bluuebunny/crossref_metadata_2025 huggingface dataset:
Thematic analysis of readmission into inpatient units for adults with intellectual disabilities: Two case studies
Authors: Daya A. , Dhillon J. , Taylor M. , Yildiran H.
Published: December 2011

This audit explores readmissions into inpatient services for adults with intellectual disabilities, using two case studies. Thirteen semi-structured interviews were conducted with professionals, to gain a multidisciplinary perspective, between February and March 2010, and analysed using thematic analysis. The main themes found in case study 1 were: narrow focus, environment, communication, early discharge, and deterioration. The main themes found in case study 2 were: deterioration, communication, discharge too soon, and environment. The aims of the audit were to contribute to good practice and provide a better understanding of readmission within our services.
Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering
Authors: Stamati Katerina , Mudera Vivek , Cheema Umber
Published: December 2011

Oxygen is one of the critically defining elements resulting in the existence of eukaryotic life on this planet. The rise and fall of this element can be tracked through time and corresponds with the evolution of diverse life forms, development of efficient energy production (oxidative phosphorylation) in single cell organisms, the evolution of multicellular organisms and the regulation of complex cell phenotypes. By understanding these events, we can plot the effect of oxygen on evolution and its direct influence on different forms of life today, from the whole organism to specific cells within multicellular organisms. In the emerging field of tissue engineering, understanding the role of different levels of oxygen for normal cell function as well as control of complex signalling cascades is paramount to effectively build 3D tissues in vitro and their subsequent survival when implanted.
De novo assembly of Euphorbia fischeriana root transcriptome identifies prostratin pathway related genes
Authors: Barrero Roberto A , Chapman Brett , Yang Yanfang , Moolhuijzen Paula , Keeble-Gagnère Gabriel , Zhang Nan , Tang Qi , Bellgard Matthew I , Qiu Deyou
Published: December 2011

Background

Euphorbia fischerianais an important medicinal plant found in Northeast China. The plant roots contain many medicinal compounds including 12-deoxyphorbol-13-acetate, commonly known as prostratin that is a phorbol ester from the tigliane diterpene series. Prostratin is a protein kinase C activator and is effective in the treatment of Human Immunodeficiency Virus (HIV) by acting as a latent HIV activator. Latent HIV is currently the biggest limitation for viral eradication. The aim of this study was to sequence, assemble and annotate theE. fischerianatranscriptome to better understand the potential biochemical pathways leading to the synthesis of prostratin and other related diterpene compounds.

Results

In this study we conducted a high throughput RNA-seq approach to sequence the root transcriptome ofE. fischeriana. We assembled 18,180 transcripts, of these the majority encoded protein-coding genes and only 17 transcripts corresponded to known RNA genes. Interestingly, we identified 5,956 protein-coding transcripts with high similarity (> = 75%) toRicinus communis, a close relative toE. fischeriana. We also evaluated the conservation ofE. fischerianagenes against EST datasets from the Euphorbeacea family, which includedR. communis,Hevea brasiliensisandEuphorbia esula. We identified a core set of 1,145 gene clusters conserved in all four species and 1,487E. fischerianaparalogous genes. Furthermore, we screenedE. fischerianatranscripts against an in-house reference database for genes implicated in the biosynthesis of upstream precursors to prostratin. This identified 24 and 9 candidate transcripts involved in the terpenoid and diterpenoid biosyntehsis pathways, respectively. The majority of the candidate genes in these pathways presented relatively low expression levels except for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (HDS) and isopentenyl diphosphate/dimethylallyl diphosphate synthase (IDS), which are required for multiple downstream pathways including synthesis of casbene, a proposed precursor to prostratin.

Conclusion

The resources generated in this study provide new insights into the upstream pathways to the synthesis of prostratin and will likely facilitate functional studies aiming to produce larger quantities of this compound for HIV research and/or treatment of patients.
The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis
Authors: Zhang Yonggang , He Jie , Deng Yao , Zhang Jie , Li Xiaobo , Xiang Zhangpeng , Huang Honglang , Tian Can , Huang Jin , Fan Hong
Published: December 2011

Background

The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility to cancer, but a large number of studies have reported inconclusive results. The aim of this study is to assess the association between the I/D polymorphism in the ACE gene and cancer risk by meta-analysis.

