bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐life effectiveness of once‐daily calcipotriol and betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: 4‐ and 12‐week interim results from the PRO‐long study
Authors: Lambert J. , Hol C.W. , Vink J.
Published: February 2014

Background

Psoriasis is most often treated using topical therapies such as the once‐daily fixed combination of calcipotriol and betamethasone dipropionate, which is available as a gel and an ointment. To date, there have been no direct comparisons of patient perspectives on the two formulations.

Objective

To describe and compare patients' perspectives on calcipotriol and betamethasone gel and ointment formulations, including real‐life effectiveness, adherence behaviour, treatment satisfaction and health‐related quality of life (QoL), during long‐term psoriasis vulgaris management, according to interim findings from the PRO‐long study.

Methods

PRO‐long is a multicentre, prospective, observational, 52‐week cohort study in patients prescribed fixed‐combination calcipotriol (50 μg/g) and betamethasone (0.5 mg/g; as dipropionate) gel or ointment for long‐term psoriasis management. Difference in effectiveness at 4 and 12 weeks was assessed by comparing the proportion of patients with controlled (mild or very mild) disease, according to the Patient's Global Assessment. Additional patient questionnaires were used to assess adherence behaviour, treatment satisfaction (nine‐item Treatment Satisfaction Questionnaire for Medication) and health‐related QoL (Skindex‐29).

Results

A total of 156 patients were included in the analysis. In single items of the adherence behaviour and treatment satisfaction questionnaires, patients preferred the gel over the ointment as convenient, easy to use and fast to apply. Post hoc analysis demonstrated significant differences between gel and ointment for convenience and application time. More patients had controlled disease at week 12 with gel (71.9%) vs. ointment (65.7%); however, the difference was not statistically significant (primary end point; P = 0.40).

Conclusion

This interim analysis supports fixed‐combination calcipotriol and betamethasone gel as more convenient, easier to use and faster to apply than the ointment formulation in real‐life conditions according to patients with psoriasis vulgaris. Furthermore, a numerical difference in patient‐reported real‐life effectiveness was seen in favour of the gel, although this was not statistically significant.
Immunogenetic factors in mycosis fungoides: can the HLA system influence the susceptibility and prognosis of the disease? Long‐term follow‐up study of 46 patients
Authors: Brazzelli V. , Rivetti N. , Badulli C. , Carugno A. , Grasso V. , De Silvestri A. , Martinetti M. , Borroni G.
Published: February 2014

Background

Mycosis fungoides (MF) is the most common and one of the least aggressive forms of cutaneous T‐cell lymphoma. Several studies have demonstrated the influence of human leucocyte antigen (HLA) genes on the susceptibility of MF, highlighting the importance of certain alleles but, until today, no studies have evaluated the relationship between HLA alleles and the prognosis of patients with MF.

Objective

The aim of this retrospective cohort study was to evaluate the polymorphism of HLA class I and class II alleles in a group of 46 MF Caucasian patients, looking for their influence in susceptibility and prognosis of the disease.

Methods

Study population included a case‐cohort sample of 46 Caucasian patients with MF that, between 1993 and 1997, underwent HLA class I and II genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow‐up of 11 years) and they were divided into three groups according to the evolution of the disease.

Results

Molecular typing at low‐resolution level revealed that HLA‐A*24, A*68, A*69, B*35 and DQB1*05:02 alleles were involved in susceptibility to MF. Correspondence analysis underlined that long‐lasting remission was characterized by HLA‐A*24 and HLA‐A*25 alleles, frequent relapse by HLA‐DRB1*01, DQA1*01:01, DQB1*05:01 alleles and death by HLA‐A*68, HLA‐B*08, HLA‐B*35, HLA‐C*03 alleles.

Conclusion

This study suggests that the prognosis of MF patients is not only correlated with clinical/pathological/serological/immunological variables but it also relies on specific HLA alleles.
Observational study on the mitotic rate and other prognostic factors in cutaneous primary melanoma arising from naevi and from melanoma de novo
Authors: Betti R. , Santambrogio R. , Cerri A. , Vergani R. , Moneghini L. , Menni S.
Published: February 2014

Background

Melanomas can arise from naevi or appear de novo. The frequency or the effect of their origin on prognosis is still debated. Mitotic rate (MR) and ulceration of melanomas have been proposed as further new prognostic indexes.

Aim

To determine the different prognostic factors in melanomas de novo and melanomas from pre‐existing naevi and whether these two melanoma groups have different MR or presence of ulceration.

Methods

All patients with confirmed primary melanomas observed in our clinic from 1996 to July 2013 were included. The distinction between the two groups of melanomas was histologically based. We compared Breslow's thickness, the number of mitosis/mm2 and the presence of ulceration between the naevus‐associated melanoma and de novo melanoma group.

Results

Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a naevus‐associated melanoma. Breslow's thickness was not significantly different in the two groups (0.77 ± 1.47 mm vs. 0.59 ± 1.35 mm). The number of patients with presence of ulceration and MR ≥1 mitosis/mm2 was not significantly different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's thickness ≥ 1 mm), the number of patients with ≥6 mitosis/mm2 was significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group.

