bluuebunny/crossref_metadata_2025 huggingface dataset:
Feedback in incident reporting – more needed
Authors: Basu Abhijit , Gopinath Deepa , Anjum Naheed , Hotchkies Susan
Published: January 2009

Purpose

The purpose of this paper is to determine the prevalence of feedback following adverse clinical incident reporting among trainee doctors in obstetrics and gynaecology within the Northwestern Deanery of England.

Design/methodology/approach

An anonymous questionnaire was circulated among the Specialist Registrar trainees within the specialty attending a regional teaching session. The questionnaire was analysed.

Findings

There were 50 responses, of those 45 (90 per cent) had been involved in an adverse clinical incident; 44 had submitted an incident form related to the incident. Three had submitted incident forms without being involved in an adverse incident. Most (80 per cent) had submitted an incident form as well as a related statement. Feedback was available to 23 (51 per cent) of those involved in adverse incidents. More of the senior trainees received feedback than the junior ones. A lecture on clinical incident reporting was available to only 35(70 per cent) of the respondents on the hospital induction day at their latest clinical placement.

Research limitations/implications

This study is limited to adverse clinical incident reporting among the trainees in a single specialty within one deanery in UK; hence the small numbers.

Practical implications

This study demonstrates the presence of awareness regarding adverse incident reporting among the trainees in a high‐risk specialty. It also shows the suboptimal rate of feedback following adverse incident reporting, which does not encourage a learning environment. It is suggested that a lecture should be dedicated to incident reporting at the junior doctors' induction day programme in every hospital.

Originality/value

This paper highlights the lack of adequate feedback following adverse clinical incident reporting.
Burden or blessing?
Authors: Grabs Anthony J.
Published: January 2009

Purpose

The purpose of this paper is to present possible benefits of establishing a national trauma database to assist patient safety and continued clinical excellence in Australia.

Design/methodology/approach

The paper outlines how the management of trauma patients is organised.

Findings

It is shown that to continue to engage clinicians, rationalisation of clinical governance structure is required. This will require leadership to improve efficacy and reduce duplication of workloads.

Originality/value

It is concluded that, given the right conditions, Australia could commence a national trauma database similar to the American or British systems where minimum data sets are recorded and reap the benefits with improved safety and outcome in trauma patients on a national basis.
The role of the GP trainer: medicolegal aspects
Authors: Mackenzie Peter , Anthony Sandy
Published: January 2009

Purpose

The purpose of this paper is to consider the medicolegal aspects of working as a GP trainer.

Design/methodology/approach

A brief review of the legislation and guidance affecting GP trainers. From this, an analysis of the major risks GP trainers face, and the steps they should take to minimise those risks, is conducted.

Findings

There are a number of high‐risk areas for GP trainers. Lack of awareness of a GP registrar's competencies can lead to problems. There is risk in a GP registrar being unfamiliar with the practice, its procedures and physical layout. Out‐of‐hours training is particularly hazardous. A GP registrar who is poorly performing can present a serious risk to patient safety.

Practical implications

GP trainers should put in place procedures to mitigate these risks. A realistic assessment of a GP registrar's skills; a comprehensive induction; adequate supervision out of hours and systems for dealing with poor performance are essential elements of a GP trainer's role.

Originality/value

The paper highlights the benefit for GP trainers in considering the risks they may face and taking steps to address them.
A critical review of patient satisfaction
Authors: Gill Liz , White Lesley
Published: January 2009

Purpose

This paper aims to review the patient satisfaction literature, specifically meta‐analyses, which critically analyses its theory and use; then to present evidence for perceived service quality as a separate and more advanced construct.

Design/methodology/approach

Papers that judiciously review the development and application of patient satisfaction were identified; along with studies addressing the conceptual and methodological deficiencies associated with the concept; and the current perceived service quality theory.

Findings

Patient satisfaction has been extensively studied and considerable effort has gone into developing survey instruments to measure it. However, most reviews have been critical of its use, since there is rarely any theoretical or conceptual development of the patient satisfaction concept. The construct has little standardisation, low reliability and uncertain validity. It continues to be used interchangeably with, and as a proxy for, perceived service quality, which is a conceptually different and superior construct.

Practical implications

The persistent use of patient satisfaction to evaluate the client's perception of the quality of a health service is seriously flawed. The key to solving this dilemma may be for the healthcare sector to focus on perceived health service quality by considering the specific concepts and models that can be found in the services marketing literature. This literature offers more advanced consumer theories which are better differentiated and tested than existing healthcare satisfaction models.

Originality/value

The paper points out that there is an urgent need for differentiation and standardisation of satisfaction and service quality definitions and constructs, and argues for research to focus on measuring perceived health service quality.
Do types of organizational culture matter in nurse job satisfaction and turnover intention?
Authors: San Park Jae , Hyun Kim Tae
Published: January 2009

Purpose

The purpose of the study is to examine whether and how different types of organizational culture are associated with job satisfaction and turnover intention among hospital nurses in Korea, where the work culture is often considered different from that of Western countries.

