bluuebunny/crossref_metadata_2025 huggingface dataset:
The sustainable future of implementation research: On the development of the field and its paradoxes
Authors: Hupe Peter , Sætren Harald
Published: March 2014

As fashionable as implementation studies were in the 1970s and 1980s, as en vogue it has become currently, four decades later, to consider implementation as an obsolete research theme. It is clear that in the study of government, new themes and concepts have been put on the agenda. In the ‘age of governance’, that study takes place under a variety of headings beyond ‘implementation’. At the same time, a continued attention to what happens with policies-on-paper can be observed. In this special issue, the development of implementation research as a scholarly field is assessed. A closer look reveals some paradoxes, but also steady advancement.
Critical role of DNA methylation in the pathogenesis of systemic lupus erythematosus: new advances and future challenges
Authors: Miao C-G , Yang J-T , Yang Y-Y , Du C-L , Huang C , Huang Y , Zhang L , Lv X-W , Jin Y , Li J
Published: March 2014

Systemic lupus erythematosus (SLE) is a systemic multi-organ autoimmune disease with different immunological characteristics and clinical manifestations characterized by an autoantibody response to nuclear and cytoplasmic antigens; the etiology of this disease remains largely unknown. Most recent genome-wide association studies demonstrate that genetics significantly predispose to SLE onset, but the incomplete disease concordance rates between monozygotic twins indicates a role for other complementary factors in SLE pathogenesis. Recently, much evidence strongly supports other molecular mechanisms involved in the regulation of gene expression ultimately causing autoimmune disease, and several studies, both in clinical settings and experimental models, have demonstrated that epigenetic modifications may hold the key to a better understanding of SLE initiation and development. DNA methylation changes the structure of chromatin, being typically able to modulate the fine interactions between promoter-transcription factors and encoding genes within the transcription machinery. Alteration in DNA methylation has been confirmed as a major epigenetic mechanism that may potentially cause a breakdown of immune tolerance and perpetuation of SLE. Based on recent findings, DNA methylation treatments already being used in oncology may soon prove beneficial to patients with SLE. We herein discuss what we currently know, and what we expect in the future.
Non-neoplastic findings at colonoscopy after positive faecal occult blood testing: Data from the English Bowel Cancer Screening Programme
Authors: Bevan Roisin , Lee Thomas JW , Nickerson Claire , Rubin Greg , Rees Colin J
Published: March 2014

Background

The aim of the English Bowel Cancer Screening Programme (BCSP) is to diagnose early colorectal cancer and advanced adenomas. However, other findings are also reported at screening colonoscopy. Small studies demonstrate findings other than cancer or adenomas (non-neoplastic findings (NNF)) in 11–25%.

Objectives and setting

Describe the frequency and nature of NNF within the BSCP.

Methods

Data were obtained from the BCSP national database for all individuals undergoing colonoscopic investigation after positive faecal occult blood testing between August 2006 and November 2011. Data included demographics, smoking status, neoplastic findings and NNF.

Results

121728 colonoscopies were analysed. ≥1 NNF were found in 26251 cases (21.6%). Diverticular disease (18875 cases) and haemorrhoids (7011) were the most frequently reported. Inflammatory bowel disease (IBD) was reported in 2152 cases. Individuals with a neoplastic diagnosis were less likely to have an NNF than those without (19.8% v 24.4%, p < 0.001). After adjustment for confounding using multivariable analysis, older age was still associated with a small but statistically significant risk of NNF.

Conclusions

The BCSP generates a significant volume of NNF. A small proportion of individuals were found to have inflammatory bowel disease (IBD) - an important diagnosis with implications for long-term management. BCSP participants should be aware that findings other than neoplasia may be detected and the relevance of these findings to that individual is not known. Reporting of NNF varies between colonoscopists, and potential underreporting is a limitation of this study. Further study is required to establish the impact of NNF on primary and secondary care.
Establishing cross-border co-operation between professional organizations: Police, fire brigades and emergency health services in Dutch border regions
Authors: Princen Sebastiaan , Geuijen Karin , Candel Jeroen , Folgerts Oddy , Hooijer Ragna
Published: March 2014

