bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological responses in humans to the smallpox vaccine LC16m8
Authors: Johnson Benjamin F. , Kanatani Yasuhiro , Fujii Tatsuya , Saito Tomoya , Yokote Hiroyuki , Smith Geoffrey L.
Published: June 2011

In response to potential bioterrorism with smallpox, members of the Japanese Self-Defense Forces were vaccinated with vaccinia virus (VACV) strain LC16m8, an attenuated smallpox vaccine derived from VACV strain Lister. The serological response induced by LC16m8 to four virion-surface proteins and the intracellular mature virus (IMV) and extracellular enveloped virus (EEV) was investigated. LC16m8 induced antibody response against the IMV protein A27 and the EEV protein A56. LC16m8 also induced IMV-neutralizing antibodies, but unlike the VACV strain Lister, did not induce either EEV-neutralizing antibody or antibody to EEV protein B5, except after revaccination. Given that B5 is the only target for EEV-neutralizing antibody and that neutralization of both IMV and EEV give optimal protection against orthopoxvirus challenge, these data suggest that immunity induced by LC16m8 might be less potent than that deriving from strain Lister. This potential disadvantage should be balanced against the advantage of the greater safety of LC16m8.
Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75
Authors: Cáceres Lucía , Necakov Aleksandar S. , Schwartz Carol , Kimber Sandra , Roberts Ian J.H. , Krause Henry M.
Published: June 2011

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.
Putting genetic interactions in context through a global modular decomposition
Authors: Bellay Jeremy , Atluri Gowtham , Sing Tina L. , Toufighi Kiana , Costanzo Michael , Ribeiro Philippe Souza Moraes , Pandey Gaurav , Baller Joshua , VanderSluis Benjamin , Michaut Magali , Han Sangjo , Kim Philip , Brown Grant W. , Andrews Brenda J. , Boone Charles , Kumar Vipin , Myers Chad L.
Published: June 2011

Genetic interactions provide a powerful perspective into gene function, but our knowledge of the specific mechanisms that give rise to these interactions is still relatively limited. The availability of a global genetic interaction map in Saccharomyces cerevisiae, covering ∼30% of all possible double mutant combinations, provides an unprecedented opportunity for an unbiased assessment of the native structure within genetic interaction networks and how it relates to gene function and modular organization. Toward this end, we developed a data mining approach to exhaustively discover all block structures within this network, which allowed for its complete modular decomposition. The resulting modular structures revealed the importance of the context of individual genetic interactions in their interpretation and revealed distinct trends among genetic interaction hubs as well as insights into the evolution of duplicate genes. Block membership also revealed a surprising degree of multifunctionality across the yeast genome and enabled a novel association of VIP1 and IPK1 with DNA replication and repair, which is supported by experimental evidence. Our modular decomposition also provided a basis for testing the between-pathway model of negative genetic interactions and within-pathway model of positive genetic interactions. While we find that most modular structures involving negative genetic interactions fit the between-pathway model, we found that current models for positive genetic interactions fail to explain 80% of the modular structures detected. We also find differences between the modular structures of essential and nonessential genes.
Injecting Zebrafish with DNA or RNA Constructs Encoding Fluorescent Protein Reporters: Figure 1.
Authors: Godinho Leanne
Published: July 2011

INTRODUCTION

In the last two decades, the small tropical freshwater-dwelling zebrafish has emerged as a popular model for developmental biologists. The exceptional optical accessibility of zebrafish embryos coupled with the ability to use genetic tools to indelibly tag cells have been exploited to watch developmental events as they unfold. Moreover, because zebrafish are vertebrates, the knowledge gained through such studies is broadly applicable. Injecting zebrafish with constructs that encode fluorescent proteins is a versatile method for labeling cells and tissues for imaging. The method, described here, can be used to generate transiently or stably transfected organisms showing ubiquitous or mosaic patterns of fluorescence.
Live Imaging of Zebrafish Development: Table 1.
Authors: Godinho Leanne
Published: July 2011

INTRODUCTION

In the last two decades, the small tropical freshwater-dwelling zebrafish has emerged as a popular model for developmental biologists. The exceptional optical accessibility of zebrafish embryos coupled with the ability to use genetic tools to indelibly tag cells have been exploited to watch developmental events as they unfold. Moreover, zebrafish are vertebrates. Thus, the knowledge gained through such studies is broadly applicable. This article outlines the advantages of using zebrafish to study development by in vivo microscopy, highlights the kinds of developmental questions that can be addressed, presents strategies for fluorescently labeling cellular and subcellular structures, and discusses general parameters that need to be taken into account for repetitive in vivo imaging.
The SINA E3 Ligase OsDIS1 Negatively Regulates Drought Response in Rice
Authors: Ning Yuese , Jantasuriyarat Chachawan , Zhao Qingzhen , Zhang Huawei , Chen Songbiao , Liu Jinling , Liu Lijing , Tang Sanyuan , Park Chan Ho , Wang Xuejun , Liu Xionglun , Dai Liangying , Xie Qi , Wang Guo-Liang
Published: July 2011

