bluuebunny/crossref_metadata_2025 huggingface dataset:
Dim Nighttime Light Impairs Cognition and Provokes Depressive-Like Responses in a Diurnal Rodent
Authors: Fonken Laura K. , Kitsmiller Emily , Smale Laura , Nelson Randy J.
Published: August 2012

Circadian disruption is a common by-product of modern life. Although jet lag and shift work are well-documented challenges to circadian organization, many more subtle environmental changes cause circadian disruption. For example, frequent fluctuations in the timing of the sleep/wake schedule, as well as exposure to nighttime lighting, likely affect the circadian system. Most studies of these effects have focused on nocturnal rodents, which are very different from diurnal species with respect to their patterns of light exposure and the effects that light can have on their activity. Thus, the authors investigated the effect of nighttime light on behavior and the brain of a diurnal rodent, the Nile grass rat. Following 3 weeks of exposure to standard light/dark (LD; 14:10 light [~150 lux] /dark [0 lux]) or dim light at night (dLAN; 14:10 light [~150 lux] /dim [5 lux]), rats underwent behavioral testing, and hippocampal neurons within CA1, CA3, and the dentate gyrus (DG) were examined. Three behavioral effects of dLAN were observed: (1) decreased preference for a sucrose solution, (2) increased latency to float in a forced swim test, and (3) impaired learning and memory in the Barnes maze. Light at night also reduced dendritic length in DG and basilar CA1 dendrites. Dendritic length in the DG positively correlated with sucrose consumption in the sucrose anhedonia task. Nighttime light exposure did not disrupt the pattern of circadian locomotor activity, and all grass rats maintained a diurnal activity pattern. Together, these data suggest that exposure to dLAN can alter affective responses and impair cognition in a diurnal animal.
Dissociation of Ultradian and Circadian Phenotypes in Female and Male Siberian Hamsters
Authors: Prendergast Brian J. , Cisse Yasmine M. , Cable Erin J. , Zucker Irving
Published: August 2012

Three experiments addressed whether pronounced alterations in the circadian system yielded concomitant changes in ultradian timing. Female Siberian hamsters were housed in a 16L:8D photoperiod after being subjected to a disruptive phase-shifting protocol that produced 3 distinct permanent circadian phenotypes: some hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal locomotor activity (ENTR), others displayed free-running CRs (FR), and a third cohort was circadian arrhythmic (ARR). The period of the ultradian locomotor rhythm (UR) did not differ among the 3 circadian phenotypes; neuroendocrine generation of URs remains viable in the absence of coherent circadian organization and appears to be mediated by substrates functionally and anatomically distinct from those that generate CRs. Pronounced light-dark differences in several UR characteristics in ENTR hamsters were completely absent in circadian arrhythmic hamsters. The disruptive phase-shifting protocol may compromise direct visual input to ultradian oscillators but more likely indirectly affects URs by interrupting visual afference to the circadian system. Additional experiments documented that deuterium oxide and constant light, each of which substantially lengthened the period of free-running CRs, failed to change the period of concurrently monitored URs. The resistance of URs to deuteration contrasts with the slowing of virtually all other biological timing processes, including CRs. Considered together, the present results point to the existence of separable control mechanisms for generation of circadian and ultradian rhythms.
Acute Behavioral Responses to Light and Darkness in Nocturnal Mus musculus and Diurnal Arvicanthis niloticus
Authors: Shuboni D.D. , Cramm S. , Yan L. , Nunez A.A. , Smale Laura
Published: August 2012

The term masking refers to immediate responses to stimuli that override the influence of the circadian timekeeping system on behavior and physiology. Masking by light and darkness plays an important role in shaping an organism’s daily pattern of activity. Nocturnal animals generally become more active in response to darkness (positive masking) and less active in response to light (negative masking), and diurnal animals generally have opposite patterns of response. These responses can vary as a function of light intensity as well as time of day. Few studies have directly compared masking in diurnal and nocturnal species, and none have compared rhythms in masking behavior of diurnal and nocturnal species. Here, we assessed masking in nocturnal mice ( Mus musculus) and diurnal grass rats ( Arvicanthis niloticus). In the first experiment, animals were housed in a 12:12 light-dark (LD) cycle, with dark or light pulses presented at 6 Zeitgeber times (ZTs; with ZT0 = lights on). Light pulses during the dark phase produced negative masking in nocturnal mice but only at ZT14, whereas light pulses resulted in positive masking in diurnal grass rats across the dark phase. In both species, dark pulses had no effect on behavior. In the 2nd experiment, animals were kept in constant darkness or constant light and were presented with light or dark pulses, respectively, at 6 circadian times (CTs). CT0 corresponded to ZT0 of the preceding LD cycle. Rhythms in masking responses to light differed between species; responses were evident at all CTs in grass rats but only at CT14 in mice. Responses to darkness were observed only in mice, in which there was a significant increase in activity at CT 22. In the 3rd experiment, animals were kept on a 3.5:3.5-h LD cycle. Surprisingly, masking was evident only in grass rats. In mice, levels of activity during the light and dark phases of the 7-h cycle did not differ, even though the same animals had responded to discrete photic stimuli in the first 2 experiments. The results of the 3 experiments are discussed in terms of their methodological implications and for the insight they offer into the mechanisms and evolution of diurnality.
Large Ventral Lateral Neurons Determine the Phase of Evening Activity Peak across Photoperiods in Drosophila melanogaster
Authors: Potdar Sheetal , Vasu Sheeba
Published: August 2012

