bluuebunny/crossref_metadata_2025 huggingface dataset:
Capecitabine non-adherence: Exploration of magnitude, nature and contributing factors
Authors: Bhattacharya Debi , Easthall Claire , Willoughby Kerri Anne , Small Matthew , Watson Steven
Published: February 2012

Objectives: The prescribing of oral chemotherapy agents previously available only in the intravenous formulation, such as capecitabine, has afforded many benefits including reduced administration costs and improved patient acceptability. However, it has introduced the new challenge of ensuring patient adherence to therapy. It is therefore necessary to quantify adherence, and with a view to improving services, explore factors that may impact on medication taking behavior.

Methods: Patients with a diagnosis of breast or colorectal cancer and prescribed capecitabine were recruited from a UK teaching hospital. Data regarding self-reported adherence, beliefs about medicines, side effects, and satisfaction with information received about capecitabine were recorded.

Results: Non-adherence was reported by 23.3% of the 43 participants. Capecitabine therapy was perceived necessary by 97.6%, but almost one-third of participants had strong concerns. Side effects were reported by 80% of participants, with Palmar–Plantar erythrodysesthesia and fatigue most troubling participants. Complete satisfaction with information received was reported by 65% of participants; however, dissatisfaction about how to tell if capecitabine is working and the proposed duration of therapy was expressed by 42.9% and 37.3% of participants, respectively.

Conclusions: Adherence to capecitabine is high with a strong conviction that the therapy is necessary. However, concerns were expressed regarding the experience of side effects. Patients have unmet information needs regarding the processes involved with monitoring capecitabine efficacy and determination of therapy duration. Healthcare professionals may therefore wish to consider a greater focus on involving patients in the monitoring of their care with respect to efficacy and planned treatment schedules.
Genre in Discourse, Discourse in Genre
Authors: Collin Ross
Published: February 2012

Focusing on matters of power and difference, this article examines rhetorical theories of genre and James Gee’s theory of Discourse. Although both theories offer productive ways of understanding literate practice, it is argued, they are limited in crucial respects. Genre theory offers few ways of understanding how and why some social actors have an easier time than others in producing generic texts and getting their texts deemed “legitimate” by recognized authorities. Gee’s theory, meanwhile, does not explain precisely how and where (i.e., at which conceptual level) communicants come to match Discourse to situation. This article contends that these limitations may be surpassed if the two theories are brought together in a particular way. In this new approach, genres and Discourses are viewed as mutually constitutive forms: Genres exist within Discourses and Discourses exist within genres. In adopting this approach, it is argued, researchers may study how particular genres are made to elicit performances of Discourses connected to particular social groups.
Advancing Systems Thinking in Evaluation
Authors: Hargreaves Margaret B. , Podems Donna
Published: February 2012

This article reviews four books published in 2010 and 2011 on the topic of systems thinking in evaluation: Developmental Evaluation: Applying Complexity Concepts to Enhance Innovation and Use by Michael Q. Patton; Purposeful Program Theory: Effective Use of Theories of Change and Logic Models by Sue Funnell and Patricia Rogers; Systems Concepts in Action: A Practitioner's Toolkit by Bob Williams and Richard Hummelbrunner, and Evaluation in the Face of Uncertainty: Anticipating Surprise and Responding to the Inevitable by Jonathan Morell. These books describe the interdisciplinary landscape of systems theories, encompassing general systems theory, systems dynamics, complexity theory, network theory, and learning systems, and how they can be used to improve evaluation practice. The books appeal to many different and sometimes overlapping audiences. Separately, they address specific information needs about how to incorporate systems concepts into different aspects of evaluation design, data collection, analysis, and reporting. Together, the books complement and reinforce each other, creating a cohesive picture of the state of the art of systems thinking by encouraging thinking about situational dynamics in an often complicated and complex world. The books’ authors also advance systems thinking in evaluation by inviting their readers to test out the books’ ideas and methods in their own evaluation work.
The impact of child problem behaviors of children with ASD on parent mental health: The mediating role of acceptance and empowerment
Authors: Weiss Jonathan A. , Cappadocia M. Catherine , MacMullin Jennifer Anne , Viecili Michelle , Lunsky Yona
Published: February 2012

