic floor weakness. Enterocoele is seen more frequently in females particularly after hysterectomy.
Evidence‐based prescription of antibiotics in urology: a 5‐year review of microbiology
Authors: DasGupta Ranan , Sullivan Rebecca , French Gary , O’Brien Timothy
Published: July 2009

OBJECTIVE

To analyse the results of positive urine cultures over a 5‐year period in a large hospital and urology department (amongst both inpatients and outpatients), assess the prevalence of different organisms and the resistance profiles of a range of antibiotics, and thus provide information on which organisms are likely to cause urosepsis.

METHODS

The use of antibiotics should be based on knowledge of which pathogens are present and what resistance patterns are emerging, particularly relevant in surgical disciplines like urology, as antibiotics are now routinely administered peri‐operatively, whereby evidence‐based prescription is preferable to generic guidelines. We therefore examined almost 25 000 positive urine cultures in our hospital over a 5‐year period, and focused on the infections encountered amongst urology patients during this time.

RESULTS

A significant proportion of inpatient urinary infection (40%) is caused by Gram‐positive bacteria such as Streptococcus faecalis, underlining the need for including Gram‐positive cover during urological prophylaxis. The commonest pathogen remains Escherichia coli among both inpatients and outpatients. The ineffectiveness of common antibiotics such as ciprofloxacin and trimethoprim was identified, as was the increase in gentamicin resistance.

CONCLUSION

We propose using an aminoglycoside with a penicillin for high‐risk cases (e.g. endoscopic stone surgery) while low‐risk cases (e.g. flexible cystoscopy with no risk factors) might be managed without such prophylaxis. Pathogenic patterns and resistance rates should be monitored regularly.
Erythrocytosis in offspring of mothers with Type 1 diabetes—are factors other than insulin critical determinants?
Authors: Nelson S. M. , Freeman D. J. , Sattar N. , Lindsay R. S.
Published: July 2009

Aim  Maternal diabetes is associated with polycythaemia and thrombocytopaenia in the offspring; however, the relationship with fetal hormones is unknown. We assessed the association of maternal glycaemic control, birthweight and fetal hormones with haematological indices in pregnancies complicated by maternal diabetes.

Methods  Prospective study using cord blood samples from 89 offspring of mothers with Type 1 diabetes (OT1DM) and 34 control offspring. Full blood count, insulin, leptin, adiponectin, cortisol, insulin‐like growth factor 1 (IGF‐1), insulin‐like growth factor binding protein 3, intercellular adhesion molecule 1 and C‐reactive protein were measured in the umbilical vein at birth.

Results  Haematocrit was higher in OT1DM (OT1DM 0.55 ± 0.17%, control offspring 0.51 ± 0.06%; P = 0.02). The difference in platelets count was not statistically significant [OT1DM 214 × 109/l (173–259); control offspring 253 × 109/l (180–310), P = 0.06]. Maternal glycated haemoglobin (HbA1c) showed a moderate positive correlation with fetal haematocrit (r = 0.30, P = 0.02). Cord platelet counts were negatively associated with birthweight in OT1DM (r = −0.27, P = 0.01). In multivariate models, cord insulin was not associated with haematocrit, but cord leptin was negatively associated with platelets in control offspring (P < 0.001) and OT1DM (P = 0.046), with additional contributions from male sex (P = 0.08) in OT1DM, and IGF‐1 (P = 0.04) and insulin (P = 0.04) in control offspring.

Conclusions  Fetal haematocrit is increased in response to diabetes in pregnancy and is related to maternal glycaemic control. Fetal hyperinsulinism, hyperleptinaemia or macrosomia, although readily demonstrable in this cohort, do not emerge as determinants of raised fetal haematocrit in OT1DM. Both increased birthweight and fetal leptin are negatively associated with platelet count.
Psychosocial adjustment to diabetes‐related lower limb amputation
Authors: Coffey L. , Gallagher P. , Horgan O. , Desmond D. , MacLachlan M.
Published: July 2009

Aim  To examine psychosocial adjustment in persons with lower limb amputations related to diabetes.