Conclusions

When mitosis ≥ 1 mm/mm2, the results obtained do not show a better or worse prognosis based on Breslow's thickness, ulceration and MR in melanomas associated with naevus vs. melanomas de novo. When ≥6 mitosis/mm2 are considered, the number of patients in the de novo melanoma group with thick melanoma is highly more represented. The debate about the cut‐off value of mitosis ≥1 mm2 is open.
High‐definition optical coherence tomography and reflectance confocal microscopy in the in vivo visualization of a reaction to permanent make‐up
Authors: Maier T. , Flaig M.J. , Ruzicka T. , Berking C. , Pavicic T.
Published: February 2014

Background and Objectives

After permanent make‐up treatments, eczematous and granulomatous reactions may occur which need anti‐inflammatory treatment. For the definite diagnosis oftentimes biopsies are recommended. In vivo imaging such as reflectance confocal microscopy (RCM) and high‐definition optical coherence tomography (HD‐OCT) has been successfully used in the non‐invasive diagnosis of various dermatoses before.

Methods

Here, we report on non‐invasive imaging of a reaction towards permanent make‐up in a 40‐year‐old woman by using HD‐OCT and RCM.

Results

Both in HD‐OCT and in RCM subepidermal pigment and granulomatous changes could be visualized and correlated with the histopathological findings. Regression of the lesions in response to topical steroids and intralesional injections of steroids and 5‐fluorouracil is reported and treatment options are discussed.

Conclusion

Non‐invasive imaging techniques such as HD‐OCT and RCM allow the visualization and localization of exogenous pigment and help in the evaluation of adverse reactions due to permanent make‐up tattooing.
Selective maintenance of recombination between the sex chromosomes
Authors: Otto S. P.
Published: February 2014

A hallmark of many sex chromosomes is the dramatically reduced rate of recombination between them in the heterogametic sex (e.g. between the X and Y). Sexually antagonistic selection is thought to be the main selective driver of this reduced recombination, with tighter linkage strengthening the association between alleles favourable to females and the X, as well as alleles favourable to males and the Y. Nevertheless, many sex chromosomes retain substantial levels of recombination over millions of years, and some old sex chromosomes remain homomorphic with few signs of recombination suppression and the chromosomal degradation expected to follow. This paper explores the selective factors that can maintain recombination between the sex chromosomes. Specifically, by analysing the dynamics of genes that modify the rate of recombination, I present results demonstrating that certain forms of selection – all involving overdominance in males – can positively maintain recombination in the pseudo‐autosomal region. To understand these cases, one has to revise our standard view of sexual antagonistic selection as involving two partners (males and females) to three partners (the X in females, the X in males and the Y).
The search for Pleiades in trait constellations: functional integration and phenotypic selection in the complex flowers of Morrenia brachystephana (Apocynaceae)
Authors: Baranzelli M. C. , Sérsic A. N. , Cocucci A. A.
Published: February 2014

Pollinator‐mediated natural selection on single traits, such as corolla tube or spur length, has been well documented. However, flower phenotypes are usually complex, and selection is expected to act on several traits that functionally interact rather than on a single isolated trait. Despite the fact that selection on complex phenotypes is expectedly widespread, multivariate selection modelling on such phenotypes still remains under‐explored in plants. Species of the subfamily Asclepiadoideae (Apocynaceae) provide an opportunity to study such complex flower contrivances integrated by fine‐scaled organs from disparate developmental origin. We studied the correlation structure among linear floral traits (i) by testing a priori morphological, functional or developmental hypotheses among traits and (ii) by exploring the organization of flower covariation, considering alternative expectations of modular organization or whole flower integration through conditional dependence analysis (CDA) and integration matrices. The phenotypic selection approach was applied to determine whether floral traits involved in the functioning of the pollination mechanism were affected by natural selection. Floral integration was low, suggesting that flowers are organized in more than just one correlation pleiad; our hypothetical functional correlation matrix was significantly correlated with the empirical matrix, and the CDA revealed three putative modules. Analyses of phenotypic selection showed significant linear and correlational gradients, lending support to expectations of functional interactions between floral traits. Significant correlational selection gradients found involved traits of different floral whorls, providing evidence for the existence of functional integration across developmental domains.
Comparative genetic analysis of Arabidopsis purple acid phosphatases AtPAP10, AtPAP12, and AtPAP26 provides new insights into their roles in plant adaptation to phosphate deprivation
Authors: Wang Liangsheng , Lu Shan , Zhang Ye , Li Zheng , Du Xiaoqiu , Liu Dong
Published: February 2014