The dual-oscillator model, originally proposed as a mechanism for how vertebrates adapt to seasonal changes, has been invoked to explain circadian entrainment in Drosophila melanogaster. Distinct subsets of neurons have been designated as “morning” and “evening” oscillators that function as regulators of rhythmic activity/rest behavior. Some studies have led to a model in which a subset of 8 “morning” cells (4 bilaterally located small ventral lateral neurons) and another subset of approximately 130 “evening” cells exert different levels of dominance within the circadian circuit in different seasons. However, many studies propose a more integrative neuronal network, with the whole network orchestrating activity/rest rhythms in different seasons, as opposed to hierarchical dominance among neurons. Within the circadian network, our understanding of the role of the large ventral lateral neurons (l-LNv) has thus far been limited to conveying light information to the clocks and as light-activated neurons mediating arousal. In support of the framework of a more distributed model, we report an important circadian clock–related role for the l-LNv in electrical activity–dependent phasing of the evening peak across a range of photoperiods. Further, we propose a model in which l-LNv enable adaptation to seasonal changes by regulating the phase of the evening peak. Additionally, we demonstrate a hitherto unknown role for the small ventral lateral neurons (s-LNv) in the arousal circuit, thus showing that neuronal function is flexible such that certain neurons can play more than one role in distinct circuits.
The Input Signal Step Function (ISSF), a Standard Method to Encode Input Signals in SBML Models with Software Support, Applied to Circadian Clock Models
Authors: Adams R.R. , Tsorman N. , Stratford K. , Akman O.E. , Gilmore S. , Juty N. , Le Novère N. , Millar A.J. , Millar A.J.
Published: August 2012

Time-dependent light input is an important feature of computational models of the circadian clock. However, publicly available models encoded in standard representations such as the Systems Biology Markup Language (SBML) either do not encode this input or use different mechanisms to do so, which hinders reproducibility of published results as well as model reuse. The authors describe here a numerically continuous function suitable for use in SBML for models of circadian rhythms forced by periodic light-dark cycles. The Input Signal Step Function (ISSF) is broadly applicable to encoding experimental manipulations, such as drug treatments, temperature changes, or inducible transgene expression, which may be transient, periodic, or mixed. It is highly configurable and is able to reproduce a wide range of waveforms. The authors have implemented this function in SBML and demonstrated its ability to modify the behavior of publicly available models to accurately reproduce published results. The implementation of ISSF allows standard simulation software to reproduce specialized circadian protocols, such as the phase-response curve. To facilitate the reuse of this function in public models, the authors have developed software to configure its behavior without any specialist knowledge of SBML. A community-standard approach to represent the inputs that entrain circadian clock models could particularly facilitate research in chronobiology.
‘Children of Kinegawa’ and the transformation of the ‘buraku identity’ in Japan
Authors: Cangià Flavia
Published: August 2012

The present article explores the way children engaged with the buraku issue in Japan shape the collective discourses concerning the ‘buraku minority identity’, and re-design the ‘Otherness’, through being rooted in non-ethnic and universal standards, such as local attachment, socioeconomic values, community and family-based relationships. The author illustrates this by introducing the various social fields in which children participate in the representation of the ‘buraku culture’, with a focus on children in Kinegawa and surroundings, in Tokyo.
Delegation of childcare as a corner stone of children’s interethnic relations
Authors: Huber Véronique Pache
Published: August 2012

Adopting a diachronic perspective, this article explains that childcare and education was, since Ancient times, delegated to non-related persons (governesses, wet nurses, nannies, domestic workers), who provided services in the domestic domain. Since these various professionals belonged often to other ethnic/national groups than their employers, children have been major actors in the establishment of interethnic/cultural relations.
Non-linear phenomena occurring during the start-up process of a travelling-wave looped-tube thermoacoustic engine
Authors: Abduljalil Abdulrahman S , Yu Zhibin , Jaworski Artur J
Published: August 2012