Methods  Thirty‐eight participants with diabetes‐related lower limb amputations, recruited from two limb‐fitting centres, completed three psychological self‐report assessments: the Trinity Amputation and Prosthesis Experience Scales (TAPES); the Hospital Anxiety and Depression Scale (HADS); and the Amputation Body Image Scale—Revised (ABIS‐R).

Results  Over 18% of participants scored above the normal range (> 8) for depression on the HADS and 18.5% scored above the normal range for anxiety. Both depression (ρ = 0.75, P < 0.01) and anxiety (ρ = 0.62, P < 0.01) scores were significantly associated with body image disturbance, as measured using the ABIS‐R. Significant relationships were also observed between body image disturbance and three TAPES subscales measuring psychosocial adjustment [general adjustment (ρ = −0.48, P < 0.01), social adjustment (ρ = −0.51, P < 0.01), adjustment to limitations (ρ = −0.45, P < 0.05)].

Conclusions  Individuals with diabetes‐related amputations may be at elevated risk for psychological distress as a result of their co‐morbid medical condition. Regular screening for anxiety and depression and the provision of appropriate follow‐up care may therefore be advisable in this population.
Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism
Authors: Tassone F. , Procopio M. , Gianotti L. , Visconti G. , Pia A. , Terzolo M. , Borretta G.
Published: July 2009

Aims  An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients.

Subjects and methods  One hundred and twenty‐two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty‐one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting‐ and oral glucose tolerance test‐derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite.

Results  Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = −0.30, P = 0.001; R = −0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: β = −0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: β = −0.29, P = 0.005, R2 = 0.16).

Conclusions  Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition.
Decision Comprehensiveness and Corporate Entrepreneurship: The Moderating Role of Managerial Uncertainty Preferences and Environmental Dynamism
Authors: Heavey Ciaran , Simsek Zeki , Roche Frank , Kelly Aidan
Published: August 2009

abstract

Although comprehensiveness is considered among the most salient and enduring strategic decision‐making characteristics in organizations, its influence on firm behaviour has remained elusive. As a first step, our study builds and tests a model that specifies the influence of comprehensiveness on the firm's pursuit of corporate entrepreneurship. Our core argument is that while comprehensiveness helps decision‐makers gain the knowledge needed to escape the ignorance and overcome doubt associated with this pursuit, this beneficial influence is conditional upon managerial uncertainty preferences, together with the level of dynamism in the external environment. Findings from a large sample study of CEOs from 349 SMEs provide general support for this argument and associated hypotheses.
What is Reflection‐In‐Action? A Phenomenological Account
Authors: Yanow Dvora , Tsoukas Haridimos
Published: August 2009

abstract

Building on the work of Donald Schön and phenomenological treatments of practice, we propose a phenomenological theory of reflection‐in‐action that develops this concept further, thereby transcending a number of limitations we find in his theorizing. Our theory includes: an appreciation for the evaluative dimensions built into competent practice that encourage, if not require, reflecting; a further theorizing of the character of surprise; and a fuller delineation of the character of improvisation in relation to practice and its surprises. We begin with a phenomenological account of cognition in relation to work, especially in its form of professional practice. We reframe Schön's arguments in phenomenological, especially Heideggerian, terms and take account of relatively recent theorizing about knowledge‐based work, illustrating these discussions with a vignette drawn from field research in the world of practice. We conclude with a discussion of the implications of these arguments for practitioners as well as for further theorizing.
Development of aptitude at altitude
Authors: Hogan Alexandra M. , Virues‐Ortega Javier , Botti Ana Baya , Bucks Romola , Holloway John W. , Rose‐Zerilli Matthew J. , Palmer Lyle J. , Webster Rebecca J. , Baldeweg Torsten , Kirkham Fenella J.
Published: August 2009