Induction and secretion of acid phosphatases (APases) is thought to be an adaptive mechanism that helps plants survive and grow under phosphate (Pi) deprivation. In Arabidopsis, there are 29 purple acid phosphatase (AtPAP) genes. To systematically investigate the roles of different AtPAPs, we first identified knockout or knock‐down T‐DNA lines for all 29 AtPAP genes. Using these atpap mutants combined with in‐gel and quantitative APase enzyme assays, we demonstrated that AtPAP12 and AtPAP26 are two major intracellular and secreted APases in Arabidopsis while AtPAP10 is mainly a secreted APase. On Pi‐deficient (P−) medium or P− medium supplemented with the organophosphates ADP and fructose‐6‐phosphate (Fru‐6‐P), growth of atpap10 was significantly reduced whereas growth of atpap12 was only moderately reduced, and growth of atpap26 was nearly equal to that of the wild type (WT). Overexpression of the AtPAP12 or AtPAP26 gene, however, caused plants to grow better on P− or P− medium supplemented with ADP or Fru‐6‐P. Interestingly, Pi levels are essentially the same for the WT and overexpressing lines, although these two types of plants have significantly different growth phenotypes. These results suggest that the APases may have other roles besides enhancing internal Pi recycling or releasing Pi from external organophosphates for plant uptake.
Homeodomain leucine‐zipper proteins and their role in synchronizing growth and development with the environment
Authors: Brandt Ronny , Cabedo Marc , Xie Yakun , Wenkel Stephan
Published: February 2014

The Arabidopsis (Arabidopsis thaliana L.) genome encodes for four distinct classes of homeodomain leucine‐zipper (HD‐ZIP) transcription factors (HD‐ZIPI to HD‐ZIPIV), which are all organized in multi‐gene families. HD‐ZIP transcription factors act as sequence‐specific DNA‐binding proteins that are able to control the expression level of target genes. While HD‐ZIPI and HD‐ZIPII proteins are mainly associated with environmental responses, HD‐ZIPIII and HD‐ZIPIV are primarily known to act as patterning factors. Recent studies have challenged this view. It appears that several of the different HD‐ZIP families interact genetically to align both morphogenesis and environmental responses, most likely by modulating phytohormone‐signaling networks.
The Aβ‐clearance protein transthyretin, like neprilysin, is epigenetically regulated by the amyloid precursor protein intracellular domain
Authors: Kerridge Caroline , Belyaev Nikolai D. , Nalivaeva Natalia N. , Turner Anthony J.
Published: February 2014

Proteolytic cleavage of the amyloid precursor protein (APP) by the successive actions of β‐ and γ‐secretases generates several biologically active metabolites including the amyloid β‐peptide (Aβ) and the APP intracellular domain (AICD). By analogy with the Notch signalling pathway, AICD has been proposed to play a role in transcriptional regulation. Among the cohort of genes regulated by AICD is the Aβ‐degrading enzyme neprilysin (NEP). AICD binds to the NEP promoter causing transcriptional activation by competitive replacement with histone deacetylases (HDACs) leading to increased levels of NEP activity and hence increased Aβ clearance. We now show that the Aβ‐clearance protein transthyretin (TTR) is also epigenetically up‐regulated by AICD. Like NEP regulation, AICD derived specifically from the neuronal APP isoform, APP695, binds directly to the TTR promoter displacing HDAC1 and HDAC3. Cell treatment with the tyrosine kinase inhibitor Gleevec (imatinib) or with the alkalizing agent NH4Cl causes an accumulation of ‘functional’ AICD capable of up‐regulating both TTR and NEP, leading to a reduction in total cellular Aβ levels. Pharmacological regulation of both NEP and TTR might represent a viable therapeutic target in Alzheimer's disease.

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Amyloid precursor protein (APP) intracellular domain (AICD) regulates expression of the amyloid (Aβ)‐degrading enzyme neprilysin (NEP). The Aβ‐clearance protein transthyretin (TTR) is also epigenetically regulated by AICD, derived specifically from the neuronal APP695 isoform. Cell treatment with agents up‐regulating ‘functional’ AICD increases production of TTR and NEP and reduces Aβ levels which might represent a viable therapeutic target in Alzheimer's disease.
Inhibition of Rho‐kinase protects cerebral barrier from ischaemia‐evoked injury through modulations of endothelial cell oxidative stress and tight junctions
Authors: Gibson Claire L. , Srivastava Kirtiman , Sprigg Nikola , Bath Philip M. W. , Bayraktutan Ulvi
Published: February 2014

Ischaemic strokes evoke blood–brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho‐kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho‐kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil‐ versus vehicle‐treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post‐ischaemia or 4 h post‐ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress‐ and tight junction‐related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen–glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin‐5. Cotreatment of cells with Y‐27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho‐kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions.

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Inhibition of Rho‐kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle‐treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y‐27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition‐mediated BBB protection.
Interferon regulatory factor 8 protects against cerebral ischaemic‐reperfusion injury
Authors: Xiang Mei , Wang Lang , Guo Sen , Lu Yan‐Yun , Lei Hao , Jiang Ding‐Sheng , Zhang Yan , Liu Yi , Zhou Yan , Zhang Xiao‐Dong , Li Hongliang
Published: February 2014