This article reports the investigation of non-linear start-up processes in a looped-tube thermoacoustic engine. The engine utilises air as working gas, and has the fundamental frequency of around 111 Hz. It is observed that the mean pressure and the input heat power are the two key parameters controlling the start-up behaviour of the engine. When these are varied, a range of non-linear transient phenomena are observed, which include the ‘on–off’ effect, ‘fishbone-like’ oscillations (i.e. the quasi-periodic pressure amplitude bursts followed by a quasi steady state), and the normal smooth start-up process. The experiments show that the ‘fishbone-like’ bursts are a new mode of pressure amplitude growth. A series of experiments have been conducted to investigate in detail the influence of mean pressure, input heat power and regenerator type on the occurrence of such quasi-periodic amplitude bursts. It is observed that the duration of the pressure amplitude bursts depends on the combination of the heating power and the mean pressure. The observations suggest that there are strong interactions between the acoustic and temperature fields within the regenerator. It is thought that these can lead to the reported quasi-periodic unsteady behaviour of the engine.
Quality, stability and radical scavenging activity of olive oils after Chétoui olives (Olea europaea L.) storage under modified atmospheres
Authors: Yahia L Ben , Baccouri B , Ouni Y , Hamdi S
Published: August 2012

At the industrial scale, the major source of olive oil deterioration is the poor handling of the raw material during the time separating harvesting from processing. The objective of this work was to verify the effect of modified atmospheres and cold storage in relation to quality parameters of the extracted oils. Olives (cv Chétoui) intended for oil extraction, were stored for 21 days at two different temperatures (ambient temperature 14 ± 2 °C and 5 °C) and under two different modified atmospheres 21% O2 – 0% CO2 and 2% O2 – 5% CO2. Oils quality was ascertained with analytical parameters: free fatty acids, peroxide value, K232, K270 as suggested by European regulation. Oxidative stability, total phenols content, radical scavenging activity and fatty acids composition were carried out in order to measure the hydrolytic and oxidative degradation of oils. Olive oils quality parameters were significantly affected by treatments with especially a beneficial effect on primary oxidation indicators and free acidity. Most efficient treatments, with regard to oils phenolic content and involved parameters, were 21% O2 – 0% CO2 at ambient temperature (636.25 mg ca/kg) and 2% O2 – 5% CO2 under 5 °C (637.50 mg ca/kg). Those two treatments improved individually oil samples phenolic content of 25% but not at the same storage period.
Quality, microstructure, biochemical and immunochemical characteristics of hypoallergenic pasta
Authors: Susanna S , Prabhasankar P
Published: August 2012

Celiac disease is an immune-mediated enteropathy, characterized by lifelong intolerance to gluten in genetically susceptible individuals. This study aims to develop hypoallergenic pasta using blends of Triticum durum semolina, 40% of other non-wheat flours and additives. Formulated pasta samples were evaluated for product quality characteristics and also subjected to biochemical analysis. Results showed that cooking loss ranged from 6.9% to 7.4%, which were within the acceptable range of 8%. Color change was low and in vitro protein digestibility of the pasta was found to be insignificant. Pasting characteristics of the hypoallergenic flour showed the increased peak viscosity and decreased gelatinization temperature. The scanning electron microscopy results demonstrated less-affected microstructure of gluten network. Texture profile analysis and descriptive sensory analysis revealed that optimized hypoallergenic pasta with xanthan gum as additive was acceptable and comparable with control. SDS-PAGE pattern showed distinct protein profile and decreased intensity, which was supported by Dot-Blot. In conclusion, the hypoallergenic pasta prepared by replacing T durum flour by 40% of other non-gluten flours could be useful for celiac patients because of its low antigenic activity.
Continuity in the Provider of Home Health Aide Services and the Likelihood of Patient Improvement in Activities of Daily Living
Authors: Russell David , Rosati Robert J. , Peng Timothy R. , Barrón Yolanda , Andreopoulos Evie
Published: August 2012

Receiving care from the same provider over time is an important dimension of continuity in home healthcare. In the present study, we examine whether continuity in the provider of home health aide services is associated with the likelihood of improvement in Activities of Daily Living (ADLs). To address this research question, we retrieved clinical and administrative records from a population of cases receiving home health aide services at a large, urban, not-for-profit Medicare-certified home healthcare agency ( N =16,541). Results revealed that cases which had high levels of continuity in the provider of home health aide services had a significantly greater likelihood of improvement in ADLs compared to cases with the lowest level of continuity.
Interrater Reliability of the Five-Times-Sit-to-Stand Test
Authors: Wallmann Harvey W. , Evans Nicole S. , Day Christopher , Neelly Kurt R.
Published: August 2012