Raising a child with an autism spectrum disorder (ASD) has often been associated with higher levels of parenting stress and psychological distress, and a number of studies have examined the role of psychological processes as mediators of the impact of child problem behavior on parent mental health. The current study examined the relations among child problem behavior, parent mental health, psychological acceptance, and parent empowerment. Participants included 228 parents of children diagnosed with ASD, 6–21 years of age. As expected, psychological acceptance and empowerment were negatively related to the severity of parent mental health problems. When acceptance and empowerment were compared with each other through a test of multiple mediation, only psychological acceptance emerged as a significant partial mediator of the path between child problem behavior and parent mental health problems. As child problem behavior increased, parent psychological acceptance decreased, resulting in an increase in parent mental health problems. These findings suggest that for problems that are chronic and difficult to address, psychological acceptance may be an important factor in coping for parents of young people with ASD, in line with the growing literature on positive coping as compared with problem-focused coping.
Enhancing parental well-being and coping through a family-centred short course for Iranian parents of children with an autism spectrum disorder
Authors: Samadi Sayyed Ali , McConkey Roy , Kelly Greg
Published: February 2012

Parents of children with Autism Spectrum Disorders (ASD) generally experience high levels of stress and report poorer emotional well-being and family functioning compared to parents of children with other disabilities. They also tend to rely on emotional rather than problem-focused coping strategies. Seven group-based sessions were offered to two groups of parents of children with ASD in Iran (37 in all). In addition to providing information about ASD emphasis was placed on families sharing their experiences and learning from one another. A pre-post, cross-over design was used to evaluate the specific impact of the course. The changes found among the parents in the first group were replicated with the second group. Moreover the changes were sustained up to 15 weeks after the course ended. Although there were variations across the parents, in general they reported feeling less stress, had better emotional wellbeing and family functioning and made more use of problem-focused coping strategies. The changes were attributed mainly to an increase in the informal supports among the parents and their feelings of empowerment. A resource pack has been developed to enable the group sessions to be easily repeated and for facilitators to be trained in its use.
Practicing Qi and consuming Ki: Folk epistemology and consumption rituals in Japan
Authors: Minowa Yuko
Published: February 2012

Folk epistemology is a study of the commonsense knowledge and internalized beliefs of ordinary people. This paper discusses consumer knowledge in the context of consumption rituals in Japan. Studying the development of local knowledge is imperative in consumer research, despite accelerating globalization, because knowledge and reasoning cannot be separated from the history in which they are embedded. Prior research tended to treat knowledge projects and consumption rituals as sequential conceptions. The purpose of this study is to propose a model of transcendental consumption rituals, underpinned by cultural pragmatics and ontological liquidity. The proposed model entails a holistic approach to consumer rituals, synthesizing both synchronic and diachronic aspects of the rituals. Metaphors in language and tacit knowledge influence folk epistemology of consumption rituals. Ontological viscosity and the spiritual center of gravity are proposed to better explain the dynamism of consumer rituals in a relatively monolithic culture.
A proposed method for the calculation of light emitting diode road lighting
Authors: Zalewski S
Published: February 2012

Light emitting diode (LED) technology creates a new opportunity for designing road lighting. Multi-source LED luminaires can be designed to make their light distribution conform to specific road layouts. However, using Standard EN 13201 to calculate LED road lighting can lead to serious errors. The proposed sub-points method is based on the same principle as Standard EN 13201 but protects against a dangerous fault. It allows one to keep the same luminance measure method of verification, giving a more accurate result but needs a different measure of luminous intensity distribution.
Plotlessness, Ethnography, Ethology
Authors: Sydnor Synthia , Fagen Robert
Published: February 2012