Interferon regulatory factor 8 (IRF8), a transcriptional regulator in the IRF family, has been implicated in innate immunity, immune cell differentiation and tumour cell apoptosis. In the present study, we found that IRF8 is constitutively expressed in the brain and suppressed after cerebral ischaemia in a time‐dependent manner. IRF8 knockout (IRF8‐KO) mice, wild type (WT) mice, neuron‐specific IRF8 transgenic (TG) mice and non‐transgenic mice were used in a transient cerebral ischaemic model. The IRF8 knockout mice exhibited aggravated apoptosis, inflammation and oxidative injury in the ischaemic brain, eventually leading to poorer stroke outcomes, whereas neuron‐specific IRF8 transgenic mice showed a marked inhibition of apoptosis and improved stroke outcomes. To model ischaemia/reperfusion conditions in vitro, primary cortical neurons were cultured and subjected to transient oxygen and glucose deprivation for 60 min. Similar to the in vivo study, IRF8 knockdown by Ad‐shIRF8 resulted in increased apoptosis, whereas IRF8 over‐expression by Ad‐IRF8 significantly decreased neuronal apoptosis. These data indicate that IRF8 is strongly protective in ischaemic stroke by regulating neuronal apoptosis, the inflammatory response and oxidative stress.

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In the present study, we found that the transcriptional factor IRF8 plays a protective role in the cerebral ischaemic‐reperfusion injury by attenuating neuronal apoptosis, oxidative stress and inflammation. Besides the known function of IRF8 in regulating the inflammatory gene expression, we first demonstrated that IRF8 can directly modulate apoptosis and oxidative stress by controlling the relative genes expression.
Protective Effect of Leptin and Ghrelin against Toxicity Induced by Amyloid‐β Oligomers in a Hypothalamic cell Line
Authors: Gomes S. , Martins I. , Fonseca A. C. R. G. , Oliveira C. R. , Resende R. , Pereira C. M. F.
Published: February 2014

In addition to cognitive decline, Alzheimer's disease (AD) patients also exhibit an unexplained weight loss that correlates with disease progression. In young and middle‐aged AD patients, large amounts of amyloid‐β (Aβ) deposits were observed in the hypothalamus, a brain region involved in the control of feeding and body weight through the action of peripheral metabolic peptides, which have recently been shown to have neuroprotective effects. Moreover, levels of peripheral metabolic peptides, such as leptin and ghrelin, are changed in AD patients. The present study aimed to investigate the role of Aβ peptide in the survival of hypothalamic cells and to explore the receptor‐mediated protective effect of leptin and ghrelin against Aβ‐induced toxicity in these cells. Using the mHypoE‐N42 cell line, we demonstrated for the first time that oligomeric Aβ is toxic to hypothalamic cells, leading to cell death. It was also demonstrated that leptin and ghrelin protect these cells against AβO‐induced cell death through the activation of the leptin and ghrelin receptors, respectively. Furthermore, ghrelin and leptin prevented superoxide production, calcium rise and mitochondrial dysfunction triggered by AβO. Taken together, these results suggest that peripheral metabolic peptides, in particular leptin and ghrelin, might be considered as preventive strategies for ameliorating hypothalamic alterations in AD.
Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum
Authors: Saburkina Inga , Gukauskiene Ligita , Rysevaite Kristina , Brack Kieran E. , Pauza Audrys G. , Pauziene Neringa , Pauza Dainius H.
Published: February 2014

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure‐distended whole hearts and whole‐mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517–2788; aged) vs. 2118 ± 108 (range 1513–2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well‐developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans.
Elevated expression of CX3C chemokine receptor 1 mediates recruitment of T cells into bone marrow of patients with acquired aplastic anaemia
Authors: Ren J. , Hou X. Y. , Ma S. H. , Zhang F. K. , Zhen J. H. , Sun L. , Sun Y. X. , Hao Y. L. , Cheng Y. F. , Hou M. , Xu C. G. , Zhang M. H. , Peng J.
Published: February 2014

Objective

Acquired aplastic anaemia (AA) is a T‐cell‐mediated, organ‐specific autoimmune disease characterized by haematopoietic stem cell destruction in the bone marrow. The exact molecular mechanism of T‐cell trafficking into the bone marrow is unclear in AA. Very late activation antigen‐4 (VLA‐4) and CX3C chemokine receptor 1 (CX3CR1) play active roles in many autoimmune diseases. Therefore, we investigated whether VLA‐4 and CX3CR1 also contribute to T‐cell migration into the bone marrow in acquired AA.

Design, setting and subjects

Expression levels of CX3CR1 and VLA‐4 and their ligands [fractalkine (CX3CL1) and vascular cell adhesion molecule‐1 (VCAM‐1)] were examined in 63 patients with AA and 21 healthy control subjects. T‐cell chemotaxis and adhesion were analysed in 17 patients with severe AA. We also prospectively evaluated the expression pattern of CX3CR1 during treatment with antithymocyte globulin plus cyclosporine in 11 patients with severe AA.

Results

The proportion of peripheral and bone marrow CD4+ and CD8+ T cells expressing CX3CR1 and the level of CX3CL1 was increased in patients with AA. However, there was no significant difference in VLA‐4 expression or VCAM‐1 levels. Functional studies demonstrated that chemotaxis towards autologous bone marrow plasma or soluble CX3CL1 was significantly higher in T cells from AA patients and could be blocked by CX3CR1 inhibitors. CX3CR1‐mediated T‐cell adhesion was also upregulated in these patients. The expression of CX3CR1 was associated with the efficacy of immunosuppressive therapy.