The sit-to-stand (STS) task, an important activity required to maintain functional independence, can be used to assess physical performance. The purpose of this study was to determine the interrater reliability of the five-times-sit-to-stand test (FTSTS). Ninety-two subjects, mean age of 65 years, performed the FTSTS without the use of the upper extremities. A video recording of each subject’s performance was independently assessed to determine the test completion time by three clinicians with similar education and years of clinical experience. An intraclass correlation coefficient (ICC2,1) was used to determine the interrater reliability of the FTSTS. Statistical analysis revealed excellent interrater reliability among all three researchers: ICC = 1.000. When clinicians with equal education and clinical experience administer the FTSTS, it has excellent interrater reliability.
Increasing Teachers’ Knowledge About ADHD and Learning Disorders
Authors: Aguiar Ana P. , Kieling Renata R. , Costa Adriana C. , Chardosim Neusa , Dorneles Beatriz V. , Almeida Mariana R. , Mazzuca Ana C. , Kieling Christian , Rohde Luis A.
Published: August 2012

Objective: To investigate elementary school teachers’ baseline knowledge about ADHD and learning disorders (LD) and the impact of a strategy to increase awareness of these disorders. Method: A total of 37 teachers were selected from four elementary schools in the catchment area of the University Hospital, in Porto Alegre, Brazil. To evaluate teachers’ knowledge, two self-report questionnaires about ADHD and LD were applied before and after an awareness program on these disorders. Results: The intervention significantly increased teachers’ knowledge of both disorders, even after adjustment for confounding factors ( p < .001). In the repeated measures ANCOVA, only teachers’ previous knowledge of ADHD/LD ( p < .001) was significant in predicting score change in knowledge before and after the intervention. Conclusion: Results suggest the efficacy of a brief psychoeducational intervention program for increasing teacher awareness and knowledge about ADHD and LD. Future studies are warranted to confirm the efficacy and evaluate the long-term impact of this intervention.
Belief and affect: On the mental pre-cursors of health-related cognition and behaviour
Authors: Forgas Joseph P
Published: August 2012

This paper will discuss the importance of concepts such as belief and affect to the theory and practice of health psychology, and the potential contribution of the revised conceptualisation of belief proposed in the target article will be considered. In the first half of the paper a number of important differences between the new approach and established empirical approaches to the study of beliefs will be highlighted. The second half of the paper will focus on the important relationship between affect and beliefs, one of the key issues addressed in the target paper. A number of recent theories linking affect and belief will be reviewed, and recent empirical research demonstrating the psychological mechanisms linking affect and belief will be discussed. In light of the considerable achievements of this line of inquiry, it is concluded that the proposed new approach and definition of belief does not as yet offer a preferable alternative to understanding the role of belief in health-related cognition and behaviour.
Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the FANCD2 protein
Authors: Rego Meghan A. , Kolling Frederick W. , Vuono Elizabeth A. , Mauro Maurizio , Howlett Niall G.
Published: August 2012

The Fanconi anemia (FA)–BRCA pathway is critical for the repair of DNA interstrand crosslinks (ICLs) and the maintenance of chromosome stability. A key step in FA-BRCA pathway activation is the covalent attachment of monoubiquitin to FANCD2 and FANCI. Monoubiquitinated FANCD2 and FANCI localize in chromatin-associated nuclear foci where they interact with several well-characterized DNA repair proteins. Importantly, very little is known about the structure, function, and regulation of FANCD2. Herein, we describe the identification and characterization of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) ubiquitin-binding domain (UBD) in FANCD2, and demonstrate that the CUE domain mediates noncovalent binding to ubiquitin in vitro. We show that although mutation of the CUE domain destabilizes FANCD2, the protein remains competent for DNA damage-inducible monoubiquitination and phosphorylation. Importantly, we demonstrate that the CUE domain is required for interaction with FANCI, retention of monoubiquitinated FANCD2, and FANCI in chromatin, and for efficient ICL repair. Our results suggest a model by which heterodimerization of monoubiquitinated FANCD2 and FANCI in chromatin is mediated in part through a noncovalent interaction between the FANCD2 CUE domain and monoubiquitin covalently attached to FANCI, and that this interaction shields monoubiquitinated FANCD2 from polyubiquitination and proteasomal degradation.
Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation
Authors: Nitschké Maximilian , Aebischer David , Abadier Michael , Haener Simone , Lucic Matije , Vigl Benjamin , Luche Hervé , Fehling Hans Jörg , Biehlmaier Oliver , Lyck Ruth , Halin Cornelia
Published: August 2012