This article explores the conditions under which local and regional governments will establish and sustain cross-border co-operation in the fields of police, fire fighting and emergency health services. It argues that understanding this type of cross-border co-operation requires a focus on the way in which professionals define and apply their professional standards in cross-border contexts. Moreover, it requires a focus on individual organizations and professionals working in them, rather than ‘government’ or ‘the state’ as a whole, since cross-border co-operation in these areas typically develops as a result of disparate and unconnected initiatives taken by governmental actors in a given border region. Based on four studies of cross-border co-operation in Dutch border regions, we argue that differences in legal, organizational and cultural backgrounds between the participating countries can be and are overcome by street-level professionals and their organizations, who act as ‘regionauts’ in exploring opportunities for cross-border co-operation. In this type of ‘bottom-up’ cross-border co-operation, motivation among participants is the key to establishing co-operation, and solutions to differences between work routines will be developed along the way. As a result, the establishment of cross-border co-operation often is an experimental, pragmatic enterprise, which is greatly affected by local intra- and inter-organizational dynamics. This opens the potential for pragmatic, flexible and creative solutions. Yet, at the same time it also runs the risk of producing unaccountable cross-border arrangements that are insufficiently embedded in legal and professional safeguards against error and abuse.
Indian Renaissance in the Twenty-First Century: Management Education, Thoughts and Practices for the Betterment of Business, Nation and Society
Authors: Bhattacharya Shubhasheesh , Bhattacharya Sonali
Published: March 2014

The article talks about the glorious past of the Indian ethos, management thoughts and practices, the current situation in India and a suggested roadmap for the future, to regain the past glory. Governance of the country is influenced and affected by the political, social, environmental factors and youth activism; which suggests that there is a strong linkage between the values of the people, their actions and the quality of governance. Quality of governance of a country is an indicator of the maturity and well-being of the society. A new conceptual model has been suggested showing the linkage between youth activism and quality of governance, determining the health of the society. The model is prepared based on evidence from India. The focus of the article is the need to impart quality management education embedded with universal values, for the betterment of business, nation and society.
The Evaluation of a Food Allergy and Epinephrine Autoinjector Training Program for Personnel Who Care for Children in Schools and Community Settings
Authors: Wahl Ann , Stephens Hilary , Ruffo Mark , Jones Amanda L.
Published: March 2014

With the dramatic increase in the incidence of food allergies, nurses and other school personnel are likely to encounter a child with food allergies. The objectives of this study were to assess the effectiveness of in-person training on enhancing knowledge about food allergies and improving self-confidence in preventing, recognizing, and treating food allergy reactions and to collect information about prior training and participation in response to food allergy incidents. A total of 4,818 individuals at 247 schools and community sites participated in the training program, which was delivered by a licensed registered nurse. Written evaluations, online surveys, and phone interviews were used to measure the impact including content retention, confidence, and behavior changes. The results of this study show that in-person training can increase participant’s knowledge about food allergies and improve self-confidence in preventing, recognizing, and treating allergic reactions and that these gains were sustained over time.
Efficacy of a Latino Mother–Child Communication Intervention in Elementary Schools
Authors: McNaughton Diane B. , Cowell Julia Muennich , Fogg Louis
Published: March 2014

Children of Latino immigrants in the United States encounter ecological stressors that heighten their risk for depressive symptoms, externalizing behavior, and problems in school. Studies have shown that affirming parent–child communication is protective of child depressive symptoms and accompanying problems. The purpose of this study was to assess the efficacy of an adapted mother–child communication intervention for Latino immigrant mothers and their fourth- to sixth-grade children delivered after school. The intervention, Family Communication (“Comunicación Familiar”), was delivered at children’s elementary schools in six sessions lasting 2 hr each. Significant improvements were found in children’s reports of problem-solving communication, with their mother and mothers’ reports of reduced family conflict. Strengths of the intervention are improved mother–child communication, acquisition of communication skills that can transfer to relationships within the classroom, and a design that allows delivery by nurses or other professional members of the school support team.
Cost-Effectiveness Analysis of Plasma Versus Recombinant Factor VIIa for Placing Intracranial Pressure Monitors in Pretransplant Patients With Acute Liver Failure
Authors: Pham Huy P. , Sireci Anthony N. , Kim Chong H. , Schwartz Joseph
Published: March 2014

