bluuebunny/crossref_metadata_2025 huggingface dataset:
Semiquantitative assessment of the microdistribution of fluorescence‐labeled monoclonal antibody in small peritoneal disseminations of ovarian cancer
Authors: Kosaka Nobuyuki , Ogawa Mikako , Paik David S. , Paik Chang H. , Choyke Peter L. , Kobayashi Hisataka
Published: October 2009

(Cancer Sci 2010; 101: 820–825)

Uniform antibody microdistribution throughout tumor nodules is crucial for antibody‐targeted therapy, because non‐uniform microdistribution leads to suboptimal therapeutic effect, a commonly observed limitation of therapeutic antibodies. Herein, we evaluated the microdistribution of different doses of intraperitoneally injected fluorescence‐labeled full‐antibody trastuzumab (15, 50, and 150 μg) and its Fab fragment (trastuzumab‐Fab: 15 and 50 μg) in a mouse model of ovarian cancer with peritoneal disseminated tumor. A semiquantitative approach (central/peripheral accumulation ratio; C/P ratio) was developed using in situ fluorescence microscopy. Furthermore, we compared the microdistribution of intact trastuzumab with a mixed injection of trastuzumab and trastuzumab‐Fab or serial injections of trastuzumab using in situ multicolor fluorescence microscopy. Fluorescence images after the administration of 15 or 50 μg trastuzumab and 15 μg trastuzumab‐Fab demonstrated antibody accumulation in the tumor periphery, whereas administration of 150 μg trastuzumab and 50 μg trastuzumab‐Fab showed relatively uniform accumulation throughout the tumor nodule. Using serial injections (19‐h interval) of trastuzumab‐rhodamine green and carboxytetramethylrhodamine (TAMRA), it was observed that the latterly injected trastuzumab‐TAMRA was distributed more centrally than trastuzumab‐rhodamine green injected first, whereas no difference was observed in the control mixed‐injection group. Moreover, the mixed injection of trastuzumab and trastuzumab‐Fab showed that trastuzumab‐Fab distributed more centrally than the same amount of co‐injected trastuzumab. Our results suggest that the strategies of increasing dose and using Fab fragments can be used to achieve a uniform antibody distribution within peritoneal disseminated nodules after intraperitoneal injection. Furthermore, serial‐injection and mixed‐injection strategies can modify antibody microdistribution within tumors and have the potential for preferential delivery of anticancer drugs to either the tumor periphery or its center.
Identification of transgelin‐2 as a biomarker of colorectal cancer by laser capture microdissection and quantitative proteome analysis
Authors: Zhang Yanbin , Ye Yingjiang , Shen Danhua , Jiang Kewei , Zhang Hui , Sun Wei , Zhang Jiyang , Xu Feng , Cui Zhirong , Wang Shan
Published: November 2009

To search for potential protein markers of colorectal cancer (CRC), the changes in protein expression levels between microdissected tumor cells and normal mucosa epithelia were analyzed by an acetylation stable isotopic labeling method coupled with linear quadrupole ion trap fourier transform mass spectrometry (LTQ‐FTMS). In total, 137 proteins were up‐regulated or down‐regulated significantly in cancer by at least two‐fold. Based on gene ontology analysis, the largest part of differential proteins were unknown for both subcellular localization and biological process. In particular, the significant up‐regulation of transgelin‐2 (TAGLN2) in CRC was validated by Western blot analysis and further evaluated by immunohistochemistry in paired tumor and normal mucosa samples from 120 consecutive CRC patients, 20 adenomas, and eight synchronous hepatic metastases of CRC. TAGLN2 expression was frequently observed in cancer cells, precancerous lesions, and hepatic metastases, whereas in normal epithelia expression was rarely observed. The overexpression of TAGLN2 was associated with lymph node and distant metastasis, advanced clinical stage (P < 0.001), and shorter overall survival in CRCs. Cox regression analysis indicated that high tumor‐TAGLN2 expression represents an independent prognostic factor. Consequently, over‐expression of TAGLN2 may serve as a new biomarker for predicting progression and prognosis of CRC. (Cancer Sci 2009)
Review article: the gastrointestinal complications of myositis
Authors: EBERT E. C.
Published: November 2009

Aliment Pharmacol Ther 31, 359–365

Background  The inflammatory myopathies are a group of acquired diseases characterized by a proximal myopathy caused by an inflammatory infiltrate of the skeletal muscle. The three major diseases are dermatomyositis, polymyositis and inclusion body myositis.

Aims  To review the gastrointestinal manifestations of myositis.

Methods  Over 110 articles in the English literature were reviewed.