Conclusion

The present findings demonstrate that CX3CR1 plays a pivotal role in recruitment of T cells into the bone marrow in acquired AA and is a potential therapeutic target for treatment of this disorder.
Collaborative crafting in call centre teams
Authors: McClelland Giles P. , Leach Desmond J. , Clegg Chris W. , McGowan Ian
Published: February 2014

Job crafting research has typically examined the antecedents and outcomes of individual‐level crafting. In this study, we test a model of team‐level or collaborative job crafting using data collected from 242 call centre teams and supervisors' ratings of team performance. The focus on teams with narrowly defined tasks and limited decision‐making responsibility are unique features of this study. As predicted, collaborative crafting was found to relate positively to team efficacy, team control, and team interdependence, which in turn were found to relate positively to work engagement and team performance. The implications for theory development, future research, and practice are discussed.

Practitioner points

Even in a work environment characterized by low control, there remain opportunities for collaborative job crafting.

Collaborative crafting is associated with higher employee engagement and team performance.

Call centre supervisors and managers need to be aware of the potential benefits of collaborative crafting to ensure it is not inhibited by their behaviours (such as enhanced monitoring).

As positive consequences are associated with collaborative crafting, organizations should consider team training to enhance the collaborative crafting capability of teams.
Regression of oral lichenoid lesions after replacement of dental restorations
Authors: Mårell L. , Tillberg A. , Widman L. , Bergdahl J. , Berglund A.
Published: February 2014

The aim of the study was to determine the prognosis and to evaluate the regression of lichenoid contact reactions (LCR) and oral lichen planus (OLP) after replacement of dental restorative materials suspected as causing the lesions. Forty‐four referred patients with oral lesions participated in a follow‐up study that was initiated an average of 6 years after the first examination at the Department of Odontology, i.e. the baseline examination. The patients underwent odontological clinical examination and answered a questionnaire with questions regarding dental health, medical and psychological health, and treatments undertaken from baseline to follow‐up. After exchange of dental materials, regression of oral lesions was significantly higher among patients with LCR than with OLP. As no cases with OLP regressed after an exchange of materials, a proper diagnosis has to be made to avoid unnecessary exchanges of intact restorations on patients with OLP.
Primary care‐based facial pain unit inVantaa: the first experiences 2003–2009
Authors: Kotiranta U. , Suni J. , Kauppila T.
Published: February 2014

As an attempt to tackle the challenge in serving facial pain patients, the first primary care‐based facial pain unit was founded in 2003 as part of public dental primary care ofVantaa,Finland. Data were collected, consisting of sex, age, sources of referrals, reasons for seeking care, diagnoses made, therapeutic procedures, and numbers of visits to dentists and phone consultations. To describe the development of the present pain management system, we divided the observation periods into two parts: 2003–2006 and 2007–2009 and compared frequencies of the studied parameters between the two follow‐up periods. During 2003–2006, 370 patients were examined and the number of visits was 659, corresponding patients′ number was 437 and visits′ number 960 during 2007–2009. Referrals to the primary care facial pain unit came from primary care dentists (80%), respective primary care pain unitGPs (6%), oral hygienists (3%) and ordinaryGPs (2%). Four percentage of the patients′ referrals came from secondary and tertiary care clinics of various types and 5% from private sector dentists and specialists. The average number of telephone consultations per year increased from 51 to 300 between study periods. During the follow‐up period, the main reason for seeking care from our unit was temporomandibular disorders. Education in self‐care, oral appliance therapy and physiotherapy were mostly used as management for these pain problems. The facial pain management unit in primary health care could be a useful model to serve increasing numbers of chronic facial pain patients.
Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas
Authors: Hildebrand Laura C. , Carvalho Ana L. , Lauxen Isabel S. , Nör Jacques E. , Cerski Carlos T. S. , Sant'Ana Filho Manoel
Published: February 2014

Background

CD44 and aldehyde dehydrogenase 1 (ALDH1) are considered putative markers of highly tumorigenic cells (i.e., cancer stem‐like cells) in head and neck squamous cell carcinomas. This small subset of cells is believed to be the primary responsible for tumor initiation and progression. The objectives of this study were (i) to evaluate the patterns of CD44 and ALDH1 expression in the tumor center and in the invasive front, as well as in adjacent non‐tumor epithelium, and (ii) to correlate these findings with clinical parameters.

Materials and methods

The sample comprised 44 patients with primary head and neck squamous cell carcinomas. Hematoxylin and eosin (HE) staining was used for histopathological tumor grading and for morphological analysis of adjacent non‐tumor epithelium. Semiquantitative analysis was performed in histological sections immunostained for CD44 and ALDH1.

Results

ALDH1 immunostaining in the invasive front showed positive association with tumor size, regional metastasis, tumor histopathological grading, and disease progression. Moreover, expression of this marker in both tumor invasive front and adjacent non‐tumor epithelium was related with more aggressive tumors. CD44 immunostaining was heterogeneous in all areas evaluated and did not show association with clinical data.