Dendritic cell (DC) migration via lymphatic vessels to draining lymph nodes (dLNs) is crucial for the initiation of adaptive immunity. We imaged this process by intravital microscopy (IVM) in the ear skin of transgenic mice bearing red-fluorescent vasculature and yellow-fluorescent DCs. DCs within lymphatic capillaries were rarely transported by flow, but actively migrated within lymphatics and were significantly faster than in the interstitium. Pharmacologic blockade of the Rho-associated protein kinase (ROCK), which mediates nuclear contraction and de-adhesion from integrin ligands, significantly reduced DC migration from skin to dLNs in steady-state. IVM revealed that ROCK blockade strongly reduced the velocity of interstitial DC migration, but only marginally affected intralymphatic DC migration. By contrast, during tissue inflammation, ROCK blockade profoundly decreased both interstitial and intralymphatic DC migration. Inhibition of intralymphatic migration was paralleled by a strong up-regulation of ICAM-1 in lymphatic endothelium, suggesting that during inflammation ROCK mediates de-adhesion of DC-expressed integrins from lymphatic-expressed ICAM-1. Flow chamber assays confirmed an involvement of lymphatic-expressed ICAM-1 and DC-expressed ROCK in DC crawling on lymphatic endothelium. Overall, our findings further define the role of ROCK in DC migration to dLNs and reveal a differential requirement for ROCK in intralymphatic DC crawling during steady-state and inflammation.
Multiple trait multiple interval mapping of quantitative trait loci from inbred line crosses
Authors: Costa E Silva Luciano Da , Wang Shengchu , Zeng Zhao-Bang
Published: August 2012

Background

Although many experiments have measurements on multiple traits, most studies performed the analysis of mapping of quantitative trait loci (QTL) for each trait separately using single trait analysis. Single trait analysis does not take advantage of possible genetic and environmental correlations between traits. In this paper, we propose a novel statistical method for multiple trait multiple interval mapping (MTMIM) of QTL for inbred line crosses. We also develop a novel score-based method for estimating genome-wide significance level of putative QTL effects suitable for the MTMIM model. The MTMIM method is implemented in the freely available and widely used Windows QTL Cartographer software.

Results

Throughout the paper, we provide compelling empirical evidences that: (1) the score-based threshold maintains proper type I error rate and tends to keep false discovery rate within an acceptable level; (2) the MTMIM method can deliver better parameter estimates and power than single trait multiple interval mapping method; (3) an analysis ofDrosophiladataset illustrates how the MTMIM method can better extract information from datasets with measurements in multiple traits.

Conclusions

The MTMIM method represents a convenient statistical framework to test hypotheses of pleiotropic QTL versus closely linked nonpleiotropic QTL, QTL by environment interaction, and to estimate the total genotypic variance-covariance matrix between traits and to decompose it in terms of QTL-specific variance-covariance matrices, therefore, providing more details on the genetic architecture of complex traits.
Nasogastric tube insertion in anesthetized and intubated patients: a new and reliable method
Authors: Tsai Yung-Fong , Luo Chiao-Fen , Illias Amina , Lin Chih-Chung , Yu Huang-Ping
Published: August 2012

Background

The “Rusch” intubation stylet is used to make endotracheal tube intubation easy. We designed this study to evaluate the usage of this equipment in the guidance of nasogastric tube (NGT) insertion.

Methods

A total of 103 patients, aged 23 to 70 years, undergoing gastrointestinal or hepatic surgeries that required intraoperative NGT insertions were enrolled into our study. The patients were randomly allocated to the control group (Group C) or the stylet group (Group S) according to a computerized, random allocation software program. In the control group, the NGT was inserted with the patient’s head in an intubating position. In the stylet group, the NGT was inserted with the assistance of a “Rusch” intubation stylet tied together at the tips by a slipknot. The success rates of the two methods, the durations of the insertions, and the occurrences of complications were recorded. All of the failed cases in the control group were subjected to the new technique used in the stylet group, and the successful rescue rate was also evaluated.

Results

Successful insertions were recorded for 52/53 patients (98.1%) in Group S and for 32/50 patients (64%) in Group C. The mean insertion times were 39.5 ± 19.5 seconds in Group C and 40.3 ± 23.2 seconds in Group S. Successful rescues of failure cases in Group C were achieved in 17/18 patients (94.4%) with the assistance of a “Rusch” intubation stylet.

Conclusions

The “Rusch” intubation stylet-guided method is reliable with a high success rate of NGT insertion in anesthetized and intubated patients.

