bluuebunny/crossref_metadata_2025 huggingface dataset:
A literature review of children’s and young people’s participation in decisions relating to health care
Authors: Moore Lucie , Kirk Susan
Published: September 2010

Aims and objectives.  To review and critique the research literature on children’s and young people’s participation in health care decision‐making, to highlight gaps in the research and to identify implications for nursing practice.

Background.  Children have a right to participate in decisions about their lives. The recognition of this, along with greater acknowledgement of children’s capabilities, has led to an increasing awareness that children’s views must be given value in both national policy and individual decisions. Health professionals have also been given explicit direction to ensure that children are actively involved in decision‐making.

Design.  Literature review.

Method.  Search of electronic databases and manual searching of journals and reference lists between 1990–2009.

Results.  Children want to be involved in discussions about their care but it is unclear to what extent this happens in practice. The research conducted has interpreted participation in different ways. Studies have compared decisions of differing importance in terms of risk and many have a wide age range in their samples, including children who are arguably too young for meaningful participation. However, this heterogeneity is often overlooked in the reporting of studies. Aspects of practice which can help or hinder participation are identified but there is little evidence on the outcome benefits of participation. In addition, there has been an over‐reliance on interviews as the method of data collection.

Conclusions.  Research using a combination of observation and interviewing would provide more in‐depth knowledge about participation in practice. In addition, studies should consider decisions of similar consequence and children at an age when participation is appropriate.

Relevance to clinical practice.  The need for health professionals to ensure children are protected is undisputed but should not prevent children’s rights to participate from being enacted. Practitioners, therefore, need further guidance on how to facilitate the participation of children.
Coping strategies, social support and responsibility in chemical intolerance
Authors: Nordin Maria , Andersson Linus , Nordin Steven
Published: September 2010

Aims and objectives.  To study coping strategies, social support and responsibility for improvement in chemical intolerance (CI).

Background.  Limited knowledge of CI among health professionals and lay persons places demands on the chemically intolerant individual’s coping strategies and perception of social support and ability to take responsibility for improvement. However, there is sparse literature on these issues in CI.

Design.  A cross‐sectional, questionnaire‐based, quasi‐experimental study.

Method.  Fifty‐nine persons with mild, 92 with moderate and 31 with severe CI participated by rating (i) usage and effectiveness of six problem‐ and six emotion‐focused coping strategies, (ii) emotional, instrumental and informative support provided by various sources and (iii) society’s and the inflicted individual’s responsibility for improvement.

Results.  The participants reported that the most commonly used and effective coping strategies were avoiding odorous/pungent environments and asking persons to limit their use of odorous/pungent substances (problem‐focused strategies) as well as accepting the situation and reprioritising (emotion‐focused strategies). High intolerance severity was associated with problem‐focused coping strategies and relatively low intolerance with emotion‐focused strategies. More emotional than instrumental and informative support was perceived, predominantly from the partner and other family members. Responsibility attributed to society was also found to increase from mild to moderate/severe intolerance.

Conclusions.  Certain coping strategies are more commonly used and perceived as more effective than others in CI. However, intolerance severity plays a role regarding both coping strategies and responsibility. Emotional support appears to be the most available type of support.

Relevance to clinical practice.  For improved care, certain coping strategies may be suggested by nurses, the healthcare system needs to provide better social support to these patients and the issue of responsibility for improvement may be discussed with the patient.
Managing pain in children: where to from here?
Authors: Twycross Alison
Published: September 2010

Aims and objectives.  The aims of this study are to review research published in the past 15 years to provide insight into the factors impacting on the management of pain in children and identify strategies that can be used to improve pain management practices.

Background.  The evidence to guide nurses’ pain management practices is readily available, in the form of clinical guidelines. However, children’s nurses’ pain management practices continue to fall short of the ideal with children experiencing moderate to severe unrelieved pain. Several factors have been suggested as providing an explanation for this. There is a need to explore the impact each of these factors have on pain management practices further. With this in mind, a literature review was undertaken.

Design.  Literature review.

Methods.  A computerised literature search was carried out using CINAHL, Medline and the British Nursing Index. The search terms used were as follows: pain, pain assessment, pain management, education, quality and nurses. Articles published in the last 15 years were included in the review.

Results.  Several themes emerged from this review of the literature as possible explanations for why children’s pain is still not managed effectively. These include knowledge deficits; incorrect or outdated beliefs about pain and pain management; the decision‐making strategies used and organisational culture.

Conclusions.  Improving pain management requires a multifactorial approach encompassing: education, institutional support, attitude shifts and change leaders. Issues that need addressing include education, decision‐making strategies and organisational practices. Further research needs to be carried out to determine other factors that impact on pain management practices.