Conclusion

Collectively, these data suggest that ALDH1 immunostaining in the invasive front and in adjacent non‐tumor epithelium may help identify tumors with a more aggressive behavior, potentially contributing to improving treatment customization and the monitoring of patients with head and neck cancer.
Long‐Term Effects of Fathers' Depressed Mood on Youth Internalizing Symptoms in Early Adulthood
Authors: Reeb Ben T. , Wu Ed Y. , Martin Monica J. , Gelardi Kristina L. , Chan Sut Yee Shirley , Conger Katherine J.
Published: February 2014

While an accumulating body of research has documented increased risk of psychopathology among children of depressed fathers, most studies have used cross‐sectional design, and little is known about offspring outcomes beyond childhood. Using prospective data from a community sample (N = 395), we found that paternal depressive symptoms when children were in early adolescence (age 13) predicted offspring depressive and anxiety symptoms at age 21, controlling for baseline youth symptoms, maternal depressive symptoms, and other known correlates of internalizing problems in early adulthood. Associations were not moderated by maternal depressive symptoms or child gender. These results suggest that the unique and long‐term effects of paternal depression on children's risk of mood disorders may persist into adulthood.
Longitudinal Prediction of Mid‐Adolescent Psychosocial Outcomes From Early Adolescent Family Help Seeking and Family Support
Authors: Heerde Jessica A. , Toumbourou John W. , Hemphill Sheryl A. , Olsson Craig A.
Published: February 2014

This study examined whether family help seeking and family support represented the same or distinct constructs and prospective associations between emergent constructs and psychosocial outcomes. Data were from 1,713 school‐based adolescents participating in a randomized controlled trial, in Victoria, Australia. Family help seeking emerged as a single factor, distinct from family support, and was prospectively associated with improved psychosocial outcomes. Father closeness predicted lower depressive symptoms. Family help seeking predicted higher help seeking for peers. Interactions between family help seeking and family support on psychosocial outcomes were not apparent. Findings highlight the importance of examining family help seeking and family support separately in future studies of adolescents' help‐seeking behavior.
A Proposal on How the Regulator Should Set Minimum Interest Rate Guarantees in Participating Life Insurance Contracts
Authors: Schmeiser Hato , Wagner Joël
Published: February 2014

We consider a contingent claim model framework for participating life insurance contracts and assume a competitive market with minimum solvency requirements as provided by Solvency II. In a first step, the implications of the regulator's imposing a particular interest rate guarantee on the insurer's asset allocation are analyzed in a reference situation. We study the sensitivity of the interaction between the interest rate guarantee and the asset allocation when the risk‐free interest rate changes. Particular attention is paid to the current market situation where the guaranteed interest rate is often close to the risk‐free interest rate. In a second step, we assess at what level the interest rate guarantee should be set by the regulator in order to maximize policyholders' utility. We show that the results yielded by the proposed concept to derive an optimal value for the interest rate guarantee are very stable for various model parameters.
Beyond the borderline: Outcomes for inborn infants born at ≤500 grams
Authors: Keir Amy , McPhee Andrew , Wilkinson Dominic
Published: February 2014

Aim

To report survival, morbidity and neurodevelopmental outcome in a cohort of extremely low birthweight infants.

Methods

Retrospective cohort study of all inborn infants born alive with birthweights ≤500 g ≥22 weeks gestation at Women's and Children's Hospital, Adelaide, Australia, over a 6‐year period (2005–2010). Outcome data including standardised medical and psychological assessments at 12 and 36 months corrected age were collated from follow‐up.

Results

A total of 36 eligible infants were born over the study period (mean gestational age (GA) 24.4 (range 22.0–30.0) weeks; birthweight 443 (330–500) grams). Twenty‐six of the 36 (72%) infants were small for gestational age (SGA).Ten of the 36 infants received compassionate care and died in the delivery or operating room. Twenty‐six of the 36 infants were admitted to the neonatal intensive care unit (NICU), of whom 12 (46%) died during their admission. At age 12 months corrected, 2/14 (14%) of survivors had none/minimal, 4/14 (29%) had mild and 8/14 (57%) had moderate/severe neurodevelopmental disability. Overall, the survival rate was 39%, and survival without neurodevelopmental disability was 6%. Only 1/10 appropriate‐for‐gestational‐age (AGA) infants survived to discharge (and had severe disability), whereas 13/26 (50%) of all SGA infants in the study survived to discharge. Of all infants admitted to the NICU, 11/26 (42%) survived without severe neurodevelopmental disability at latest follow‐up.

