bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurses' attitude towards ‘difficult’ and ‘good’ patients in eight public hospitals
Authors: Khalil Doris D
Published: October 2009

The paper is part of a large‐scale study exploring violence in nursing conducted between 2005 and 2006. There were various objectives for each aspect of the study. Qualitative descriptive survey was selected. The population were all nurses licensed with the South African Nursing Council. Non‐probability sampling technique was utilized to distribute confidential questionnaires to nurses employed in the eight public hospitals during 2006. Good patients were rewarded with tender loving care although difficult patients were ignored or needed interventions deliberately delayed. Because of the severe shortage of qualified staff, nurses had to rationale care in order to meet needs of all their patients. However, nurses found to violate health‐care consumers were counselled, disciplined and/or dismissed.
Nursing prioritization of the patient need for care: A tacit knowledge embedded in the clinical decision‐making literature
Authors: Lake Sarah , Moss Cheryle , Duke Jan
Published: October 2009

Every day in clinical settings, nurses practise in complex and dynamic situations. Nurses work to achieve emergent order in these situations through nursing prioritization of the patient need for care. As direct research on nursing prioritization had not been reported, a study, using critical realism as method, was designed to discern the profession's embedded understanding from within the clinical decision‐making literature. The research synthesizes a tacit knowledge on nursing prioritization of the patient need for care from key international literature (from 1966 to 2003). Nursing prioritization was discerned in both education and practice literatures; interrelationships between these and theoretical approaches were also identified. Nursing prioritization of the patient need for care was revealed both as a non‐sequential decision‐making process throughout unfolding patient situations and as an advanced skill of nursing practice. Increasing confidence with this skill is the hallmark of developing expertise.
Factors strengthening and weakening vaccination competence
Authors: Nikula Anne E , Rapola Satu PT , Hupli Maija I , Leino‐Kilpi Helena T
Published: October 2009

The purpose of this study was to describe factors strengthening and weakening vaccination competence. The data were collected by focus group and individual interviews with 40 participants, consisting of health‐care professionals, students and clients, and were then analysed by content analysis. The results could be classified into four categories: vaccinator professional conduct, education, client conduct and the vaccination environment. Successful client encounters, comprehensive knowledge of vaccinating, adequate education, clients' positive attitude, suitable physical environment and centralization of vaccinations were considered strengthening factors, whereas their opposites weakened vaccination competence. The two most important factors were vaccinator professional conduct and education, and therefore these factors should be considered the most in education, clinical practice and administration. Further research is necessary to determine how well current education, clinical practice and administration support factors strengthening, and help alleviate factors weakening vaccination competence.
Facilitating collaborative development in practice
Authors: Tolson Debbie , Bennett John , Currie Kay , Mohammed Toby A , Middleton Alan R
Published: October 2009

The promotion of stakeholder partnerships features within practice development work and is intuitively appealing, but in reality meaningful partnerships can be problematic. We report the findings of four parallel Nominal group Technique Interviews undertaken with groups of professional (nurses from practice and academia) and lay stakeholder representatives during a seminar event. The group work sought to explore the mechanisms, which could facilitate meaningful practice development partnerships between nurses, academic nurses and people. The most highly ranked suggestions included creating a culture where practice development is seen as everyone's business and establishing a unified collaborative infrastructure. A range of enabling and inhibiting conditions were explored and the complexity of achieving consensus decision‐making processes that would allow realization of the policy rhetoric was exposed.
Initial evaluation of a new safety needle system at a clinical setting in Taiwan
Authors: Feng Tsui‐Hsia , Liu Hsueh‐Erh
Published: October 2009

Needle‐protective devices have been investigated for decades for preventing health‐care workers from infecting blood‐borne pathogens. This initial evaluation of a new safety needle system in a disposable conventional syringe (new safety syringe) in a clinical setting was to see how nurses view its safety, usability and compatibility. A convenient sample of 205 nurses was involved and completed a user evaluation questionnaire. The results showed 163 nurses (88.1%) would use the safety syringes if the hospital provided safety syringes. Over 50% agreed that the new device was able to maintain the sterile principles and was easy to operate. Less than 25% disagreed that the new device ‘does not spend more work time’ and ‘does not affect the standard procedure while changing needle’. Positive attitude towards the new device associated with higher ‘job position’ and more ‘work experience’. Further evaluation of reducing incidence of needle‐stick injuries is required.
Nursing the dying: A descriptive survey of Australian undergraduate nursing curricula
Authors: Johnson Amanda , Chang Esther , O'Brien Louise
Published: October 2009