Trial registration

Institutional Review Board of Chang Gung Memorial Hospital (IRB: 98-2669B) and Australian New Zealand Clinical Trials Registry (ACTRN12611000423910)
Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non–small cell lung cancer (WJOG 5910L)
Authors: Takeda Masayuki , Okamoto Isamu , Yamanaka Takeharu , Nakagawa Kazuhiko , Nakanishi Yoichi
Published: August 2012

Background

Bevacizumab, a humanized antibody to vascular endothelial growth factor (VEGF), shows clinical activity against human cancer, with its addition to standard chemotherapy having been found to improve outcome in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However, there have been no evidence-based studies to support the continued use of bevacizumab beyond disease progression in such patients treated with the drug in first-line therapy. We have now designed a randomized phase II trial to examine the clinical benefit and safety of continued bevacizumab treatment in patients with advanced nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet.

Methods/Design

WJOG 5910L was designed as a multicenter, open-label, randomized, phase II trial by the West Japan Oncology Group of docetaxel (arm A) versus docetaxel plus bevacizumab (arm B) in patients with recurrent or metatstatic nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. Patients in arm A will receive docetaxel at 60 mg/m2 and those in arm B will receive docetaxel at 60 mg/m2 plus bevacizumab at 15 mg/kg, with each drug administered on day 1 every 21 days until progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival, with secondary endpoints including response rate, overall survival, and safety, for patients treated in either arm.

Trial registration

UMIN (University Hospital Medical Information Network in Japan) 000004715
Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen
Authors: Zhao Jun , Zhao Mingfang , Jin Bo , Yu Ping , Hu Xuejun , Teng Yuee , Zhang Jingdong , Luo Ying , Zhang Lingyun , Zheng Shuang , Zhou Qiyin , Li Heming , Liu Yunpeng , Qu Xiujuan
Published: August 2012

Background

Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC.

Methods

In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed.

Results

The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy.

Conclusions

This study showed that the reduction in plasma fibrinogen levels induced by chemotherapy might be as a promising biomarker as CEA and CA125 for evaluating the efficacy of chemotherapy in advanced NSCLC. In addition, basal plasma fibrinogen levels could be used as an independent prognostic parameter for the OS of patients with advanced NSCLC.
Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma
Authors: Bose Pinaki , Klimowicz Alexander C , Kornaga Elizabeth , Petrillo Stephanie K , Matthews T Wayne , Chandarana Shamir , Magliocco Anthony M , Brockton Nigel T , Dort Joseph C
Published: August 2012

Background

Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique.

Methods

Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model.

Results

Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p = 0.013].

Conclusions

The AQUA technique used in our study eliminates observer bias and provides reliable and reproducible estimates for biomarker expression. AQUA also provides essential measures of quality control that cannot be achieved with manual biomarker scoring techniques. Our results support the use of Bax protein expression as a prognostic marker in conjunction with other clinico-pathological variables when designing personalized treatment strategies for OSCC patients.
The effects of low-dose Nepsilon-(carboxymethyl)lysine (CML) and Nepsilon-(carboxyethyl)lysine (CEL), two main glycation free adducts considered as potential uremic toxins, on endothelial progenitor cell function
Authors: Zhu Jinzhou , Yang Ke , Jing Yajun , Du Run , Zhu Zhenbin , Lu Lin , Zhang Ruiyan
Published: August 2012

Background

Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD). Endothelial progenitor cell (EPCs) dysfunction plays a key role in this pathogenesis. Uremic retention toxins have been reported to be in associated with EPC dysfunction. Advanced glycation end-products (AGEs) free adducts, including Nepsilon-(carboxymethyl)lysine (CML) and Nepsilon-(carboxyethyl)lysine (CEL), are formed by physiological proteolysis of AGEs and released into plasma for urinary excretion. They are retained in CKD patients and are considered to be potential uremic toxins. Though AGEs have been demonstrated to impair EPC function in various ways, the effect of AGE free adducts on EPC function has not been studied. Thus, we examined the role of CML and CEL in the regulation of growth-factor-dependent function in cultured human EPCs and the mechanisms by which they may affect EPC function.

Methods

Late outgrowth EPCs were incubated with different concentrations of CML or CEL for up to 72 hours. Cell proliferation was determined using WST-1 and BrdU assays. Cell apoptosis was tested with annexin V staining. Migration and tube formation assays were used to evaluate EPC function.

Results

Though CML and CEL were determined to have anti-proliferative effects on EPCs, cells treated with concentrations of CML and CEL in the range found in CKD patients had no observable impairment on migration or tube formation. CML and CEL did not induce EPC apoptosis. The reduced growth response was accompanied by significantly less phosphorylation of mitogen-activated protein kinases (MAPKs).