Conclusions

There was a high risk of death or impairment in this cohort of infants. Survival was rare for AGA infants weighing ≤500 g at birth. Our study provides an evidence base to assist counselling and decision‐making.
Congenital diaphragmatic hernia
Authors: Leeuwen Lisette , Fitzgerald Dominic A
Published: February 2014

Congenital diaphragmatic hernia is an uncommon congenital anomaly of the diaphragm with pulmonary hypoplasia and persistent pulmonary hypertension as serious consequences. Despite recent advances in therapy, congenital diaphragmatic hernia remains a challenging condition. Best treatment strategies are still largely unknown, and practice strategies vary widely among different centres. Additionally, as congenital diaphragmatic hernia is a relatively uncommon condition, it is difficult to recruit sufficient numbers of patients for clinical trials. In recent years, survival rates of congenital diaphragmatic hernia patients appear to have increased. With the progressively improved survival rates, the long‐term prognosis and quality of life of patients have become an increasingly important issue. Survivors have been shown to be at risk for many long‐term morbidities, which highlights the importance of long‐term follow‐up of these children. The aim of this review is to give an overview of the current knowledge regarding congenital diaphragmatic hernia.
Pharmacokinetics and pharmacodynamics of intravenous baclofen in dogs: a preliminary study
Authors: Scherkenbach Lisa A , Coles Lisa D , Patterson Edward E , Cloyd James C , Krach Linda E , Kriel Robert L
Published: February 2014

Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating baclofen withdrawal syndrome.

Objectives

To complete a preliminary study of IV baclofen in dogs.

Methods

Single bolus IV doses (0.5, 2 and 3 mg/kg) as well as multiple dose regimens were evaluated. Sedation and clinical tolerability was assessed by modified Glasgow Coma Scale and Discomfort and Behaviour Scale.

Key findings

Baclofen concentration-time profiles following single IV boluses were best fit by a two-compartment model which was used to predict plasma concentrations for the multiple dose regimens. The mean distribution and elimination half-lives were 11 min and 222 min, respectively. Maximum clinical effect did not occur until approximately 120 min. The discomfort score increased proportionately with increased single IV bolus doses. Multiple dose regimens resulted in greater than proportionate discomfort scores based on total dose and were generally not as well tolerated.

Conclusions

If projected for human use, our data suggests that initial IV baclofen doses will need to be reduced by approximately one-third of the usual oral dose, and clinicians should observe patients for several hours before administering subsequent doses.
Targeting interleukin-1β reduces intense acute swimming-induced muscle mechanical hyperalgesia in mice
Authors: Borghi Sergio M , Zarpelon Ana C , Pinho-Ribeiro Felipe A , Cardoso Renato D R , Cunha Thiago M , Alves-Filho José C , Ferreira Sergio H , Cunha Fernando Q , Casagrande Rubia , Verri Waldiceu A
Published: February 2014

Objectives

The role of interleukin (IL)-1β in intense acute swimming-induced muscle mechanical hyperalgesia was investigated in mice.

Methods

Untrained mice were submitted to one session of intense acute swimming for 120 min or were submitted to sham conditions (30 s exposure to water), and muscle mechanical hyperalgesia (before and 6–48 h after swimming session), IL-1β production (skeletal muscle and spinal cord), myeloperoxidase activity, reduced glutathione (GSH) levels (skeletal muscle and spinal cord), and cortisol, glucose, lactate and creatine kinase (CK) levels (plasma) were analysed.

Key findings

Intense acute swimming-induced muscle mechanical hyperalgesia was dose-dependently inhibited by IL-1ra treatment. IL-1β levels were increased in soleus, but not gastrocnemius muscle and spinal cord 2 and 4 h after the session, respectively. Intense acute swimming-induced increase of myeloperoxidase activity and reduced GSH levels in soleus muscle were reversed by IL-1ra treatment. In the spinal cord, exercise induced an increase of GSH levels, which was reduced by IL-1ra. Finally, IL-1ra treatment reduced plasma levels of CK, an indicator of myocyte damage.

Conclusions

IL-1β mediates intense acute swimming-induced muscle mechanical hyperalgesia by peripheral (soleus muscle) and spinal cord integrative mechanisms and could be considered a potential target to treat exercise-induced muscle pain.
Beneficial effects of melatonin on in vitro bovine embryonic development are mediated by melatonin receptor 1
Authors: Wang Feng , Tian XiuZhi , Zhang Lu , Gao Chao , He ChangJiu , Fu Yao , Ji PengYun , Li Yu , Li Ning , Liu GuoShi
Published: February 2014

In the current study, a fundamental question, that is, the mechanisms related to the beneficial effects of melatonin on mammalian embryonic development, was addressed. To examine the potential beneficial effects of melatonin on bovine embryonic development, different concentrations of melatonin (10−11, 10−9, 10−7, 10−5, 10−3 m) were incubated with fertilized embryos. Melatonin in the range of 10−11 to 10−5 m significantly promoted embryonic development both in early culture medium (CR1aa +3 mg/mL BSA) and in later culture medium (CR1aa + 6%FBS). The most effective concentrations applied in the current studies were 10−9 and 10−7 m. Using quantitative real‐time PCR with immunofluorescence and Western blot assays, the expression of melatonin receptor MT1 and MT2 genes was identified in bovine embryos. Further studies indicate that the beneficial effects of melatonin on bovine embryo development were mediated by the MT1 receptor. This is based on the facts that luzindole, a nonselective MT1 and MT2 antagonist, blocked the effect on melatonin‐induced embryo development, while 4‐P‐PDOT, a selective MT2 antagonist, had little effect. Mechanistic explorations uncovered that melatonin application during bovine embryonic development significantly up‐regulated the expression of antioxidative (Gpx4, SOD1, bcl‐2) and developmentally important genes (SLC2A1, DNMT1A, and DSC2) while down‐regulating expression of pro‐apoptotic genes (P53, BAX, and Caspase‐3). The results obtained from the current studies provide new information regarding the mechanisms by which melatonin promotes bovine embryonic development under both in vitro and in vivo conditions.
Morphology of Gambierdiscus scabrosus sp. nov. (Gonyaulacales): a new epiphytic toxic dinoflagellate from coastal areas of Japan
Authors: Nishimura Tomohiro , Sato Shinya , Tawong Wittaya , Sakanari Hiroshi , Yamaguchi Haruo , Adachi Masao
Published: February 2014