Ubiquitin-regulated protein degradation is a critical regulatory mechanism that controls a wide range of biological processes in plants. Here, we report that OsDIS1 (for Oryza sativa drought-induced SINA protein 1), a C3HC4 RING finger E3 ligase, is involved in drought-stress signal transduction in rice (O. sativa). The expression of OsDIS1 was up-regulated by drought treatment. In vitro ubiquitination assays showed that OsDIS1 possessed E3 ubiquitin ligase activity and that the conserved region of the RING finger was required for the activity. Transient expression assays in Nicotiana benthamiana leaves and rice protoplasts indicated that OsDIS1 was localized predominantly in the nucleus. Overexpression of OsDIS1 reduced drought tolerance in transgenic rice plants, while RNA interference silencing of OsDIS1 enhanced drought tolerance. Microarray analysis revealed that a large number of drought-responsive genes were induced or suppressed in the OsDIS1 overexpression plants under normal and drought conditions. Yeast two-hybrid screening showed that OsDIS1 interacted with OsNek6 (for O. sativa NIMA-related kinase 6), a tubulin complex-related serine/threonine protein kinase. Coexpression assays in N. benthamiana leaves indicated that OsNek6 was degraded by OsDIS1 via the 26S proteasome-dependent pathway and that this degradation was abolished by the OsDIS1(H71Y) mutation, which is essential for its E3 ligase activity. Together, these results demonstrate that OsDIS1 plays a negative role in drought stress tolerance through transcriptional regulation of diverse stress-related genes and possibly through posttranslational regulation of OsNek6 in rice.
Development of membrane type‐1 matrix metalloproteinase‐specific activatable fluorescent probe for malignant tumor detection
Authors: Shimizu Yoichi , Temma Takashi , Sano Kohei , Ono Masahiro , Saji Hideo
Published: June 2011

Membrane type‐1 matrix metalloproteinase (MT1‐MMP) is a protease that activates pro‐MMP‐2 and pro‐MMP13, which are related to tumor malignancy. Therefore, probes that specifically image MT1‐MMP would be useful for malignant tumor diagnosis. In the present study, we prepared rhodamine X‐conjugated anti‐MT1‐MMP antibody (anti‐MT1‐MMP mAb‐ROX) as an activatable fluorescent probe and evaluated its usefulness for MT1‐MMP‐specific imaging. Anti‐MT1‐MMP mAb‐ROX was obtained in a quenched form with approximately three ROX molecules per mAb. Its fluorescence intensity increased approximately 14‐fold in the presence of detergent, which is suitable for activatable systems. C6 glioma cells and MCF‐7 human breast adenocarcinoma cells were used as MT1‐MMP‐positive and MT1‐MMP‐negative models, respectively. The fluorescence intensity of C6 cells treated with anti‐MT1‐MMP mAb‐ROX, but not ROX‐conjugated isotype control antibody (NC Ab‐ROX), increased with time and was significantly higher than that of MCF‐7 cells at 6 h (P < 0.001). The fluorescence intensity of cells treated with anti‐MT1‐MMP mAb‐ROX was also suppressed by pre‐treatment with a MT1‐MMP endocytosis inhibitor (P < 0.05). Furthermore, the probes were intravenously administered to C6 and MCF‐7 xenografted mice. The tumor‐to‐muscle (T/M) ratio of the anti‐MT1‐MMP mAb‐ROX group was 15.1 ± 3.2 at 48 h and was significantly higher than that of the NC Ab‐ROX group (T/M ratio = 4.6 ± 3.0, P < 0.05) in C6 xenografted mice, while the T/M ratio of the anti‐MT1‐MMP mAb‐ROX and NC Ab‐ROX groups was not different in MCF‐7 xenografted mice. These findings suggest that anti‐MT1‐MMP mAb‐ROX is a promising probe for specifically detecting MT1‐MMP‐expressing tumors. (Cancer Sci 2011; 102: 1897–1903)
Intoxicated workers: findings from a national Australian survey
Authors: Pidd Ken , Roche Ann M. , Buisman‐Pijlman Femke
Published: June 2011

Aims  To identify prevalence of alcohol and drug use and intoxication at work.

Participants  A total of 9828 Australian workers ≥14 years old.

Setting  Australia 2007.

Measurements  Work‐place alcohol use and drug use, intoxication at work, industry and occupation of employment.

Design  Secondary analysis of a large nationally representative survey involving descriptive and weighted multivariate logistic regressions.

Findings  Differential patterns were identified by drug type, worker characteristics and occupational setting, controlling for demographic variables. Nearly 9% of workers surveyed (8.7%) usually drank alcohol at work and 0.9% usually used drugs at work. Attending work under the influence of alcohol was more prevalent (5.6%) than attending work under the influence of drugs (2.0%), and significantly more likely among young, male, never married workers with no dependent children. Hospitality industry workers were 3.5 times more likely than other workers to drink alcohol and two to three times more likely to use drugs at work or attend work under the influence of alcohol or drugs. Other high‐risk industries and occupations included construction, financial services, tradespersons and unskilled workers.

