bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein–Barr virus‐associated T/natural killer‐cell lymphomas in the elderly: The first consensus meeting in Kofu 2013
Authors: Hamada Toshihisa , Nakamura Shigeo , Ko Young‐Hyeh , Yoshino Tadashi , Ohshima Koichi , Matsuzawa Takamitsu , Miura Keiko , Takahashi Toshifumi , Nomura Hisashi , Hoshino Tomomi , Suzuki Daisuke , Shimada Shinji , Iwatsuki Keiji
Published: January 2014

From a clinicopathological conference on nine elderly patients with Epstein–Barr virus (EBV)‐associated T/natural killer (NK)‐cell lymphoma, we have addressed the patients' backgrounds, clinical manifestations, histopathological findings, cytogenesis, complications and prognoses. Among these elderly patients (>65 years old), seven patients had extranodal NK/T‐cell lymphoma, nasal type (ENKL) with an NK‐cell phenotype, and two patients had EBV+ T‐cell lymphomas or lymphoproliferative disorders (LPD) with cutaneous lesions mimicking pityriasis lichenoides et varioliformis acuta (PLEVA) or hydroa vacciniforme (HV). No patients had a previous episode of EBV‐related symptoms such as infectious mononucleosis, chronic active EBV infection, HV or hypersensitivity to mosquito bites. Elderly patients with ENKL may show the centroblastoid variant. EBV+CD8+CD56+/− lymphocytes may be responsible for the development of PLEVA or HV‐like cutaneous lesions in the elderly.
Meeting report on the possible proposal of an extranodal primary cutaneous variant in the lymphoma type of adult T‐cell leukemia‐lymphoma
Authors: Tsukasaki Kunihiro , Imaizumi Yositaka , Tokura Yoshiki , Ohshima Kouichi , Kawai Kazuhiro , Utsunomiya Atae , Amano Masahiro , Watanabe Toshiki , Nakamura Shigeo , Iwatsuki Keiji , Kamihira Shimeru , Yamaguchi Kazunari , Shimoyama Masanori
Published: January 2014

Based on the advances in research on the clinicopathophysiology of adult T‐cell leukemia‐lymphoma (ATL), Japanese researchers collected and evaluated cases of smoldering ATL exhibiting primary cutaneous manifestation but showing poor prognosis. Macroscopic findings of skin eruptions were categorized into the patch, plaque, multipapular, nodulotumoral, erythrodermic and purpuric types, as previously reported. Pathological findings were divided into low or high grade based on epidermotropism, tumor cell size and perivascular infiltration. Eight eligible cases were evaluated among 14 collected cases. Macroscopic findings were nodulotumoral in six cases, a subcutaneous tumor in one case and plaque in one case, and the number and size were heterogeneous in each case. Pathological findings of all eight cases were T‐cell lymphoma, high‐grade type (pleomorphic, medium or large size), with prominent perivascular infiltration and scant epidermotropism. To diagnose such cases as the “lymphoma type of ATL, extranodal primary cutaneous variant”, it is essential to examine each case carefully, including cutaneous lesions at onset, lymph nodes and other organ involvement using computed tomography (CT) and/or positron emission tomography/CT, as well as the percentage of abnormal lymphocytes in peripheral blood. Based on the results of an ongoing nationwide survey on ATL, ATL with cutaneous lesions will be analyzed to investigate the incidence and prognosis of the so‐called “lymphoma type of ATL, extranodal primary cutaneous variant”.
Rhodobacter sphaeroides, a novel tumor‐targeting bacteria that emits natural near‐infrared fluorescence
Authors: Kwon Seong Young , Jiang Sheng‐Nan , Zheng Jin Hai , Choy Hyon E. , Min Jung‐Joon
Published: January 2014

Several optical imaging techniques have been used to monitor bacterial tropisms for cancer. Most such techniques require genetic engineering of the bacteria to express optical reporter genes. This study investigated a novel tumor‐targeting strain of bacteria, Rhodobacter sphaeroides 2.4.1 (R. sphaeroides), which naturally emits near‐infrared fluorescence, thereby facilitating the visualization of bacterial tropisms for cancer. To determine the penetration depth of bacterial fluorescence, various numbers of cells (from 108 to 1010 CFU) of R. sphaeroides and two types of Escherichia coli, which stably express green fluorescent protein (GFP) or red fluorescent protein (RFP), were injected s.c. or i.m. into mice. Bacterial tropism for cancer was determined after i.v. injection of R. sphaeroides (108 CFU) into mice implanted s.c. with eight types of tumors. The intensity of the fluorescence signal in deep tissue (muscle) from R. sphaeroides was much stronger than from E. coli‐expressing GFP or RFP. The near‐infrared fluorescence signal from R. sphaeroides was visualized clearly in all types of human or murine tumors via accumulation of bacteria. Analyses of C‐reactive protein and procalcitonin concentrations and body weights indicated that i.v. injection of R. sphaeroides does not induce serious systemic immune reactions. This study suggests that R. sphaeroides could be used as a tumor‐targeting microorganism for the selective delivery of drugs to tumor tissues without eliciting a systemic immune reaction and for visualizing tumors.
Geographic distance is more relevant than elevation to patterns of outbreeding in Ranunculus bulbosus
Authors: Matter Philippe , Kettle Chris J. , Frei Esther R. , Ghazoul Jaboury , Pluess Andrea R.
Published: January 2014

Mountain ecosystems can exert different selection pressures on plant populations over small scales due to steep environmental gradients.