This paper reports on the results of a descriptive study that explored death and dying education in Australian undergraduate nursing curricula conducted as phase one of a two‐phase, longitudinal mixed‐method study. A descriptive study using survey method was selected. Thirty‐nine Deans of Nursing (or their equivalent position title) were invited to participate. The study setting involved university schools of nursing (or equivalent title) in the six states and two territories of Australia. A mailed survey was self‐administered by participants. Descriptive statistics were used to generate a description of the current curricula practices used by Australian undergraduate nursing programmes to provide death and dying education. A response rate of 76% (n = 26) was achieved. The results show death and dying education has a minimal and inconsistent presence in Australian undergraduate nursing programmes. The main conclusions include: (i) little evidence exists of significant change to the provision of death and dying education in undergraduate nursing curricula since the 1960s; (ii) the conceptualization of death and dying education in Australian undergraduate nursing curricula is poorly designed and underdeveloped; (iii) what constitutes the ‘best’ death and dying education experiences remains unclear with little evidence to support decision‐making; and (iv) reform of undergraduate nursing curricula is required to enhance graduate preparation to deliver contemporary practice especially in the area of caring for dying patients and their families.
Registered nurse incentives to return to practice in the United States
Authors: Langan Joanne C , Tadych Rita A , Kao Chia‐Chan , Israel Heidi
Published: October 2009

This US study uniquely listened to registered nurses with current licenses who do not work as nurses or are unemployed. An electronic survey was advertised in 13 Boards of Nursing newsletters. Investigated was why nurses left nursing, what would entice them to return to nursing, and what skill review is essential to competent and confident return to nursing practice. Herzberg's theory was used to study factors affecting registered nurses' decision to practise nursing. Data were analysed using SPSS and manifest content analysis. Nurses (n = 127) identified various work conditions as the primary reasons for leaving nursing. Work condition improvement, recognition of one's work, opportunities for professional growth and family needs consideration were identified as key enticing factors for returning to nursing. Many respondents identified needing review of medicines, intravenous skills, new technologies and a refresher course. Acting on their voiced concerns will enhance nurse recruitment and retention.
Aragonite and omphacite‐bearing metapelite from Besshi region, Sambagawa belt in central Shikoku, Japan and its implication
Authors: Kouketsu Yui , Enami Masaki
Published: October 2009

Aragonite and omphacite‐bearing metapelite occurs in the albite–biotite zone of the Togu (Tohgu) area, Besshi region, Sambagawa metamorphic belt, central Shikoku, Japan. This metapelite consists of alternating graphite‐rich and graphite‐poor layers that contain garnet, phengite, chlorite, epidote, titanite, calcite, albite, and quartz. A graphite‐poor layer contains a 1.5‐cm ivory‐colored lens that mainly consists of phengite, calcite, albite, and garnet. Aragonite, omphacite, and paragonite occur as inclusions in the garnet of the ivory lens. The aragonite has a composition that is close to the CaCO3 end‐member: the FeCO3 and MnCO3 components are both less than 0.3 mol% and the SrCO3 component is about 1 mol%. The aragonite + omphacite + quartz assemblage in garnet indicates equilibrium conditions of P > 1.1–1.3 GPa and T = 430–550°C. Quartz grains sealed in garnet of the aragonite and omphacite‐bearing sample and other metapelites in the Togu area preserve a high residual pressure that is equivalent to the Sambagawa eclogite samples. These facts suggest that: (i) the Togu area experienced eclogite facies metamorphism; and (ii) thus, eclogite facies metamorphism covered the Sambagawa belt more extensively than previously recognized.
ORIGINAL ARTICLE: Lack of association between elevated mean red cell volume and haematological toxicity in patients receiving long‐term methotrexate for rheumatoid arthritis
Authors: White D. H. N. , Chapman P. T. , O'Donnell J. L. , James J. , Frampton C. , Stamp L. K.
Published: October 2009

Aims: It has been suggested that elevated mean red cell volume (MCV) may be a predictor of haematological toxicity in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). We wished to identify whether there was an association between MCV, red cell folate and haematological toxicity in patients on MTX monotherapy for the long‐term management of RA.

Methods: Evidence of haematological toxicity was sought by note review of patients recruited in a cross‐sectional study of MTX monotherapy in RA. Retrospective data included MCVs from before MTX initiation and after 3 and 6 months of treatment. Data were collected prospectively every 6 months for up to 2 years after enrolment. Any record of cytopenia or the development of haematological malignancy was recorded from commencement of MTX until the present day. Red cell folate concentrations were tested on enrolment to the study.

Results: A total of 165 patients was included, 74.5% female, median disease duration 7 years (range 3 months–57 years). The median duration of MTX treatment was 74.9 months (range 10–241 months) giving 1030.2 patient‐years of MTX exposure. Twenty‐four patients (14.5%) had a MCV > 98 fL on study entry. Evidence of haematological abnormality was found in six patients (3.6%); chronic lymphocytic leukaemia (1), persistent lymphocytosis (1), persistent monocytosis (1) and neutropenia (3). There was no association between red cell folate or MCV and haematological toxicity.