Millions of people currently live at altitudes in excess of 2500 metres, where oxygen supply is limited, but very little is known about the development of brain and behavioural function under such hypoxic conditions. We describe the physiological, cognitive and behavioural profile of a large cohort of infants (6–12 months), children (6–10 years) and adolescents (13–16 years) who were born and are living at three altitude locations in Bolivia (∼500 m, ∼2500 m and ∼3700 m). Level of haemoglobin oxygen saturation and end‐tidal carbon dioxide were significantly lower in all age groups living above 2500 metres, confirming the presence of hypoxia and hypocapnia, but without any detectable detriment to health. Infant measures of neurodevelopment and behaviour yielded comparable results across altitude groups. Neuropsychological assessment in children and adolescent groups indicated a minor reduction in psychomotor speed with increasing altitude, with no effect of age. This may result from slowing of underlying brain activity in parallel with reduced cerebral metabolism and blood flow, evidenced here by reduced cerebral blood flow velocity, particularly in the basilar artery, in children and adolescents. The proportion of European, Native American and African genetic admixture was comparable across altitude groups, suggesting that adaptation to high altitude in these children occurred in response to chronic hypoxic exposure irrespective of ethnic origin. Thus, psychomotor slowing is proposed to be an adaptive rather than a deficient trait, perhaps enabling accuracy of mental activity in hypoxic conditions.
OUTLINING ETHICAL ISSUES IN NANOTECHNOLOGIES
Authors: SPAGNOLO ANTONIO G. , DALOISO VIVIANA
Published: July 2009

Nanotechnologies are an expression of the human ability to control and manipulate matter on a very small scale. Their use will enable an even and constant monitoring of human organisms, in a new and perhaps less invasive way. Debates at all levels – national, European and international – have pointed out the common difficulty of giving a complete, clear definition of nanotechnologies. This is primarily due to the variety of their components, to the fact that there is not just one technology but several.

The most significant medical applications of nanotechnologies are in the diagnostic and the therapeutic fields, eg biosensors and molecular imaging, providing diagnosis and drug delivery with no invasive methods involved.

Like any other emerging field, such technologies imply new possibilities for improving health but, on the other hand, they are still at an experimental stage and therefore should be implemented under rigorous safety testing before going on general release. For this purpose, the ethical, legal and social implications (ELSI) of nanotechnologies have been elaborated by study groups, in order to develop solutions before the results of the tests are diffused into medical practice.

The aim of this paper is to define some of the ethical issues concerning biomedical applications and to evaluate whether there is a need for new or additional guidelines and regulations.
BUSINESS AND FINANCIAL METHOD PATENTS, INNOVATION, AND POLICY
Authors: Hall Bronwyn H.
Published: July 2009

Court decisions in the 1990s are widely viewed as having opened the door to a flood of business method and financial patents at the US Patent and Trademark Office, and to have also impacted other patent offices around the world. A number of scholars, both legal and economic, have critiqued both the quality of these patents and the decisions themselves. This paper reviews the history of business method and financial patents briefly and then explores what economists know about the relationship between the patent system and innovation, in order to draw some tentative conclusions about their likely impact. It concludes by finding some consensus in the literature about the problems associated with this particular expansion of patentable subject matter, highlighting the remaining areas of disagreement, and reviewing the various policy recommendations.
Leg‐attached data loggers do not modify the diving performances of a foot‐propelled seabird
Authors: Ropert‐Coudert Y. , Kato A. , Poulin N. , Grémillet D.
Published: July 2009

Global location sensors (GLS) are increasingly being used to determine animal position at sea. Their small size and weight means that they can be attached to the leg of volant birds with supposedly little impact on the flight ability. However, very few studies have investigated the impact that foot‐attached devices may have on the diving ability of foot‐propelled seabirds. We compared the diving activity of two groups of free‐ranging great cormorants Phalacrocorax carbo carbo, both groups carrying identical time‐depth recorders attached to the tail, and one group also having leg‐attached GLS. Our results showed that there were no differences between the two groups in any of the diving parameters investigated, at least over the short term. Caution should be exercised when extrapolating to other species, especially those smaller than great cormorants, and also when deploying GLS over longer periods.
Calcineurin dephosphorylates glycogen synthase kinase‐3 beta at serine‐9 in neuroblast‐derived cells
Authors: Kim Yeni , Lee Yun‐Il , Seo MiRan , Kim So‐Young , Lee Ji‐Eun , Youn Hong‐Duk , Kim Yong‐Sik , Juhnn Yong‐Sung
Published: July 2009