Conclusion  More than one in 20 Australian workers admit to having worked under the influence of alcohol and almost one in 50 report attending work under the influence of psychoactive drugs. The rates are higher for some industries, such as the hospitality industry, than others.
Co‐occurrence of obsessive‐compulsive disorder and substance use disorder in the general population
Authors: Blom Rianne M. , Koeter Maarten , van den Brink Wim , de Graaf Ron , ten Have Margreet , Denys Damiaan
Published: June 2011

Aim  Very little is known about the relationship between obsessive–compulsive disorder (OCD) and substance use disorder (SUD). The aim of this study is to compare the co‐occurrence of OCD with SUD to the co‐occurrence of SUD with other psychiatric disorders in a representative community sample.

Design  In order to examine the association of SUD and OCD, logistic regression analyses were used generating odds ratios and 95% confidence intervals for life‐time prevalence and 12‐month prevalence.

Setting and participants  Cross‐sectional data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a large representative sample of the Dutch population (n = 7076).

Measurements  The Composite International Diagnostic Interview (CIDI) 1.1 was used to assess Diagnostic and Statistical Manual of Mental Disorders Axis I criteria for psychiatric disorders.

Findings  The life‐time and 12‐month odds of being diagnosed with SUD in subjects with OCD are significantly higher than the odds of SUD for people without a psychiatric disorder. In men, the co‐occurrence of substance dependence and OCD is significantly higher than the co‐occurrence of substance dependence and other psychiatric disorders, whereas in women this co‐occurrence does not differ significantly.

Conclusions  The co‐occurrence of substance dependence in obsessive–compulsive disorder is higher than the co‐occurrence of substance dependence in other non‐obsessive–compulsive disorder DSM disorders, especially in men.
Physicians' reported needs of drug information at point of care in Sweden
Authors: Rahmner Pia Bastholm , Eiermann Birgit , Korkmaz Seher , Gustafsson Lars L. , Gruvén Magnus , Maxwell Simon , Eichle Hans‐Georg , Vég Anikó
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The computerization of health care has increased dramatically in the last decades in most European countries, but no standardization of any of the information support systems has been established on common ground.

• The Summary of Product Characteristics (SmPC) is available all over Europe in written form and in some of the countries even electronically, but the structure and the content of the information vary.

• The physicians' needs for useful and reliable information about drugs at point of care are a question of patient safety.

WHAT THIS STUDY ADDS

• A qualitative approach, in this case focus group discussions, proved advantagous compared with questionnaires.

• Knowledge gained from physicians' experiences promoted the work of restructuring and organizing the e‐SmPC database.

• Most of the required information from physicians appeared to be possible to transfer from current SmPCs to clinical decisions support systems.

AIMS

Relevant and easily accessible drug information at point‐of‐care is essential for physicians' decision making when prescribing. However, the information available by using Clinical Decision Support Systems (CDSSs) often does not meet physicians' requirements. The Summary of Product Characteristics (SmPC) is statutory information about drugs. However, the current structure, content and format of SmPCs make it difficult to incorporate them into CDSSs and link them to relevant patient information from the Electronic Health Records. The aim of the study was to evaluate the perceived needs for drug information among physicians in Sweden.

METHODS

We recruited three focus group discussions with 18 physicians covering different specialities. The information from the groups was combined with a questionnaire administered at the beginning of the group discussions.

RESULTS

Physicians reported their needs for knowledge databases at the point of drug prescribing. This included more consistent information about existing and new drugs. They also wished to receive automatically generated alerts for severe drug–drug interactions and adverse effects, and to have functions for calculating glomerular filtration rate to enable appropriate dose adjustments to be made for elderly patients and those with impaired renal function. Additionally, features enhancing electronic communication with colleagues and making drug information more searchable were suggested.

CONCLUSIONS

The results from the current study showed the need for knowledge databases which provide consistent information about new and existing drugs. Most of the required information from physicians appeared to be possible to transfer from current SmPCs to CDSSs. However, inconsistencies in the SmPC information have to be reduced to enhance their utility.
Complete skin examination is essential in the assessment of dermatology patients: findings from 483 patients
Authors: Moran B. , McDonald I. , Wall D. , O’Shea S.J. , Ryan C. , Ryan A.J. , Kirby B.
Published: June 2011

Background Dermatological teaching has traditionally stressed that complete skin examination is essential in the assessment of patients with potential skin disease.

Objectives To determine whether complete skin examination results in increased diagnoses of skin malignancies that would not have been discovered otherwise.

Methods New patients (n =483) attending a dermatology clinic in a university teaching hospital and private dermatology practice had a complete skin examination, as is our normal practice. These patients were seen over a 9-month period (January–September 2009). All patients were examined by the same consultant dermatologist. Data were collected on patients’ sex, age, presenting complaint and findings on complete skin examination.

Results Two nodular malignant melanomas with mean Breslow thickness of 0·6 mm (0·4%) and one melanoma in situ were identified at sites distant from the patient’s presenting complaint. Sixteen patients (3·3%) had a basal cell carcinoma that would not have been discovered if the presenting lesion alone had been examined. Thirty-three patients (6·8%) had actinic keratoses or squamous cell carcinoma in situ and nine (1·9%) had dysplastic naevi. A further 21 patients (4·3%) had a suspicious lesion biopsied or excised with subsequent benign histology. Seventy-three patients (15·1%) had other benign dermatological diagnoses requiring treatment or investigation.