The authors of this article hail from perhaps disparate fields of biology and cultural studies. The authors use ethnography and ethology, which have offered parallel modernist responses to the challenge posed by Otherness, as touchstones for exploring modernist responses to the theories/methods of the research texts that are produced and performed in their respective disciplines; for example, ethnography typically promises a supreme moment of insight, an intellectual epiphany, when the trained ethnographer’s patient and painstaking field work finally cracks the code of the alien culture to reveal the philosophical and metaphysical essence that constitutes that culture’s previously baffling Otherness. Similarly, field studies of animal behavior promise a royal road to the Umwelten (encompassing worlds, milieux) of natures and cultures far more alien and “Other” than even the most exotic forms of the human condition. The article highlights that scholars in 20th-century ethnography—and, to a lesser extent, ethology—began to question these philosophical and methodological bases and that by the beginning of the 21st century, their criticisms and answers to such dilemmas sparked a range of interrelated responses, which the article briefly overviews: epistemological decentering and recontextualizing of inquiry; illumination of the tensions between, and experimentation with traditional and avant-garde rhetorical, statistical, evidence-based, performance and literary forms necessary for presentation of research; and return to and/or finer articulation of the goals of ethology and ethnography. Within these responses the authors are particularly interested in understanding “plotlessness,” a concept that emerges from recent ethnographic and ethological investigations of “Other-ology” but that is rarely dissected in ethnography. The authors further explore and refine the idea of plotlessness, especially in regard to possible commonalities that this idea might reveal in thinking about play, broadly and loosely conceived, and the “openings” that play may afford present, and future work and thought in ethnography and ethology. Reminding readers of thought on the imperatives of play, on the ordinary/extraordinary nature of play, the authors push play as an all-encompassing paradigm for scholarship across the disciplines and much more (play as core of the ontological-epistemological human condition?).
Association Study of Clusterin Polymorphism rs11136000 With Late Onset Alzheimer’s Disease in Chinese Han Population
Authors: Ma Jian-Fang , Liu Li-hua , Zhang Yu , Wang Ying , Deng Yu-Lei , Huang Yue , Wang Gang , Xu Wei , Cui Pei-Jing , Fei Qing-Zhou , Ding Jian-Qing , Tang Hui-Dong , Chen Sheng-Di
Published: February 2012

Objective: We conducted a case–control study to investigate whether clusterin polymorphism (rs11136000) was associated with late-onset Alzheimer’s disease in Chinese Han population. Methods: Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was performed on genotype rs11136000 and APOEε4 in 127 patients with late-onset Alzheimer’s disease and 143 control individuals. Previous published data from other Chinese samples was also included for further meta-analysis. Results: APOEε4 was demonstrated to increase the risk of Alzheimer’s disease in Chinese population (odds ratio = 2.35, 95% confidence interval: 1.40-3.96). There is no significant association between clusterin rs11136000 with late-onset sporadic AD in our small cohort. However, meta-analysis revealed significant allele and genotype differences between Alzheimer’s disease and controls following a recessive model. Conclusion: Clusterin (rs11136000) was associated with Alzheimer’s disease in Chinese Han population.
Characterization of HIV-Associated Hodgkin's Lymphoma in HIV-Infected Patients
Authors: Ruiz Marco , Parsons Christopher , Cole John
Published: February 2012

Introduction

Although the incidence and prevalence of AIDS-defining malignancies has decreased in the era of highly active antiretroviral therapy (HAART), the incidence and prevalence of Hodgkin's lymphoma (HL) in the HIV-infected population continues to rise. Compared with the general population, HIV-infected patients exhibit a 5-10-fold increased risk for developing HL.

Methods

A retrospective review of charts and electronic records from 2000-2010 at the HIV outpatient clinic (HOP)-Louisiana State University in New Orleans was conducted, and pathologically confirmed cases of HIV-HL were identified within this cohort.

Results

We found a prevalence of 6.3 cases per 1,000 patients per year of HIV-HL over a period of 10 years in our HIV outpatient clinic. The mean absolute CD4 count before treatment was 284 cells/mm3 and after treatment was 194 cells/mm3. The average time from the diagnosis of HIV infection to the diagnosis of HIV-HL was 7.6 years. The most common histopathologic type was mixed cellularity followed by lymphocytic predominance. The majority of patients had 6 cycles delivered. In terms of HL staging 87% presented with advanced stages (III B or IV). To the best of our knowledge 5 out of the 14 patients remain alive.

Conclusions

Patients in our cohort were older than most patients identified in other cohorts. All of our patients had coexisting chronic illnesses associated with inflammation, as well as detectable HIV viral loads and CD4 count >200, suggesting a role for both HIV- and non-HIV-associated inflammation in HIV-HL pathogenesis in this population. The role of HIV virus and other oncogenic viruses (EBV, HPV, and others) in the pathogenesis of Hodgkin's lymphoma in this group of patients needs to be elucidated.
Emotional, Social, and Cognitive Intelligence and Personality as Predictors of Sales Leadership Performance
Authors: Boyatzis Richard E. , Good Darren , Massa Raymond
Published: February 2012