This study examined the role of calcineurin, a major calcium‐dependent protein phosphatase, in dephosphorylating Ser‐9 and activating glycogen synthase kinase‐3β (GSK‐3β). Treatment with calcineurin inhibitors increased phosphorylation of GSK‐3β at Ser‐9 in SH‐SY5Y human neuroblastoma cells. The over‐expression of a constitutively active calcineurin mutant, calcineurin A beta (1–401), led to a significant decrease in phosphorylation at Ser‐9, an increase in the activity of GSK‐3β, and an increase in the phosphorylation of tau. Km of calcineurin for a GSK‐3β phosphopeptide was 469.3 μM, and specific activity of calcineurin was 15.2 nmol/min/mg. In addition, calcineurin and GSK‐3β were co‐immunoprecipitated in neuron‐derived cells and brain tissues, and calcineurin formed a complex only with dephosphorylated GSK‐3β. We conclude that in vitro, calcineurin can dephosphorylate GSK‐3β at Ser‐9 and form a stable complex with GSK‐3β, suggesting the possibility that calcineurin regulates the dephosphorylation and activation of GSK‐3βin vivo.
Acute‐phase proteins as indicators of bacterial infection in patients with cirrhosis
Authors: Tsiakalos Aristotelis , Karatzaferis Aggelos , Ziakas Panayiotis , Hatzis Gregorios
Published: July 2009

Background: Cirrhosis is associated with elevated levels of acute‐phase proteins (APP), irrespective of the presence of infection. This condition limits the clinical application of APP determination in cirrhotic patients with bacterial infections.

Aims: To weigh the diagnostic value of several APP in cirrhotics with or without bacterial infection, and to correlate them with the clinical outcome.

Methods: We investigated 88 consecutive cirrhotic patients (67 males, 21 females; range 28–85 years) with mean age (SD) 58.9 (13.8) on admission, according to a standard protocol for infection. We measured the following APP: C‐reactive protein (CRP), fibrinogen (FIB), haptoglobin (Hpt), ferritin (Fer), β2‐microglobulin (β2‐mg), C3, C4 and C1 inhibitor.

Results: From the 88 patients, 19 (21.6%) had documented infection at the entry based on clinical, radiological and microbiological data. This group of patients did not differ in basic demographics from those without infection. CRP [17.5 (20.7) vs 77.1 (43.9), P<0.001], β2‐mg [4.4 (4.1) vs 5.6 (2.2), P<0.001] and ferritin [461.2 (776.4) vs 825.8 (870), P=0.03] were significantly higher in infection, whereas C3 was significantly lower. No significant differences were noted in the remaining APP levels between the two groups. After receiver operating characteristic curves were fitted, CRP was the best diagnostic test for infection (area under the curve 0.91), followed by β2‐mg, ferritin, FIB, C1 inhibitor, C4, Hpt and C3.

Conclusions: Serum CRP is the best test, among the examined APP, to discriminate bacterial infection in cirrhotics. A cut‐off value of >55.8 mg/L has high sensitivity (79%) and specificity (96%), with the best diagnostic accuracy (92%).
Dynamic Capability Building in Service Value Networks for Achieving Service Innovation
Authors: Agarwal Renu , Selen Willem
Published: July 2009