Conclusions In a 9-month period, in a sample of 483 new patients, three patients (0·6%) had potentially lethal skin malignancies identified that would not have been diagnosed without a complete skin examination. Sixteen (3·3%) patients had basal cell carcinomas that would have been missed without complete skin examination. This study confirms the traditional teaching that complete skin examination has the potential to reduce morbidity and mortality from cutaneous malignancy.
Laser and intense pulsed light therapy for the treatment of hypertrophic scars: a systematic review
Authors: Vrijman C. , van Drooge A.M. , Limpens J , Bos J.D. , van der Veen J.P.W. , Spuls P.I. , Wolkerstorfer A.
Published: June 2011

Hypertrophic scars are difficult to improve and remain a therapeutic challenge. Several lasers and light sources have been evaluated in the past decades and have been shown to improve hypertrophic scars. However, a systematic review is not available. To assess current evidence of efficacy of all laser and intense pulsed light therapies used in the treatment of hypertrophic scars, we performed a systematic review searching electronic databases MEDLINE, EMBASE and CENTRAL. The quality of the controlled clinical trials was evaluated according to the Cochrane Collaboration’s tool for assessing risk of bias. Thirteen articles involving seven different lasers met the inclusion criteria. Most evidence was found for the pulsed dye laser (PDL) 585 nm (eight studies), followed by the PDL 595 nm (two studies), whereas limited evidence (one trial per laser) was available for the fractional nonablative laser 1540 nm, CO2 laser 10 600 nm, low-level laser therapy, Nd:YAG laser 532 nm and Erbium:YAG laser 2940 nm. Treatment recommendations should be formulated with caution as current evidence is insufficient for comparing the efficacy of different laser therapies. The PDL 585 nm showed a low efficacy for the treatment of hypertrophic scars. With moderate efficacy, the PDL 595 nm is promising, although more research is necessary. Little evidence was found for the efficacy of other lasers. Future research, with a low risk of bias, well-defined scar characteristics, validated outcome measures, standardized measurement methods, follow-up periods of at least 6 months and well-defined laser settings, is needed.
Lymphomas in sub‐Saharan Africa – what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?
Authors: Naresh Kikkeri N. , Raphael Martine , Ayers Leona , Hurwitz Nina , Calbi Valeria , Rogena Emily , Sayed Shahin , Sherman Omar , Ibrahim Hazem A.H. , Lazzi Stefano , Mourmouras Vasileios , Rince Patricia , Githanga Jessie , Byakika Bessie , Moshi Emma , Durosinmi Muheez , Olasode Babatunde J. , Oluwasola Olayiwola A. , Akang Effiong E. , Akenòva Yetunde , Adde Melissa , Magrath Ian , Leoncini Lorenzo
Published: June 2011

Approximately 30 000 cases of non‐Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub‐Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub‐Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub‐Saharan African centres is presented. Among children (<18 years of age), BL accounted for 82% of all NHL, and among adults, diffuse large B‐cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T‐cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub‐Saharan Africa for fostering high‐quality translational research.
Mannose-binding lectin deficiency linked to cytomegalovirus (CMV) reactivation and survival in lung transplantation
Authors: Kwakkel-van Erp J M , Paantjens A W M , van Kessel D A , Grutters J C , van den Bosch J M M , van de Graaf E A , Otten H G
Published: June 2011

Despite the use of immunosuppressives mainly influencing T and B cell responses, the prevalence of the bronchiolitis obliterans syndrome (BOS) after lung transplantation is high. Mannose-binding lectin (MBL) is a pattern recognition molecule of complement and an important component of the innate immunity. MBL is associated with rejection, infection and survival in other solid organ transplantations. In this study the relation between functional MBL levels and cytomegalovirus (CMV) reactivations and the development of BOS and survival after lung transplantation was investigated. MBL levels were measured in 85 patients before and in 57 of these patients after lung transplantation. The relation of MBL on survival, CMV reactivation and the development of BOS were investigated with Kaplan–Meier (log-rank) survival analysis. MBL levels decreased on average by 20% (P < 0·001) after transplantation and eventually returned to pretransplant levels. Fourteen of the 85 patients had deficient pretransplant MBL levels and these patients had a tendency towards a better survival compared to those with normal MBL levels (P = 0·08). Although no correlation was found between MBL deficiency and the development of BOS, more CMV reactivations occurred in recipients with deficient versus normal levels of MBL (P = 0·03). Our results suggest that MBL deficiency is associated with CMV reactivations and a longer overall survival, but not with the development of BOS.
Expansion of T helper type 17 lymphocytes in patients with chronic granulomatous disease
Authors: Horváth R , Rožková D , Lašťovička J , Poloučková A , Sedláček P , Šedivá A , Špíšek R
Published: June 2011