Both plasma- and recombinant activated factor VII (rFVIIa)-based algorithms can be used to correct coagulopathy in preliver transplant patients with acute liver failure requiring intracranial pressure monitor (ICPM) placement. A decision model was created to compare the cost-effectiveness of these methods. A 70-kg patient could receive either 1 round of plasma followed by coagulation testing or 2 units of plasma and 40 μg/kg rFVIIa. Intracranial pressure monitor is placed without coagulation testing after rFVIIa administration. In the plasma algorithm, the probability of ICPM placement was estimated based on expected international normalized ratio (INR) after plasma administration. Risks of rFVIIa thrombosis and transfusion reactions were also included. The model was run for patients with INRs ranging from 2 to 6 with concomitant adjustments to model parameters. The model supported the initial use of rFVIIa for ICPM placement as a cost-effective treatment when INR ≥2 (with incremental cost-effectiveness ratio of at most US$7088.02).
Soy food frequency questionnaire does not correlate with baseline isoflavone levels in patients with bladder cancer
Authors: Kolesar Jill M , Pomplun Marcia , Havighurst Tom , Stublaski Jeanne , Wollmer Barbara , Kim KyungMann , Tangrea Joseph A , Parnes Howard L , House Margaret G , Gee Jason , Messing Edward , Bailey Howard H
Published: March 2014

Background

The isoflavone genistein, a natural soy product with receptor tyrosine kinase-inhibiting activity, as well as phytoestrogenic and other potential anticarcinogenic effects, is being studied as an anticancer agent. Since isoflavones are commonly consumed in food products containing soy proteins, a method to control for baseline isoflavone consumption is needed.

Methods

HPLC was used to evaluate baseline plasma and urine concentrations of isoflavone in fifty-four participants with bladder cancer enrolled on a phase II chemoprevention study of G-2535. The soy food frequency questionnaire was used to assess participant’s baseline soy intake. The association between baseline isoflavone concentrations and intakes for genistein and daidzein was assessed by the Spearman’s rank correlation coefficient.

Results

The majority of participants had no detectable genistein or daidzein in plasma at baseline. The median and range of values were 0 (0–1480) nmol/L for genistein, and 0 (0–1260) nmol/L for daidzein. In urine, the median and range of values were 91.0 (0–9030) nmol/L for genistein and 623 (0–100,000) nmol/L for daidzein. The median and range of weekly estimated genistein intake was 0 (0–236) mg/wk; the median and range of weekly estimated daidzein intake was 0 (0–114) mg/wk. There was no relationship to soy intake as measured by the food frequency questionnaire and baseline isoflavone levels in plasma or urine and the Spearman’s rank correlation coefficients were not significant.

Conclusion

The soy food frequency questionnaire did not correlate with plasma or urine concentrations of either isoflavone.

Impact

Alternative methods for controlling for soy consumption, including measuring plasma and urine concentrations, in isoflavone chemoprevention trials should be considered.
Pilot study to evaluate the role of Mycoplasma species in cat bite abscesses
Authors: Torres-Henderson Camille , Hesser Jeff , Hyatt Doreene R , Hawley Jennifer , Brewer Melissa , Lappin Michael R
Published: March 2014

Mycoplasma species are common inhabitants of the feline oral cavity, and so likely contaminate many cat bite abscesses. The objectives of this study were to determine whether Mycoplasma species are common contaminants of cat bite abscesses and whether they are are associated with β-lactam-resistant clinical disease. Twenty-six privately owned cats with clinical evidence of an abscess suspected to be from a cat bite were included in the study. Samples from each cat were evaluated by aerobic and anaerobic culture, as well as Mycoplasma species culture and polymerase chain reaction (PCR). All cats were initially treated with appropriate wound management and were administered an antibiotic of the β-lactam class (amoxicillin, amoxicillin clavulanate or cefovecin sodium). Mycoplasma species DNA was amplified by PCR from 4/26 samples (15.4%); one of these cases was concurrently culture positive. Adequate DNA for sequencing was present for 2/4 positive PCR samples; one was most homologous with Mycoplasma felis, and the other was most homologous with Mycoplasma equigenitalium and Mycoplasma elephantis. Of the 26 cats, 25 responded to the initial treatment by day 7. The cat that failed initial treatment was positive for M equigenitalium or M elephantis DNA on days 0 and 12, and ultimately responded to administration of enrofloxacin and clindamycin. The results suggest that while Mycoplasma species can contaminate cat bite abscesses, routine wound management and β-lactam antibiotic therapy is adequate for treatment in most cases of abscess. However, as Mycoplasma species infections do not respond to β-lactam class antibiotic therapy, these organisms should be on the differential list for cats with abscesses that fail treatment with this antibiotic class.
A tele-oncology model replacing face-to-face specialist cancer care: perspectives of patients in North Queensland
Authors: Sabesan Sabe , Kelly Jenny , Evans Rebecca , Larkins Sarah
Published: March 2014