Service organizations increasingly create new service offerings that are the result of collaborative arrangements operating on a value network level. This leads to the notion of “elevated service offerings,” our definition of service innovation, implying new or enhanced service offerings that can only be eventuated as a result of partnering, and one that could not be delivered on individual organizational merits. Using empirical data from a large telecommunications company, we demonstrate through structural equation modeling (SEM) that higher‐order dynamic capabilities in services are generated as a result of collaboration between stakeholders. Furthermore, it is through collaboration and education of the stakeholders that additional higher‐order capabilities emerge (customer engagement [CuE], collaborative agility [CA], entrepreneurial alertness [EA], and collaborative innovative capacity), all of which influence the service innovation outcome. Our study also reveals empirical evidence for an ongoing process of continuous dynamic capability building in accordance with the changing dynamics of business. Managers of service organizations should recognize the potential embedded in these higher‐order skill sets, starting from collaboration, learning, and management of creative ideas for both strategic and operational benefits. Moreover, the capabilities of CA, EA, and CuE are even more important in managing the flexibility, timely delivery, and reliability of service offerings. Managers should take measures to inculcate, promote, and manage these dynamic capability skill sets to foster innovation in services.
Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis
Authors: Proesmans M , Sauer K , Govaere E , Raes M , De Bilderling G , De Boeck K
Published: July 2009

Aim:  To evaluate the long‐term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis.

Methods:  Fifty eight patients (aged ≤ 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27).

Results:  During the 3‐month treatment period, there were no statistical significant differences between the two groups for symptom‐free days and nights (48.5 [interquartile range 33.0.0–66.0] for montelukast vs 57.0 [29.0–71.0] for placebo p = 0.415) nor disease‐free days and nights (44.5 days [26.0–54.0] vs 53.0 [22.3–71.0]; p = 0.266). During the 1 year follow‐up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups.

Conclusion:  Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment.
Oligomerization is required for the activity of recombinant soluble LOX‐1
Authors: Cao Wei , Calabro Valerie , Root Adam , Yan Grace , Lam Khetemenee , Olland Stephane , Sanford Jocelyn , Robak Angela , Zollner Richard , Lu Zhijian , Ait‐Zahra Mostafa , Agostinelli Rita , Tchistiakova Lioudmila , Gill Davinder , Harnish Douglas , Paulsen Janet , Shih Heather H.
Published: July 2009

LOX‐1 is a scavenger receptor that functions as the primary receptor for oxidized low‐density lipoprotein (OxLDL) in endothelial cells. The binding of OxLDL to LOX‐1 is believed to lead to endothelial activation, dysfunction, and injury, which constitute early atherogenic events. Because of its potential pathological role in atherosclerosis, LOX‐1 has been proposed as a therapeutic target for the treatment of this disease. In order to antagonize the ligand‐binding function of cell surface LOX‐1, we generated a series of recombinant human LOX‐1–crystallizable fragment (Fc) fusion proteins and subsequently characterized their biochemical properties and ligand‐binding activities in vitro. Consistent with the notion that oligomerization of cell surface LOX‐1 is required for high‐avidity binding of ligands, we found that LOX‐1–Fc fusion protein containing four ligand‐binding domains per Fc dimer, but not the one containing two ligand‐binding domains, exhibited ligand‐binding activity. Optimal ligand‐binding activity could be achieved via crosslinking of LOX‐1–Fc fusion proteins with a polyclonal antibody against Fc. The crosslinked LOX‐1–Fc protein also effectively inhibited the binding and internalization of OxLDL by cell surface LOX‐1. These findings demonstrate that functional oligomerization is required for recombinant LOX‐1–Fc to function as an effective antagonist.

Structured digital abstract

MINT‐7213199: LOX1 (uniprotkb:P78380) and LOX1 (uniprotkb:P78380) physically interact (MI:0914) by molecular sieving (MI:0071)
Effects of Long‐Term Mildronate Treatment on Cardiac and Liver Functions in Rats
Authors: Liepinsh Edgars , Kuka Janis , Svalbe Baiba , Vilskersts Reinis , Skapare Elina , Cirule Helena , Pugovics Osvalds , Kalvinsh Ivars , Dambrova Maija
Published: August 2009