Relevance to clinical practice.  Despite the evidence to guide practice being readily available children continue to experience unrelieved pain. The strategies identified in this article may help to ensure that pain is relieved effectively.
Mapping the pinhole formation pathway of S21
Authors: Pang Ting , Park Taehyun , Young Ry
Published: September 2010

Phage holins are small, lethal membrane proteins of two general types: canonical holins, like λ S105, which oligomerizes and forms large membrane holes of unprecedented size; and pinholins, like S2168 of lambdoid phage 21, which forms homo‐heptameric channels, or pinholes, with a lumen of < 2 nm. Pinholes depolarize the membrane, leading to activation of secreted endolysins and murein degradation. S2168 has two transmembrane domains, TMD1 and TMD2. TMD2 alone lines the pinhole, making heterotypic interactions involving two surfaces, A and B. Mutational analysis on S2168 suggested that S2168 initially forms inactive dimer, with TMD1 inhibiting TMD2 both in cis and trans. When TMD1 exits the membrane to the periplasm, it liberates TMD2 to participate in the pathway to pinhole formation. In this study, further mutational analysis suggests a refined pinhole formation pathway, with the existence of at least two intermediate states. We propose that the pathway begins in the activated dimer state, with a homotypic TMD2 interface involving the A surface. Evidence is presented for a further oligomeric state involving a heterotypic A:B interaction. Moreover, the data suggest that a glycine‐zipper motif present in the A interface of TMD2 is involved in every stage downstream of the inactive dimer.
Experimental test of a trade‐off between moult and immune response in house sparrowsPasser domesticus
Authors: MORENO‐RUEDA G.
Published: September 2010

A trade‐off between immune system and moulting is predicted in birds, given that both functions compete for resources. However, it is unclear whether such a trade‐off exists during post‐breeding moult. This study tests such a trade‐off in the house sparrow (Passer domesticus). Males injected with an antigen (lipopolysaccharide) significantly moulted slower than sham‐injected males. Moreover, males whose seventh primaries were plucked to simulate moult showed smaller immune response to phytohaemagglutinin than control males, in which seventh primaries were clipped. A trade‐off between moult speed and body mass was also found. The results show a clear trade‐off between moult and immune response in the house sparrow: immune response negatively affected moult and moult negatively affected immune response. These findings suggest that only individuals in good condition may have an efficient moult and simultaneously respond effectively in terms of immunity to pathogens, which could explain how plumage traits honestly indicate parasite resistance in birds.
Detection of HHV‐8 (human herpesvirus‐8) genomes in induced peripheral blood mononuclear cells (PBMCs) from US blood donors
Authors: Qu L. , Triulzi D. J. , Rowe D. T. , Jenkins F. J.
Published: September 2010

Background  Human herpesvirus‐8 (HHV‐8) causes Kaposi’s sarcoma and can be detected and induced in peripheral blood mononuclear cells (PBMCs) from infected individuals. The prevalence of viral genomes in induced/cultured PBMCs from healthy blood donors has not been systematically studied.

Materials and Methods  PBMCs from 164 donors were purified and stored as two equal aliquots in liquid nitrogen. One aliquot was used for CD19+ B‐cell purification with a fraction reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in culture media containing n‐butyrate and tetradecanoyl phorbol acetate. DNA was extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs harvested at days 2 and 4 of culture. A sensitive real‐time PCR with a DNA equivalent of 3 × 105 cells per reaction was run in duplicate for all samples along with a quantitative HHV‐8 DNA standard ranging from 1·6 to 200 copies.

Results  For all 164 donors, HHV‐8 genomes were not detected in the DNA equivalent of 3–6 × 105 of PBMCs and induced/cultured PBMCs with a real‐time PCR assay (95% CI: 0–3·5/164). HHV‐8 DNA was not detected from DNA equivalent of 1·5 (0·5–5·6) × 105 CD19+ B cells from 139/164 donors. HHV‐8 antibodies were detected in 7 of the 164 donors (4·3%).

Conclusions  HHV‐8 genomes were not detected from PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level of detectable HHV‐8 genomes in blood donors seems to be extremely low, if they exist.
White pines,Ribes, and blister rust: a review and synthesis
Authors: Geils Brian W. , Hummer Kim E. , Hunt Richard S.
Published: September 2010

For over a century, white pine blister rust (Cronartium ribicola) has linked white pines (Strobus) with currants and gooseberries (Ribes) in a complex and serious disease epidemic in Asia, Europe, and North America. Because of ongoing changes in climate, societal demands for forests and their amenities, and scientific advances in genetics and proteomics, our current understanding and management of the white pine blister rust pathosystem has become outdated. Here, we present a review and synthesis of international scope on the biology and management of blister rust, white pines,Ribes, and other hosts. In this article, we provide a geographical and historical background, describe the taxonomy and life cycle of the rust, discuss pathology and ecology, and introduce a series of invited papers. These review articles summarize the literature on white pines,Ribes, and blister rust with respect to their status, threats, and management through genetics and silviculture. Although the principal focus is on North America, the different epidemics in Europe and Asia are also described. In the final article, we discuss several of the key observations and conclusions from the preceding review articles and identify prudent actions for research and management of white pine blister rust.
Blister rust and western forest biodiversity: ecology, values and outlook for white pines
Authors: Tomback D. F. , Achuff P.
Published: September 2010

Eight white pine species are widely distributed among the forests of western Canada and the United States. The different forest communities with these species contribute biodiversity to the western landscape. The trees themselves provide various ecosystem services, including wildlife habitat and watershed protection. White pine communities range in elevation from lower to upper treeline, in successional stage from seral to climax, and in stand type from krummholz to closed‐canopy forest. Many white pine species are moderately to strongly fire‐dependent for regeneration; several species are extreme stress tolerators and persistent on harsh sites. Among the white pines are the oldest‐living trees, the world’s largest pines, species dependent on birds for seed dispersal, species important for grizzly bear habitat and species of high commercial timber value. The principal threats to white pine populations are blister rust (Cronartium ribicola, pathogen), fire suppression, succession, mountain pine beetle and climate change. Severe population declines in several white pine species are attributed to losses caused by these factors acting either alone or together, and sometimes in concert with logging and other land‐use changes. The importance and particular interactions of these threats vary by region and species. For example, many northern and western populations of whitebark pine are seriously declining from a combination of mountain pine beetle outbreaks and severe blister rust infestations. As whitebark pines provide many keystone services on high‐elevation sites, their loss would impact forest composition and structure, succession, biodiversity, and ecosystem services. Although there are serious challenges to science‐based management and conservation (especially in remote American wilderness areas), prompt and effective intervention promoting regeneration of blister rust‐resistant white pines could mitigate these severe impacts.
Horticulture of Ribes
Authors: Hummer K. E. , Dale A.
Published: September 2010

The genus Ribes L., known as currants and gooseberries, contains more than 150 diverse species indigenous throughout the northern hemisphere and along the Rocky Mountain, Sierra Nevada and Sierra Madres in North America through mountain ranges of Central America to the Andes in South America. Beginning in the 1400s, four main crop types, black currants (Ribes, subgenus: Ribes, section: Botrycarpum), red and white currants (Ribes, subgenus: Ribes, section: Ribes) and gooseberries (Ribes, subgenus: Grossularia) were domesticated from European species. American and Eurasian species were selected and combined into the germplasm base of European and American breeding programmes in the 1900s. Black currants (R. nigrum and hybrids) are a major economic crop in many European countries but are minor in North America, although they can be produced successfully in the northern states and southern portion of the Canadian provinces. Ribes plants can be hosts for white pine blister rust, caused by Cronartium ribicola. This disease was introduced from Asia through Europe into North America ca. 1900. Restrictions were imposed on currants and gooseberries in the United States when the rust was observed on this continent. Although some states have recently repealed these restrictions, by 2009, 12 states continue to have 40‐year‐old laws prohibiting or restricting Ribes cultivation. The purpose of this paper is to describe the cultivation of currants and gooseberries and their interaction with rust. Ribes production has a potentially great economic value in American, niche markets that could help sustain small‐acreage, berry farmers.
A review of genetic approaches to the management of blister rust in white pines
Authors: King J. N. , David A. , Noshad D. , Smith J.
Published: September 2010

Since introduced a century ago,Cronartium ribicolahas devastated many populations of North American white pines. However, significant genetic resistance to white pine blister rust occurs naturally and can be exploited. In this review, we discuss the progress and different approaches to breeding for resistance in North American white pines. Three broad categories of resistance are: (1) ontogenetic resistance, (2) R‐gene resistance and (3) partial resistance. Ontogenetic resistance is associated with increased host age and indicated by higher susceptibility to infection in primary needles and young seedlings then in grafts and older trees. R‐gene resistance (major gene resistance) is an example of the classic gene‐for‐gene system common in many rust diseases. R‐gene resistance provides immunity but may not be durable. Host resistance and the corresponding rust virulence which defeats it are well described for sugar pine and western white pine. Host plants with partial resistance are able to retard or tolerate disease development without eliminating the pathogen. Partial resistance is also called slow‐rusting resistance or low‐level resistance and is revealed in seedlings by several responses, including slow‐canker‐growth, difficult‐to‐infect, needle‐shed and bark‐reaction. Most of these seedling responses are presumed to be multigenic; but needle‐shed may be controlled by recessive genes. Long‐term, field trials for verification of screening and selection results are sparse. Although 100% higher survival of selected material over unselected occurs in some trials, mortality is high under conditions of high hazard and heavy inoculum load. In several, long‐term trials, some full‐sib crosses expressed a strong phenotypic resistance that indicates specific combining ability between complimentary parents. These and other observations suggest that we might yet find strong and durable resistance. Study of Eurasian white pines infected by blister rust fungi could help us better understand endemic pathosystems. Different strategies are identified for deploying material selected for either R‐gene or partial resistance. Current research suggests that resistance is more complex than previously modelled, but new molecular techniques offer useful methods for investigating the white pine blister rust pathosystem.
White pine blister rust in Korea, Japan and other Asian regions: comparisons and implications for North America
Authors: Kim M.‐S. , Klopfenstein N. B. , Ota Y. , Lee S. K. , Woo K.‐S. , Kaneko S.
Published: September 2010

This article briefly reviews the history of white pine blister rust, attributed to Cronartium ribicola, and addresses current research and management issues in South Korea, Japan and other regions of eastern Asia (China, Russia and Himalaya). For each region, the distribution, damage, aecial hosts, telial hosts and management of C. ribicola and other blister rust fungi on native and introduced white pines are summarized. In addition, blister rust behaviours in eastern Asia and North America are compared; and the potential evolutionary and management implications are discussed.
Selected Metabolic and Hormonal Profiles during Maintenance of Spontaneous Ovarian Cysts in Dairy Cows
Authors: Probo M , Comin A , Cairoli F , Faustini M , Kindahl H , De Amicis I , Veronesi MC
Published: September 2010

Contents

Information is lacking regarding the relationship between metabolic and hormonal profiles and the maintenance of spontaneous ovarian cyst disease in dairy cows. For this reason, the concentrations of non‐esterified fatty acids (NEFA), insulin‐like growth factor I (IGF‐I) and cortisol (C) were investigated during the spontaneous course of ovarian cyst disease in dairy cows (n = 6) between the 7th and 16th weeks post‐partum (PP). The control group consisted of normally cycling cows (n = 6). Blood samples were collected twice a day, and plasma was analysed using different techniques. Progesterone and 15‐ketodihydro‐PGF2α plasma profiles were investigated to confirm the ovulatory or anovulatory conditions of the cows. Cortisol plasma levels were not significantly different among sampling times within each group or between the two groups. NEFA plasma levels were significantly higher in cycling cows compared to cystic cows at the 16th week PP (p < 0.01), but with rather low values, indicating by now sparse mobilization of fat stores. Insulin‐like growth factor I plasma concentrations were higher in cystic cows during the 8th, 10th, 11th (p < 0.01) and 16th week PP (p < 0.05), indicating that the presence of ovarian cysts coincides with increased IGF‐I levels. These results suggest no influence of cortisol and NEFA levels in cysts maintenance, while a possible involvement of IGF‐I can be suspected not only in the pathogenesis, as already known, but also in the maintenance of spontaneous cystic ovarian disease in cattle.
Randomized trial comparing pulse calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism in haemodialysis patients
Authors: KIATTISUNTHORN KRAIWIPORN , WUTYAM KITTIKARN , INDRANOI ARTIT , VASUVATTAKUL SOMKIAT
Published: September 2010

Aim:  Calcitriol and alfacalcidol are used extensively for the treatment of secondary hyperparathyroidism. Unfortunately, there is limited published data comparing the efficacy and tolerability of both active vitamin D sterols. This study was undertaken to determine whether calcitriol provides a therapeutic advantage to alfacalcidol.

Methods:  This was a randomized, active controlled study. Patients with intact parathyroid hormone (iPTH) >32 pmol/L were randomized to receive orally calcitriol or alfacalcidol after each haemodialysis for up to 24 weeks. Reduction of PTH, changes of plasma albumin‐corrected calcium and phosphorus were analysed. The initial dose of alfacalcidol was twice that of calcitriol.

Results:  Sixteen patients were randomized into each group. At baseline, plasma albumin‐corrected calcium, phosphorus and PTH were no different between groups. At 24 weeks, PTH changes were −50.8 ± 31.8% and −49.4 ± 32.5% from the baseline in the calcitriol and alfacalcidol groups, respectively (P = 0.91). The patients who achieved target PTH of 16–32 pmol/L were 82% in the calcitriol and 67% in the alfacalcidol group (P = 0.44). Plasma albumin‐corrected calcium and phosphorus were not significantly different but showed trends toward gradually increasing from baseline in both groups (calcium, 6.0 ± 7.2% vs 10.9 ± 6.5% (P = 0.10); phosphorus, 13.0 ± 29.4% vs 16.7 ± 57.2% (P = 0.83) in calcitriol and alfacalcidol, respectively). The mean dose of calcitriol and alfacalcidol were 4.1 and 6.9 µg/week, respectively (P < 0.0001).

Conclusion:  Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5–2.0 times that of calcitriol. The two drugs are equally efficacious and lead to similar changes in calcium and phosphorus.
When Curiosity Breeds Intimacy: Taking Advantage of Intimacy Opportunities and Transforming Boring Conversations
Authors: Kashdan Todd B. , McKnight Patrick E. , Fincham Frank D. , Rose Paul
Published: September 2010

Curious people seek knowledge and new experiences. In 3 studies, we examined whether, when, and how curiosity contributes to positive social outcomes between unacquainted strangers. Study 1 (98 college students) showed that curious people expect to generate closeness during intimate conversations but not during small talk; less curious people anticipated poor outcomes in both situations. We hypothesized that curious people underestimate their ability to bond with unacquainted strangers during mundane conversations. Studies 2 (90 college students) and 3 (106 college students) showed that curious people felt close to partners during intimate and small‐talk conversations; less curious people only felt close when the situation offered relationship‐building exercises. Surprise at the pleasure felt during this novel, uncertain situation partially mediated the benefits linked to curiosity. We found evidence of slight asymmetry between self and partner reactions. Results could not be attributed to physical attraction or positive affect. Collectively, results suggest that positive social interactions benefit from an open and curious mind‐set.
Deterrence and Incapacitation Effects in a Closed Area: A Case Study of Auto Theft in Taiwan
Authors: Tao Hung‐Lin , Kuo Ling‐Chih
Published: September 2010

Deterrence and incapacitation effects of auto theft are estimated with a full consideration of substitution effects across crime types and across districts in a closed area in which none of the effects will leak out. It is found that the increase in the cleared rate of auto theft crime in a certain district and in other districts strongly deters the auto theft in that district, indicating that the across‐district deterrence effect dominates the across‐district substitution effect. The across‐crime deterrence effect significantly exceeds the across‐crime substitution effect for close crime (general theft), but is insignificant for distant crime (violence).
The origin and evolution of lignin biosynthesis
Authors: Weng Jing‐Ke , Chapple Clint
Published: September 2010

Lignin, a phenolic polymer derived mainly from hydroxycinnamyl alcohols, is ubiquitously present in tracheophytes. The development of lignin biosynthesis has been considered to be one of the key factors that allowed land plants to flourish in terrestrial ecosystems. Lignin provides structural rigidity for tracheophytes to stand upright, and strengthens the cell wall of their water‐conducting tracheary elements to withstand the negative pressure generated during transpiration. In this review, we discuss a number of aspects regarding the origin and evolution of lignin biosynthesis during land plant evolution, including the establishment of its monomer biosynthetic scaffold, potential precursors to the lignin polymer, as well as the emergence of the polymerization machinery and regulatory system. The accumulated knowledge on the topic, as summarized here, provides us with an evolutionary view on how this complex metabolic system emerged and developed.

Contents

Summary
273

I.
Introduction
273

II.
Emergence of the monolignol biosynthetic scaffold
274

III.
Occurrence and elaboration of lignification in tracheophytes
280

IV.
Concluding remarks
282

Acknowledgements
282

References
282
Fire and the spread of flowering plants in the Cretaceous
Authors: Bond William J. , Scott Andrew C.
Published: September 2010

Commentary p913
Application of Deep Hole Drilling to the Measurement and Analysis of Residual Stresses in Steel Shrink‐Fitted Assemblies
Authors: Hosseinzadeh F. , Mahmoudi A. H. , Truman C. E. , Smith D. J.
Published: September 2010

Abstract:  Residual stress measurement of shrink‐fitted assemblies was achieved through finite element simulations and experiments using the deep hole drilling technique. Shrink‐fitted assemblies using stainless steel and cast iron were manufactured and residual stresses measured using a combination of deep hole and centre hole drilling. The results from the finite element simulations demonstrated that modifications to the deep hole drilling method were required to account for plastic relaxation during the measurement process. This was verified through the experimental measurements. The results from both the stainless steel and cast iron assemblies provided a clear demonstration that the final residual stress state was a consequence of the machining and assembly of the components.
Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons
Authors: Wyrembek Paulina , Lebida Katarzyna , Mercik Katarzyna , Szczuraszek Katarzyna , Szczot Marcin , Pollastro Federica , Appendino Giovanni , Mozrzymas Jerzy W
Published: September 2010

Background and purpose:  Oenanthotoxin (OETX), a polyacetylenic alcohol from plants of the genus Oenanthe, has recently been identified as potent inhibitor of GABA‐evoked currents. However, the effects of OETX on the inhibitory postsynaptic currents (IPSCs), as well as the pharmacological mechanism(s) underlying its effects on GABAA receptors, remain unknown. The purpose of this study was to elucidate the mechanism underlying the inhibition of GABAergic currents by OETX.

Experimental approach:  Effects of OETX on GABAergic currents were studied using the patch clamp technique on rat cultured hippocampal neurons. Miniature IPSCs (mIPSCs) were recorded in the whole‐cell configuration, while the current responses were elicited by ultrafast GABA applications onto the excised patches.

Key results:  OETX potently inhibited both mIPSCs and current responses, but its effect was much stronger on synaptic currents. Analysis of the effects of OETX on mIPSCs and evoked currents disclosed a complex mechanism: allosteric modulation of both GABAA receptor binding and gating properties and a non‐competitive, probably open channel block mechanism. In particular, OETX reduced the binding rate and nearly abolished receptor desensitization. A combination of rapid clearance of synaptic GABA and OETX‐induced slowing of binding kinetics is proposed to underlie the potent action of OETX on mIPSCs.