Conclusion: Neutropenia and pancytopenia are rare side‐effects of MTX therapy in this cohort. Elevated MCV or low mean red cell folate does not appear to be associated with haematological malignancy or toxicity in this cohort of patients on long‐term MTX therapy.
Prevalence of hepatitis B virus infection in non‐Hodgkin lymphoma: a systematic review and meta‐analysis
Authors: Nath A. , Agarwal R. , Malhotra P. , Varma S.
Published: October 2009

Background and aim: A recent meta‐analysis has demonstrated an association between hepatitis C virus and non‐Hodgkin lymphoma (NHL). There is also evidence on the association between hepatitis B virus (HBV) and NHL. The aim of this study was to evaluate this evidence using a meta‐analytic approach.

Methods: We searched the MEDLINE database from 1962 to 2008 for case–control studies that have reported the association of HBV with NHL. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the prevalence of HBV infection and pooled the results using three different statistical models.

Results: Our search yielded 12 studies with 11 studies (3262 NHL patients, 1 523 205 controls) evaluating HBV infection in NHL and one study (3888 HBV‐infected individuals, 205 203 controls) that had investigated for NHL in HBV infection. The OR of detecting HBV infection in NHL when compared with the control population was 2.56 (95% CI, 2.24–2.92) by the fixed effects model; 2.61 (95% CI, 2.29–2.98) by the exact method and 2.67 (95% CI, 2.04–3.49) by the random effects model suggesting a high prevalence of HBV carrier state in lymphoma. There was evidence of statistical heterogeneity which disappeared after exclusion of retrospective studies on sensitivity analysis.

Conclusions: The results of this study suggest a possible causal relation between HBV infection and NHL which needs to be confirmed by experimental and epidemiological studies. In countries where prevalence of HBV infection is 1% or more, it may be prudent to screen patients with NHL for occult HBV infection.
Prognostic value of trisomy 8 in primary myelodysplastic syndrome
Authors: Ma Y. , Wang X. , Xu X. , Lin G.
Published: October 2009

Background:  According to the International Prognostic Scoring System (IPSS), sole +8 is categorized as intermediate cytogenetic subgroup. But as some myelodysplastic syndrome (MDS) patients with +8 perhaps progress quickly to acute leukaemia and have shorter survival, some reports have suggested that +8 should be categorized into poor risk cytogenetic group. The aim of this study was to clarify the prognostic role of +8 in MDS patients by comparing patients with normal karyotype, 20q‐ and ‐7/7q‐.

Methods:  The consecutive samples of 435 MDS patients in Shanghai were collected by prospective methods and diagnosed according to World Health Organization classification. Cytogenetic analysis was performed using conventional G‐banding karyotyping and fluorescence in situ hybridization techniques. Prognosis was estimated by univariate Log‐rank method and multivariate Cox proportional hazard models.

Results:  Of 424 cases completing the cytogenetic analysis, 71 (16.7%) had +8, including 38 patients with sole +8 (9.0%). No significant difference in median survival was observed between patients with sole +8 and that with +8 and one of other abnormalities. The +8 clone size was not linked to survival. The median survival of patients with +8, normal karyotype and complex karyotype was 25 months, 38.1 months and 5.9 months respectively. However, no significant difference was observed between patients with 20q‐ (21.4 months) and ‐7/7q‐ (25.8 months). Trisomy 8 was an independent prognostic factor by Cox regression model.

Conclusion:  There is no significant difference in prognosis between patients with +8 and patients with 20q‐ or ‐7/7q‐. Trisomy 8, 20q‐ and ‐7/7q‐ are categorized as intermediate cytogenetic risk according to our primary study.
What is the role of invasive versus non‐invasive coronary angiography in the investigation of patients suspected to have coronary heart disease?
Authors: Chow C. K. , Sheth T.
Published: October 2009

The improved technology of multi‐slice cardiac CT angiography (CTA) has enabled production of high quality images of the coronary arteries. The sensitivity and specificity of the test in identifying patients with obstructive coronary lesions in 64‐slice and later generations of scanners is high. To enable effective use of CTA in the clinical setting, a better understanding of this technology, particularly in comparison to invasive coronary angiography, is needed. In this article we discuss the characteristics of CTA in comparison to invasive coronary angiography and discuss the role of CTA in the diagnosis of coronary artery disease (CAD). Newer CTA scanners and individualized scanning protocols can minimize radiation exposure from CTA. CTA can provide more information than invasive coronary angiography on the type and burden of atherosclerotic plaque in the coronary tree. CTA is most useful in those at intermediate risk of CAD.
A survey of Australian clinical registries: can quality of care be measured?
Authors: Evans S. M. , Bohensky M. , Cameron P. A. , McNeil J.
Published: October 2009

Background:  Clinical quality registries gather and analyse information to monitor and enhance the quality of care received by patients. The aim of the present study was to determine the attributes of Australian clinical registries to identify their capacity to accurately assess quality of care.

Methods:  A survey was distributed to registry custodians managing multi‐site clinical outcome registries. They were asked to self‐report on general aspects of registries, including coverage, length of operation, data collection process, data management, quality of data and registry governance structures.