Hyper-immunoglobulin (Ig)E syndrome (HIES) is a primary immunodeficiency associated with mutations in STAT3 resulting in impaired development of T helper type 17 (Th17) lymphocytes. HIES patients with a reduced frequency of Th17 cells present with infections caused by Staphylococcus aureus and/or Candida strains. The same spectrum of pathogens is present in patients with chronic granulomatous disease (CGD).We analysed the characteristics of the Th17 compartment in HIES and CGD. HIES patients showed very low numbers of Th17 cells. By contrast, the frequency of Th17 cells and production of Th17-derived cytokines was significantly higher among CGD patients when compared to both control samples and HIES. Naive CD4+ cells in CGD patients had a normal capacity to differentiate into IL-17-producing cells and the numbers of Th17 cells in the CGD patients normalized following successful bone marrow transplantation. Our findings complement recent data on the importance of Th17 cells for elimination of infections with C. albicans and S. aureus.
Lung transplantation affects expression of the chemokine receptor type 4 on specific T cell subsets
Authors: Paantjens A W M , van de Graaf E A , Kwakkel-van Erp J M , Hoefnagel T , van Kessel D A , van den Bosch J M M , Otten H G
Published: June 2011

Alloreactive T cells that infiltrate the graft after lung transplantation (LTx) play a role in chronic rejection. Chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and monocyte chemotactic protein-1 (MCP-1) are produced locally in the lung and attract T cells via chemokine receptor 4 (CCR4). In a TARC gradient, cells expressing CCR4++ migrate more efficiently than CCR4+-expressing cells. In this study, we compared the CCR4 expression of T cells in blood from 20 lung transplant recipients to healthy controls. We then examined whether CCR4 expression is associated with the occurrence of chronic rejection. The CCR4++ expression was decreased on CD4 T cells from LTx patients (P < 0·0001) when compared to healthy controls. The analysis of CD4 T cell subsets showed that this decrease was present on central memory, effector memory and terminally differentiated T cells (P = 0·0007, P < 0·0001 and P = 0·05, respectively), while a trend was found for naive CD4 T cells (P = 0·06). Also, the expression of CCR4+ on regulatory T cells (Tregs) was decreased in LTx patients when compared to healthy controls (P = 0·02). Interestingly, the CCR4++ expression on CD4 effector memory T cells was decreased in patients developing chronic rejection sometimes more than a year before the clinical diagnosis when compared to patients who did not (P = 0·04). The analysis of CD8 T cell subsets only showed the CCR4+ expression to be increased significantly on effector memory and terminally differentiated CD8 T cells (P = 0·02, P = 0·03, respectively) in LTx patients, but no relation was found in chronic rejection. In conclusion, the expression of CCR4 on T cell subsets was altered after LTx and appears to be related to chronic rejection.
Association of serum retinol‐binding protein 4 with insulin resistance and metabolic parameters during olanzapine therapy
Authors: Faghihi Toktam , Radfar Mania , Abdoli Elahe , Amini Homayoun , Rezaei Hemami Mohsen , Larijani Bagher
Published: June 2011

Objective  Retinol‐binding protein 4 (RBP4) has been shown to be associated with insulin resistance (IR), metabolic indices and metabolic syndrome (MetS) in various patient populations and in obesity. We investigated the association between metabolic parameters, IR and RBP4 during olanzapine therapy.

Design  A prospective study.

Patients  Thirty‐seven participants with psychiatric disorder who were atypical antipsychotic naive and newly initiated on olanzapine were assessed.

Measurements  Fasting RBP4, anthropometric and metabolic variables were measured before and after 3 months of olanzapine therapy.

Results  Participants who developed MetS showed higher RBP4 levels compared with those without MetS, although not significant (P = 0·053). The variation in RBP4 level was correlated with changes in systolic blood pressure (r = 0·423, P = 0·009), diastolic blood pressure (r = 0·390, P = 0·017), total cholesterol (r = 0·446, P = 0·006) and low‐density lipoprotein (LDL) (r = 0·407, P = 0·012). Multiple linear regression analysis illustrated that end‐point log insulin level was the most significant independent predictor of final log RBP4 levels (standardized ß = 0·353, P = 0·024).

Conclusions  Our results suggest that RBP4 levels might be associated with at least some olanzapine‐induced metabolic abnormalities and cardiovascular disease risk factors.
Sex hormone–binding globulin at the crossroad of body composition, somatotropic axis and insulin/glucose homeostasis in young healthy men
Authors: Vanbillemont Griet , Lapauw Bruno , De Naeyer Hélène , Roef Greet , Kaufman Jean‐Marc , Taes Youri E. C.
Published: June 2011

Objectives  Sex hormone–binding globulin (SHBG) modulates the bioavailability of sex steroids at tissue level. Genetic, hormonal and lifestyle‐related factors determine the SHBG levels, and low SHBG levels are a known risk factor for the development of the metabolic syndrome, diabetes and cardiovascular diseases. We investigated to what extent different determinants contribute to the variation in SHBG levels in healthy young men.

Design and patients  Healthy male siblings (n = 677) aged 25–45 year were recruited in a cross‐sectional, population‐based study.

Measurements  Lean and fat mass were measured using dual‐energy X‐ray absorptiometry (DXA), and immunoassays were used to determine the serum hormonal levels. Additional information about smoking and physical activity was obtained using questionnaires. Carriers of two SHBG polymorphisms, the Asp327Asn polymorphism and the (TAAAA)n repeat polymorphism, were identified.