Conclusions and implications:  OETX shows a complex blocking mechanism of GABAA receptors, and the impact of this toxin is more potent on mIPSCs than on currents evoked by exogenous GABA. Such effects on GABAergic currents are compatible with the convulsions and epileptic‐like activity reported for OETX.
Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS‐1E beta‐cells
Authors: Øzbay LA , Smidt K , Mortensen DM , Carstens J , Jørgensen KA , Rungby J
Published: September 2010

BACKGROUND AND PURPOSEIntroducing the calcineurin inhibitors cyclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) decrease survival rates.

EXPERIMENTAL APPROACHWe sought, in a beta‐cell culture model, to elucidate the pathogenic mechanisms behind NODAT and the relative contribution of the calcineurin inhibitors. INS‐1E cells were incubated at basal and stimulatory glucose concentrations, while exposed to pharmacologically relevant doses of CsA, Tac and vehicle for 6 or 24 h.

RESULTSTac inhibited basal (P< 0.05), but not glucose‐stimulated insulin secretion (GSIS) after 6 h of exposure. After 24 h, both agents inhibited basal and GSIS (P< 0.05). Calcineurin phosphatase activity was decreased by both drugs during all conditions. Apoptosis was only seen with CsA treatment, which also induced a slight suppression of calcineurin and insulin mRNA, as well as increased levels of the sterol receptor element binding protein (SREBP)‐1c, a transcription factor thought to suppress genes essential for beta‐cell function and induce insulin resistance. Expression levels of nuclear factor of activated T‐cells (NFAT)‐c1, ‐c2, ‐c3 and ‐c4 were not decreased notably by either drug.

CONCLUSIONS AND IMPLICATIONSTac had acute inhibitory effects on basal insulin secretion, but prolonged exposure (24 h) to Tac or CsA revealed similar suppression of insulin secretion. These prolonged effects were mirrored by a total inhibition of calcineurin activity in beta‐cells. CsA showed greater inhibition of beta‐cell survival and transcriptional markers, essential for beta‐cell function.
Transabdominal cervical cerclage
Authors: UMSTAD Mark P. , QUINN Michael A. , ADES Alex
Published: September 2010

Background:  Transabdominal cervical cerclage has been performed via laparotomy for over four decades. A laparoscopic approach has recently been developed and offers the potential for lower morbidity.

Aims:  The experience of one operator with transabdominal cervical cerclage via laparotomy is reviewed to establish a baseline with which to compare results from the laparoscopic approach.

Methods:  Transabdominal cervical cerclage was performed with Mersilene tape. The pregnancy outcome prior to transabdominal cervical cerclage was compared with the outcomes after its insertion.

Results:  Prior to transabdominal cervical cerclage, there were 58 pregnancies of which 18 ended with a first trimester pregnancy loss. Twenty‐eight of the 36 pregnancies delivering between 13‐ and 26‐week gestation resulted in a pregnancy loss. Three of the four children delivered after 26‐week gestation survived. Following transabdominal cervical cerclage, there were no first trimester pregnancy losses. Of the 23 pregnancies after transabdominal cerclage, one was terminated at 18‐week gestation for spina bifida and the remaining 22 babies were delivered at a mean gestation of 36.2 weeks. Maternal morbidity was limited to a single wound infection. Respiratory distress was the only significant neonatal morbidity with all babies recovering completely.

Conclusions:  Transabdominal cervical cerclage via laparotomy is a safe and successful method of treating women who need a cervical cerclage but are unable to have a vaginal suture. A baseline has been established with which to compare the results from laparoscopic transabdominal cervical cerclage in the future.
Silicon Nitride for High‐Temperature Applications
Authors: Klemm Hagen
Published: September 2010

In this paper, a summary of the development of high‐temperature silicon nitride (T>1200°C) is provided. The high‐temperature capacity of various advanced commercial silicon nitrides and materials under development was analyzed in comparison with a silicon nitride without sintering additives produced by hot isostatic pressing. Based on this model Si3N4composed of only crystalline Si3N4grains and amorphous silica in the grain boundaries the influence of various sintering additive systems will be evaluated with focus on the high‐temperature potential of the resulting materials. The specific design of the amorphous grain‐boundary films is the key factor determining the properties at elevated temperatures. Advanced Si3N4with Lu2O3or Sc2O3as sintering additive are characterized by a superior elevated temperature resistance caused by effective crystallization of the grain‐boundary phase. Nearly clean amorphous films between the Si3N4grains comparable to that of Si3N4without sintering additives were found to be the reason of this behavior. Benefit in the long‐term stability of Si3N4at elevated temperatures was observed in composites with SiC and MoSi2caused by a modified oxidation mechanism. The insufficient corrosion stability in hot gas environments at elevated temperatures was found to be the main problem of Si3N4for application in advanced gas turbines. Progress has been achieved in the development of potential material systems for environmental barrier coatings (EBC) for Si3N4; however, the long‐term stability of the whole system EBC‐base Si3N4has to be subject of comprehensive future studies. Besides the superior high‐temperature properties, the whole application process from cost‐effective industrial production, reliability and failure probability, industrial handling up to specific conditions during the application have to be focused in order to bring advanced Si3N4currently available to industrial application.
Intragraft immunological events associated with EBV DNAemia in liver transplant patients
Authors: LOGINOV RAISA , HALME LEENA , AROLA JOHANNA , HÖCKERSTEDT KRISTER , LAUTENSCHLAGER IRMELI
Published: September 2010

Loginov R, Halme L, Arola J, Höckerstedt K, Lautenschlager I. Intragraft immunological events associated with EBV DNAemia in liver transplant patients. APMIS 2010; 118: 888–94.