Leaders of sales organizations must recruit and inspire salespeople to grow the organization. Skepticism remains about the role of emotional and social intelligence (ESI) in effective leadership. ESI is criticized as not providing distinctive variance in leadership performance beyond general intelligence and personality. This study assessed the role of the behavioral level of ESI competencies on leader performance. The number of new recruits was shown to predict new cash invested 6 years later. ESI significantly predicted leader performance (i.e., recruitment) whereas measures of generalized intelligence and personality did not. Adaptability and influence were two competencies distinctively predicting sales leadership performance.
Laparoscopic Surgery in the Management of Hypersplenism and Esophagogastric Varices
Authors: Ando Keiichi , Kurokawa Tsuyoshi , Nagata Hiroshi , Arikawa Takashi , Yasuda Akira , Ito Nobuhiro , Kotake Katsuhiro , Nonami Toshiaki
Published: February 2012

Background. Owing to recent advances in laparoscopic surgery, devascularization of the upper stomach with splenectomy (Spx) or Hassab’s procedure (Has) as well as Spx for patients with portal hypertension have been attempted laparoscopically in some facilities, the results of which have been reported. This article describes the authors’ surgical techniques and their results. Methods. Between August 1999 and August 2010, the authors treated 110 cases of portal hypertension with Spx or Has. Among these patients, 56 who simultaneously underwent additional major operations were eliminated from the study, leaving 54 patients eligible. They included 38 with open surgeries and 16 with laparoscopic surgeries, which consisted of 10 splenectomies and 6 Has operations. The perioperative data for the 2 groups were compared. Results. Purely laparoscopic Spx (L-Spx) was completed for 9 patients. Conversion from laparoscopic to hand-assisted laparoscopic surgery (HALS) was necessary for 1 patient because of poor visualization. Operative time was significantly longer in L-Spx than in the open method. Postoperative hospital stays were shorter for L-Spx. HALS was used for all 6 laparoscopic Has patients. There was no conversion from the laparoscopic to the open method. Operative time was significantly longer for laparoscopic Has than for open Has. Postoperative complication rates were significantly reduced, and postoperative hospital stays were significantly shorter for laparoscopic Has. Conclusions. Although the data are still preliminary, laparoscopic surgery for patients with portal hypertension may prove to be a successful strategy.
Reducing collapse in high aspect ratio structures
Authors: Zhou Jie , Liu Gang , Cui Huanhuan , Xiong Ying , Tian Yangchao
Published: February 2012

Many defects are generated during micro- and nano-fabrication processes, especially for high aspect ratio structures. The aspect ratio of structures is an important parameter for subsequent processes. However, the top of high aspect ratio structures usually adheres to each other; moreover, pattern with high aspect ratio even can collapse or peel off from the substrate during the drying process, which is mainly ascribed to the capillary force. In this paper, a new method that puts supporting structures on the fabrication structures to reduce collapse has been proposed. The conventional method and new method were compared by calculating the deformations for different line widths and aspect ratios. The new method was also applied in fabricating nanostructures. The results indicated that the new method can effectively decrease the deformation and increase the aspect ratio.
An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data
Authors: Tvete Ingunn F , Olsen Inge C , Fagerland Morten W , Meland Nils , Aldrin Magne , Smerud Knut T , Holden Lars
Published: February 2012

Background In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate.

Methods We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis.

Results Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available.

Limitations We assume equality of the various carry-over effects over time.

Conclusions The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.
RETRACTED: Conceptual Paper
Authors: Dasgupta Mayuk
Published: February 2012

“Conceptual Paper: Organizational Learning and Its Practices” by Mayuk Dasgupta, SAGE Open, February 1, 2012, DOI: 10.1177/2158244011432198
Human CD300a binds to phosphatidylethanolamine and phosphatidylserine, and modulates the phagocytosis of dead cells
Authors: Simhadri Venkateswara R. , Andersen John F. , Calvo Eric , Choi Seung-Chul , Coligan John E. , Borrego Francisco
Published: February 2012