We explored the experiences of patients using the Townsville Tele-oncology clinic, where most patients are no longer seen face-to-face. All medical oncology patients who received services via telehealth at the Townsville Cancer Centre in 2012 were invited to participate in an interview. None refused. Thirty two patients were interviewed by telephone and three via videoconference at their local health service facility. Data analysis identified five major themes (quality of the consultation; communication and relationships; familiarity with technology and initial fears; local services and support; and lack of coordination of services between the local rural hospital and the major regional hospital) and each major theme included a number of sub-themes. Most patients interviewed (69%) had not seen their oncology specialist face-to-face, but 86% of them found the video-consultation to be of high quality and were extremely satisfied with the interaction. The acceptance of teleconsultation appeared to be linked to the patients' trust with their local health system and staff. Overall, the tele-oncology model that replaced face-to-face care in North Queensland was accepted and welcomed by patients.
A study of automated self-assessment in a primary care student health centre setting
Authors: Poote Aimee E , French David P , Dale Jeremy , Powell John
Published: March 2014

We evaluated the advice given by a prototype self-assessment triage system in a university student health centre. Students attending the health centre with a new problem used the automated self-assessment system prior to a face-to-face consultation with the general practitioner (GP). The system’s rating of urgency was available to the GP, and following the consultation, the GP recorded their own rating of the urgency of the patient’s presentation. Full data were available for 154 of the 207 consultations. Perfect agreement, where both the GP and the self-assessment system selected the same category of advice, occurred in 39% of consultations. The association between the GP assessment and the self-assessment rankings of urgency was low but significant (rho = 0.19, P = 0.016). The self-assessment system tended to be risk averse compared to the GP assessments, with advice for more urgent level of care seeking being recommended in 86 consultations (56%) and less urgent advice in only 8 (5%). This difference in assessment of urgency was significant ( P < 0.001). The agreement between self-assessed and GP-assessed urgency was not associated with symptom site or socio-demographic characteristics of the user. Although the self-assessment system was more risk averse than the GPs, which resulted in a high proportion of patients being triaged as needing emergency or immediate care, the self-assessment system successfully identified a proportion of patients who were felt by the GP to have a self-limiting condition that did not need a consultation. In its prototype form, the self-assessment system was not a replacement for clinician assessment and further refinement is necessary.
Studying the community corrections field: Applying neo-institutional theories to a hidden element of mass social control
Authors: DeMichele Matthew
Published: March 2014

The growth in US incarcerated populations has produced unintended negative consequences for other justice system agencies. The community corrections field is faced with two related problems stemming from prison growth: (1) significant growth in populations under supervision and (2) populations with higher needs for service. I apply a theoretical framework adapted from organizational sociological research to address change and stasis as isomorphic processes. Criminologists rarely situate the community corrections field within broader theoretical perspectives. Instead, correctional researchers have studied the emergence, adjustment, and use of prisons in modern society, with community supervision considered a part of institutional corrections. I argue that contemporary explanations for correction policies need to be refined to account for specific trends within the community corrections field.
Adolescents with chronic pain and associated functional disability
Authors: Wojtowicz Andrea A , Banez Gerard A
Published: March 2014

The purpose of this research was to describe the biopsychosocial characteristics of adolescents with chronic pain and functional disability. Data were obtained from a registry of 100 adolescents (mean age = 15.84, SD = 2.72; 21 males) admitted to an interdisciplinary pain rehabilitation program. Clinician ratings were used to categorize coping and personality styles. The most common chief complaint at admission was limb pain ( n = 44), followed by headache ( n = 21) and abdominal pain ( n = 17). Eighteen patients presented with other types of pain. The most frequent triggers to pain were physical trauma, medical condition or disability, and surgery or another medical procedure. Sleep problems, mental health difficulties, and high academic performance were common. Seven previously identified pain-associated disability factors, including passive or dependent coping style, chronic illness in a parent, personality consistent with alexithymia, unresolved family problems, early pain experiences, learning/developmental difficulties, and perfectionistic personality, were common. Ninety-eight adolescents presented with two or more of these contributing factors. Fifty-six adolescents had four or more of the factors. Adolescents with chronic pain and associated disability presented with numerous biopsychosocial factors that relate to their impairment. The understanding and attention to these factors will be important for successful rehabilitation.
The Chronicles of Long Kesh: Provisional Irish Republican memoirs and the contested memory of the hunger strikes
Authors: Hopkins Stephen
Published: March 2014