Results  Weight, BMI, whole body fat mass and truncal fat mass were negatively associated with SHBG levels. Body composition characteristics did not differ between SHBG genotype groups, indicating that body composition controls SHBG levels rather than the other way around. The associations may be mediated by adipokines because leptin and adiponectin were, respectively, inversely and positively associated with SHBG levels. Insulin and glucose were negatively associated with SHBG levels, as well as IGF‐1 and IGF‐BP3, while no associations were found with free thyroid hormone status.

Conclusions  In conclusion, we found that fat mass, insulin and IGF‐1 levels are important negative determinants of SHBG levels in young healthy men. The association with fat mass could be mediated by the effects of adiponectin and/or leptin on SHBG synthesis.
The impact of intensified exercise training on insulin resistance and fitness in overweight and obese women with and without polycystic ovary syndrome
Authors: Harrison Cheryce L. , Stepto Nigel K. , Hutchison Samantha K. , Teede Helena J.
Published: June 2011

Objective  To evaluate mechanisms of insulin resistance (IR) in overweight and obese women with and without polycystic ovary syndrome (PCOS) and explore relationships between IR, fitness and body mass index (BMI) at baseline and following exercise intervention.

Design  Prospective controlled intensified exercise intervention study.

Patients  A total of 20 overweight (BMI > 25 kg/m2) and obese (>30 kg/m2), reproductive‐aged PCOS women and 13 non‐PCOS overweight, healthy controls of comparable BMI and age were studied at baseline. Measures were repeated in 13 PCOS and eight control women following three 1‐h exercise sessions per week over 12 weeks.

Measurements  Insulin resistance was measured by glucose infusion rate on euglycaemic hyperinsulinaemic clamp, and fitness was assessed by VO2max.

Results  At baseline, PCOS women were 46% more insulin resistant than controls (175·6 vs 257·2 mg/m2/min, P < 0·05) with IR independently associated with VO2max and BMI in the PCOS group only (P < 0·01). Postexercise IR improved across both groups (P < 0·01). In PCOS women, IR improved by 16% (P < 0·05) but was not restored to the same level as controls (P < 0·05). Improvement in IR and in VO2max was related to the PCOS group (r2 = 0·85, P < 0·05), yet change in IR and in fitness was not related. No associations were found in controls.

Conclusions  While intensified exercise improves IR in PCOS women, a higher IR persisted following exercise in PCOS women, and a clear relationship between improved IR and improved fitness was not found. Therefore, other mechanisms of, and therapies for, IR must be explored in PCOS as IR remains higher than observed in non‐PCOS controls.
Visceral fat positively correlates with cholesterol synthesis in dyslipidaemic patients
Authors: Lupattelli Graziana , Pirro Matteo , Mannarino Massimo R. , Siepi Donatella , Roscini Anna R. , Schillaci Giuseppe , Mannarino Elmo
Published: June 2011

Eur J Clin Invest 2011

Background  Quantification of plasma noncholesterol sterols allows the study of cholesterol absorption and synthesis. A pattern of low cholesterol absorption and high synthesis has been demonstrated in patients with obesity and insulin resistance. To understand the relationship between cholesterol absorption/synthesis and visceral obesity, we investigated surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) in dyslipidaemic patients with different representation of abdominal fat, estimated by ultrasonographic measurement of visceral fat area (VFA).

Methods  In 126 patients with primary hyperlipaemias, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled with mass spectrometry. Visceral and subcutaneous fats were evaluated by ultrasonography. The study population was divided into two groups on the basis of VFA median values, below/equal and above 154 cm2.

Results  Patients with higher VFA had significantly higher lathosterol levels (median 109 vs. 76 × 102μmol/mmol cholesterol P < 0·004), body mass index, waist circumference, blood pressure, triglycerides, insulin, homoeostatic model assessment (HOMA)‐IR and lower high‐density lipoprotein (HDL)‐C. VFA was positively correlated with lathosterol (ρ = 0·35, P < 0·001) and negatively with HDL‐C (ρ = −0·43, P < 0·001), campesterol (ρ = −0·23, P = 0.01) and sitosterol (ρ = −0·35, P < 0·001). VFA was an independent predictor of lathosterol values (β = 0·389, P < 0·0001, P of the model < 0·0001);age, systolic blood pressure, BMI, waist circumference, triglycerides, HDL‐C and HOMA failed to enter the final equation.

Conclusions  In hyperlipidaemic patients, the amount of visceral fat correlates with cholesterol synthesis; the use of ultrasonographic detection of abdominal adiposity allows a better characterization of cholesterol pathway, potentially useful for a tailored therapeutic approach.
Using a climatic niche model to predict the direct and indirect impacts of climate change on the distribution of Douglas‐fir in New Zealand
Authors: Watt Michael S. , Stone Jeffrey K. , Hood Ian A. , Manning Lucy K.
Published: June 2011