Results:  A total of 28 registries were identified and all provided responses to the survey. The majority of the registries require modifications to their procedures in order to provide useful and reliable information for quality improvement purposes. Thirteen registries (46%) did not assess or recruited fewer than 80% of the eligible population and 23 (82%) did not formally audit reliability of coding at the clinical level. Five (18%) did not collect the information required for basic risk adjustment of outcome measures. While most registries produced reports for providers and interested parties, the approach to disseminating this information was highly variable.

Conclusion:  Clinical registries provide the most credible information about quality of care. However, most key registries in Australia require some adaptation of procedures in order to accomplish this task. Funding should be provided to enable registries to make the necessary changes.
Obstructive sleep apnoea – an update
Authors: Chan A. S. L. , Phillips C. L. , Cistulli P. A.
Published: October 2009

Obstructive sleep apnoea (OSA) is a common disorder characterized by the repetitive complete or partial collapse of the upper airway during sleep. It results in intermittent hypoxaemia and hypercapnia, cortical arousals and surges of sympathetic activity. The occurrence of OSA has also been linked to serious long‐term adverse health consequences; such as hypertension, metabolic dysfunction, cardiovascular disease, neurocognitive deficits and motor vehicle accidents. There have been several advances in the field of particular clinical importance: (i) the development of portable monitoring as part of a simplified clinical algorithm for the diagnosis of OSA in selected patients; (ii) growing awareness of the cardio‐metabolic health consequences of OSA and (iii) emerging evidence to support a range of non‐continuous positive airway pressure (CPAP) treatment modalities, such as oral appliances.
Numerical discrimination in newborn infants as revealed by event‐related potentials to tone sequences
Authors: Ruusuvirta Timo , Huotilainen Minna , Fellman Vineta , Näätänen Risto
Published: October 2009

Humans are able to attentively discriminate number from 6 months of age. However, the age of the emergence of this ability at the pre‐attentive stage of processing remains unclear. Event‐related potentials (ERPs) were recorded in newborn human infants aged from 3 to 5 days. At 500‐ms intervals, the infants were passively exposed to 200‐ms sequences of four tones. Each tone could be either 1000 or 1500 Hz in frequency. In most sequences (standards), the ratio of the tones of one frequency to those of the other frequency in a sequence was 2 : 2. In the remaining sequences (deviants, P = 0.1), this ratio was either 3 : 1 or 4 : 0. The mismatch response of ERPs could not be found for 3 : 1 deviants, but it was a robust finding for 4 : 0 deviants, showing the neurophysiological ability of the infants to register the larger deviant–standard difference. The findings suggest very early sensitivity to auditory numerical information in infancy.
IQ‐ArfGEF/BRAG1 is associated with synaptic ribbons in the mouse retina
Authors: Katsumata Osamu , Ohara Naoki , Tamaki Hideaki , Niimura Tomoko , Naganuma Hideaki , Watanabe Masahiko , Sakagami Hiroyuki
Published: October 2009

IQ‐ArfGEF/BRAG1 is a guanine nucleotide exchange factor for ADP ribosylation factors (Arfs), which are implicated in membrane trafficking and actin cytoskeleton dynamics. In this study, we examined the immunohistochemical localization of IQ‐ArfGEF/BRAG1 in the adult mouse retina using light and electron microscopy. IQ‐ArfGEF/BRAG1 was distributed in a punctate manner and colocalized well with RIBEYE in both the outer and inner plexiform layers. Immunoelectron microscopic analysis showed that IQ‐ArfGEF/BRAG1 was localized at the synaptic ribbons of photoreceptors. When heterologously expressed in HeLa cells, IQ‐ArfGEF/BRAG1 was recruited to RIBEYE‐containing clusters and formed an immunoprecipitable complex with RIBEYE. Furthermore, immunoprecipitation analysis showed that anti‐IQ‐ArfGEF/BRAG1 antibody efficiently pulled down RIBEYE from retinal lysates. These findings indicate that IQ‐ArfGEF/BRAG1 is a novel component of retinal synaptic ribbons and forms a protein complex with RIBEYE.
Fear conditioning enhances spontaneous AMPA receptor‐mediated synaptic transmission in mouse hippocampal CA1 area
Authors: Zhou Ming , Conboy Lisa , Sandi Carmen , Joëls Marian , Krugers Harm J.
Published: October 2009

AMPA receptor‐mediated synaptic modifications in the amygdala have been reported to sustain cued fear conditioning. However, the hippocampal formation is also critically involved in fear learning. Therefore, we examined whether fear conditioning is also accompanied by changes in AMPA receptor‐mediated synaptic transmission in the hippocampus. We focused on spontaneous miniature excitatory post‐synaptic currents (mEPSCs). Young adult mice were trained using tone/footshock pairings and contextual/cued memories were tested 3–4 h and 1 day later. We found that the mEPSC frequency was significantly enhanced when recorded 3 h, but not 24 h, after fear conditioning training. Fear training induced a slight enhancement in the mEPSC amplitude at 3 h after training. The increased mEPSC frequency and amplitude were absent in animals that were only exposed to footshock or novelty or unpaired tone/footshock training. This implies that learning the association between context, tone and footshock transiently enhances hippocampal CA1 spontaneous synaptic transmission, which may contribute to the encoding of the fearful event.
Hypocretin /orexin contributes to the expression of some but not all forms of stress and arousal
Authors: Furlong Teri M. , Vianna Daniel M. L. , Liu Lu , Carrive Pascal
Published: October 2009

