bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, double-blind, placebo-controlled multicentre study to evaluate the efficacy and safety of diclofenac 4% spray gel in the treatment of acute uncomplicated ankle sprain
Authors: Predel Hans-Georg , Giannetti Bruno , Seigfried Bernd , Novellini Roberto , Menke Georg 
Published: August 2013

Objective A prospective, randomized, double-blind, placebo-controlled, parallel-group multicentre study to evaluate the efficacy and safety of diclofenac 4% spray gel for the treatment of acute, uncomplicated ankle sprain. Methods Outpatients with acute, uncomplicated, one-sided ankle sprain were randomly assigned to receive diclofenac 4% spray gel or placebo (vehicle) three times daily for 14 ± 1 days. The main efficacy endpoint was the intra-individual response to treatment (≥50% decrease in swelling of the injured ankle after a treatment period of ≤10 days). Results The response rate was significantly higher in the diclofenac group ( n = 118) than the placebo group ( n = 114) (91.5% vs. 82.5%). After 3–4 days’ treatment, diclofenac spray significantly reduced swelling, spontaneous pain, pain on active movement and tenderness compared with placebo. Diclofenac spray was well tolerated, with a low overall rate of adverse events. Conclusions Diclofenac 4% spray gel rapidly relieves pain and improves mobility in patients with acute, uncomplicated ankle sprain and is well tolerated. It may be a useful treatment option for other acute soft tissue injuries.
Caregiver Burden and Needs in Frontotemporal Dementia
Authors: Diehl-Schmid Janine , Schmidt Eva-Maria , Nunnemann Sabine , Riedl Lina , Kurz Alexander , Förstl Hans , Wagenpfeil Stefan , Cramer Barbara 
Published: August 2013

Background: It is well known that burden among caregivers of patients with frontotemporal dementia (FTD) is high. However, little is known about the specific problems, the factors that contribute to caregiver burden, and the needs of the FTD caregivers—particularly those needs that are accessible by external support strategies. Objective: We developed a standardized questionnaire that addressed burdens, problems, and the actual needs of FTD caregivers. A total of 94 caregivers were interviewed. Results: It appears that changes in the patients’ behavior and in the interpersonal relations between caregivers and patients are associated with caregiver depression. The most important needs and requests of the caregivers included information and psychosocial support through educated staff, financial support as well as the education of medical staff about the disease. Conclusions: Support strategies should focus on information and psychosocial support. Given the low prevalence of FTD, internet- and telephone-based strategies appear suitable.
Fuzzy approximation of Euler-Lagrange quadratic mappings
Authors: Kim Hark-Mahn , Rassias John M , Lee Juri 
Published: August 2013

Abstract
In this article, we consider the Hyers-Ulam stability of the Euler-Lagrange quadratic functional equation

f
(
k
x
+
l
y
)
+
f
(
k
x
−
l
y
)
=
k
l

[
f
(
x
+
y
)
+
f
(
x
−
y
)
]

+
2
(
k
−
l
)

[
k
f
(
x
)
−
l
f
(
y
)
]

in fuzzy Banach spaces, where k, l are nonzero rational numbers with

k
≠
l

.
Evaluation of estrogenic, antiestrogenic and genotoxic activity of nemorosone, the major compound found in brown Cuban propolis
Authors: Camargo Mariana S , Prieto Aline M , Resende Flavia A , Boldrin Paula K , Cardoso Cassia RP , Fernández Mariana F , Molina-Molina José Manuel , Olea Nicolás , Vilegas Wagner , Cuesta-Rubio Osmany , Varanda Eliana A 
Published: August 2013

Abstract

Background
Brown propolis is the major type of propolis found in Cuba; its principal component is nemorosone, the major constituent of Clusia rosea floral resins. Nemorosone has received increasing attention due to its strong in vitro anti-cancer action. The citotoxicity of nemorosone in several human cancer cell lines has been reported and correlated to the direct action it has on the estrogen receptor (ER). Breast cancer can be treated with agents that target estrogen-mediated signaling, such as antiestrogens. Phytoestrogen can mimic or modulate the actions of endogenous estrogens and the treatment of breast cancer with phytoestrogens may be a valid strategy, since they have shown anti-cancer activity.