Abstract: Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by loweringl‐carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long‐term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate,l‐carnitine and γ‐butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. Thel‐carnitine‐lowering effect of mildronate was dose‐dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long‐term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.
Vascular Access in Patients Treated With Chronic Hemodialysis for 30 Years or More
Authors: Buturović‐Ponikvar Jadranka , Peršič Vanja , Malovrh Marko , Ponikvar Rafael
Published: July 2009

The aim of our study was to evaluate vascular access in patients treated with chronic hemodialysis for 30 years or more. Patients who had started dialysis in 1978 or earlier were identified from the Slovenian Renal Replacement Therapy Registry. The data on vascular access on April 2008 are presented. Sixteen patients were still alive, seven men and nine women aged 62 ± 12 years (46–84), and they had been treated for 32 ± 1.7 years (30–35), mainly with chronic HD. They had started HD at the age of 30 ± 12 years (13–50), and none had diabetes. The vascular access in nine was a native arteriovenous (AV) fistula, on the forearm in eight patients, and a brachiobasilic fistula in one patient. Four patients had their primary AV fistulas still in use (maximum 35 years). In the remaining five patients, multiple salvage procedures had been performed or new AV fistulas created. The vascular access in four patients was the polytetrafluoroethylene (PTFE) graft, functioning for 1–8 years. In three patients, a non‐cuffed, single‐lumen hemodialysis catheter (a precurved jugular in two patients and a subclavian in one) locked with 30% citrate, with mupirocin at the exit site, was used for 5–12 years. The catheters were exchanged approximately once every two years over a guide‐wire because of mechanical damage. None of these three patients had had catheter‐related sepsis or exit‐site infection. Before catheters, these patients had had multiple AV fistulas and PTFE grafts. Although native AV fistula is the predominant type of vascular access, a greater than 30‐year survival on hemodialysis is possible with the combined use of AV fistula, PTFE graft, and a non‐cuffed hemodialysis catheter locked with citrate.
Encapsulating Peritoneal Sclerosis in Patients on Peritoneal Dialysis in Slovenia
Authors: Lindič Jelka , Rupnik Alijana Trošt , Tomažič Janez , Škoberne Andrej , Guček Andrej , Ferluga Dušan , Pintar Tadeja , Aleš Andreja , Kovač Damjan , Kveder Radoslav , Pajek Jernej , Savicki‐Ponikvar Barbara , Bren Andrej
Published: July 2009

Encapsulating peritoneal sclerosis (EPS) is a rare complication in patients on peritoneal dialysis (PD), the prevalence of which increases with the time spent on PD. Various causative factors have been proposed, but the pathogenesis still remains unclear. The aim of our retrospective study was to analyze the basic clinical characteristics and outcomes of five patients diagnosed with EPS out of 423 patients treated with PD between January 1983 and December 2003. One patient was admitted due to ultrafiltration failure of the peritoneal membrane, and four patients were admitted for acute peritonitis. All of our patients presented with clinical symptoms suggestive of obstructive ileus. We confirmed the diagnosis of EPS with a computer tomography scan, a diagnostic laparotomy or laparoscopy, and a biopsy of the parietal peritoneum. We treated all of our patients with catheter removal, transferal to hemodialysis, antibiotics, complete parenteral nutrition, methylprednisolone, and tamoxifen for 6 months. One patient was treated with surgical enterolysis and died of septic complications, another patient died of sudden cardiac death during treatment. Three patients were doing well for 4–7 months after the treatment was started. The incidence of EPS was 1.2% and the mortality rate was 40%. EPS is a rare complication in longstanding PD patients in our institution. Despite treatment with hemodialysis, complete parenteral nutrition, steroids, tamoxifen and surgical intervention, the mortality rate is high and comparable to other reports.
Vascular Access Recirculation in Hemodialysis Patients With Two Noncuffed, Single‐lumen, Jugular Catheters in the Same Jugular Vein
Authors: Kovač Janko , Buturović‐Ponikvar Jadranka , Ponikvar Rafael
Published: July 2009