CD300a is an immunoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 family of paired activating/inhibitory receptors. It has been shown that its ligation inhibits activation signals on cells of both myeloid and lymphoid lineages. The ligands for CD300a have not been identified. Here, we show that a CD300a-Ig fusion protein specifically binds to apoptotic cells that are evolutionary apart, such as human and insect cells, suggesting that the ligand has to be conserved. Using surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays, we identified phosphatidylethanolamine (PE) and phosphatidylserine (PS), 2 phospholipids that translocate to the outer leaflet of the plasma membrane of dead cells, as the ligands for CD300a. Mutational and structural modeling studies identified residues that are involved in the binding of CD300a to PE and PS and that form a cavity where the hydrophilic heads of PE and PS, can penetrate. CD300a down-regulates the uptake of apoptotic cells by macrophages and its ectopic expression in CD300a-negative cell lines also decreased the engulfment of dead cells. Collectively, our results indicate that PE and PS are ligands for CD300a, and that this interaction plays an important role in regulating the removal of dead cells.
Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA-induced pressor responses in rats
Authors: Keng Nien-Tzu , Lin Hsun-Hsun , Lin Huei-Ru , Hsieh Wei-Kung , Lai Chih-Chia
Published: February 2012

Background

Acute exposure of ethanol (alcohol) inhibits NMDA receptor function. Our previous study showed that acute ethanol inhibited the pressor responses induced by NMDA applied intrathecally; however, prolonged ethanol exposure may increase the levels of phosphorylated NMDA receptor subunits leading to changes in ethanol inhibitory potency on NMDA-induced responses. The present study was carried out to examine whether acute ethanol exposure influences the effects of ketamine, a noncompetitive NMDA receptor antagonist, on spinal NMDA-induced pressor responses.

Methods

The blood pressure responses induced by intrathecal injection of NMDA were recorded in urethane-anesthetized rats weighing 250-275 g. The levels of several phosphorylated residues on NMDA receptor GluN1 subunits were determined by western blot analysis.

Results

Intravenous injection of ethanol or ketamine inhibited spinal NMDA-induced pressor responses in a dose-dependent and reversible manner. Ketamine inhibition of NMDA-induced responses was synergistically potentiated by ethanol when ethanol was applied just before ketamine. However, ketamine inhibition was significantly reduced when applied at 10 min after ethanol administration. Western blot analysis showed that intravenous ethanol increased the levels of phosphoserine 897 on GluN1 subunits (pGluN1-serine 897), selectively phosphorylated by protein kinase A (PKA), in the lateral horn regions of spinal cord at 10 min after administration. Intrathecal administration of cAMPS-Sp, a PKA activator, at doses elevating the levels of pGluN1-serine 897, significantly blocked ketamine inhibition of spinal NMDA-induced responses.

Conclusions

The results suggest that ethanol may differentially regulate ketamine inhibition of spinal NMDA receptor function depending on ethanol exposure time and the resulting changes in the levels of pGluN1-serine 897.
Conservation and divergence of chemical defense system in the tunicate Oikopleura dioica revealed by genome wide response to two xenobiotics
Authors: Yadetie Fekadu , Butcher Stephen , Førde Hilde E , Campsteijn Coen , Bouquet Jean-Marie , Karlsen Odd A , Denoeud France , Metpally Raghu , Thompson Eric M , Manak J Robert , Goksøyr Anders , Chourrout Daniel
Published: February 2012

Background

Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics have not been well investigated in most invertebrates. Here, we performed genome survey for key defensome genes inOikopleura dioicagenome, and explored genome-wide gene expression using high density tiling arrays with over 2 million probes, in response to two model xenobiotic chemicals - the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo).

Results

Oikopleuragenome surveys for key genes of the chemical defensome suggested a reduced repertoire. Not more than 23 cytochrome P450 (CYP) genes could be identified, and neither CYP1 family genes nor their transcriptional activator AhR was detected. These two genes were present in deuterostome ancestors. As in vertebrates, the genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways.

Conclusions

Oikopleurahas the smallest number of CYP genes among sequenced animal genomes and lacks the AhR signaling pathway. However it appears to have basic xenobiotic inducible biotransformation genes such as a conserved genotoxic stress response gene set. Our genome survey and expression study does not support a role of AhR signaling pathway in the chemical defense of metazoans prior to the emergence of vertebrates.
Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors
Authors: Pereira Luísa , Soares Pedro , Máximo Valdemar , Samuels David C
Published: February 2012

Background

The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level.

Methods

Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO.

Results

The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors.

Conclusions

Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype.
Copper-transporting P-type adenosine triphosphatase (ATP7A) is associated with platinum-resistance in non-small cell lung cancer (NSCLC)
Authors: Li Zhuang-hua , Qiu Miao-zhen , Zeng Zhao-lei , Luo Hui-yan , Wu Wen-jing , Wang Feng , Wang Zhi-qiang , Zhang Dong-sheng , Li Yu-hong , Xu Rui-hua
Published: February 2012

Background

Copper export protein ATP7A is important for maintaining copper homeostasis. Recent studies have shown that copper transporters are also involved in the transport of platinum. The goal of this study was to determine the role of ATP7A in the platinum-resistance of non-small cell lung cancer (NSCLC).