Hypocretin/orexin has a well‐established role in wakefulness and in the maintenance of arousal. Because stress is associated with arousal, it has been proposed that hypocretin is also involved in stress. However, it is not clear if this is true for all forms of stress. To clarify this issue, we compared four conditions combining high arousal with no or low stress (wakefulness and exploration) or high stress (contextual fear and restraint) in the rat. We looked at Fos expression in hypocretin neurons, hypocretin‐1 levels in cerebrospinal fluid and cardiovascular and behavioural changes after pharmacological blockade with the dual hypocretin receptor antagonist, almorexant. Fos expression in hypocretin neurons was highest with wakefulness and exploration, also high with fear but not significant with restraint. Hypocretin‐1 levels were consistent with this pattern, although the differences were not as marked. Hypocretin receptor blockade with almorexant reduced the pressor, tachycardic and locomotor responses of wakefulness and exploration as well as the pressor and sympathetic component of the tachycardic response of fear. In contrast, almorexant did not reduce the pressor and tachycardic responses of restraint and nor did it reduce the pressor, tachycardic and locomotor responses of another stressor, i.e. cold exposure. Thus, hypocretin is not involved in all forms of stress. Comparison of the different conditions suggests that, regardless of stress, hypocretin involvement occurs when the arousal associated with the response includes increased attention to environmental cues. When it does, hypocretin will at least contribute to the cardiovascular response. The findings are of clinical relevance to some forms of psychological stress.
Intrinsic activity and positive feedback in motor circuits in organotypic spinal cord slice cultures
Authors: Magloire Vincent , Streit Jürg
Published: October 2009

In co‐cultures of embryonic rat spinal cord slices and skeletal muscle, spinal motoneurons innervate muscle fibres and drive muscle contractions. However, multi‐electrode array (MEA) recordings show that muscle contractions often appear in the absence of population activity in the spinal cord networks. Such uncorrelated muscle activity persists when the population bursts in the neuronal networks are prevented by un‐coupling the network with the glutamatergic antagonists CNQX and d‐APV. By contrast, the uncorrelated muscle activity is fully suppressed by the muscular nicotinic antagonist d‐tubocurarine. Together, these findings confirm the previous finding that motoneurons drive muscle fibres in this preparation and suggest that they are intrinsically spiking in the absence of synaptic input. Intracellular recordings from spinal neurons support this suggestion. Analysing the correlated muscle activity, we found that in 15% of the population bursts, muscle activity appears at the beginning or before neuronal activity, suggesting that in these cases motoneurons initiate the population activity. Both the total number of population bursts and the percentage of such bursts that are initiated by muscle activity are reduced by a block of nicotinic receptors. Uncorrelated muscle and neuronal activity is reduced by the gap junction blocker carbenoxolone, suggesting that electrical coupling is involved in the generation of this activity. Together, these findings suggest that intrinsic firing of motoneurons may contribute to the activation of population bursts through cholinergic positive feedback loops in cultured spinal networks.
Balancing needs and means: the dilemma of the β‐cell in the modern world
Authors: Leibowitz G. , Kaiser N. , Cerasi E.
Published: October 2009

The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of β‐cell function coexists. This is demonstrated by the fact that near‐physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin‐deficient type 1 diabetics. The normal β‐cell adapts well to the demands of insulin resistance. Also in hyperglycaemic states some degree of adaptation does exist and helps limit the severity of disease. We demonstrate here that the mammalian target of rapamycin (mTOR) system might play an important role in this adaptation, because blocking mTORC1 (complex 1) by rapamycin in the nutritional diabetes model Psammomys obesus caused severe impairment of β‐cell function, increased β‐cell apoptosis and progression of diabetes. On the other hand, under exposure to high glucose and FFA (gluco‐lipotoxicity), blocking mTORC1 in vitro reduced endoplasmic reticulum (ER) stress and β‐cell death. Thus, according to the conditions of stress, mTOR may have beneficial or deleterious effects on the β‐cell. β‐Cell function in man can be reduced without T2DM/impaired glucose tolerance (IGT). Prospective studies have shown subjects with reduced insulin response to present, several decades later, an increased incidence of IGT/T2DM. From these and other studies we conclude that T2DM develops on the grounds of β‐cells whose adaptation capacity to increased nutrient intake and/or insulin resistance is in the lower end of the normal variation. Inborn and acquired factors that limit β‐cell function are diabetogenic only in a nutritional/metabolic environment that requires high functional capabilities from the β‐cell.
Cell–cell interactions in the endocrine pancreas
Authors: Jain R. , Lammert E.
Published: October 2009