This article analyses the recent struggle for control of the Provisional Irish Republican movement’s collective memory of the 1980–1981 hunger strikes, during which 10 Republicans died.2 It proceeds through an examination and interpretation of the published memoir-writing of some of the key protagonists within the broad Irish Republican movement. In particular, it examines the controversy surrounding the allegations made by Richard O’Rawe (former Public Relations Officer for the Irish Republican Army prisoners at the time of the 1981 strike), in his two volumes of memoir, Blanketmen (2005) and Afterlives (2010). The article addresses the role of dissent in the movement’s collective memory and the specific role of ‘memory entrepreneurs’ in the contestation of the Irish Republican ‘official’ memory of the hunger strikes.
Percutaneous in situ versus open arthrodesis of the distal interphalangeal joint
Authors: Renfree K. J.
Published: March 2014

We compared the results of percutaneous in situ arthrodesis with open arthrodesis of the distal interphalangeal joint with a headless compression screw. In the percutaneous in situ arthrodesis group (17 joints), the screw was inserted from the fingertip across the unprepared joint. In the open group (12 joints), flat cancellous surfaces were prepared before screw insertion. Solid fusion was found in 10/17 joints (59%) with percutaneous in situ arthrodesis and in 11/12 joints (92%) with open arthrodesis. Among the other seven joints with percutaneous in situ arthrodesis, six had fibrous union and were asymptomatic at a mean of 18 months, and one failed, requiring revision. One joint with open arthrodesis had fibrous union and was asymptomatic 12 months after surgery. We conclude that open arthrodesis is better than the percutaneous method, as a greater percentage achieve bone union. The open approach allows osteophyte removal and slightly better correction of angular deformity in the coronal plane.
Teleophthalmology in Diabetic Retinopathy
Authors: Surendran Thandalam Sundararajan , Raman Rajiv
Published: March 2014

Over the past decade, there have been rapid strides in progress in the fields of telecommunication and medical imaging. There is growing evidence regarding use of teleophthalmology for screening of diabetic retinopathy. This article highlights some pertinent questions regarding use of telescreening for diabetic retinopathy. It deals with evidence regarding accuracy of diagnosis, patients satisfaction and cost-effectiveness. The American Telemedicine Association have given certain guidelines for teleheath practices for diabetic retinopathy. The article discusses regarding these guidelines. Finally, a working model for diabetic retinopathy screening through teleophthalmology has been described. Telescreening for diabetic retinopathy seems to be a cost-effective, accurate, and reliable method for screening for diabetic retinopathy. The American Telemedicine Association has set up guidelines for telescreening that should be adhered to provide quality screening services to people with diabetes.
Specificity of Implicit-Shame Associations
Authors: Clerkin Elise M. , Teachman Bethany A. , Smith April R. , Buhlmann Ulrike
Published: March 2014

In this study, we investigated the specificity of implicit-shame associations across individuals diagnosed with body dysmorphic disorder ( n = 30), obsessive-compulsive disorder ( n = 30), and social anxiety disorder ( n = 29) and individuals in a mentally healthy control group ( n = 33). All participants completed a series of Implicit Association Tests that tapped into shame associated with each disorder. Planned contrasts indicated that compared with individuals in the other groups, individuals in the body dysmorphic disorder group had greater body-relevant implicit shame and those in the obsessive-compulsive disorder group had greater implicit shame tied to obsessive thoughts. The social anxiety disorder group did not differ significantly from the other groups on implicit performance-relevant shame, although in comparison with the other clinical groups, means were in the expected direction. Our comparative design adds to existing cognitive-behavioral conceptualizations of body dysmorphic, obsessive-compulsive, and social anxiety disorders that have traditionally focused on strategic forms of cognition within a single disorder.
Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”
Authors: Tomljenovic Lucija , Colafrancesco Serena , Perricone Carlo , Shoenfeld Yehuda
Published: March 2014

We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.
Anthropomorphic Figurines at Perdigões Enclosure: Naturalism, Body Proportion and Canonical Posture as Forms of Ideological Language
Authors: Valera António Carlos , Evangelista Lucy Shaw
Published: March 2014

This paper focusses on a set of anthropomorphic figurines. It suggests that realistic human proportion and canonical body posture were pursued in the carving of these objects as a means of expressing ideology, in a context of diversified forms of manipulation of bodies in funerary practices. It is argued that, against a background of predominantly schematic art, the more realistic and canonical anthropomorphic representation of the human body was used to communicate a set of ideological statements in a more controlled and immediate way, in a period of ontological and cosmological transition.
Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αIIbβ3, and platelet factor 4
Authors: Arman Mònica , Krauel Krystin , Tilley Dorothea O. , Weber Claudia , Cox Dermot , Greinacher Andreas , Kerrigan Steven W. , Watson Steve P.
Published: March 2014