Methods

Sensitivities to platinums were detected by MTT assay and drug-resistance related genes were analyzed by real-time PCR and immunoblotting between DDP-sensitive A549 and the corresponding DDP-resistant cell subline (A549/DDP). ATP7A expression was evaluated by immunohistochemistry in tumor tissues of unresectable NSCLC patients who received cisplatin-basing chemotherapy.

Results

The expression of ATP7A was significantly higher in A549/DDP cell subline than in A549 cells at both mRNA and protein levels. The silencing of ATP7A expression in A549/DDP by siRNA partially reversed DDP-resistance (29.62%) and increased cell apoptosis. ATP7A expression was detected in 41.6%of NSCLC patients, but not in adjacent stroma nor normal lung tissues. ATP7A-positive patients had a significantly poorer histological grade (p = 0.039) and poorer response to platinum-basing chemotherapy (p = 0.001) compared with ATP7A-negative patients. Cox's proportional hazards analysis showed that ATP7A expression was an independent prognostic factor for overall survival (p = 0.045).

Conclusions

ATP7A overexpression played an important role in platinum-resistance of NSCLC, and was a negative prognostic factor of NSCLC patients treated with platinum-based chemotherapy.
Reduction of graphene oxide by an in-situ photoelectrochemical method in a dye-sensitized solar cell assembly
Authors: Chen Chen , Long Mingce , Xia Min , Zhang Chunhua , Cai Weimin
Published: February 2012

Reduction of graphene oxide [GO] has been achieved by an in-situ photoelectrochemical method in a dye-sensitized solar cell [DSSC] assembly, in which the semiconductor behavior of the reduced graphene oxide [RGO] is controllable. GO and RGO were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, high-resolution transmission electron microscope, and Fourier-transform infrared spectroscopy. It was found that the GO film, which assembled in the DSSC assembly as the counter electrode, was partly reduced. An optimized photoelectrochemical assembly is promising for modulating the reduction degree of RGO and controlling the band structure of the resulting RGO. Moreover, this method appeared to be a green progress for the production of RGO electrodes.
Physical, social and societal functioning of children with congenital adrenal hyperplasia (CAH) and their parents, in a Dutch population
Authors: Sanches Sarita A , Wiegers Therese A , Otten Barto J , Claahsen-van der Grinten Hedi L
Published: February 2012

Background

Most research concerning congenital adrenal hyperplasia (CAH) and related conditions caused by primary adrenal insufficiency, such as Addison's or Cushing's disease, has focused on medical aspects rather than on patients' quality of life. Therefore, our objective was to investigate the physical, social and societal functioning of children with CAH and their parents in a Dutch population.

Methods

The study is descriptive and cross-sectional. Self-designed questionnaires, based on questionnaires developed in the Netherlands for different patient groups, were sent to parents of children with CAH between 0 and 18 years old. Participants were recruited through the Dutch patient group for Adrenal Disease (NVACP) and six hospitals in the Netherlands. Three different questionnaires were designed for parents: for children aged 0 - 4, aged 4 - 12 and aged 12 - 18. Additionally, a fourth questionnaire was sent to adolescents with CAH aged 12 - 18. Main outcome measures were experienced burden of the condition, self-management and participation in several areas, such as school and leisure time.

Results

A total of 106 parents returned the questionnaire, 12 regarding pre-school children (0-4 years), 63 regarding primary school children (4-12 years), and 32 regarding secondary school children (12-18 years), combined response rate 69.7%. Also, 24 adolescents returned the questionnaire. Children and adolescents with CAH appear to be capable of self-management at a young age. Experienced burden of the condition is low, although children experience several health related problems on a daily basis. Children participate well in school and leisure time. Few children carry a crisis card or emergency injection with them.

Conclusions

Overall, our research shows that, according to their parents, children with CAH experience few negative effects of the condition and that they participate well in several areas such as school and leisure time. However, improvements can be made concerning the measures parents and children must take to prevent an adrenal crisis.
Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells
Authors: Barra Viviana , Schillaci Tiziana , Lentini Laura , Costa Giuseppe , Di Leonardo Aldo
Published: February 2012

Background

Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood.