Methods

A search was performed in Pubmed database, Embase database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI) database and Weipu database, covering all studies until August 31, 2010. Statistical analysis was performed by using Revman4.2 and STATA 10.0.

Results

A total of 25 case-control studies comprising 3914 cancer patients and 11391 controls were identified. No significant association was found between the I/D polymorphism and over all cancer risks (OR = 0.88, 95%CI = 0.73-1.06, P = 0.17 for DD+DI vs. II). In the subgroup analysis by ethnicity, no significant association was found among Asians and Europeans for the comparison of DD+DI vs. II. In the subgroup analysis by cancer types, no significant associations were found among lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated the lack of associations between this polymorphism and cancer risks.

Conclusions

This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of cancer.
Factors associated with caregiver burden in a child and adolescent psychiatric facility in Lagos, Nigeria: a descriptive cross sectional study
Authors: Dada Mobolaji U , Okewole Niran O , Ogun Oluyemi C , Bello-Mojeed Mashudat A
Published: December 2011

Background

Definitions of burden of care stress the effect of the patient's mental illness on the family. There are generally very few studies in this environment on caregiver burden in child/adolescent mental ill-health. This study aimed to identify patient and caregiver characteristics that are associated with caregiver burden.

Method

Caregivers of patients attending the Child and Adolescent Clinic of the Neuropsychiatric Hospital, Yaba, Lagos [n = 155] were consecutively recruited over a one-month period. The caregivers were administered a sociodemographic questionnaire, the General Health Questionnaire, Zarit Burden Interview, and the Columbia Impairment Scale. Scoring on the Children's Global Assessment Scale was done by clinicians.

Results

Most caregivers observed in this study were females (80.5%), with mothers of the patients accounting for 78% of all the caregivers. A higher percentage of the patients were males (52.8%). Moderate to severe/severe burden was recorded among 25.2% of caregivers. Factors associated with caregiver burden were patient's level of functioning [r = 0.489, p < 0.001], psychiatric morbidity in the caregiver [r = 0.709, p < 0.001], level of impairment as assessed by the caregiver [r = 0.545, p < 0.001], and child's level of education [t = 3.274, p = 0.001]. Each one independently predicted caregiver burden.

Conclusion

The study reveals a high level of burden among the caregivers of children and adolescents with mental health problems.
Sexual Knowledge, attitudes and behaviors among unmarried migrant female workers in China: a comparative analysis
Authors: Tang Jie , Gao Xiaohui , Yu Yizhen , Ahmed Niman Isse , Zhu Huiping , Wang Jiaji , Du Yukai
Published: December 2011

Background

In recent years, many studies have focused on adolescent's sex-related issues in China. However, there have been few studies of unmarried migrant females' sexual knowledge, attitudes and behaviors, which is important for sexual health education and promotion.

Methods

A sample of 5156 unmarried migrant female workers was selected from three manufacturing factories, two located in Shenzhen and one in Guangzhou, China. Demographic data, sexual knowledge, attitudes and behaviors were assessed by self-administered questionnaires. Multivariate logistic regression analysis was conducted to examine the factors associated with premarital sexual intercourse.

Results

The average age of the unmarried female workers included in the sample was 20.2 years, and majority of them showed a low level of sex-related knowledge. Females from the west of China demonstrated a significant lower level of sex-related knowledge than those from the eastern or central provinces (p < 0.05). Approximately 13% of participants held a favorable attitude towards premarital sexual intercourse, and youths from the east/central were more likely to have favorable attitudes compared with those from the west (p < 0.05). About 17.0% of the unmarried female workers reported having engaged in premarital sexual intercourse, and females from the east/central were more likely to have experienced premarital sexual intercourse than those from the west (p < 0.05). Multivariate analysis revealed that age, education, current residential type, dating, sexual knowledge, attitudes, and pattern of communication were significantly associated with premarital sexual intercourse.