Methods
The aim of the present investigation was to assess the capacity of nemorosone to interact with ERs, by Recombinant Yeast Assay (RYA) and E-screen assays, and to determine by comet assay, if the compound causes DNA-damaging in tumoral and non-tumoral breast cells.

Results
Nemorosone did not present estrogenic activity, however, it inhibited the 17-β-estradiol (E2) action when either of both methods was used, showing their antiestrogenicity. The DNA damage induced by the benzophenone in cancer and normal breast cells presented negative results.

Conclusion
These findings suggest that nemorosone may have therapeutic application in the treatment of breast cancer.
RACK(1) to the future – a historical perspective
Authors: Ron Dorit , Adams David R , Baillie George S , Long Aideen , O’Connor Rosemary , Kiely Patrick A 
Published: August 2013

Abstract
This perspective summarises the first and long overdue RACK1 meeting held at the University of Limerick, Ireland, May 2013, in which RACK1’s role in the immune system, the heart and the brain were discussed and its contribution to disease states such as cancer, cardiac hypertrophy and addiction were described. RACK1 is a scaffolding protein and a member of the WD repeat family of proteins. These proteins have a unique architectural assembly that facilitates protein anchoring and the stabilisation of protein activity. A large body of evidence is accumulating which is helping to define the versatile role of RACK1 in assembling and dismantling complex signaling pathways from the cell membrane to the nucleus in health and disease. In this commentary, we first provide a historical perspective on RACK1. We also address many of the pertinent and topical questions about this protein such as its role in transcription, epigenetics and translation, its cytoskeletal contribution and the merits of targeting RACK1 in disease.
Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA
Authors: López Virginia , González-Peramato Pilar , Suela Javier , Serrano Alvaro , Algaba Ferrán , Cigudosa Juan C , Vidal August , Bellmunt Joaquim , Heredero Oscar , Sánchez-Carbayo Marta 
Published: August 2013

AbstractBackgroundArray-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer.MethodsUrinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181).ResultsQuality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH.ConclusionsGenomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patients.
Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study
Authors: Sakem Benjamin , Nock Cristina , Stanga Zeno , Medina Pedro , Nydegger Urs E , Risch Martin , Risch Lorenz 
Published: August 2013

AbstractBackgroundVitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity.MethodsA total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups - severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml) - were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed.ResultsAbout 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer.ConclusionsApproximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.
Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs
Authors: Chan Jackie KW , Charrier Jessica G , Kodani Sean D , Vogel Christoph F , Kado Sarah Y , Anderson Donald S , Anastasio Cort , Van Winkle Laura S 
Published: August 2013

AbstractBackgroundUrban particulate matter (PM) has been epidemiologically correlated with multiple cardiopulmonary morbidities and mortalities, in sensitive populations. Children exposed to PM are more likely to develop respiratory infections and asthma. Although PM originates from natural and anthropogenic sources, vehicle exhaust rich in polycyclic aromatic hydrocarbons (PAH) can be a dominant contributor to the PM2.5and PM0.1fractions and has been implicated in the generation of reactive oxygen species (ROS).ObjectivesCurrent studies of ambient PM are confounded by the variable nature of PM, so we utilized a previously characterized ethylene-combusted premixed flame particles (PFP) with consistent and reproducible physiochemical properties and 1) measured the oxidative potential of PFP compared to ambient PM, 2) determined the ability of PFPs to generate oxidative stress and activate the transcription factor usingin vitroandex vivomodels, and 3) we correlated these responses with antioxidant enzyme expressionin vivo.MethodsWe compared oxidative stress response (HMOX1) and antioxidant enzyme (SOD1, SOD2, CAT, and PRDX6) expressionin vivoby performing a time-course study in 7-day old neonatal and young adult rats exposed to a single 6-hour exposure to 22.4 μg/m3PFPs.ResultsWe showed that PFP is a potent ROS generator that induces oxidative stress and activates Nrf2. Induction of the oxidative stress responsive enzyme HMOX1in vitrowas mediated through Nrf2 activation and was variably upregulated in both ages. Furthermore, antioxidant enzyme expression had age and lung compartment variations post exposure. Of particular interest was SOD1, which had mRNA and protein upregulation in adult parenchyma, but lacked a similar response in neonates.ConclusionsWe conclude that PFPs are effective ROS generators, comparable to urban ambient PM2.5,that induce oxidative stress in neonatal and adult rat lungs. PFPs upregulate a select set of antioxidant enzymes in young adult animals, that are unaffected in neonates. We conclude that the inability of neonatal animals to upregulate the antioxidant response may, in part, explain enhanced their susceptibility to ultrafine particles, such as PFP.
Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection
Authors: Kratzer Ingrid , Liddelow Shane A , Saunders Norman R , Dziegielewska Kate M , Strazielle Nathalie , Ghersi-Egea Jean-Francois 
Published: August 2013