Key Points

FcγRIIA activation is key for platelet aggregation in response to bacteria, and depends on IgG and αIIbβ3 engagement. PF4 binds to bacteria and reduces the lag time for platelet aggregation.
BCRgt: a Bayesian cluster regression-based genotyping algorithm for the samples with copy number alterations
Authors: Yang Shengping , Cui Xiangqin , Fang Zhide
Published: March 2014

Background

Accurate genotype calling is a pre-requisite of a successful Genome-Wide Association Study (GWAS). Although most genotyping algorithms can achieve an accuracy rate greater than 99% for genotyping DNA samples without copy number alterations (CNAs), almost all of these algorithms are not designed for genotyping tumor samples that are known to have large regions of CNAs.

Results

This study aims to develop a statistical method that can accurately genotype tumor samples with CNAs. The proposed method adds a Bayesian layer to a cluster regression model and is termed a Bayesian Cluster Regression-based genotyping algorithm (BCRgt). We demonstrate that high concordance rates with HapMap calls can be achieved without using reference/training samples, when CNAs do not exist. By adding a training step, we have obtained higher genotyping concordance rates, without requiring large sample sizes. When CNAs exist in the samples, accuracy can be dramatically improved in regions with DNA copy loss and slightly improved in regions with copy number gain, comparing with the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM).

Conclusions

In conclusion, we have demonstrated that BCRgt can provide accurate genotyping calls for tumor samples with CNAs.
Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion
Authors: Cai Kun , Mulatz Kirk , Ard Ryan , Nguyen Thanh , Gee Stephen H
Published: March 2014

Background

Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process.

Methods

To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ.

Results

DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated their invasiveness.

Conclusion

Elevated DGKζ expression contributes to increased Rho GTPase activation and the enhanced motility of metastatic cancer cells. These findings warrant further investigation of the clinical relevance of DGKζ upregulation in colon and other cancers. Interfering with DGKζ function could provide a means of inhibiting invasion and metastasis.
Negative differential resistance and carrier transport of electrically bistable devices based on poly(N-vinylcarbazole)-silver sulfide composites
Authors: Li Jiantao , Tang Aiwei , Li Xu , Cao Yapeng , Wang Miao , Ning Yu , Lv Longfeng , Lu Qipeng , Lu Yunzhang , Hu Yufeng , Hou Yanbing , Teng Feng
Published: March 2014

An electrically bistable device has been fabricated based on poly(N-vinylcarbazole) (PVK)-silver sulfide (Ag2S) composite films using a simple spin-coating method. Current–voltage (I-V) characteristics of the as-fabricated devices exhibit a typical electrical bistability and negative differential resistance (NDR) effect. The NDR effect can be tuned by varying the positive charging voltage and the charging time. The maximum current ratio between the high-conducting state (ON state) and low-conducting state (OFF state) can reach up to 104. The carrier transport mechanisms in the OFF and ON states are described by using different models on the basis of the experimental result.
DNA-encapsulated silver nanodots as ratiometric luminescent probes for hypochlorite detection
Authors: Park Soonyoung , Choi Sungmoon , Yu Junhua
Published: March 2014

DNA-encapsulated silver nanodots are noteworthy candidates for bio-imaging probes, thanks to their excellent photophysical properties. The spectral shift of silver nanodot emitters from red to blue shows excellent correlations with the concentration of reactive oxygen species, which makes it possible to develop new types of probes for reactive oxygen species (ROS), such as hypochlorous acid (HOCl), given the outstanding stability of the blue in oxidizing environments. HOCl plays a role as a microbicide in immune systems but, on the other hand, is regarded as a disease contributor. Moreover, it is a common ingredient in household cleaners. There are still great demands to detect HOCl fluxes and their physiological pathways. We introduce a new ratiometric luminescence imaging method based on silver nanodots to sensitively detect hypochlorite. The factors that influence the accuracy of the detection are investigated. Its availability has also been demonstrated by detecting the active component in cleaners.

PACS

82; 82.30.Nr; 82.50.-m
Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses
Authors: Clay Candice C , Donart Nathan , Fomukong Ndingsa , Knight Jennifer B , Overheim Katie , Tipper Jennifer , Van Westrienen Jesse , Hahn Fletcher , Harrod Kevin S
Published: March 2014

Background

Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure.

Results

Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age.