Epstein–Barr virus (EBV) may cause post‐transplant lymphoproliferative disorder, but most EBV infections after liver transplantation (Ltx) are clinically silent reactivations. In this study, we investigated the intragraft immunological events associated with EBV DNAemia. Altogether, 105 adult Ltx patients were monitored for EBV DNAemia. Fourteen (13%) patients developed EBV DNAemia during the first year after transplantation. Liver biopsies obtained associated with EBV DNAemia, without evidence of other herpes or hepatitis viruses or rejection, were available from five patients. The numbers of lymphocytes positive for B‐cell marker (CD20), T‐cell markers (CD3, CD4 and CD8) and IL‐2R, adhesion molecules (ICAM‐1, VCAM‐1 and ELAM‐1) and their ligands [lymphocyte function‐associated antigen‐1 (LFA‐1), very late antigen (VLA‐4) and Sialyl Lewis X (sLeX)] were demonstrated in liver biopsies by immunohistochemistry, and zero‐biopsies from donor livers were used as controls. EBV DNAemia was associated with increased number of CD20‐positive (22 ± 30, p = 0.09) and significantly increased numbers of CD3 (80 ± 16, p = 0.001)‐, CD4 (23 ± 8, p = 0.009)‐ and CD8 (38 ± 8, p = 0.001)‐positive lymphocytes in the graft. ICAM‐1, but not VCAM‐1 or ELAM‐1, was strongly expressed and the number of LFA‐1‐positive cells was significantly increased (48 ± 10, p = 0.0002). Low‐level EBV DNAemia was associated with B‐ and especially T‐cell infiltration of the graft, as well as an increase in ICAM‐1 and the number of LFA‐1‐positive cells. However, EBV DNAemia or these immunological events did not have any effect on the liver transplant.
Molecular and functional aspects of the hairless (hr) gene in laboratory rodents and humans
Authors: Panteleyev A. A. , Paus R. , Ahmad W. , Sundberg J. P. , Christiano A. M.
Published: September 2010

For many years, hairless and rhino mouse mutants have provided a useful and extensively exploited model for studying different aspects of skin physiology, including skin aging, pharmacokinetic evaluation of drug activity and cutaneous absorption, skin carcinogenesis, and skin toxicology. Interestingly, however, hairless and rhino mice have rarely been studied for their primary cellular defect ‐ hairlessness ‐ and thus, the hairless gene itself and its physiological functions have been largely overlooked for decades. The recent identification of the human homolog of the hairless gene on human Chromosome 8p12 confirmed the clinical significance of the phenomenon of “hairlessness” in humans, which was predicted on the basis of similarities between hairless mice and a congenital hair disorder characterized by atrichia with papules. Mutations in the hairless gene of mice provide instructive models for further studies ofhrgene function, and may facilitate insights into the pathophysiology of different human disorders associated with the disruption ofhrgene activity. We provide an overview of current data on the structure and expression patterns of thehrgene, and of mutations at the hairless locus in mice and humans, including the genetic basis of different alleles, the pathology of hairlessness, reproductive and immunological defects, and susceptibility to dioxin toxicity. On the basis of our current understanding of hairlessness, we speculate on the putative functions of thehrgene product in skin physiology, and particularly, in hair follicle biology.
In vivo control of B‐cell survival and antigen‐specific B‐cell responses
Authors: Chan Tyani D. , Gardam Sandra , Gatto Dominique , Turner Vivian M. , Silke John , Brink Robert
Published: September 2010

Summary:  Targeted modification of the mouse genome provides the capability to manipulate complex physiological processes in a precise and controlled manner. Investigation of B‐lymphocyte biology has benefited not only from the targeted modification of genes controlling B‐cell survival and responsiveness, but also from the manipulation of antigen specificity made possible by targeting endogenous immunoglobulin loci. In this review, we discuss recent results obtained from our laboratory using gene‐targeted mouse models to investigate the in vivo regulation of B‐cell survival and responsiveness. The control of BAFF‐dependent survival signals by the TRAF2‐ and TRAF3‐signaling proteins is discussed as is the potential involvement of these molecules in B‐lineage malignancies. We also outline the development and use of the SWHEL model for analyzing antigen‐specific B‐cell responses in vivo. This includes insights into the control of early decision‐making during T‐dependent B‐cell differentiation, the affinity maturation and plasma cell differentiation of germinal center B cells, and the identification of EBI2 as a key regulator of B‐cell migration and differentiation.
B‐cell targeted therapies in human autoimmune diseases: an updated perspective
Authors: Townsend Michael J. , Monroe John G. , Chan Andrew C.
Published: September 2010