Conclusion

The unmarried migrant female workers lack sexual knowledge and a substantial proportion of them are engaged in premarital sexual behaviors. Interventions aimed at improving their sexual knowledge and related skills are needed.
A high-performance quantum dot superluminescent diode with a two-section structure
Authors: Li Xinkun , Jin Peng , An Qi , Wang Zuocai , Lv Xueqin , Wei Heng , Wu Jian , Wu Ju , Wang Zhanguo
Published: December 2011

Based on InAs/GaAs quantum dots [QDs], a high-power and broadband superluminescent diode [SLD] is achieved by monolithically integrating a conventional SLD with a semiconductor optical amplifier. The two-section QD-SLD device exhibits a high output power above 500 mW with a broad emission spectrum of 86 nm. By properly controlling the current injection in the two sections of the QD-SLD device, the output power of the SLD can be tuned over a wide range from 200 to 500 mW while preserving a broad emission spectrum based on the balance between the ground state emission and the first excited state emission of QDs. The gain process of the two-section QD-SLD with different pumping levels in the two sections is investigated.
Temporal pattern of expression and colocalization of microglia/macrophage phenotype markers following brain ischemic injury in mice
Authors: Perego Carlo , Fumagalli Stefano , De Simoni Maria-Grazia
Published: December 2011

Background

Emerging evidence indicates that, similarly to what happens for peripheral macrophages, microglia can express different phenotypes depending on microenvironmental signals. In spite of the large literature on inflammation after ischemia, information on M/M phenotype marker expression, their colocalization and temporal evolution in the injured brain is lacking. The present study investigates the presence of microglia/macrophage phenotype markers, their temporal expression, whether they are concomitantly expressed by the same subpopulation, or they are expressed at distinct phases or locations in relation to the ischemic lesion.

Methods

Volume of ischemic lesion, neuronal counts and TUNEL staining were assessed in C57Bl/6 mice at 6-12-24-48 h and 7d after permanent occlusion of the middle cerebral artery. At the same time points, the expression, distribution in the lesioned area, association with a definite morphology and coexpression of the microglia/macrophage markers CD11b, CD45, CD68, Ym1, CD206 were assessed by immunostaining and confocal microscopy.

Results

The results show that: 1) the ischemic lesion induces the expression of selected microglia/macrophage markers that develop over time, each with a specific pattern; 2) each marker has a given localization in the lesioned area with no apparent changes during time, with the exception of CD68 that is confined in the border zone of the lesion at early times but it greatly increases and invades the ischemic core at 7d; 3) while CD68 is expressed in both ramified and globular CD11b cells, Ym1 and CD206 are exclusively expressed by globular CD11b cells.

Conclusions

These data show that the ischemic lesion is accompanied by activation of specific microglia/macrophage phenotype that presents distinctive spatial and temporal features. These different states of microglia/macrophages reflect the complexity of these cells and their ability to differentiate towards a multitude of phenotypes depending on the surrounding micro-environmental signals that can change over time. The data presented in this study provide a basis for understanding this complex response and for developing strategies resulting in promotion of a protective inflammatory phenotype.
Type of diet modulates the metabolic response to sleep deprivation in rats
Authors: Martins Paulo JF , Fernandes Leandro , de Oliveira Allan C , Tufik Sergio , D'Almeida Vânia
Published: December 2011

Background

Evidence suggests that sleep loss is associated with an increased risk of obesity and diabetes; however, animal models have failed to produce weight gain under sleep deprivation (SD). Previous studies have suggested that this discrepancy could be due to more extreme SD conditions in experimental animals, their higher resting metabolic rate than that of humans, and the decreased opportunity for animals to ingest high-calorie foods. Thus, our objective was to determine whether diets with different textures/compositions could modify feeding behavior and affect the metabolic repercussions in SD in rats.

Methods

Three groups of male rats were used: one was designated as control, one was sleep deprived for 96 h by the platform technique (SD-96h) and one was SD-96h followed by a 24-h recovery (rebound). In the first experiment, the animals were fed chow pellets (CPs); in the second, they received high-fat diet and in the third, they were fed a liquid diet (LD).

Results

We observed that SD induces energy deficits that were related to changes in feeding behavior and affected by the type of diet consumed. Regardless of the diet consumed, SD consistently increased animals' glucagon levels and decreased their leptin and triacylglycerol levels and liver glycogen stores. However, such changes were mostly avoided in the rats on the liquid diet. SD induces a wide range of metabolic and hormonal changes that are strongly linked to the severity of weight loss.