A new epiphytic dinoflagellate is described,
G

ambierdiscus scabrosus sp. nov., from tidal pools and rocky shores along the coastal areas of Japan. Cells are 63.2 ± 5.7 μm in depth, 58.2 ± 5.7 μm in width, and 37.3 ± 3.5 μm in length. The plate formula of
G

. scabrosus is Po, 4′, 0a, 6′′, 6c, ?s, 5′′′, 0p, and 2′′′′. Morphologically,
G

. scabrosus resembles
G

. belizeanus as follows: anterioposteriorly compressed cell shape, narrow 2′′′′ plate, and areolated surface. Despite this similarity, the cells of
G

. scabrosus can be distinguishable by the presence of the asymmetric shaped 3′′ plate and the rectangular shaped 2′ plate.
Rural and Urban Primary Care Physician Professional Beliefs and Quality Improvement Behaviors
Authors: Kirchhoff Anne C. , Hart Gary , Campbell Eric G.
Published: February 2014

Purpose

We evaluated whether primary care physicians (PCPs) from urban and rural practices differ on attitudes and behaviors related to quality improvement (QI) activities, patient relationships, and professionalism/self‐regulation.

Methods

Data from a national survey that assessed physician attitudes and behaviors based on the Physician Charter on Medical Professionalism were used. Of the 1,891 survey respondents, N = 840 were PCPs (n = 274 family medicine (response rate = 67.5%); n = 257 general internal medicine (60.8%); and n = 309 pediatricians (72.7%)). Using Rural‐Urban Commuting Area (RUCA) codes, PCPs were classified as urban and rural according to their practice ZIP code.

Findings

A total of n = 691 physicians were urban and n = 127 rural. Attitudes regarding participating in QI did not differ by practice location; however, rural PCPs were more likely to have reviewed an other physician's records for QI than urban PCPs (65.6% vs 48.0%, P < .001). Rural physicians were more likely to agree that physicians should talk with their patients about the cost of care than urban PCPs (40.5% vs 29.2%, P = .02). While all PCPs endorsed attitudes regarding the importance of professional behaviors (eg, reporting impaired/incompetent colleagues, disclosing medical errors) at generally similar levels, their behaviors differed. More rural physicians had a personal knowledge of an impaired/incompetent physician than urban physicians (20.7% vs 12.7%, P = .02).

Conclusions

PCPs from rural and urban areas share similar attitudes regarding the importance of participating in QI and fulfilling professional responsibilities. However, certain behaviors (eg, knowledge of impaired colleagues) do differ. These results should be confirmed in larger studies of rural PCPs.
Associations Between Premature Ejaculation, Lower Urinary Tract Symptoms, and Erectile Dysfunction in Middle-Aged Korean Policemen
Authors: Lee Jun Ho
Published: February 2014

Introduction

There is controversy concerning the relationship between premature ejaculation (PE) and erectile dysfunction (ED), as well as the scan data regarding the association between PE and lower urinary tract symptoms (LUTS).

Aims

We performed this study to evaluate the association between PE and ED or LUTS.

Methods

A total of 2,591 policemen aged 40–59 years who had participated in a health examination were included in this study. PE, LUTS, and ED were evaluated using the premature ejaculatory diagnostic tool (PEDT), the International Prostate Symptoms Score (IPSS), and the International Index of Erectile Function questionnaire-5 (IIEF), respectively. Spearman's correlation test, the multiple linear regression test, and logistic regression analyses were used to evaluate the relationship between PE and ED or LUTS.

Main Outcome Measures

Associations between PEDT, IPSS, and IIEF.

Results

The middle age of the study group was 49.1 years, and the middle PEDT, IIEF, and IPSS was 7.5, 17.0, and 10.7, respectively. By univariate analysis, PEDT showed a significant correlation with IPSS (r = 0.310, P < 0.001) and IIEF (r = −0.413, P < 0.001). After adjusting for age, components of metabolic syndrome, testosterone, and IIEF, PEDT was significantly correlated with IPSS (Beta = 0.166, P < 0.001). PEDT was also significantly correlated with IIEF after adjusting for age, components of metabolic syndrome, testosterone, and IPSS (Beta = −0.274, P < 0.001). Additionally, the severity of LUTS or ED was associated with the PE positive ratio (P trend < 0.001). The odds ratio (OR) for PE also increased with the severity of LUTS or ED after adjusting for potential confounding factors.

Conclusions

ED and LUTS were significantly and independently correlated with PE.