Cell–cell communication within any given tissue is an important aspect of correct organ function. The islets of Langerhans forming the endocrine pancreas are composed of α‐, β‐, δ‐, ε‐ and PP‐cells, and interactions between these cells are required for fine‐tuning glucose homeostasis of the body. The endocrine cells communicate through homotypic or heterotypic cell‐cell adhesion, or in a paracrine fashion, and this communication is involved in the regulated secretion of islet hormones. This review discusses how islet hormones, secreted molecules and ions influence the endocrine cells and how cell adhesion molecules such as neural cell adhesion molecule, cadherins, connexin‐36, Eph receptors and ephrin ligands, as well as extracellular matrix proteins, modulate pancreatic islet function.
The roles of telomeres and telomerase in β‐cell regeneration
Authors: Liew C. W. , Holman A. , Kulkarni R. N.
Published: October 2009

Telomerase is a specialized reverse transcriptase that is responsible for extending and preserving the end of the chromosomes (telomeres). Telomerase plays a key role in regulating the lifespan of mammalian cells and is involved in critical aspects of cellular ageing processes. In this review, we will briefly summarize our current understanding of the functions of telomeres, telomerase and their regulation. Considering that compensatory islet hyperplasia and β‐cell regeneration play important roles in the prevention and/or delay of the onset of overt diabetes, we will also examine current literature regarding the effects of diabetes on telomere shortening and provide insights from our own studies on the role of telomerase in β‐cell regeneration.
Adult human β‐cell neogenesis?
Authors: Demeterco C. , Hao E. , Lee S.‐H. , Itkin‐Ansari P. , Levine F.
Published: October 2009

Prospects for inducing endogenous β‐cell regeneration in the pancreas, one of the most attractive approaches to reverse type 1 and type 2 diabetes, have gained substantially from recent evidence that cells in the adult pancreas exhibit more plasticity than previously recognized. There are two major pathways to β‐cell regeneration, β‐cell replication and β‐cell neogenesis. Substantial evidence for a role for both processes exists in different models. While β‐cell replication clearly occurs during development and early in life, the potential for replication appears to decline substantially with age. In contrast, we have demonstrated that the exocrine compartment of the adult human pancreas contains a facultative stem cell that can differentiate into β‐cells under specific circumstances. We have favoured the idea that, similar to models described in liver regeneration, β‐cell mass can be increased either by neogenesis or replication, depending on the intensity of different stimuli or stressors. Understanding the nature of endocrine stem/progenitor cells and the mechanism by which external stimuli mobilize them to exhibit endocrine differentiation is central for success in therapeutic approaches to induce meaningful endogenous β‐cell neogenesis.
β‐Cells at the crossroads: choosing between insulin granule production and proliferation
Authors: Liu Yanmei , Mziaut Hassan , Ivanova Anna , Solimena Michele
Published: October 2009

Pancreatic β‐cells are the sole source of insulin, the major hormonal regulator of glycaemia. In physiological and pathological conditions with increased insulin demand, β‐cells adjust their insulin output either through increased insulin secretory granule (ISG) biogenesis and secretion, or hyperplasia. Failure of these compensatory mechanisms eventually results in hyperglycaemia and diabetes mellitus. Both of these major adaptive behaviours are positively regulated by several extrinsic factors, such as glucose, GLP‐1, insulin and growth hormones (GH). Still unclear, however, it is how β‐cells in response to these stimuli opt for one or the other strategy at a given time. Here we review recent advances concerning the factors and pathways that enhance ISG biogenesis and β‐cell replication, and propose the existence of ‘switch factors' that play a key role in regulating the shift between these two adaptive responses.
Zinc, a regulator of islet function and glucose homeostasis
Authors: Wijesekara N. , Chimienti F. , Wheeler M. B.
Published: October 2009

It is well known that zinc is required in pancreatic β‐cells in the process of insulin biosynthesis and the maturation of insulin secretory granules. In fact, the zinc level in pancreatic islets is amongst the highest in the body and reduction in its levels in the pancreas has been associated with diabetes. High concentrations of zinc can also be toxic because of enhanced oxidative damage. The link between zinc, diabetes and islet dysfunction has recently been reiterated by genomewide association studies that identified an islet cell membrane zinc transporter, SLC30A8 (ZnT8), as one of the risk loci for type 2 diabetes. Here we explore the importance of both zinc and ZnT8 to islet biology and whole body glucose homeostasis.
Islet protein profiling
Authors: Bergsten P.
Published: October 2009