Conclusions

The LD, but not the CP or high-fat diets, favored energy intake, consequently lessening the energy deficit induced by SD.
Transcriptome analysis of anti-fatty liver action by Campari tomato using a zebrafish diet-induced obesity model
Authors: Tainaka Toshiyuki , Shimada Yasuhito , Kuroyanagi Junya , Zang Liqing , Oka Takehiko , Nishimura Yuhei , Nishimura Norihiro , Tanaka Toshio
Published: December 2011

Background

High dietary intake of vegetable products is beneficial against obesity and its related diseases such as dyslipidemia, nonalcoholic fatty liver disease, and cancer. We previously developed a diet-induced obesity model of zebrafish (DIO-zebrafish) that develops visceral adiposity, dyslipidemia, and liver steatosis. Zebrafish is a polyphagous animal; thus we hypothesized that DIO-zebrafish could be used for transcriptome analysis of anti-obesity effects of vegetables.

Results

Each vegetable exhibited different effects against obesity. We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish. Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain.

Conclusions

Campari tomato ameliorates diet-induced obesity, especially dyslipidemia and liver steatosis via downregulation of gene expression related to lipogenesis. DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products.
Intimal aortic sarcoma mimicking ruptured thoracoabdominal type IV aneurysm. a rare case report and review of the literature
Authors: Dedeilias Panagiotis , Koletsis Efstratios , Nenekidis Ioannis , Chatziioannou Achilles , Tsipas Pantelis , Dimaka Konstantina , Anagnostakou Vania , Apostolakis Efstratios
Published: December 2011

Primary intimal aortic sarcoma represents a very rare and highly lethal medical entity. Diagnosis is made either by embolic events caused by the tumor or by surrounding tissue symptoms such as pain. Herein we report an extremely rare case of a 51-year-old man previously operated for ascending aortic aneurysm, who presented with clinical and radiological findings suggestive of a ruptured thoracoabdominal type IV aneurysm. The patient underwent radical resection of the aorta and surrounding tissue with placement of a composite 4-branched graft. The diagnosis was made by frozen section and regular histopathologic examination of the specimen and the patient received adjuvant chemotherapy. Nine months after surgery the patient is still alive and has no signs of recurrence. We review the literature and discuss the option of postoperative chemotherapy.
Noise filtering tradeoffs in spatial gradient sensing and cell polarization response
Authors: Chou Ching-Shan , Bardwell Lee , Nie Qing , Yi Tau-Mu
Published: December 2011

Background

Cells sense chemical spatial gradients and respond by polarizing internal components. This process can be disrupted by gradient noise caused by fluctuations in chemical concentration.

Results

We investigated how external gradient noise affects spatial sensing and response focusing on noise-filtering and the resultant tradeoffs. First, using a coarse-grained mathematical model of gradient-sensing and cell polarity, we characterized three negative consequences of noise: Inhibition of the extent of polarization, degradation of directional accuracy, and production of a noisy output polarization. Next, we explored filtering strategies and discovered that a combination of positive feedback, multiple signaling stages, and time-averaging produced good results. There was an important tradeoff, however, because filtering resulted in slower polarization. Simulations demonstrated that a two-stage filter-amplifier resulted in a balanced outcome. Then, we analyzed the effect of noise on a mechanistic model of yeast cell polarization in response to gradients of mating pheromone. This analysis showed that yeast cells likely also combine the above three filtering mechanisms into a filter-amplifier structure to achieve impressive spatial-noise tolerance, but with the consequence of a slow response time. Further investigation of the amplifier architecture revealed two positive feedback loops, a fast inner and a slow outer, both of which contributed to noise-tolerant polarization. This model also made specific predictions about how orientation performance depended upon the ratio between the gradient slope (signal) and the noise variance. To test these predictions, we performed microfluidics experiments measuring the ability of yeast cells to orient to shallow gradients of mating pheromone. The results of these experiments agreed well with the modeling predictions, demonstrating that yeast cells can sense gradients shallower than 0.1% μm-1, approximately a single receptor-ligand molecule difference between front and back, on par with motile eukaryotic cells.