Conclusions

Our study revealed that CML and CEL at uremic concentrations have low biological toxicity when separately tested. The biologic effects of AGE free adducts on the cardiovascular system merit further study.
Microwave characterisation of carbon nanotube powders
Authors: Porch Adrian , Odili Daniel I , Childs Peter A
Published: August 2012

We have used a 3-GHz microwave host cavity to study the remarkable electronic properties of metallic, single-walled carbon nanotubes. Powder samples are placed in its magnetic field antinode, which induces microwave currents without the need for electrical contacts. Samples are shown to screen effectively the microwave magnetic field, implying an extremely low value of sheet resistance (< 10 μΩ) within the graphene sheets making up the curved nanotube walls. Associated microwave losses are large due to the large surface area, and also point to a similar, very small value of sheet resistance due to the inherent ballistic electron transport.
Erratum to Fixed point theorems for contraction mappings in modular metric spaces, Fixed Point Theory Appl. 2011, 2011:93
Authors: Mongkolkeha Chirasak , Sintunavarat Wutiphol , Kumam Poom
Published: August 2012

This article is written due to a small gap in our published paper. In this erratum, we point out and fix the problem to set our existed results at the best of their perfection.
Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome (22q11.2 deletion syndrome) and unaffected siblings
Authors: Radoeva Petya D , Coman Ioana L , Antshel Kevin M , Fremont Wanda , McCarthy Christopher S , Kotkar Ashwini , Wang Dongliang , Shprintzen Robert J , Kates Wendy R
Published: August 2012

Background

Velo-cardio-facial syndrome (VCFS, MIM#192430, 22q11.2 Deletion Syndrome) is a genetic disorder caused by a deletion of about 40 genes at the q11.2 band of one copy of chromosome 22. Individuals with VCFS present with deficits in cognition and social functioning, high risk of psychiatric disorders, volumetric reductions in gray and white matter (WM) and some alterations of the WM microstructure. The goal of the current study was to characterize the WM microstructural differences in individuals with VCFS and unaffected siblings, and the correlation of WM microstructure with neuropsychological performance. We hypothesized that individuals with VCFS would have decreased indices of WM microstructure (fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD)), particularly in WM tracts to the frontal lobe, and that these measures would be correlated with cognitive functioning.

Methods

Thirty-three individuals with VCFS (21 female) and 16 unaffected siblings (8 female) participated in DTI scanning and neuropsychological testing. We performed an atlas-based analysis, extracted FA, AD, and RD measures for 54 WM tracts (27 in each hemisphere) for each participant, and used MANOVAs to compare individuals with VCFS to siblings. For WM tracts that were statistically significantly different between VCFS and siblings (pFDR < 0.05), we assessed the correlations between DTI and neuropsychological measures.

Results

In VCFS individuals as compared to unaffected siblings, we found decreased FA in the uncinate fasciculus, and decreased AD in multiple WM tracts (bilateral superior and posterior corona radiata, dorsal cingulum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, superior cerebellar peduncle, posterior thalamic radiation, and left anterior corona radiata, retrolenticular part of the internal capsule, external capsule, sagittal stratum). We also found significant correlations of AD with measures of executive function, IQ, working memory, and/or social cognition.

Conclusions

Our results suggest that individuals with VCFS display abnormal WM connectivity in a widespread cerebro-anatomical network, involving tracts from/to all cerebral lobes and the cerebellum. Future studies could focus on the WM developmental trajectory in VCFS, the association of WM alterations with psychiatric disorders, and the effects of candidate 22q11.2 genes on WM anomalies.
Comparative effectiveness of post-discharge interventions for hospitalized smokers: study protocol for a randomized controlled trial
Authors: Japuntich Sandra J , Regan Susan , Viana Joseph , Tymoszczuk Justyna , Reyen Michele , Levy Douglas E , Singer Daniel E , Park Elyse R , Chang Yuchiao , Rigotti Nancy A
Published: August 2012

Background

A hospital admission offers smokers an opportunity to quit. Smoking cessation counseling provided in the hospital is effective, but only if it continues for more than one month after discharge. Providing smoking cessation medication at discharge may add benefit to counseling. A major barrier to translating this research into clinical practice is sustaining treatment during the transition to outpatient care. An evidence-based, practical, cost-effective model that facilitates the continuation of tobacco treatment after discharge is needed. This paper describes the design of a comparative effectiveness trial testing a hospital-initiated intervention against standard care.