Gene flow between lower‐ and higher‐elevation plant populations could lead to the increased integration of potentially adaptive genes and thereby to outbreeding vigour under current rapid climatic changes. Alternatively, gene flow across elevation could disrupt gene complexes leading to outbreeding depression.

We explored the responses of higher (1800 m a.s.l.) and lower (1200 m a.s.l.) Ranunculus bulbosusL. populations to intra‐ and interelevational and short‐ as well as long‐distance gene flow by means of controlled crosses and assessment of the offspring's germination, growth and fitness.

Outbreeding differed between elevations of origin: higher populations were negatively affected by pollen flow from lower populations at the earliest life stages, but tended to be positively affected in terms of growth later on while gene flow across small vs. large distances had no impact on growth traits. Lower populations were not significantly affected by the elevational origin of pollen per se.

However, fitness of offspring of populations from both higher and lower elevations was jointly affected by elevational and regional origins of pollen, in which case the gene flow distance had a comparatively stronger positive impact on fitness (outbreeding vigour) than elevational origin.

Synthesis: Our results indicate that compared to gene flow at regional scales, gene flow across elevational gradients has a minor effect on R. bulbosus. The lack of outbreeding depression suggests that potentially adaptive genes might well be integrated across populations resulting in an increased resilience of R. bulbosus and potentially similar montane plant species in changing climatic conditions.
Transcriptome resources for the perennial sunflower Helianthus maximiliani obtained from ecologically divergent populations
Authors: Kawakami Takeshi , Darby Brian J. , Ungerer Mark C.
Published: January 2014

Next‐generation sequencing (NGS) technologies provide a rapid means to generate genomic resources for species exhibiting interesting ecological and evolutionary variation but for which such resources are scant or nonexistent. In the current report, we utilize 454 pyrosequencing to obtain transcriptome information for multiple individuals and tissue types from geographically disparate and ecologically differentiated populations of the perennial sunflower species Helianthus maximiliani. A total of 850 275 raw reads were obtained averaging 355 bp in length. Reads were assembled, postprocessing, into 16 681 unique contigs with an N50 of 898 bp and a total length of 13.6 Mb. A majority (67%) of these contigs were annotated based on comparison with the Arabidopsis thaliana genome (TAIR10). Contigs were identified that exhibit high similarity to genes associated with natural variation in flowering time and freezing tolerance in other plant species and will facilitate future studies aimed at elucidating the molecular basis of clinal life history variation and adaptive differentiation in H. maximiliani. Large numbers of gene‐associated simple sequence repeats (SSRs) and single‐nucleotide polymorphisms (SNPs) also were identified that can be deployed in mapping and population genomic analyses.
Core Content for Wilderness Medicine Fellowship Training of Emergency Medicine Graduates
Authors: Lipman Grant S. , Weichenthal Lori , Stuart Harris N. , McIntosh Scott E. , Cushing Tracy , Caudell Michael J. , Macias Darryl J. , Weiss Eric A. , Lemery Jay , Ellis Mark A. , Spano Susanne , McDevitt Marion , Tedeschi Christopher , Dow Jennifer , Mazzorana Vicki , McGinnis Henderson , Gardner Angela F. , Auerbach Paul S.
Published: January 2014

Wilderness medicine is the practice of resource‐limited medicine under austere conditions. In 2003, the first wilderness medicine fellowship was established, and as of March 2013, a total of 12 wilderness medicine fellowships exist. In 2009 the American College of Emergency Physicians Wilderness Medicine Section created a Fellowship Subcommittee and Taskforce to bring together fellowship directors, associate directors, and other interested stakeholders to research and develop a standardized curriculum and core content for emergency medicine (EM)‐based wilderness medicine fellowships. This paper describes the process and results of what became a 4‐year project to articulate a standardized curriculum for wilderness medicine fellowships. The final product specifies the minimum core content that should be covered during a 1‐year wilderness medicine fellowship. It also describes the structure, length, site, and program requirements for a wilderness medicine fellowship.
Pericardial, intra‐abdominal, and subcutaneous adipose tissue in patients with major depressive disorder
Authors: Kahl K. G. , Hueper K. , Schweiger U. , Gutberlet M. , Detlef A.‐M. , Weiss C. , von Bohlen A. , Pul R. , Lichtinghagen R. , Wacker F. , Hartung D.
Published: January 2014

Objective

Major depressive disorder (MDD) is associated with an increased risk for developing coronary artery disease (CAD). Recently, pericardial adipose tissue, a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of CAD. Therefore, we investigated pericardial adipose tissue volumes in patients with MDD and compared them to healthy comparison subjects.