Conclusions

Spatial noise impedes the extent, accuracy, and smoothness of cell polarization. A combined filtering strategy implemented by a filter-amplifier architecture with slow dynamics was effective. Modeling and experimental data suggest that yeast cells employ these elaborate mechanisms to filter gradient noise resulting in a slow but relatively accurate polarization response.
First trimester myomectomy as an alternative to termination of pregnancy in a woman with a symptomatic uterine leiomyoma: a case report
Authors: Leach Kara , Khatain Larissa , Tocce Kristina
Published: December 2011

Introduction

Performing a myomectomy during pregnancy is extremely rare due to the risk of pregnancy loss, hemorrhage and hysterectomy. Favorable outcomes have been demonstrated with select second trimester gravid myomectomies. Literature documenting first trimester surgical management of myomas during pregnancy is scant. Patients with symptomatic myomas failing conservative management in the first trimester may be counseled to abort the pregnancy and then undergo myomectomy. Reports focusing on myomectomy in the first trimester are needed to permit more thorough options counseling for patients failing conservative management in the first trimester.

Case presentation

A 30-year-old Caucasian primagravid (G1P0) was referred for termination of her pregnancy at 10 weeks due to a 14 cm myoma causing severe pain, constipation and urine retention. Her referring physician planned an interval myomectomy following the abortion. Instead, our patient underwent myomectomy at 11 weeks. Two leiomyomas were successfully removed; she delivered a healthy infant at term.

Conclusion

Patients in the first trimester should not be counseled that termination followed by myomectomy is the best option for symptomatic myomas, failing conservative treatment. Management should be individualized after taking into account the patient's symptoms, gestational age and the location of the myomas in relation to the placenta. Any field providing women's health services will be impacted by the ability to offer more thorough options counseling for women with refractory myomas in the first trimester.
High level expression of Acidothermus cellulolyticusβ-1, 4-endoglucanase in transgenic rice enhances the hydrolysis of its straw by cultured cow gastric fluid
Authors: Chou Hong Li , Dai Ziyu , Hsieh Chia Wen , Ku Maurice SB
Published: December 2011

Background

Large-scale production of effective cellulose hydrolytic enzymes is the key to the bioconversion of agricultural residues to ethanol. The goal of this study was to develop a rice plant as a bioreactor for the large-scale production of cellulose hydrolytic enzymes via genetic transformation, and to simultaneously improve rice straw as an efficient biomass feedstock for conversion of cellulose to glucose.

Results

In this study, the cellulose hydrolytic enzyme β-1, 4-endoglucanase (E1) gene, from the thermophilic bacterium Acidothermus cellulolyticus, was overexpressed in rice through Agrobacterium-mediated transformation. The expression of the bacterial E1 gene in rice was driven by the constitutive Mac promoter, a hybrid promoter of Ti plasmid mannopine synthetase promoter and cauliflower mosaic virus 35S promoter enhancer, with the signal peptide of tobacco pathogenesis-related protein for targeting the E1 protein to the apoplastic compartment for storage. A total of 52 transgenic rice plants from six independent lines expressing the bacterial E1 enzyme were obtained that expressed the gene at high levels without severely impairing plant growth and development. However, some transgenic plants exhibited a shorter stature and flowered earlier than the wild type plants. The E1 specific activities in the leaves of the highest expressing transgenic rice lines were about 20-fold higher than those of various transgenic plants obtained in previous studies and the protein amounts accounted for up to 6.1% of the total leaf soluble protein. A zymogram and temperature-dependent activity analyses demonstrated the thermostability of the E1 enzyme and its substrate specificity against cellulose, and a simple heat treatment can be used to purify the protein. In addition, hydrolysis of transgenic rice straw with cultured cow gastric fluid for one hour at 39°C and another hour at 81°C yielded 43% more reducing sugars than wild type rice straw.

Conclusion

Taken together, these data suggest that transgenic rice can effectively serve as a bioreactor for the large-scale production of active, thermostable cellulose hydrolytic enzymes. As a feedstock, direct expression of large amount of cellulases in transgenic rice may also facilitate saccharification of cellulose in rice straw and significantly reduce the costs for hydrolytic enzymes.
Indoleamine 2,3‐dioxygenase expression in patients with allergic rhinitis: a case‐control study
Authors: Luukkainen Annika , Karjalainen Jussi , Honkanen Teemu , Lehtonen Mikko , Paavonen Timo , Toppila‐Salmi Sanna
Published: December 2011

Background

Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated.

Objective

Our aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non‐atopic patients.

Methods

IDO expression was immunohistochemically evaluated from nasal specimens obtained in‐ and off‐season from otherwise healthy non‐smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis) and non‐allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in‐ and off‐season in either healthy or allergic subjects.

Conclusions

There is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.
The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study
Authors: Zhang Jie , Delzell Elizabeth , Xie Fenglong , Baddley John W , Spettell Claire , Mcmahan Raechele M , Fernandes Joaquim , Chen Lang , Winthrop Kevin , Curtis Jeffrey R
Published: December 2011

Introduction

Zostavax, a live attenuated vaccine, has been approved in the United States for use in older individuals to reduce the risk and severity of herpes zoster (HZ), also known as shingles. The vaccine is contraindicated in individuals taking anti-tumor necrosis factor alpha (anti-TNF) therapies or other biologics commonly used to treat autoimmune diseases because of the safety concern that zoster vaccine may be associated with a short-term HZ risk. The objective of the study was to examine the use, safety (short-term HZ risk after vaccination), and effectiveness of zoster vaccine in individuals with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases.

Methods

We conducted a cohort study of patients aged 50 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases by using administrative claims data from a nationwide health plan from January 1, 2005, to August 31, 2009. We examined the extent to which zoster vaccine was used; assessed factors associated with vaccine use (Cox proportional hazards regression); and compared the incidence rates of herpes zoster (HZ) between vaccinated and unvaccinated patients.

Results

Among 44,115 patients with the autoimmune diseases, 551 (1.2%) received zoster vaccine, and 761 developed HZ. Zoster vaccine use increased continuously after approval in 2006. Younger and healthier patients, those who had an HZ infection within the past 6 months, and those who were not using anti-TNF therapies were more likely to receive the vaccine. Approximately 6% of vaccinated patients were using anti-TNF therapies at the time of vaccination. The incidence rates of HZ were similar in vaccinated and unvaccinated patients (standardized incidence ratio, 0.99; 95% confidence interval, 0.29 to 3.43).

Conclusions

Use of the zoster vaccine was uncommon among older patients with autoimmune diseases, including those not exposed to immunosuppressive medications. The short-term risk of HZ did not appear to be increased in vaccinated patients, even among those using immunosuppressive therapies (for example, biologics) at the time of vaccination. However, our study was limited by the small number of vaccinated patients, and further evidence is needed to confirm the vaccine's safety and efficacy in this population.
Primary care physicians' perspectives towards managing rheumatoid arthritis: room for improvement
Authors: Garneau Katie L , Iversen Maura D , Tsao Hsun , Solomon Daniel H
Published: December 2011

Introduction

Many people with rheumatoid arthritis (RA) do not receive care from a rheumatologist. We surveyed primary care physicians (PCPs) to better understand their attitudes, knowledge, and practices regarding the optimal treatment of RA.

Methods

Randomly selected PCPs practicing in the US were surveyed. The survey encompassed their experience with RA, use of disease modifying anti-rheumatic drugs (DMARDs), and experience with rheumatology referrals. Logistic regression analyses described the responses and examined the correlation between physician variables and use of DMARDs.

Results

E-mail invitations were opened by 1, 103 PCPs and completed by 267 (25%). Most respondents were men (68%) in practice for over 10 years (64%) who reported 6 or more RA patients under their care in the last year (71%). The majority reported some RA training after medical school (59%), but only one-third felt very confident managing this condition. Most (81%) reported prescribing DMARDs, but 37% do not initiate them, with only 9% reporting being very confident starting a DMARD. In unadjusted analyses, several respondent characteristics were strongly associated with not prescribing DMARDs, but none was significant after adjustment. Almost half (44%) of PCPs noted that patients report difficulty getting appointments with rheumatologists.

Conclusions

We found many PCPs are uncomfortable managing RA with DMARDs, despite common beliefs that their patients lack access to a rheumatologist. Lack of accessibility to rheumatologists and discomfort in prescribing DMARDs for patients with RA are potential barriers to optimal treatment.
Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells
Authors: Oh Keunhee , Ko Eunyoung , Kim Hee Sung , Park Ae Kyung , Moon Hyeong-Gon , Noh Dong-Young , Lee Dong-Sup
Published: December 2011

Introduction

Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis.

Methods

To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study.

Results

IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival (P = 0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only (P = 0.013).

Conclusions

We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer.
Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion
Authors: Victor Bernadette C , Anbalagan Arulselvi , Mohamed Mona M , Sloane Bonnie F , Cavallo-Medved Dora
Published: December 2011

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real time the degradation of type IV collagen by IBC cells. IBC patient biopsies were examined for expression of cathepsin B and caveolin-1.

Results

Both cell lines expressed comparable levels of cathepsin B and uPA. In contrast, levels of caveolin-1 and uPAR were greater in SUM149 cells. We observed that uPA, uPAR and enzymatically active cathepsin B were colocalized in caveolae fractions isolated from SUM149 cells. Using a live-cell proteolysis assay, we demonstrated that both IBC cell lines degrade type IV collagen. The SUM149 cells exhibit predominantly pericellular proteolysis, consistent with localization of proteolytic pathway constitutents to caveolar membrane microdomains. A functional role for cathepsin B was confirmed by the ability of CA074, a cell impermeable and highly selective cathepsin B inhibitor, to significantly reduce pericellular proteolysis and invasion by SUM149 cells. A statistically significant co-expression of cathepsin B and caveolin-1 was found in IBC patient biopsies, thus validating our in vitro data.

Conclusion

Our study is the first to show that the proteolytic activity of cathepsin B and its co-expression with caveolin-1 contributes to the aggressiveness of IBC.
Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: Support for the 2009 IDSA treatment guidelines for candidiasis
Authors: Kett Daniel H , Shorr Andrew F , Reboli Annette C , Reisman Arlene L , Biswas Pinaki , Schlamm Haran T
Published: December 2011

Introduction

During the past decade, the incidence of Candida infections in hospitalized patients has increased, with fluconazole being the most commonly prescribed systemic antifungal agent for these infections. However, the 2009 Infectious Diseases Society of America (IDSA) candidiasis guidelines recommend an echinocandin for the treatment of candidemia/invasive candidiasis in patients who are considered to be "moderately severe or severely" ill. To validate these guidelines, clinical trial data were reviewed.

Methods

A secondary analysis of data from a previously published prospective, randomized, double-blind clinical trial was performed; it compared anidulafungin with fluconazole for the treatment of invasive candidiasis and candidemia. Patients with critical illness were identified at study entry by using the following criteria: Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥ 15, evidence of severe sepsis (sepsis and one or more end-organ dysfunctions) present, and/or patient was in intensive care. Global response rates were compared at the end of intravenous study treatment (the primary end point of the original study) and all-cause mortality at 14 and 28 days from study entry in this group.

Results

The patients (163 (66.5%) of 245) fulfilled at least one criterion for critical illness (anidulafungin, n = 89; fluconazole, n = 74). No significant differences were found in baseline characteristics between the two treatment groups. The global response rate was 70.8% for anidulafungin and 54.1% for fluconazole (P = 0.03; 95% confidence interval (CI): 2.0 to 31.5); all-cause mortality was 10.1% versus 20.3% at 14 days (P = 0.08; 95% CI, -0.9 to 21.3) and was 20.2% versus 24.3% at 28 days (P = 0.57; 95% CI, -8.8 to 17.0) for anidulafungin and fluconazole, respectively.

Conclusions

In this post hoc analysis, anidulafungin was more effective than fluconazole for treatment of severely ill patients with candidemia, thus supporting the 2009 IDSA guidelines.

Trial registration

Clinicaltrials.gov NCT00058682.
Acute phase proteins and white blood cell levels for prediction of infectious complications in status epilepticus
Authors: Sutter Raoul , Tschudin-Sutter Sarah , Grize Leticia , Widmer Andreas F , Marsch Stephan , Rüegg Stephan
Published: December 2011

Introduction

Infections in status epilepticus (SE) patients result in severe morbidity making early diagnosis crucial. As SE may lead to inflammatory reaction, the value of acute phase proteins and white blood cells (WBC) for diagnosis of infections during SE may be important. We examined the reliability of C-reactive protein (CRP), procalcitonin (PCT), and WBC for diagnosis of infections during SE.

Methods

All consecutive SE patients treated in the ICU from 2005 to 2009 were included. Clinical and microbiological records, and measurements of CRP and WBC during SE were analyzed. Subgroup analysis was performed for additional PCT measurements in the first 48 hours of SE.

Results

A total of 22.5% of 160 consecutive SE patients had infections during SE. Single levels of CRP and WBC had no association with the presence of infections. Their linear changes over the first three days after SE onset were significantly associated with the presence of infections (P = 0.0012 for CRP, P = 0.0137 for WBC). Levels of PCT were available for 31 patients and did not differ significantly in patients with and without infections. Sensitivity of PCT and CRP was high (94% and 83%) and the negative predictive value of CRP increased over the first three days to 97%. Specificity was low, without improvement for different cut-offs.

Conclusions

Single levels of CRP and WBC are not reliable for diagnosis of infections during SE, while their linear changes over time significantly correlate with the presence of infections. In addition, low levels of CRP and PCT rule out hospital-acquired infections in SE patients.
SpeCond: a method to detect condition-specific gene expression
Authors: Cavalli Florence MG , Bourgon Richard , Huber Wolfgang , Vaquerizas Juan M , Luscombe Nicholas M
Published: December 2011

Transcriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html.
Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: Signorello Lisa B. , Mulvihill John J. , Green Daniel M. , Munro Heather M. , Stovall Marilyn , Weathers Rita E. , Mertens Ann C. , Whitton John A. , Robison Leslie L. , Boice John D.
Published: December 2011

Purpose

Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses.

Methods

Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression.

Results

One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors.

Conclusion

Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.
Arab Spring: A Partial Awakening
Authors: Cannistraro Vincent
Published: December 2011

The Arab Spring has affected interests of the Western democracies in the Middle and Near Eastern nations, and the instability will compel changes in American policies for the region. There have been political revisions and in some cases nontraditional modifications in moribund autocracies and dictatorships across the Arab world, reaching to the Arab and Persian Gulfs. The awakening has been enervated by violent responses from more cohesive and profound dictatorships in Syria and Libya, but the “leaderless” model of the awakening can quickly bring together disparate groups working toward a common goal. As the process across the Arab world unfolds, American interests will need to be addressed in ways different from the past. New American wars will not be a promising option. The region’s challenges require a serious and consistent policy toward resolving the core issues of instability, and that includes overcoming domestic opinion and lobbies that work against a two-state solution for Israel and Palestine. The current demographic prospect is that Israel will lose its Zionist hopes by the forced integration of Palestinians who have lost their own hope of a viable and independent nation.
Stakes Matter in Ultimatum Games
Authors: Andersen Steffen , Ertaç Seda , Gneezy Uri , Hoffman Moshe , List John A
Published: December 2011

One of the most robust findings in experimental economics is that individuals in one-shot ultimatum games reject unfair offers. Puzzlingly, rejections have been found robust to substantial increases in stakes. By using a novel experimental design that elicits frequent low offers and uses much larger stakes than in the literature, we are able to examine stakes' effects over ranges of data that are heretofore unexplored. Our main result is that proportionally equivalent offers are less likely to be rejected with high stakes. In fact, our paper is the first to present evidence that as stakes increase, rejection rates approach zero. JEL: C72, C78, C91
The Cross Section of Foreign Currency Risk Premia and Consumption Growth Risk: Reply
Authors: Lustig Hanno , Verdelhan Adrien
Published: December 2011

The consumption growth beta of an investment strategy that goes long in high interest rate currencies and short in low interest rate currencies is large and significant. Consumption risk price differs significantly from zero, even after accounting for the sampling uncertainty introduced by the estimation of the consumption betas. The constant in the regression of average returns on consumption betas is not significant. Additionally, this investment strategy's consumption and market betas increase during recessions and times of crisis, when risk prices are high, implying that the unconditional betas understate its riskiness. JEL: C58, E21, F31, G11, G12
Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14
Authors: de Veer Simon J. , Swedberg Joakim E. , Parker Edward A. , Harris Jonathan M.
Published: December 2011

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme’s active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (kcat/Km=3.81±0.4×106 m-1 s-1) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.