Abstract

Background
The choroid plexuses are the interface between the blood and the cerebrospinal fluid (CSF) contained within the ventricular spaces of the central nervous system. The tight junctions linking adjacent cells of the choroidal epithelium create a physical barrier to paracellular movement of molecules. Multispecific efflux transporters as well as drug-metabolizing and antioxidant enzymes functioning in these cells contribute to a metabolic barrier. These barrier properties reflect a neuroprotective function of the choroid plexus. The choroid plexuses develop early during embryogenesis and provide pivotal control of the internal environment throughout development when the brain is especially vulnerable to toxic insults. Perinatal injuries like hypoxia and trauma, and exposure to drugs or toxic xenobiotics can have serious consequences on neurogenesis and long-term development. The present study describes the developmental expression pattern of genes involved in the neuroprotective functions of the blood–CSF barrier.

Methods
The transcriptome of rat lateral ventricular choroid plexuses isolated from fifteen-day-old embryos, nineteen-day old fetuses, two-day old pups, and adults was analyzed by a combination of Affymetrix microarrays, Illumina RNA-Sequencing, and quantitative RT-PCR.

Results
Genes coding for proteins involved in junction formation are expressed early during development. Overall perinatal expression levels of genes involved in drug metabolism and antioxidant mechanisms are similar to, or higher than levels measured in adults. A similar developmental pattern was observed for multispecific efflux transporter genes of the Abc and Slc superfamilies. Expression of all these genes was more variable in choroid plexus from fifteen-day-old embryos. A large panel of transcription factors involved in the xenobiotic- or cell stress-mediated induction of detoxifying enzymes and transporters is also expressed throughout development.

Conclusions
This transcriptomic analysis suggests relatively well–established neuroprotective mechanisms at the blood-CSF barrier throughout development of the rat. The expression of many transcription factors early in development raises the possibility of additional protection for the vulnerable developing brain, should the fetus or newborn be exposed to drugs or other xenobiotics.
Individual differences effects on the psychological refractory period
Authors: Laguë-Beauvais Maude , Gagnon Christine , Castonguay Nathalie , Bherer Louis 
Published: August 2013

AbstractThe goal of this study was to assess the impact of individual neuropsychological differences on the ability to share attention between concurrent tasks. Participants (n = 20) were trained on six single task practice sessions and dual-task was assessed with reaction time performance on a psychological refractory period (PRP) paradigm. Neuropsychological test scores were also acquired. Furthermore, one of the known variables that can influence performances on neuropsychological tests is gender, which was added as a potential predictor. Results show that the small PRP group was associated with better performances in processing speed, inhibition, flexibility and working memory on neuropsychological tests. Gender also had an impact on the PRP, males having a lower PRP than females. A multiple regression was performed to determine which variables explained the most PRP duration, which showed that 49.1% of the variance of the PRP length could be explained by gender, reaction times of the PRP practice trials at the sixth session, the denomination and flexibility conditions of the Modified Stroop Task as well as results on the Symbol Search Test. Gender was the variable that explained the PRP variance the most (23%). Processing speed also seemed to be a great determinant of the PRP as well as the ability to alternate between task-sets as assessed by the Flexibility condition of the Modified Stroop Task. Thus, this study reveals that good performances on certain neuropsychological tests could predict one’s ease to manage two tasks simultaneously with a higher chance for males to perform better.
Dentoalveolar class III treatment using retromolar miniscrew anchorage
Authors: Poletti Laura , Silvera Aimara A , Ghislanzoni Luis T Huanca 
Published: August 2013