Climate change is likely to have major impacts on the distribution of planted and natural forests. Herein, we demonstrate how a process‐based niche model (CLIMEX) can be extended to globally project the potential habitat suitable for Douglas‐fir. Within this distribution, we use CLIMEX to predict abundance of the pathogen
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haeocryptopus gaeumannii and severity of its associated foliage disease, Swiss needle cast. The distribution and severity of the disease, which can strongly reduce growth rate of Douglas‐fir, is closely correlated with seasonal temperatures and precipitation. This model is used to project how climate change during the 2080s may alter the area suitable for Douglas‐fir plantations within New Zealand. The climate change scenarios used indicate that the land area suitable for Douglas‐fir production in the North Island will be reduced markedly from near 100% under current climate to 36–64% of the total land area by 2080s. Within areas shown to be suitable for the host in the North Island, four of the six climate change scenarios predict substantial increases in disease severity that will make these regions at best marginal for Douglas‐fir by the 2080s. In contrast, most regions in the South Island are projected to sustain relatively low levels of disease, and remain suitable for Douglas‐fir under climate change over the course of this century.
Long‐term impacts of agricultural practices and climatic variability on carbon storage in a permanent pasture
Authors: Klumpp Katja , Tallec Tiphaine , Guix Noëlle , Soussana Jean‐François
Published: June 2011

Intra‐ and interannual variability of precipitation can lead to major modifications of grassland production and carbon storage capacity. Greater understanding of how climatic variability affects net CO2 exchange [i.e. net ecosystem exchange (NEE)] of grazed grasslands is important to adapt grassland management and reduce risks of carbon losses. Since 2002, we continuously measured NEE (i.e. eddy covariance technique) on an upland grassland site (7 ha), divided in two paddocks grazed by heifers (intensive: 1 LSU ha−1 yr−1, 213 kg N ha−1 yr−1 and extensive: 0.5 LSU ha−1 yr−1, no fertilization). For years with dry and warm growing seasons (i.e. 2003, 2005 and 2008), absolute annual NEE was higher in the intensive paddock compared with the extensive paddock. The opposite was observed during years of ample seasonal rainfall and soil moisture (i.e. 2004, 2006 and 2007). Contrasted management led to two distinct plant communities being different in leaf area index (LAI), soil bulk density and soil water holding capacity. Differences in annual NEEs could thus be assigned to interactions between in carbon and water fluxes during dry and wet growth periods. Dry growth periods led to a reduction in weekly gross primary productivity (GPP) in the extensively managed paddock, whereas the GPP was maintained in the intensive paddock. In turn, during wet growth periods, GPP was similar in both paddocks, whereas N amendment and frequent defoliation significantly increased ecosystem respiration in the intensive paddock, presumably through a higher heterotrophic respiration following on a better C substrate quality and availability (rhizodeposition and senescent fine roots). In the extensive paddock, where plant cover was denser (reducing soil temperature) and less decomposable, C losses through heterotrophic respiration were comparatively smaller under wet conditions. Our results demonstrate that grassland subjected to a moderately intensive management could be more resilient in terms of carbon storage during drought and heat waves, presumably because of a trade‐off between heterotrophic and autotrophic respiration.
Effects of cattle grazing on herbage quality in a herbaceous Mediterranean rangeland
Authors: Henkin Z. , Ungar E. D. , Dvash L. , Perevolotsky A. , Yehuda Y. , Sternberg M. , Voet H. , Landau S. Y.
Published: June 2011

The main objective of this study was to determine to what extent grazing pressure and timing modulate the seasonal progression of herbage quality in hilly Mediterranean grassland systems. The study was conducted during six consecutive years between 2003 and 2008 at the Karei Deshe experimental farm, in eastern Galilee, Israel, dominated by rich hemicryptophytic grassland. Treatments included two different grazing intensities, heavy and moderate, with 1·1 and 0·55 cows ha−1, respectively, and management that included a continuous and a seasonal stocking system that was divided at both intensities into early and late grazing. Herbage samples were analysed for digestibility, crude protein, neutral detergent fibre and acid detergent fibre contents. Significant differences in herbage quality were found between seasons and years. Herbage quality was significantly higher in paddocks grazed continuously or early in the season. Herbage quality increased with increasing grazing intensity as younger herbage and continued re‐growth were maintained during the green season. The greater difference between herbage qualities was found at the peak of the growing season. The significant differences found in herbage quality emphasize the importance of the decision‐making process aimed at improving cattle grazing management in Mediterranean rangelands and its consequences for the sustainability of the system.
rFVIIa administered by continuous infusion during surgery in patients with severe congenital FVII deficiency
Authors: TRAN H. T. T. , TJØNNFJORD G. E. , PAUS A. , HOLME P. A.
Published: June 2011

Summary. The use of recombinant FVIIa (rFVIIa) to control bleed in individuals with FVII deficiency has been proven to be effective. The main problems associated with its use are that it requires frequent bolus injections to counteract its short half‐life and high cost. Our study aimed to evaluate whether any advantage could be gained by providing rFVIIa by continuous infusion during surgery with regard to haemostatic efficacy, safety and cost. The prospective study included 10 patients with severe FVII deficiency, who underwent 25 surgical procedures (13 major and 12 minor procedures) and were treated with rFVIIa administered by continuous infusion. Tranexamic acid was given concomitantly every 8 h. Prothrombin time, FVII:C assay and thrombin generation assay were used to monitor the treatment. The mean total dose given was 10 mg during a major surgery and 4.4 mg during a minor surgery for a mean treatment duration of 7.5 and 4.0 days respectively. This corresponds to a reduction of 70–90% in drug usage and medication cost compared with bolus injections. Except for one major perioperative bleeding, excellent haemostasis was achieved in all procedures. One patient developed a transient inhibitory activity. None of these events affected the postoperative course or prolonged the hospital stay. Our study demonstrated that continuous infusion of rFVIIa during surgery is safe, effective and highly cost effective.
Identification and characterization of the cysteine protease inhibitor gene MdCPI from Musca domestica
Authors: Dong X. , Liu F. , Zhang D. , Tang T. , Ge X.
Published: June 2011