Design/methodology/approach

The sample for the study consists of 527 nurses working in two public hospitals in Korea. Perceived organizational culture was assessed by a previously validated 20‐item instrument, and job satisfaction and turnover intention were measured by self‐report questionnaires. Factor analysis was employed to construct four different types of culture (consensual, rational, developmental, and hierarchical). The relationship among organizational culture, job satisfaction, and turnover intention was tested by structural equation modeling (SEM).

Findings

Among the different types of culture, consensual culture and rational culture had significant, positive associations with the nurses' job satisfaction. In addition, consensual culture exhibited the strongest, negative association with the turnover intention of the nurses, while hierarchical culture showed a significant, positive association.

Research limitations/implications

Consensual culture that emphasizes teamwork and values human relations was most strongly associated with higher job satisfaction and lower turnover intention of nurses in Korea. However, caution is needed in inferring that organizational culture is the cause of the nursing outcomes because this study is designed as a cross‐sectional study; thus, an association alone was proven and not causality.

Practical implications

Managers should be aware that understanding the organizational culture can help them to determine where to strive to help improve nurses' job satisfaction and retention rate.

Originality/value

The results of the study may be useful to health administrators who wish to decrease nurse turnover. Improving nurses' job satisfaction in the work environment may reduce turnover and help ensure a stable and qualified workforce.
Retention strategies for professional nurses in South Africa
Authors: Pillay Rubin
Published: January 2009

Purpose

One of the major challenges facing health systems in developing countries is the international migration of professional nurses, coupled with migration from rural to urban areas and gravitation to the private sector from the public sector. This study aims to determine what the future work plans of professional nurses in South Africa are and to determine appropriate, contextually relevant strategies to retain nurses where they are needed most.

Design/methodology/approach

This is a cross‐sectional survey of professional nurses conducted throughout South Africa using a pre‐tested and self‐administered questionnaire. A total of 569 professional nurses participated in the study.

Findings

Of the respondents, 34.8 percent indicated an intention to change their sector of employment within the next five years while only 30.2 percent reported that they would most likely be still in their current positions as professional nurses in five years' time. Younger nurses, nurses in the public sector and nurses from the more rural provinces were also significantly less likely to be in their current positions within the next five years. Public sector nurses felt that employment security, workplace organisation and the working environment were the most important factors. Private sector nurses, however, rated workplace organisation, employment security and professional practice as being most important.

Originality/value

The paper presents evidence that health provision in South Africa is facing an imminent crisis with the overwhelming majority of nurses planning to leave their current positions. The findings suggest that most nurses, irrespective of whether they intend to stay or leave, feel that the same issues need to be addressed if they are to be persuaded to remain in their current positions. This implies that a homogeneous approach could be adopted across sectors and geographic regions to promote health organisations in a more attractive way to nurses.
“Gerry Robinson and the UK NHS: did he really make a difference?”
Authors: Towill Denis R.
Published: January 2009

Purpose

This paper seeks to exploit the TV series “inquest” held 12 months after the original programme to assess the impact of Gerry Robinson (if any) on healthcare delivery effectiveness observed at Rotherham General Hospital, UK, in particular, to explicitly identify the positive features in such a way as to better enable transferability of “good practice” between healthcare organisations.

Design/methodology/approach

The approach adopted is to first chronicle the areas of perceived progress and delivery shortfalls. Thence via careful reference to the established literature to identify the engineering change modus operandi most likely to yield benefits in typical healthcare scenarios. Additionally, to confirm the expected and identify the unexpected barriers to change.

Findings

As with any highly publicised programme, the Hawthorne Effect on the various “actors” is not entirely negligible. A positive step forward is confirmation that actively involving coal‐face players, including physicians, nurses, and support staff in the success gets results. Examples unfortunately emerge where physicians‐led innovation is stifled by either internal or external bureaucracy.

Originality/value

Some reasonably reliable narrative evidence is presented describing what may actually work in healthcare delivery performance improvement programmes.
The domestic savings and economic growth relationship in China
Authors: Hooi Lean Hooi , Song Yingzhe
Published: January 2009

Purpose

The purpose of this paper is to examine the relationship between the growth of domestic savings and economic growth in China.

Design/methodology/approach

Cointegration and causality tests cover the country as a whole and four of selected representative provinces for the period of 1955‐2004.

Findings

China's economic growth is found to have a long‐running relationship with household savings and enterprise savings. Bilateral causality exists between the domestic savings growth and the economic growth in the short‐run. In the long‐run, a unidirectional causality exists running from the domestic savings growth to the economic growth. However, the provinces show a different statistical relationship between these two variables.

Research limitations/implications

The data are not up to date and are limited to the annual frequency.

Practical implications

It would be useful to the policy makers to understand the dynamics involved and where necessary, to make adjustments to the prevailing and future economic policies in order to achieve the rapid and desired economic development and sustainable economic growth.