Abstract
In this article, we report the successful use of miniscrews in the distalization of the lower dentition to correct an Angle class III malocclusion with lower anterior crowding in a dolichofacial adult patient. Conventional intraoral and extraoral appliances have many disadvantages, including the need for patient cooperation, potential for anchorage loss, and vertical extrusion of upper molars and lower incisors. Extrusion should be prevented or minimized when treating long-faced patients with reduced overbite. After third molar extractions, miniscrews were placed in the retromolar area. A sliding jig was applied to distalize the lower molars, while the anterior teeth were bonded and retracted secondarily to avoid round tripping. After 18 months of treatment, molar and canine class I relationship with normal overjet and overbite were achieved. In addition, there was an esthetic improvement in the profile with only a small increase of the lower anterior facial height. These results remained stable at a 12-month follow-up.
A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains
Authors: Simon Michelle M , Greenaway Simon , White Jacqueline K , Fuchs Helmut , Gailus-Durner Valérie , Wells Sara , Sorg Tania , Wong Kim , Bedu Elodie , Cartwright Elizabeth J , Dacquin Romain , Djebali Sophia , Estabel Jeanne , Graw Jochen , Ingham Neil J , Jackson Ian J , Lengeling Andreas , Mandillo Silvia , Marvel Jacqueline , Meziane Hamid , Preitner Frédéric , Puk Oliver , Roux Michel , Adams David J , Atkins Sarah , Ayadi Abdel , Becker Lore , Blake Andrew , Brooker Debra , Cater Heather , Champy Marie-France , Combe Roy , Danecek Petr , di Fenza Armida , Gates Hilary , Gerdin Anna-Karin , Golini Elisabetta , Hancock John M , Hans Wolfgang , Hölter Sabine M , Hough Tertius , Jurdic Pierre , Keane Thomas M , Morgan Hugh , Müller Werner , Neff Frauke , Nicholson George , Pasche Bastian , Roberson Laura-Anne , Rozman Jan , Sanderson Mark , Santos Luis , Selloum Mohammed , Shannon Carl , Southwell Anne , Tocchini-Valentini Glauco P , Vancollie Valerie E , Westerberg Henrik , Wurst Wolfgang , Zi Min , Yalcin Binnaz , Ramirez-Solis Ramiro , Steel Karen P , Mallon Ann-Marie , de Angelis Martin Hrabě , Herault Yann , Brown Steve DM 
Published: August 2013

Abstract
Background
The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.

Results
We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.

Conclusions
Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.
Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions
Authors: Álvarez-Rodríguez Lorena , López-Hoyos Marcos , Calvo-Alén Jaime , Aurrecoechea Elena , Villa Ignacio , Martínez-Taboada Víctor Manuel 
Published: August 2013

ABSTRACTThis study was conducted to evaluate phagocyte function in patients with age-related chronic inflammatory conditions. It included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age-matched HCs. Serum IL-8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL-8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL-8 and the migratoty capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P&lt;0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age-restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age-restricted inflammatory disorders and may have a pathogenic role.
Cavum septum pellucidum and psychopathy
Authors: Toivonen Päivi , Könönen Mervi , Niskanen Eini , Vaurio Olli , Repo-Tiihonen Eila , Seppänen Allan , Aronen Hannu J. , Vanninen Ritva , Tiihonen Jari , Laakso Mikko P. 
Published: August 2013

SummaryThe presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.