Method

In this case‐control study at a university medical center, 50 male and female in‐patients with MDD and 25 healthy men and women were examined. The main outcome measures were the volumes of pericardial adipose tissue, intra‐abdominal adipose tissue (IaAT) and subcutaneous adipose tissue (ScAT) which were measured using magnetic resonance imaging.

Results

The pericardial adipose tissue volumes were greater in men and women with MDD compared with the healthy comparison group following adjustments for the effects of age, weight, height, and physical activity.

Conclusion

This study expands our knowledge about the alterations in body composition that occur in patients with MDD. The findings are highly relevant for understanding the comorbidity between heart disease and depressive disorders.
The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice
Authors: Slavkin HC
Published: January 2014

Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can ‘mimic’ biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of ‘personalized medicine and dentistry’, the utilization of stem cell therapy for an array of diseases and disorders, the ‘proof of principle’ to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes.
New‐Build Gentrification and the Everyday Displacement of Polish Immigrant Tenants in Greenpoint, Brooklyn
Authors: Stabrowski Filip
Published: January 2014

In response to research that has downplayed or denied the reality of gentrification‐induced displacement, critical urban geographers have called for rethinking the concept of displacement. This article takes up that call by examining the impact of new‐build gentrification on the everyday place‐making abilities of Polish immigrant tenants in Greenpoint, Brooklyn. Based on nearly four years of work as a tenant organizer, this article looks at the forms of “everyday displacement”—the ongoing loss of the agency, freedom, and security to “make place”—experienced by immigrant tenants who struggle to remain in the neighborhood. Drawing upon Lefebvre's spatial triad and Blomley's work on the social relations of property, this article argues that everyday displacement is experienced through the production of new spaces of prohibition, appropriation, and insecurity that constitute a form of neighborhood erasure.
Input–output characteristics of soleus homonymous Ia afferents and corticospinal pathways during upright standing differ between young and elderly adults
Authors: Baudry S. , Penzer F. , Duchateau J.
Published: January 2014

Aim

This study investigated the effects of ageing on the excitability of soleus homonymous Ia afferents and corticospinal pathways during bipedal upright standing.

Methods

The input–output relations for the Hoffmann (H) reflex and motor‐evoked potential (MEP) were computed for the soleus in response to electrical nerve stimulation and transcranial magnetic stimulation, respectively, in young (n = 16) and elderly (n = 16) adults. In subsets of subjects, the input–output relations were compared between normal and supported upright standing, and corticomotoneuronal excitability was assessed during upright standing with an H‐reflex conditioning method. For the H‐reflex and MEP threshold, maximal amplitude (Hmax, MEPmax) and the slope of the input–output relation (Hslope, MEPslope) were measured and normalized to the corresponding M‐wave value.

Results

In normal standing, the Hmax/Mmax [mean (SD); young: 48.3 (14.2)%; elderly: 17.3 (6.4)%] and Hslope/Mslope were significantly (P < 0.05) lower in elderly than in young adults, whereas the MEPmax/Mmax [young: 13.6 (7.5)%; elderly: 24.5 (12.8)%] and MEPslope/Mslope were greater in elderly adults (P < 0.05). The Hslope/Mslope and MEPslope/Mslope decreased and increased, respectively, from supported to normal standing for both age groups but more so in elderly adults. Furthermore, the conditioned H reflex was greater (P < 0.05) in elderly [175.1 (34.3)%] than in young adults [141.8 (29.8)%] during normal standing.

Conclusion

This is the first study that clearly indicates lower efficacy of Ia afferents to discharge spinal motor neurones accompanied by greater corticospinal excitability in elderly adults, suggesting an increased contribution of the descending drive in controlling soleus activity during upright standing with ageing.
Model‐based clinical pharmacology profiling of ipilimumab in patients with advanced melanoma
Authors: Feng Yan , Masson Eric , Dai David , Parker Susan M. , Berman David , Roy Amit
Published: January 2014

Aim

Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T‐lymphocyte antigen‐4. The objective of the present study was to characterize the clinical pharmacology profile of ipilimumab using a population pharmacokinetic (PPK) approach.

Methods

The PPK model was developed using 2095 ipilimumab serum concentration values from 499 patients with unresectable stage III or IV melanoma from four phase II studies, with ipilimumab doses ranging from 0.3 to 10 mg kg−1. The structural PK model was determined by developing a base PPK model. The effect of covariates on model parameters was assessed by a full covariate model, which incorporated all pre‐specified covariate‐parameter relationships into the base model. The final model was developed by backward elimination, followed by exclusion of covariates determined not to be of clinical relevance to ipilimumab, and was rigorously validated against both internal and external datasets.

Results

Ipilimumab PK was linear and time‐invariant, with dose‐proportional exposures over the available dose range, yielding a terminal half‐life of approximately 15 days. Clearance of ipilimumab increased with increasing body weight and baseline serum lactate dehydrogenase concentrations, but was not affected by age, gender, concomitant budesonide, Eastern Cooperative Oncology Group performance status or prior systemic anticancer therapy. Furthermore, ipilimumab exposure was not affected by moderate renal impairment or mild hepatic impairment.

Conclusions

Ipilimumab concentration–time data were well described by a linear, two compartment, zero order i.v. infusion model. The model confirms that a body weight‐normalized dosing regimen is appropriate for ipilimumab therapy in patients with advanced melanoma.
Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa‐carbidopa intestinal gel infusion vs. oral tablets
Authors: Othman Ahmed A. , Dutta Sandeep
Published: January 2014

Aims

Levodopa‐carbidopa intestinal gel (LCIG) provides continuous levodopa‐carbidopa delivery through intrajejunal infusion. This study characterized the population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG or frequent oral administration of levodopa‐carbidopa tablets (LC‐oral) in subjects with advanced Parkinson's disease (PD).

Methods

A non‐linear mixed‐effects model of levodopa pharmacokinetics was developed using serial plasma concentrations from an LCIG phase 1 study and a phase 3 double‐blind, double‐dummy study of the efficacy and safety of LCIG compared with LC‐oral in advanced PD patients (n = 68 for model development; 45 on LCIG and 23 on LC‐oral). The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG.

Results

The final model was a two compartment model with a transit compartment for absorption, first order elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%) relative to LC‐oral, different first order transit absorption rate constants (LCIG = 9.2 h–1 vs. LC‐oral = 2.4 h–1; corresponding mean absorption time of 7 min for LCIG vs. 25 min for LC‐oral) and different residual (intra‐subject) variability for LCIG (15% proportional error, 0.3 μg ml−1 additive error) vs. LC‐oral (29% proportional error, 0.59 μg ml−1 additive error). Estimated oral clearance and steady‐state volume of distribution for levodopa were 24.8 l h−1 and 131 l, respectively.

Conclusions

LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra‐subject variability in levodopa concentrations relative to LC‐oral administration.
Reconsidering Union Activism and Its Meaning
Authors: Fiorito Jack , Padavic Irene , DeOrtentiis Philip S.
Published: January 2014

Membership mobilization is widely regarded as critical for union revitalization. Estimates of the level of activism vary widely, and studies reveal puzzling inconsistencies between union members' beliefs and intentions. Drawing from Ajzen's theory of planned behaviour, we address both issues using a sample of faculty union members. Results show both consistency and discrepancy between summary self‐reports of activism and specific participation behaviours, helping account for the widely varying estimates of activism levels found in other studies. Results also indicate an important role for perceived control, a factor rarely examined in prior research on activism.
Leucocyte complement receptor 1 (CR1/CD35) transcript and its correlation with the clinical disease activity in rheumatoid arthritis patients
Authors: Anand D , Kumar U , Kanjilal M , Kaur S , Das N
Published: January 2014

In view of the exaggerated complement activation in rheumatoid arthritis (RA) and significance of complement receptor 1 (CR1/CD35) as a complement regulatory protein (CRP), we aimed to determine the leucocyte-complement receptor 1 (L-CR1) transcript levels and the relationship of this protein with the clinical disease activity of RA patients. Sixty-six controls and 45 RA patients were enrolled. L-CR1 transcript levels were correlated with the levels of circulating immune complexes (CIC), C3, C4 and C3d in controls and patients and with disease activity score 28 (DAS28) in patients only. CIC levels were determined by polyethylene glycol (PEG) precipitation, C3 and C4 levels by nephlometry and C3d levels by enzyme-linked immunosorbent assay (ELISA). Eleven patients were recruited for follow-up of L-CR1 and DAS28 levels at weeks 0, 12 and 24. Appropriate statistical methods were used for the data analysis. L-CR1 (P < 0·01) transcript levels were decreased in patients compared to controls. L-CR1 levels correlated negatively with DAS28, CIC and C3d. DAS28 correlated positively with levels of CIC, C3 and C3d. Levels of CIC correlated positively with C3 and C3d. Levels of C3 correlated positively with C3d in patients and with C4 in both controls and patients. Levels of L-CR1 increased with decline in DAS28 scores in follow-up patients. Observations were statistically significant. Lower levels of L-CR1 transcript in patients compared to controls, their correlations with the levels of CIC, C3d and DAS28 at different time-points in RA patients suggest CR1 as a potential disease marker for RA.
Photons: Evolution of a Course in Data Structures
Authors: Duchowski A. T.
Published: January 2014

This paper presents the evolution of a data structures and algorithms course based on a specific computer graphics problem, namely, photon mapping, as the teaching medium. The paper reports development of the course through several iterations and evaluations, dating back 5 years. The course originated as a problem‐based graphics course requiring sophomore students to implement Hoppe et al.'s algorithm for surface reconstruction from unorganized points found in their SIGGRAPH '92 paper of the same title. Although the solution to this problem lends itself well to an exploration of data structures and code modularization, both of which are traditionally taught in early computer science courses, the algorithm's complexity was reflected in students' overwhelmingly negative evaluations. Subsequently, because implementation of the kd‐tree was seen as the linchpin data structure, it was again featured in the problem of ray tracing trees consisting of more than 250 000 000 triangles. Eventually, because the tree rendering was thought too specific a problem, the photon mapper was chosen as the semester‐long problem considered to be a suitable replacement. This paper details the resultant course description and outline, from its now three semesters of teaching.
Systematic review of the limited evidence base for treatments of Eustachian tube dysfunction: a health technology assessment
Authors: Norman G. , Llewellyn A. , Harden M. , Coatesworth A. , Kimberling D. , Schilder A. , McDaid C.
Published: January 2014

Background

The Health Technology Assessment programme commissioned a wide‐ranging review of treatments for adult Eustachian tube dysfunction. Treatments range from advice and observation and pharmacological treatments to surgical options.

Objective

(i) To assess the evidence for interventions for adults with a clinical diagnosis of Eustachian tube dysfunction and (ii) to identify priorities for future research.

Type of review

Systematic review (PROSPERO registration CRD42012003035) adhering to PRISMA guidance.

Search

An extensive search of 15 databases including MEDLINE, EMBASE and CENTRAL (up to October 2012).

Evaluation method

Controlled and uncontrolled studies of interventions for adult Eustachian tube dysfunction were included. Because of insufficient data, the protocol was amended to also include controlled studies with mixed adult/child populations. Risk of bias was assessed. Narrative synthesis was employed due to high clinical heterogeneity.

Results

Interventions assessed were pharmacological treatments [two randomised controlled trials (RCTs), one controlled non‐randomised trial (CCT), 159 patients]; mechanical pressure equalisation devices (one randomised controlled trial, one CCT, 48 patients); and surgery, including laser tuboplasty (seven case series, 192 patients), balloon dilatation (three case series, 103 patients), myringotomy without grommet insertion (two case series, 121 patients), transtubal steroids (one case series, 11 patients) and laser coagulation (one retrospective controlled study, 40 patients). All studies had high risk of bias except two pharmacological trials; one had low risk and one unclear risk. No evidence was found for many treatments. The single low risk of bias RCT (n = 91; 67% adults) showed no effect of nasal steroids and favoured placebo for improved middle ear function (RR 1.20, 95% CI 0.91–1.58) and symptoms (P = 0.07). Other studies showed improvements in middle ear function for mechanical devices, antihistamine/ephedrine and nasal decongestant, but they had significant methodological weaknesses including insufficient length of follow‐up. None of the surgical studies were adequately controlled, and many reported high levels of co‐intervention. Therefore, observed benefits for tuboplasty and balloon dilatation in symptoms, middle ear function or hearing could not be reliably attributed to the interventions assessed. There was variability in definitions of the condition.

Conclusion

Eustachian tube dysfunction is a poorly defined condition. Due to the limited and poor‐quality evidence, it is inappropriate to make conclusions on the effectiveness of any intervention; the evidence base is insufficient to guide recommendations for a trial of any particular intervention. Consensus on diagnostic criteria for Eustachian tube dysfunction is required to inform inclusion criteria of future trials.
Successful treatment for graft‐versus‐host disease after pancreas transplantation
Authors: Chang Jei wen , Sageshima Junichiro , Ciancio Gaetano , Mattiazzi Adela , Chen Linda , Tsai Hsin‐Lin , Ruiz Phillip , Burke George W.
Published: January 2014

Graft‐versus‐host disease (GVHD) after pancreas transplantation is a rare but serious complication: All previously reported cases were fatal. We herein report three cases of GVHD after pancreas transplantation with favorable outcomes. Patients with a history of kidney (and pancreas) transplantation subsequently received a pancreas (and kidney) transplantation (i.e., pancreas retransplantation or pancreas after kidney transplantation) and developed acute GVHD. All of them responded to increased immunosuppression (e.g., steroid bolus, antithymocyte globulin) and retained normal graft function. Because the clinical manifestations are non‐specific, vigilance is necessary to make an accurate diagnosis. We underscored the importance of a biopsy of involved organs and the clinicopathologic correlation in the early diagnosis of GVHD. Augmented immunosuppression to prevent progression from a self‐limited disease to life‐threatening pancytopenia or sepsis may be most critical to improve outcome.
Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients
Authors: Wozniak Laura J. , Venick Robert S. , Gordon Burroughs Sherilyn , Ngo Khiet D. , Duffy John P. , Farmer Douglas G.
Published: January 2014

The Cylex Immune Cell Function Assay measures cell‐mediated immunity based on ATP production by stimulated CD4 + cells. We hypothesized that this test would discriminate acute cellular rejection (ACR) from infectious enteritis (IE) in pediatric intestinal transplant (ITx) recipients with allograft dysfunction. We retrospectively analyzed 224 Cylex assays drawn in 47 children who received 53 ITx. Samples were classified as stable, ACR, or IE based on clinical status. ATP values were analyzed using Kruskal–Wallis and t‐tests. Overall, there was a statistically significant difference in ATP values based on clinical status (p = 0.03); however, overlap was observed between groups. The median ATP value during ACR was significantly greater than during stable periods (p = 0.02). No difference was seen in IE vs. stability (p = 0.8). The difference in median ATP value in ACR vs. IE approached significance (p = 0.1). Relative to previous levels, ACR episodes were associated with a median ATP increase of 101 ng/mL and IE episodes with a decrease of 3 ng/mL (p = 0.3). These data indicate that the Cylex assay has limited utility in differentiating ACR from IE, largely due to interpatient variability. Following longitudinal intrapatient trends may be an adjunctive tool in discriminating IE from ACR and guiding immunosuppression adjustments in select patients.
Continuous expression of Otx in the anterior neural lineage is supported by different transcriptional regulatory mechanisms during the development of Halocynthia roretzi
Authors: Oonuma Kouhei , Hirose Dan , Takatori Naohito , Saiga Hidetoshi
Published: January 2014

The process of establishing the anterior–posterior axis is an important event in the development of bilateral animals. Otx, which encodes a homeodomain transcription factor, is continuously expressed in the anterior part of the embryo in a wide range of animals. This pattern of expression is thought to be important for the formation of anterior neural structures, but the regulatory mechanism that sustains the expression is not known. Here, using embryos of the ascidian, Halocynthia roretzi, we investigated how the transcription of Otx is maintained in the cells of the anterior neural lineage during embryogenesis. We identified an enhancer region sufficient to mimic the Otx expression pattern from the gastrula to tailbud stages. Several putative transcription factor binding sites that are required for generating the Otx expression pattern were also identified. Distinct sets of sites were required at different developmental stages, suggesting that distinct transcriptional mechanisms regulate Otx transcription in each of the gastrula, neurula and tailbud stages. Along with previous studies on the transcriptional regulatory mechanism of Otx during the pre‐gastrula stages, the present results provide the first overview of the mechanism that sustains Otx expression in the anterior neural lineage during ascidian embryogenesis and demonstrate the complexity of a developmental mechanism that maintains Otx transcription.
Relations between maternal interactive behavior and mastery motivation in children with developmental disabilities
Authors: Liao Hua‐Fang , Morgan George
Published: January 2014

This commentary is on the original article by Miller et al. on pages 267–274 of this issue.
Horizontal migration of click beetle (Agriotes spp.) larvae depends on food availability
Authors: Sonnemann Ilja , Grunz Sonja , Wurst Susanne
Published: January 2014

It is generally thought that soil animals face specific foraging conditions because movement through soil is highly energy consuming. The hypothesis tested here is that root‐feeding click beetle larvae (wireworms, Agriotes spp.; Coleoptera: Elateridae), to minimize energy loss, only migrate horizontally through soil when located in food‐depleted surroundings. Larvae were placed at either end of a root density gradient created by the grass Holcus lanatus L. (Poaceae), and their position in the gradient was recorded after 12 days of migration. Larval migration depended on the food situation at the starting point, with larvae moving from food‐depleted to food‐rich areas, but not leaving food‐rich areas. Larvae spread further around food‐rich areas when together with conspecifics than when being alone, presumably to avoid cannibalism. Food density‐dependent migration may have to be taken into account when using trap‐crops to control Agriotes larvae. Success may depend on the timing of trap‐crop establishment relative to the target crop to generate an effective food gradient.
Comparison of the perceived relevance of oral biology reported by students and interns of a Pakistani dental college
Authors: Farooq I. , Ali S.
Published: January 2014

Objectives

The purpose of this study was to analyse and compare the perceived relevance of oral biology with dentistry as reported by dental students and interns and to investigate the most popular teaching approach and learning resource.

Methods

A questionnaire aiming to ask about the relevance of oral biology to dentistry, most popular teaching method and learning resource was utilised in this study. Study groups encompassed second‐year dental students who had completed their course and dental interns. The data were obtained and analysed statistically.

Results

The overall response rate for both groups was 60%. Both groups reported high relevance of oral biology to dentistry. Perception of dental interns regarding the relevance of oral biology to dentistry was higher than that of students. Both groups identified student presentations as the most important teaching method. Amongst the most important learning resources, textbooks were considered most imperative by interns, whereas lecture handouts received the highest importance score by students.

Conclusions

Dental students and interns considered oral biology to be relevant to dentistry, although greater relevance was reported by interns. Year‐wise advancement in dental education and training improves the perception of the students about the relevance of oral biology to dentistry.
High‐throughput, high‐content screening for novel pigmentation regulators using a keratinocyte/melanocyte co‐culture system
Authors: Lee Ju Hee , Chen Hongxiang , Kolev Vihren , Aull Katherine H. , Jung Inhee , Wang Jun , Miyamoto Shoko , Hosoi Junichi , Mandinova Anna , Fisher David E.
Published: January 2014

Skin pigmentation is a complex process including melanogenesis within melanocytes and melanin transfer to the keratinocytes. To develop a comprehensive screening method for novel pigmentation regulators, we used immortalized melanocytes and keratinocytes in co‐culture to screen large numbers of compounds. High‐throughput screening plates were subjected to digital automated microscopy to quantify the pigmentation via brightfield microscopy. Compounds with pigment suppression were secondarily tested for their effects on expression of microphthalmia transcription factor (MITF) and several pigment regulatory genes, and further validated in terms of non‐toxicity to keratinocytes/melanocytes and dose‐dependent activity. The results demonstrate a high‐throughput, high‐content screening approach, which is applicable to the analysis of large chemical libraries using a co‐culture system. We identified candidate pigmentation inhibitors from 4000 screened compounds including zoxazolamine, 3‐methoxycatechol and alpha‐mangostin, which were also shown to modulate expression of MITF and several key pigmentation factors and are worthy of further evaluation for potential translation to clinical use.
Nuclear envelope localization of Ran‐binding protein 2 and Ran‐GTPase‐activating protein 1 in psoriatic epidermal keratinocytes
Authors: Yasuda Kayo , Sugiura Kazumitsu , Takeichi Takuya , Ogawa Yasushi , Muro Yoshinao , Akiyama Masashi
Published: January 2014

The nuclear localization signal (NLS)‐containing proteins LEDGF and STAT3 localize to the nucleus in both the spinous and basal layers of the epidermis in psoriatic skin, where they function as transcription factors or co‐factors to activate epidermal keratinocytes (KCs). However, the mechanism underlying the localization of these proteins remains to be elucidated. We investigated the differential nucleocytoplasmic transport of NLS‐containing proteins as a potential pathogenic mechanism for psoriasis vulgaris. Nucleoporins play an important role in the Ran‐GTP‐dependent nucleocytoplasmic transport of NLS‐containing proteins. We showed, using immunohistochemical staining, that the nucleoporins Ran‐binding protein 2 (RanBP2) and Ran‐GTPase‐activating protein 1 (RanGAP1) have greater expression on the nuclear envelope in psoriatic epidermal KCs than in KCs from healthy controls. We then studied the signalling pathways involved in the regulation of these proteins in HaCaT cells. The two major downstream pathways of epidermal growth factor receptor (EGFR) signalling activated in psoriatic KCs are the MAPK/Erk/1/2 and the phosphatidylinositol‐3‐kinase/Akt pathways. Therefore, we treated HaCaT cells with inhibitors to disrupt the MAP kinase kinase 1 (MEK1), PI3‐kinase, or mTOR pathways. RanBP2 and RanGAP1 protein expression levels were significantly greater in the nuclear envelope of HaCaT cells that were not treated with inhibitors than in cells treated with a combination of PI3‐kinase and MEK1 inhibitors or mTOR and MEK1 inhibitors. These results suggest that adequate nuclear envelope expression of RanBP2 and RanGAP1 could be a prerequisite for nucleocytoplasmic transport in KCs in psoriatic epidermis.
Involvement of caspase 8 and c‐FLIPL in the proangiogenic effects of the tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL)
Authors: Cantarella Giuseppina , Di Benedetto Giulia , Ribatti Domenico , Saccani‐Jotti Gloria , Bernardini Renato
Published: January 2014

Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), a cytokine of the tumour necrosis factor superfamily, is a potent cell‐apoptosis inducer, although its effects vary as a function of concentration. In fact, low concentrations of TRAIL are associated with non‐apoptotic effects, such as cell proliferation. Here, the effects of TRAIL at different concentrations have been evaluated on mitogenesis and migration on human umbilical vein endothelial cells (HUVEC) in vitro, as well as in the chick embryo chorioallantoic membrane (CAM) angiogenesis model in vivo. At low concentrations, TRAIL promoted either mitogenesis or migration of HUVEC, evaluated using the wound healing method. Cleavage of caspase 8 was evaluated along with expression of the caspase 8‐like molecule, cellular FLICE‐inhibitory protein (long form) (c‐FLIPL). Low concentrations of TRAIL failed to induce caspase 8 processing, whereas high concentrations induced apoptosis of HUVEC and activation of caspase 8. Moreover, TRAIL induced a significant angiogenic response in the CAM assay in vivo, comparable with that of vascular endothelial growth factor. These data suggest that the non‐apoptotic effects of TRAIL include mitogenesis and increased mobility of endothelial cells, and eventually angiogenesis. In addition, the results demonstrate that the c‐FLIPL level is also modulated by differences in TRAIL concentration, suggesting its involvement in the divergent effects of TRAIL. In conclusion, this study envisions a proangiogenic role of TRAIL, suggesting that TRAIL may represent a target for pharmacological manipulation.
Orodental status and medical problems of stroke inpatients undergoing rehabilitation at a rehabilitation hospital in Japan
Authors: Asahi Yoshinao , Omichi Shiro , Ono Takahiro
Published: January 2014

Background and objective

Many stroke patients may have oral problems and systemic diseases, but clinical information on treatment provided to stroke patients for dental problems during inpatient rehabilitation is rare. The objective of this study was to research stroke inpatients' requirements for dental treatment and the accompanying risks.

Methods

We included 165 stroke patients undergoing inpatient rehabilitation at Morinomiya Hospital during the year 2010 and researched the causes of stroke and the patients' orodental status, underlying diseases, antithrombotic drugs prescribed and special considerations or difficulties in the treatment.