Cysteine proteinase inhibitors (CPIs) are involved in many vital cellular processes such as signalling pathways, apoptosis, immune response and development; however, no CPIs have yet been reported from the housefly Musca domestica. Here we report the isolation and characterization of a housefly CPI gene designated MdCPI. The gene contains an open reading frame of 357 bp encoding a protein of 118 amino acid residues with a putative signal peptide of 17 amino acid residues. Protein alignment demonstrated a high homology to that of Sarcophaga crassipalpis (identity = 51%). Phylogenetic analysis suggested that all CPIs from dipterans, including the housefly, belong to the I25A family and may be descended from a single common ancestor. The gene was expressed in and purified from Escherichia coli. Biochemical studies showed that MdCPI exerts an inhibiting function on papain, which is a classical assay to confirm CPIs. Real‐time quantitative PCR and immunolocalization analysis revealed that MdCPI is specifically expressed in haemocytes and fat bodies. It is highly down‐regulated in larvae and markedly up‐regulated in the pupal stage, suggesting that it may be related to development.
Being concerned: caregiving for Taiwanese mothers of a child with cerebral palsy
Authors: Huang Yu‐Ping , Kellett Ursula , St John Winsome
Published: June 2011

Aims and objectives.  This article explores the Chinese social context and provides insight into Taiwanese mothers’ challenging experiences when a disabled child is born into their families.

Background.  International research indicates that barriers to maternal caregiving for a disabled child revolve around challenging relationships. Giving birth to a disabled child creates a huge challenge for mothers in Chinese society.

Design.  Data were collected using in‐depth interviews and journaling methods. A hermeneutic phenomenological approach, informed by the philosophical world views of Heidegger and Gadamer, provided theoretical guidance in revealing and interpreting mothers’ experiences.

Method.  Interviews were carried out with a purposeful sample of 15 mothers who were primary caregivers for a child aged between 0–18 years who was diagnosed with cerebral palsy and used Mandarin or Taiwanese as their primary language.

Results.  Shared meanings revealed four modes of being concerned: (1) experiencing burden as a sole primary caregiver; (2) managing the challenges by balancing demands; (3) being marginalised by others; and (4) encountering limited or no professional support.

Conclusions.  Taiwanese mothers face the strain of managing barriers to caregiving in contexts in which their children are not supported or acknowledged as being important contributors to family and Chinese society at large. This study highlights how the family can be important to caregiving mothers in traditional Chinese family life. Poor support and dynamics will emerge when family members regard disability as a loss of face or a stigma.

Relevance to clinical practice.  By learning from Taiwanese mothers who accommodate barriers to caregiving on a daily basis, nurses can seize the impetus to explore ways of reconceptualising nursing practice with families and people with disabilities. The aim is to explore ways that will ultimately align intentions and caring processes and foster coping and positive reward in caring, thereby creating a context that is stress reducing and therapeutic.
Informal stroke caregivers’ self‐appraised problem‐solving abilities as a predictor of well‐being and perceived social support
Authors: Lui May H‐L , Lee Diana TF , Greenwood Nan , Ross Fiona M
Published: June 2011

Aim.  To describe the relationship between self‐appraised problem‐solving abilities and psychological distress, burden and perceived social support in informal, family stroke caregivers.

Background.  Previous research suggests that self‐appraised problem‐solving abilities play a significant role in the well‐being of family caregivers of patients with chronic illness. However, little is known about its role in caregivers of stroke survivors.

Design.  Prospective correlational study.

Methods.  One week before discharge, 103 family caregivers of survivors of a first stroke were assessed for their perceived problem‐solving abilities, social support, anxiety, depression and physical well‐being. At three months postdischarge, 85 of these caregivers (83% retention) were reassessed on the same measures. In addition, their levels of burden and perceived difficulties were also measured.

Results.  Using multiple regression, overall self‐appraised problem‐solving abilities and its subscale ‘confidence in problem‐solving’ at one week before discharge were significant predictors of caregiver perceived social support (R2 = 29%) and perceived physical well‐being (R2 = 42%) at three months postdischarge. Other relationships were non‐significant.

Conclusions.  Caregivers’ perceived social support and physical well‐being were significantly predicted by confidence in problem‐solving.

Relevance to clinical practice.  This study is timely given the challenges facing health systems in Hong Kong to effectively manage chronic illness through family‐centred care. The significant relationships between caregiver self‐appraised problem‐solving, perceived social support and well‐being suggest that interventions maximising caregiver confidence in problem‐solving might be valuable in supporting family caregivers of stroke survivors. Nurses working with families caring for stroke survivors both close to discharge and in the early transition stages back at home may be in an ideal position to offer this support.