Summary:  The advent of therapies that specifically target the B‐lymphocyte lineage in human disease has rejuvenated interest in the mechanistic biology by which B cells mediate autoimmunity. B cells have a multitude of effector functions including production of self‐reactive antibodies, ability to present antigen to T lymphocytes in the context of costimulation, involvement in generation and maintenance of neo‐organogenesis at sites of disease, and opposing function through production of both immunostimulatory and immunomodulatory cytokines. In this review, we first discuss the role of B cells in driving autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and Sjögren’s syndrome, and discuss how studies in these diseases have revealed differentially important roles for the multiple B‐cell effector functions. These data reveal the complex and interrelated roles of B cells working in concert with other components of the innate and adaptive immune system to drive pathogenesis. We then focus on data from mouse and human in which B cells in the setting of disease have been targeted with drugs directed against CD20, CD22, and the BAFF (B‐cell activating factor belonging to the tumor necrosis factor family)/APRIL (a proliferation inducing ligand) pathways. Pre‐clinical studies in animal models in addition to and clinical trials targeting B cells have added further to the understanding of the differential roles B cells play in disease both through demonstration of clinical efficacy in the context of B‐cell depletion or modulation, and also by failure of B‐cell targeting in some diseases and disease patient subgroups. Moving forward, it will be imperative to apply these lessons to new interventional trials to ensure better targeting of the B‐cell lineage and concomitantly better selection of patients most likely to benefit from these therapies.
COMPARATIVE MAGNETIC RESONANCE IMAGING FINDINGS BETWEEN GLIOMAS AND PRESUMED CEREBROVASCULAR ACCIDENTS IN DOGS
Authors: CERVERA VICENTE , MAI WILFRIED , VITE CHARLES H. , JOHNSON VICTORIA , DAYRELL‐HART BETSY , SEILER GABRIELA S.
Published: September 2010

Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge‐shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10–47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0–12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (κ=0.48, P<0.01).
Identification of carbonic anhydrase 9 as a contributor to pingyangmycin‐induced drug resistance in human tongue cancer cells
Authors: Zheng Guopei , Zhou Min , Ou Xinrong , Peng Bo , Yu Yanhui , Kong Fangren , Ouyang Yongmei , He Zhimin
Published: September 2010

Drug resistance is the major obstacle to successful cancer treatment. To understand the mechanisms responsible for drug resistance in tongue cancer, Tca8113 cells derived from moderately differentiated human tongue squamous cell carcinoma were exposed to stepwise escalated concentrations of pingyangmycin (PYM) to develop the resistant cell line called Tca8113/PYM, which showed over 18.78‐fold increased resistance to PYM as compared with Tca8113 cells, and cross‐resistance to cisplatin, pirarubicin, paclitaxel, adriamycin, and mitomycin. We found that the resistance was not associated with multidrug resistance transporter 1 (p170, p‐gp), multidrug resistance‐associated protein 1 and breast cancer resistance protein overexpression, so we hypothesized that Tca8113/PYM cells must have some other resistance mechanism selected by PYM. To test this hypothesis, the global gene expression profiles between Tca8113 and Tca8113/PYM cells were compared by cDNA microarray. Eighty‐nine genes and thirteen expressed sequence tags with differential expression levels between the two cell lines were identified. Some differential expression levels were validated with real‐time PCR and western blot. Furthermore, the functional validation showed that both carbonic anhydrase (CA) inhibitor acetazolamide application and CA9 silencing with CA9 antisense oligonucleotides contribute to the medium pH increase of Tca8113/PYM cells and enhanced PYM chemosensitivity. Moreover, both acetazolamide and CA9 antisense oligonucleotides significantly increased PYM‐induced caspase 3 activation in Tca8113/PYM cells. Thus, our study suggests that the resistance of Tca8113/PYM cells is probably associated with CA9 and other differential expression molecules, and that CA9 may be an important marker for prediction of PYM responsiveness in tongue cancer chemotherapy.
A comparison of three rotary systems and hand instrumentation technique for the elimination of Enterococcus faecalis from the root canal
Authors: Gorduysus Melahat , Nagas Emre , Torun Ozgur Yildirim , Gorduysus Omer
Published: September 2010

The aim of this study was to compare the in vitro reduction of a bacterial population in a root canal by mechanical instrumentation using three rotary systems and hand instrumentation technique. The root canals contaminated with a suspension of Enterococcus faecalis were instrumented using ProTaper, K3, HeroShaper and K‐file hand instrumentation technique. Later the root canals were sampled. After serial dilutions, samples were incubated in culture media for 24 h. Bacterial colonies were counted and the results were given as number of colony‐forming units per millilitre. The results showed that all the canal instrumentation systems reduced the number of bacterial cells in the root canals. Statistically, ProTaper instruments were more effective in reducing the number of bacteria than the other rotary files or hand instruments.