Conclusions

This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.
Sources of Individual Variability: Mirnas That Predispose to Neuropathic Pain Identified Using Genome-Wide Sequencing
Authors: Bali Kiran Kumar , Hackenberg Michael , Lubin Avigail , Kuner Rohini , Devor Marshall
Published: March 2014

Background:

We carried out a genome-wide study, using microRNA sequencing (miRNA-seq), aimed at identifying miRNAs in primary sensory neurons that are associated with neuropathic pain. Such scans usually yield long lists of transcripts regulated by nerve injury, but not necessarily related to pain. To overcome this we tried a novel search strategy: identification of transcripts regulated differentially by nerve injury in rat lines very similar except for a contrasting pain phenotype. Dorsal root ganglia (DRGs) L4 and 5 in the two lines were excised 3 days after spinal nerve ligation surgery (SNL) and small RNAs were extracted and sequenced.

Results:

We identified 284 mature miRNA species expressed in rat DRGs, including several not previously reported, and 3340 unique small RNA sequences. Baseline expression of miRNA was nearly identical in the two rat lines, consistent with their shared genetic background. In both lines many miRNAs were nominally up- or down-regulated following SNL, but the change was similar across lines. Only 3 miRNAs that were expressed abundantly (rno-miR-30d-5p, rno-miR-125b-5p) or at moderate levels (rno-miR-379-5p) were differentially regulated. This makes them prime candidates as novel PNS determinants of neuropathic pain. The first two are known miRNA regulators of the expression of Tnf, Bdnf and Stat3, gene products intimately associated with neuropathic pain phenotype. A few non-miRNA, small noncoding RNAs (sncRNAs) were also differentially regulated.

Conclusions:

Despite its genome-wide coverage, our search strategy yielded a remarkably short list of neuropathic pain-related miRNAs. As 2 of the 3 are validated regulators of important pro-nociceptive compounds, it is likely that they contribute to the orchestration of gene expression changes that determine individual variability in pain phenotype. Further research is required to determine whether some of the other known or predicted gene targets of these miRNAs, or of the differentially regulated non-miRNA sncRNAs, also contribute.
Impact of completeness of revascularization by coronary intervention on exercise capacity early after acute ST-elevation myocardial infarction
Authors: Zhao Wei , Bai Jin , Zhang Fuchun , Guo Lijun , Gao Wei
Published: March 2014

Background

The importance of achieving complete revascularization by percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) on exercise capacity remains unclear.

Objective

To compare exercise capacity early after acute ST-elevation myocardial infarction (STEMI), in patients receiving PCI with stenting, between those completely revascularized (CR) and those incompletely revascularized (IR).

Methods

We retrospectively reviewed 326 patients [single-vessel disease (SVD) group, 118 patients; multivessel disease (MVD) with CR group, 112 patients; MVD with IR group, 96 patients] who underwent cardiopulmonary exercise testing 7–30 days after STEMI to measure peak oxygen uptake (VO2peak), oxygen uptake at anaerobic threshold (VO2AT), and peak oxygen pulse. Demographic data, presence of concomitant diseases, STEMI characteristics, and echocardiography and angiography findings were evaluated.

Results

Most patients were male (89.0%) and mean age was 55.6 ± 11.2 years. Ischemic ST deviation occurred in 7.1%, with no significant difference between groups. VO2peak and VO2AT did not differ significantly between groups, despite a trend to be lower in the CR and IR groups compared with the SVD group. Peak oxygen pulse was significantly higher in the SVD group than in the IR group (p = 0.005). After adjustment for age, gender, body mass index, cardiovascular risk factors, MI characteristics and echocardiography parameters, CR was not an independent predictor of VO2peak (OR = −0.123, 95% confidence interval [CI] -2.986 to 0.232, p = 0.093), VO2AT (OR = 0.002, 95% CI 1.735 to 1.773, p = 0.983), or peak oxygen pulse (OR = −0.102, 95% CI −1.435 to 0.105, p = 0.090).

Conclusion

CR in patients with STEMI treated with PCI for multivessel disease might show no benefit on short-term exercise tolerance over IR.
Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways
Authors: Singel Stina M , Batten Kimberly , Cornelius Crystal , Jia Gaoxiang , Fasciani Gail , Barron Summer L , Wright Woodring E , Shay Jerry W
Published: March 2014

Introduction

Metastasis is the main cause of breast cancer morbidity and mortality. Processes that allow for tumor cell migration and invasion are important therapeutic targets. Here we demonstrate that receptor-interacting protein kinase 2 (RIP2), a kinase known to be involved in inflammatory processes, also has novel roles in cancer cell migration and invasion.

Methods

A total of six breast cancer expression databases, including The Cancer Genome Atlas, were assessed for RIP2 expression among various clinical subtypes and its role as a prognostic biomarker. mRNA fluorescence in situ hybridization (FISH) for RIP2 was performed on 17 stage III breast cancers to determine if there was a correlation between RIP2 expression and lymph node involvement. RNA-interference was used to knock-down RIP2 expression in MDA-MB-231, Htb126, SUM149PT, MCF7, T47D, and HCC1428 cells. Cell migration and invasion were measured in vitro by scratch/wound healing and transwell migration assays. A xenograft mouse model was used to assess tumor growth and chemosensitivity to docetaxel in vivo in MDA-MB-231 cells with and without RIP2 small hairpin RNA knockdown. Western blot and immunofluorescence imaging were used to evaluate protein expressions.

Results

Interrogation of expression databases showed that RIP2 expression is significantly over-expressed in triple-negative breast cancers (TNBC: estrogen-receptor (ER) negative, progesterone-receptor (PR) negative, Her2/neu- (Her2) negative), compared to other clinical subtypes. High RIP2 expression correlates with worse progression-free survival using a combined breast cancer expression array dataset consisting of 946 patients. Multivariate analysis shows RIP2 as an independent prognostic biomarker. Knock-down of RIP2 significantly decreases migration in both scratch/wound healing and transwell migration assays in MDA-MB-231, Htb126, SUM149PT, MCF7, and T47D cells and is correlated with decreased Nuclear Factor-kappaB and c-Jun N-terminal kinase (JNK) activation. Finally, RIP2 knock-down leads to increased sensitivity to docetaxel and decreased tumor mass and lung metastases in a xenograft mouse model.

Conclusion

These results highlight RIP2 as a pro-metastasis kinase in patients with advanced breast cancer. These results also illustrate a novel role for this kinase in addition to its known role in inflammation, and suggest that targeting RIP2 may improve outcomes in advanced breast cancer patients, in which it is overexpressed.
Evidence for Decreased Expression of ADAMTS-1 Associated With Impaired Oocyte Quality in PCOS Patients
Authors: Xiao Shan , Li Yubin , Li Tao , Chen Minghui , Xu Yanwen , Wen Yangxing , Zhou Canquan
Published: March 2014

Context:

Polycystic ovary syndrome (PCOS) is the most common cause of dysfunctional ovulation-affecting female fertility. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS-1) is required for normal ovulation and subsequent fertilization, and the expression of ADAMTS-1 may be altered in PCOS granulosa cell (GC)-reflecting abnormalities in ovulatory signaling.

Objective:

The purpose of this paper is to analyze the differential expression of ADAMTS-1 in PCOS patients associated with impaired oocyte quality.

Design and Setting:

A prospective comparative experimental study was performed at a clinical reproductive medicine center.

Patients:

Women with PCOS (n = 40) and normovulatory controls (n = 40) undergoing controlled ovarian hyperstimulation and in vitro fertilization were recruited in our study.

Main Outcome Measures:

Differential expression of ADAMTS-1 in GCs was analyzed with immunocytochemistry in PCOS patients and normal controls, and ADAMTS-1 mRNA expression was quantified by RT-PCR. Furthermore, the correlation between ADAMTS-1 mRNA and oocyte quality was analyzed.

Results:

The expression of ADAMTS-1 was decreased in PCOS patients compared with normally ovulating women and was closely related to lower oocyte recovery, oocyte maturity, and fertilization rate.

Conclusion:

Our study provides evidence that the dysregulated expression of ADAMTS-1 in PCOS may influence oocyte quality-via GCs-oocyte paracrine and endocrine mechanism.
Minireview: The Versatile Roles of Lysine Deacetylases in Steroid Receptor Signaling
Authors: Kadiyala Vineela , Smith Catharine L.
Published: March 2014

Lysine deacetylases have been known to regulate nuclear receptor function for many years. In the unliganded state, nuclear receptors that form heterodimers with retinoid X receptors, such as the retinoic acid and thyroid hormone receptors, associate with deacetylases to repress target genes. In the case of steroid receptors, binding of an antagonist ligand was initially reported to induce association of deacetylases to prevent activation of target genes. Since then, deacetylases have been shown to have diverse functions in steroid receptor signaling, from regulating interactions with molecular chaperones to facilitating their ability to activate transcription. The purpose of this review is to summarize recent studies on the role of deacetylases in steroid receptor signaling, which show deacetylases to be highly versatile regulators of steroid receptor function.