Results  Dysphagia to solids and liquids occurs in patients with myositis. The pharyngo‐oesophageal muscle tone is lost and therefore patients develop nasal speech, hoarseness, nasal regurgitation and aspiration pneumonia. There is tongue weakness, flaccid vocal cords, poor palatal motion and pooling of secretions in the distended hypopharynx. Proximal oesophageal skeletal muscle dysfunction is demonstrated by manometry with low amplitude/absent pharyngeal contractions and decreased upper oesophageal sphincter pressures. Patients exhibit markedly elevated creatine kinase and lactate dehydrogenase levels consistent with muscle injury. Myositis can be associated with inflammatory bowel disease, coeliac disease and interferon treatment of hepatitis C. Corticosteroids and other immunosuppressive drugs comprise the mainstay of treatment. Inclusion body myositis responds poorly to these agents and therefore a myotomy is usually indicated.

Conclusion  Myositis mainly involves the skeletal muscles in the upper oesophagus with dysphagia, along with proximal muscle weakness.
Diffuse (anergic) cutaneous leishmaniasis responding to amphotericin B
Authors: Morrison B. , Mendoza I. , Delgado D. , Reyes Jaimes O. , Aranzazu N. , Paniz Mondolfi A. E.
Published: November 2009

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen-specific immunodeficiency that often presents with multiple disfiguring non-ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.
Glomeruloid peritoneal implants in ovarian serous borderline tumours – distinction between invasive and non‐invasive implants and pathogenesis
Authors: Lee Eung‐Seok , Leong Anthony S‐Y , Kim Insun S , Kim Young‐Sik , Lee Ju‐Han , Cho Hyun‐Yee
Published: November 2009

Aims:  To determine whether or not the glomeruloid implants (GI) composed of papillary cores within clear spaces lined by mesothelial cells or tumour cells located in superficial or deep peritoneal tissue in ovarian serous borderline tumours (SBTs) are invasive.

Methods and results:  We examined the differences in incidence, histological and immunohistochemical findings among three groups: 100 GI with mesothelial cells lining clear space (type I), 100 GI with tumour cells lining clear space (type II), and 100 invasive implants with clefts but no lining cells from 30 cases of SBT with peritoneal implants. The type I lesion had characteristics of non‐invasive implants with a tendency for smooth contours (100/100), superficial location (71/100), absence of desmoplasia (100/100) and absence of surrounding destructive invasion (100/100), In contrast, type II GI had irregular contours (67/100), deep location (93/100), presence of desmoplastic reaction (100/100) and presence of destructive invasion (12/100). Immunohistological studies suggested intermediate forms between the two types of lesions.

Conclusions:  Type I GI are non‐invasive implants, whereas type II GI are invasive implants and it is important to evaluate the presence and nature of cells lining the clear space in determining whether implants associated with ovarian SBTs are invasive or not.
Tumour microvessel endothelial cell KIT and stem cell factor expression in human solid tumours
Authors: Sihto Harri , Tynninen Olli , Halonen Maija , Puputti Marjut , Karjalainen‐Lindsberg Marja‐Liisa , Kukko Heli , Joensuu Heikki
Published: November 2009

Aims:  To assess KIT receptor tyrosine kinase and stem cell factor (SCF, KIT ligand) expression in tumour microvessel endothelial cells.

Methods and results:  KIT and SCF expression were studied in 248 human tumours consisting of 15 different histological types using immunohistochemistry and in situ hybridization for KIT messenger RNA. Moderate to strong intratumoral endothelial cell KIT expression was present in 11 of the 15 tumour types, and was most common in glioblastoma (58%), mixed embryonal carcinoma with teratoma (33%) and renal clear cell carcinoma (29%). Results of in situ hybridization were in line with those obtained with immunohistochemistry in the cases studied (n = 9). Marked SCF expression was uncommon in tumour endothelial cells, but frequent in perinecrotic tumour cells. Patients with glioblastoma with moderate to strong endothelial cell KIT expression had more favourable survival than those whose tumour showed little or no expression (P = 0.024). Glioblastoma patients whose tumour expressed SCF had an unfavourable outcome compared with those with tumour with weak or no expression (P = 0.034).

Conclusions:  Intratumoral microvessels of several types of human malignant tumours express KIT. Tumour cell SCF expression and absence of marked endothelial cell KIT expression are novel adverse prognostic features in glioblastoma.
Automated image analysis for high‐throughput quantitative detection of ER and PR expression levels in large‐scale clinical studies: The TEAM Trial Experience
Authors: Faratian Dana , Kay Charlene , Robson Tammy , Campbell Fiona M , Grant Margaret , Rea Dan , Bartlett John M S
Published: November 2009

Aims:  Routine immunohistochemistry is regarded as a semiquantitative method for the evaluation of in situ protein expression. Analysis of tissue biomarkers in large clinical trials is central to the development of novel targeted approaches to therapy, requires the analysis of tens of thousands of data points, and frequently makes use of high‐throughput analysis of tissue microarrays (TMAs). The aim of this study was to investigate the potential of image analysis for accurate and reproducible quantitative evaluation of biomarkers.