Originality/value

The paper assesses the cointegration and causality relationship between the growth of domestic savings and economic growth in China.
Economic growth and food policy in urban China
Authors: Kiminami Lily , Kiminami Akira
Published: January 2009

Purpose

The purpose of this paper is to clarify the influence that economic growth gives to the food consumption in urban China by taking income gap into consideration. It also proposes an appropriate food policy corresponding to the consumers’ diversified needs for food under the process of economic growth.

Design/methodology/approach

Various kinds of methodologies are employed such as the interview analysis, food tasting investigation, group discussion, retail price investigation and the questionnaire survey, etc. for the case study from Shanghai.

Findings

Food policy for China in the current stage should be considered to supply food with a constant quality to the poorest segment of the population at cheap price and to correspond to the diversified needs of the general public for food (including high quality and safety intention of top‐tier population).

Originality/value

Not only the existence of income gap but also the realities of the difference in the food consumption among the poorest segment, the general public and the rich layer of the population are clarified. The food policy which attempts to correspond to the diversified needs for food and to realize a sustainable development of the society is proposed.
Access flexibility, trust and performance in achieving competitiveness
Authors: Hua Song , Ranjan Chatterjee Samir , Kang‐kang Yu
Published: January 2009

Purpose

This paper aims to advance research in the challenging area of achieving competitiveness through supply chain flexibility fit and trust development.

Design/methodology/approach

A structured survey questionnaire was administered to a potential list of 773 participants resulting in 348 valid responses. An empirical study was conducted on these responses.

Findings

Leveraging of flexibility in supply chain access structures and improving of trust relationships can ensure significant performance improvement.

Research limitations/implications

The research relies on the use of cross sectional data instead of longitudinal data, thereby limiting the generalisibility of the findings.

Practical implications

The strong evidence of relationship between improved performance and capability of supply chain linkages provides Chinese business managers with practical guidelines for improving competitive edge.

Originality/value

The value of the paper lies in the originality of the data and context‐relevant findings. No previous study of this nature had been undertaken in China.
Building Chinese global brands through soft technology transfer
Authors: Ille Francis R.
Published: January 2009

Purpose

The purpose of this paper is to examine the different strategies implemented by a number of successful Chinese firms currently striving to build global brands in order to improve their export capabilities. A particular emphasis is put on the transfer of marketing technology for brand engineering in order to achieve this goal.

Design/methodology/approach

The analysis uses case study methodology to understand what many prominent Chinese exporting firms have achieved, and develops a theory about their general strategy. Five firms have been chosen: Lenovo, Haier, Cosco, Tsingtao, Geely. Aside from these five, information is also given on the branding strategy of Li Ning and Suntech Power. A great part of the information collected is coming from “desk research”, except for Haier, Lenovo and Tsingtao for which personal contacts and visits took place in 2005 and 2006.

Findings

The findings suggest that some of the most successful Chinese firms in the field of development of brand image either use some marketing tools, such as increasing their communication spending, improving quality control, emphasizing their corporate social responsibility visibility, or by seeking a partnership through mergers/acquisition with successful foreign brands. A basic global branding model has been defined as consistent with Chinese firms’ experience.

Research limitations/implications

The study was limited to seven firms to be considered among the most successful Chinese businesses. It does not intend to be perceived as statistically representative. The period of observation of the effect of the strategy which was implemented was short and during a time of booming Chinese economy. It was impossible to isolate the extraneous variables linked to the economic or competitive situation, knowing that they could affect the observations on the firms that were studied.

Originality/value

Though the entry strategies on the Chinese market as well as inbound foreign direct investments have been the object of a great number of publications, the outbound strategies of Chinese exporting firms, as well as the impact of technology transfer, has been covered less frequently. Therefore, this paper can have value for candidates for the improvement of global branding.
Effect of proton pump inhibition on the gastric volume: assessed by magnetic resonance imaging
Authors: BABAEI A. , BHARGAVA V. , AALAM S. , SCADENG M. , MITTAL R. K.
Published: January 2009

Background  Proton pump inhibitor (PPI) therapy is known to suppress gastric acid secretion. Thus PPI therapy may decrease gastric volume and gastric contents available for gastro‐oesophageal reflux by decreasing acid secretion.

Aim  To determine the effect of PPI therapy on the gastric volume after a standard meal.

Methods  A total of nine healthy subjects were studied using magnetic resonance imaging, before and after a standard liquid meal mixed with a paramagnetic contrast to help demarcate the gastric region. Images were acquired for a total of 90 min after the meal. Studies were conducted before and following esomeprazole twice daily for 7 days. Images were analysed to determine the gastric liquid volume.

Results  Gastric volume, 15 min after the meal peaked to 611 ± 37 mL on the control day and 539 ± 30 mL following the PPI administration (P < 0.001). Average gastric volume remained significantly lower (56 ± 9 mL, P < 0.05) on the PPI therapy from 5 to 75 min after the meal.