Results

To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1 depletion slowed down proliferation of near-diploid human tumor cells (HCT116) and triggered G1 arrest in primary human fibroblasts (IMR90), by inducing p53 stabilization and, in turn, p21waf1 transactivation. Remarkably, p53 increase was not caused by DNA damage and was not observed after p14-ARF post-transcriptional silencing. Interestingly, DNMT1 silenced cells with p53 or p14-ARF depleted did not arrest in G1 but, instead, underwent DNA hypomethylation and became aneuploid.

Conclusion

Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation.
A longitudinal study on diarrhoea and vomiting in young dogs of four large breeds
Authors: Sævik Bente K , Skancke Ellen M , Trangerud Cathrine
Published: February 2012

Background

Prospective studies to document the occurrence of canine diarrhoea and vomiting are relatively scarce in dogs, and the majority of published studies are based on information from clinical records. This study investigates the incidence risk of diarrhoea and vomiting as well as potential risk factors.

Methods

A cohort study of 585 privately owned dogs of four breeds: Newfoundland, Labrador retriever, Leonberger, and Irish wolfhound. The owners maintained a continuous log regarding housing, exercise, nutrition, and health of their dogs. Episodes of diarrhoea and vomiting were recorded in a consecutive manner in a booklet. The owners completed the questionnaires and reported information at three, four, six, 12, 18, and 24/25 months of age, called observational ages.

Associations with potential risk factors for diarrhoea and vomiting were investigated in separate generalized estimating equation analyses.

Results

The incidence of both diarrhoea and vomiting was influenced by breed. Both diarrhoea and vomiting were relatively common in young dogs, occurring most frequently during the first months of life. After three months of age, the odds of diarrhoea were significantly lower when compared to the observational period seven weeks to three months (OR ranging from 0.31 to 0.70 depending on the period). More males than females suffered from diarrhoea (OR = 1.42). The occurrence of diarrhoea was more common in dogs that also experienced episode(s) of vomiting during the study period (OR = 5.43) andvice versa(OR = 5.50). In the majority of dogs episodes of diarrhoea and vomiting did not occur at the same time. Dogs in urban areas had higher odds (OR = 1.88) of getting diarrhoea compared to dogs living in rural areas. The occurrence of both diarrhoea and vomiting demonstrated a seasonal variation with higher incidence during the summer months.

Conclusion

Both diarrhoea and vomiting occurred most frequently during the first months of life. The incidence of diarrhoea and vomiting was significantly different between breeds. Diarrhoea occurred more frequently in males and in dogs living in urban areas. Also, a positive association between the occurrence of diarrhoea and vomiting in the same dog was found.
Evaluation of performance of two different chest tubes with either a sharp or a blunt tip for thoracostomy in 100 human cadavers
Authors: Ortner Clemens M , Ruetzler Kurt , Schaumann Nikolaus , Lorenz Veit , Schellongowski Peter , Schuster Ernst , Salem Ramez M , Frass Michael
Published: February 2012

Background

Emergent placement of a chest tube is a potentially life-saving procedure, but rate of misplacement and organ injury is up to 30%. In principle, chest tube insertion can be performed by using Trocar or Non-trocar techniques. If using trocar technique, two different chest tubes (equipped with sharp or blunt tip) are currently commercially available. This study was performed to detect any difference with respect to time until tube insertion, to success and to misplacement rate.

Methods

Twenty emergency physicians performed five tube thoracostomies using both blunt and sharp tipped tube kits in 100 fresh human cadavers (100 thoracostomies with each kit). Time until tube insertion served as primary outcome. Complications and success rate were examined by pathological dissection and served as further outcomes parameters.

Results

Difference in mean time until tube insertion (63s vs. 59s) was statistically not significant. In both groups, time for insertion decreased from the 1st to the 5th attempt and showed dependency on the cadaver's BMI and on the individual physician. Success rate differed between both groups (92% using blunt vs. 86% using sharp tipped kits) and injuries and misplacements occurred significantly more frequently using chest tubes with sharp tips (p = 0.04).