Methods and results:  We showed, in 397 cases of breast cancer from the Phase III TEAM clinical trial, excellent correlations between semiautomated image analysis of TMAs and manual scoring of oestrogen receptor (ER) and progesterone receptor (PR) levels (interclass correlation coefficients 0.93 and 0.96 respectively). Two or more TMA cores were excellently correlated with manual scores, and using more than three cores increased the number of cases available for analysis to >92%. TMAs are confirmed as representative of whole sections for immunohistochemical analysis of the tissue biomarkers ER and PR.

Conclusions:  Semiautomated image analysis is appropriate for the analysis of tissue biomarkers within large clinical trials. These data provide support for the use of TMAs and image analysis in translational research.
The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion – the prognostic contribution of related molecular markers
Authors: Afonso Julieta , Santos Lúcio Lara , Amaro Teresina , Lobo Francisco , Longatto‐Filho Adhemar
Published: November 2009

Aims:  Bladder cancer is the second most common malignancy of the urogenital region. The majority of bladder cancer deaths occur as a consequence of metastatic disease. Blood vessel density (BVD), a surrogate marker for angiogenesis, has been shown to be predictive of progression and poor prognosis, as well as lymphatic vessel density (LVD). The aim of this study was to evaluate, in human urothelial bladder cancer (UBC), the clinical and prognostic significance of angiogenesis, lymphangiogenesis and lymphovascular invasion, assessed with the use of specific immunohistochemical markers.

Methods and results:  Immunohistochemistry for CD31 (a blood vessel endothelial cell marker), D2‐40 (a lymphatic vessel endothelial cell marker), vascular endothelial growth factor (VEGF)‐C and VEGF‐receptor 3 antibodies was performed in 83 patients with urothelial carcinoma who underwent radical cystectomy. The classic histopathological characteristics, associated with lymphovascular invasion and loco‐regional dissemination, had a negative influence on 5‐year overall survival (OS) rates. BVD and LVD were correlated with advanced and poorly differentiated UBC with lymphovascular invasion. Blood vessel invasion (BVI) by malignant emboli assessed by CD31 staining, and lymphatic vessel invasion (LVI) by isolated malignant cells assessed by D2‐40 staining significantly affected OS. VEGF‐C overexpression was correlated with both BVI and LVI by single malignant cells assessed by CD31 and D2‐40, respectively. BVI by malignant emboli assessed by CD31 staining remained as an independent prognostic factor.

Conclusions:  Patients with UBC with embolic BVI assessed by CD31 and LVI by isolated malignant cells assessed by D2‐40 have a worse prognosis and may benefit from adjuvant therapies.
The role of vascular CXCR4 expression in colorectal carcinoma
Authors: Ingold Barbara , Schulz Stefan , Budczies Jan , Neumann Ulf , Ebert Matthias P A , Weichert Wilko , Röcken Christoph
Published: November 2009

Aims:  The chemokine receptor CXCR4 plays a prominent role in the biology of many different tumours, promoting angiogenesis and metastasis. The impact of CXCR4 expression on tumour biology has been described in various gastrointestinal malignancies, but data on its in situ expression and clinicopathological correlations are sparse. Using a novel specific rabbit anti‐CXCR4 antibody, the aim was to assess CXCR4 expression immunohistochemically on tissue microarrays generated from 402 colorectal cancers (CRCs) and compare it with CXCL12 expression and various clinicopathological parameters.

Methods and results:  CXCR4‐expressing tumour cells were observed in 31% of the cases, and expression correlated only with blood vessel invasion (P = 0.049). Furthermore, CXCR4 was found in tumour microvessels in 25% of CRCs. This pattern of CXCR4 expression correlated significantly with T‐ (P = 0.008), N‐ (P = 0.009), M‐ (P = 0.043), L‐ (P = 0.014) and V‐category (P = 0.043) as well as with International Union Against Cancer (UICC) stage (P = 0.001). Furthermore, in node negative CRCs, vascular CXCR4 expression was an independent adverse prognostic factor [hazard ratio 2.87 (1.31–6.29), P = 0.009]. No correlation with CXCL12 expression was found.

Conclusions:  Our data provide evidence that CXCR4 plays an important role in tumour angiogenesis of CRC. Therefore, the CXCR4 pathway is a promising therapeutic target for anti‐angiogenic therapies in CRC.
Trematode infection causes malformations and population effects in a declining New Zealand fish
Authors: Kelly David W. , Thomas Harriet , Thieltges David W. , Poulin Robert , Tompkins Daniel M.
Published: November 2009

1. Animal malformations engender wide public and scientific concern because of associated environmental health risks. This is highlighted by increased incidence of limb malformations in amphibians associated with trematode infections and disturbance. Malformations may signal new emerging disease threats, but whether the phenomenon is broadly applicable across taxa, or has population‐scale impacts, is unknown.