Islet protein profiling is defined as generation of extended protein expression data sets from islets or islet cells. Islets from rodent control and animal models of type 1 and type 2 diabetes mellitus and healthy humans and insulin‐ and glucagon‐producing cell lines have been used. Protein profiling entails separation, differential expression determination, identification and expression analysis. Protein/peptide separation is either gel‐based or by chromatography. Differential expression is based on comparison of visualized spots/proteins between gels or by sample labelling in gel‐free systems. Identification of proteins is made by tryptic fragmentation of proteins, fragment mass determination and mass comparison with protein databases. Analysis of expression data sets interprets the complex protein changes into cellular mechanisms to generate hypotheses. The importance of such protein expression sets to elucidate islet cellular events is evidenced by the observation that only about 50% of the differentially expressed proteins and transcripts showed concordance when measured in parallel. Using protein profiling, different areas related to islet dysfunction in type 1 and type 2 diabetes mellitus have been addressed, including dysfunction induced by elevated levels of glucose and fatty acids and cytokines. Because islets from individuals with type 1 or type 2 diabetes mellitus have not yet been protein profiled, islets from rat (BB‐DP) and mouse (NOD,ob/ob, MKR) models of the disease have been used, and mechanisms responsible for islet dysfunction delineated offering avenues of intervention.
Glucose regulation of islet stress responses and β‐cell failure in type 2 diabetes
Authors: Jonas J. C. , Bensellam M. , Duprez J. , Elouil H. , Guiot Y. , Pascal S. M. A.
Published: October 2009

Pancreatic β‐cells exposed to high glucose concentrations display altered gene expression, function, survival and growth that may contribute to the slow deterioration of the functional β‐cell mass in type 2 diabetes. These glucotoxic alterations may result from various types of stress imposed by the hyperglycaemic environment, including oxidative stress, endoplasmic reticulum stress, cytokine‐induced apoptosis and hypoxia. The glucose regulation of oxidative stress‐response and integrated stress‐response genes in cultured rat islets follows an asymmetric V‐shaped profile parallel to that of β‐cell apoptosis, with a large increase at low glucose and a moderate increase at high vs. intermediate glucose concentrations. These observations suggest that both types of stress could play a role in the alteration of the functional β‐cell mass under states of prolonged hypoglycaemia and hyperglycaemia. In addition, β‐cell demise under glucotoxic conditions may also result from β‐cell hypoxia and, in vivo, from their exposure to inflammatory cytokines released locally by non‐endocrine islet cells. A better understanding of the relative contribution of each type of stress to β‐cell glucotoxicity and of their pathophysiological cause in vivo may lead to new therapeutic strategies to prevent the slow deterioration of the functional β‐cell mass in glucose intolerant and type 2 diabetic patients.
Towards better understanding of the contributions of overwork and glucotoxicity to the β‐cell inadequacy of type 2 diabetes
Authors: Weir G. C. , Marselli L. , Marchetti P. , Katsuta H. , Jung M. H. , Bonner‐Weir S.
Published: October 2009

Type 2 diabetes (T2D) is characterized by reduction of β‐cell mass and dysfunctional insulin secretion. Understanding β‐cell phenotype changes as T2D progresses should help explain these abnormalities. The normal phenotype should differ from the state of overwork when β‐cells compensate for insulin resistance to keep glucose levels normal. When only mild hyperglycaemia develops, β‐cells are subjected to glucotoxicity. As hyperglycaemia becomes more severe, so does glucotoxicity. β‐Cells in all four of these situations should have separate phenotypes. When assessing phenotype with gene expression, isolated islets have artefacts resulting from the trauma of isolation and hypoxia of islet cores. An advantage comes from laser capture microdissection (LCM), which obtains β‐cell‐rich tissue from pancreatic frozen sections. Valuable data can be obtained from animal models, but the real goal is human β‐cells. Our experience with LCM and gene arrays on frozen pancreatic sections from cadaver donors with T2D and controls is described. Although valuable data was obtained, we predict that the approach of taking fresh samples at the time of surgery is an even greater opportunity to markedly advance our understanding of how β‐cell phenotype evolves as T2D develops and progresses.
Genetic and biochemical pathways of β‐cell failure in type 2 diabetes
Authors: Talchai C. , Lin H. V. , Kitamura T. , Accili D.
Published: October 2009

We review mechanisms of β‐cell failure in type 2 diabetes. A wealth of information indicates that it is caused by impaired insulin secretion and decreased β‐cell mass. Interestingly, there appears to be a link between these two mechanisms. The earliest reaction to peripheral insulin resistance is an increase in insulin production, owing primarily to increased secretion, and to a lesser extent to decreased clearance. Experimental animal models indicate that hyperinsulinaemia promotes an increase in β‐cell mass, largely via increased β‐cell replication. In contrast, following the onset of overt diabetes, there is a slowly progressive loss of β‐cell function and mass, both in animal models and in diabetic humans. It is of great interest that most diabetes‐associated genes identified in genome‐wide association studies appear to be enriched in the β‐cell and to have the potential to regulate mass and/or function. Here, we review evidence derived from experimental animal models to unravel the mechanisms underlying β‐cell dysfunction. We focus primarily on signalling pathways, as opposed to nutrient sensing, and specifically on the notion that insulin and growth factor signalling via Foxo1 in pancreatic β‐cells links insulin secretion with cellular proliferation and survival.
Role and therapeutic potential of microRNAs in diabetes
Authors: Kolfschoten I. G. M. , Roggli E. , Nesca V. , Regazzi R.
Published: October 2009

The discovery in mammalian cells of hundreds of small RNA molecules, called microRNAs, with the potential to modulate the expression of the majority of the protein‐coding genes has revolutionized many areas of biomedical research, including the diabetes field. MicroRNAs function as translational repressors and are emerging as key regulators of most, if not all, physiological processes. Moreover, alterations in the level or function of microRNAs are associated with an increasing number of diseases. Here, we describe the mechanisms governing the biogenesis and activities of microRNAs. We present evidence for the involvement of microRNAs in diabetes mellitus, by outlining the contribution of these small RNA molecules in the control of pancreatic β‐cell functions and by reviewing recent studies reporting changes in microRNA expression in tissues isolated from diabetes animal models. MicroRNAs hold great potential as therapeutic targets. We describe the strategies developed for the delivery of molecules mimicking or blocking the function of these tiny regulators of gene expression in living animals. In addition, because changes in serum microRNA profiles have been shown to occur in association with different human diseases, we also discuss the potential use of microRNAs as blood biomarkers for prevention and management of diabetes.
Bariatric surgery: unstressing or boosting the β‐cell?
Authors: Mingrone G. , Castagneto M.
Published: October 2009

Bariatric surgery is the most effective therapy for severe obesity in terms of reduction of morbidity and mortality and quality of life improvement. Different bariatric procedures distinctly differ with regard to their effectiveness to reduce body weight and to improve morbidities, such as type 2 diabetes. In this regard, the most effective procedures are bilio‐pancreatic diversion (BPD) and duodenal switch procedure curing 98.9% of the diabetes patients, followed by Roux‐en‐Y gastric bypass (RYGB) with 83.7% success rate, by gastroplasty with 71.6% and by gastric banding with 47.9%. Interestingly, a net improvement up to resolution of type 2 diabetes has been consistently reported few days after RYGB and BPD. RYGB promotes incretin secretion which, in turn, stimulates insulin secretion while insulin sensitivity is slightly improved. Rarely, the long‐term effect of incretin hypersecretion might result in hypertrophy and hyperplasia of the islets of Langerhans, otherwise known as nesidioblastosis, associated with hyperinsulinaemia and severe postprandial hypoglycaemia. In contrast, BDP improves insulin resistance to a greater extent and results, in the long run, in supra‐normal values of insulin sensitivity with subsequent reduction of insulin secretion. The mechanism allowing diabetes resolution after surgical intestinal manipulation is extremely interesting but only partially understood.
Peripheral arterial disease in diabetes—a review
Authors: Jude E. B. , Eleftheriadou I. , Tentolouris N.
Published: October 2009

Diabet. Med. 27, 4–14 (2010)

Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle‐brachial pressure index (ABI) has emerged as the relatively simple, non‐invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low‐grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non‐diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD.
Variable Selection for Panel Count Data via Non‐Concave Penalized Estimating Function
Authors: TONG XINGWEI , HE XIN , SUN LIUQUAN , SUN JIANGUO
Published: October 2009

Abstract. Variable selection is an important issue in all regression analyses, and in this paper we discuss this in the context of regression analysis of panel count data. Panel count data often occur in long‐term studies that concern occurrence rate of a recurrent event, and their analysis has recently attracted a great deal of attention. However, there does not seem to exist any established approach for variable selection with respect to panel count data. For the problem, we adopt the idea behind the non‐concave penalized likelihood approach and develop a non‐concave penalized estimating function approach. The proposed methodology selects variables and estimates regression coefficients simultaneously, and an algorithm is presented for this process. We show that the proposed procedure performs as well as the oracle procedure in that it yields the estimates as if the correct submodel were known. Simulation studies are conducted for assessing the performance of the proposed approach and suggest that it works well for practical situations. An illustrative example from a cancer study is provided.
Citizenship, Volunteering and Active Ageing
Authors: Lie Mabel , Baines Susan , Wheelock Jane
Published: October 2009

Many voluntary organizations depend greatly on the unpaid services of older volunteers, a significant number of whom are women. At the same time, shifts in welfare policy have been towards emphasizing individual economic autonomy and self‐provisioning, often to the detriment of older, more vulnerable members of society. Using data from an organization working for and with older people in the North‐East of England and through in‐depth qualitative interviews, our study found that volunteering is an expression of citizenship for older people. In our analysis, we identify two strands in the meanings of citizenship for older people: volunteering as leisure and work, and volunteering as care and civic consciousness. These correspond with liberal conceptualizations of citizenship and republican models of citizenship. Data from our in‐depth interviews demonstrate a strong commitment to society and fellow citizens among older people that counterbalances individualistic and instrumental reasons for volunteering promoted by the state and market. Our findings suggest that government views of volunteering as a route to paid work, as a panacea for society and therefore needing to be more ‘work‐like’, are discordant with the perspectives of older volunteers. Rather than the neo‐liberal views of the ‘citizen‐worker’ or ‘citizen‐consumer’, citizenship that is based on the ‘common good’ and feminist perspectives of ‘caring citizenship’ are arguably more beneficial to society. Finally, we describe the pressures and constraints facing older people that could discourage formal volunteering in the future.