Methods/design

A two-arm randomized controlled trial compares the effectiveness of standard post-discharge care with a multi-component smoking cessation intervention provided for three months after discharge. Current smokers admitted to Massachusetts General Hospital who receive bedside smoking cessation counseling, intend to quit after discharge and are willing to consider smoking cessation medication are eligible. Study participants are recruited following the hospital counseling visit and randomly assigned to receive Standard Care or Extended Care after hospital discharge. Standard Care includes a recommendation for a smoking cessation medication and information about community resources. Extended Care includes up to three months of free FDA-approved smoking cessation medication and five proactive computerized telephone calls that use interactive voice response technology to provide tailored motivational messages, offer additional live telephone counseling calls from a smoking cessation counselor, and facilitate medication refills. Outcomes are assessed at one, three, and six months after hospital discharge. The primary outcomes are self-reported and validated seven-day point prevalence tobacco abstinence at six months. Other outcomes include short-term and sustained smoking cessation, post-discharge utilization of smoking cessation treatment, hospital readmissions and emergency room visits, and program cost per quit.

Discussion

This study tests a disseminable smoking intervention model for hospitalized smokers. If effective and widely adopted, it could help to reduce population smoking rates and thereby reduce tobacco-related mortality, morbidity, and health care costs.

Trial registration

United States Clinical Trials Registry NCT01177176.
Translationally Controlled Tumour Protein (TCTP) is present in human cornea and increases in herpetic keratitis
Authors: Batisti Cinzia , Ambrosio Maria R , Rocca Bruno J , Tosi Gian M , Sanchez Jean C , Arcuri Felice , Cintorino Marcella , Tripodi Sergio A
Published: August 2012

Background

Translationally Controlled Tumour protein is a multifunctional calcium binding protein which has an important role in apoptosis, calcium levels balance and immunological response. The aim of this study was to evaluated the presence and distribution of TCTP in healthy human corneas and to identify and characterize the presence and distribution of this protein in human normal cornea. Since recent studies suggest that apoptosis, calcium levels and immunological mechanisms play a role in the pathogenesis of herpetic stromal keratitis, we studied TCTP expression in this disease.

Methods

We evaluated the expression of TCTP at both RNA messanger and protein level by using reverse transcriptase analysis, immunoblotting and immunohistochemistry in 10 healthy samples cornea: four obtained after penetrating keratoplasty and six from eyes enucleated for other pathologies. Finally, we analysed by immunohistochemistry ten paraffin-embedded samples of Herpes simplex virus keratitis collected at Siena Department of Human Pathology and Oncology: 5 had clinically quiescent disease and 5 had active corneal inflammation.

Results

Reverse transcriptase and immunoblotting demonstrated TCTP expression in cornea as a 22,000 Da molecular weight band corresponding to the molecular weight of this protein. Immunohistochemically, all the layers of normal corneal epithelium showed TCTP cytoplasmic expression. TCTP was, also, observed in keratocytes and in the endothelium. In Herpes simplex virus keratitis samples, strong expression of TCTP was evident in stromal cells, in the inflammatory infiltrate and in neo-vessels.

Conclusions

In this preliminary study we demonstrated, for the first time, the presence of TCTP in human cornea, suggesting a potential role in the pathogenesis of herpes virus keratitis.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3306813447428149
Rationalization of paclitaxel insensitivity of yeast β-tubulin and human βIII-tubulin isotype using principal component analysis
Authors: Das Lalita , Bhattacharya Bhabatarak , Basu Gautam
Published: August 2012

Background

The chemotherapeutic agent paclitaxel arrests cell division by binding to the hetero-dimeric protein tubulin. Subtle differences in tubulin sequences, across eukaryotes and among β-tubulin isotypes, can have profound impact on paclitaxel-tubulin binding. To capture the experimentally observed paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin, within a common theoretical framework, we have performed structural principal component analyses of β-tubulin sequences across eukaryotes.

Results

The paclitaxel-resistance of human βIII tubulin isotype and yeast β-tubulin uniquely mapped on to the lowest two principal components, defining the paclitaxel-binding site residues of β-tubulin. The molecular mechanisms behind paclitaxel-resistance, mediated through key residues, were identified from structural consequences of characteristic mutations that confer paclitaxel-resistance. Specifically, Ala277 in βIII isotype was shown to be crucial for paclitaxel-resistance.

Conclusions

The present analysis captures the origin of two apparently unrelated events, paclitaxel-insensitivity of yeast tubulin and human βIII tubulin isotype, through two common collective sequence vectors.
Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes
Authors: Yu Jiandong , Qian Hao , Wang Jin-Hui
Published: August 2012

Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners.