bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal inversions, local adaptation and geographic structure
Authors: Kemppainen Petri , Knight Christopher G. , Sarma Devojit K. , Hlaing Thaung , Prakash Anil , Maung Maung Yan Naung , Somboon Pradya , Mahanta Jagadish , Walton Catherine
Published: January 2015

Recent advances in sequencing allow population‐genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction‐site‐associated DNA sequence (RAD‐seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well‐characterized single nucleotide polymorphism (SNP) data set from 21 three‐spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single‐outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population‐genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population‐demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population‐genomic data set, making it especially valuable for nonmodel species.
Alcohol confounds relationship between cannabis misuse and psychosis conversion in a high‐risk sample
Authors: Auther A. M. , Cadenhead K. S. , Carrión R. E. , Addington J. , Bearden C. E. , Cannon T. D. , McGlashan T. H. , Perkins D. O. , Seidman L. , Tsuang M. , Walker E. F. , Woods S. W. , Cornblatt B. A.
Published: January 2015

Objective

Cannabis use has been examined as a predictor of psychosis in clinical high‐risk (CHR) samples, but little is known about the impact of other substances on this relationship.

Method

Substance use was assessed in a large sample of CHR participants (N = 370, mean age = 18.3) enrolled in the multisite North American Prodrome Longitudinal Study Phase 1 project. Three hundred and forty‐one participants with cannabis use data were divided into groups: No Use (NU, N = 211); Cannabis Use without impairment (CU, N = 63); Cannabis Abuse/Dependence (CA/CD, N = 67). Participants (N = 283) were followed for ≥2 years to determine psychosis conversion.

Results

Alcohol (45.3%) and cannabis (38.1%) were the most common substances. Cannabis use groups did not differ on baseline attenuated positive symptoms. Seventy‐nine of 283 participants with cannabis and follow‐up data converted to psychosis. Survival analysis revealed significant differences between conversion rates in the CA/CD group compared with the No Use (P = 0.031) and CU group (P = 0.027). CA/CD also significantly predicted psychosis in a regression analysis, but adjusting for alcohol use weakened this relationship.

Conclusion

The cannabis misuse and psychosis association was confounded by alcohol use. Non‐impairing cannabis use was not related to psychosis. Results highlight the need to control for other substance use, so as to not overstate the cannabis/psychosis connection.
Do eating disorders in parents predict eating disorders in children? Evidence from a Swedish cohort
Authors: Bould H. , Sovio U. , Koupil I. , Dalman C. , Micali N. , Lewis G. , Magnusson C.
Published: January 2015

Objective

We investigated whether parental eating disorders (ED) predict ED in children, using a large multigeneration register‐based sample.

Method

We used a subset of the Stockholm Youth Cohort born 1984–1995 and resident in Stockholm County in 2001–2007 (N = 286 232), The exposure was a diagnosed eating disorder in a parent; the outcome was any eating disorder diagnosis in their offspring, given by a specialist clinician, or inferred from an appointment at a specialist eating disorder clinic. A final study sample of 158 697 (55.4%) had data on these variables and confounding factors and contributed a total of 886 241 person years to the analysis.

Results

We found good evidence in support of the hypothesis that ED in either parent are independently associated with ED in their female children (HR 1.97 (95% CI: 1.17–3.33), P = 0.01) and that ED in mothers are independently associated with ED in their female children (HR 2.35 (95% CI: 1.39–3.97) P = 0.001). Numbers were too low to permit separate analysis of ED in parents and their male children.

Conclusion

Eating disorders in parents were associated with ED in children. This study adds to our knowledge about the intergenerational transmission of ED, which will help identify high‐risk groups and brings about the possibility of targeted prevention.
Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular fluid of aggressive and chronic periodontitis patients
Authors: Ghallab NA , Hamdy E , Shaker OG
Published: January 2015

Background

The aim of this study was to investigate malondialdehyde (MDA), superoxide dismutase (SOD) and melatonin levels in the gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) as biomarkers for oxidative stress.

Methods

The study comprised 65 subjects: 15 healthy individuals, 25 CP patients and 25 GAgP patients. Plaque index, gingival index, pocket depth, clinical attachment level measurements and GCF samples were obtained from all subjects. MDA, SOD and melatonin levels were determined utilizing enzyme‐linked immunosorbent assay.

Results

GCF‐MDA levels were significantly higher in the GAgP group compared to the CP and control groups (p < 0.001) and significantly higher in the CP group than the C group (p < 0.001). SOD and melatonin GCF levels were significantly higher in the control than the GAgP and CP groups (p < 0.05), and significantly lower in the GAgP than the CP group (p < 0.05). The CP group demonstrated a significant negative correlation between GCF‐MDA and melatonin concentrations. A positive correlation was observed between SOD and CAL in the CP group and PD in the GAgP group.

Conclusions

MDA, melatonin and SOD could be considered as biomarkers for oxidative stress in periodontal diseases and might be useful diagnostic aids in distinguishing CP and GAgP patients.
Can e‐learning system enhance learning culture in the workplace? A comparison among companies in South Korea
Authors: Yoo Sun Joo , Huang Wenhao David
Published: January 2015

How organizations need to act in order to develop their learning capacities has always been a focal interest of research and practice in the workplace. In practice, an e‐learning system is often utilized to foster professional development as it is capable of delivering information and knowledge to individuals across organizations. However, the effect of e‐learning systems on fostering the development of learning organizations in South Korean companies remains unsubstantiated by empirical research. Hence, in this study, a total of 327 datasets from three Korean companies (A, B and C) were analyzed to investigate this research question: can utilizing an e‐learning system accelerate the process of companies becoming learning organizations? The results showed that only the e‐learning systems of Company A and Company C, but not of Company B, facilitated the development of learning organizations. The study concluded that employees' acceptance levels toward e‐learning systems must be considered in order to effectively promote long‐term implementation of e‐learning systems that would lead to the development of learning organizations.
The repertoire of resistance: Non‐compliance with directives in Milgram's ‘obedience’ experiments
Authors: Hollander Matthew M.
Published: January 2015

This paper is the first extensive conversation‐analytic study of resistance to directives in one of the most controversial series of experiments in social psychology, Stanley Milgram's 1961–1962 study of ‘obedience to authority’. As such, it builds bridges between interactionist and experimental areas of social psychology that do not often communicate with one another. Using as data detailed transcripts of 117 of the original sessions representing five experimental conditions, I show how research participants’ resistance to experimental progressivity takes shape against a background of directive/response and complaint/remedy conversational sequences – sequence types that project opposing and competing courses of action. In local contexts of competing sequential relevancies, participants mobilize six forms of resistance to the confederate experimenter's directives to continue. These range along a continuum of explicitness, from relatively subtle resistance that momentarily postpones continuation to techniques for explicitly trying to stop the experiment. Although both ‘obedient’‐ and ‘defiant’‐outcome participants use all six of the forms, evidence is provided suggesting precisely how members of the two groups differ in manner and frequency of resistance.
Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2
Authors: Farinha A , Lavreysen H , Peeters L , Russo B , Masure S , Trabanco A A , Cid J , Tresadern G
Published: January 2015

Background and Purpose

The activation of the metabotropic glutamate receptor 2 (mGlu2) reduces glutamatergic transmission in brain regions where excess excitatory signalling is implicated in disorders such as anxiety and schizophrenia. Positive allosteric modulators (PAMs) can provide a fine‐tuned potentiation of these receptors' function and are being investigated as a novel therapeutic approach. An extensive set of mutant human mGlu2 receptors were used to investigate the molecular determinants that are important for positive allosteric modulation at this receptor.

Experimental Approach

Site‐directed mutagenesis, binding and functional assays were employed to identify amino acids important for the activity of nine PAMs. The data from the radioligand binding and mutagenesis studies were used with computational docking to predict a binding mode at an mGlu2 receptor model based on the recent structure of the mGlu1 receptor.

Key Results

New amino acids in TM3 (R635, L639, F643), TM5 (L732) and TM6 (W773, F776) were identified for the first time as playing an important role in the activity of mGlu2 PAMs.

Conclusions and Implications

This extensive study furthers our understanding of positive allosteric modulation of the mGlu2 receptor and can contribute to improved future design of mGlu2 PAMs.
Beyond traditional pharmacology: new tools and approaches
Authors: Gurevich E V , Gurevich V V
Published: January 2015

Traditional pharmacology is defined as the science that deals with drugs and their actions. While small molecule drugs have clear advantages, there are many cases where they have proved to be ineffective, prone to unacceptable side effects, or where due to a particular disease aetiology they cannot possibly be effective. A dominant feature of the small molecule drugs is their single mindedness: they provide either continuous inhibition or continuous activation of the target. Because of that, these drugs tend to engage compensatory mechanisms leading to drug tolerance, drug resistance or, in some cases, sensitization and consequent loss of therapeutic efficacy over time and/or unwanted side effects. Here we discuss new and emerging therapeutic tools and approaches that have potential for treating the majority of disorders for which small molecules are either failing or cannot be developed. These new tools include biologics, such as recombinant hormones and antibodies, as well as approaches involving gene transfer (gene therapy and genome editing) and the introduction of specially designed self‐replicating cells. It is clear that no single method is going to be a ‘silver bullet’, but collectively, these novel approaches hold promise for curing practically every disorder.

Linked Articles

This article is part of a themed section on 5th BPS Focused Meeting on Cell Signalling. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐13
Divergent effects of the ‘biased’ 5‐HT1A receptor agonists F15599 and F13714 in a novel object pattern separation task
Authors: van Goethem N P , Schreiber R , Newman‐Tancredi A , Varney M , Prickaerts J
Published: January 2015

Background and Purpose

Pattern separation, that is, the formation of distinct representations from similar inputs, is an important hippocampal process implicated in cognitive domains like episodic memory. A deficit in pattern separation could lead to memory impairments in several psychiatric and neurological disorders. Hence, mechanisms by which pattern separation can be increased are of potential therapeutic interest.

Experimental approach

5‐HT1A receptors are involved in spatial memory. Herein we tested the ‘biased’ 5‐HT1A receptor agonists F15599, which preferentially activates post‐synaptic heteroreceptors, and F13714, which preferentially activates raphe‐located autoreceptors, in rats in a novel spatial task assessing pattern separation, the object pattern separation (OPS) task.

Key Results

The acetylcholinesterase inhibitor donepezil, which served as a positive control, significantly improved spatial pattern separation at a dose of 1 mg·kg−1, p.o. F15599 increased pattern separation at 0.04 mg·kg−1, i.p., while F13714 decreased pattern separation at 0.0025 mg·kg−1, i.p. The selective 5‐HT1A receptor antagonist WAY‐100635 (0.63 mg·kg−1, s.c.) counteracted the effects of both agonists. These data suggest that acute preferential activation of post‐synaptic 5‐HT1A heteroreceptors improves spatial pattern separation, whereas acute preferential activation of raphe‐located 5‐HT1A autoreceptors impairs performance.

Conclusions and Implications

We successfully established and validated a novel, simple and robust OPS task and observed a diverging profile of response with ‘biased’ 5‐HT1A receptor agonists based on their targeting of receptors in distinct brain regions. Our data suggest that the post‐synaptic 5‐HT1A receptor consists of a potential novel molecular target to improve pattern separation performance.
GPCR‐mediated EGF receptor transactivation regulates TRPV4 action in the vasculature
Authors: Saifeddine Mahmoud , El‐Daly Mahmoud , Mihara Koichiro , Bunnett Nigel W , McIntyre Peter , Altier Christophe , Hollenberg Morley D , Ramachandran Rithwik
Published: January 2015

Background and Purpose

Transient receptor potential vanilloid‐4 (TRPV4) is a calcium‐permeant ion channel that is known to affect vascular function. The ability of TRPV4 to cause a vasoconstriction in blood vessels has not yet been mechanistically examined. Further in neuronal cells, TRPV4 signalling can be potentiated by GPCR activation. Thus, we studied the mechanisms underlying the vascular contractile action of TRPV4 and the GPCR‐mediated potentiation of such vasoconstriction, both of which are as yet unappreciated aspects of TRPV4 function.

Experimental Approach

The mechanisms of TRPV4‐dependent regulation of vascular tone in isolated mouse aortae were studied using wire myography. TRPV4‐dependent calcium signalling and prostanoid production was studied in cultured human umbilical vein endothelial cells (HUVECs).

Key Results

In addition to the well‐documented vasorelaxation response triggered by TRPV4 activation, we report here a TRPV4‐triggered vasoconstriction in the mouse aorta that involves a COX‐generated Tx receptor (TP) agonist that acts in a MAPK and Src kinase signalling dependent manner. This constriction is potentiated by activation of the GPCRs for angiotensin (AT1 receptors) or proteinases (PAR1 and PAR2) via transactivation of the EGF receptor and a process involving PKC. TRPV4‐dependent vascular contraction can be blocked by COX inhibitors or with TP antagonists. Further, TRPV4 activation in HUVECs stimulated Tx release as detected by an elisa.

Conclusion and Implications

We conclude that the GPCR potentiation of TRPV4 action and TRPV4‐dependent Tx receptor activation are important regulators of vascular function and could be therapeutically targeted in vascular diseases.
Glial cell line‐derived neurotrophic factor‐mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain
Authors: Kimura M , Sakai A , Sakamoto A , Suzuki H
Published: January 2015

Background and Purpose

The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line‐derived neurotrophic factor (GDNF), a well‐established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.

Experimental Approach

Rats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α2‐adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF‐mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF.

Key Results

Both mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U0126 into the LC.

Conclusions and Implications

GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
GPCR dimerization in brainstem nuclei contributes to the development of hypertension
Authors: Sun Gwo‐Ching , Ho Wen‐Yu , Chen Bo‐Rung , Cheng Pei‐Wen , Cheng Wen‐Han , Hsu Mei‐Chi , Yeh Tung‐Chen , Hsiao Michael , Lu Pei‐Jung , Tseng Ching‐Jiunn
Published: January 2015

Background and Purpose

μ‐Opioid receptors, pro‐opiomelanocortin and pro‐enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose‐dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α2A‐adrenoceptors. We hypothesized that α2A‐adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.

Experimental Approach

We microinjected μ‐opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α2A‐adrenoceptor heterodimers was assessed with immunofluorescence and co‐immunoprecipitation methods, along with proximity ligation assays.

Key Results

Immunofluorescence staining revealed colocalization of α2A‐adrenoceptors and μ receptors in NTS neurons. Co‐immunoprecipitation revealed interactions between α2A‐adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α2A‐adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin‐1 and μ receptor/α2A‐adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D‐Ala2, MePhe4, Gly5‐ol]‐enkephalin (DAMGO), but not that of the α2A‐adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α2A‐adrenoceptor heterodimer formation and BP elevation. The NO‐dependent BP‐lowering effect of α2A‐adrenoceptor agonists was blunted following increased formation of μ receptor/α2A‐adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO‐treated normotensive rats.

Conclusions and Implications

Increases in endogenous μ receptor agonists in the NTS induced μ receptor/α2A‐adrenoceptor heterodimer formation and reduced the NO‐dependent depressor effect of α2A‐adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.
9‐Phenanthrol inhibits recombinant and arterial myocyte TMEM16A channels
Authors: Burris Sarah K , Wang Qian , Bulley Simon , Neeb Zachary P , Jaggar Jonathan H
Published: January 2015

Background and Purpose

In arterial smooth muscle cells (myocytes), intravascular pressure stimulates membrane depolarization and vasoconstriction (the myogenic response). Ion channels proposed to mediate pressure‐induced depolarization include several transient receptor potential (TRP) channels, including TRPM4, and transmembrane protein 16A (TMEM16A), a Ca2+‐activated Cl− channel (CaCC). 9‐Phenanthrol, a putative selective TRPM4 channel inhibitor, abolishes myogenic tone in cerebral arteries, suggesting that either TRPM4 is essential for pressure‐induced depolarization, upstream of activation of other ion channels or that 9‐phenanthrol is non‐selective. Here, we tested the hypothesis that 9‐phenanthrol is also a TMEM16A channel blocker, an ion channel for which few inhibitors have been identified.

Experimental Approach

Patch clamp electrophysiology was used to measure rat cerebral artery myocyte and human recombinant TMEM16A (rTMEM16A) currents or currents generated by recombinant bestrophin‐1, another Ca2+‐activated Cl− channel, expressed in HEK293 cells.

Key Results

9‐Phenanthrol blocked myocyte TMEM16A currents activated by either intracellular Ca2+ or Eact, a TMEM16A channel activator. In contrast, 9‐phenanthrol did not alter recombinant bestrophin‐1 currents. 9‐Phenanthrol reduced arterial myocyte TMEM16A currents with an IC50 of ∼12 μM. Cell‐attached patch recordings indicated that 9‐phenanthrol reduced single rTMEM16A channel open probability and mean open time, and increased mean closed time without affecting the amplitude.

Conclusions and Implications

These data identify 9‐phenanthrol as a novel TMEM16A channel blocker and provide an explanation for the previous observation that 9‐phenanthrol abolishes myogenic tone when both TRPM4 and TMEM16A channels contribute to this response. 9‐Phenanthrol may be a promising candidate from which to develop TMEM16A channel‐specific inhibitors.
Easy as ABCABC: Abstract Language Facilitates Performance on a Concrete Patterning Task
Authors: Fyfe Emily R. , McNeil Nicole M. , Rittle‐Johnson Bethany
Published: January 2015

The labels used to describe patterns and relations can influence children's relational reasoning. In this study, 62 preschoolers (Mage = 4.4 years) solved and described eight pattern abstraction problems (i.e., recreated the relation in a model pattern using novel materials). Some children were exposed to concrete labels (e.g., blue‐red‐blue‐red) and others were exposed to abstract labels (e.g., A‐B‐A‐B). Children exposed to abstract labels solved more problems correctly than children exposed to concrete labels. Children's correct adoption of the abstract language into their own descriptions was particularly beneficial. Thus, using concrete learning materials in combination with abstract representations can enhance their utility for children's performance. Furthermore, abstract language may play a key role in the development of relational thinking.
Survival outcome of patients with nasopharyngeal carcinoma: a nationwide analysis of 13 407 patients in Taiwan
Authors: Huang W.‐Y. , Lin C.‐L. , Lin C.‐Y. , Jen Y.‐M. , Lo C.‐H. , Sung F.‐C. , Kao C.‐H.
Published: January 2015

Objectives

We reported the contemporary survival outcome of patients with nasopharyngeal carcinoma (NPC) and analysed the factors affecting survival.

Design

A retrospective cohort study.

Setting

A nationwide population‐based study in Taiwan.

Participants

We identified 13 407 patients with newly diagnosed NPC from 2002 to 2010.

Material and Methods

The multivariate Cox proportional hazards model was performed to measure the mortality‐association risk factor in patients with NPC after adjusting for NPC treatment and socio‐demographic characteristics.

Results

The 1‐, 2‐, 5‐ and 8‐year overall survival (OS) rates were 89.6%, 80.4%, 65.2% and 56.5%, respectively. The factors associated with mortality risk were sex (men versus women, HR  =  1.45), age (>60 versus ≤ 40 years, HR  =  3.61), geographic region of residence (eastern Taiwan versus northern Taiwan HR   =   1.39), income (<15 840 versus >25  000, HR   =   1.87) and treatment modality (chemotherapy alone versus radiotherapy alone, HR   =   2.25).

Conclusion

The contemporary 5‐year OS rate was 65.2% in Taiwan. Male patients, old age, residing in eastern Taiwan, low income and receiving chemotherapy alone were independent predictors for poor OS.
Fascin expression in cholesteatoma: correlation with destruction of the ossicular chain and extent of disease
Authors: Binnetoglu A. , Sari M. , Baglam T. , Erbarut Seven I. , Yumusakhuylu A.C. , Topuz M.F. , Batman C.
Published: January 2015

Objective

Fascin is an actin‐bundling protein found in cell membrane protrusions and increases cell motility. The expression of fascin in epithelial neoplasms has been described only recently. No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease.

Method

Cholesteatoma specimens of 28 patients and external auditory canal (EAC) skin specimens of the same patients (as the control group) were collected from mastoidectomies. Immunohistochemical technique was used to investigate the fascin expression in all cholesteatoma tissues and EAC skin specimens. Immunohistochemical staining was assessed semiquantitatively based on the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA) was performed to statistically analyse the relationships between fascin expression and intraoperative evaluation destruction of ossicular chain and extent of the disease.

Results

Immunohistochemically, there was no or very low fascin expression observed in normal epithelial cells of EAC skin, while expressed in cholesteatoma tissue. Also, fascin expression in cholesteatoma tissues was significantly correlated with destruction of ossicular chain and extent of the disease.

Conclusions

Fascin expression is usually found in cholesteatoma epithelium and is correlated with destruction of the ossicular chain and extent of disease. Considering all of the correlations between the clinical and histopathological findings, ‘fascin immunoexpression scoring’ may be used for histological grading of cholesteatoma.
Melatonin potentiates cisplatin‐induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells
Authors: Plaimee P. , Weerapreeyakul N. , Barusrux S. , Johns N. P.
Published: January 2015

Objectives

Melatonin produces anti‐cancer effects via several mechanisms, including by induction of apoptosis. In this way, it has been shown to be of use, in combination with chemotherapeutic drugs, for cancer treatment. The study described here has evaluated effects of melatonin on cytotoxicity, apoptosis and cell cycle arrest induced with the chemotherapeutic agent cisplatin, in human lung adenocarcinoma cisplatin‐sensitive cell line (SK‐LU‐1), which previously had only limit data.

Materials and methods

Cells of the SK‐LU‐1 line were treated with melatonin alone at 1–5 mm concentration or cisplatin alone 10–200 μm, for 48 h in culture. Cytotoxicity was measured by MTT reduction assay. Apoptosis induction was detected by annexin V/PI staining using flow cytometric analysis and DAPI nuclear staining. Change in mitochondrial membrane potential (ΔΨm) was quantified using DiOC6(3) reagent and activities of caspases‐3/7 were also investigated. DNA fractions were measured using propidium iodide (PI) staining.

Results

Melatonin or cisplatin alone had 50% (IC50) cytotoxicity at 5 mm or 34 μm concentrations respectively. Combination of 1 or 2 mm melatonin and cisplatin significantly augmented cytotoxicity of cisplatin by reducing its IC50 to 11 and 4 μm, respectively. Consistently, combined treatment increased population of apoptotic cells by elevating mitochondrial membrane depolarization, activating caspases‐3/7 and inducing cell cycle arrest in the S phase, compared to treatment with cisplatin alone.

Conclusion

These data demonstrate that melatonin enhanced cisplatin‐induced cytotoxicity and apoptosis in SK‐LU‐1 lung cancer cells. SK‐LU‐1 cell population growth inhibition was mediated by cell cycle arrest in the S phase. These findings suggest that melatonin has the potential to be used for NSCLC treatment in combination with a chemotherapeutic agent such as cisplatin.
Acinetobacter baumannii infection in solid organ transplant recipients
Authors: Kitazono Hidetaka , Rog Dominik , Grim Shellee A. , Clark Nina M. , Reid Gail E.
Published: January 2015

Introduction

Acinetobacter baumannii can cause serious infection in susceptible patients, but little has been published regarding risk factors for infection and outcomes in solid organ transplant (SOT) recipients.

Methods

We identified A. baumannii infection among adult SOT recipients that occurred between January 2001 and March 31, 2008 at a Chicago transplant center and evaluated characteristics of these infections and outcomes.

Results

Thirty‐three individuals developed A. baumannii infection during the study period. Seventy‐nine percent had healthcare‐associated infection with respiratory tract as the most common site of infection (64%). Eighty‐two percent of patients had received antibiotics within two wk prior to A. baumannii infection and multidrug resistance (MDR) or extensive resistance (XDR) occurred in 85%. The median time to onset of infection was five months after transplant. The 30‐d mortality was 24% and was associated with XDR. Administration of an appropriate antibiotic within three d was associated with lower 30‐d mortality (OR 0.16, p = 0.047). All isolates tested against colistin were susceptible.

Conclusion

SOT recipients with A. baumannii infection had high mortality associated with delay in appropriate antibiotic therapy and XDR organisms. The use of colistin‐containing treatment regimens should be considered in these patients when A. baumannii infection is suspected or identified in patients who have received prior antibiotics.
Design as Choreography: Information in Action
Authors: Overhill Heidi
Published: January 2015

Museum exhibitions are conventionally understood to be educational, meaning that they convey information to visitors. The content of this information is understood to include visual, auditory, and written media, as well as content from tactile, spatial, and social encounters. This article asserts that visitors also gain knowledge through bodily kinesthetic experiences while in the exhibition setting. Emerging research in other areas has revealed connections between physical posture and cognitive issues, such as emotion and attitude, but this has not yet been applied to museum practice. I suggest that exhibition planning could exploit bodily experience more explicitly as a form of information; and that body‐aware practices like sports, dance, and yoga offer intellectual content suitable for exploration in a museum setting.
Dialogical Curating: Towards Aboriginal Self‐Representation in Museums
Authors: Unruh Leanne
Published: January 2015

This essay proposes the idea of dialogical curating based on Grant Kester's term “dialogical art.” This term refers to the idea of allowing conversation with source communities to influence the process and outcome of an artwork, or in this case, a curated exhibition. I argue that in the examples of The District Six Museum in Cape Town, South Africa and The Museum of Anthropology at the University of British Columbia, the curatorial strategies used and discourses concerning the display of aboriginal objects can be called dialogical. By exploring methods of aboriginal self‐representation—such as alternative research and education methodologies as well as collaboration—it is possible to imagine a curatorial practice that is not a methodology, but a discourse that contributes to the processes of de‐colonization.
Measuring disaster recovery: bouncing back or reaching the counterfactual state?
Authors: Cheng Shaoming , Ganapati Emel , Ganapati Sukumar
Published: January 2015

How should one measure the recovery of a locale from a disaster? The measurement is crucial from a public policy and administration standpoint to determine which places should receive disaster assistance, and it affects the performance evaluation of disaster recovery programmes. This paper compares two approaches to measuring recovery: (i) bouncing back to pre‐disaster conditions; and (ii) attaining the counterfactual state. The former centres on returning to normalcy following disaster‐induced losses, whereas the latter focuses on attaining the state, using quasi‐experimental design, which would have existed if the disaster had not occurred. Both are employed here to assess two housing recovery indicators (total new units and their valuations) in Hurricane Katrina‐affected counties (rural and urban). The examination reveals significantly different outcomes for the two approaches: counties have not returned to their pre‐disaster housing conditions, but they do exhibit counterfactual recovery. Moreover, rural counties may not be as vulnerable as assumed in the disaster recovery literature.
The impact of humanitarian context conditions and individual characteristics on aid worker retention
Authors: Korff Valeska P. , Balbo Nicoletta , Mills Melinda , Heyse Liesbet , Wittek Rafael
Published: January 2015

High employee turnover rates constitute a major challenge to effective aid provision. This study examines how features of humanitarian work and aid workers’ individual characteristics affect retention within one humanitarian organisation, Médecins Sans Frontières (MSF) Holland. The study extends existing research by providing new theoretical explanations of employment opportunities and constraints and by engaging in the first large‐scale quantitative analysis of aid worker retention. Using a database of field staff (N=1,955), a logistic regression is performed of the likelihood of reenlistment after a first mission. The findings demonstrate that only 40 per cent of employees reenlist for a second mission with MSF Holland, and that workplace location and security situation, age, and gender have no significant effect. Individuals are less likely to reenlist if they returned early from the first mission for a personal reason, are in a relationship, are medical doctors, or if they come from highly developed countries. The paper reflects on the findings in the light of policy.
Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire
Authors: Mehta S. N. , Nansel T. R. , Volkening L. K. , Butler D. A. , Haynie D. L. , Laffel L. M. B.
Published: January 2015

Aims

To evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self‐report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers.

Methods

A total of 273 parent‐child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8–18 years) had Type 1 diabetes for ≥1 year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self‐administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child.

Results

The children (49% female) had a mean ± sd (range) age 13.3 ± 2.9 (8–18) years and their mean ± sd HbA1c was 71 ± 15 mmol/mol (8.6 ± 1.4%). Internal consistency was good for parents (α = 0.83) and children (α = 0.79). Test‐retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient = 0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient = 0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r = –0.41, P < 0.0001; children: r = –0.27, P < 0.0001). Psychometrics were stronger in the children aged ≥13 years compared with those aged < 13 years, but were acceptable in both age groups. Mean ± sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n = 181) than in children receiving multiple daily injections (n = 92) according to parent (75.9 ± 11.8 vs. 70.5 ± 15.5; P = 0.004) and child report (72.2 ± 12.1 vs. 67.6 ± 13.9; P = 0.006).

Conclusions

The Diabetes Management Questionnaire is a brief, valid self‐report measure of adherence to contemporary diabetes self‐management for people aged 8–18 years who are receiving either multiple daily injections or insulin pump therapy.
PROFIT‐MAXIMIZING GATE REVENUE SHARING IN SPORTS LEAGUES
Authors: Peeters Thomas
Published: January 2015

In this article, I examine how sports leagues can use gate revenue sharing to coordinate talent investments and maximize club profits. Gate revenue sharing reduces incentives to invest in talent. Initially lower investments boost profits, because total costs go down, but investing less also shrinks revenues, which harms profits at higher levels of sharing. The league maximizes profits by setting a sharing rule, which balances these two effects. Gate revenue sharing decreases talent investments more strongly in leagues with heterogeneous rather than homogeneous local market sizes. As a result, the profit‐maximizing level of sharing is higher for relatively homogeneous leagues. This implies that more balanced leagues are expected to share more gate revenues than less balanced leagues. It also explains why gate revenue sharing is widely used in the U.S. major leagues, while it is largely absent in European soccer. (JEL L41, L83)
The effect of topical treatment with doxycycline compared to saline on 66 avulsed permanent teeth – a retrospective case–control study
Authors: Tsilingaridis Georgios , Malmgren Barbro , Skutberg Caroline , Malmgren Olle
Published: January 2015

Background/Aim

Tooth avulsion in young growing individuals is an uncommon but very severe dental trauma. The aim of this retrospective case–control study was to evaluate the effect of topical treatment with doxycycline on avulsed permanent teeth compared with treatment with only saline regarding pulp survival and periodontal healing.

Material and method

Sixty‐six avulsed teeth in 50 patients (34 boys and 16 girls) between the ages six and 18 years were included in this study. Thirty teeth were soaked in a 0.05 mg ml−1 doxycycline solution for 5 min, before replantation and 36 teeth in saline solution. Root development was categorized with respect to root formation and development of the apex into three groups, one‐half‐root formation to full root formation with open apex, full root formation with half‐closed apex and full root formation with closed apex. Pulp survival and periodontal healing were assessed as successful when at the end of the observation period no pulp necrosis or ankylosis‐related resorption was diagnosed. The mean observation time was 48 months.

Results

In the doxycycline group, 27 were diagnosed with pulp necrosis, 15 with ankylosis‐related resorption and nine were extracted. In the saline group, 30 were diagnosed with pulp necrosis, 23 with ankylosis‐related resorption and 11 were extracted. Regarding pulp survival and periodontal healing, no significant differences were found between the two groups. Teeth with immature root development showed significantly less pulp necrosis (P < 0.05) compared to teeth with full root formation regardless if treated topically with doxycycline or not. No significant differences were found between the two groups regarding age, storage, root development, splinting duration and observation time although the saline group had significantly longer extra‐oral time (P < 0.001) than the doxycycline group.

Conclusions

This study indicates that avulsed permanent teeth soaked in doxycycline do not show a better treatment outcome regarding pulp survival and periodontal healing compared with avulsed teeth placed only in saline solution. This finding is consistent regardless of root development, storage and extra‐oral time.
Education for Epiphany: The Case of Plato's Lysis
Authors: Jonas Mark E.
Published: January 2015

While a great deal has been written on Plato's Lysis in philosophy and philology journals over the last thirty years, nothing has been published on Lysis in the major Anglo‐American philosophy of education journals during that time. Nevertheless, this dialogue deserves attention from educators. In this essay, Mark Jonas argues that Lysis can serve as a model for educators who want to move their students beyond mere aporia, but also do not want to dictate answers to students. Although the dialogue ends in Socrates's affirmation of aporia, his affirmation is actually meant to persuade his interlocutors to reflect on an epiphany they had previously experienced. In what follows, Jonas offers a close reading of relevant passages of Lysis, demonstrating the way that Socrates leads his interlocutors to an epiphany without forcing his answers upon them.
“Listen Then, or, Rather, Answer”: Contemporary Challenges to Socratic Education
Authors: Fullam Jordan
Published: January 2015

The popularity of Jacques Rancière in recent work in educational philosophy has rejuvenated discussion of the merits and weaknesses of Socratic education, both in Plato's dialogues and in invocations of Socrates in contemporary educational practice. In this essay Jordan Fullam explores the implications of this trend through comparing Rancière's educational thought to an analysis of the relationship between dialectic and stultification in Plato's Republic. This task clarifies what is useful in the recent wave of scholarship that brings Rancière's work to bear upon Socratic education, and what we might redeem in the practice of teaching that Plato assigns to the character of Socrates in the Republic. Fullam also draws on the educational literature on Socratic education to provide further context to explore the usefulness of both Rancière and Socrates for contemporary teaching.
A randomized controlled study of neuromuscular electrical stimulation in oropharyngeal dysphagia secondary to acquired brain injury
Authors: Terré R. , Mearin F.
Published: January 2015

Background and purpose

To evaluate the effectiveness of neuromuscular electrical stimulation (NMES) treatment in patients with oropharyngeal dysphagia secondary to acquired brain injury.

Methods

Twenty patients with neurological oropharyngeal dysphagia (14 stroke and six severe traumatic brain injury) were enrolled in a prospective randomized study, with patients and assessors blinded (to group allocation): 10 patients underwent NMES and conventional swallowing therapy and 10 patients underwent sham electrical stimulation (SES) and conventional swallowing therapy. Both groups completed 20 sessions. At baseline, at the end of treatment (1 month) and at 3‐month follow‐up, clinical, videofluoroscopic and esophageal manometric analyses were done. Feeding swallowing capacity was evaluated using the functional oral intake scale (FOIS).

Results

Mean FOIS score before treatment was 1.9 for the NMES group and 2.1 for the SES group. After treatment, the NMES group increased by 2.6 points (4.5 points) compared with only 1 point (3.1 points) for the SES group (P = 0.005). At 3 months of follow‐up, mean scores were 5.3 and 4.6 respectively; thus, both groups improved similarly. At that time point (3 months), tracheal aspiration persisted in six patients in each group. However, a significant improvement in relation to the bolus viscosity at which aspiration appeared was found in the NMES group versus the SES group (P = 0.015). Also, a significant increase (P = 0.04) in pharyngeal amplitude contraction was observed at the end of treatment (1 month) in the NMES group compared with the SES group.

Conclusion

Neuromuscular electrical stimulation significantly accelerated swallowing function improvement in patients with oropharyngeal dysphagia secondary to acquired brain injury.
N‐terminal pro‐B‐type natriuretic peptide and the risk of stroke and transient ischaemic attack: the Rotterdam Study
Authors: Portegies M. L. P. , Kavousi M. , Leening M. J. G. , Bos M. J. , van den Meiracker A. H. , Hofman A. , Franco O. H. , Koudstaal P. J. , Ikram M. A.
Published: January 2015

Background and purpose

Amino‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population‐based Rotterdam Study, the association of NT‐proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated.

Methods

NT‐proBNP was measured in 1997–2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow‐up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex.

Results

During 22 058 person‐years 195 men suffered a stroke and 118 a TIA. During 31 825 person‐years 230 women suffered a stroke and 187 a TIA. Higher NT‐proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29–1.76] and in women (HR 1.24; 95% CI 1.05–1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26–1.82) but not in men (HR 1.02; 95% CI 0.83–1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow‐up did not change the associations.

Conclusions

Higher NT‐proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.
Causation of cerebral microbleeds: more work is urgently needed
Authors: Krieger D. W.
Published: January 2015

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