Conclusion

Data suggest that chest drain insertion with trocars is associated with a 6-14% operator-related complication rate. No difference in average time could be found. However, misplacements and organ injuries occurred more frequently using sharp tips. Consequently, if using a trocar technique, the use of blunt tipped kits is recommended.
Mandibular distraction in neonates: indications, technique, results
Authors: Sesenna Enrico , Magri Alice S , Magnani Cinzia , Brevi Bruno C , Anghinoni Marilena L
Published: February 2012

Background

The Pierre Robin Sequence features were first described by Robin in 1923 and include micrognathia, glossoptosis and respiratory distress with an incidence estimated as 1:8,500 to 1:20,000 newborns. Upper airway obstruction and feeding difficulties are the main concerns related to the pathology. Mandibular distraction should be considered a treatment option (when other treatments result inadequate).

Patients and methods

Ten patients between the ages of 1 month and 2 years with severe micrognathia and airway obstruction were treated with Mandibular Distraction Osteogenesis (MDO).

All patients underwent fibroscopic examination of the upper airway and a radiographic imaging and/or computed tomography scans to detect malformations and to confirm that the obstruction was caused by posterior tongue displacement. All patients were evaluated by a multidisciplinary team. Indications for surgery included frequent apneic episodes with severe desaturation (70%). Gavage therapy was employed in all patients since oral feeding was not possible. The two tracheotomy patients were 5 months and 2 years old respectively, and the distraction procedure was performed to remove the tracheotomy tube. All patients were treated with bilateral mandibular distraction: two cases with an external multivector distraction device, six cases with an internal non-resorbable device and two cases with an internal resorbable device. In one case, the patient with Goldenhar's Syndrome, the procedure was repeated.

Results

The resolution of symptoms was obtained in all patients, and, when present, tracheotomy was removed without complications. Of the two patients with pre-existing tracheotomies, in the younger patient (5 months old) the tracheotomy was removed 7 days postoperatively. In the Goldenhar's syndrome case (2 years old) a Montgomery device was necessary for 6 months due to the presence of tracheotomy-inducted tracheomalacia. Patients were discharged when the endpoint was obtained: symptoms and signs of airway obstruction were resolved, PAS and maxillomandibular relationship improved, and tracheotomy, when present, removed. During the follow-up, no injury to the inferior alveolar nerve was noted and scarring was significant in only the two cases treated with external devices.

Conclusion

Mandibular Distraction Osteogenesis is a good solution in solving respiratory distress when other procedures are failed in paediatric patients with severe micrognatia.
Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies
Authors: Liu Chih Long , Tangsombatvisit Stephanie , Rosenberg Jacob M , Mandelbaum Gil , Gillespie Emily C , Gozani Or P , Alizadeh Ash A , Utz Paul J
Published: February 2012

Introduction

Autoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones.

Methods

We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen.

Results

We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE.

Conclusions

Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
Flavivirus infection induces indoleamine 2,3-dioxygenase in human monocyte-derived macrophages via tumor necrosis factor and NF-κB
Authors: Yeung Amanda W S , Wu Wei , Freewan Mohammed , Stocker Roland , King Nicholas J C , Thomas Shane R
Published: February 2012

Infection with West Nile virus (WNV) via a mosquito bite results in local viral replication in the skin, followed by viremia. Thus, tissue macrophages are ideally located to prevent the dissemination of WNV throughout the host. The current study shows that WNV infection of human monocyte-derived macrophages (MDM) results in increased WNV mRNA, protein, and infectious virions at 24 h p.i. with a decline in titer after 48 h. Concomitant with viral control was the robust induction of indoleamine 2,3-dioxygenase (IDO) and resultant metabolism of L-tryptophan (L-Trp) to kynurenine. In WNV-exposed cultures, IDO protein was induced primarily in noninfected versus viral-infected MDM. Whereas WNV infection increased the production of IFN-α, IFN-β, and TNF, only antibody neutralization of TNF attenuated IDO expression and activity. WNV infection also activated NF-κB, and inhibition of this pathway with BMS-345541 abrogated IDO induction. Similar results were also obtained with MDM infected with the related flavivirus, Japanese encephalitis virus. Whereas IDO-mediated L-Trp metabolism can exhibit antiviral properties, inhibition of IDO activity in MDM with L-1-MT or the addition of excess L-Trp did not affect viral control. However, culturing MDM in L-Trp-deficient medium or overexpression of IDO in cells prior to infection significantly attenuated WNV replication, which was reversed by adding excess L-Trp. Together, these data support that although IDO is not required by MDM for the clearance of established viral infection, the spread of flavivirus infection is limited by IDO expressed in uninfected, neighboring cells.