Results

Cerebral infarction was the most common causes of stroke. Many patients had hypertension, heart disease or diabetes mellitus, and 54.5% had been prescribed antithrombotic drugs. Dentists diagnosed 57.0% patients with untreated dental cavities. Approximately 30% did not use dentures despite having a requirement. In total, 142 patients underwent dental treatment including periodontal treatment, prosthetic treatment and tooth extraction under management of circulation and haemostasis such as monitoring vital signs and surgical splints in cases of the difficult extraction.

Conclusion

The current study revealed a high requirement for dental treatment among stroke patients and demonstrated the effectiveness of performing dental treatment during inpatient rehabilitation of these patients.
Effects of nitrogen rate on nitrate–nitrogen accumulation in forage kale and rape crops
Authors: Chakwizira E. , Johnstone P. , Fletcher A. L. , Meenken E. D. , de Ruiter J. M. , Brown H. E.
Published: January 2014

Nitrogen fertilizer is applied to supplement soil nitrogen supply to maximize forage brassica crop dry‐matter production. However, nitrogen fertilizer applications in excess of that required to maximize growth result in potentially toxic nitrate–nitrogen (NO3–N) concentrations in grazeable plant tissues. Three experiments, two for forage kale at Lincoln (Canterbury) and one for forage rape at Hastings (Hawke's Bay) in New Zealand were grown under different rates of nitrogen (0–500 kg N ha−1) to determine the effect of different rates of nitrogen on NO3–N content of different plant parts of the crops. One of the kale experiments was grown with either full irrigation or no rain and no irrigation over summer, hereafter referred to as summer drought. The NO3–N concentration on a whole plant (weighted average) basis increased from 0·1 mg g−1 dry matter for the control plots to 2·30 mg g−1 for the 500 kg N ha−1 plots for forage kale. It increased from 0·99 for the control plots to 3·37 mg g−1 for the 200 kg N ha−1 plots for forage rape crops. However, NO3–N concentration increased with N supply under the summer‐drought plots from an average of 0·33 mg g−1 when ≤120 kg N ha−1 was applied to 2·30 mg g−1 for the 240 kg N ha−1 treatments but was unaffected by N supply under irrigation. The NO3–N concentrations were higher in the stems and the petiole (which included the midrib of the leaf) than leaves in all three experiments. The NO3–N concentration was highest at the bottom of the kale stem and decreased towards the top. We recommend N application rates based on soil tests results, and for conditions similar to the current studies up to 300 kg N ha−1 under irrigation and adjusted lower N rates for regions prone to dry summers.
TRANSLATION AND POETIC THINKING
Authors: Pajević Marko
Published: January 2014

Based on the theories of Wilhelm von Humboldt and Henri Meschonnic, this article addresses the question of how ‘poetic thinking’ – that is, the transforming power in the interaction of form of language and form of life – illuminates the relationship between culture and language with regard to translation; and, as a corollary, what part does innovation play in translation? This implies the necessity of addressing the specificities of a language as well as comparing poetic and cultural approaches. In each text, there are images, sounds and constellations which constitute meaning. It is these which are to be recreated in literary translation. It is argued that the literary is that which cannot be said differently; hence, when translating literature, we are necessarily ourselves writing literature. That is the crucial point in the poetics of translation. The specificity of a text is always due to the author, rather than to the language. In literature, the force of speech trumps that of the language itself. This poetics of translation is illustrated by an analysis of translations into German and American English of some lines from Jean‐Luc Nancy, demonstrating different perspectives on what language and philosophy ‘do’ within the act of translating.

Auf der Grundlage der Theorien von Wilhelm von Humboldt und Henri Meschonnic geht dieser Artikel der Frage nach, wie ‘Poetisches Denken’ – also die transformierende Kraft in der Wechselwirkung von Sprach‐ und Lebensform – die Beziehung zwischen Kultur und Sprache in Bezug auf Übersetzung erhellt; und folglich, welche Rolle Innovation beim Übersetzen spielt. Das wirft ebenfalls die Frage auf nach der Spezifizität einer Sprache. Unter diesem Gesichtspunkt werden der poetische und der kulturelle Übersetungsansatz miteinander verglichen. In jedem Text gibt es Bilder, Klänge und Konstellationen, welche Sinn konstituieren. Diese müssen in einer literarischen Übersetzung erneut geschaffen werden. Ich behaupte, dass das Dichterische dasjenige ist, was nicht anders gesagt werden kann. Dementsprechend muss man, wenn man Literatur übersetzt, notwendigerweise selbst Literatur schreiben. Das ist der springende Punkt in der Poetik der Übersetzung. Die Spezifizität eines Textes geht immer, statt auf die Sprache, auf den Autoren zurück. In der Literatur übertrumpft das jeweilige Sprechen die Sprache. Diese Poetik der Übersetzung wird illustriert anhand der Analyse einer deutschen und einer amerikanischen Übersetzung einiger Zeilen von Jean‐Luc Nancy, wobei verschiedene Perspektiven darauf deutlich werden, was Sprache und Philosophie beim Übersetzen ‘machen’.