2. Malformations are widely reported in fish and, until now, have been attributed mainly to contaminants. We tested whether the trematode Telogaster opisthorchis caused severe malformations, leading to population effects, in Galaxias anomalus, a threatened New Zealand freshwater fish.

3. Experimental infection of larval fish caused increasing spinal malformation and mortality with infection intensity that closely matched field patterns. Field malformation frequency peaked in January (65%), before declining sharply in February (25%) and remaining low thereafter.

4. The peak occurred during a ‘critical window’ of larval development, with the decline coincident with a population crash, indicating that malformation was causing mortality in the field.

5. The occurrence of such critical developmental windows may explain why this mechanism of population impact has been overlooked. With global environmental stressors predicted to enhance trematode infections, our results show that parasite‐induced malformation, and its population‐scale impacts, could be more widespread than previously considered.
Silviculture enhances the recovery of overexploited mahogany Swietenia macrophylla
Authors: Verwer Caspar , Peña‐Claros Marielos , Van Der Staak Daniël , Ohlson‐Kiehn Kristen , Sterck Frank J.
Published: November 2009

Big leaf mahogany Swietenia macrophylla is the most valuable timber species in the tropics but its future as a commercial timber species is at risk. This study evaluates whether recovery of overexploited mahogany populations is enhanced by actively managing the species and its surrounding forest. We assessed the effect of four different management interventions that varied in their intensities of harvesting and silvicultural treatments. We tested the hypothesis that intensive forest management stimulates population growth rates.

Data were gathered over a 4‐year period in the plots (326 ha) of the Long Term Silvicultural Research Program in Bolivia. Plants > 1·3 m tall were identified and monitored in the plots, while seedlings and saplings (< 1·3 m tall) were recorded and measured around 58 adult mahogany trees. Population growth rate was simulated using population matrices based on observed vital rates.

The application of silvicultural treatments only had an effect on seedling and sapling survival; survival being lowest in the unlogged forest and highest at intermediate levels of treatment application. Growth of larger trees tended to increase with management intensity, and was dependent on crown position and liana infestation. Removal of lianas and other competing trees had a positive effect on growth rates.

Model simulations suggested that the recovery of overexploited mahogany population is enhanced by the application of intermediate levels of silvicultural treatments. Recovery is dependent on the retention of large seed trees (> 70 cm diameter at 1·3 m height) that produce large numbers of seedlings. Harvesting simulations indicate that mahogany populations can only be sustainably harvested by increasing the cutting cycle length, reducing harvesting intensity and by maintaining optimal growing conditions.

Synthesis and applications. Mahogany is the most valuable timber species in the tropics, and its range has dramatically decreased mostly due to commercial harvesting. The results of simulation modelling based on field and experimental data suggest that overexploited populations are recovering and that sustainable harvesting will be possible in the future when cutting cycle length is increased, harvesting intensity is reduced and silvicultural treatments are applied regularly throughout the cutting cycle.
Increasing the utility of Indicator Species Analysis
Authors: Bakker Jonathan D.
Published: November 2009

The identification of species associated with or indicative of groups of samples is a common aspect of ecological research, including studies of environmental management. Indicator Species Analysis (ISA) permits statistically rigorous assessments of these indicator species, but its usage is currently restricted to simple designs.

I describe three improvements that greatly increase the utility of ISA. First, exact permutation tests require that the correct exchangeable units be permuted; these exchangeable units may vary among factors. Secondly, the consistency of indicators can be assessed using meta‐analytic techniques to combine the results from multiple sites. Thirdly, while ISAs are classically conducted using abundance data, a simplified ISA can be conducted using binary (presence/absence) data.

These improvements are illustrated by identifying indicators of grazing treatment (inside or outside exclosure) at three sites in a southwestern ponderosa pinePinus ponderosaforest. Most indicators were consistent among sites, and the number of significant indicators was reduced 37–40% by combining results from multiple sites. Species that occurred at multiple sites were more likely to be indicators than those present at a single site.

Simplified ISAs produced very similar results to classical ISAs: both methods identified the same group as having the maximum Indicator Value in > 93% of tests. Compared to abundance data, however, the presence/absence data used in a simplified ISA are easily collected and efficiently published in data tables or appendices.

Synthesis and applications. Meta‐analytic techniques and simplified Indicator Species Analyses can increase the ability to analyse new or previously published data, and permit rigorous assessments of the consistency of indicator status spatially or temporally. Other recommendations to improve the utility of ISA include identifying organisms to as fine a taxonomic resolution as possible, providing detailed descriptions of groups and typologies, ensuring adequate sample sizes within groups, reporting the sample size and frequency of all species in all groups, and publishing data for all species – whether or not they are significant indicators – to prevent publication bias in future meta‐analyses.
Assessing the long‐term contribution of nurse plants to restoration of Mediterranean forests through Markovian models
Authors: Siles G. , Rey P. J. , Alcántara J. M. , Ramírez J. M.
Published: November 2009

Based on short‐term experimental data, facilitative interactions between woody plants (nurse‐recruit interactions) have been described as essential for the restoration of Mediterranean forests. However, the long‐term effects of nurse plants on vegetation dynamics are unknown. This study aims to project post‐fire vegetation dynamics from easily retrieved data, and to asses the long‐term contribution of nurse plants to forest restoration.

In an area burned 20 years ago, we compared post‐fire dynamics in three states of regeneration: pioneer scrubland; spontaneous pine regeneration stands; and late successional scrubland. For each regeneration state, we obtained an interaction matrix with the frequency of recruitment of a given species under the canopy of every other species in the community. These matrices provided the raw data to develop Markov chain models of community dynamics. We used sensitivity analyses to explore how small shifts in replacement probabilities between species (or between functional groups) may affect the similarity of the projected community to an undisturbed reference community.

Plots in the pioneer state had the lowest frequency of facilitative interactions. Matrix projection showed that, under the current frequency of facilitation, these pioneer scrublands would remain so in the long term. By contrast, the building state had the highest frequency of facilitation, and its projection suggested that it should reach a steady state very similar to the reference community. These results confirm that nurse facilitative effects are fundamental for a secondary successional trajectory of the post‐fire dynamics.

Sensitivities showed that secondary succession may be launched in the pioneer state by increasing the frequency of seedlings of tall shrubs, evergreen and deciduous trees under small shrubs.

Synthesis and applications. Our Markov chain successional model is an analytical tool which can be applied rapidly and easily to determine successional trajectories for forest restoration. It allows: (i) evaluation of post‐fire dynamics and identification of areas in need of intensive intervention (i.e. where secondary succession remains arrested leading to stasis in the pioneer state); (ii) assessment of the role of long‐term facilitative nurse effects on restoration; and (iii) identification of species‐pair combinations and functional nurse groups of value for further planting efforts.
Socioeconomic instability and the availability of health resources: their effects on infant mortality rates in Macau from 1957–2006
Authors: Chan Moon Fai , Ng Wai I , Van Iat Kio
Published: November 2009

Aim. To investigate the effects of socioeconomic instability and the availability of health resources on infant mortality rate.

Background. In 1960, the infant mortality rate was 46·3 infants per 1000 live births in Macau but by 2006 it had declined to 2·7 infants per 1000 live births.

Design. A retrospective design collecting yearly data for the Macau covering the period from 1957–2006. The infant mortality rate was the dependent variable and demographics, socioeconomic status and health resources are three main explanatory variables to determine the mortality rate.

Methods. Regression modelling.

Results. Results show that higher birth (Beta = 0·029,p = 0·004) and unemployment rates (Beta = −0·120,p = 0·036) and more public expenditure on health (Beta = −0·282,p < 0·001) were significantly more likely to reduce the infant mortality rate.

Conclusions. These results indicate that the socioeconomically disadvantaged are at a significantly higher risk for infant mortality. In contrast, more public expenditure on health resources significantly reduces the risk for infant mortality. This study provides further international evidence that suggests that improving aspects of the healthcare system may be one way to compensate for the negative effects of social inequalities on health outcomes.

Relevance to clinical practice. The implication of these results is that more effort, particularly during economic downturns, should be put into removing the barriers that impede access to healthcare services and increasing preventive care for the population that currently has less access to health care in communities where there is a scarcity of medical resources. In addition, efforts should be made to expand and improve the coverage of prenatal and infant healthcare programmes to alleviate regional differences in the use of health care and improve the overall health status of infants in Macau.
Health care professionals’ perceptions of hospital‐based cardiac rehabilitation in mainland China: an exploratory study
Authors: Wang Wenru , Chair Sek Ying , Thompson David R , Twinn Sheila F
Published: November 2009

Aim.  To explore Chinese health care professionals’ perceptions of cardiac rehabilitation for patients with coronary heart disease in mainland China.

Background.  Coronary heart disease is a rapidly growing major health problem in mainland China and little is known about the current provision of rehabilitation for this population.

Design.  A qualitative study.

Methods.  Face‐to‐face interviews were conducted with 18 Chinese health care professionals. The interviews were tape‐recorded, transcribed and content analysis was used to identify categories.

Results.  Content analysis of the data revealed three major categories: underdeveloped cardiac rehabilitation services, multiple obstacles to the establishment of a cardiac rehabilitation programme and a perceived need for professional guidance to patients.

Conclusion.  The current situation of cardiac rehabilitation in hospitals of China is poor with multiple obstacles prohibiting the development of cardiac rehabilitation services in the country and this has resulted in high rates of recurrence of heart attacks, coronary risk factors going undetected and/or untreated and psychological distress being observed among Chinese coronary heart disease patients.

Relevance to clinical practice.  The findings provide useful pointers for Chinese health professionals to explore ways of providing an effective, safe, convenient and culturally sensitive rehabilitation programme for Chinese patients with coronary heart disease.
Translation and back‐translation in qualitative nursing research: methodological review
Authors: Chen Hsiao‐Yu , Boore Jennifer RP
Published: November 2009

Aims.  To examine the effects of the procedure of translation and the techniques used on the collection and interpretation of original language qualitative data for English presentation.

Background.  Nursing and health research increasingly use qualitative research for a broadened perspective on practice and research. In numerous qualitative nursing research papers, data are collected in the original language (example Chinese) and the findings are presented in English. No standardised procedures exist for evaluating the influences of translation on the trustworthiness of qualitative data in nursing research.

Design.  Translation and back‐translation related literature review was conducted.

Methods.  This is a methodological review paper.

Discussion.  This paper discusses the factors influencing the quality of translation including translator, back‐translation, culture and language. Additionally, the translation procedures reported in the literature and the author’s experiences are considered.

Conclusions. The translation procedures described in qualitative nursing research can be summarised as:

1 Verbatim transcription of the content in original language, and then analysis of content;

2 Two bilingual translators are necessary to translate the emerged concepts and categories;

3 Back translate is employed;

4 An expert panel committee is involved in reaching final agreement on the translation.

Relevance to clinical practice.  Development of the translation procedures could provide qualitative nursing researchers with a guide when collecting data in one language and presenting results in another language. In this way, the necessary rigour in qualitative nursing research could be achieved.
Living with home‐based haemodialysis: insights from older people
Authors: Namiki Satoko , Rowe Jennifer , Cooke Marie
Published: November 2009

Aims and objectives.  To understand the challenges older people living with end‐stage kidney disease and home haemodialysis face in their everyday life.

Background.  As the treatment of end‐stage kidney disease has advanced, two aspects have emerged; increased life expectancy of end‐stage kidney disease patients and psychosocial adaptation to a changed life. There is limited information regarding older peoples’ experiences of adaptation to end‐stage kidney disease and home haemodialysis.

Design.  This qualitative study took place in Australia and involved participants who were over 60 years of age and undergoing home haemodialysis.

Methods.  Four participants aged between 60–75 years, with end‐stage kidney disease and currently enrolled in a programme of home haemodialysis took part. Data were collected via in‐depth audio‐recorded interviews and subjected to a qualitative thematic analysis.

Results.  Three themes were generated that provide insight into participants’ everyday activities, significant relationships, challenges and hopes for the future.

Conclusion.  Findings indicated a transformed care dynamic, positive appraisal and active everyday engagement by participants. A positive outlook on life in the present enabled participants to look to their future with purpose and hope. Outstanding systems of partnership significantly facilitated this view.

Relevance to clinical practice.  Knowledge from the study may contribute to the development of patient–care partnerships that facilitate and promote independence for older people being treated for chronic illnesses.
A systematic review of body temperature variations in older people
Authors: Lu Shu‐Hua , Leasure Angela‐Renee , Dai Yu‐Tzu
Published: November 2009

Aim.  The purpose of this systematic review was to determine the extent to which the research literature indicates body temperature norms in the geriatric population.

Objectives.  The specific questions addressed were to examine normal body temperature values in persons 60 years of age and older; determine differences in temperature values depending on non‐invasive measurement site and measurement device used; and, examine the degree and extent of temperature variability according to time of day and time of year.

Background.  The traditional ‘normal’ temperature of 98·6 °F/37 °C may in fact be lower in older people due to the ageing process. Age‐associated changes in vasomotor sweating function, skeletal muscle response, temperature perception and physical behaviours may influence the ability to maintain optimum temperature.

Design.  A systematic literature review.

Methods.  A search of multiple databases yielded 22 papers which met inclusion criteria. Studies were included which focused on temperature measurement, sampled persons 60 years of age and older, collected data from non‐invasive temperature measurement sites and which used a prospective study design. Studies were independently appraised using a structured appraisal format.

Results.  Temperature normal values by site were rectal 98·8 °F/37·1 °C, ear‐based 98·3 °F/36·8 °C, urine 97·6 °F/36·5 °C, oral 97·4 °F/36·3 °C and axillary 97·1 °F/36·2 °C. Temperature exhibited a 0·7 °F/0·4 °C diurnal and 0·2 °F/0·1 °C circannual variation.

Conclusions.  Synthesis of data indicated that normal body temperature values in older people by sites were rectal 0·7 °F/0·4 °C, ear‐based 0·3 °F/0·2 °C, oral 1·2 °F/0·7 °C, axillary 0·6 °F/0·3 °C lower than adults’ acceptable value from those traditionally found in nursing textbooks.

Relevance to clinical practice.  Given the fact that normal body temperature values were consistently lower than values reported in the literature, clinicians may need to re‐evaluate the point at which interventions for abnormal temperatures are initiated.
Effects of a therapeutic lifestyle‐change programme on cardiac risk factors after coronary artery bypass graft
Authors: Lin Hsin‐Hsin , Tsai Yun‐Fang , Lin Pyng‐Jing , Tsay Pei‐Kwei
Published: November 2009

Aims.  The aim of this study was to explore the behavioural and clinical impact of a therapeutic lifestyle‐change intervention for cardiac risk factors in patients after coronary artery bypass graft surgery.

Background.  Coronary atherosclerosis‐induced cardiovascular disease involves a progressive process. Progression of coronary atherosclerosis remains a significant problem after coronary artery intervention, requiring patients to make ongoing modifications in their lifestyle to reduce cardiac risk factors.

Design.  A prospective quasi‐experimental design was used.

Methods.  Patients who received coronary artery bypass graft surgery at a medical centre in Taiwan were sampled by convenience and assigned to two groups. The control group (n = 37) and experimental group (n = 36) both received routine postoperative rehabilitation, with the experimental group also receiving the therapeutic lifestyle‐change programme. Measures of behavioural and clinical outcomes were compared before surgery, one and three months after discharge.

Results.  The results revealed that the amount of cigarette smoking, blood pressure control, frequency of physical activity and dietary behaviour were modified in both groups. Both groups improved significantly in blood lipid profiles and fasting glucose levels from presurgery to the first month after discharge and the experimental group improved even more (p < 0·05). Similar findings were also noted for changes in cigarette smoking and dietary behaviour. Three months after discharge, blood pressure control and frequency of physical activity in the experimental group were significantly higher than in the control group.

Conclusions.  Incorporating a therapeutic lifestyle‐change intervention into a postoperative cardiac rehabilitation programme effectively modified cardiac risk factors and may improve postoperative recovery and prognosis.

Relevance to clinical practice.  Guidelines for Taiwanese patients with cardiovascular disease should stress and support implementation of and adherence to therapeutic lifestyle changes in addition to drug therapy.
Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology
Authors: Oberdörster G.
Published: October 2009

Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano‐enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico‐chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos‐like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano‐specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists.
Lipid‐based nanotherapeutics for siRNA delivery
Authors: Schroeder A. , Levins C. G. , Cortez C. , Langer R. , Anderson D. G.
Published: October 2009

RNA interference (RNAi) is a specific gene‐silencing mechanism triggered by small interfering RNA (siRNA). The application of RNAi in the clinic requires the development of safe and effective delivery systems. Inspired by progress with lipid‐based systems in drug delivery, efforts have been dedicated to the development of liposomal siRNA delivery systems. Many of the lipid‐based delivery vehicles self‐assemble with siRNA through electrostatic interactions with charged amines, generating multi‐lamellar lipoplexes with positively charged lipid bilayers separated from one another by sheets of negatively charged siRNA strands. Internalization of lipid‐based siRNA delivery systems into cells typically occurs through endocytosis; accordingly, delivery requires materials that can facilitate endosomal escape. The size of the carrier is important as carriers <100 nm in diameter have been reported to have higher accumulation levels in tumours, hepatocytes and inflamed tissue, whereas larger particles tend to be taken up by Kupffer cells or other components of the reticuloendothelial system (RES). To reduce RES uptake and increase circulation time, carriers have been modified on the surface with hydrophilic materials, such as polyethyleneglycol. Herein, we review the molecular and structural parameters of lipid‐based siRNA delivery systems.
When it comes to inbreeding: slower is better
Authors: REED DAVID H.
Published: November 2009

The extent to which genetic diversity is lost from inbred populations is important for conservation biology, evolutionary ecology, and plant and animal breeding. This importance stems from the fact that the amount of genetic diversity a population has is expected to correlate with evolutionary potential. A population’s ability to avert extinction during rapidly changing environmental conditions, or the magnitude of response to selection on a trait, depend on the ability of the genome to maintain potentially adaptive genetic variation in the face of random genetic drift. Although a few previous studies have demonstrated that the rate of inbreeding affects the amount of genetic diversity maintained, the elegant work of Demontis et al., in this issue, clearly demonstrates that slow inbreeding maintains more genetic diversity than fast inbreeding and that the primary mechanism could be balancing selection. In their study, populations that took 19 generations, rather than one generation, to reach the same level of inbreeding maintained 10% higher levels of allelic richness and 25% higher levels of heterozygosity. The use of specifically chosen molecular markers not expected to be neutral makes this study especially noteworthy, as the study provides evidence concerning the mechanisms underlying the maintenance of genetic diversity in the face of inbreeding.
Identification of novel sources of resistance to Pea enation mosaic virus in chickpea germplasm
Authors: Larsen R. C. , Porter L. D.
Published: November 2009

Chickpea can be seriously affected by Pea enation mosaic virus (PEMV) in the Pacific Northwest region of the USA and other areas of the world. Use of pesticides to manage PEMV vector transmission is ineffective and PEMV‐resistant chickpeas have not been identified. Therefore, the Cicer core collection consisting of 499 wild Plant Introduction (PI) accessions and improved cultivars representing 25 countries and two chickpea phenotypes (Desi and Kabuli) was evaluated for resistance to PEMV based on a 1 to 5 scale where 1 = symptomless and 5 = severe mosaic and stunting. Eight accessions were considered resistant to PEMV based on mean disease severity values equal to or less than 1·9 in repeated greenhouse tests. All of the resistant accessions to PEMV were of the Desi type and all originated from Iran or India. PI 450763 was the only Kabuli accession that demonstrated tolerance to PEMV. PEMV resistance was not detected in commercial chickpea cultivars or advanced breeding lines currently grown in the USA and Canada. This is the first report of chickpea germplasm with resistance to PEMV.
The rice yellow mottle virus P1 protein exhibits dual functions to suppress and activate gene silencing
Authors: Lacombe Séverine , Bangratz Martine , Vignols Florence , Brugidou Christophe
Published: November 2009

In plants RNA silencing is a host defense mechanism against viral infection, in which double‐strand RNA is processed into 21–24‐nt short interfering RNA (siRNA). Silencing spreads from cell to cell and systemically through a sequence‐specific signal to limit the propagation of the virus. To counteract this defense mechanism, viruses encode suppressors of silencing. The P1 protein encoded by the rice yellow mottle virus (RYMV) displays suppression activity with variable efficiency, according to the isolates that they originated from. Here, we show that P1 proteins from two RYMV isolates displaying contrasting suppression strength reduced local silencing induced by single‐strand and double‐strand RNA in Nicotiana benthamiana leaves. This suppression was associated with a slight and a severe reduction in 21‐ and 24‐nt siRNA accumulation, respectively. Unexpectedly, cell‐to‐cell movement and systemic propagation of silencing were enhanced in P1‐expressing Nicotiana plants. When transgenically expressed in rice, P1 proteins induced specific deregulation of DCL4‐dependent endogenous siRNA pathways, whereas the other endogenous pathways were not affected. As DCL4‐dependent pathways play a key role in rice development, the expression of P1 viral proteins was associated with the same severe developmental defects in spikelets as in dcl4 mutants. Overall, our results demonstrate that a single viral protein displays multiple effects on both endogenous and exogenous silencing, not only in a suppressive but also in an enhancive manner. This suggests that P1 proteins play a key role in maintaining a subtle equilibrium between defense and counter‐defense mechanisms, to insure efficient virus multiplication and the preservation of host integrity.
The nucleotide sugar transporters AtUTr1 and AtUTr3 are required for the incorporation of UDP‐glucose into the endoplasmic reticulum, are essential for pollen development and are needed for embryo sac progress in Arabidopsis thaliana
Authors: Reyes Francisca , León Gabriel , Donoso Maribel , Brandizzí Federica , Weber Andreas P.M. , Orellana Ariel
Published: November 2009

Uridine 5′‐diphosphate (UDP)‐glucose is transported into the lumen of the endoplasmic reticulum (ER), and the Arabidopsis nucleotide sugar transporter AtUTr1 has been proposed to play a role in this process; however, different lines of evidence suggest that another transporter(s) may also be involved. Here we show that AtUTr3 is involved in the transport of UDP‐glucose and is located at the ER but also at the Golgi. Insertional mutants in AtUTr3 showed no obvious phenotype. Biochemical analysis in both AtUTr1 and AtUTr3 mutants indicates that uptake of UDP‐glucose into the ER is mostly driven by these two transporters. Interestingly, the expression of AtUTr3 is induced by stimuli that trigger the unfolded protein response (UPR), a phenomenon also observed for AtUTr1, suggesting that both AtUTr1 and AtUTr3 are involved in supplying UDP‐glucose into the ER lumen when misfolded proteins are accumulated. Disruption of both AtUTr1 and AtUTr3 causes lethality. Genetic analysis showed that the atutr1 atutr3 combination was not transmitted by pollen and was poorly transmitted by the ovules. Cell biology analysis indicates that knocking out both genes leads to abnormalities in both male and female germ line development. These results show that the nucleotide sugar transporters AtUTr1 and AtUTr3 are required for the incorporation of UDP‐glucose into the ER, are essential for pollen development and are needed for embryo sac progress in Arabidopsis thaliana.