Conclusions  Proton pump inhibitor therapy causes a significant reduction in the gastric contents volume during first 75 min after the meal. In addition to increasing the gastric pH, PPI therapy may decrease the frequency of gastro‐oesophageal reflux by decreasing the volume of gastric contents.
Distinct regulatory roles of transforming growth factor‐β and interleukin‐4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells
Authors: Prochazkova Jana , Fric Jan , Pokorna Katerina , Neuwirth Ales , Krulova Magdalena , Zajicova Alena , Holan Vladimir
Published: January 2009

The development and function of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) are strictly regulated by cytokines. Here we show that transforming growth factor‐β (TGF‐β) and interleukin‐4 (IL‐4) play a crucial and antagonistic role in the development of Tregs. Additionally, these cytokines also have distinct effects on the maintenance of natural (nTregs) and antigen‐induced (iTregs) Tregs. Using double‐staining and tracking of proliferation of purified and carboxyflourescein succinimidyl ester (CFSE)‐labelled mouse T‐cell subpopulations we demonstrated that CD4+ CD25+ Foxp3+ iTregs develop upon alloantigenic stimulation in the presence of TGF‐β exclusively from CD4+ CD25− Foxp3− precursors. Both the induction of Foxp3 expression and Treg proliferation were prevented when the cells were stimulated in the presence of IL‐4. By contrast, nTregs did not proliferate in the presence of the antigen and TGF‐β, and partially lost their Foxp3 expression. IL‐4 not only prevented the development of iTregs, but also down‐regulated the level of Foxp3 mRNA and decreased the number of Foxp3+ cells in a population of iTregs. Further analyses proved that IL‐4 decreased the expression of Foxp3 only in a population of iTregs, whereas it substantially supported the survival of nTregs. Functional experiments showed that Tregs induced in the presence of alloantigen and TGF‐β inhibited, on a per‐cell basis, cell proliferation comparably to nTregs, and their suppressive capacity was not modulated by IL‐4. These data suggest that TGF‐β and IL‐4 differentially regulate the development of Tregs and distinctly sustain Foxp3 expression and the number of nTregs and iTregs, but have no influence on the suppressive activity of Tregs on a per‐cell basis.
Body mass index and risk of all‐cause and cardiovascular mortality in hospitalized elderly patients with diabetes mellitus
Authors: Weiss A. , Boaz M. , Beloosesky Y. , Kornowski R. , Grossman E.
Published: January 2009

Aims  Obesity is linked to increased morbidity and mortality risk in both the general population and in patients with diabetes mellitus; however, recent reports suggest that, in hospitalized elderly individuals, the association between body mass index (BMI) and mortality may be inverse. The present study sought to investigate the association between BMI and survival in hospitalized elderly individuals with diabetes mellitus.

Methods  The medical records of 470 patients (226 males, mean age of 81.5 ± 7.0 years) admitted to an acute geriatric ward between 1999 and 2000 were reviewed. Of the 140 patients with diabetes mellitus, 122 had more than 6 months of follow‐up and were included in this analysis. Patients were followed up until 31 August 2004. Mortality data were extracted from death certificates.

Results  During a mean follow‐up of 3.7 ± 1.6 years, 69 (56.6%) subjects died, 31 (25.4%) from cardiovascular causes. Those who died from any cause had lower baseline BMI than those who survived (24.0 ± 4.0 vs. 27.1 ± 4.3 kg/m2; P < 0.0001). Similarly, those who died of cardiovascular causes had lower baseline BMI than those who did not (23.7 ± 3.6 vs. 25.9 ± 4.5, P = 0.01). BMI was inversely associated with all‐cause [relative risk (RR) 0.89, 95% confidence interval (CI) 0.83–0.96, P = 0.002] and cardiovascular death (RR 0.83, 95% CI 0.74–0.93, P = 0.002) even after controlling for age, sex, smoking, dyslipidaemia and reason for hospital admission.

Conclusions  In very elderly subjects with diabetes mellitus, increased BMI was associated with reduced mortality risk.
Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium–hydrogen exchange in hypertensive patients with Type 2 diabetes1
Authors: Pikilidou M. I. , Lasaridis A. N. , Sarafidis P. A. , Befani C. D. , Koliakos G. G. , Tziolas I. M. , Kazakos K. A. , Yovos J. G. , Nilsson P. M.
Published: January 2009

Aims/hypothesis To investigate the effect of oral calcium (Ca2+) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca2+([Ca2+]i) and the transmembrane sodium–hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.

Patients and methods In this parallel randomized controlled single‐blinded trial, 31 patients were allocated to receive either 1500 mg of Ca2+orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8‐week period insulin sensitivity, [Ca2+]iand the first isoform of NHE (NHE‐1) activity were measured.

Results At the end of the study, subjects who received Ca2+supplementation showed higher insulin sensitivity (ΔM‐value 0.32 ± 0.5 mmol/minP < 0.05) and lower [Ca2+]i(125.0 ± 24.7 to 80.4 ± 10.6 nmol/l,P < 0.05, mean ± sem) and NHE‐1 activity (79.5 ± 10.0 to 52.1 ± 6.4 mmol Na/l red cell/h,P < 0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca2+]isignificantly determined insulin sensitivity change (β = −0.36,P < 0.05).

Conclusions/interpretation Oral Ca2+supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca2+. NHE‐1 activity was also reduced after Ca2+supplementation but its role in insulin sensitivity requires further investigation.
A randomized trial investigating the 12‐month changes in physical activity and health outcomes following a physical activity consultation delivered by a person or in written form in Type 2 diabetes: Time2Act
Authors: Kirk A. , Barnett J. , Leese G. , Mutrie N.
Published: January 2009

Background and aims  Physical activity is a cornerstone of Type 2 diabetes management but is underutilized. Physical activity consultations increase physical activity in people with Type 2 diabetes but resources are often limited. Time2Act is a randomized control trial to study the 12‐month effectiveness of a physical activity consultation delivered by a person or in written form, in contrast to standard care, for people with Type 2 diabetes.

Methods  A total of 134 inactive people with Type 2 diabetes in a contemplation or preparation stage were randomized to either intervention or standard care. Objective (accelerometer) and subjective (7‐day recall) physical activity levels were measured over 1 week, along with physiological [blood pressure, body mass index (BMI), waist circumference] and biochemical [glycated haemoglobin (HbA1c), total and high‐density lipoprotein (HDL) cholesterol] measures at baseline, 6 and 12 months.

Results  Neither a physical activity consultation delivered by a person nor in written form was better than standard care at increasing physical activity levels or improving health outcomes in the full study cohort. Total and HDL cholesterol, waist circumference and both systolic and diastolic blood pressure improved over 12 months in all groups, whilst HbA1c improved over 6 months. In a subgroup (baseline pedometer steps < 5000/day), the physical activity consultation delivered by a person significantly increased physical activity over 12 months and the standard care group significantly decreased.

Conclusions  More research is needed which not only investigates the most economical and effective methods to promote physical activity, but also the best setting to conduct physical activity consultations and the participant factors affecting uptake of physical activity in Type 2 diabetes.
Sudomotor dysfunction is associated with foot ulceration in diabetes
Authors: Tentolouris N. , Marinou K. , Kokotis P. , Karanti A. , Diakoumopoulou E. , Katsilambros N.
Published: January 2009

Aim  To examine the relationship between sudomotor dysfunction and foot ulceration (FU) in patients with diabetes.

Methods  Ninety patients with either Type 1 or Type 2 diabetes [30 without peripheral sensorimotor neuropathy (PN), 30 with PN but without FU and 30 with FU] were recruited in this cross‐sectional study. Assessment of PN was based on neuropathy symptom score (NSS), neuropathy disability score (NDS) and vibration perception threshold (VPT). Sudomotor dysfunction was assessed using the sympathetic skin response (SSR). Cardiac autonomic nervous system activity was assessed by the battery of the classical autonomic function tests.

Results  Patients with foot ulcers had longer duration of diabetes, higher values of VPT and NDS and lower values of the autonomic functions tests in comparison with the other study groups. Sudomotor dysfunction and cardiac autonomic neuropathy were significantly more common in the FU group. Multivariate logistic regression analysis after adjustment for gender, body mass index, duration of diabetes and glycated haemoglobin (HbA1c) demonstrated that the odds ratio (95% confidence intervals) of FU increased with measures of neuropathy such as NDS ≥ 6 (10.2, 6.2–17.3) and VPT ≥ 25 volts (19.8, 9.9–47.5), but was also significantly increased with absent SSR (15.3, 5.3–38.4).

Conclusions  Sudomotor dysfunction is associated with increased risk of FU and should be included in the screening tests for identification of diabetic patients at risk of ulceration.
Managing young people with Type 1 diabetes in a ‘rave’ new world: metabolic complications of substance abuse in Type 1 diabetes
Authors: Lee P. , Greenfield J. R. , Campbell L. V.
Published: January 2009

The taxing transition from adolescence towards adulthood intensifies the impact of a chronic illness such as Type 1 diabetes. It is not uncommon for young people with Type 1 diabetes to use recreational drugs for emotional relief to escape the day‐to‐day burden of chronic disease. Despite increasing use, especially in the setting of ‘rave’ parties, there is professional lack of understanding of the impact of recreational drug use on glycaemia and metabolic complications. The current review describes the prevalence of substance abuse in Type 1 diabetes and the acute impact of designer drugs on its management. We propose a practical approach to improve care of young people with Type 1 diabetes using designer drugs.
Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors
Authors: Levinger I. , Goodman C. , Peake J. , Garnham A. , Hare D. L. , Jerums G. , Selig S.
Published: January 2009

Aims  Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in individuals with a high number of metabolic risk factors (HiMF, 2.9 ± 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 ± 0.5).

Methods  Twenty‐eight men and 27 women aged 50.8 ± 6.5 years (mean ± sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40–50% of one repetition maximum (1RM) to 75–85% of 1RM], blood samples were obtained for the measurement of pro‐inflammatory cytokines, C‐reactive protein (CRP), γ‐glutamyltransferase (GGT) and alanine aminotransferase (ALT).

Results  At baseline, HiMF had higher interleukin‐6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P < 0.05). RT did not significantly alter inflammatory markers or hepatic enzymes (all P > 0.05).

Conclusions  HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in individuals with HiMF.
Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage
Authors: Deguchi T. , Hashiguchi T. , Horinouchi S. , Uto T. , Oku H. , Kimura K. , Makisumi K. , Arimura K.
Published: January 2009

Aim  To identify the relationship between vascular endothelial growth factor (VEGF) and diabetic polyneuropathy (DPN).

Methods  Two hundred and twenty diabetic patients participated, 113 with DPN and 107 without DPN. All patients were also classified according to the four stages of DPN (no neuropathy: stage 0; asymptomatic neuropathy: stage 1; symptomatic neuropathy: stage 2; disabling neuropathy: stage 3). Serum VEGF concentration was measured using an enzyme‐linked immunosorbent assay (ELISA) and levels between the patients with and without DPN and also between the different stages of DPN, were compared.

Results  The mean serum VEGF level in all patients was 264.6 ± 218.8 pg/ml. The mean serum VEGF level was higher in patients with DPN (310.1 ± 224.3 pg/ml) than in the patients without DPN (216.5 ± 204.0 pg/ml, P = 0.0014). Serum VEGF was higher in the ‘symptomatic’ stage (stage 2, 364.8 ± 225.9 pg/ml) in comparison with the ‘asymptomatic’ (stage 1, 256.7 ± 224.4 pg/ml, P = 0.015) and ‘disabling’ (stage 3, 180.3 ± 109.4 pg/ml, P = 0.042) stages. The mean serum VEGF level in patients with diabetic retinopathy (261.1 ± 210.6 pg/ml) and in patients with diabetic nephropathy (241.5 ± 185.7 pg/ml) was not increased.

Conclusions  The serum VEGF level is increased in patients with DPN, particularly in patients in the neurologically active ‘symptomatic’ stage.
Not all roads lead to Rome—a review of quality of life measurement in adults with diabetes
Authors: Speight J. , Reaney M. D. , Barnard K. D.
Published: January 2009

Aims  Quality of life (QoL) is recognized widely as an important health outcome in diabetes, where the burden of self‐management places great demands on the individual. However, the concept of QoL remains ambiguous and poorly defined. The aim of our review is to clarify the measurement of QoL in terms of conceptualization, terminology and psychometric properties, to review the instruments that have been used most frequently to assess QoL in diabetes research and make recommendations for how to select measures appropriately.

Methods  A systematic literature search was conducted to identify the ten measures most frequently used to assess QoL in diabetes research (including clinical trials) from 1995 to March 2008.

Results  Six thousand and eight‐five abstracts were identified and screened for instrument names. Of the ten instruments most frequently used to assess ‘QoL’, only three actually do so [i.e. the generic World Health Organization Quality of Life (WHOQOL) and the diabetes‐specific Diabetes Quality of Life (DQOL) and Audit of Diabetes‐Dependent Quality of Life (ADDQoL)]. Seven instruments more accurately measure health status [Short‐Form 36 (SF‐36), EuroQoL 5‐Dimension (EQ‐5D)], treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and psychological well‐being [Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Well‐Being Questionnaire (W‐BQ), Problem Areas in Diabetes (PAID)].

Conclusions  No single measure can suit every purpose or application but, when measures are selected inappropriately and data misinterpreted, any conclusions drawn are fundamentally flawed. If we value QoL as a therapeutic goal, we must ensure that the instruments we use are both valid and reliable. QoL assessment has the proven potential to identify ways in which treatments can be tailored to reduce the burden of diabetes. With careful consideration, appropriate measures can be selected and truly robust assessments undertaken successfully.
Distinct conformational changes in activated agonist‐bound and agonist‐free glycine receptor subunits
Authors: Pless Stephan A. , Lynch Joseph W.
Published: January 2009

Ligand binding to Cys‐loop receptors produces either global conformational changes that lead to activation or local conformational changes that do not. We found that the fluorescence of a fluorophore tethered to R271C in the extracellular M2 region of the α1 glycine receptor increases during glycine activation but not during ivermectin activation. This prompted the hypothesis that this signal reports a glycine‐mediated conformational change not essential for activation. We tested this by investigating whether the fluorescence signal depended on whether the fluorophore was attached to a glycine‐free or a glycine‐bound subunit. Agonist‐free subunits were created by incorporating T204A and R65K mutations, which disrupted glycine binding to both (+) and (−) subunit interfaces. In heteromeric receptors comprising wild‐type and R65K,T204A,R271C triple‐mutant subunits, the fluorescence response exhibited a drastically reduced glycine sensitivity relative to the current response. Two conclusions can be drawn from this. First, because the labeled glycine‐free subunits were activated by glycine binding to neighboring wild‐type subunits, our results provide evidence for a cooperative activation mechanism. However, because the fluorescent label on glycine‐free subunits does not reflect movements at the channel gate, we conclude that glycine binding also produces a local non‐concerted conformational change that is not essential for receptor activation.
Phosphatidylinositol 3 kinase–Akt signaling serves as a circadian output in the retina
Authors: Ko Michael L. , Jian Kuihuan , Shi Liheng , Ko Gladys Y.‐P.
Published: January 2009

The daily rhythm of L‐type voltage‐gated calcium channels (L‐VGCCs) is part of the cellular mechanism underlying the circadian regulation of retina physiology and function. However, it is not completely understood how the circadian clock regulates L‐VGCC current amplitudes without affecting channel gating properties. The phosphatidylinositol 3 kinase–protein kinase B (PI3K–Akt) signaling pathway has been implicated in many vital cellular functions especially in trophic factor‐induced ion channel trafficking and membrane insertion. Here, we report that PI3K–Akt signaling participates in the circadian phase‐dependent modulation of L‐VGCCs. We found that there was a circadian regulation of Akt phosphorylation on Thr308 that peaked at night. Inhibition of PI3K or Akt significantly decreased L‐VGCC current amplitudes and the expression of membrane‐bound L‐VGCCα1D subunit only at night but not during the subjective day. Photoreceptors transfected with a dominant negative Ras had significantly less expression of phosphorylated Akt and L‐VGCCα1D subunit compared with non‐transfected photoreceptors. Interestingly, both PI3K–Akt and extracellular signal‐related kinase were downstream of Ras, and they appeared to be parallel and equally important pathways to regulate L‐VGCC rhythms. Inhibition of either pathway abolished the L‐VGCC rhythm indicating that there were multiple mechanisms involved in the circadian regulation of L‐VGCC rhythms in retina photoreceptors.
Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson’s disease by disturbing calcium flux
Authors: Marongiu Roberta , Spencer Brian , Crews Leslie , Adame Anthony , Patrick Christina , Trejo Margarita , Dallapiccola Bruno , Valente Enza Maria , Masliah Eliezer
Published: January 2009

Parkinson’s disease (PD) is characterized by accumulation of α‐synuclein (α‐syn) and degeneration of neuronal populations in cortical and subcortical regions. Mitochondrial dysfunction has been considered a potential unifying factor in the pathogenesis of the disease. Mutations in genes linked to familial forms of PD, including SNCA encoding α‐syn and Pten‐induced putative kinase 1 (PINK1), have been shown to disrupt mitochondrial activity. We investigated the mechanisms through which mutant Pink1 might disrupt mitochondrial function in neuronal cells with α‐syn accumulation. For this purpose, a neuronal cell model of PD was infected with virally‐delivered Pink1, and was analyzed for cell survival, mitochondrial activity and calcium flux. Mitochondrial morphology was analyzed by confocal and electron microscopy. These studies showed that mutant (W437X) but not wildtype Pink1 exacerbated the alterations in mitochondrial function promoted by mutant (A53T) α‐syn. This effect was associated with increased intracellular calcium levels. Co‐expression of both mutant Pink1 and α‐syn led to alterations in mitochondrial structure and neurite outgrowth that were partially ameliorated by treatment with cyclosporine A, and completely restored by treatment with the mitochondrial calcium influx blocker Ruthenium Red, but not with other cellular calcium flux blockers. Our data suggest a role for mitochondrial calcium influx in the mechanisms of mitochondrial and neuronal dysfunction in PD. Moreover, these studies support an important function for Pink1 in regulating mitochondrial activity under stress conditions.
Pre‐synaptic nicotinic and D2receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens
Authors: Grilli Massimo , Zappettini Stefania , Zoli Michele , Marchi Mario
Published: January 2009

The existence of pre‐synaptic auto‐ and hetero receptors which modulate neurotransmitter release is well documented. Emerging evidence show that in some cases these pre‐synaptic receptors may also cross‐talk with each other. The aim of the present work was to investigate whether acetylcholine receptors (nAChRs) and dopamine (DA) autoreceptors, which are both able to modulate DA release, functionally interact on the same nerve endings. We used rat and mouse nucleus accumbens synaptosomes pre‐labeled with [3H]DA and exposed to nicotinic and dopaminergic receptor ligands. Both nicotinic agonists and 4‐aminopyridine (4‐AP) provoked [3H]DA release which was inhibited by quinpirole and blocked by sulpiride and raclopride. Both the inhibitory effect of quinpirole and the stimulatory effect of (−)nicotine did not change when the nAChRs or the DA receptors were desensitized. (−)Nicotine and 4‐AP were able to stimulate [3H]DA overflow also in mouse synaptosomes and this overflow was partially inhibited by quinpirole. In the β2knockout mice quinpirole was still able to inhibit the [3H]DA overflow elicited by 4‐AP. To conclude: in rat and mouse the (−)nicotine evoked‐release can be modulated by D2/D3autoreceptors present on the DA terminals and nAChRs function is independent from D2/D3autoreceptors which themselves may function independently from the activation of nAChRs.
Defining Macropinocytosis
Authors: Kerr Markus C. , Teasdale Rohan D.
Published: January 2009

Macropinocytosis represents a distinct pathway of endocytosis in mammalian cells. This actin‐driven endocytic process is not directly co‐ordinated by the presence of cargo but can be induced upon activation of growth factor signalling pathways. The capacity to dissect the contribution of macropinocytosis to cellular processes has been hampered by a lack of unique molecular markers and defining features. While aspects of macropinosome formation and maturation are common to those shared by the other endocytic pathways, a number of key differences have recently begun to emerge and will be discussed in this study. It is now well established that macropinocytosis significantly contributes to antigen presentation by the immune system and is exploited by a range of pathogens for cellular invasion and avoidance of immune surveillance.
A Novel Strategy for the Invasive Toxin: Hijacking Exosome‐Mediated Intercellular Trafficking
Authors: Zhang Fan , Sun Shan , Feng Du , Zhao Wen‐Long , Sui Sen‐Fang
Published: January 2009

Toxins penetrate mammalian cells through various means. In this study, we report a unique strategy used by trichosanthin (TCS), a plant toxin with ribosome‐inactivating activity, to penetrate host cells. We found that in both JAR and K562 cells, endocytosed TCS is incorporated into intraluminal vesicles of the multivesicular body (MVB) and is then secreted in association with these vesicles upon fusion of the MVB with the plasma membrane. The secreted TCS‐loaded vesicles secreted by K562 cells move throughout the intercellular space and target syngeneic and specific allogeneic cells. Subsequent internalization permits delivery of the toxin into the cytosol, resulting in ribosomal inactivation and cell death. Thus, our findings provide a novel mechanism by which foreign proteins pass between and penetrate into mammalian cells.
Centrosome Function: Sometimes Less Is More
Authors: Rusan Nasser M. , Rogers Gregory C.
Published: January 2009

Tight regulation of centrosome duplication is critical to ensure that centrosome number doubles once and only once per cell cycle. Superimposed onto this centrosome duplication cycle is a functional centrosome cycle in which they alternate between phases of quiescence and robust microtubule (MT) nucleation and MT‐anchoring activities. In vertebrate cycling cells, interphase centrioles accumulate less pericentriolar material (PCM), reducing their MT nucleation capacity. In mitosis, centrosomes mature, accumulating more PCM to increase their nucleation and anchoring capacities to form robust MT asters. Interestingly, functional cycles of centrosomes can be altered to suit the cell’s needs. Some interphase centrosomes function as a microtubule‐organizing center by increasing their ability to anchor MTs to form centrosomal radial arrays. Other interphase centrosomes maintain their MT nucleation capacity but reduce/eliminate their MT‐anchoring capacity. Recent work demonstrates that Drosophila cells take this to the extreme, whereby centrioles lose all detectable PCM during interphase, offering an explanation as to how centrosome‐deficient flies develop to adulthood. Drosophila stem cells further modify the functional cycle by differentially regulating their two centrioles – a situation that seems important for stem cell asymmetric divisions, as misregulation of centrosome duplication in stem/progenitor cells can promote tumor formation. Here, we review recent findings that describe variations in the functional cycle of centrosomes.
Glycosylation Directs Targeting and Activation of Cystatin F from Intracellular and Extracellular Sources
Authors: Colbert Jeff D , Plechanovová Anna , Watts Colin
Published: January 2009

Cystatin F is a cysteine protease inhibitor that is selectively expressed in immune cells and unlike other cystatin family members is targeted to a significant extent to intracellular compartments. Initially made as an inactive glycosylated disulfide‐linked dimer, cystatin F is converted to an active monomer by proteolytic cleavage following transport to the endosomal/lysosomal system. This active form of cystatin F targets cathepsin C/DPPI and probably other cathepsins in immune cells. We show that efficient targeting of cystatin F to the endocytic pathway is dependent not on its unique dimeric conformation but rather on its oligosaccharide chains. We demonstrate the unusual addition of N‐linked sugars to an Asn‐X‐Cys motif in cystatin F and provide evidence that the mannose 6‐phosphate sorting machinery is used to divert cystatin F from the secretory pathway and to mediate its uptake from extracellular pools. These studies identify a function for the oligosaccharides on cystatin F and raise the possibility that cystatin F might regulate proteases in trans by secretion in an inactive form by one cell and subsequent internalization and activation by another cell.