Having achieved excellent results with single‐lumen temporary hemodialysis catheters as a long‐term vascular access in our center, in this study we examined the amount of vascular access recirculation in the case of using two single‐lumen catheters in a single jugular vein. In 11 adult end‐stage renal disease patients on chronic hemodialysis (HD), vascular access recirculation was studied using a thermodilution technique during dialysis at our center. The vascular access in all patients consisted of two pre‐curved, 15 cm‐long, 8‐Fr catheters inserted in the right jugular vein. Recirculation measurements were performed with the blood flow set to 250 mL/min in all patients. In five patients, additional measurements were performed with the blood flow set to 200 mL/min. During 16 HD procedures, 55 recirculation measurements were taken. The rate of recirculation was <15% in 50 measurements, between 15% and 20% in four measurements, and >20% in one measurement. The average recirculation rate during a single procedure was <15% in 10 patients, and 16.2% in one patient. We did not find any significant differences in the recirculation rates measured either at higher or lower blood flow rates. The clinical importance of vascular access recirculation was noted in a single patient. Vascular access recirculation in hemodialysis patients with two single‐lumen catheters in the same jugular vein is mostly acceptable. Some measures for preventing clinically important recirculation are also suggested.
OXIDATIVE STABILITY OF BRINED ANCHOVIES WITH EXTRACTS FROM BLUEBERRY (VACCINUM SP.) FRUITS AND LEAVES
Authors: TURHAN SADETTIN , TEMIZ HASAN , KOCA A. FAIK
Published: July 2009

The hot‐water extracts from blueberry (Vaccinum sp.) fruits and leaves were examined for their total phenolic content, ferric reducing antioxidant power and 2,2‐diphenyl‐1‐picrylhydrazyl–scavenging activity. It was observed that water extracts from blueberry leaves contained higher total phenolic content, ferric reducing antioxidant power and lower 2,2‐diphenyl‐1‐picrylhydrazyl–scavenging activity than those from blueberry fruits. Oxidative stability of brined anchovies with extracts obtained from blueberry fruits and leaves was investigated during storage at 4C for 28 days. Brining with blueberry fruit and leaf extracts slowed down the lipid oxidation of anchovies. The highest antioxidant effect (peroxide value, thiobarbituric acid reactive substance and oxidative rancidity) was observed with brined anchovies with blueberry leaf extracts. The antioxidant potency of blueberry fruit extract was approximately equal to that of blueberry leaf extract. The highest polyunsaturated fatty acid percent was observed in the brined anchovies with blueberry leaf extract, but no significant difference with blueberry fruit extract was observed (P > 0.05). These results suggest that brining with blueberry fruits and leaves extracts could enhance oxidative stability of fish.

PRACTICAL APPLICATIONS

Lipid oxidation is one of the main problems during the storage of salted anchovies. One of the methods for protection against oxidation is using antioxidants. Brining with blueberry fruit and leaf extracts slowed down the lipid oxidation of anchovies. According to these results, blueberry fruit and leaf extracts can be used to extend the shelf life of brined anchovies.
A Wet/Wet Differential Pressure Sensor for Measuring Vertical Hydraulic Gradient
Authors: Fritz Brad G. , Mackley Rob D.
Published: July 2009

Vertical hydraulic gradient is commonly measured in rivers, lakes, and streams for studies of groundwater–surface water interaction. While a number of methods with subtle differences have been applied, these methods can generally be separated into two categories; measuring surface water elevation and pressure in the subsurface separately or making direct measurements of the head difference with a manometer. Making separate head measurements allows for the use of electronic pressure sensors, providing large datasets that are particularly useful when the vertical hydraulic gradient fluctuates over time. On the other hand, using a manometer‐based method provides an easier and more rapid measurement with a simpler computation to calculate the vertical hydraulic gradient. In this study, we evaluated a wet/wet differential pressure sensor for use in measuring vertical hydraulic gradient. This approach combines the advantage of high‐temporal frequency measurements obtained with instrumented piezometers with the simplicity and reduced potential for human‐induced error obtained with a manometer board method. Our results showed that the wet/wet differential pressure sensor provided results comparable to more traditional methods, making it an acceptable method for future use.